Volume-checking tool

Tool, consisting of a graduated storage vessel and a control panel, can determine the amount of gas entrained by fluid in a closed system, the amount of fluid remaining in a dried system of known volume, or the volume of a container of unknown size

Forecasting the Response of Earth’s Surface to Future Climatic and Land Use Changes: A Review of Methods and Research Needs

In the future, Earth will be warmer, precipitation events will be more extreme, global mean sea level will rise, and many arid and semiarid regions will be drier. Human modifications of landscapes will also occur at an accelerated rate as developed areas increase in size and population density. We now have gridded global forecasts, being continually improved, of the climatic and land use changes (C&LUC) that are likely to occur in the coming decades. However, besides a few exceptions, consensus forecasts do not exist for how these C&LUC will likely impact Earth-surface processes and hazards. In some cases, we have the tools to forecast the geomorphic responses to likely future C&LUC. Fully exploiting these models and utilizing these tools will require close collaboration among Earth-surface scientists and Earth-system modelers. This paper assesses the state-of-the-art tools and data that are being used or could be used to forecast changes in the state of Earth’s surface as a result of likely future C&LUC. We also propose strategies for filling key knowledge gaps, emphasizing where additional basic research and/or collaboration across disciplines are necessary. The main body of the paper addresses cross-cutting issues, including the importance of nonlinear/threshold-dominated interactions among topography, vegetation, and sediment transport, as well as the importance of alternate stable states and extreme, rare events for understanding and forecasting Earth-surface response to C&LUC. Five supplements delve into different scales or process zones (global-scale assessments and fluvial, aeolian, glacial/periglacial, and coastal process zones) in detail

The value of preventing malaria in Tembien, Ethiopia

The authors measure the monetary value households place on preventing malaria in Tembien, Tigray Region, Ethiopia. They estimate a household demand function for a hypothetical malaria vaccine and compute the value of preventing malaria as the household's maximum willingness to pay to provide vaccines for all family members. They contrast willingness to pay with the traditional costs of illness (medical costs and time lost because of malaria). Their results indicate that the value of preventing malaria with vaccines is about US$36 a household a year, or about 15 percent of imputed annual household income. This is, on average, about two or three times the expected household cost of illness. Despite the great benefits from preventing malaria, the fact that vaccine demand is price inelastic suggests that it will be difficult to achieve significant market penetration unless the vaccine is subsidized. The authors obtain similar results for insecticide-treated bed nets. Their estimates of household demand functions for bed nets suggest that at a price that might permit cost recovery (US$6 a bed net), only a third of the population of a 200-person village would sleep under bed nets.Early Child and Children's Health,Public Health Promotion,Disease Control&Prevention,Health Monitoring&Evaluation,Economic Theory&Research,Health Monitoring&Evaluation,Economic Theory&Research,Climate Change,Environmental Economics&Policies,Early Child and Children's Health

Human Heme Oxygenase Oxidation of 5- and 15-Phenylhemes

Human heme oxygenase-1 (hHO-1) catalyzes the O2- dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the -meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IX . Surprisingly, a 15-methyl substituent caused exclusive cleavage at the -meso- rather than at the normal, unsubstituted -meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the porphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IX and oxidizes 15- phenylheme at the -meso position to give 10-phenylbiliverdin IX . The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-Å crystal structures of the hHO-1 complexes with 1- and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141–150 and in the proximal Lys18 and Lys22. In the 5-phenylhemehHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26–42 near the -meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity.Fil: Wang, Jingling. University of California; Estados UnidosFil: Niemevz, Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Lad, Latesh. University of California; Estados UnidosFil: Huang, Liusheng. University of California; Estados UnidosFil: Alvarez, Diego Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Buldain, Graciela Yolanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Poulos, Thomas L.. University of California; Estados UnidosFil: Ortiz de Montellano, Paul R.. University of California; Estados Unido

