Structural Basis of Microtubule Stabilization by Discodermolide

Microtubule‐stabilizing agents (MSAs) are widely used in chemotherapy. Using X‐ray crystallography we elucidated the detailed binding modes of two potent MSAs, (+)‐discodermolide (DDM) and the DDM–paclitaxel hybrid KS‐1‐199‐32, in the taxane pocket of β‐tubulin. The two compounds bind in a very similar hairpin conformation, as previously observed in solution. However, they stabilize the M‐loop of β‐tubulin differently: KS‐1‐199‐32 induces an M‐loop helical conformation that is not observed for DDM. In the context of the microtubule structure, both MSAs connect the β‐tubulin helices H6 and H7 and loop S9–S10 with the M‐loop. This is similar to the structural effects elicited by epothilone A, but distinct from paclitaxel. Together, our data reveal differential binding mechanisms of DDM and KS‐1‐199‐32 on tubulin.     

Carbohydrate–Lectin Interactions: An Unexpected Contribution to Affinity

Uropathogenic E. coli exploit PapG‐II adhesin for infecting host cells of the kidney; the expression of PapG‐II at the tip of bacterial pili correlates with the onset of pyelonephritis in humans, a potentially life‐threatening condition. It was envisaged that blocking PapG‐II (and thus bacterial adhesion) would provide a viable therapeutic alternative to conventional antibiotic treatment. In our search for potent PapG‐II antagonists, we observed an increase in affinity when tetrasaccharide 1 , the natural ligand of PapG‐II in human kidneys, was elongated to hexasaccharide 2 , even though the additional Siaα(2–3)Gal extension is not in direct contact with the lectin. ITC studies suggest that the increased affinity results from partial desolvation of nonbinding regions of the hexasaccharide; this is ultimately responsible for perturbation of the outer hydration layers. Our results are in agreement with previous observations and suggest a general mechanism for modulating carbohydrate–protein interactions based on nonbinding regions of the ligand.     

A new hyper-heuristic as a general problem solver: an implementation in HyFlex

This study provides a new hyper-heuristic design using a learning-based heuristic selection mechanism together with an adaptive move acceptance criterion. The selection process was supported by an online heuristic subset selection strategy. In addition, a pairwise heuristic hybridization method was designed. The motivation behind building an intelligent selection hyper-heuristic using these adaptive hyper-heuristic sub-mechanisms is to facilitate generality. Therefore, the designed hyper-heuristic was tested on a number of problem domains defined in a high-level framework, i.e., HyFlex. The framework provides a set of problems with a number of instances as well as a group of low-level heuristics. Thus, it can be considered a good environment to measure the generality level of selection hyper-heuristics. The computational results demonstrated the generic performance of the proposed strategy in comparison with other tested hyper-heuristics composed of the sub-mechanisms from the literature. Moreover, the performance and behavior analysis conducted for the hyper-heuristic clearly showed its adaptive characteristics under different search conditions. The principles comprising the here presented algorithm were at the heart of the algorithm that won the first international cross-domain heuristic search competition.     

Quantification of aboveground rangeland productivity and anthropogenic degradation on the Arabian Peninsula using Landsat imagery and field inventory data

The productivity of semi-arid rangelands on the Arabian Peninsula is spatially and temporally highly variable, and increasing grazing pressure as well as the likely effects of climatic change further threatens vegetation resources. Using the Al Jabal al Akhdar mountains in northern Oman as an example, our objectives were to analyse the availability and spatial distribution of aboveground net primary production (ANPP) and the extent and causes of vegetation changes during the last decades with a remote sensing approach. A combination of destructive and non-destructive biomass measurements by life-form specific allometric equations was used to identify the ANPP of the ground vegetation (< 50 cm) and the leaf and twig biomass of phanerophytes. The ANPP differed significantly among the life forms and the different plant communities, and the biomass of the sparsely vegetated ground was more than 50 times lower (mean = 0.22 t DM ha^− 1) than the biomass of phanerophytes (mean = 12.3 t DM ha^− 1). Among the different vegetation indices calculated NDVI proved to be the best predictor for rangeland biomass.Temporal trend analysis of Landsat satellite images from 1986 to 2009 was conducted using a pixel-based least square regression with the annual maximum Normalized Differenced Vegetation Index (NDVI_max) as a dependent variable. Additionally, linear relationships of NDVI_max and annual rainfall along the time series were calculated. The extent of human-induced changes was analysed using the residual trends method. A strongly significant negative biomass trend detected for 83% of the study area reflected a decrease in annual rainfall but even without clear evidence of deforestation of trees and shrubs, human-induced vegetation degradation due to settlement activities were also important.     

