Anisotropy resolved multidimensional emission spectroscopy (ARMES): A new tool for protein analysis

Structural analysis of proteins using the emission of intrinsic fluorophores is complicated by spectral overlap. Anisotropy resolved multidimensional emission spectroscopy (ARMES) overcame the overlap problem by the use of anisotropy, with chemometric analysis, to better resolve emission from different fluorophores. Total synchronous fluorescence scan (TSFS) provided information about all the fluorophores that contributed to emission while anisotropy provided information about the environment of each fluorophore. Here the utility of ARMES was demonstrated via study of the chemical and thermal denaturation of human serum albumin (HSA).     

A fluorescence anisotropy method for measuring protein concentration in complex cell culture media

The rapid, quantitative analysis of the complex cell culture media used in biopharmaceutical manufacturing is of critical importance. Requirements for cell culture media composition profiling, or changes in specific analyte concentrations (e.g. amino acids in the media or product protein in the bioprocess broth) often necessitate the use of complicated analytical methods and extensive sample handling. Rapid spectroscopic methods like multi-dimensional fluorescence (MDF) spectroscopy have been successfully applied for the routine determination of compositional changes in cell culture media and bioprocess broths. Quantifying macromolecules in cell culture media is a specific challenge as there is a need to implement measurements rapidly on the prepared media. However, the use of standard fluorescence spectroscopy is complicated by the emission overlap from many media components. Here, we demonstrate how combining anisotropy measurements with standard total synchronous fluorescence spectroscopy (TSFS) provides a rapid, accurate quantitation method for cell culture media. Anisotropy provides emission resolution between large and small fluorophores while TSFS provides a robust measurement space. Model cell culture media was prepared using yeastolate (2.5 mg mL^–1) spiked with bovine serum albumin (0 to 5 mg mL^–1). Using this method, protein emission is clearly discriminated from background yeastolate emission, allowing for accurate bovine serum albumin (BSA) quantification over a 0.1 to 4.0 mg mL^–1range with a limit of detection (LOD) of 13.8 μg mL^–1.     

Relativity,Gravitation and Cosmology,by Robert J.A. Lambourne

Physique des Particules. Edited by C. de Witt and C. Itzykson. (Gordon and Breech, 1973.) [Pp. xvi+537.] £13.55. Scope: Summer school lectures. Level: Specialist/post-graduate.

Colour Centres and Imperfections in Insulators and Semiconductors. By P. D. Townsend and J. C. Kelly. (Sussex University Press, 1973.) [Pp. vii + 229.] Hard £5.00; paper £3.00. Scope: Textbook. Level: Specialist/post-graduate; undergraduate (fina1 year).

The Physics of Elementary Particles. By L. J. Tassie. (Longmans, 1973.) [Pp. xi+255.] £2.95. Scope: Textbook. Level: Undergraduate.

Particles and Nuclei. Vol. 1, Part 1. By N. N. Bogolyubov. (Plenum Press, 1972.) [Pp. 189.] $46. Scope: Library. Level: For specialists only.

Particles and Nuclei. Vol. 2. By N. N. Bogulyubov. (Plenum Press, 1972.) [Pp. 309.] $92.00. Scope: Library. Level: For specialists only.

The Large Scale Structure of Space-Time. By S. W. Hawking and G. F. R. ELLIS. (Cambridge University Press 1973). [Pp. xi+391.] £10.00. Scope: Treatise/Textbook. Level: Specialist/post-graduate.

General Physics Workbook. (Physics Problems and how to solve them.) By Foster Strong. (W. H. Freeman and Son, San Franciso, Oct, 1972.) [pp. 502.] £2.50. Scope: Textbook. Level: Undergraduate; School.

Planck's Original Papera in Quantum Physics. Edited by Hans Kangro. (Taylor and Francis, 1972.) [Pp. viii+ 60.] 75p. Scope: Textbook. Level: Undergraduate.

Quantum Physics and Ordinary Language. By T. Bergstein. (Macmillan, 1972.) [Pp. xii+ 81.] £3.00. Scope: Treatise. Level: General reader.

The Use of the Scanning Electron Microscope. By J. W. S. Hearle, J. T. Sparrow and P. M. Cross. (Pergamon, 1972.) [Pp. xi+278.] £8.80. Scope: Survey. Level: Specialist/post-graduate.

