bluuebunny/crossref_metadata_2025 huggingface dataset:
The Syntax and Sense of theAhuna Vairiia
Authors: AHMADI AMIR
Published: October 2012

One may conclude from the lull in publications on the GāthicAhuna Vairiiathat a satisfactory understanding of the stanza is at hand. This is, however, not the case. The last substantial treatment of the stanza is from Humbach (1991 II) in his 1991 two-volume edition of the Old Avestan texts. Somewhat less extensive is the discussion we find in Kellens’ and Pirart's monumental three-volume edition and study of the Old Avestan texts (1991). In 1975, Insler published a detailed article on theAhuna Vairiia. The late 1950s saw the appearance of four studies of the stanza by distinguished Avesta scholars: Benveniste, Humbach, Duchesne-Guillemin and Hinz. As for the number of translations there are, it virtually equals the number of scholars in the field. The source of the difficulties is the syntax of the stanza. The disagreements are due for the most part to the scholar's analysis of syntactic units. Thus the variety of translations may be reduced to a few basic types.
Visualization of ATP with Luciferin-Luciferase Reaction in Mouse Skeletal Muscles Using an “In Vivo Cryotechnique”
Authors: Terada N. , Saitoh Y. , Saitoh S. , Ohno N. , Fujishita K. , Koizumi S. , Ohno S.
Published: October 2012

Adenosine triphosphate (ATP) is a well-known energy source for muscle contraction. In this study, to visualize localization of ATP, a luciferin-luciferase reaction (LLR) was performed in mouse skeletal muscle with an “in vivo cryotechnique” (IVCT). First, to confirm if ATP molecules could be trapped and detected after glutaraldehyde (GA) treatment, ATP was directly attached to glass slides with GA, and LLR was performed. The LLR was clearly detected as an intentional design of the ATP attachment. The intensity of the light unit by LLR was correlated with the concentration of the GA-treated ATP in vitro. Next, LLR was evaluated in mouse skeletal muscles with IVCT followed by freeze-substitution fixation (FS) in acetone-containing GA. In such tissue sections the histological structure was well maintained, and the intensity of LLR in areas between muscle fibers and connective tissues was different. Moreover, differences in LLR among muscle fibers were also detected. For the IVCT-FS tissue sections, diaminobenzidine (DAB) reactions were clearly detected in type I muscle fibers and erythrocytes in capillaries, which demonstrated flow shape. Thus, it became possible to perform microscopic evaluation of the numbers of ATP molecules in the mouse skeletal muscles with IVCT, which mostly reflect living states.
Aging Increases Nuclear Chromatin Entropy of Erythroid Precursor Cells in Mice Spleen Hematopoietic Tissue
Authors: Pantic Igor , Pantic Senka , Paunovic Jovana
Published: October 2012

Despite recent advances in hematopoietic tissue research, effects of aging on hematopoietic erythroid precursor (EP) cells are unclear. In this article we present results suggesting that chromatin textural entropy of EP cells in mouse spleen increases with age, while chromatin homogeneity decreases. The experiment was conducted on a total of 32 male Swiss white mice. Spleen tissue was acquired from four age groups: 10 days, 1 month, 4 months, and 7 months old mice. A total of 640 randomly selected, nonoverlapping EP cell nuclei (20 per animal) were analyzed using the gray level co-occurrence matrix method. There was statistically highly significant difference between the age groups, both in chromatin entropy (ANOVA,F= 12.99,p< 0.0001) and in homogeneity (ANOVA,F= 7.05,p< 0.001). When the individual groups were compared (ANOVApost hoctest), statistical difference was detected in all group pairs, except between the animals 4 months and 7 months old, either in chromatin entropy or homogeneity. The detected increase of chromatin disorder in mouse juvenile period/early adulthood suggests that cell intrinsic factors such as epigenetic dysregulation and DNA damage accumulation may have an important role in EP cell aging.
Improving Fabrication and Application of Zach Phase Plates for Phase-Contrast Transmission Electron Microscopy
Authors: Hettler Simon , Gamm Björn , Dries Manuel , Frindt Nicole , Schröder Rasmus R. , Gerthsen Dagmar
Published: October 2012

