Design of an Ultrafast G Protein Switch Based on a Mouse Melanopsin Variant

The primary goal of optogenetics is the light-controlled noninvasive and specific manipulation of various cellular processes. Herein, we present a hybrid strategy for targeted protein engineering combining computational techniques with electrophysiological and UV/visible spectroscopic experiments. We validated our concept for channelrhodopsin-2 and applied it to modify the less-well-studied vertebrate opsin melanopsin. Melanopsin is a promising optogenetic tool that functions as a selective molecular light switch for G protein-coupled receptor pathways. Thus, we constructed a model of the melanopsin G_q protein complex and predicted an absorption maximum shift of the Y211F variant. This variant displays a narrow blue-shifted action spectrum and twofold faster deactivation kinetics compared to wild-type melanopsin on G protein-coupled inward rectifying K⁺ (GIRK) channels in HEK293 cells. Furthermore, we verified the in vivo activity and optogenetic potential for the variant in mice. Thus, we propose that our developed concept will be generally applicable to designing optogenetic tools.     

Investigations of ductile damage during the process chains of toothed functional components manufactured by sheet-bulk metal forming

Sheet-bulk metal forming processes combine conventional sheet forming processes with bulk forming of sheet semi-finished parts. In these processes the sheets undergo complex forming histories. Due to in- and out-of-plane material flow and large accumulated plastic strains, the conventional failure prediction methods for sheet metal forming such as forming limit curve fall short. As a remedy, damage models can be applied to model damage evolution during those processes. In this study, damage evolution during the production of two different toothed components from DC04 steel is investigated. In both setups, a deep drawn cup is upset to form a circumferential gearing. However, the two final products have different dimensions and forming histories. Due to combined deep drawing and upsetting processes, the material flow on the cup walls is three-dimensional and non-proportional. In this study, the numerical and experimental investigations for those parts are presented and compared. Damage evolution in the process chains is simulated with a Lemaitre damage criterion. Microstructural analysis by scanning electron microscopy is performed in the regions with high mechanical loading. It is observed that the evolution of voids in terms of void volume fraction is strongly dependent on the deformation path. The comparison of simulation results with microstructural data shows that the void volume fraction decreases in the upsetting stage after an initial increase in the drawing stage. Moreover, the concurrent numerical and microstructural analysis provides evidence that the void volume fraction decreases during compression in sheet-bulk metal forming.     

Degradation of Lake Ziway,Ethiopia: A study of the environmental perceptions of school students

Lake Ziway in Ethiopia is a freshwater lake supporting multitude uses, including irrigation, fishing, water supply and recreation. However, the lake is being degraded primarily because of various land‐ and water‐use activities in its watershed. Recognizing these human impacts on the lake's water quality and quantity, the perceptions of school students were surveyed under the belief that the future of the lake is largely dependent on this younger generation. The goal of this study was to better understand how students actually recognize the extent to which various human activities impact the water quantity and quality of Lake Ziway. As major stakeholders in their communities, the perceptions of school students from four high schools regarding the changes to the lake over time were investigated. Students were contacted by purposive sampling, based on criteria of student academic performances, and their proximity to the lake. Their perceptions were studied on the basis of an interview survey. The majority of students indicated that high levels of human activities, especially water abstractions and water pollution, were the main lake impacts. Students believe there is a lack of sustainable utilization and protection of the lake. They suggested coordinated activities among all lake stakeholders in the participation and decision‐making process to properly manage the lake. Provision of awareness to both local administrations and local communities, concern for establishing an appropriate regulatory body and allocating a sufficient budget, and strict controls on flower farm practices in the lakeshore, also was considered to be of high priority as a means of conserving the sustainability of the lake. The result derived from this survey has important implications for facilitating improved school curricula, and for federal, regional and district level water resource management authorities, in setting priorities and developing policies for the sustainability of Lake Ziway.     

(R)-acetoin-female sex pheromone of the summer chafer Amphimallon solstitiale (L.)

