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We test a range of standard generalized Born (GB) models and protein force fields for a set of five experimentally characterized, designed peptides comprising alternating blocks of glutamate and lysine, which have been shown to differ significantly in α-helical content. Sixty-five combinations of force fields and GB models are evaluated in >800 μs of molecular dynamics simulations. GB models generally do not reproduce the experimentally observed α-helical content, and none perform well for all five peptides. These results illustrate that these models are not usefully predictive in this context. These peptides provide a useful test set for simulation methods.

The design of peptides that assemble in membranes to form functional ion channels is challenging. Specifically, hydrophobic interactions must be designed between the peptides and at the peptide–lipid interfaces simultaneously. Here, we take a multi-step approach towards this problem. First, we use rational de novo design to generate water-soluble α-helical barrels with polar interiors, and confirm their structures using high-resolution X-ray crystallography. These α-helical barrels have water-filled lumens like those of transmembrane channels. Next, we modify the sequences to facilitate their insertion into lipid bilayers. Single-channel electrical recordings and fluorescent imaging of the peptides in membranes show monodisperse, cation-selective channels of unitary conductance. Surprisingly, however, an X-ray structure solved from the lipidic cubic phase for one peptide reveals an alternative state with tightly packed helices and a constricted channel. To reconcile these observations, we perform computational analyses to compare the properties of possible different states of the peptide.

Historic Native American and modern civilizations have been forcing the unstable use of the Colorado River and adjacent land resources for centuries. Much can be learned from past Native American cultures that created irrigation systems to offset low rainfall. These lessons learned can be applied to our modern civilization. We can learn a lot from their previous behavior and experiences and could apply the lessons learned to our current disappearing Colorado River situation. Little of the Colorado River water flow reaches the international border with Mexico near Yuma, Arizona. Intensive consumption, mostly in the United States, has dried up the lower 160 km of the river. Since the 1960s, the Colorado River has rarely flowed into the Gulf of California and when it does it becomes is a major international news event. The Colorado River Delta is drought prone and its headwater tributaries are a vital source of water for 40 million people. The Colorado River has whitewater rapids, canyons, and many United States National Parks. The tributary and river flow is managed by an extensive system of dams, aqueducts, and reservoirs. Most years the entire Colorado River flow is used for United States agricultural irrigation and domestic water supply purposes. The agricultural and urban needs in the United States are continuing to grow and it appears the days of Colorado River flowing into Mexico and the Gulf of California are numbered and declining every decade. The Colorado River is disappearing and restoration efforts appear to be too little too late. If the Colorado River valley is ever going to recover management lessons and failures learned from the Native Americans, including the Hohokam, must be applied. A balanced approach to water management is needed and must include aggressive conservation and efficiency measures.

We performed a series of six plate impact experiments on polyimide and modeled them using new reactant and products equations of state combined with an Arrhenius rate model. The first experiment was diagnosed with embedded electromagnetic velocity gauges through which we directly observed attenuation of the lead shock to an approximately constant state over a propagation distance of roughly 4 mm. Simulated gauge profiles were in excellent qualitative agreement with experiment and suggested a sluggish chemical reaction that did not proceed to completion. The remaining five experiments were conducted in a transmission geometry and diagnosed velocimetrically at the sample/window interface. All five of these yielded profiles with a sharp shock followed by a more gradual approach to maximum interface velocity that was “rounded” to varying degree. These profiles proved difficult to interpret unambiguously due to the convolution of the reactive wave upon first shock with reflection of the lead wave and reshock or release by the window. Comparison with thermochemical calculations strongly suggests that the point of maximum interface velocity corresponds to the equilibrium reshock or release locus. We discuss the implications of this point for the practice of impedance matching based on the reflected Hugoniot of reactive materials such as polymers. The reactant and thermochemical products equations of state are developmental SESAME tables 97710 and 97720, respectively.

We test a range of standard implicit solvent models and protein forcefields for a set of 5 experimentally characterized, designed α-helical peptides. 65 combinations of forcefield and implicit solvent models are evaluated in >800 µs of molecular dynamics simulations. The data show that implicit solvent models generally fail to reproduce the experimentally observed secondary structure content, and none performs well for all 5 peptides. The results show that these models are not usefully predictive.

The physical, chemical and biological attributes of the Yukon River and tributary basins impact soil erosion, sediment transport and sediment delivery. The glacier, snow and permafrost melting, runoff, erosion, transport, deposition and storage of gravelly, sandy, silty and clayey sediments determine the habitat distribution and water quality within the river channels and floodplains. The ecological functioning, with food and nutrient delivery, migratory cues, breeding, habitats, and riparian and floodplain ecological cycles are all dependent on the transported sediment at specific times of the year. Annual temperatures have been rising since the 1840s which could contribute to higher runoff water flows and greater sedimentation. The primary objective was to document the sedimentation in the Yukon watershed with little soil erosion as a result of agriculture or urban development. The causes of the soil erosion and sedimentation were permafrost, alpine glacial melting, drilling for gas and oil, road construction, gold mining, cold war military sites, pipeline construction, forest fires and steep slopes.