Zach phase plates (PPs) are promising devices to enhance phase contrast in transmission electron microscopy. The Zach PP shifts the phase of the zero-order beam by a strongly localized inhomogeneous electrostatic potential in the back focal plane of the objective lens. We present substantial improvements of the Zach PP, which overcome previous limitations. The implementation of a microstructured heating device significantly reduces contamination and charging of the PP structure and extends its lifetime. An improved production process allows fabricating PPs with reduced dimensions resulting in lower cut-on frequencies as revealed by simulations of the electrostatic potential. Phase contrast with inversion of PbSe nanoparticles is demonstrated in a standard transmission electron microscope with LaB6cathode by applying different voltages.
ON THIN OR SLENDER BODIES
Authors: TUCK E. O. , STOKES Y. M.
Published: October 2012

This is a review of thin-body and slender-body theories, with indications of some new applications. Topics discussed include bodies with near-constant surface pressure, subsonic and supersonic aerodynamics, ship hydrodynamics, slender bodies in Stokes flow, slender footings in elastic media, and slender moonpools. Mathematical features of the thin- and slender-body approximations are also discussed, especially nonlocal convolution terms modelling three-dimensionality in the otherwise two-dimensional near field, end effects, and the role of the logarithm of the slenderness ratio. This review was presented by the first author as the IMA Lighthill Memorial Lecture at the British Applied Mathematics Colloquium (BAMC) 2004.
UK Pension Reforms: Is Gender Still an Issue?
Authors: Ginn Jay , MacIntyre Ken
Published: October 2012

The UK Pensions Commission confirmed that women's domestic roles are crucial to their pension disadvantage. As a result, measures enacted in the Pensions Acts of 2007 and 2008 aimed to make state pensions more inclusive for those with periods out of the labour market for family caring, as well as encouraging more saving through private pensions by those with low to moderate earnings. Will these legislative changes, and subsequent reforms and plans, substantially reduce future gender inequality in UK pensions? In this article, we suggest the benefits to women will be patchy and overall less than expected. We first review the interaction of male-oriented pension schemes with the gendered division of caring labour and how this has changed for later cohorts of women. We then analyse, from a gender perspective, the pension reforms and proposals since 2007. Finally, we consider policy alternatives that would give women a better deal in pensions and conclude with an assessment of the mixed effects of pension reforms.
The 2010 U.S. health care reform: approaching and avoiding how other countries finance health care
Authors: White Joseph
Published: October 2012

This article describes and analyzes the U.S. health care legislation of 2010 by asking how far it was designed to move the U.S. system in the direction of practices in all other rich democracies. The enacted U.S. reform could be described, extremely roughly, as Japanese pooling with Swiss and American problems at American prices. Its policies are distinctive, yet nevertheless somewhat similar to examples in other rich democracies, on two important dimensions: how risks are pooled and the amount of funds redistributed to subsidize care for people with lower incomes. Policies about compelling people to contribute to a finance system would be further from international norms, as would the degree to which coverage is set by clear and common substantive standards – that is, standardization of benefits. The reform would do least, however, to move the United States toward international practices for controlling spending. This in turn is a major reason why the results would include less standard benefits and incomplete coverage. In short, the United States would remain an outlier on coverage less because of a failure to make an effort to redistribute – a lack of solidarity – than due to a failure to control costs.
The new global lithological map database GLiM: A representation of rock properties at the Earth surface
Authors: Hartmann Jens , Moosdorf Nils
Published: October 2012

