Ternatin and improved synthetic variants kill cancer cells by targeting the elongation factor-1A ternary complex.

Cyclic peptide natural products have evolved to exploit diverse protein targets, many of which control essential cellular processes. Inspired by a series of cyclic peptides with partially elucidated structures, we designed synthetic variants of ternatin, a cytotoxic and anti-adipogenic natural product whose molecular mode of action was unknown. The new ternatin variants are cytotoxic toward cancer cells, with up to 500-fold greater potency than ternatin itself. Using a ternatin photo-affinity probe, we identify the translation elongation factor-1A ternary complex (eEF1A·GTP·aminoacyl-tRNA) as a specific target and demonstrate competitive binding by the unrelated natural products, didemnin and cytotrienin. Mutations in domain III of eEF1A prevent ternatin binding and confer resistance to its cytotoxic effects, implicating the adjacent hydrophobic surface as a functional hot spot for eEF1A modulation. We conclude that the eukaryotic elongation factor-1A and its ternary complex with GTP and aminoacyl-tRNA are common targets for the evolution of cytotoxic natural products

Hydrogeology and Geochemistry of Glacial Deposits in Northeastern Kansas

Twelve counties (Atchison, Brown, Doniphan, Douglas, Jackson, Jefferson, Johnson, Leavenworth, Nemaha, Shawnee, Wabaunsee, and Wyandotte) in northeastern Kansas were glaciated during the Pleistocene Epoch. The glacial deposits consist of till, fluvial, loess, and lacustrine deposits locally totalling thicknesses of 400 ft (120 m). A major buried valley 3 mi (5 km) wide, 400 ft (120 m) deep, and 75 mi (120 km) long trends eastward across southern Nemaha, northern Jackson, and central Atchison counties. Several smaller tributary valleys can be identified in Atchison, Nemaha, Brown, Jackson, and Jefferson counties. Other buried valleys generally trend southward to the Kansas River valley or northward into Nebraska and Missouri. The glacial deposits filling the buried valleys locally are clayey. However, most valleys contain at least some water-bearing sand and gravel. Wells drilled into the best water-bearing sand and gravel deposits may yield as much as 900 gallons per minute (gpm; 0.06 m3/sm3/s), but less than 500 gpm (0.03 m3/s) is more common. The alluvial deposits of the Kansas and Missouri river valleys are the major sources of ground water in northeastern Kansas. Wells in these aquifers may have yields of 5,000 gpm (0.3 m3/s), but yields are more commonly less than 3,000 gpm (0.2 m3/s). We analyzed data from 80 pump tests using computer programs to find the best fit for transmissivity (1) and storage (S) values on glacial, alluvial, and bedrock aquifers. Transmissivities in the Missouri River valley alluvium ranged from 200,000 gallons per day per foot (gpd/ft) to 600,000 gpd/ft (2,000-7,000 m2/d), and storage values were between 0.001 and 0.0004. Tests in the Kansas River valley alluvium indicated transmissivities in the range 50,000-600,000 gpd/ft (600-7,000 m2/d) and storage values of 0.03. In the main buried valley across northeastern Kansas, the glacial deposits had T and S values of 2,500-25,600 gpd/ft (31.0-318 m2/d) and 0.00002-0.002, respectively. In the smaller buried valleys the glacial deposits had T values ranging from 1,500 gpd/ft to 100,000 gpd/ft (19-1,200 m2/d). Because of increasing population size in northeastern Kansas, appropriations of water for public and industrial water supplies have been increasing. Most of the pumpage comes from wells in the Kansas and Missouri river valleys. However, in 1981 the Division of Water Resources reported allocations of 1,466 acre-ft of water from wells tapping glacial aquifers associated with the main buried channel across Nemaha, Jackson, and Atchison counties and an additional 837 acre-ft from tributaries associated with the main buried channel. Nemaha County has the largest appropriation of water from the glacial aquifer (1,549 acre-ft/yr in 1983), and Wyandotte County has the largest appropriation of water from the alluvial aquifers (54,250 acre-ft/yr in 1983). Shawnee County has the largest number of ground-water appropriation rights (217). In 1981, for the 12-county study area, the Division of Water Resources found that 773 wells have ground-water appropriation rights. These 773 wells have appropriation rights for 140,484 acre-ft of water from alluvial aquifers, 5,290 acre-ft from glacial aquifers, and 2,146 acre-ft from Pennsylvanian and Permian rock aquifers. Maps for each county show the depth to bedrock, total thickness of Pleistocene sand and gravel deposits, estimated yield of wells, depth to water in wells and test holes, and the saturated thickness of Pleistocene deposits. A bedrock topographic map for the twelve counties was prepared from outcrop data and information from more than 5,000 water well, oil and gas, and test-hole logs. Ground waters from alluvial deposits are hard calcium bicarbonate waters that may have iron concentrations of several milligrams per liter. Sand and gravel associated with the glacial deposits generally yield hard calcium bicarbonate waters and may contain appreciable amounts of iron, manganese, sulfate, and chloride locally. Nitrate concentrations above 45 mg/L are noted in a number of wells of varying depth and aquifer source

Hydrogeology and Geochemistry of Glacial Deposits in Northeastern Kansas

Twelve counties (Atchison, Brown, Doniphan, Douglas, Jackson, Jefferson, Johnson, Leavenworth, Nemaha, Shawnee, Wabaunsee, and Wyandotte) in northeastern Kansas were glaciated during the Pleistocene Epoch. The glacial deposits consist of till, fluvial, loess, and lacustrine deposits locally totalling thicknesses of 400 ft (120 m). A major buried valley 3 mi (5 km) wide, 400 ft (120 m) deep, and 75 mi (120 km) long trends eastward across southern Nemaha, northern Jackson, and central Atchison counties. Several smaller tributary valleys can be identified in Atchison, Nemaha, Brown, Jackson, and Jefferson counties. Other buried valleys generally trend southward to the Kansas River valley or northward into Nebraska and Missouri. The glacial deposits filling the buried valleys locally are clayey. However, most valleys contain at least some water-bearing sand and gravel. Wells drilled into the best water-bearing sand and gravel deposits may yield as much as 900 gallons per minute (gpm; 0.06 m3/sm3/s), but less than 500 gpm (0.03 m3/s) is more common. The alluvial deposits of the Kansas and Missouri river valleys are the major sources of ground water in northeastern Kansas. Wells in these aquifers may have yields of 5,000 gpm (0.3 m3/s), but yields are more commonly less than 3,000 gpm (0.2 m3/s). We analyzed data from 80 pump tests using computer programs to find the best fit for transmissivity (1) and storage (S) values on glacial, alluvial, and bedrock aquifers. Transmissivities in the Missouri River valley alluvium ranged from 200,000 gallons per day per foot (gpd/ft) to 600,000 gpd/ft (2,000-7,000 m2/d), and storage values were between 0.001 and 0.0004. Tests in the Kansas River valley alluvium indicated transmissivities in the range 50,000-600,000 gpd/ft (600-7,000 m2/d) and storage values of 0.03. In the main buried valley across northeastern Kansas, the glacial deposits had T and S values of 2,500-25,600 gpd/ft (31.0-318 m2/d) and 0.00002-0.002, respectively. In the smaller buried valleys the glacial deposits had T values ranging from 1,500 gpd/ft to 100,000 gpd/ft (19-1,200 m2/d). Because of increasing population size in northeastern Kansas, appropriations of water for public and industrial water supplies have been increasing. Most of the pumpage comes from wells in the Kansas and Missouri river valleys. However, in 1981 the Division of Water Resources reported allocations of 1,466 acre-ft of water from wells tapping glacial aquifers associated with the main buried channel across Nemaha, Jackson, and Atchison counties and an additional 837 acre-ft from tributaries associated with the main buried channel. Nemaha County has the largest appropriation of water from the glacial aquifer (1,549 acre-ft/yr in 1983), and Wyandotte County has the largest appropriation of water from the alluvial aquifers (54,250 acre-ft/yr in 1983). Shawnee County has the largest number of ground-water appropriation rights (217). In 1981, for the 12-county study area, the Division of Water Resources found that 773 wells have ground-water appropriation rights. These 773 wells have appropriation rights for 140,484 acre-ft of water from alluvial aquifers, 5,290 acre-ft from glacial aquifers, and 2,146 acre-ft from Pennsylvanian and Permian rock aquifers. Maps for each county show the depth to bedrock, total thickness of Pleistocene sand and gravel deposits, estimated yield of wells, depth to water in wells and test holes, and the saturated thickness of Pleistocene deposits. A bedrock topographic map for the twelve counties was prepared from outcrop data and information from more than 5,000 water well, oil and gas, and test-hole logs. Ground waters from alluvial deposits are hard calcium bicarbonate waters that may have iron concentrations of several milligrams per liter. Sand and gravel associated with the glacial deposits generally yield hard calcium bicarbonate waters and may contain appreciable amounts of iron, manganese, sulfate, and chloride locally. Nitrate concentrations above 45 mg/L are noted in a number of wells of varying depth and aquifer source

Use of Vegetation Monitoring and Professional Sharpshooting in White-Tailed Deer (Odocoileus virginianus) Management at Eagle Creek Park in Indianapolis

High white-tailed deer abundance at Eagle Creek Park (ECP) in Indianapolis necessitated active management to improve park habitat conditions. Significant deer impacts on local natural areas were first noted in the late 1990’s. Multiple years of deer browse monitoring, beginning in 2003, documented greatly impacted vegetation with heavy to severe browse damage in the park. After an initial managed hunt in 2014, population reductions have been accomplished exclusively at night by professional sharpshooters. Positive results are being evidenced through increasing pounds of venison per deer harvested and significant recovery of impacted vegetation communities

Characterizing Batteries by In Situ Electrochemical Atomic Force Microscopy: A Critical Review

Although lithium, and other alkali ion, batteries are widely utilized and studied, many of the chemical and mechanical processes that underpin the materials within, and drive their degradation/failure, are not fully understood. Hence, to enhance the understanding of these processes various ex situ, in situ and operando characterization methods are being explored. Recently, electrochemical atomic force microscopy (EC-AFM), and related techniques, have emerged as crucial platforms for the versatile characterization of battery material surfaces. They have revealed insights into the morphological, mechanical, chemical, and physical properties of battery materials when they evolve under electrochemical control. This critical review will appraise the progress made in the understanding batteries using EC-AFM, covering both traditional and new electrode–electrolyte material junctions. This progress will be juxtaposed against the ability, or inability, of the system adopted to embody a truly representative battery environment. By contrasting key EC-AFM literature with conclusions drawn from alternative characterization tools, the unique power of EC-AFM to elucidate processes at battery interfaces is highlighted. Simultaneously opportunities for complementing EC-AFM data with a range of spectroscopic, microscopic, and diffraction techniques to overcome its limitations are described, thus facilitating improved battery performance

A mutli-technique search for the most primitive CO chondrites

As part of a study to identify the most primitive COs and to look for weakly altered CMs amongst the COs, we have conducted a multi-technique study of 16 Antarctic meteorites that had been classified as primitive COs. For this study, we have determined: (1) the bulk H, C and N abundances and isotopes, (2) bulk O isotopic compositions, (3) bulk modal mineralogies, and (4) for some selected samples the abundances and compositions of their insoluble organic matter (IOM). Two of the 16 meteorites do appear to be CMs – BUC 10943 seems to be a fairly typical CM, while MIL 090073 has probably been heated. Of the COs, DOM 08006 appears to be the most primitive CO identified to date and is quite distinct from the other members of its pairing group. The other COs fall into two groups that are less primitive than DOM 08006 and ALH 77307, the previously most primitive CO. The first group is composed of members of the DOM 08004 pairing group, except DOM 08006. The second group is composed of meteorites belonging to the MIL 03377 and MIL 07099 pairing groups. These two pairing groups should probably be combined. There is a dichotomy in the bulk O isotopes between the primitive (all Antarctic finds) and the more metamorphosed COs (mostly falls). This dichotomy can only partly be explained by the terrestrial weathering experienced by the primitive Antarctic samples. It seems that the more equilibrated samples interacted to a greater extent with 16O-poor material, probably water, than the more primitive meteorites