Variable and feature selection have become the focus of much research in areas of application for which datasets with tens or hundreds of thousands of variables are available. These areas include text processing of internet documents, gene expression array analysis, and combinatorial chemistry. The objective of variable selection is three-fold: improving the prediction performance of the predictors, providing faster and more cost-effective predictors, and providing a better understanding of the underlying process that generated the data. The contributions of this special issue cover a wide range of aspects of such problems: providing a better definition of the objective function, feature construction, feature ranking, multivariate feature selection, efficient search methods, and feature validity assessment methods.

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An introduction to variable and feature selection

THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

I. Introduction: Conceptual vs Fundamental andComputational Aspects of DFT1793II. Fundamental and Computational Aspects of DFT 1795A. The Basics of DFT: The Hohenberg−KohnTheorems1795B. DFT as a Tool for Calculating Atomic andMolecular Properties: The Kohn−ShamEquations1796C. Electronic Chemical Potential andElectronegativity: Bridging Computational andConceptual DFT1797III. DFT-Based Concepts and Principles 1798A. General Scheme: Nalewajski’s ChargeSensitivity Analysis1798B. Concepts and Their Calculation 18001. Electronegativity and the ElectronicChemical Potential18002. Global Hardness and Softness 18023. The Electronic Fukui Function, LocalSoftness, and Softness Kernel18074. Local Hardness and Hardness Kernel 18135. The Molecular Shape FunctionsSimilarity 18146. The Nuclear Fukui Function and ItsDerivatives18167. Spin-Polarized Generalizations 18198. Solvent Effects 18209. Time Evolution of Reactivity Indices 1821C. Principles 18221. Sanderson’s Electronegativity EqualizationPrinciple18222. Pearson’s Hard and Soft Acids andBases Principle18253. The Maximum Hardness Principle 1829IV. Applications 1833A. Atoms and Functional Groups 1833B. Molecular Properties 18381. Dipole Moment, Hardness, Softness, andRelated Properties18382. Conformation 18403. Aromaticity 1840C. Reactivity 18421. Introduction 18422. Comparison of Intramolecular ReactivitySequences18443. Comparison of Intermolecular ReactivitySequences18494. Excited States 1857D. Clusters and Catalysis 1858V. Conclusions 1860VI. Glossary of Most Important Symbols andAcronyms1860VII. Acknowledgments 1861VIII. Note Added in Proof 1862IX. References 1865

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Conceptual density functional theory.

Solid tumours contain regions at very low oxygen concentrations (hypoxia), often surrounding areas of necrosis. The cells in these hypoxic regions are resistant to both radiotherapy and chemotherapy. However, the existence of hypoxia and necrosis also provides an opportunity for tumour-selective therapy, including prodrugs activated by hypoxia, hypoxia-specific gene therapy, targeting the hypoxia-inducible factor 1 transcription factor, and recombinant anaerobic bacteria. These strategies could turn what is now an impediment into a significant advantage for cancer therapy.

Exploiting tumour hypoxia in cancer treatment.

A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Moller–Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr_2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.

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Advances in molecular quantum chemistry contained in the Q-Chem 4 program package

An improved method for computing potential-derived charges is described which is based upon the CHELP program available from QCPE.1 This approach (CHELPG) is shown to be considerably less dependent upon molecular orientation than the original CHELP program. In the second part of this work, the CHELPG point selection algorithm was used to analyze the changes in the potential-derived charges in formamide during rotation about the CN bond. In order to achieve a level of rotational invariance less than 10% of the magnitude of the electronic effects studied, an equally-spaced array of points 0.3 A apart was required. Points found to be greater than 2.8 A from any nucleus were eliminated, along with all points contained within the defined VDW distances from each of the atoms. The results are compared to those obtained by using CHELP. Even when large numbers of points (ca. 3000) were sampled using the CHELP selection routine, the results did not indicate a satisfactory level of rotatational invariance. On the basis of these results, the original CHELP program was found to be inadequate for analyzing internal rotations.

Determining atom-centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis

We describe a methodology for performing variable ranking and selection using support vector machines (SVMs). The method constructs a series of sparse linear SVMs to generate linear models that can generalize well, and uses a subset of nonzero weighted variables found by the linear models to produce a final nonlinear model. The method exploits the fact that a linear SVM (no kernels) with l1-norm regularization inherently performs variable selection as a side-effect of minimizing capacity of the SVM model. The distribution of the linear model weights provides a mechanism for ranking and interpreting the effects of variables. Starplots are used to visualize the magnitude and variance of the weights for each variable. We illustrate the effectiveness of the methodology on synthetic data, benchmark problems, and challenging regression problems in drug design. This method can dramatically reduce the number of variables and outperforms SVMs trained using all attributes and using the attributes selected according to correlation coefficients. The visualization of the resulting models is useful for understanding the role of underlying variables.

