Sparse Pseudospectral Approximation Method

Multivariate global polynomial approximations - such as polynomial chaos or stochastic collocation methods - are now in widespread use for sensitivity analysis and uncertainty quantification. The pseudospectral variety of these methods uses a numerical integration rule to approximate the Fourier-type coefficients of a truncated expansion in orthogonal polynomials. For problems in more than two or three dimensions, a sparse grid numerical integration rule offers accuracy with a smaller node set compared to tensor product approximation. However, when using a sparse rule to approximately integrate these coefficients, one often finds unacceptable errors in the coefficients associated with higher degree polynomials. By reexamining Smolyak's algorithm and exploiting the connections between interpolation and projection in tensor product spaces, we construct a sparse pseudospectral approximation method that accurately reproduces the coefficients of basis functions that naturally correspond to the sparse grid integration rule. The compelling numerical results show that this is the proper way to use sparse grid integration rules for pseudospectral approximation

Cysteinyl-tRNA Deacylation Can Be Uncoupled from Protein Synthesis

Aminoacyl-tRNA synthetases (ARSs) are critical components of protein translation, providing ribosomes with aminoacyl-tRNAs. In return, ribosomes release uncharged tRNAs as ARS substrates. Here, we show that tRNA deacylation can be uncoupled from protein synthesis in an amino acid specific manner. While tRNAs coupled to radiolabeled Met, Leu Lys, or Ser are stable in cells following translation inhibition with arsenite, radiolabeled Cys is released from tRNA at a high rate. We discuss possible translation independent functions for tRNACys

Non-invasive intravital imaging of cellular differentiation with a bright red-excitable fluorescent protein

A method for non-invasive visualization of genetically labelled cells in animal disease models with micron-level resolution would greatly facilitate development of cell-based therapies. Imaging of fluorescent proteins (FPs) using red excitation light in the “optical window” above 600 nm is one potential method for visualizing implanted cells. However, previous efforts to engineer FPs with peak excitation beyond 600 nm have resulted in undesirable reductions in brightness. Here we report three new red-excitable monomeric FPs obtained by structure-guided mutagenesis of mNeptune, previously the brightest monomeric FP when excited beyond 600 nm. Two of these, mNeptune2 and mNeptune2.5, demonstrate improved maturation and brighter fluorescence, while the third, mCardinal, has a red-shifted excitation spectrum without reduction in brightness. We show that mCardinal can be used to non-invasively and longitudinally visualize the differentiation of myoblasts and stem cells into myocytes in living mice with high anatomical detail

Gender Differences in Factors Associated with Adherence to Antiretroviral Therapy

OBJECTIVE: To identify gender differences in social and behavioral factors associated with antiretroviral adherence. DESIGN: Prospective cohort study. SETTING: Methadone maintenance program. PARTICIPANTS: One hundred thirteen HIV-seropositive current or former opioid users. MEASUREMENTS AND MAIN RESULTS: Participants were surveyed at baseline about social and behavioral characteristics and at monthly research visits about drug and alcohol use and medication side effects. Electronic monitors (MEMS) were used to measure antiretroviral adherence. Median adherence among women was 27% lower than among men (46% vs. 73%; P < .05). In gender-stratified multivariate models, factors associated with worse adherence in men included not belonging to an HIV support group (P < .0001), crack/cocaine use (P < .005), and medication side effects (P = .01). Among women, alcohol use (P = .005), heroin use (P < .05), and significant medication side effects (P < .005) were independently associated with worse adherence. In a model including both men and women, worse adherence was associated with lack of long-term housing (P < .005), not belonging to any HIV support groups (P < .0005), crack or cocaine use (P < .01), and medication side effects (P < .0005). In addition, worse adherence was associated with the interaction between female gender and alcohol use (P ≤ .05). CONCLUSIONS: In this cohort of current and former opioid users, gender-stratified analysis demonstrated that different social and behavioral factors are associated with adherence in men and women. Among both men and women, worse adherence was associated with lack of long-term housing, not belonging to an HIV support group, crack/cocaine use, and medication side effects. Among women only, alcohol use was associated with worse adherence