Solving an Inverse First-Passage-Time Problem for Wiener Process Subject to Random Jumps from a Boundary

We study an inverse first-passage-time problem for Wiener process X(t) subject to random jumps from a boundary c. Let be given a threshold S > X(0); and a distribution function F on [0, + ∞). The problem consists of finding the distribution of the jumps which occur when X(t) hits c, so that the first-passage time of X(t) through S has distribution F.     

Multivariable passive RFID vapor sensors: roll-to-roll fabrication on a flexible substrate

We demonstrate roll-to-roll (R2R) fabrication of highly selective, battery-free radio frequency identification (RFID) sensors on a flexible polyethylene terephthalate (PET) polymeric substrate. Selectivity of our developed RFID sensors is provided by measurements of their resonance impedance spectra, followed by the multivariate analysis of spectral features, and correlation of these spectral features to the concentrations of vapors of interest. The multivariate analysis of spectral features also provides the ability for the rejection of ambient interferences. As a demonstration of our R2R fabrication process, we employed polyetherurethane (PEUT) as a "classic" sensing material, extruded this sensing material as 25, 75, and 125-μm thick films, and thermally laminated the films onto RFID inlays, rapidly producing approximately 5000 vapor sensors. We further tested these RFID vapor sensors for their response selectivity toward several model vapors such as toluene, acetone, and ethanol as well as water vapor as an abundant interferent. Our RFID sensing concept features 16-bit resolution provided by the sensor reader, granting a highly desired independence from costly proprietary RFID memory chips with a low-resolution analog input. Future steps are being planned for field-testing of these sensors in numerous conditions.     

Insights on cytochrome p450 enzymes and inhibitors obtained through QSAR studies

The cytochrome P450 (CYP) superfamily of heme enzymes play an important role in the metabolism of a large number of endogenous and exogenous compounds, including most of the drugs currently on the market. Inhibitors of CYP enzymes have important roles in the treatment of several disease conditions such as numerous cancers and fungal infections in addition to their critical role in drug-drug interactions. Structure activity relationships (SAR), and three-dimensional quantitative structure activity relationships (3D-QSAR) represent important tools in understanding the interactions of the inhibitors with the active sites of the CYP enzymes. A comprehensive account of the QSAR studies on the major human CYPs 1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and a few other CYPs are detailed in this review which will provide us with an insight into the individual/common characteristics of the active sites of these enzymes and the enzyme-inhibitor interactions.     

N,N'-dimethyl-N,N'-diarylurea anion radicals: an intramolecular reductive elimination

The one-electron reduction of tertiary N,N'-dimethyl-N,N'-diarylureas (aryl = phenyl, beta-naphthyl, alpha-naphthyl), in HMPA, results in anion radicals that undergo novel intramolecular reductive elimination reactions leading to the formation of the anion radicals of the corresponding biaryls. These results are due to face to face pi-pi stacking interactions involving the two aromatic rings in the urea systems. The overlapping p(pi)() orbitals on the ipso carbons of opposing aryl groups evolve into a sigma bond leading to the formation of the biaryl anion radical. In the case of the N,N'-dimethyl-N,N'-di-2-pyrenylurea system, there is a node in the LUMO of the number 2 carbon, and the parent anion radical remains intact.     

Synthesis of gold(I) fluoroalkyl and fluoroalkenyl-substituted phosphine complexes and factors affecting their crystal packing

A series of gold(I) phosphine complexes of the type [AuCl{PR(2)(R(f))}] (R = Et, i-Pr, Cy; R(f) = CF = CF(2); R = Ph, R(f) = C = CFH, CCl = CF(2), C ≡ CCF(3), CF(3), i-C(3)F(7), s-C(4)F(9)) have been prepared and most have been structurally characterised. All of the complexes are monomeric in the solid state, and a number of secondary interactions are observed--including short intramolecular AuF distances, metal-bound Au-ClH non-classical hydrogen bonds, fluorous domains and phenyl embraces. Only in the case of [AuCl{PEt(2)(CF = CF(2))}] is an aurophilic interaction with an AuAu contact less than the sum of the van der Waals radii observed. Even then, the distance, 3.3458(10) ?, is longer than that previously observed for the related complex with R = Ph; R(f) = CF = CF(2).     

A study of benzobisoxazole and benzobisthiazole compounds and polymers under hydrolytic conditions

The stability of benzobisoxazole and benzobisthiazole compounds and polymers under hydrolytic conditions was studied. 2,6-Bis(4-tert-butylphenyl)benzo[1,2-d;4,5-d′]bisoxazole (1) dissolved in acetonitrile containing sulfuric acid and water at 80°C is stable. A suspension of 2,6-bis[4-(2-benzoxazoyl)phenyl]benzo[1,2-d;5,4-d′]bisoxazole (2) in 0.2 N H₂SO₄ or 0.2 N NaOH solution at 100°C for 21 days is stable. The intrinsic viscosity of a poly(p-phenylene)benzobisoxazole (PBO) fiber sample soaked in 0.2 N H₂SO₄, water with 1 wt % polyphosphoric acid (PPA), or 0.2 N NaOH remained the same. Under very severe hydrolytic conditions such as dissolution of compound 2 or PBO in PPA or methanesulfonic acid with residual water followed by coagulation in water, benzobisoxazole underwent bond cleavage to generate carboxylic acid and o-aminophenol functional groups. This is in contrast to an earlier hypothesis that the decrease in intrinsic viscosity under these conditions was due to chain association. Poly(p-phenylene)benzobisthiazole (PBT) also underwent bond cleavage under these very severe conditions, which are unlikely to be encountered in normal applications. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2637–2643, 1999     

Itaconic acid is a mammalian metabolite induced during macrophage activation

Itaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and (13)C-labeling, we have detected ITA in both macrophage-like VM-M3 and RAW 264.7 tumor cell lines as well as stimulated and unstimulated primary murine macrophages. Macrophage activation by addition of lipopolysaccharide and IFN-γ markedly increased ITA production and secretion. Crude cell extracts synthesize ITA via decarboxylation of cis-aconitate, indicative of a novel mammalian cis-aconitic decarboxylase activity. Our results highlight a previously unidentified biosynthetic pathway related to TCA cycle metabolism in mammalian cells and a novel metabolite that likely plays a role in macrophage-based immune response.     

A Potent,Selective and Cell‐Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3)

PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is essential for maturation of ribosomes, may have a role in lipogenesis, and is implicated in several diseases. A potent, selective, and cell‐active PRMT3 inhibitor would be a valuable tool for further investigating PRMT3 biology. Here we report the discovery of the first PRMT3 chemical probe, SGC707, by structure‐based optimization of the allosteric PRMT3 inhibitors we reported previously, and thorough characterization of this probe in biochemical, biophysical, and cellular assays. SGC707 is a potent PRMT3 inhibitor (IC₅₀=31±2 nM , K_D=53±2 nM ) with outstanding selectivity (selective against 31 other methyltransferases and more than 250 non‐epigenetic targets). The mechanism of action studies and crystal structure of the PRMT3‐SGC707 complex confirm the allosteric inhibition mode. Importantly, SGC707 engages PRMT3 and potently inhibits its methyltransferase activity in cells. It is also bioavailable and suitable for animal studies. This well‐characterized chemical probe is an excellent tool to further study the role of PRMT3 in health and disease.