Vibriophage VcA-3 as an epidemic strain marker for the U.S. Gulf Coast Vibrio cholerae O1 clone.

Toxigenic and nontoxigenic Vibrio cholerae O1, El Tor biotype strains, which are endemic to the U.S. Gulf Coast, can be lysogenic for bacteriophage VcA-3. To evaluate the presence of VcA-3 as an indicator of toxigenicity and as an epidemic strain marker, phage production and the presence of phage and cholera toxin genes were assayed in 98 strains of V. cholerae O1 (35 U.S. and 63 foreign strains). By using a HindIII chromosomal digest for Southern blot analysis, 39 of the study strains hybridized with the VcA-3 probe in 10 banding patterns. The 15 toxigenic and 6 of the 20 nontoxigenic U.S. isolates gave four VcA-3-related patterns. Among the foreign isolates, 12 of 12 toxigenic classical biotype strains, 1 of 43 toxigenic El Tor biotype strains, and 3 of 8 nontoxigenic atypical strains gave six patterns that were clearly distinct from that of VcA-3. Compared with Southern blot analysis, the phage production assay had a sensitivity of 1.0 and a specificity of 0.48, while the colony hybridization assay had a sensitivity of 1.0 and a specificity of 0.77 for identification of VcA-3. Neither assay reliably identified the toxigenic Gulf Coast clone. The presence of VcA-3, as defined by Southern blot analysis, always separated toxigenic U.S. from foreign isolates and often from nontoxigenic U.S. isolates of V. cholerae O1

Analytical, Optimal, and Sparse Optimal Control of Traveling Wave Solutions to Reaction-Diffusion Systems

This work deals with the position control of selected patterns in reaction-diffusion systems. Exemplarily, the Schl\"{o}gl and FitzHugh-Nagumo model are discussed using three different approaches. First, an analytical solution is proposed. Second, the standard optimal control procedure is applied. The third approach extends standard optimal control to so-called sparse optimal control that results in very localized control signals and allows the analysis of second order optimality conditions.Comment: 22 pages, 3 figures, 2 table

PT-symmetric models in curved manifolds

We consider the Laplace-Beltrami operator in tubular neighbourhoods of curves on two-dimensional Riemannian manifolds, subject to non-Hermitian parity and time preserving boundary conditions. We are interested in the interplay between the geometry and spectrum. After introducing a suitable Hilbert space framework in the general situation, which enables us to realize the Laplace-Beltrami operator as an m-sectorial operator, we focus on solvable models defined on manifolds of constant curvature. In some situations, notably for non-Hermitian Robin-type boundary conditions, we are able to prove either the reality of the spectrum or the existence of complex conjugate pairs of eigenvalues, and establish similarity of the non-Hermitian m-sectorial operators to normal or self-adjoint operators. The study is illustrated by numerical computations.Comment: 37 pages, PDFLaTeX with 11 figure

Finite element approximation of sparse parabolic control problems

We study the finite element approximation of an optimal control problem governed by a semilinear partial differential equation and whose objective function includes a term promoting space sparsity of the solutions. We prove existence of solution in the absence of control bound constraints and provide the adequate second order sufficient conditions to obtain error estimates. Full discretization of the problem is carried out, and the sparsity properties of the discrete solutions, as well as error estimates, are obtained.The first two authors were partially supported by the Spanish Ministerio de Economía y Competitividad under project MTM2014-57531-P

Improved approximation rates for a parabolic control problem with an objective promoting directional sparsity

We discretize a directionally sparse parabolic control problem governed by a linear equation by means of control approximations that are piecewise constant in time and continuous piecewise linear in space. By discretizing the objective functional with the help of appropriate numerical quadrature formulas, we are able to show that the discrete optimal solution exhibits a directional sparse pattern alike the one enjoyed by the continuous solution. Error estimates are obtained and a comparison with the cases of having piecewise approximations of the control or a semilinear state equation are discussed. Numerical experiments that illustrate the theoretical results are included.The first two authors were partially supported by the Spanish Ministerio de Economía y Competitividad under projects MTM2014-57531-P and MTM2017-83185-P

Micro-pharmacokinetics: quantifying local drug concentration at live cell membranes

Fundamental equations for determining pharmacological parameters, such as the binding afnity of a ligand for its target receptor, assume a homogeneous distribution of ligand, with concentrations in the immediate vicinity of the receptor being the same as those in the bulk aqueous phase. It is, however, known that drugs are able to interact directly with the plasma membrane, potentially increasing local ligand concentrations around the receptor. We have previously reported an infuence of ligand-phospholipid interactions on ligand binding kinetics at the β2-adrenoceptor, which resulted in distinct “micro-pharmacokinetic” ligand profles. Here, we directly quantifed the local concentration of BODIPY630/650-PEG8-S-propranolol (BY-propranolol), a fuorescent derivative of the classical β-blocker propranolol, at various distances above membranes of single living cells using fuorescence correlation spectroscopy. We show for the frst time a signifcantly increased ligand concentration immediatel adjacent to the cell membrane compared to the bulk aqueous phase. We further show a clear role of both the cell membrane and the β2-adrenoceptor in determining high local BY-propranolol concentrations at the cell surface. These data suggest that the true binding afnity of BY-propranolol for the β2-adrenoceptor is likely far lower than previously reported and highlights the critical importance of understanding the “micro-pharmacokinetic” profles of ligands for membrane-associated proteins

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

Protein Diffusion in Mammalian Cell Cytoplasm

We introduce a new method for mesoscopic modeling of protein diffusion in an entire cell. This method is based on the construction of a three-dimensional digital model cell from confocal microscopy data. The model cell is segmented into the cytoplasm, nucleus, plasma membrane, and nuclear envelope, in which environment protein motion is modeled by fully numerical mesoscopic methods. Finer cellular structures that cannot be resolved with the imaging technique, which significantly affect protein motion, are accounted for in this method by assigning an effective, position-dependent porosity to the cell. This porosity can also be determined by confocal microscopy using the equilibrium distribution of a non-binding fluorescent protein. Distinction can now be made within this method between diffusion in the liquid phase of the cell (cytosol/nucleosol) and the cytoplasm/nucleoplasm. Here we applied the method to analyze fluorescence recovery after photobleach (FRAP) experiments in which the diffusion coefficient of a freely-diffusing model protein was determined for two different cell lines, and to explain the clear difference typically observed between conventional FRAP results and those of fluorescence correlation spectroscopy (FCS). A large difference was found in the FRAP experiments between diffusion in the cytoplasm/nucleoplasm and in the cytosol/nucleosol, for all of which the diffusion coefficients were determined. The cytosol results were found to be in very good agreement with those by FCS