Functional Chromatography Reveals Three Natural Products that Target the Same Protein with Distinct Mechanisms of Action

Access to lead compounds with defined molecular targets continues to be a barrier to the translation of natural product resources. As a solution, we developed a system that uses discrete, recombinant proteins as the vehicles for natural product isolation. Here, we describe the use of this functional chromatographic method to identify natural products that bind to the AAA+ chaperone, p97, a promising cancer target. Application of this method to a panel of fungal and plant extracts identified rheoemodin, 1‐hydroxydehydroherbarin, and phomapyrrolidone A as distinct p97 modulators. Excitingly, each of these molecules displayed a unique mechanism of p97 modulation. This discovery provides strong support for the application of functional chromatography to the discovery of protein modulators that would likely escape traditional high‐throughput or phenotypic screening platforms.     

X-ray diffraction from shock-loaded polycrystals

X-ray diffraction was demonstrated from shock-compressed polycrystalline metals on nanosecond time scales. Laser ablation was used to induce shock waves in polycrystalline foils of Be, 25-125 microm thick. A second laser pulse was used to generate a plasma x-ray source by irradiation of a Ti foil. The x-ray source was collimated to produce a beam of controllable diameter, which was directed at the Be sample. X-rays were diffracted from the sample, and detected using films and x-ray streak cameras. The diffraction angle was observed to change with shock pressure. The diffraction angles were consistent with the uniaxial (elastic) and isotropic (plastic) compressions expected for the loading conditions used. Polycrystalline diffraction will be used to measure the response of the crystal lattice to high shock pressures and through phase changes.     

马尼托瓦克移动式起重机专用KZ~(TM)100型缆绳

正在CONEXPO-CON/AGG 2014上,马尼托瓦克展示了配备KZT~(TM)100型缆绳的Grove RT770E型起重机。KZ~(TM)100型缆绳是首次专为移动式起重机设计的合成纤维卷扬缆绳,这项创新成果由马尼托瓦克携手合成纤维缆绳制造商Samson公司共同研制,由马尼托瓦克独家销售,从2014年下半年开始作为Grove系列越野起重机的选购件供应给客户。KZ~(TM)100型卷扬缆绳具有许多优点:质量比钢丝绳轻80%:采用转矩中性平衡结构,可消除负荷旋转和缆绳缠绕     

Rethinking Project Management: Researching the actuality of projects

This paper puts forth the somewhat controversial position that what is needed to improve project management in practice is not more research on what should be done or the frequency and/or use of traditional project management practices. We argue that while a great deal is written about traditional project management we know very little about the “actuality” of project based working and management. This paper formulates a research approach that takes seriously practitioner’s lived experience of projects. We explore the ontological, epistemological and methodological assumptions underlying this kind of research and provide examples of some project management research originating from this perspective. We conclude by summarizing the findings from these studies and providing insights into the map ahead for future such research. In this kind of work the attention is refocused on praxis, on context-dependent judgement, on situational ethics and on reflexivity which enables social actors to see how power actually functions in context.     

A practical study of white‐clawed crayfish (Austropotamobius pallipes) mitigation during in‐channel construction works,North‐East England

The article provides a unique opportunity to study a large white‐clawed crayfish mitigation exercise on the River Wansbeck, Northumberland in North East England. The translation was necessary to allow the construction of a dam on the river to reduce flood risk to the town of Morpeth. The study provides an assessment of the methodology used for the capture and translocation activities, and provides an insight into the speed of colonisation and population establishment in a 300‐m diversion channel and the structure of translocated populations. Over 3500 + white‐clawed crayfish were caught when the natural channel was dewatered, with 5400 animals removed the following year when the diversion channel was closed. Average density based on the number of white‐clawed crayfish caught was estimated as in excess of 5 per 1 m². The study demonstrates the importance of the River Wansbeck for white‐clawed crayfish.     

