Kinetic analysis of N-alkylaryl carboxamide hexitol nucleotides as substrates for evolved polymerases

Six 1′,5′-anhydrohexitol uridine triphosphates were synthesized with aromatic substitutions appended via a carboxamide linker to the 5-position of their bases. An improved method for obtaining such 5-substituted hexitol nucleosides and nucleotides is described. The incorporation profile of the nucleotide analogues into a DNA duplex overhang using recently evolved XNA polymerases is compared. Long, mixed HNA sequences featuring the base modifications are generated. The apparent binding affinity of four of the nucleotides to the enzyme, the rate of the chemical step and of product release, plus the specificity constant for the incorporation of these modified nucleotides into a DNA duplex overhang using the HNA polymerase T6G12_I521L are determined via pre-steady-state kinetics. HNA polymers displaying aromatic functional groups could have significant impact on the isolation of stable and high-affinity binders and catalysts, or on the design of nanomaterials

Recursive least squares semi-blind beamforming for MIMO using decision directed adaptation and constant modulus criterion

A new semi-blind adaptive beamforming scheme is proposed for multi-input multi-output (MIMO) induced and space- division multiple-access based wireless systems that employ high order phase shift keying signaling. A minimum number of training symbols, very close to the number of receiver antenna elements, are used to provide a rough initial least squares estimate of the beamformer0s weight vector. A novel cost function combining the constant modulus criterion with decision-directed adaptation is adopted to adapt the beamformer weight vector. This cost function can be approximated as a quadratic form with a closed-form solution, based on which we then derive the recursive least squares (RLS) semi-blind adaptive beamforming algorithm. This semi-blind adaptive beamforming scheme is capable of converging fast to the minimum mean-square-error beamforming solution, as demonstrated in our simulation study. Our proposed semi-blind RLS beamforming algorithm therefore provides an e±cient detection scheme for the future generation of MIMO aided mobile communication systems

Exploring the suitability of RanBP2-type Zinc Fingers for RNA-binding protein design.

Transcriptomes consist of several classes of RNA that have wide-ranging but often poorly described functions and the deregulation of which leads to numerous diseases. Engineering of functionalized RNA-binding proteins (RBPs) could therefore have many applications. Our previous studies suggested that the RanBP2-type Zinc Finger (ZF) domain is a suitable scaffold to investigate the design of single-stranded RBPs. In the present work, we have analyzed the natural sequence specificity of various members of the RanBP2-type ZF family and characterized the interaction with their target RNA. Surprisingly, our data showed that natural RanBP2-type ZFs with different RNA-binding residues exhibit a similar sequence specificity and therefore no simple recognition code can be established. Despite this finding, different discriminative abilities were observed within the family. In addition, in order to target a long RNA sequence and therefore gain in specificity, we generated a 6-ZF array by combining ZFs from the RanBP2-type family but also from different families, in an effort to achieve a wider target sequence repertoire. We showed that this chimeric protein recognizes its target sequence (20 nucleotides), both in vitro and in living cells. Altogether, our results indicate that the use of ZFs in RBP design remains attractive even though engineering of specificity changes is challenging

Spatial analysis of poverty and prosperity in the U.S. counties

Title from PDF of title page (University of Missouri--Columbia, viewed on October 22, 2010).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Dissertation advisor: Dr. Kenneth E. Pigg.Vita.Ph. D. University of Missouri--Columbia 2010.[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Prosperity is often associated with income. This study goes beyond the economic determinant of prosperity and develops a prosperity index by using indicators of education, employment, housing occupancy, and poverty status for all contiguous U.S. counties and non-metro counties. A spatial approach has been used to analyze the data as the data was spatially distributed. Using OLS, spatial lag, and spatial error methods, three models were developed and compared. Spatial error model explained higher percent of variation among three models. Labor markets variables were found to be important predictors of prosperity in all-counties and non-metro counties. The results showed that high prosperous counties had higher economic opportunities, higher urban influence, higher social capital, lower income inequality, lower percent of minority population, higher percent of employed female population, higher civic agricultural activities, lower percent of people working in low paying service sectors, and more jobs in manufacturing sectors. A major contribution of this study to sociology is that spatial effect should be taken into consideration while dealing with spatially correlated data.Includes bibliographical reference

A minimum approximate-BER beamforming approach for PSK modulated wireless systems

A beamforming algorithm is introduced based on the general objective function that approximates the bit error rate for the wireless systems with binary phase shift keying and quadrature phase shift keying modulation schemes. The proposed minimum approximate bit error rate (ABER) beamforming approach does not rely on the Gaussian assumption of the channel noise. Therefore, this approach is also applicable when the channel noise is non-Gaussian. The simulation results show that the proposed minimum ABER solution improves the standard minimum mean squares error beamforming solution, in terms of a smaller achievable system's bit error rate

Amyloid-like fibril formation by polyQ proteins: a critical balance between the polyQ length and the constraints imposed by the host protein

Nine neurodegenerative disorders, called polyglutamine (polyQ) diseases, are characterized by the formation of intranuclear amyloid-like aggregates by nine proteins containing a polyQ tract above a threshold length. These insoluble aggregates and/or some of their soluble precursors are thought to play a role in the pathogenesis. The mechanism by which polyQ expansions trigger the aggregation of the relevant proteins remains, however, unclear. In this work, polyQ tracts of different lengths were inserted into a solvent-exposed loop of the β-lactamase BlaP and the effects of these insertions on the properties of BlaP were investigated by a range of biophysical techniques. The insertion of up to 79 glutamines does not modify the structure of BlaP; it does, however, significantly destabilize the enzyme. The extent of destabilization is largely independent of the polyQ length, allowing us to study independently the effects intrinsic to the polyQ length and those related to the structural integrity of BlaP on the aggregating properties of the chimeras. Only chimeras with 55Q and 79Q readily form amyloid-like fibrils; therefore, similarly to the proteins associated with diseases, there is a threshold number of glutamines above which the chimeras aggregate into amyloid-like fibrils. Most importantly, the chimera containing 79Q forms amyloid-like fibrils at the same rate whether BlaP is folded or not, whereas the 55Q chimera aggregates into amyloid-like fibrils only if BlaP is unfolded. The threshold value for amyloid-like fibril formation depends, therefore, on the structural integrity of the β-lactamase moiety and thus on the steric and/or conformational constraints applied to the polyQ tract. These constraints have, however, no significant effect on the propensity of the 79Q tract to trigger fibril formation. These results suggest that the influence of the protein context on the aggregating properties of polyQ disease-associated proteins could be negligible when the latter contain particularly long polyQ tracts

Multiple CFOs in OFDM-SDMA Uplink: Interference Analysis and Compensation

In OFDM-based space division multiple access (SDMA) systems, multiple users are served by a multiantenna base station simultaneously on the same frequency resources. In the uplink, each user's signal may be distorted by an independent carrier frequency offset (CFO), which impairs the orthogonality of the subcarrier signals and, if not properly compensated, results in performance degradations. We analyze the influence of multiusers' CFOs on the signal transmission in the OFDM-SDMA uplink and derive suitable bounds for the achievable signal-to-interference conditions. By modifying the signal model suitably, we develop a simple scheme for partial compensation of the CFO distortions. It allows to maintain the subcarrier-wise channel equalization and thus is well suited to be applied for a real-time system implementation. However, as CFOs impair the cyclic structure of the OFDM symbols, our scheme is not able to compensate for the entire distortion. The remaining interference is treated as additional noise, which limits the supported size of the CFOs