Ligand Binding to Dynamically Populated G-Quadruplex DNA

Several small-molecule ligands specifically bind and stabilize G-quadruplex (G4) nucleic acid structures, which are considered to be promising therapeutic targets. G4s are polymorphic structures of varying stability, and their formation is dynamic. Here, we investigate the mechanisms of ligand binding to dynamically populated human telomere G4 DNA by using the bisquinolinium based ligand Phen-DC3 and a combination of single-molecule FRET microscopy, ensemble FRET and CD spectroscopies. Different cations are used to tune G4 polymorphism and folding dynamics. We find that ligand binding occurs to pre-folded G4 structures and that Phen-DC3 also induces G4 formation in unfolded single strands. Following ligand binding to dynamically populated G4s, the DNA undergoes pronounced conformational redistributions that do not involve direct ligand-induced G4 conformational interconversion. On the contrary, the redistribution is driven by ligand-induced G4 folding and trapping of dynamically populated short-lived conformation states. Thus, ligand-induced stabilization does not necessarily require the initial presence of stably folded G4s.     

Fluorescent Amino Acid Initiated de novo Cyclic Peptides for the Label-Free Assessment of Cell Permeability**

The major obstacle in applying peptides to intracellular targets is their low inherent cell permeability. Standard approaches to attach a fluorophore (e. g. FITC, TAMRA) can change the physicochemical properties of the parent peptide and influence their ability to penetrate and localize in cells. We report a label-free strategy for evaluating the cell permeability of cyclic peptide leads. Fluorescent tryptophan analogues 4-cyanotryptophan (4CNW) and β-(1-azulenyl)-L-alanine (AzAla) were incorporated into in vitro translated macrocyclic peptides by initiator reprogramming. We then demonstrate these efficient blue fluorescent emitters are good tools for monitoring peptide penetration into cells.     

Optimization of Mixing and Mass Transfer in In-line Multi-Jet Ozone Contactors Using Computational Fluid Dynamics

Typical ozone mixing and mass transfer calculations are lumped approaches based on ideal operating conditions and can misrepresent behavior in real-life installations. This article models the effect of local hydrodynamics and mixing on the overall mass transfer of ozone into water with the aid of multiphase computational fluid dynamics (CFD). CFD models were validated with measured data from a pipeline ozone contactor installation which was optimized for more rapid, uniform mixing and mass transfer. Results emphasize the sensitivity of mixing quality to nozzle placement, size, orientation and spacing relative to main pipeline diameter and flows.     

A naturalistic study of commuter cyclists in the greater Stockholm area

Few naturalistic studies have been carried out with commuter cyclists to discover the types of problems they encounter on a daily basis. The study presented here has been commissioned by the City of Stockholm municipality and focuses specifically on commuter cyclists in the Greater Stockholm area. The aim of the study was to describe and pinpoint accessibility and safety problems, but also to generate an accessible geographical interface that could serve as a traffic planning tool for cycle network improvement. Statistical surveys in the Stockholm area have shown a rapid growth in the number of cyclists as well as an increase in problems associated with an overburdened cycle infrastructure. Given the heightened emphasis on transport system sustainability, the City of Stockholm is faced with the challenging task of trying to maintain and encourage the upward trend in commuter cycling through a process that involves problem identification, classification, prioritisation and resolution. An innovative methodology involving the use of GPS logging devices and small video cameras was developed and supported with analysis software designed specifically for the purposes of this study. Experienced commuter cyclists were recruited to cycle 17 different major cycle routes to and from the suburbs and inner city area during morning and afternoon peak traffic hours during the main cycle season. Over 500 safety and accessibility/mobility problems were identified and recorded from the data collected from 16 commuter cyclists. The method and representation of data proved successful for strategic traffic planning work at City of Stockholm and has since provided invaluable input for and the development of a new cycle plan for Greater Stockholm. Indirectly, the results of this work have also contributed to longer term safety and environmental targets.     

