Significant pKa perturbation of nucleobases is an intrinsic property of the sequence context in DNA and RNA

The pH titration and NMR studies (pH 6.6-12.5) in the heptameric isosequential ssDNA and ssRNA molecules, [d/r(5'-CAQ1GQ2AC-3', with variable Q1/Q2)], show that the pKa of the central G residue within the heptameric ssDNAs (DeltapKa = 0.67 +/- 0.03) and ssRNAs (DeltapKa = 0.49 +/- 0.02) is sequence-dependent. This variable pKa of the G clearly shows that its pseudoaromatic character, hence, its chemical reactivity, is strongly modulated and tuned by its sequence context. In contradistinction to the ssDNAs, the electrostatic transmission of the pKa of the G moiety to the neighboring A or C residues in the heptameric ssRNAs (as observed by the response of the aromatic marker protons of As or Cs) is found to be uniquely dependent upon the sequence composition. This demonstrates that the neighboring As or Cs in ssRNAs have variable electrostatic efficiency to interact with the central G/G-, which is owing to the variable pseudoaromatic characters (giving variable chemical reactivities) of the flanking As or Cs compared to those of the isosequential ssDNAs. The sequence-dependent variation of pKa of the central G and the modulation of its pKa transmission through the nearest-neighbors by variable electrostatic interaction is owing to the electronically coupled nature of the constituent nucleobases across the single strand, which demonstrates the unique chemical basis of the sequence context specificity of DNA or RNA in dictating the biological interaction, recognition, and function with any specific ligand.     

New propranolol analogues: binding and chiral discrimination by cellobiohydrolase Cel7A

Novel propranolol analogues have been designed and synthesised and their enantioselective binding to the cellulose degrading enzyme, Cel7A, has been evaluated. Affinity and enantioselectivity have been determined by capillary electrophoresis experiments. Ligands with significantly improved affinity and selectivity have been obtained and an analysis of the results has led to insights concerning the relation between the changes in ligand structure and selectivity as well as affinity to the protein.     

Compton scattering from the deuteron and extracted neutron polarizabilities

Differential cross sections for Compton scattering from the deuteron were measured at MAX-Lab for incident photon energies of 55 and 66 MeV at nominal laboratory angles of 45 degrees, 125 degrees, and 135 degrees. Tagged photons were scattered from liquid deuterium and detected in three NaI spectrometers. By comparing the data with theoretical calculations in the framework of a one-boson-exchange potential model, the sum and the difference of the isospin-averaged nucleon polarizabilities, alpha(N)+beta(N)=17.4+/-3.7 and alpha(N)-beta(N)=6.4+/-2.4 (in units of 10(-4) fm(3)), have been determined. By combining the latter with the global-averaged value for alpha(p)-beta(p) and using the predictions of the Baldin sum rule for the sum of the nucleon polarizabilities, we have obtained values for the neutron electric and magnetic polarizabilities of alpha(n)=8.8+/-2.4(total)+/-3.0(model) and beta(n)=6.5-/+2.4(total)-/+3.0(model), respectively.     

The association between whole body vibration exposure and musculoskeletal disorders in the Swedish work force is confounded by lifting and posture

This was a cross-sectional study based on material representing the Swedish work-force from a survey conducted in 1999, 2001 and 2003 by Statistics Sweden. Exposure to whole body vibration (WBV) was prevalent among agricultural, forestry, fishery workers and among plant and machinery operators based on a sample of 40,000 employed persons. Approximately 70% responders, that are 9798 persons answered both the interview and the questionnaire for the analysis of exposure-response. Exposure to WBV at least half the working time was associated with prevalence ratios above two for musculoskeletal symptoms in the low back, neck, shoulder/arm and hand among workers. When the exposure factors lifting and frequent bending were added to a multivariate analysis, surprisingly the magnitude of association was low between low back symptoms and WBV exposure. Interestingly, the relation between WBV exposure and symptoms in the neck, shoulder/arm and hand had the same or higher magnitude of association even when the possible confounders were in the model. For the neck, low back and shoulder/arm there was a visible increase in prevalence ratio (as high as 5 times) when combined exposures of WBV, lifting, frequent bending, twisted posture and noise were included in the analysis.     

Bilayer disk capillary electrophoresis: a novel method to study drug partitioning into membranes

CE in the presence of lipid bilayer disks was introduced as a new approach in membrane partitioning studies. The disks were used as a pseudostationary phase in the partial-filling mode of CE and the partitioning of cationic drugs was determined. The migration times of the analytes increased linearly with the lipid amount in the system. An appropriate algorithm for the calculation of a partition coefficient is presented. In the disk-shaped bilayers, which have excellent stability and shelf life, all of the lipids are readily available for interaction and the disks can be used as realistic cell membrane models.     

In vitro drug sensitivity-gene expression correlations involve a tissue of origin dependency

A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper shows that these discrepancies can be viewed as a weighting of drug-drug distances, the weights depending on which cell lines the two drugs differ in.     

Maximally stable Gaussian partitions with discrete applications

Gaussian noise stability results have recently played an important role in proving results in hardness of approximation in computer science and in the study of voting schemes in social choice. We prove a new Gaussian noise stability result generalizing an isoperimetric result by Borell on the heat kernel and derive as applications: