Mass spectrometry (MS) has many advantages as a quantitative detection technology for applications within drug discovery. However, current methods of liquid sample introduction to a detector are slow ...and limit the use of mass spectrometry for kinetic and high-throughput applications. We present the development of an acoustic mist ionization (AMI) interface capable of contactless nanoliter-scale “infusion” of up to three individual samples per second into the mass detector. Installing simple plate handling automation allowed us to reach a throughput of 100 000 samples per day on a single mass spectrometer. We applied AMI-MS to identify inhibitors of a human histone deacetylase from AstraZeneca’s collection of 2 million small molecules and measured their half-maximal inhibitory concentration. The speed, sensitivity, simplicity, robustness, and consumption of nanoliter volumes of sample suggest that this technology will have a major impact across many areas of basic and applied research.
X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between ...pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallization conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. We report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). Additional samples were screened to demonstrate that these methods can be applied to rare samples.
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•Acoustic methods inject crystal-containing droplets directly from microplate wells•On-demand acoustic injection uses crystals efficiently without orifices or clogging•Diffraction patterns from crystals measuring several tens of μm are of high quality•Complete datasets can be obtained from fewer than 50,000 crystals
Acoustic droplet ejection provides an automated tool for efficient use of protein crystals in SFX experiments. Roessler et al. used this method to deliver crystal-containing droplets into the XFEL beam to coincide with each X-ray pulse.
Acoustic liquid handling uses high-frequency acoustic signals that are focused on the surface of a fluid to eject droplets with high accuracy and precision for various life science applications. Here ...we present a multiwell source plate, the Echo Qualified Reservoir (ER), which can acoustically transfer over 2.5 mL of fluid per well in 25-nL increments using an Echo 525 liquid handler. We demonstrate two Labcyte technologies-Dynamic Fluid Analysis (DFA) methods and a high-voltage (HV) grid-that are required to maintain accurate and precise fluid transfers from the ER at this volume scale. DFA methods were employed to dynamically assess the energy requirements of the fluid and adjust the acoustic ejection parameters to maintain a constant velocity droplet. Furthermore, we demonstrate that the HV grid enhances droplet velocity and coalescence at the destination plate. These technologies enabled 5-µL per destination well transfers to a 384-well plate, with accuracy and precision values better than 4%. Last, we used the ER and Echo 525 liquid handler to perform a quantitative polymerase chain reaction (qPCR) assay to demonstrate an application that benefits from the flexibility and larger volume capabilities of the ER.
Between 1817 and 1838 professors at the University of Pennsylvania, South Carolina College, Yale College, and Columbia College published six syllabi for earth science courses. All stressed geology. ...These syllabi give unique insight into classrooms of almost 200 years ago. The greatest difference between the six syllabi involved historical geology. Some pioneer professors viewed observation as the only basis for interpreting geological history. Others viewed Biblical revelation as the dominant, or at least an important, guide to deciphering the history of Planet Earth. Eventually differing approaches to historical interpretation led to a well-documented religion-geology confrontation. It culminated in a much-publicized attempt to impeach a college president who taught an observation-based geology course. After 1832, the year of this failed impeachment, known syllabi continued to emphasize observation. By 1834 the once exonerated college president and his entire faculty were fired. By 1840 research in the Alps showed that widely distributed high altitude earth-surface sediments of mixed clastic character, generally called the Drift, are of glacial origin. This observation-based view was gradually accepted by much of the scientific community. Before 1840 some earth science teachers saw all occurrences of the Drift as clear proof that the Flood of Noah covered the entire planet, including the highest mountains. The Drift and the Noachian Flood were major themes in some science classrooms. Today, the Drift is less controversial. Evolution is the new battleground but the conflict is the same. It is an impasse between the interpretation of Biblical revelation and the interpretation of observation.
Geology was widely taught in American secondary schools during much of the nineteenth century. As geology evolved so did textbooks. As schools and teaching changed so did textbooks. This study ...examines nineteenth century secondary school geology texts and a crucial government report. It fits these nineteen publications into a general cultural context, tracing the gradual expansion and abrupt decline of geological education in American's nineteenth century secondary schools.
X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between ...pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallization conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. Lastly, we report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). In addition, samples were screened to demonstrate that these methods can be applied to rare samples
James Merrill Safford Stearns, Richard G
Earth sciences history,
1985, Letnik:
4, Številka:
1
Journal Article
Recenzirano
James Merrill Safford (1822-1907), famous for geological investigations of Tennessee, taught chemistry and biology, as well as geology, for 52 years. He held administrative posts in medicine, and his ...teaching, even of geology, was mostly to would-be physicians, engineers and pharmacists. His education in Silliman's laboratory at Yale, during 1847, probably was the key to his success.
Earthquakes are a common occurrence in west Tennessee. Yet it is difficult to recognize related faults within the alluvial valley because of the unconsolidated sediments. Therefore, a synergetic ...approach to the analysis of lineament patterns was applied through the use of Landsat satellite and gravity anomaly data. Landsat satellite images were evaluated for lineament identification using different spectral bands, seasons, enhancement, and image interpretation techniques. Gravity trends were delineated on the gravity anomaly map of west Tennessee, and gravity lineaments were identified and mapped. The Landsat and gravity lineaments were quantitatively analyzed and compared by means of two-dimensional histograms and rose diagrams. The results indicated that the primary direction of both Landsat and gravity lineaments was NE; N36-63E for Landsat and N27-72E for gravity. Weaker trends were found in N50-55W for Landsat and N60-70W for gravity. The NE trend of the lineaments corresponded to faults and was in accordance with reactivation of the Reelfoot rift near the Mississippi River. These results suggest that deeper features, maybe at the earthquake focal depth, probably extend to the land surface as Landsat detectable lineaments.
Subsurface data show that in the northern Mississippi Embayment Cretaceous, Paleocene, and lower Eocene deposition occurred in a single sedimentary cycle.
The Cumberland Plateau overthrust, a continuous series of thrust and cross faults, extends southwest across the Cumberland Plateau of Tennessee from its junction with the Valley and Ridge thrusts ...near the north end of the Sequatchie Valley anticline. The strata involved vary in competency and hence control the structural pattern.
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