Dual mechanisms of HNO generation by a nitroxyl prodrug of the diazeniumdiolate (NONOate) class

Here we describe a novel caged form of the highly reactive bioeffector molecule, nitroxyl (HNO). Reacting the labile nitric oxide (NO)- and HNO-generating salt of structure iPrHN-N(O)═NO(-)Na(+) (1, IPA/NO) with BrCH(2)OAc produced a stable derivative of structure iPrHN-N(O)═NO-CH(2)OAc (2, AcOM-IPA/NO), which hydrolyzed an order of magnitude more slowly than 1 at pH 7.4 and 37 °C. Hydrolysis of 2 to generate HNO proceeded by at least two mechanisms. In the presence of esterase, straightforward dissociation to acetate, formaldehyde, and 1 was the dominant path. In the absence of enzyme, free 1 was not observed as an intermediate and the ratio of NO to HNO among the products approached zero. To account for this surprising result, we propose a mechanism in which base-induced removal of the N-H proton of 2 leads to acetyl group migration from oxygen to the neighboring nitrogen, followed by cleavage of the resulting rearrangement product to isopropanediazoate ion and the known HNO precursor, CH(3)-C(O)-NO. The trappable yield of HNO from 2 was significantly enhanced over 1 at physiological pH, in part because the slower rate of hydrolysis for 2 generated a correspondingly lower steady-state concentration of HNO, thus, minimizing self-consumption and enhancing trapping by biological targets such as metmyoglobin and glutathione. Consistent with the chemical trapping efficiency data, micromolar concentrations of prodrug 2 displayed significantly more potent sarcomere shortening effects relative to 1 on ventricular myocytes isolated from wild-type mouse hearts, suggesting that 2 may be a promising lead compound for the development of heart failure therapies.     

Discrete spectrum in a critical coupling case of Jacobi matrices with spectral phase transitions by uniform asymptotic analysis

For a two-parameter family of Jacobi matrices exhibiting first-order spectral phase transitions, we prove discreteness of the spectrum in the positive real axis when the parameters are in one of the transition boundaries. To this end, we develop a method for obtaining uniform asymptotics, with respect to the spectral parameter, of the generalized eigenvectors. Our technique can be applied to a wide range of Jacobi matrices.     

Decay Bounds on Eigenfunctions and the Singular Spectrum of Unbounded Jacobi Matrices

Bounds on the exponential decay of generalized eigenfunctionsof bounded and unbounded selfadjoint Jacobi matrices in are established. Two cases are considered separatelyand lead to different results: (i) the case in which the spectralparameter lies in a general gap of the spectrum of the Jacobimatrix and (ii) the case of a lower semibounded Jacobi matrixwith values of the spectral parameter below the spectrum. Itis demonstrated by examples that both results are sharp. Weapply these results to obtain a "many barriers-type" criterionfor the existence of square-summable generalized eigenfunctionsof an unbounded Jacobi matrix at almost every value of the spectralparameter in suitable open sets. In particular, this leads toexamples of unbounded Jacobi matrices with a spectral mobilityedge, i.e., a transition from purely absolutely continuous spectrumto dense pure point spectrum.     

Difluoroethylene as a chain transfer agent during ring-opening metathesis polymerization (ROMP) of norbornene by a ruthenium alkylidene complex: A computational study

The polynorbornene chain transfer reaction pathways to ethylene (2a), trans-1,2-difluoroethylene (2b) and trans-1,4-dichloro-2-butene (2c) by (1,3-diphenyl-4,5-dihydroimidazol-2-ylidene) (PCy₃)Cl₂RuCHPh (I) have been studied at B3LYP/LACVP^∗ level of theory. The calculations show that the free Gibbs activation energy of metathesis reaction is dependent on the volume of substituents directly linked to the double bond of an olefin. Highest activation energy is observed for 2c with highest molecular volume. The activation energy is lower for 2a with small molecular volume. Compared to 2a and 2c, fluorinated olefin 2b binds more strongly to the 14 electron Ru-alkylidene catalyst to form tighter transition state. Therefore, sterical factor is the most important contribution to the activation energy for Ru-alkylidene mediated olefin metathesis.     

