A Garratt-Braverman cyclization route towards the synthesis of phenanthridine derivatives and their DNA-binding studies

Garratt-Braverman cyclization has been employed to synthesize a series of dihydroisofuran fused phenanthridine derivatives. The established protocol proposes a simpler synthetic alternative to have access to these therapeutically relevant cytotoxic scaffolds. Single crystal X-ray data unambiguously confirmed the structures of the synthesized phenanthridine derivatives. UV–Vis absorption titration with calf-thymus DNA followed by fluorescence-based competitive ethidium bromide displacement assay established the synthesized target compounds as potent DNA-intercalating agents with intrinsic binding constant of the range 10³-10⁵. Results obtained from the molecular docking further justified the spectroscopically obtained results.     

A Singular System with Precise Dosing and Spatiotemporal Control of CRISPR‐Cas9

Several genome engineering applications of CRISPR‐Cas9, an RNA‐guided DNA endonuclease, require precision control of Cas9 activity over dosage, timing, and targeted site in an organism. While some control of Cas9 activity over dose and time have been achieved using small molecules, and spatial control using light, no singular system with control over all the three attributes exists. Furthermore, the reported small‐molecule systems lack wide dynamic range, have background activity in the absence of the small‐molecule controller, and are not biologically inert, while the optogenetic systems require prolonged exposure to high‐intensity light. We previously reported a small‐molecule‐controlled Cas9 system with some dosage and temporal control. By photocaging this Cas9 activator to render it biologically inert and photoactivatable, and employing next‐generation protein engineering approaches, we have built a system with a wide dynamic range, low background, and fast photoactivation using a low‐intensity light while rendering the small‐molecule activator biologically inert. We anticipate these precision controls will propel the development of practical applications of Cas9.     

Scaling behavior in on‐chip field‐amplified sample stacking

Field amplified sample stacking (FASS) uses differential electrophoretic velocity of analyte ions in the high‐conductivity background electrolyte zone and low conductivity sample zone for increasing the analyte concentration. The stacking rate of analyte ions in FASS is limited by molecular diffusion and convective dispersion due to nonuniform electroosmotic flow (EOF). We present a theoretical scaling analysis of stacking dynamics in FASS and its validation with a large set of on‐chip sample stacking experiments and numerical simulations. Through scaling analysis, we have identified two stacking regimes that are relevant for on‐chip FASS, depending upon whether the broadening of the stacked peak is dominated by axial diffusion or convective dispersion. We show that these two regimes are characterized by distinct length and time scales, based on which we obtain simplified nondimensional relations for the temporal growth of peak concentration and width in FASS. We first verify the theoretical scaling behavior in diffusion‐ and convection‐dominated regimes using numerical simulations. Thereafter, we show that the experimental data of temporal growth of peak concentration and width at varying electric fields, conductivity gradients, and EOF exhibit the theoretically predicted scaling behavior. The scaling behavior described in this work provides insights into the effect of varying experimental parameters, such as electric field, conductivity gradient, electroosmotic mobility, and electrophoretic mobility of the analyte on the dynamics of on‐chip FASS.     

Consistency and variations in optical characteristics of four-layer polymeric waveguides

In the present work, four-layer polymeric waveguides have been fabricated and characterized by interchanging the film layer. Using polyvinyl alcohol (PVA) and styrene acrylonitrile (SAN) polymer it has been shown that polymers do not loose their own property in multilayer structure and better efficiency can be achieved in the form of low propagation losses and mode filtration. Due to high contrast of PVA and SAN films, a broad spectrum of refractive index in four-layer structure has been achieved.     

Evidence of primordial non-Gaussianity (fNL) in the Wilkinson microwave anisotropy probe 3-year data at 2.8sigma

We present evidence for primordial non-Gaussianity of the local type (fNL) in the temperature anisotropy of the cosmic microwave background. Analyzing the bispectrum of the Wilkinson Microwave Anisotropy Probe 3-year data up to lmax=750 we find 27相似文献   

Isometries of absolute order unit spaces

Positivity - We prove that a unital, bijective linear map between absolute order unit spaces is an isometry if and only if it is absolute value preserving. We deduce that, on (unital) JB-algebras,...     

Bistable characteristics of thick-walled axisymmetric domes

We apply a finite element analysis to examine the stability of spherical, thick-walled domes undergoing large deformation. We identify three energetic states, mono-stable, bi-stable, and pseudo-bi-stable that uniquely characterize the behavior of the dome during deformation. An empirical relation is developed using finite element simulations relating the stability of the dome to pertinent geometric parameters like height, length and thickness, which is verified experimentally. Using this relation, similar domes can be designed to have desired stability characteristics.     

C−C Bond Formation of Benzyl Alcohols and Alkynes Using a Catalytic Amount of KOtBu: Unusual Regioselectivity through a Radical Mechanism

We report a C?C bond‐forming reaction between benzyl alcohols and alkynes in the presence of a catalytic amount of KO^tBu to form α‐alkylated ketones in which the C=O group is located on the side derived from the alcohol. The reaction proceeds under thermal conditions (125 °C) and produces no waste, making the reaction highly atom efficient, environmentally benign, and sustainable. Based on our mechanistic investigations, we propose that the reaction proceeds through radical pathways.