Lower-rim ferrocenyl substituted calixarenes: new electrochemical sensors for anions

New ferrocene substituted calix[4 and 5]arenes have been prepared and the crystal structure of a lower-rim substituted bis ferrocene calix[4]arene (7) has been elucidated. The respective ferrocene/ferrocenium redox-couples of compounds 6 (a calix[4]arene tetra ferrocene amide) and 8 (a calix[5]arene pentaferrocene amide) are shown to be significantly cathodically perturbed in the presence of anions by up to 160 mV in the presence of dihydrogen phosphate

An adaptive embedded mesh procedure for leading-edge vortex flows

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76634/1/AIAA-1989-80-667.pd

Uncertainty Quantification of Power Spectrum and Spectral Moments Estimates Subject to Missing Data

In this paper, the challenge of quantifying the uncertainty in stochastic process spectral estimates based on realizations with missing data is addressed. Specifically, relying on relatively relaxed assumptions for the missing data and on a kriging modeling scheme, utilizing fundamental concepts from probability theory, and resorting to a Fourier-based representation of stationary stochastic processes, a closed-form expression for the probability density function (PDF) of the power spectrum value corresponding to a specific frequency is derived. Next, the approach is extended for also determining the PDF of spectral moments estimates. Clearly, this is of significant importance to various reliability assessment methodologies that rely on knowledge of the system response spectral moments for evaluating its survival probability. Further, utilizing a Cholesky decomposition for the PDF-related integrals kept the computational cost at a minimal level. Several numerical examples are included and compared against pertinent Monte Carlo simulations for demonstrating the validity of the approach

Predicting Gene Expression from Sequence

AbstractWe describe a systematic genome-wide approach for learning the complex combinatorial code underlying gene expression. Our probabilistic approach identifies local DNA-sequence elements and the positional and combinatorial constraints that determine their context-dependent role in transcriptional regulation. The inferred regulatory rules correctly predict expression patterns for 73% of genes in Saccharomyces cerevisiae, utilizing microarray expression data and sequences in the 800 bp upstream of genes. Application to Caenorhabditis elegans identifies predictive regulatory elements and combinatorial rules that control the phased temporal expression of transcription factors, histones, and germline specific genes. Successful prediction requires diverse and complex rules utilizing AND, OR, and NOT logic, with significant constraints on motif strength, orientation, and relative position. This system generates a large number of mechanistic hypotheses for focused experimental validation, and establishes a predictive dynamical framework for understanding cellular behavior from genomic sequence

Artery tertiary lymphoid organs control multi-layered territorialized atherosclerosis B cell responses in aged ApoE-/- mice

Objective: Explore aorta B cell immunity in aged ApoE-/- mice. Approach and Results: Transcript maps, FACS, immunofluorescence analyses, cell transfers, and Ig-ELISPOT assays showed multi-layered atherosclerosis B cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B cell-related transcriptomes were identified and transcript atlases revealed highly territorialized B cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B cell genes including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm though intima plaques preferentially expressed molecules involved in non-B effector responses towards B cell-derived mediators, i.e. Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B cell recruitment. ATLO B-2 B cells included naïve, transitional, follicular, germinal center, switched IgG1+, IgA+, and IgE+ memory cells, plasmablasts, and long-lived plasma cells (PCs). ATLOs recruited large numbers of B-1 cells whose subtypes were skewed towards IL-10+ B-1b cells versus IL-10- B-1a cells. ATLO B-1 cells and PCs constitutively produced IgM and IgG and a fraction of PCs expressed IL-10. Moreover, ApoE-/- mice showed increased germinal center B cells in renal lymph nodes, IgM-producing PCs in the bone marrow, and higher IgM and anti-MDA-LDL IgG serum titers. Conclusions: ATLOs orchestrate dichotomic, territorialized, and multi-layered B cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging

QM/MM Simulations Reveal the Determinants of Carbapenemase Activity in Class A β-lactamases

[Image: see text] β-lactam antibiotic resistance in Gram-negative bacteria, primarily caused by β-lactamase enzymes that hydrolyze the β-lactam ring, has become a serious clinical problem. Carbapenems were formerly considered “last resort” antibiotics because they escaped breakdown by most β-lactamases, due to slow deacylation of the acyl-enzyme intermediate. However, an increasing number of Gram-negative bacteria now produce β-lactamases with carbapenemase activity: these efficiently hydrolyze the carbapenem β-lactam ring, severely limiting the treatment of some bacterial infections. Here, we use quantum mechanics/molecular mechanics (QM/MM) simulations of the deacylation reactions of acyl-enzyme complexes of eight β-lactamases of class A (the most widely distributed β-lactamase group) with the carbapenem meropenem to investigate differences between those inhibited by carbapenems (TEM-1, SHV-1, BlaC, and CTX-M-16) and those that hydrolyze them (SFC-1, KPC-2, NMC-A, and SME-1). QM/MM molecular dynamics simulations confirm the two enzyme groups to differ in the preferred acyl-enzyme orientation: carbapenem-inhibited enzymes favor hydrogen bonding of the carbapenem hydroxyethyl group to deacylating water (DW). QM/MM simulations of deacylation give activation free energies in good agreement with experimental hydrolysis rates, correctly distinguishing carbapenemases. For the carbapenem-inhibited enzymes, free energies for deacylation are significantly higher than for the carbapenemases, even when the hydroxyethyl group was restrained to prevent interaction with the DW. Analysis of these simulations, and additional simulations of mutant enzymes, shows how factors including the hydroxyethyl orientation, the active site volume, and architecture (conformations of Asn170 and Asn132; organization of the oxyanion hole; and the Cys69-Cys238 disulfide bond) collectively determine catalytic efficiency toward carbapenems

An Efficient Complex Modal Decomposition Method For Inelastic Stochastic Design Spectrum-Based Analysis

An efficient stochastic modal decomposition method for random vibration analysis of non-classically damped nonlinear multi-degree-of-freedom (MDOF) systems is proposed in accordance with contemporary aseismic code provisions (e.g., EC8). Specifically, relying on statistical linearization and state-variable formulation, the complex eigenvalue problem considering inelastic MDOF structural systems subject to stochastic seismic processes is formulated and solved. To this aim, equivalent linear modal properties (EMPs), i.e., natural frequencies and damping ratios, are appropriately defined and evaluated based on an iterative scheme involving the determination of the system response covariance matrix as well. Note that the stochastic excitations are characterized by power spectra compatible in a stochastic sense with a given elastic response uniform hazard spectrum (UHS) of specified modal damping ratio. Next, the system EMPs are utilized in conjunction with the response elastic UHS for determining peak nonlinear responses in modal coordinates. Further, modal participation factors are evaluated for the complex-valued mode shapes and the generalized complete-quadratic-combination (CQC) is employed as the modal combination rule for determining the peak total responses. The reliability of the proposed framework is assessed by considering a 3-storey nonlinear frame structure exposed to the Eurocode 8 elastic response spectrum. Nonlinear response time-history analysis (RHA) involving a large ensemble of Eurocode 8 spectrum compatible accelerograms is conducted to assess the accuracy of the proposed approach