De novo protein design is advancing rapidly. However, most designs are for single states. Here we report a de novo designed peptide that forms multiple α-helical-bundle states that are accessible and interconvertible under the same conditions. Usually in such designs amphipathic α helices associate to form compact structures with consolidated hydrophobic cores. However, recent rational and computational designs have delivered open α-helical barrels with functionalisable cavities. By placing glycine judiciously in the helical interfaces of an α-helical barrel, we obtain both open and compact states in a single protein crystal. Molecular dynamics simulations indicate a free-energy landscape with multiple and interconverting states. Together, these findings suggest a frustrated system in which steric interactions that maintain the open barrel and the hydrophobic effect that drives complete collapse are traded-off. Indeed, addition of a hydrophobic co-solvent that can bind within the barrel affects the switch between the states both in silico and experimentally., So far most of the de novo designed proteins are for single states only. Here, the authors present the de novo design and crystal structure determination of a coiled-coil peptide that assembles into multiple, distinct conformational states under the same conditions and further characterise its properties with biophysical experiments, NMR and MD simulations.

The design of peptides that assemble in membranes to form functional ion channels is challenging. Specifically, hydrophobic interactions must be designed between the peptides and at the peptide-lipid interfaces simultaneously. Here, we take a multi-step approach towards this problem. First, we use rational de novo design to generate water-soluble α-helical barrels with polar interiors, and confirm their structures using high-resolution X-ray crystallography. These α-helical barrels have water-filled lumens like those of transmembrane channels. Next, we modify the sequences to facilitate their insertion into lipid bilayers. Single-channel electrical recordings and fluorescent imaging of the peptides in membranes show monodisperse, cation-selective channels of unitary conductance. Surprisingly, however, an X-ray structure solved from the lipidic cubic phase for one peptide reveals an alternative state with tightly packed helices and a constricted channel. To reconcile these observations, we perform computational analyses to compare the properties of possible different states of the peptide.

MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the "last-resort" antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono- rather than multinuclear member of the alkaline phosphatase superfamily.

Allosteric regulation of the enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) controls the entry into aromatic amino acid biosynthesis in plants and microorganisms. DAH7PS has acquired a diverse range of allosteric machinery to enable this functionality. This review provides an overview of the current knowledge of the structural basis of allostery in this enzyme family and the evolutionary relationships between the different solutions to allosteric control of aromatic metabolite biosynthesis.

The chemical reaction zone (CRZ) of detonating explosives is defined by the leading, inert shock front, which compresses the explosive to the von Neumann (vN) spike condition on the unreacted Hugoniot, and the Chapman-Jouget (CJ) sonic locus condition, according to the Zel’dovich/von Neumann/Doering (ZND) one-dimensional theory of detonation. The CRZ is often measured using optical velocimetry techniques at a windowed interface; the window affects the reaction zone dynamics due to wave interactions from the interface. Fluoropolymer windows are attractive as they provide a near impedance match to most common explosives with initial densities 0ρ = 1.8-2.0 g/cm3. Poly(chlorotrifluoroethylene-co-vinylidene fluoride) (Kel-F 800, Lot 30013) was purchased from 3M Inc., St. Paul, Minnesota. Small (150 mm × 150 mm × 50 mm) billets were prepared by compression molding the polymer at 90 °C and ∼50,000 psi by Afton Plastics. This method resulted in a semi-transparent, golden-colored billet from which window samples were machined and polished to an optical clarity for experiments. To extend the window correction for Kel-F 800 (see D. M. Dattelbaum et al., Proceedings of the 15th International Detonation Symposium (2014)), a series of gas gun-driven plate impact experiments were performed using both VISAR (532 nm) and PDV (1550 nm) velocimetry methods to extend the window correction to a larger range of initial shock pressures and densities.

Optical pyrometry is a well-developed, broadly applicable method to determine temperature in dynamic compression experiments. However, it measures radiation from only the skin depth of the radiant material, is highly susceptible to spurious backgrounds, and requires an often-unmeasurable free parameter—the sample dynamic emissivity. Raman spectroscopy offers a method to determine temperature directly from fundamental theory, but it is practically limited in applications to a small subset of shock experiments. In this work, we describe an experiment allowing simultaneous application of Raman and pyrometric temperature techniques to benchmark a specific instance of pyrometry. We attempted both measurements on multiple experiments and compare the successful temperature results between the separate but highly repeatable shots. We find that dynamic shock temperatures inferred from Raman spectroscopy and pyrometry generally agree within the uncertainties of each measurement, although those uncertainties are larger than typical for a specially designed pyrometry experiment on a shocked metal sample.

