Multicategory Classification by Support Vector Machines

We examine the problem of how to discriminate between objects of three or more classes. Specifically, we investigate how two-class discrimination methods can be extended to the multiclass case. We show how the linear programming (LP) approaches based on the work of Mangasarian and quadratic programming (QP) approaches based on Vapnik's Support Vector Machine (SVM) can be combined to yield two new approaches to the multiclass problem. In LP multiclass discrimination, a single linear program is used to construct a piecewise-linear classification function. In our proposed multiclass SVM method, a single quadratic program is used to construct a piecewise-nonlinear classification function. Each piece of this function can take the form of a polynomial, a radial basis function, or even a neural network. For the k > 2-class problems, the SVM method as originally proposed required the construction of a two-class SVM to separate each class from the remaining classes. Similarily, k two-class linear programs can be used for the multiclass problem. We performed an empirical study of the original LP method, the proposed k LP method, the proposed single QP method and the original k QP methods. We discuss the advantages and disadvantages of each approach.     

Comparison of agarose and dextran-grafted agarose strong ion exchangers for the separation of protein aggregates

The control of aggregate levels in recombinant protein based drugs is a primary concern during process development and manufacture. In recent years, a novel class of dextran-grafted ion exchange matrices has gained popularity for process scale protein purification due to increased mass transfer rates and higher dynamic binding capacity compared to conventional matrices. Using bovine serum albumin and a monoclonal antibody as model proteins, we studied Sepharose FF and Sepharose XL ion exchangers for the separation of protein aggregates. Experimental results comparing linear gradient elution, stepwise elution, and flow-through chromatography for aggregate separation are described. Differences in performance for the various ion exchangers are discussed and modeled. Strategies for the optimization of protein aggregate separation are provided.     

Encapsulated sulfates: insight to binding propensities

Two crystal structures of sulfate inclusion complexes in an aza- and amido-cryptand represent the first examples of encapsulated sulfate in synthetic cryptand receptors and indicate penta- and octa-coordination, respectively.     

Cascaded z-filters for efficient single-scan suppression of zero-quantum coherence

A simple and robust method to suppress zero-quantum coherence (ZQC) in NMR experiments, in a single scan and with very high suppression ratio, is described. It is an appreciable improvement on a previous technique by Thrippleton and Keeler [Angew. Chem. Int. Ed. 42 (2003) 3938]. The method, called a z-filter cascade, preserves longitudinal, or z-magnetization, with high efficiency. Losses depend mostly on T1 relaxation but not T2 relaxation mechanisms. At the same time, suppression of ZQC can be essentially complete in a single scan. The time duration of the z-filter cascade scales inversely to representative chemical shift differences between the coupled spins, and is typically a few tens of milliseconds. The high efficiency of the zero-quantum suppression and excellent retention of the desired z-magnetization, in a single scan without resort to phase cycling or difference spectroscopy, makes the z-filter cascade a useful new pulse sequence building block for a whole range of NMR experiments. In cases where unwanted residual ZQC may have previously contributed to baseline " t1-noise" in two-dimensional NMR spectra, the z-filter cascade can deliver a noteworthy improvement in spectral quality.     

Reconstitution and biochemical characterization of a new pyridoxal-5'-phosphate biosynthetic pathway

The substrates for Bacillus subtilis PLP synthase (YaaD and YaaE) are identified, and the first reconstitution of PLP biosynthesis using this pathway is described. Three partial reactions catalyzed by YaaD are also identified.     

Anion binding motifs: topicity and charge in amidocryptands

An expanded amidocryptand with propyl linkages provides multitopic sites for binding anions and water molecules. Upon quaternization of the two bridgehead amines, the molecular shape changes from an inverted Y to that of a bowl, which is filled with water and topped by the anion.