Hillslope Asymmetry Maps Reveal Widespread, Multi-Scale Organization

Hillslope asymmetry is the condition in which oppositely-facing hillslopes within an area have differing average slope angles, and indicates aspect-related variability in hillslope evolution. As such, the presence, orientation and magnitude of asymmetry may be a useful diagnostic for understanding process dominance. We present a new method for quantifying and mapping the spatial distribution of hillslope asymmetry across large areas. Resulting maps for the American Cordillera of the Western Hemisphere and the western United States reveal that hillslope asymmetry is widespread, with distinct trends at continental to drainage scales. Spatial patterns of asymmetry correlate with latitude along the American Cordillera, mountain-range orientation for many ranges in the western United States, and elevation in the Idaho Batholith of the Northern Rocky Mountains. Spatial organization suggests that non-stochastic, process-driven controls cause these patterns. The hillslope asymmetry metric objectively captures previously-documented extents and frequencies of valley asymmetry for the Gabilan Mesa of the central California Coast Range. Broad-scale maps of hillslope asymmetry are of interest to a wide range of disciplines, as spatial patterns may reflect the influence of tectonics, atmospheric circulation, topoclimate, geomorphology, hydrology, soils and ecology on landscape evolution. These maps identify trends and regions of hillslope asymmetry, allow possible drivers to be spatially constrained, and facilitate the extrapolation of site-specific results to broader regions

Structural Basis for Isoform Selective Nitric Oxide Synthase Inhibition by Thiophene-2-Carboximidamides

The over production of nitric oxide in the brain by neuronal nitric oxide synthase (nNOS) is associated with a number of neurodegenerative diseases. Although inhibiting nNOS is an important therapeutic goal, it is important not to inhibit endothelial NOS (eNOS) owing to the critical role played by eNOS in maintaining vascular tone. While it has been possible to develop nNOS selective aminopyridine inhibitors, many of the most potent and selective inhibitors exhibit poor bioavailability properties. Our group and others have turned to more biocompatible thiophene-2-carboximidamides (T2C) inhibitors as potential nNOS selective inhibitors. We have used crystallography and computational methods to better understand how and why 2 commercially developed T2C inhibitors exhibit selectivity for human nNOS over human eNOS. As with many of the aminopyridine inhibitors, a critical active site Asp residue in nNOS vs Asn in eNOS is largely responsible for controlling selectivity. We also present thermodynamic integration results to better understand the change in pKa and thus charge of inhibitors once bound to the active site. In addition, relative free energy calculations underscore the importance of enhanced electrostatic stabilization of inhibitors bound to the nNOS active site compared to eNOS

Evolutionary History of a Specialized P450 Propane Monooxygenase

The evolutionary pressures that shaped the specificity and catalytic efficiency of enzymes can only be speculated. While directed evolution experiments show that new functions can be acquired under positive selection with few mutations, the role of negative selection in eliminating undesired activities and achieving high specificity remains unclear. Here we examine intermediates along the ‘lineage’ from a naturally occurring C12–C20 fatty acid hydroxylase (P450BM3) to a laboratory-evolved P450 propane monooxygenase (P450PMO) having 20 heme domain substitutions compared to P450BM3. Biochemical, crystallographic, and computational analyses show that a minimal perturbation of the P450BM3 fold and substrate-binding pocket accompanies a significant broadening of enzyme substrate range and the emergence of propane activity. In contrast, refinement of the enzyme catalytic efficiency for propane oxidation (not, vert, similar 9000-fold increase in kcat/Km) involves profound reshaping and partitioning of the substrate access pathway. Remodeling of the substrate-recognition mechanisms ultimately results in remarkable narrowing of the substrate profile around propane and enables the acquisition of a basal iodomethane dehalogenase activity as yet unknown in natural alkane monooxygenases. A highly destabilizing L188P substitution in a region of the enzyme that undergoes a large conformational change during catalysis plays an important role in adaptation to the gaseous alkane. This work demonstrates that positive selection alone is sufficient to completely respecialize the cytochrome P450 for function on a nonnative substrate

Engineered ascorbate peroxidase as a genetically-encoded reporter for electron microscopy

Electron microscopy (EM) is the standard method for imaging cellular structures with nanometer resolution, but existing genetic tags are inactive in most cellular compartments1 or require light and are difficult to use2. Here we report the development of a simple and robust EM genetic tag, called “APEX,” that is active in all cellular compartments and does not require light. APEX is a monomeric 28 kDa peroxidase that withstands strong EM fixation to give excellent ultrastructural preservation. We demonstrate the utility of APEX for high-resolution EM imaging of a variety of mammalian organelles and specific proteins. We also fused APEX to the N- or C-terminus of the mitochondrial calcium uniporter (MCU), a newly identified channel whose topology is disputed3,4. MCU-APEX and APEX-MCU give EM contrast exclusively in the mitochondrial matrix, suggesting that both the N-and C-termini of MCU face the matrix