In Pseudomonas aeruginosa (Pae), the shikimate pathway end product, chorismate, serves as the last common precursor for the biosynthesis of both primary aromatic metabolites, including phenylalanine, tyrosine and tryptophan, and secondary aromatic metabolites, including phenazine-1-carboxylic acid (PCA) and pyocyanin (PYO). The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyses the first committed step of the shikimate pathway, en route to chorismate. P. aeruginosa expresses multiple, distinct DAH7PSs that are associated with either primary or secondary aromatic compound biosynthesis. Here we report the structure of a type II DAH7PS, encoded by phzC as part of the duplicated phenazine biosynthetic cluster, from P. aeruginosa (PAO1) revealing for the first time the structure of a type II DAH7PS involved in secondary metabolism. The omission of the structural elements α2a and α2b, relative to other characterised type II DAH7PSs, leads to the formation of an alternative, dimeric, solution-state structure for this type II DAH7PS with an oligomeric interface that has not previously been characterised and that does not facilitate the formation of aromatic amino acid allosteric binding sites. The sequence similarity and, in particular, the common N-terminal extension suggest a common origin for the type II DAH7PSs from P. aeruginosa. The results described in the present study support an expanded classification of the type II DAH7PSs as type IIA and type IIB based on sequence characteristics, structure and function of the resultant proteins, and on defined physiological roles within primary or secondary metabolism.

In coiled-coil (CC) protein structures α-helices wrap around one another to form rope-like assemblies. Most natural and designed CCs have two–four helices and cyclic (Cn) or dihedral (Dn) symmetry. Increasingly, CCs with five or more helices are being reported. A subset of these higher-order CCs is of interest as they have accessible central channels that can be functionalised; they are α-helical barrels. These extended cavities are surprising given the drive to maximise buried hydrophobic surfaces during protein folding and assembly in water. Here, we show that α-helical barrels can be maintained by the strategic placement of β-branched aliphatic residues lining the lumen. Otherwise, the structures collapse or adjust to give more-complex multi-helix assemblies without Cn or Dn symmetry. Nonetheless, the structural hallmark of CCs—namely, knobs-into-holes packing of side chains between helices—is maintained leading to classes of CCs hitherto unobserved in nature or accessed by design., Higher order coiled coils with five or more helices can form α-helical barrels. Here the authors show that placing β-branched aliphatic residues along the lumen yields stable and open α-helical barrels, which is of interest for the rational design of functional proteins; whereas, the absence of β-branched side chains leads to unusual low-symmetry α-helical bundles.

Because of their special organization, multifunctional enzymes play crucial roles in improving the performance of metabolic pathways. For example, the bacterium Prevotella nigrescens contains a distinctive bifunctional protein comprising a 3-deoxy-d-arabino heptulosonate-7-phosphate synthase (DAH7PS), catalyzing the first reaction of the biosynthetic pathway of aromatic amino acids, and a chorismate mutase (CM), functioning at a branch of this pathway leading to the synthesis of tyrosine and phenylalanine. In this study, we characterized this P. nigrescens enzyme and found that its two catalytic activities exhibit substantial hetero-interdependence and that the separation of its two distinct catalytic domains results in a dramatic loss of both DAH7PS and CM activities. The protein displayed a unique dimeric assembly, with dimerization solely via the CM domain. Small angle X-ray scattering (SAXS)-based structural analysis of this protein indicated a DAH7PS-CM hetero-interaction between the DAH7PS and CM domains, unlike the homo-association between DAH7PS domains normally observed for other DAH7PS proteins. This hetero-interaction provides a structural basis for the functional interdependence between the two domains observed here. Moreover, we observed that DAH7PS is allosterically inhibited by prephenate, the product of the CM-catalyzed reaction. This allostery was accompanied by a striking conformational change as observed by SAXS, implying that altering the hetero-domain interaction underpins the allosteric inhibition. We conclude that for this C-terminal CM-linked DAH7PS, catalytic function and allosteric regulation appear to be delivered by a common mechanism, revealing a distinct and efficient evolutionary strategy to utilize the functional advantages of a bifunctional enzyme.

We describe de novo-designed α-helical barrels (αHBs) that bind and discriminate between lipophilic biologically active molecules. αHBs have five or more α-helices arranged around central hydrophobic channels the diameters of which scale with oligomer state. We show that pentameric, hexameric, and heptameric αHBs bind the environmentally sensitive dye 1,6-diphenylhexatriene (DPH) in the micromolar range and fluoresce. Displacement of the dye is used to report the binding of nonfluorescent molecules: palmitic acid and retinol bind to all three αHBs with submicromolar inhibitor constants; farnesol binds the hexamer and heptamer; but β-carotene binds only the heptamer. A co-crystal structure of the hexamer with farnesol reveals oriented binding in the center of the hydrophobic channel. Charged side chains engineered into the lumen of the heptamer facilitate binding of polar ligands: a glutamate variant binds a cationic variant of DPH, and introducing lysine allows binding of the biosynthetically important farnesol diphosphate.