Momentum and energy propagation in tapered granular chains

We study momentum and energy propagation in 1D tapered chains of spherical granules which interact according to a Hertz potential. In this work we apply the binary collision approximation, which is based on the assumption that transfer of energy along the chain occurs via a succession of two-particle collisions. Although the binary theory correctly captures the trends of increase or decrease of kinetic energy and momentum, the actual values of these quantities are not in good quantitative agreement with those obtained by numerically integrating the full equations of motion. To address this difficulty we have developed a mixed numerical/analytical correction algorithm to provide an improved estimate of the velocity of the particles during pulse propagation. With this corrected velocity we are in turn able to correctly predict the momentum and kinetic energy along the chain for several tapering configurations, specifically for forward linear, forward exponential, backward linear and backward exponential tapering.     

Subjective evaluation of natural high‐saturated images on a wide gamut display

In previous studies of image evaluation using wide color gamut displays, it is unclear to what degree people prefer the chroma‐varying images, especially the images that are more saturated than the most preferred image. Here, we present a study using a wide color gamut display, which measured viewers' most preferred level of image chroma (experiment 1) and their subjective evaluation of images that were less or more saturated than the previously most preferred one (experiment 2). The results showed that (a) the subjects' preferences for the original or for more saturated images depended on the images' original chroma and (b) the subjective evaluation of the images, that is, Valence and Arousal, did not deteriorate when the chroma of images increased more than the most preferred level. Such results indicate that the increase of the image chroma in wider color gamut displays can have a substantial influence on the impression images have on viewers.     

Fabrication of CNT-SiC/SiC composites by electrophoretic deposition

Due to the outstanding mechanical and thermal properties of carbon nanotubes (CNTs), they are considered suitable reinforcement for structural materials. In this study, for the first time, electrophoretic deposition (EPD) was used to deposit (multi-walled) CNTs onto SiC fibres (SiC_f) to form an effective CNT interphase layer for SiC_f/SiC composites. This deposition was followed by electrophoretic infiltration of the CNT-coated SiC fibre mats with SiC powder to fabricate a new CNT-SiC-fibre-reinforced SiC-matrix (SiC_f/SiC) composite for fusion applications. In these EPD experiments, a commercial aqueous suspension of negatively charged CNTs and an optimized aqueous suspension of negatively charged SiC particles were used. The CNT-coatings on the SiC fibres were firm and homogenous, and uniformly distributed nanotubes were observed on the fibre surfaces. In a following step of EPD, a thick SiC layer was formed on the fibre mat when the CNT-coated SiC fibres were in contact with the positive electrode of the EPD cell; however, spaces between the fibres were not fully filled with SiC. Conversely, when CNT-coated SiC fibres were isolated from the electrode, the SiC particles were able to gradually fill the fibre mat resulting in relatively high infiltration, which leads to dense composites.     

Biofunctional Silk/Neuron Interfaces

Silk fibroin (SF) is a biocompatible and slowly biodegradable material with excellent mechanical properties and huge potential for use as biofunctional interface in electronic devices that aim to stimulate and control neural network activity and peripheral nerve repair. It is shown that SF films act as material interfaces that support the adherence and neurite outgrowth of dorsal root ganglion (DRG) neurons and preserve neuronal functions. Silk films preserve the capability of neuronal cells to fire and DRG neurons on silk films retain the intracellular free Ca²⁺ concentration ([Ca²⁺]_i) response to capsaicin, a typical noxious stimulus for this neuronal culture model. It is also demonstrated that nerve growth factor (NGF)‐functionalized silk films promote neurite outgrowth and modulate functional properties of DRG neurons. The results show that silk preserves DRG neuronal physiology and is a promising biomaterial platform for the future development of devices with goals including functional recovery of injured neurons, neurite functional outgrowth in vitro, or functional electrostimulation in vivo.     

Integrating ecosystem services in Swedish environmental assessments: an empirical analysis

Given the growing number of policies and laws that encourage inclusion of ecosystem services (ES) in processes, we have investigated environmental impact assessments (EIA) and strategic environmental assessments (SEA) conducted in Sweden in order to analyse whether ES may be integrated to enhance and improve environmental assessment of today. Representative Swedish environmental projects were reviewed. Three cases with different geographic and environmental settings were selected to allow us to study consideration of a wide range of different ES. We investigated the processes and discussions taking place using documentation from the cases. We formalized and labelled the expected impacts into an ES framework. Summarizing each case, we described conformities and divergences in explicit and implicit prioritizations between the actors. We discussed the benefits of integrating ES into current practices and possible improvements in the processes and methodologies. When ES could be integrated into EIAs and SEAs more aspects would be visualized and a larger stakeholder engagement stimulated leading to improved support for decision-making.