Lithology describes the geochemical, mineralogical, and physical properties of rocks. It plays a key role in many processes at the Earth surface, especially the fluxes of matter to soils, ecosystems, rivers, and oceans. Understanding these processes at the global scale requires a high resolution description of lithology. A new high resolution global lithological map (GLiM) was assembled from existing regional geological maps translated into lithological information with the help of regional literature. The GLiM represents the rock types of the Earth surface with 1,235,400 polygons. The lithological classification consists of three levels. The first level contains 16 lithological classes comparable to previously applied definitions in global lithological maps. The additional two levels contain 12 and 14 subclasses, respectively, which describe more specific rock attributes. According to the GLiM, the Earth is covered by 64% sediments (a third of which are carbonates), 13% metamorphics, 7% plutonics, and 6% volcanics, and 10% are covered by water or ice. The high resolution of the GLiM allows observation of regional lithological distributions which often vary from the global average. The GLiM enables regional analysis of Earth surface processes at global scales. A gridded version of the GLiM is available at the PANGEA Database (http://dx.doi.org/10.1594/PANGAEA.788537).
Infiltration of Martian outflow channel floodwaters into lowland cavernous systems
Authors: Rodriguez J. Alexis P. , Bourke Mary , Tanaka Kenneth L. , Miyamoto Hideaki , Kargel Jeffrey , Baker Victor , Fairén Alberto G. , Davies Richard J. , Bridget Lynne , Santiago Rogelio Linares , Hernández Mario Zarroca , Berman Daniel C.
Published: October 2012

The hydrosphere of Mars has remained mostly concealed within the subsurface for the past ∼3.5 Gyr. Localized rupturing of the permafrost‐capped crust led to voluminous groundwater discharges that carved some of the largest known channels in the solar system. However, our knowledge of the nature of the flows and their ultimate fate remains incomplete, partly because diagnostic landforms at outflow channel termini have been largely destroyed or buried. The Hebrus Valles outflow channels were excavated by fluid discharges that emanated from two point sources, and they mostly terminate in systems of fractures and depressions within the northern plains. Our investigation indicates that outflow channel floodwaters were captured and reabsorbed into the subsurface in zones where caverns developed within the northern plains. These findings imply that the study region comprises the only known location in the Martian northern lowlands where the fate of outflow channel discharges can be assessed with confidence. We propose that evacuation of subsurface materials via mud volcanism was an important process in cavern formation. Our conceptual model provides a hypothesis to account for the fate of sediments and fluids from some of the Martian outflow channels. It also reveals a mechanism for lowland cavern formation and upper crustal volatile enrichment after the development of the Martian global cryosphere.
Geologic heterogeneity can produce aseismic slip transients
Authors: Skarbek R. M. , Rempel A. W. , Schmidt D. A.
Published: October 2012

Slow slip and tectonic tremor in subduction zones take place at depths where there is abundant evidence for distributed shear over broad zones (∼10–103 m) composed of rocks with marked differences in mechanical properties. Here we model quasi‐dynamic rupture along faults composed of material mixtures characterized by different rate‐and‐state‐dependent frictional properties to determine the parameter regime capable of producing slow slip in an idealized subduction zone setting. Keeping other parameters fixed, the relative proportions of velocity‐weakening (VW) and velocity‐strengthening (VS) materials control the sliding character (stable, slow, or dynamic) along the fault. The stability boundary between slow and dynamic is accurately described by linear analysis of a double spring‐slider system with VW and VS blocks. Our results place bounds on the volume fractions of VW material present in heterogeneous geological assemblages that host slow slip and tremor in subduction zones.
Harmonic minimization waveforms for modulated heating experiments at HAARP
Authors: Jin G. , Spasojevic M. , Cohen M. B. , Inan U. S.
Published: October 2012

Modulated High Frequency (few MHz) heating of the D‐region ionosphere under the auroral electrojet is capable of generating extremely low frequency (ELF) radio waves in the few kilohertz range by affecting the conductivity of theD‐region. The HF heating is nonlinear and results in the generation of harmonics at integer multiples of the ELF modulation frequency with ∼1% of the total power outside the fundamental when sinusoidal amplitude modulation is applied to the HF carrier. For the purpose of harmonic minimization, we present a modulation scheme designed to create a sinusoidal change in the Hall conductivity at a particular altitude in the ionosphere. The modulation waveform is generated by inverting a numerical HF heating model, starting from the desired conductivity time series, and obtaining the HF power envelope at the bottom of the ionosphere. The inverted envelopes (referred to as inv‐sin waveforms) are highly sensitive to the assumed ionospheric density profile and simulations indicate that these waveforms have less harmonic distortion compared to sinusoidal modulation when the actual ionospheric density is similar to or less dense than the one assumed. Experimental results indicate that sinusoidal amplitude modulation may still be preferred since it is more robust to the highly variable ionospheric profile while square wave modulation is more efficient in generation of ELF waves when harmonic distortion is not important. The inv‐sin waveforms are more efficient than sinusoidal modulation while still suffering from less harmonic distortion than square wave modulation suggesting a tradeoff between harmonic distortion and ELF generation efficiency.
Relative dispersion of surface drifters in a barrier reef region
Authors: Mantovanelli A. , Heron M. L. , Heron S. F. , Steinberg C. R.
Published: October 2012