Understanding and quantifying the strength or elastic limit of diamond single crystals is of considerable scientific and technological importance, and has been a subject of long standing theoretical and experimental interest. To examine the effect of crystalline anisotropy on strength and deformation of shocked diamond single crystals, plate impact experiments were conducted to measure wave profiles at various elastic impact stresses up to \ensuremath{\sim}120 GPa along [110] and [111] crystal orientations. Using laser interferometry, particle velocity histories and shock velocities in the diamond samples were measured and were compared with similar measurements published previously for shock compression along the [100] direction. Wave profiles for all three orientations showed large elastic wave amplitudes followed by time-dependent inelastic deformation. From the measured wave profiles, the elastic limits were determined under well characterized uniaxial strain loading conditions. The measured elastic wave amplitudes for the [110] and [111] orientations were lower for higher elastic impact stress (stress attained for an elastic diamond response), consistent with the result reported previously for [100] diamond. The maximum resolved shear stress (MRSS) on the {111}⟨110⟩ slip systems was determined for each orientation, revealing significant orientation dependence. The MRSS values for the [100] and [110] orientations (\ensuremath{\sim}33 GPa) are 25%--30% of theoretical estimates; the MRSS value for the [111] orientation is significantly lower (\ensuremath{\sim}23 GPa). Our results demonstrate that the MRSS depends strongly on the stress component normal to the {111} planes or the resolved normal stress (RNS), suggesting that the RNS plays a key role in inhibiting the onset of inelastic deformation. Lower elastic wave amplitudes at higher peak stress and the effect of the RNS are inconsistent with typical dislocation slip mechanisms of inelastic deformation, suggesting instead an inelastic response characteristic of shocked brittle solids. The present results show that the elastic limit (or material strength) of diamond single crystals cannot be described using traditional isotropic approaches, and typical plasticity models cannot be used to describe the inelastic deformation of diamond. Analysis of the measured wave profiles beyond the elastic limit, including characterization of the peak state, requires numerical simulations that incorporate a time-dependent, anisotropic, inelastic deformation response. Development of such a material description for diamond is an important need.

The high pressure dynamic response of polymers is important to a wide variety of applications. The details of compressibility and reactivity can have a large effect on overall behaviors of dynamic systems even when polymers are used in small amounts. Polyethylene is of broad interest for a variety of applications, as an ingredient and as a pure material. It is also of significant interest as a model system to understand the correlating effects of polymer dynamics in a material with a relatively simple chemical composition that can have highly varied properties through the alteration of molecular weight and associated crystallinity of the material. Although a variety of Hugoniot and dynamic information is available for polyethylene, it is a challenge to obtain information on the product equation of state at pressures high enough to achieve decomposition. Following recent successes in producing deep release states in compressed epoxy material, a series of plate impact experiments was performed in the same configuration on high density and ultra-high molecular weight polyethylene at pressures where there is only limited Hugoniot data. The experimental wave profiles are presented and the Hugoniot states are compared to previous results. In ongoing work, the release profiles are intended to calibrate a product equation of state.The high pressure dynamic response of polymers is important to a wide variety of applications. The details of compressibility and reactivity can have a large effect on overall behaviors of dynamic systems even when polymers are used in small amounts. Polyethylene is of broad interest for a variety of applications, as an ingredient and as a pure material. It is also of significant interest as a model system to understand the correlating effects of polymer dynamics in a material with a relatively simple chemical composition that can have highly varied properties through the alteration of molecular weight and associated crystallinity of the material. Although a variety of Hugoniot and dynamic information is available for polyethylene, it is a challenge to obtain information on the product equation of state at pressures high enough to achieve decomposition. Following recent successes in producing deep release states in compressed epoxy material, a series of plate impact experiments was performed in the same c...

A series of gas-gun experiments was conducted to obtain product isentropes for 70/30 weight percent Epon 828 epoxy resin/Jeffamine T-403 curing agent. Thin epoxy flyers backed by a low-density syntactic foam impacted lithium fluoride (LiF) windows at velocities up to 6.3 km/s, creating stresses in excess of those required for reaction (∼25 GPa). Following this, a rarefaction fan from the back of the thin flyer reduced the pressure in the epoxy products. VISAR and PDV were used to measure the velocity of the epoxy/LiF interface. Numerical simulations using several different treatments for the reactant-to-product transformation were conducted and the results compared with measured wave profiles. The best agreement with experiment was obtained using separate tabular equations of state for the reactants and products and an irreversible transformation to products.A series of gas-gun experiments was conducted to obtain product isentropes for 70/30 weight percent Epon 828 epoxy resin/Jeffamine T-403 curing agent. Thin epoxy flyers backed by a low-density syntactic foam impacted lithium fluoride (LiF) windows at velocities up to 6.3 km/s, creating stresses in excess of those required for reaction (∼25 GPa). Following this, a rarefaction fan from the back of the thin flyer reduced the pressure in the epoxy products. VISAR and PDV were used to measure the velocity of the epoxy/LiF interface. Numerical simulations using several different treatments for the reactant-to-product transformation were conducted and the results compared with measured wave profiles. The best agreement with experiment was obtained using separate tabular equations of state for the reactants and products and an irreversible transformation to products.

In this work a methodology for estimating the onset of reaction for porous polymer systems is presented. Shock Hugoniot data for a well-characterized polymer, polyurethane, is used to calibrate a functional relationship that captures the onset of reaction at several initial densities. In doing so, this function is then used to estimate the volume at which reaction is initiated in polyurethane at any initial density. The function is also extended to estimate the onset of reaction in less well-characterized polymer systems, polystyrene and SX358.