Defects in Crystalline Solids. By B. Henderson. (Arnold, 1972.) [Pp. ix+203.] Cloth £6.00; Paper £3.00. Scope: Textbook. Level: Undergraduate.

An Introduction to Lattice Dynamics. By A. K. Ghatak and L. S. Khothari. (Addison-Wesley, 1972.) [Pp. vi+234.] $11.50. Scope: Textbook. Level: Post-graduate.

Case Studies in Atomic Collision Physics (2). Editors E. W. McDaniel and M. R. C. McDowell. (North-Holland, 1972.) [Pp. xiv+649.] Hfl 150.00, $47.00. Scope: Treatise/Textbook. Level: Specialist/post-graduate.

Theory of Seismic Head Waves. By V. Cerveny and R. Ravindra. (University of Toronto Press, London; Oxford University Press, 1972.) [Pp. xvi + 312.] £8.75. Scope: Treatise/textbook. Level: Specialist/postgraduate.

An Introduction to the Ionosphere and Magnetosphere. By J. A. Ratcliffe. (Cambridge University Press, 1972.) [Pp. x + 256.] £4.00. Scope: Textbook; library. Level: Postgraduate; undergraduate; school.

Optics. By C. S. Williams and A. Becklund. (John Wiley, 1972.) [Pp. xiv+397.] £7.50. Scope: Textbook; library (reference). Level: For specialists only; specialist.

Principles of Activation Analysis. By Paul Kruger. (John Wiley &; Sons Ltd., 1971.) [Pp. xi+522.] £11.75. Scope: Treatise/Textbook. Level: Undergraduate.

Colloidal and Morphological Behaviour of Block and Graft Polymers. Edited by G. E. Molau. (Plenum Press, 1971.) [Pp. xvi+ 327.] $14.50.

Spin and Isospin. By P. A. Carruthers. (Gordon &; Breach. 1971.) [Pp. ix+288.] £8.10 Scope: Textbook; library (reference). Level: For specialists only; specialist/postgraduate.

Nuclear Reactions and Nuclear Structure. By P. E. Hodgson. (Clarendon Press: Oxford University Press, 1971.) [Pp. xi+661.] £14.50. Scope: Treatise/textbook. Level: Specialist/postgraduate.

Magnetic Resonance in Metals. By J. Winter. (Clarendon Press: Oxford University Press; 1971.) [Pp. xiii+205.] £5.50.

Concepts of Atomic Physics. By D. A. Jackson. (McGraw-Hill, 1971.) [Pp. 170.] £2.50. Scope: Textbook. Level: Undergraduate.

An Introduction to the Theory of Atomic Spectra. By I. I. Sobel'Man, translated by T. F. L. LeVierge, and edited by G.K.Woodgate. (Pergamon Press, 1972.) [Pp. xvi+ 609.] £18.00. Scope: Textbook; library (reference). Level: Specialist/postgraduate.

The Jahn-Teller Effect in Molecules and Crystals. By R. Englman. (Wiley-Interscience, 1972.) [Pp. xx+ 350.] £8.00. Scope: Treatise. Level: For specialists only.

Algebraic Methods in Statistical Mechanics and Quantum Field Theory. By G. G. Emch. (Wiley-Interscience, 1972.) [Pp. xiv+ 333.] £7.85. Scope: Textbook. Level: For specialists only.

Statistical Mechanics and Quantum Field Theory. (Les Houches Summer School, 1970). Edited by C. DeWitt and R. Stora. (Gordon &; Breach, 1971.) [Pp. xvi+ 552.] £0.00. Scope: Treatise. Level: Postgraduate.

Group Theory and the Coulomb Problem. By M. J. Englefield. (John Wiley, 1972.) [Pp. viii+ 120.] £4.75. Scope: Textbook. Level: Postgraduate.

Statistical Properties of Nuclei. Edited by J. B. Garg. (Plenum Press, 1972,) [Pp. xxiv+ 665.] $37.00. Scope: Conference Proceedings. Level: For specialists only.