Extracts of Amphimallon solstitiale (L.), a well known, widely distributed and rather common European scarab beetle, were analyzed by GC-MS and GC-EAD. Acetoin -(R):(S) < 9:1 - as well as 2,3-butanediol -(2R,3R):(2S,3S) :meso = 1:1:9 - were present in extracts of both males and females. Although (2S,3S)-butanediol did not show any EAD activity, the other compounds elicited strong responses exclusively with male antennae. In contrast, several EAD active green leaf volatiles were detected equally well by male and female antennae. During preliminary field bioassays, (R)-acetoin was highly attractive to swarming males, whereas neither rac-acetoin nor the 2,3-butanediols showed activity. Therefore, (R)-acetoin is the female sex pheromone of A. solstitiale.     

Snow metamorphism as revealed by scanning electron microscopy

Current theories of snow metamorphism indicate that sublimating snow crystals have rounded shapes, while growing crystals have shapes that depend on growth rates. At slow growth rates, crystals are rounded. At moderate rates, they have flat faces with rounded edges. At fast growth rates, crystals have flat faces with sharp edges, and they have hollow faces at very fast growth rates. The main growth/sublimation mechanism is thought to be by the homogeneous nucleation of new layers at or near crystal edges. It was also suggested that the equilibrium shape of snow crystals would be temperature dependent: rounded above -10.5 degrees C, and faceted below. To test these paradigms, we have performed SEM investigations of snow samples having undergone metamorphism under natural conditions, and of snow samples subjected to isothermal metamorphism at -4 degrees and -15 degrees C in the laboratory. In general, current theories predicting crystal shapes as a function of growth rates, and of whether crystals are growing or sublimating, are verified. However, the transition in equilibrium shapes from rounded to faceted at -10.5 degrees C is not observed in our isothermal experiments that reveal a predominance of rounded shapes after more than a month of metamorphism at -4 and -15 degrees C. Some small crystals with flat faces that also have sharp angles at -15 degrees C, are observed in our isothermal experiments. These faces are newly formed, and contradict current theory. Several hypotheses are proposed to explain their occurrence. One is that they are due to sublimation at emerging dislocations.     

Variability, covariation, and invariance with respect to coordinate systems in motor control: Reply to Smeets and Louw (2007).

In their comment on the tolerance-noise covariation (TNC) method for decomposing variability by H. Müller and D. Sternad (2003, 2004b), J. B. J. Smeets and S. Louw (see record 2007-01135-017) show that covariation (C), as defined within the TNC method, is not invariant with respect to coordinate transformations and contend that it is, therefore, meaningless. Although the observation is correct, their interpretation is misleading in the following ways: (a) They equate covariation C with the known statistical quantity covariance and noise (N) with standard deviations. The two quantities C and N are conceptually different statistical measures. (b) Dependency on the reference frame is not only a feature of C but of all 3 components. However, such dependency is ubiquitous in motor control. (c) As the frame of reference in biological systems is poorly understood, the TNC method may afford evaluation of different coordinates for control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

One pediatric neurosurgeon's story

The development of pediatric neurosurgery in the United Kingdom, as experienced by one recently trained neurosurgeon in the late 1940s and the 1950s, is described.     

Measurement of the mixing quality in premix combustors

The problem of mixing fuel and air is the essential point of low emission combustion in gas turbines. In premixed combustors and fuel staged combustors the quality of the fuel–air mixture is the determinant parameter for the amount of emissions of nitric oxides (NO_x). The nearly perfect preparation of the fuel–air mixture is also a condition for trouble-free operation in catalytical combustion. Prevaporization of liquid fuels hampers the process of mixing. So the investigative work at the Department of Steam and Gas Turbines at the University of Bochum concentrated on experiments with liquid fuels. The results show that there is a great potential of reducing NO_x emission even with liquid fuels and reveal the key role of prevaporization and mixing. The experiments were carried out at a premix combustion test rig at moderate pressure. By using the technique of planar-laser induced fluorescence (LIF), highly time and spatially resolved measurements of fuel concentrations were yielded from the experiments. The optical measurements showed the structure of the mixture field of fuel and air in the zone downstream of the flameholder. The pollutant emissions were simultaneously monitored with conventional gas analysers. As the main result, the strong dependence of the pollutant emissions on the mixture could be clearly revealed. On one hand the homogeneity over the cross-section of the combustor was the main condition for low emission combustion. On the other hand the time-resolved two-dimensional LIF images of the turbulent mixture field showed that the instationary distribution also had a considerable influence on the rate of emissions. Even the mixture of static mixers contained spatial and temporal inhomogeneities, which could be observed by using the LIF-technique but not with conventional methods.