Polysulfone was shock loaded to pressures of 14.6–26.2 GPa in a series of gas gun-driven plate-impact experiments measuring material response with embedded electro-magnetic particle velocity gauges and optical velocimetry. The embedded electro-magnetic particle velocity gauges did not show a distinct two-wave structure but did show rounding that suggested a reaction but not a distinct separation of the reactants and product waves. In contrast, the transmission experiments fielded with optical velocimetry, with product pressures ranging from 21.0 to 26.2 GPa, showed well-defined two-wave structures due to shock-driven chemical decomposition of the polymer to products at a higher density. Distinct two-wave structures have not previously been published in literature during polymer compression; here, we observed these two-wave structures at both the polymer/lithium fluoride and polymer/polymethylmethacrylate interfaces. Hydrodynamic simulations of the experiments were performed using a newly constructed SESAME equation of state (EOS) for the polymer, a thermochemical EOS for the decomposition products, and an Arrhenius reaction rate model for the kinetics of the reaction. Simulation results also demonstrated two-wave structures but were unable to quantitatively reproduce either the embedded gauge or optical velocimetry data.

Allosteric regulation of enzyme activity plays important metabolic roles. Here we review the allostery of enzymes of amino-acid metabolism conferred by a discrete domain known as the ACT domain. This domain of 60-70 residues has a βαββαβ topology leading to a four-stranded β4β1β3β2 antiparallel sheet with two antiparallel helices on one face. Extensive sequence variation requires a combined sequence/structure/function analysis for identification of the ACT domain. Common features include highly varied modes of self-association of ACT domains, ligand binding at domain interfaces, and transmittal of allosteric signals through conformational changes and/or the manipulation of quaternary equilibria. A recent example illustrates the relatively facile adoption of this versatile module of allostery by gene fusion.

A 12-year cover crops study on the effects on SOC sequestration, storage, retention and loss and corn and soybean yields was conducted in southern Illinois. The use of cover crops for the maintenance and restoration of soil organic carbon (SOC) and soil productivity of previously eroded soils were evaluated. No-till (NT), chisel plow (CP), and moldboard plow (MP) treatment plots with and without cover crops were established in 2001. The plot area was on sloping with a moderately well drained, eroded soil. The average annual corn and soybean yields were statistically the same for NT, CP, and MP systems with and without cover crops. By 2012, the cover crop treatments had more SOC stock than that without cover crops for the same soil layer and tillage treatment. The NT, CP, and MP treatments all sequestered SOC with cover crops. A pre-treatment SOC stock baseline for rooting zone was used to validate the finding that cover crops sequestered SOC in the topsoil, subsoil and root zone of the NT, CP and MP treatments during the 12-year study. Additional sequestered SOC was lost as a result of being transported off of the plots and retained in lower slopes, transported to the stream or released to atmosphere.

The primary objective of this research was to determine the soil erosion rates in cropland of west central Illinois using a magnetic tracer (fly ash) and radio-cesium (cesium-137). The fly ash and cesium-137 accumulation on a stable cropland/hayland summit was determined using a spiral transect. This reference site was used as a baseline and then compared with the fly ash and cesium-137 levels in adjacent cropland landscape positions to estimate loss from erosion. The cesium-137 and fly ash data suggests that cropland lost significant sediment, fly ash and cesium-137 to erosion process especially from the upper and lower backslopes and footslope. The amount and rate of erosion predicted for each cropland landscape position using the fly ash and cesium-137 methods were determine for the 1910 to 1960, 1960 to 2009 and for the entire 100-year time periods. The fly ash and cesium-137 determined erosion amounts and annual soil erosion rate for cropland landscapes positions were highest for the upper and lower backslopes. Past backslope annual erosion rates for three different time periods were 51 Mt ha− 1 yr− 1 or less and above the tolerable soil loss rate of 11 Mt ha− 1 yr− 1 for Hickory soils. However, the predicted fly ash annual erosion rates for the last for the last 50 years using cesium-137 deposition was higher than annual erosion rates for the 1910 to 1960 time period using the difference between the two methods. The reason for the higher erosion rates for the 50 years after 1960 than before was most likely the continued use of moldboard plowing, up and down the slope plowing and the more intensive corn–soybean rotation without forages and small grains. These methods provide a way to document past cropland soil erosion amount and rates for three different time periods (1910 to 1960, 1960 to 2009 and 1910 to 2009).

Experimental data of the principal Hugoniot locus of variable density gas-phase noble and molecular gases are rare. The majority of shock Hugoniot data is either from shock tube experiments on low-pressure gases or from plate impact experiments on cryogenic, liquefied gases. In both cases, physics regarding shock compressibility, thresholds for the on-set of shock-driven ionization, and even dissociation chemistry are difficult to infer for gases at intermediate densities. We have developed an experimental target design for gas gun-driven plate impact experiments on noble gases at initial pressures between 200-1000 psi. Using optical velocimetry, we are able to directly determine both the shock and particle velocities of the gas on the principal Hugoniot locus, as well as clearly differentiate ionization thresholds. The target design also results in multiply shocking the gas in a quasi-isentropic fashion yielding off-Hugoniot compression data. We describe the results of a series of plate impact experiment...