Ruin probability in the presence of risky investments

We consider an insurance company in the case when the premium rate is a bounded non-negative random function _ct$c_t$ and the capital of the insurance company is invested in a risky asset whose price follows a geometric Brownian motion with mean return a   and volatility σ>0$\sigma >0$. If β?2a/σ²-1>0$\beta ?2a/{\sigma }^2-1>0$ we find exact the asymptotic upper and lower bounds for the ruin probability Ψ(u)$\Psi (u)$ as the initial endowment u   tends to infinity, i.e. we show that _C*u^-β?Ψ(u)?C^*u^-β$C_{*}{u}^{-\beta }?\Psi (u)?C^{*}{u}^{-\beta }$ for sufficiently large u  . Moreover if _ct=c^*e^γt$c_t=c^{*}{\mathrm{e}}^{\gamma t}$ with γ?0$\gamma ?0$ we find the exact asymptotics of the ruin probability, namely Ψ(u)∼u^-β$\Psi (u)\sim u^{-\beta }$. If β?0$\beta ?0$, we show that Ψ(u)=1$\Psi (u)=1$ for any u?0$u?0$.     

General model selection estimation of a periodic regression with a Gaussian noise

This paper considers the problem of estimating a periodic function in a continuous time regression model with an additive stationary Gaussian noise having unknown correlation function. A general model selection procedure on the basis of arbitrary projective estimates, which does not need the knowledge of the noise correlation function, is proposed. A non-asymptotic upper bound for L₂{\mathcal{L}_2} -risk (oracle inequality) has been derived under mild conditions on the noise. For the Ornstein–Uhlenbeck noise the risk upper bound is shown to be uniform in the nuisance parameter. In the case of Gaussian white noise the constructed procedure has some advantages as compared with the procedure based on the least squares estimates (LSE). The asymptotic minimaxity of the estimates has been proved. The proposed model selection scheme is extended also to the estimation problem based on the discrete data applicably to the situation when high frequency sampling can not be provided.     

Noncommutative Batalin–Vilkovisky geometry and matrix integrals

I study the new type of supersymmetric matrix models associated with any solution to the quantum master equation of the noncommutative Batalin–Vilkovisky geometry. The asymptotic expansion of the matrix integrals gives homology classes in the Kontsevich compactification of the moduli spaces, which I associated with the solutions to the quantum master equation in my previous paper. I associate with the Bernstein–Leites matrix superalgebra equipped with an odd differentiation, whose square is nonzero, the family of cohomology classes of the compactification. This family is the generating function for the products of the tautological classes. The simplest example of my matrix integrals in the case of dimension zero is a supersymmetric extension of the Kontsevich model of 2-dimensional gravity.     

Effect of oxygen deficiency on response of CR-39 on board scientific balloons

We should be careful about the effect of oxygen deficiency on polymeric track detectors even at balloon altitude. Results of balloon experiments and calibration experiments in a vacuum chamber at different pressures show that the effect of oxygen deficiency becomes serious at a pressure below 10 hPa.     

Power-Law Bounds on Transfer Matrices and Quantum Dynamics in One Dimension

 We present an approach to quantum dynamical lower bounds for discrete one-dimensional Schr?dinger operators which is based on power-law bounds on transfer matrices. It suffices to have such bounds for a nonempty set of energies. We apply this result to various models, including the Fibonacci Hamiltonian. Received: 5 June 2002 / Accepted: 20 January 2003 Published online: 28 March 2003 RID="⋆" ID="⋆" D.D. was supported in part by NSF Grant No. DMS–0227289 Communicated by M. Aizenman     

Failure of immunocompetitive capillary electrophoresis assay to detect disease-specific prion protein in buffy coat from humans and chimpanzees with Creutzfeldt-Jakob disease

The emergence of a new environmentally caused variant of Creutzfeldt-Jakob disease (vCJD), the result of food-born infection by the causative agent of bovine spongiform encephalopathy (BSE), has stimulated research on a practical diagnostic screening test. The immunocompetitive capillary electrophoresis (ICCE) assay has been reported to detect disease-specific, proteinase-resistant prion protein (PrPres) in the blood of scrapie-infected sheep. We have applied this method to blood from CJD-infected chimpanzees and humans. The threshold of detection achieved with our ICCE was 0.6 nM of synthetic peptide corresponding to the prion protein (PrP) C-terminus, and 2 nM of recombinant human PrP at the optimized conditions. However, the test was unable to distinguish between extracts of leucocytes from healthy and CJD-infected chimpanzees, and from healthy human donors and patients affected with various forms of CJD. Thus, the ICCE assay as presently performed is not suitable for use as a screening test in human transmissible spongiform encephalopathies (TSEs).