Mercury emissions to the atmosphere from anthropogenic sources in Europe in 2000 and their scenarios until 2020

The paper reviews the current state of knowledge regarding European emissions of mercury and presents estimates of European emissions of mercury to the atmosphere from anthropogenic sources for the year 2000. This information was then used as a basis for Hg emission scenario development until the year 2020. Combustion of coal in power plants and residential heat furnaces generates about half of the European emissions being 239 tonnes. The coal combustion is followed by the production of caustic soda with the use of the Hg cell process (17%). Major points of mercury emission generation in the mercury cell process include: by-product hydrogen stream, end box ventilation air, and cell room ventilation air. This technology is now being changed to other caustic soda production technologies and further reduction of Hg emissions is expected in this connection. The third category on the list of the largest Hg emitters in Europe is cement production (about 13%). The largest emissions were estimated for Russia (the European part of the country), contributing with about 27% to the European emissions, followed by Poland, Germany, Spain, Ukraine, France, Italy and the United Kingdom. Most of these countries use coal as a major source of energy in order to meet the electricity and heat demands. In general, countries in the Central and Eastern Europe generated the main part of the European emissions in 2000. Emission reductions between 20% and 80% of the 2000 emission amounts can be obtained by the year 2020, as estimated by various scenarios.     

Analysis of electromigration phenomenon in thick-film and LTCC structures at elevated temperature

Studies on electromigration phenomenon in thick-film structures on alumina and LTCC substrates are presented in this paper. The effects of storage of Au and Ag electrode patterns in temperature range up to 300 °C under voltage bias were examined. The leakage characteristics of electrodes with 100 μm spacing at 50 V dc bias as a function of time and temperature are presented and analyzed. Scanning electron microscope (SEM) equipped with the energy-dispersive X-ray spectroscopy (EDX) detector was applied for determination of metal ions transport. Test structures with Au-based conductive material are much more resistant to electromigration than Ag-based layers.     

Measuring errors and violations on the road: A bifactor modeling approach to the Driver Behavior Questionnaire

The Driver Behavior Questionnaire (DBQ) is a self-report measure of driving behavior that has been widely used over more than 20 years. Despite this wealth of evidence a number of questions remain, including understanding the correlation between its violations and errors sub-components, identifying how these components are related to crash involvement, and testing whether a DBQ based on a reduced number of items can be effective. We address these issues using a bifactor modeling approach to data drawn from the UK Cohort II longitudinal study of novice drivers. This dataset provides observations on 12,012 drivers with DBQ data collected at .5, 1, 2 and 3 years after passing their test. A bifactor model, including a general factor onto which all items loaded, and specific factors for ordinary violations, aggressive violations, slips and errors fitted the data better than correlated factors and second-order factor structures. A model based on only 12 items replicated this structure and produced factor scores that were highly correlated with the full model. The ordinary violations and general factor were significant independent predictors of crash involvement at 6 months after starting independent driving. The discussion considers the role of the general and specific factors in crash involvement.     

Using solution thermodynamics to describe the dispersion of rod-like solutes: application to dispersions of carbon nanotubes in organic solvents

We report a simple model describing the solubility of rods in solvents, expressing the final result explicitly in terms of the surface entropy and the enthalpy of mixing. This model can be combined with any expression for the mixing enthalpy depending on the requirements. For example, in one instance it predicts the dispersed concentration of rods to decrease exponentially with the Flory-Huggins parameter of the dispersion. Using a different enthalpy function, it predicts a Gaussian peak when concentration is plotted versus solvent surface energy. The model also suggests specific solvent-rod interactions to be important and shows the dispersed concentration to be very sensitive to ordering at the solvent-rod interface. We have used this model to describe experimental results for the concentration of dispersed nanotubes in various solvents. Qualitative agreement with these predictions is observed experimentally. However, we suggest that the fact that quantitative agreement is not found may be explained by solvent ordering at the nanotube surface.     

Resolution improvement in two-photon fluorescence microscopy with a single-mode fiber

The dependence of spectral broadening of an ultrashort-pulsed laser beam on the fiber length and the illumination power is experimentally characterized in order to deliver the laser for two-photon fluorescence microscopy. It is found that not only the spectral width but also the spectral blue shift increases with the fiber length and illumination power, owing to the nonlinear response in the fiber. For an illumination power of 400 mW in a 3-m-long single-mode fiber, the spectral blue shift is as large as 15 nm. Such a spectral blue shift enhances the contribution from the short-wavelength components within the pulsed beam and leads to an improvement in resolution under two-photon excitation, whereas the efficiency of two-photon excitation is slightly reduced because of the temporal broadening of the pulsed beam. The experimental measurement of the axial response to a two-photon fluorescence polymer block confirms this feature.