The effects of particle morphology and initial density is examined with respect to the shock densification response of initially porous metal (Cu) and metal-oxide (CeO2) materials. Specifically, the ability of a continuum-level compaction model to capture the measured densification trends as a function of initial density and particle morphology are investigated. Particle morphology is observed to have little effect on the densification response of both Cu and CeO2, while initial density appears to have a stronger effect. In terms of continuum-level compaction strength, Cu and CeO2 exhibit dissimilar trends.

With the pharmaceutical industry striving for efficiency, cost-effectiveness, and sustainability, computational approaches such as molecular dynamics, quantum mechanics, and hybrid Quantum Mechanical/Molecular Mechanical methods are becoming increasingly important in drug discovery and development. Thanks to major software and hardware advances, these techniques enable don’t need these words robust and accurate predictions at a fraction of the computational costs previously required. These approaches are particularly effective in supporting the design of new active pharmaceutical ingredients, shedding light on the molecular mechanisms that govern therapeutically relevant biological processes, or developing synthetic routes relying on biocatalysis.

We are developing a new diagnostic useful for the non-invasive detection of projectile passage in the launch tube of a gas gun. The sensing element consists of one or more turns of single-mode optical fiber that is epoxy-bonded around the external circumference of the launch tube. The hoop strain induced in the launch tube by the passage of the projectile causes a momentary expansion of the fiber loop. This transient change in path length is detected with high sensitivity using a fiber optic-based interferometer developed by the NSTec Special Technologies Laboratory. We have fielded this new diagnostic, along with fiber optic Bragg grating (FBG) strain gauges we previously used for this purpose, on a variety of gas guns used for shock compression studies at Los Alamos and Sandia National Laboratories. We anticipate that, when coupled with a broad-range analog demodulator circuit, the fiber optic interferometer will have improved dynamic range over that of the FBG strain gauge approach. Moreover, in contra...

Most Illinois soil landscapes are nearly level and composed of somewhat poorly drained soils on slightly higher convex landscape positions and poorly drained soils on concave landscape positions. These soils are commonly on less than 1% slopes and are not thought to have water erosion and sediment deposition problems. A plot area near Monmouth, Illinois, was selected for study. The fly ash and soil organic C (SOC) content of Muscatune and Sable soils were determined. The crop sequence was corn and soybeans for the last 27 years, and plot area had been cultivated for the last 130 years. There is no tile drainage in the plot area. The primary objective of this research was to determine the extent Muscatune soil on 1% slope was eroded in the past 100 to 130 years of cultivation. The fly ash and SOC-rich sediment being transported to and deposited on the adjacent Sable soil in the same plot area were measured using a fly ash method. Fly ash is particulate matter resulting from high-temperature combustion of coal since 1910s and can be used as a time marker in upland soil erosion and depositional studies. For the 0- to 0.50-m layer, the Sable soil fly ash content is 19% higher and the SOC is similar (4% higher) to those of the Muscatune soil. The erosion rate, using the fly ash method, was 4.35 Mg ha year, which was higher than the calculated RUSLE2 erosion rate of 3.3 Mg ha year. Approximately 0.06 m of the thickness difference of 0.21 m between Sable and Muscatune A horizons was the result of erosion of the Muscatune soil and deposition on the Sable soil. The remaining difference was as a result of higher water table and saturated soil conditions for long periods.

This document summarizes the shock and release response of Epon 828 measured in the dynamic impact experiment 2s-905. Experimentally, a thin Kel-F impactor backed by a low impedance foam impacted an Epon 828 target with embedded electromagnetic gauges. Computationally, a one dimensional simulation of the impact event was performed, and tracer particles were located at the corresponding electromagnetic gauge locations. The experimental configuration was such that the Epon 828 target was initially shocked, and then allowed to release from the high-pressure state. Comparisons of the experimental gauge and computational tracer data were made to assess the performance of equation of state (EOS) 7603, a SESAME EOS for Epon 828, on and off the principal shock Hugoniot. Results indicate that while EOS 7603 can capture the Hugoniot response to better that 1%, while the sound speeds at pressure are under-predicted by 6 - 7%.

Multifunctional proteins play a variety of roles in metabolism. Here, we examine the catalytic function of the combined 3-deoxy-d-arabino heptulosonate-7-phosphate synthase (DAH7PS) and chorismate mutase (CM) from Geobacillus sp. DAH7PS operates at the start of the biosynthetic pathway for aromatic metabolites, whereas CM operates in a dedicated branch of the pathway for the biosynthesis of amino acids tyrosine and phenylalanine. In line with sequence predictions, the two catalytic functions are located in distinct domains, and these two activities can be separated and retain functionality. For the full-length protein, prephenate, the product of the CM reaction, acts as an allosteric inhibitor for the DAH7PS. The crystal structure of the full-length protein with prephenate bound and the accompanying small angle x-ray scattering data reveal the molecular mechanism of the allostery. Prephenate binding results in the tighter association between the dimeric CM domains and the tetrameric DAH7PS, occluding the active site and therefore disrupting DAH7PS function. Acquisition of a physical gating mechanism to control catalytic function through gene fusion appears to be a general mechanism for providing allostery for this enzyme.