Brick and mortar treatment by cream emulsion for improved water repellence and thermal insulation

A novel polymer cream was applied to brick and mortar in an attempt to reduce water absorption and to improve thermal insulation for household heating energy saving. Tests were carried out on surface energy, water contact angle, thermal conductivity and sorptivity of brick and mortar with and without cream treatment. A model house was built and a heating and monitoring system was developed to quantitatively evaluate the heating energy consumption in different conditions before and after cream treatment. It was found out that cream treatment can successfully impart good water repellence and enhanced the thermal insulation of the brick and mortar. The results from contact angle and surface energy measurements showed that the materials became highly hydrophobic. Experimental results from the model house showed approximately 9% heating energy consumption reduction in dry conditions and approximately 50% in wet conditions. In addition, the internal humidity typically was reduced to almost 1/3 of that of the control. It has been demonstrated that the novel cream treatment on masonry buildings can help reduce damp problems and save household heating energy consumption which can make a significant contribution to addressing social, environmental, ecological and economic problems resulting from climate change and global warming.     

A transport-flux-based directed relation graph method for the spatially inhomogeneous instantaneous reduction of chemical kinetic mechanisms

A novel, flux-based, directed relation graph (DRG) method is proposed for adaptive and automatic generation of skeletal chemical mechanisms. Unlike many previous approaches for static mechanism reduction, the proposed method does not rely on the complete solution of a set of test problems using the detailed mechanism, but rather it simplifies the model “on the fly,” analyzing the local reaction states with an extended directed relation graph. Compared to the original DRG method of Lu and Law [T. Lu, C.K. Law, Proc. Combust. Inst. 30 (2005)], the flux-based DRG explicitly considers the effect of transport fluxes, as they provide a way to quantify the coupling of the governing equations among adjacent grid cells. The resulting numerical scheme operates on a cell-by-cell basis, so that different chemical submodels are applied in different regions of the flame. This approach leads to very large reduction ratios, in which most of the flame structure is resolved using about 30% of the chemical species employed in the full mechanism, while a more detailed model that considers roughly 70–80% of the total species is used only at ignition. The flux-based DRG method has been employed in the two-dimensional simulation of axisymmetric coflow flames for a variety of fuels and chemical kinetic mechanisms (three steady flames and one oscillating flame), with a speedup factor of about 20 obtained for the largest problem — a JP-8 flame.     

Microstructure and mechanical properties of aluminum back contact layers

The overall demand to reduce solar energy costs gives a continuous drive to reduce the thickness of silicon wafers. Handling and bowing problems associated with thinner wafers become more and more important, as these can lead to cells cracking and thus to high yield losses. In this paper the microstructure and mechanical properties of the aluminum on the rear side of a solar cell are discussed. It is shown that the aluminum back contact has a complex composite-like microstructure, consisting of five main components: (1) the back surface field layer; (2) a eutectic layer; (3) spherical (3-5 μm) hypereutectic Al-Si particles surrounded by a thin aluminum oxide layer (200 nm); (4) a bismuth-silicate glass matrix; and (5) pores (14 vol%). The Young’s modulus of the Al-Si particles is estimated by nanoindentation and the overall Young’s modulus is estimated on the basis of bowing measurements. These results are used as input parameters for the improved thermomechanical multiscale model of a solar cell.     

Kinetic modeling of Fe‐BEA as NH3‐SCR catalyst—effect of phosphorous

The focus of this work is to investigate whether a previously developed microkinetic deactivation model for hydrothermally treated Fe‐BEA as NH₃‐SCR catalyst can be applied to describe chemical deactivation of Fe‐BEA due to phosphorous exposure. The model describes the experiments well for Fe‐BEA before and after phosphorous exposure by decreasing the site density, representing deactivation of sites due to formation of metaphosphates blocking the active iron sites, while the kinetic parameters are kept constant. Furthermore, the results show that the activity for low‐temperature selective catalytic reduction (SCR) is very sensitive to loss of active monomeric iron species due to phosphorous poisoning compared to high‐temperature SCR. Finally, the ammonia inhibition simulations show that exposure to phosphorous may affect the internal transport of ammonia between ammonia storage sites buffering the active iron sites, which results in a lower SCR performance during transient conditions. © 2014 American Institute of Chemical Engineers AIChE J, 61: 215–223, 2015