Temporally and spatially heterogeneous distribution of mTHPC in a murine tumor observed by two-color confocal fluorescence imaging and spectroscopy in a whole-mount model

Efficient intratumor delivery of anticancer drugs and photosensitizers is an important factor in the success of chemotherapy and photodynamic therapy, respectively. Unfortunately, their adequate and uniform intratumor distribution is impeded by several physiological barriers and by binding to tissue components. Measurement of gross tumor drug accumulation is a routine method of investigating the uptake and clearance of chemotherapy agents and photosensitizers but tells little about their extravascular spatial distribution. We use whole-mount two-color confocal fluorescence imaging and imaging spectroscopy of unprocessed excised murine tumor fragments to investigate the intratumor distribution of the photosensitizer meso-tetrahydroxyphenyl chlorin (mTHPC) as a function of distance from blood vessels perfused with 0.2 mum diameter fluorescent microspheres. Significant mismatches between drug and perfused vasculature are caused by heterogeneities in tumor blood supply. We describe complex microscopic mTHPC gradients that reverse dramatically relative to the perfused vasculature with time after injection. This imaging technique can be applied to screen the dynamic intratumor distribution of other fluorescent photosensitizers and anticancer drugs.     

An electrospray ionization mass spectrometry investigation of 1-anilino-8-naphthalene-sulfonate (ANS) binding to proteins

The binding of 1-anilino-8-naphthalene-sulfonic acid (ANS) to various globular proteins at acidic pH has been investigated by electrospray ionization mass spectrometry (ESI-MS). Maximal ANS binding is observed in the pH range 3-5. As many as seven species of dye-bound complexes are detected for myoglobin. Similar studies were carried out with cytochrome c, carbonic anhydrase, triosephosphate isomerase, lysozyme, alpha-lactalbumin, and bovine pancreatic trypsin inhibitor (BPTI). Strong ANS binding was observed wherever molten globule states were postulated in solution. ANS binding is not observed for lysozyme and BPTI, which have tightly folded structures in the native form. Alpha-lactalbumin, which is structurally related to lysozyme but forms a molten globule at acidic pH, exhibited ANS binding. Reduction of disulfide bonds in these proteins leads to the detection of ANS binding even at neutral pH. Binding was suppressed at very low pH (<2.5), presumably due to neutralization of the charge on the sulfonate moiety. The distribution of the relative intensities of the protein bound ANS species varies with the charge state, suggesting heterogeneity of gas phase conformations. The binding strength of these complexes was qualitatively estimated by dissociating them using enhanced nozzle skimmer potentials. The skimmer voltages also affected the lower and higher charge states of these complexes in a different manner.     

Non-adiabatic coupling and conical intersection(s) between potential energy surfaces for HeH2 +

By computing the non-adiabatic coupling terms and the adiabatic-to-diabatic transformation angle along closed contours in nuclear configuration space using the CASSCF method and the aug-cc-pVTZ basis set for the lowest three electronic states of HeH₂ ⁺, we explore the conical intersection between states in near collinear and noncollinear geometries, particularly in the C _2v geometry.     

Coupled-channels calculations of intermediate energy π−C inelastic scattering and charge exchange

Coupled-channels calculations have been carried out for pion inelastic scattering and charge exchange on 1p-shell nuclei at pion energies between 120 and 226 MeV. A momentum space technique is used, with the 1p-shell shell-model wavefunctions of Cohen and Kurath. Results are presented here for A=13. Channel-coupling effects are negligible in the strong 3/2^- and 5/2^- inelastic excitations of ¹³C, but enhance the analog charge-exchange cross sections by 7 to 20%.     

Fabrication of surfactant-free quercetin-loaded PLGA nanoparticles: evaluation of hepatoprotective efficacy by nuclear scintigraphy

Journal of Nanoparticle Research - This paper investigates the global nanotechnology and nanoscience (NN) indicators in a developmental context, during three 5-year periods from 2000 to 2014....     

Predictions of a natural SUSY dark matter model for direct and indirect detection experiments

Journal of High Energy Physics - Based on the analysis of 5 fb−1 of data at the LHC, the ATLAS and CMS collaborations have presented evidence for a Higgs boson with a mass in the 125 GeV...     

Bayesian Error Propagation for a Kinetic Model of n‐Propylbenzene Oxidation in a Shock Tube

We apply a Bayesian parameter estimation technique to a chemical kinetic mechanism for n‐propylbenzene oxidation in a shock tube to propagate errors in experimental data to errors in Arrhenius parameters and predicted species concentrations. We find that, to apply the methodology successfully, conventional optimization is required as a preliminary step. This is carried out in two stages: First, a quasi‐random global search using a Sobol low‐discrepancy sequence is conducted, followed by a local optimization by means of a hybrid gradient‐descent/Newton iteration method. The concentrations of 37 species at a variety of temperatures, pressures, and equivalence ratios are optimized against a total of 2378 experimental observations. We then apply the Bayesian methodology to study the influence of uncertainties in the experimental measurements on some of the Arrhenius parameters in the model as well as some of the predicted species concentrations. Markov chain Monte Carlo algorithms are employed to sample from the posterior probability densities, making use of polynomial surrogates of higher order fitted to the model responses. We conclude that the methodology provides a useful tool for the analysis of distributions of model parameters and responses, in particular their uncertainties and correlations. Limitations of the method are discussed. For example, we find that using second‐order response surfaces and assuming normal distributions for propagated errors is largely adequate, but not always.     

On a convolution series attached to a Siegel Hecke cusp form of degree 2

We prove that the “naive” convolution Dirichlet series $D_{2}(s)$ attached to a degree 2 Siegel Hecke cusp form $F$ , has a pole at $s=1$ . As an application, we write down the asymptotic formula for the partial sums of the squares of the eigenvalues of $F$ with an explicit error term. Further, as a corollary, we are able to show that the abscissa of absolute convergence of the (normalized) spinor-zeta function attached to $F$ is $s = 1$ .