We performed a series of plate impact experiments on NH3 gas initially at room temperature and at a pressure of ∼100 psi. Shocked states were determined by optical velocimetry and the temperatures by optical pyrometry, yielding compression ratios of ∼5-10 and second shock temperatures in excess of 7500 K. A first-principles statistical mechanical (thermochemical) approach that included chemical dissociation yielded reasonable agreement with experimental results on the principal Hugoniot, even with interparticle interactions neglected. Theoretical analysis of reshocked states, which predicts a significant degree of chemical dissociation, showed reasonable agreement with experimental data for higher temperature shots; however, reshock calculations required the use of interaction potentials. We rationalize the very different shock temperatures obtained, relative to previous results for argon, in terms of atomic versus molecular heat capacities.

Resume Introduction Les patients seropositifs VIH ont un risque eleve de complications infectieuses. La vaccination est un moyen de prevenir certaines de ces infections. Depuis 2006, de nouvelles recommandations d’experts ont elargi en France les indications vaccinales. Nous avons etudie le statut vaccinal de la cohorte alsacienne des patients seropositifs VIH, pour la grippe, le pneumocoque (PNC), les hepatites A (VHA) et B (VHB) et le tetanos. Patients et methode Du 20 aout 2007 au 15 septembre 2007, les patients seropositifs VIH de la COREVIH Alsace ont ete inclus dans une etude prospective de recueil de donnees demographiques, medicales, immunovirologiques et vaccinales. Resultats Trois cent trente et un patients ont ete inclus, 49 % asymptomatiques, 29 % symptomatiques non sida, 18 % sida, chez 4 % l’information n’etant pas renseignee. Soixante et onze patients (21,4 %) etaient vaccines pour la grippe, 11 patients (3,3 %) contre le PNC, 34 patients contre l’hepatite A, soit 16,3 % des sujets non immuns, 120 patients contre l’hepatite B, soit 60 % des sujets sans marqueurs seriques et 126 (56,2 %) contre le tetanos. Les principaux motifs de non-vaccination etaient l’absence de proposition par le praticien, le manque d’efficacite attendue et la crainte d’un effet immunovirologique deletere. Conclusion Les taux de couverture vaccinale pour les vaccins recommandes chez les sujets vivants avec le VIH restent tres insuffisants et parfois inferieurs a ceux de la population generale francaise. Il parait donc necessaire de sensibiliser prescripteurs et malades sur l’interet de ces vaccinations.

Flash lamp-illuminated integrating spheres have been used to measure the dynamic reflectance at the interface between a shocked metal target and a window maintaining the shock stress. In conjunction with radiance measurements, this method was recently used to study the pressure versus temperature phase boundary of the beta phase to body-centered-tetragonal transition of tin at around 13 GPa and, in separate experiments, to show a relationship between the reflectance and the phase fraction. We have used this technique to measure the ratio, R, of the dynamic reflectance relative to the ambient value for a high-purity zirconium sample attached to a sapphire window to study the alpha to omega phase transition. Nine experiments cover the range of stress, σ, from 4 to 16 GPa at six wavelengths from 500 to 1550 nm. The two phases in zirconium differ in volume by 6 GPa. Our results show that the relative reflectance decreases upon initial shock in the alpha state but increases as the material transforms to its omega state. The slope dR/dσ changes the sign around the phase transition. For shocks below 6 GPa, dR/dσ 0. In the stress region between 6 and 10 GPa, dR/dσ varies somewhat, perhaps due to the band structure or because the transition is incomplete there.

Resume Objectif On connait peu de choses de l’impact des traitements antiretroviraux hautement actifs ou de l’infection VIH elle-meme sur la fonction ovarienne. Le but de cette etude est d’evaluer la fonction ovarienne de femmes seropositives en comparaison avec les valeurs normales issues de femmes non infectees. Patientes et methodes Etude pilote prospective utilisant des marqueurs de la fonction ovarienne : le compte folliculaire antral (CFA) defini entre le 7 e et le 10 e jour du cycle et la FSH, l’inhibine B et l’hormone antimullerienne (AMH) comme dosages hormonaux de debut de phase folliculaire. Une analyse descriptive selon l’âge est realisee. Resultats Les resultats concernant 78 femmes infectees par le VIH sont presentes. Le compte folliculaire montre un fort taux d’anomalies (63 %) survenant etonnamment tot. Les marqueurs hormonaux sont concordants avec un taux d’anomalies de 36, 57 et 23 % pour la FSH, l’inhibine B et l’AMH respectivement. Discussion et conclusion Dans notre serie, l’infection par le VIH est associee a des signes d’insuffisance ovarienne prematuree. Ceci pourrait expliquer une diminution de la fertilite mais suggere egalement une menopause prematuree dans cette population qui devrait etre etroitement suivie.