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Dimensionality reduction via sparse support vector machines

Preface.Contributors.The Electron Density Distribution of Amides and Related Compounds (C. Breneman & M. Martinov).Origin of the Amide Rotational Barrier (K. Wiberg).The Amide Linkage as a Ligand--Its Properties and the Role of Distortion (A. Greenberg).Studies in Amide Hydrolysis: The Acid, Base, and Water Reactions (R. Brown).The Thermochemistry of Amides (J. Liebman, et al.).Stereospecificity in the alpha-Lactam (Aziridinone) Synthon (R. Hoffman).beta-Lactams: Cyclic Amides of Distinction (A. Bose, et al.).Sterically Hindered Twisted Amides (S. Yamada).Photoelectron Spectroscopy of Amides and Lactams (P. Rademacher).The Role of Amides in the Noncovalent Synthesis of Supramolecular Structures in Solution, at Interfaces, and in Solids (G. Palmore & J. MacDonald).beta-Lactam Antibacterial Agents: Computational Chemistry Investigations (D. Boyd).Three-Dimensional Design of Enzyme Inhibitors with Heterocyclic Amide Bond Mimics (R. Bohacek & W. Shakespeare).Ab Initio Conformational Analysis of Protein Subunits: A Case Study of the Serine Diamide Model (A. Perczel & I. Csizmadia).Gas-Phase Ion Chemistry of Amides, Peptides, and Proteins (C. Cassady).beta-Sheet Interactions Between Proteins (S. Maitra & J. Nowick).Head-to-Tail Cyclic Peptides and Cyclic Peptide Libraries (A. Spatola & P. Romanovskis).From Crystal Structures of Oligopeptides to Protein Folding: The Importance of Peptide Bond-Side Chain Hyperconjugation (A. Cieplak).Role of the Peptide Bond in Protein Structure and Folding (N. Kallenbach, et al.).Index.

The amide linkage : structural significance in chemistry, biochemistry, and materials science

SMARTCyp is an in silico method that predicts the sites of cytochrome P450-mediated metabolism of druglike molecules. The method is foremost a reactivity model, and as such, it shows a preference for predicting sites that are metabolized by the cytochrome P450 3A4 isoform. SMARTCyp predicts the site of metabolism directly from the 2D structure of a molecule, without requiring calculation of electronic properties or generation of 3D structures. This is a major advantage, because it makes SMARTCyp very fast. Other advantages are that experimental data are not a prerequisite to create the model, and it can easily be integrated with other methods to create models for other cytochrome P450 isoforms. Benchmarking tests on a database of 394 3A4 substrates show that SMARTCyp successfully identifies at least one metabolic site in the top two ranked positions 76% of the time. SMARTCyp is available for download at http://www.farma.ku.dk/p450.

SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism.

The changes that occur during the rotation of the amino group of formamide have been studied in some detail. Geometry optimizations at the MP2/6-31G* level confirmed the relatively large increase in C-N bond length but small decrease in the C-0 length on going from the planar structure to the rotational transition state. A calculation of the force constants for formamide and for the transition state showed that the carbonyl force constant changed relatively little, but the C-N constant changed by about 30%. The path followed in the rotation was studied starting with the saddle point geometry and following it computationally down to the ground state. The geometrical changes are discussed. The electron populations were calculated for a number of structures along the reaction coordinate by numerical integration of the charge density within uniquely defined atomic volumes. The oxygen population was little affected by the rotation and the main charge shift was between carbon and nitrogen. The electrostatic potentials for the structures also were examined and converted to effective charges for spherically symmetrical atoms. All of the analyses indicated that essentially all of the interactions leading to the rotational barrier originate in the C-N bond and that the oxygen does not participate to a significant extent. The direction of the charge shift between C and N was in opposite directions for the electron populations derived by integration of the charge density, and by fitting the electrostatic potentials. However, this was due to the difference in the definition of the atoms, being anisotropic in the first case and spherically symmetrical in the second. All of the observations can be rationalized on the basis of the assumption that stabilization of the lone pair on nitrogen is the most important factor in determining both structures and energies.

Resonance interactions in acyclic systems. 3. Formamide internal rotation revisited. Charge and energy redistribution along the C-N bond rotational pathway

Curt M. Breneman

Papers

Determining atom-centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis

Dimensionality reduction via sparse support vector machines

The amide linkage : structural significance in chemistry, biochemistry, and materials science

SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism.

Resonance interactions in acyclic systems. 3. Formamide internal rotation revisited. Charge and energy redistribution along the C-N bond rotational pathway