Conformational Dynamics Underlies Different Functions of Human KDM7 Histone Demethylases

The human KDM7 subfamily histone H3 Nϵ-methyl lysine demethylases PHF8 (KDM7B) and KIAA1718 (KDM7A) have different substrate selectivities and are linked to genetic diseases and cancer. We describe experimentally based computational studies revealing that flexibility of the region linking the PHD finger and JmjC domains in PHF8 and KIAA1718 regulates interdomain interactions, the nature of correlated motions, and ultimately H3 binding and demethylation site selectivity. F279S an X-linked mental retardation mutation in PHF8 is involved in correlated motions with the iron ligands and second sphere residues. The calculations reveal key roles of a flexible protein environment in productive formation of enzyme-substrate complexes and suggest targeting the flexible KDM7 linker region is of interest from a medicinal chemistry perspective.     

On mechanical waves and Doppler shifts from moving boundaries

We investigate the propagation of infinitesimal harmonic mechanical waves emitted from a boundary with variable velocity and arriving at a stationary observer. In the classical Doppler effect, X_s(t)=vt is the location of the source with constant velocity v. In the present work, however, we consider a source co‐located with a moving boundary x=X_s(t), where X_s(t) can have an arbitrary functional form. For ‘slowly moving’ boundaries (i.e., ones for which the timescale set by the mechanical motion is large in comparison to the inverse of the frequency of the emitted wave), we present a multiple‐scale asymptotic analysis of the moving boundary problem for the linear wave equation. We obtain a closed‐form leading‐order (with respect to the latter small parameter) solution and show that the variable velocity of the boundary results not only in frequency modulation but also in amplitude modulation of the received signal. Consequently, our results extend the applicability of two basic tenets of the theory of a moving source on a stationary domain, specifically that (i) for non‐uniform boundary motion can be inserted in place of the constant velocity v in the classical Doppler formula and (ii) that the non‐uniform boundary motion introduces variability in the amplitude of the wave. The specific examples of decelerating and oscillatory boundary motion are worked out and illustrated. Copyright © 2017 John Wiley & Sons, Ltd.     

Shock and traveling wave phenomena on an externally damped, non-linear string

We examine the propagation of shocks and traveling wave phenomena on a one-dimensional string that is executing finite-amplitude, transverse vibrations in a resisting medium. As part of our study, we develop an approach that allows us to describe, albeit approximately, the evolution and propagation of a shock front using analytical methods. In addition, exact traveling wave solutions, one of which involves the Lambert W-function, of the string's equation of motion are determined and analyzed. Lastly, a possible new form of the solution to the linearized problem is presented and extensions and other applications of the present work are briefly discussed.     

2,5-Dihydro-1,2-oxaphosphole Derivatives in the Reaction of 3,3-Disubstituted Allenylphosphonic Amidoesters with Electrophilic Reagents

Abstract

The reaction of 3,3-disubstituted allenylphosphonic amidoesters with halogenes, sulfenyl and selenenylchlorides proceeds with five-membered heterocyclization and formation of 2-N,N-dialkylamino-2,5-dihydro-1,2-oxaphosphole 2-oxides:     

RNA Cleavage Catalyzed by Amphoteric Bis(acyl)guanidinium Derivatives

Described herein are two series (twelve compounds each) of very closely related guanidinium‐based receptors and their ability to catalyze hydrolytic cleavage of a unique RNA substrate – oligo‐dT flanked t rans‐ A ctivation R esponsive region of the HIV‐1 mRNA, TAR RNA. The significant difference in activities of otherwise very similar compounds is discussed, and direct and indirect evidences supporting our interpretation are presented. The results indicate that improvements in catalytic efficiency could be achieved with little modification of the structure of a relatively weak catalyst, and that a crucial feature could be a finely calibrated interplay between anion‐binding and proton‐donating abilities.     

Fast Legendre spectral method for computing the perturbation of a gradient temperature field in an unbounded region due to the presence of two spheres

The temperature distribution around two spheres is considered when the main field has a constant gradient at infinity. Bispherical coordinates are used, together with a transformation of the dependent variable that leads to separation of variables. Then the solution can be sought in Legendre series with respect to one of the bispherical coordinates. An important element of the proposed work is the effective way to reduce an essentially 3D problem to a set of three 2D problems. The Legendre spectral method is shown to have an exponential convergence which is confirmed by the computations. The efficiency is so high that even for the hard cases of two closely situated spheres, an accuracy of 10^?10 is achieved with as few as 20 terms in the expansion. Solutions with both longitudinal and transverse gradients at infinity are obtained, and the contour lines of the temperature field are presented graphically. © 2009 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2010     

On the inverse scattering approach and action-angle variables for the Dullin-Gottwald-Holm equation

The Poisson brackets for the scattering data of the Dullin-Gottwald-Holm equation are computed. Then, the action-angle variables are expressed in terms of the scattering data. We also discuss on the inverse scattering problem for this equation.     

Oxidative-Rearrangement Reactions of σ3, λ3 Dialkyl(Silylamino)Phosphines with Chlorophosphines; Formation of a P–P Bond Via a New Road to Phosphinophosphoranimines

Abstract:

Chlorophosphines react with trivalent (silylamino)phosphines via a direct oxidative addition process with elimination of trimethyl silyl chloride to produce phosphino-phosphoranimines with concomitant formation of a P-P bond. Oxidation of the phosphine center with sulfur and an exchange transformation of the phosphine are discussed.     

Potassium Fluoride Promoted Reaction of 3-Acylsubsti-Tuted 2H-1-Benzopyran-2-Ones with Acid Anhydrides. An Improved Method for the Synthesis of 4-(2-Oxoalkyl)-2H-Chroman-2-Ones. Part III1

The reaction of 3-acylsubstituted 2H-1-benzo-pyran-2-ones 1, 5 and 11a-c with acid anhydrides in the presence of potassium fluoride (KF)/molecular sieves 4A gives the 4-(2-oxoalkyl)-2-oxochromans 2, 6 and 12a-c as the main products. Also the 3-carboxylic acid derivatives, such as esters and N,N-dialkylamides, of 2H-1-benzopyran-2-one (11d-g) react with isobutyric acid anhydride in the presence of KF/molecular sieves 4A to give the corresponding 2-oxochroman-4-acetic acid derivatives.