An 8-year cover crop study was conducted in southern Illinois to evaluate the effects of conservation tillage systems on corn and soybean yields and for the maintenance and restoration of soil organic carbon (SOC) and soil productivity of previously eroded soils. In 2001, the no-till (NT), c

International audience; BACKGROUND: The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial. METHODS: Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count

Our document summarizes results from one-dimensional calculations performed to investigate the release behavior of reacted Epon 828. Two design goals were set, (1) the product phase had to be achieved upon the initial shock loading, and (2) a deep release state could be achieved. Both transmission and front surface impact geometry were investigated. Moreover, the two design criteria were met with the front surface impact design employing a modi ed projectile.

Allosteric regulation of protein function, the process by which binding of an effector molecule provokes a functional response from a distal site, is critical for metabolic pathways. Yet, the way the allosteric signal is communicated remains elusive, especially in dynamic, entropically driven regulation mechanisms for which no major conformational changes are observed. To identify these dynamic allosteric communication networks, we have developed an approach that monitors the pKa variations of ionizable residues over the course of molecular dynamics simulations performed in the presence and absence of an allosteric regulator. As the pKa of ionizable residues depends on their environment, it represents a simple metric to monitor changes in several complex factors induced by binding an allosteric effector. These factors include Coulombic interactions, hydrogen bonding, and solvation, as well as backbone motions and side chain fluctuations. The predictions that can be made with this method concerning the roles of ionizable residues for allosteric communication can then be easily tested experimentally by changing the working pH of the protein or performing single point mutations. To demonstrate the method's validity, we have applied this approach to the subtle dynamic regulation mechanism observed for Neisseria meningitidis 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase, the first enzyme of aromatic biosynthesis. We were able to identify key communication pathways linking the allosteric binding site to the active site of the enzyme and to validate these findings experimentally by reestablishing the catalytic activity of allosterically inhibited enzyme via modulation of the working pH, without compromising the binding affinity of the allosteric regulator.

A novel gas loading system was designed for the specific application of remotely loading high purity gases into targets for gas-gun driven plate impact experiments. The high purity gases are loaded into well-defined target configurations to obtain Hugoniot states in the gas phase at greater than ambient pressures.The small volume of the gas samples is challenging, as slight changing in the ambient temperature result in measurable pressure changes. Therefore, the ability to load a gas gun target and continually monitor the sample pressure prior to firing provides the most stable and reliable target fielding approach. We present the design and evaluation of a gas loading system built for the LANL 50 mm bore two-stage light gas gun. Targets for the gun are made of 6061 Al or OFHC Cu, and assembled to form a gas containment cell with a volume of approximately 1.38 cc. The compatibility of materials was a major consideration in the design of the system, particularly for its use with corrosive gases. Piping and valves are stainless steel with wetted seals made from Kalrez® and Teflon®. Preliminary testing was completed to ensure proper flow rate and that the proper safety controls were in place. The system hasmore » been used to successfully load Ar, Kr, Xe, and anhydrous ammonia with purities of up to 99.999 percent. The design of the system and example data from the plate impact experiments will be shown.« less

Temperature is notably the most difficult quantity to measure in shock compression experiments; however, it is critical for accurately constraining theoretical or tabular equations of state. Until now, the temperature achieved during the shock loading of porous materials could only be calculated. The technique presented in this report measures, for the first time, the shocked temperature of porous systems.

Fly ash, the particulate matter resulting from high temperature combustion of coal, was historically dispersed into the atmosphere and settled as fly-ash spheres on the surface soil from a variety of boilers, including those of steam locomotives and steam-powered farm machinery. In Central Illinois, fly ash provides a time marker extending back to 1850s, coinciding with the development of railroads and cultivation. Two railroads, the primary sources of fly ash, were constructed just south of the Cahokia study site in 1852 and 1854. The objectives of this study were to determine: (1) the distribution, depth of occurrence and the total amount of fly ash present in soil profiles on stable, cultivated and uncultivated summit sites with little or no soil erosion; (2) the effects of elevation, aspect, slope gradient, landscape position, distance from source, past vegetation and time on the amount and depth of fly ash; (3) the effects of erosion on sloping sideslopes; and (4) the amount of deposition of fly-ash rich sediment on footslopes and toeslopes. Total fly-ash content of soil was similar for stable, cultivated and uncultivated summits. Two mound sideslopes maintained a high amount of fly ash because of a lack of cultivation and erosion for the past 80 or more years. Erosion reduced the depth of occurrence and the amount of fly ash present on cultivated sideslopes. It appeared that fly-ash content was initially deposited uniformly within the local landscape even though there were slight variations in the aspect, elevation, slope gradient, and distance from the source. The erosion phases of the soils on all landscape positions were determined based on the amount of fly ash remaining in soil surface layers. Accelerated erosion of cultivated sideslopes resulted in the deposition of fly-ash rich sediment on the adjacent footslopes or toeslopes. The proposed fly-ash method provides a tool to assess the extent of soil translocation from a cultivated landscape and subsequent deposition.