Theoretical Solid State Physics. (Volume 1). By A. Haug. (Pergamon. 1972.) [Pp. xiv+ 497.] £7.00. Scope: Textbook. Level: Postgraduate; undergraduate.

Analytic Properties of Feynmn Diagrams in Quantum Field Theory. By I. T. Todorov. (Pergamon, 1971.) [Pp. xvi+ 152.] £3.75. Scope: Treatise. Level: For specialists only.

Progress in Solid State Chemistry, Vol. 7. Edited by H. Reiss and J. O. McCaldin. (Pergamon Press, 1972.) [Pp. xi+275.] £10.00. Scope: Survey. Level: Specialist/post-graduate.

Introduction to Particle Physics. By R. Omn$eGs. (John Wiley, 1971.) [Pp. xiii+ 414.] £6.00. Scope: Textbook. Level: Postgraduate.

Plasma, the Fourth State of Matter. By D. A. Frank-Kamenetskii. (Plenum Press, 1972.) [Pp. viii+ 159.] $14.00. Scope: Treatise. Level: Undergraduate.

Computer Aided Design. (Institution of Electrical Engineers, 1972.) [Pp. viii+ 431.] £11.90.

Trends in On-line Computer Systems. (Institution of Electrical Engineers, 1972.) [Pp. v+ 217.] £8.00. Scope: Conference proceedings. Level: Specialist/postgraduate.

Introduction to the Principles of Electromagnetism. By W. Hauser. (Addison-Wesley, 1971.) [Pp. xiv+ 623.] £7.00. Scope: Textbook. Level: Postgraduate; undergraduate.

Dynamica, Electricity and Magnetism. By E. W. Laing and W. McFarlane. (Oliver and Boyd, 1972.) [Pp. vii+ 156.] £1.75. Scope: Textbook. Level: Undergraduate.

Nineteenth Century Aether Theories. By K. F. Schaffner. (Pergamon, printed in Hungary, 1972.) [Pp. ix+ 278.] £3.25. Scope: Textbook; survey. Level: General reader; undergraduate.

Mechanics and Electrodynamics. By L. D. Landau and E. M. Lifshitz. (Pergamon. 1972.) [Pp. xiii+ 282.] £3.00. Scope: Textbook. Level: Postgraduate; undergraduate.

Theory of the Unmagnetized Plasma. By D. C. Montgomery. (Gordon and Breach, 1971.) [Pp. 416.] £7.30, Scope: Treatise. Level: Specialist/postgraduate.

Amorphous Materials. Edited by R. W. Douglas and B. Ellis. (Wiley-Interscience, 1972.) [Pp. xviii+ 550.] £9.00. Scope: Conference proceedings; survey; library. Level: For specialists only; specialist/postgraduate.     

Vinamidines and Vinamidinium Salts—Examples of Stabilized Push-Pull Alkenes

The name vinamidines has been proposed for 1,5-diazapentadienes: these compounds can be regarded as vinylogous amidines and at the same time as push-pull substituted (and thereby stabilized) alkenes. Vinamidine and vinamidinium structural elements may also form part of a ring system. Characteristic of this class of compounds are their reactivity toward electrophiles (at C_β) and nucleophiles (C_α) and their regenerative character, i.e. their tendency to undergo substitution instead of addition reactions. Reactions of vinamidinium salts with nucleophiles are of special preparative value: they lead e.g. to pyrazoles, oxazoles, pyrimidines, diazepines, quinolines, and quinolizines.     

Time-scale- and temperature-dependent mechanical properties of viscoelastic poly(3,4-ethylenedioxythiophene) films

The viscoelastic properties of thin films of poly(3,4-ethylenedioxythiophene) (PEDOT) have been studied using the method of acoustic impedance. The films were deposited on the Au electrodes of 10 MHz AT-cut quartz thickness shear mode resonators and exposed to acetonitrile solutions of 0.1 M TEABF4 and LiClO4. For p-doped films, admittance spectra as a function of potential (E), temperature (T), and time scale (frequency, via harmonics, in the range 10-110 MHz) were acquired. Shear modulus components extracted from these responses surprisingly showed virtually no variation with E (and thus film solvation) or with T, but the variation with frequency was dramatic. This qualitative behavior and the numerical values of the shear moduli contrast strongly with recently reported data for the related poly(3-hexylthiophene) system, which shares the same conducting spine but differs substantially in the substitution pattern. Accordingly, the models and interpretation for PEDOT are quite different: film dynamics are determined by free-volume effects, and side-chain motion is not a significant factor. Qualitatively similar potential and time-scale effects were seen for n-doped PEDOT, but the scope of the measurements was limited by film stability.     

