In vitro evolution of ligands to the membrane protein caveolin

Membrane proteins comprise a third of the human genome, yet present challenging targets for reverse chemical genetics. For example, although implicated in numerous diseases including multiple myeloma, the membrane protein caveolin-1 appears to offer a poor target for the discovery of synthetic ligands due to its largely unknown structure and insolubility. To break this impasse and identify new classes of caveolae controlling lead compounds, we applied phage-based, reverse chemical genetics for the discovery of caveolin-1 ligands derived from the anti-HIV therapeutic T20. Substitution of homologous residues into the T20 sequence used a process analogous to medicinal chemistry for the affinity maturation to bind caveolin. The resultant caveolin-1 ligands bound with >1000-fold higher affinity than wild-type T20. Two types of ELISAs and isothermal titration calorimetry (ITC) measurements demonstrated high affinity binding to caveolin by the T20 variants with K(d) values in the 150 nM range. Microscopy experiments with the highest affinity caveolin ligands confirmed colocalization of the ligands with endogenous caveolin in NIH 3T3 cells. The results establish the foundation for targeting caveolin and caveolae formation in living cells.     

An estimation of fracture stress in a brittle solid

The present paper reports for the first time an exact analytic expression that can be used for obtaining fracture stress σ_F, when fracture occurs in the elastic limit and also when fracture occurs after general yield (σ_F > σ_Y) in a brittle solid. The present paper may provide a new basis to fracture-safe design of brittle materials.     

Effect of grinding on the low temperature photoluminescence of certain inorganic crystals

The broadening as well as shift in the photoluminescence spectra of K₂[Pt(CN)₄] · 3 H₂O, Ba[Pt(CN)₄] · 4 H₂O, CdS:Te and Ru(C₁₅H₁₁N₃)₂I₂ · H₂O crystals take place with their grinding. The original vibronic peaks at 632 and 628 nm of CdS:Te and Ru(C₁₅H₁₁N₃)₂I₂ · H₂O crystals, respectively, disappear with the grinding. A new vibronic peak at 650 nm appears with grinding of Ru(C₁₅H₁₁N₃)₂I₂ · H₂O crystals. It is concluded that the change in the photoluminescence spectra is attributed to the creation of dislocations during the process of grinding.     

Ni(II)/Zn-Mediated chemoselective arylation of aromatic aldehydes: facile synthesis of diaryl carbinols

Direct arylation of aromatic aldehydes with aryl bromides in the presence of Ni(II)/Zn was investigated. The choice of ligand in this nickel-catalyzed coupling was critical to the formation of the secondary alcohols. Monodentate phosphine ligands were ineffective, whereas NiBr(2)(dppe)/Zn successfully catalyzed this reductive coupling reaction. The reaction conditions were mild and diarylcarbinols with a variety of functional groups such as ketone, ester, amide, and nitrile groups were readily prepared.     

Synthesis of 3-Substituted Pyrazole Derivatives by Mixed Anhydride Method and Study of Their Antibacterial Activities

A convenient synthesis of 3-substituted pyrazole derivatives by a mixed anhydride method using i-butylchloroformate and N-methylmorpholine at ?20 °C in tetrahydrofuran and study of in vitro antibacterial activities of the prepared compounds against Staphylococcus epidermidis, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus valguris by agar-diffusion method were carried out. The results suggested that the products 4a, 4b, and 4c exhibited moderate to feeble inhibition against all test bacteria at greater concentration but 4d was best against Staphylococcus epidermidis (22 mm) and worst against Pseudomonas aeruginosa (16 mm) at the greatest concentration (2.5 mg/ml), and the activities decreased with decrease in concentration.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Level density of a bose gas and extreme value statistics

We establish a connection between the level density of a gas of noninteracting bosons and the theory of extreme value statistics. Depending on the exponent that characterizes the growth of the underlying single-particle spectrum, we show that at a given excitation energy the limiting distribution function for the number of excited particles follows the three universal distribution laws of extreme value statistics, namely, the Gumbel, Weibull, and Fréchet distributions. Implications of this result, as well as general properties of the level density at different energies, are discussed.     

Ro-vibrational spectroscopy of molecules represented by a Tietz–Hua oscillator potential

Accurate low and high-lying bound states of Tietz–Hua oscillator potential are presented. The radial Schrödinger equation is solved efficiently by means of the generalized pseudospectral method that enables optimal spatial discreti zation. Both $\ell =0$ and rotational states are considered. Ro-vibrational levels of six diatomic molecules viz., H $_2$ , HF, N $_2$ , NO, O $_2$ , O $_2^+$ are obtained with good accuracy. Most of the states are reported here for the first time. A detailed analysis of variation of eigenvalues with $n, \ell $ quantum numbers is made. Results are compared with literature data, wherever possible. These are also briefly contrasted with the Morse potential results.     

Extreme statistics of complex random and quantum chaotic states

Complex random states have the statistical properties of the Gaussian and circular unitary ensemble eigenstates of random matrix theory. Even though their components are correlated by the normalization constraint, it is nevertheless possible to derive compact analytic formulas for their extreme values' statistical properties for all dimensionalities. The maximum intensity result slowly approaches the Gumbel distribution even though the variables are bounded, whereas the minimum intensity result rapidly approaches the Weibull distribution. Since random matrix theory is conjectured to be applicable to chaotic quantum systems, we calculate the extreme eigenfunction statistics for the standard map with parameters at which its classical map is fully chaotic. The statistical behaviors are consistent with the finite-N formulas.     

Zero Expectile Processes and Bayesian Spatial Regression

We introduce new classes of stationary spatial processes with asymmetric, sub-Gaussian marginal distributions using the idea of expectiles. We derive theoretical properties of the proposed processes. Moreover, we use the proposed spatial processes to formulate a spatial regression model for point-referenced data where the spatially correlated errors have skewed marginal distribution. We introduce a Bayesian computational procedure for model fitting and inference for this class of spatial regression models. We compare the performance of the proposed method with the traditional Gaussian process-based spatial regression through simulation studies and by applying it to a dataset on air pollution in California.