Pharmacokinetic Characterization of the DDAH1 Inhibitors ZST316 and ZST152 in Mice Using a HPLC-MS/MS Method

The pharmacokinetic profile of ZST316 and ZST152, arginine analogues with inhibitory activity towards human dimethylarginine dimethylaminohydrolase-1 (DDAH1), was investigated in mice using a newly developed HPLC-MS/MS method. The method proved to be reproducible, precise, and accurate for the measurement of the compounds in plasma and urine. Four-week-old female FVB mice received a single dose of ZST316 and ZST152 by intravenous bolus (30 mg/Kg) and oral gavage (60 mg/Kg). ZST316 Cmax was 67.4 µg/mL (intravenous) and 1.02 µg/mL (oral), with a half-life of 6 h and bioavailability of 4.7%. ZST152 Cmax was 24.9 µg/mL (intravenous) and 1.65 µg/mL (oral), with a half-life of 1.2 h and bioavailability of 33.3%. Urinary excretion of ZST152 and ZST316 was 12.5%–22.2% and 2.3%–7.5%, respectively. At least eight urinary metabolites were identified. After chronic intraperitoneal treatment with the more potent DDAH1 inhibitor, ZST316 (30 mg/Kg/day for three weeks), the bioavailability was 59% and no accumulation was observed. Treatment was well tolerated with no changes in body weight vs. untreated animals and no clinical signs of toxicity or distress. The results of this study show that ZST316 has a favorable pharmacokinetic profile, following intraperitoneal administration, to investigate the effects of DDAH1 inhibition in mice.     

Wigner��s ��Polanyian�� Epistemology and the Measurement Problem: The Wigner�CPolanyi Dialog on Tacit Knowledge

I analyze the long dialog that Eugene Wigner (1902-1995) and Michael Polanyi (1891–1976) carried out on Polanyi’s concept of tacit knowledge and its meaning for the measurement problem in quantum physics, focusing in particular on their ten-year correspondence between 1961 and 1971 on these subjects and the related mind-body problem. They differed in their interpretations, epistemologies, and ontologies, and consequently never resolved their differences on the measurement and mind-body problems. Nonetheless, their long dialog is significant and opens up avenues for exploring these problems further.     

Linear screening effects on large bipolarons

Summary The screening effects of the formation of large bipolarons have been studied. It is shown that the dependence of the bipolaron binding energy on the electron density does not change qualitatively by using different dielectric functions for describing electron screening. The same result is found if the electron system is described as a bipolaron gas (charged bosons).     

Polaronic and nonadiabatic phase diagram from anomalous isotope effects

Isotope effects (IEs) are powerful tools to probe directly the dependence of many physical properties on lattice dynamics. In this Letter we investigate the onset of anomalous IEs in the spinless Holstein model by employing the dynamical mean field theory. We show that the isotope coefficients of the electron effective mass and of the dressed phonon frequency are sizable also far away from the polaronic crossover and mark the importance of nonadiabatic lattice fluctuations. We draw a nonadiabatic phase diagram in which we identify a novel crossover, not related to polaronic features, where the IEs attain their largest anomalies.     

Cladding mode reorganization in high-refractive-index-coated long-period gratings: effects on the refractive-index sensitivity

We theoretically and experimentally investigated the reorganization of cladding modes in high-refractive-index- (HRI-) coated long-period gratings (LPGs), focusing on the influence of refractive-index sensitivity. When azimuthally symmetric nanoscale HRI coatings are deposited along LPG devices, a significant modification of the distribution of cladding modes occurs, depending on the layers' features (refractive index and thickness) and on the external refractive index. In particular, if these parameters are properly chosen, a transition between cladding modes and overlay modes occurs. Numerical and experimental effects of the mode transition on the sensitivity of the surrounding refractive index are described.     

Strongly correlated superconductivity and pseudogap phase near a multiband Mott insulator

Near a Mott transition, strong electron correlations may enhance Cooper pairing. This is demonstrated in the dynamical mean field theory solution of a twofold-orbital degenerate Hubbard model with an inverted on-site Hund rule exchange, favoring local spin-singlet configurations. Close to the Mott insulator (which here is a local version of a valence bond insulator) a pseudogap non-Fermi-liquid metal, a superconductor, and a normal metal appear, in striking similarity with the physics of cuprates. The strongly correlated s-wave superconducting state has a larger Drude weight than the corresponding normal state. The role of the impurity Kondo problem is underscored.     

The t#-property for integral domains

Generalizing work of Gilmer and Heinzer, we define a t#-domain to be a domain R in which for any two distinct subsets and of the set of maximal t-ideals of R. We provide characterizations of these domains, and we show that polynomial rings over t#-domains are again t#-domains. Finally, we study overrings of t#-domains.     

Microfluidic sensor based on integrated optical hollow waveguides

A simple integrated optical refractometric sensor based on hollow-core antiresonant reflecting optical waveguides is proposed. The sensor uses the antiresonant reflecting guidance mechanism and permits one to measure the refractive index of a liquid filling the core by simply monitoring the transmitted spectrum. The device has been made with standard silicon technology, and the experimental results confirm numerical simulations performed in one- and two-dimensional geometry. The sensor exhibits a linear response over a wide measurement range (1.3330-1.4450) and a resolution of 9 x 10(-4) and requires a small analyte volume.     

Catalytic activity of myoglobin immobilized on zirconium phosphonates

The adsorption and catalytic activity of myoglobin (Mb) on zirconium phosphonates (a-zirconium benzenephosphonate (alpha-ZrBP), a-zirconium carboxyethanephosphonate (alpha-ZrCEP), and a novel layered zirconium fluoride aminooctyl-N,N-bis(methylphosphonate) (ZrC8)) were investigated. The maximum adsorption was reached after 16 h of contact and was greater on hydrophobic supports such as alpha-ZrBP and ZrC8 compared to hydrophilic supports such as alpha-ZrCEP. The equilibrium adsorption isotherms fitted the Langmuir equation, suggesting the presence of a monolayer of protein molecules on the support surfaces. The catalytic activities of free Mb and of the obtained biocomposites were studied in terms of the oxidation of two aromatic substrates, o-phenylenediamine and 2-methoxyphenol (guaiacol), by hydrogen peroxide. The oxidation catalyzed by immobilized myoglobin followed the Michaelis-Menten kinetics, similar to oxidation by free Mb. The kinetic parameters, kcat and KM, were significantly affected by the adsorption process. Mb/alpha-ZrCEP was the most efficient biocatalyst obtained, probably because of the hydrophilic nature of the support. The effect of immobilization on the stability of Mb toward inactivation by hydrogen peroxide was also investigated, and an increased resistance was found. The biocomposites obtained can be stored at 4 degrees C for months without a significant loss of catalytic activity.