The ft value for the superallowed Fermi decay 38mK(β+)38Ar

The threshold energy for the reaction ³⁵Cl(α, n)^38mK has been measured to be 6674.8±3.2 keV and the Q-value for the reaction ³⁵Cl(α, p)³⁸Ar to be 837.2±2.4 keV. From the measurements a value of 5021.2±3.4 keV was obtained for the end-point energy of the decay ^38mK(b⁺)³⁸Ar. The half-life was measured as 925.6±0.7ms and hence an “effective” $\text{?t}$ value was calculated, giving the result 3106±10 s with the inclusion of outer radiative corrections to order Z²α³ and 3088±10 s allowing also for calculated charge-dependent effects.     

A collaborative hit-to-lead investigation leveraging medicinal chemistry expertise with high throughput library design, synthesis and purification capabilities

High throughput screening (HTS) campaigns, where laboratory automation is used to expose biological targets to large numbers of materials from corporate compound collections, have become commonplace within the lead generation phase of pharmaceutical discovery. Advances in genomics and related fields have afforded a wealth of targets such that screening facilities at larger organizations routinely execute over 100 hit-finding campaigns per year. Often, 10(5) or 10(6) molecules will be tested within a campaign/cycle to locate a large number of actives requiring follow-up investigation. Due to resource constraints at every organization, traditional chemistry methods for validating hits and developing structure activity relationships (SAR) become untenable when challenged with hundreds of hits in multiple chemical families per target. To compound the issue, comparison and prioritization of hits versus multiple screens, or physical chemical property criteria, is made more complex by the informatics issues associated with handling large data sets. This article describes a collaborative research project designed to simultaneously leverage the medicinal chemistry and drug development expertise of the Novartis Institutes for Biomedical Research Inc. (NIBRI) and ArQule Inc.'s high throughput library design, synthesis and purification capabilities. The work processes developed by the team to efficiently design, prepare, purify, assess and prioritize multiple chemical classes that were identified during high throughput screening, cheminformatics and molecular modeling activities will be detailed.     

Flexible isosurfaces: Simplifying and displaying scalar topology using the contour tree

The contour tree is an abstraction of a scalar field that encodes the nesting relationships of isosurfaces. We show how to use the contour tree to represent individual contours of a scalar field, how to simplify both the contour tree and the topology of the scalar field, how to compute and store geometric properties for all possible contours in the contour tree, and how to use the simplified contour tree as an interface for exploratory visualization.     

Frequency Domain Fluorescence Lifetime Study of Crude Petroleum Oils

Frequency domain (FD) fluorescence lifetime data was collected for a series of 20 crude petroleum oils using a 405 nm excitation source and over a spectral range of ~426 to ~650 nm. Average fluorescence lifetimes were calculated using three different models: discrete multi-exponential, Gaussian distribution, and Lorentzian distribution. Fitting the data to extract accurate average lifetimes using the various models proved easier and less time consuming for the FD data than with Time Correlated Single Photon Counting (TCSPC) methods however the analysis of confidence intervals to the computed average lifetimes proved cumbersome for both methods. The uncertainty in the average lifetime was generally larger for the discrete lifetime multi-exponential model when compared to the distribution-based models. For the lifetime distributions, the data from the light crude oils with long lifetimes generally fit to a single decay term. Heavier oils with shorter lifetimes required multiple decay terms. The actual value for the average lifetime is more dependant on the specific fitting model employed than the data acquisition method used. Correlations between average fluorescence lifetimes and physical and chemical parameters of the crude oils were made with a view to developing a quantitative model for predicting the gross chemical composition of crude oils. It was found that there was no significant benefit gained by using FD over TCSPC other than more rapid data analysis in the FD case. For the FD data the Gaussian distribution model for fluorescence lifetime gave the best correlations with chemical composition allowing a qualitative correlation to some bulk oil parameters.