Single-Round DNA Aptamer Selection by Combined Use of Capillary Electrophoresis and Next Generation Sequencing: An Aptaomics Approach for Identifying Unique Functional Protein-Binding DNA Aptamers

In DNA aptamer selection, existing methods do not discriminate aptamer sequences based on their binding affinity and function and the reproducibility of the selection is often poor, even for the selection of well-known aptamers like those that bind the commonly used model protein thrombin. In the present study, a novel single-round selection method (SR-CE selection) was developed by combining capillary electrophoresis (CE) with next generation sequencing. Using SR-CE selection, a successful semi-quantitative and semi-comprehensive aptamer selection for thrombin was demonstrated with high reproducibility for the first time. Selection rules based on dissociation equilibria and kinetics were devised to obtain families of analogous sequences. Selected sequences of the same family were shown to bind thrombin with high affinity. Furthermore, data acquired from SR-CE selection was mined by creating sub-libraries that were categorized by the functionality of the aptamers (e. g., pre-organized aptamers versus structure-induced aptamers). Using this approach, a novel fluorescent molecular recognition sensor for thrombin with nanomolar detection limits was discovered. Thus, in this proof-of-concept report, we have demonstrated the potential of a “DNA Aptaomics” approach to systematically design functional aptamers as well as to obtain high affinity aptamers.     

Newton Polytopes and Relative Entropy Optimization

Foundations of Computational Mathematics - Certifying function nonnegativity is a ubiquitous problem in computational mathematics, with especially notable applications in optimization. We study the...     

Long-Range 31P-31P Spin Coupling Constants in the 31P NMR Spectra of Phosphite Triesters

Abstract

Data are presented on the magnitudes of ⁵ J _pp and ⁶ J _PP spin-spin coupling constants in the ³¹P NMR spectra of a variety of novel polyphosphite triesters.     

Filling Length in Finitely Presentable Groups

We study the filling length function for a finite presentation of a group , and interpret this function as an optimal bound on the length of the boundary loop as a van Kampen diagram is collapsed to the basepoint using a combinatorial notion of a null-homotopy. We prove that filling length is well behaved under change of presentation of . We look at 'AD-pairs' (f,g) for a finite presentation : that is, an isoperimetric function f and an isodiametric function g that can be realised simultaneously. We prove that the filling length admits a bound of the form [g+1][log (f+1)+1] whenever (f,g) is an AD-pair for . Further we show that (up to multiplicative constants) if is an isoperimetric function ( ) for a finite presentation then ( ) is an AD-pair. Also we prove that for all finite presentations filling length is bounded by an exponential of an isodiametric function.Partially supported by NSF grant DMS-9800158Supported by EPSRC Award No. 98001683 and Corpus Christi College, Oxford.     

Improved measurement of Vub with inclusive semileptonic B decays

We report a new measurement of the Cabibbo-Kobayashi-Maskawa parameter Vub made with a sample of 9.7 x 10(6) BB- events collected with the CLEO II detector. Using heavy quark theory, we combine the observed yield of leptons from semileptonic B decay in the end-point momentum interval 2.2-2.6 GeV/c with recent CLEO II data on B-->X(s)gamma to find Vub = (4.08+/-0.34+/-0.44+/-0.16+/-0.24)x10(-3), where the first two uncertainties are experimental and the last two are from theory.     

A note on the magnetic susceptibility of hydrogen and its isotopomers

A wavefunction used in an earlier calculation of the nuclear shielding of the hydrogen molecule has been tested by comparing the calculated magnetic susceptibility against that of Kolos and Wolniewicz. Good agreement is obtained. The procedure of Herman and Short for averaging over the nuclear motion has also been tested by comparing the predicted susceptibilities of H₂, Hd and D₂ with those obtained from averages of the Rydberg-Klein-Rees potential curves by Jain and Sahni. Again, good agreement is found.For the first time calculated values have been obtained for the susceptibilities of the isoropomers of hydrogen which contain tritium. It is predicted that accurate susceptibility measurements should not only be able to distinguish between all the various isotopomers but should also detect the temperature dependence of the susceptibility of any one isotopomer.