The spreading of two clusters of satellite‐tracked surface drifters was quantified by ‘relative dispersion’ and ‘relative diffusivity’ (the time derivative of relative dispersion) in two regions of the southern Great Barrier Reef (GBR): a low‐density reef matrix of complex topography and a shelf lagoon over flat bathymetry. Although based on a small data set, averaged values of these parameters over a 12 day period with concurrent measurements for the two regions indicated that relative dispersion and diffusivity of drifter pairs were 182 and 52 times greater, respectively, along the reef matrix than found in the lagoon. Relative diffusivities in the southern GBR were anisotropic and varied largely in space and time within the spatial scales of 1–100 km and temporal scales of hours to 16–20 days; they were considerably enhanced by high‐frequency tidal processes. Submesoscale processes (<20 km) were important in the southern GBR, particularly in areas with complex topography where secondary circulations around the reefs and regions of steep bathymetry caused abrupt increase in dispersion. Although the dispersion was much higher along the reef matrix, the presence of ring circulations around the islands and wake eddies in the lee of islands can act as trapping mechanisms to keep particles within the reef matrix, retarding the loss to open water areas. This provides an efficient physical mechanism for both enhancing larval connectivity between reefs and, at the same time, trapping larvae when in the vicinity of reefs.
Wind‐forcing of volume transport through Lancaster Sound
Authors: Peterson Ingrid , Hamilton James , Prinsenberg Simon , Pettipas Roger
Published: October 2012

Volume and freshwater transport through Lancaster Sound are estimated from mooring measurements collected in eastern Barrow Strait for 13 years between 1998 and 2011. Estimates from 2006 to 2011 confirm the relationship between surface wind and volume transport derived from data collected between 1998 and 2006. Volume transport through Barrow Strait along the Northwest Passage is significantly correlated with northeastward winds in the Beaufort Sea, parallel to the western coasts of the Canadian Arctic Archipelago, at monthly to interannual time scales. The location and wind direction for which there is maximum correlation are consistent with the flow being driven by a sea level difference between opposite ends of the Passage, and the difference being determined by setup caused by alongshore winds in the Beaufort Sea. Monthly alongshore wind anomalies account for 43% of the variance of the transport anomalies (p < 0.01). Examination of the residuals, after subtracting the volume transport driven by the Beaufort Sea winds from the total transport, showed that they are not significantly correlated with winds in Baffin Bay (p > 0.05). The annual cycles of the total volume transport and its part attributed to the Beaufort Sea wind both have peaks in the summer and are lowest in the autumn. Correlations of the volume transport anomaly with ice velocity anomalies are lower than with surface wind anomalies.
Mechanisms for variable North Atlantic–Nordic seas exchanges
Authors: Sandø A. B. , Nilsen J. E. Ø. , Eldevik T. , Bentsen M.
Published: October 2012

The variable oceanic exchanges between the Nordic seas and the Atlantic proper have been investigated using an isopycnic coordinate ocean model for the period 1948–2007. Observed and simulated time series of volume transports in the Denmark Strait (DS), between Iceland and the Faroe Islands, and in the Faroe‐Shetland Channel (FSC) are used to evaluate the model, and the model captures much of the variability. The inflow of Atlantic Water in the FSC and the outflow of light Polar Water in the DS and of dense Overflow Water in both FSC and DS are all found to covary with an atmospheric pattern resembling the North Atlantic Oscillation. An increase in the FSC inflow is associated with a decrease in the FSC overflow and an increase in the DS overflow. The exchanges' response to the atmospheric forcing is mainly of a barotropic nature, but they are also influenced by baroclinic processes. The modeled antiphase between FSC inflow and overflow is connected to a vertical displacement of the isopycnal separating the two water masses in the channel and along the path of the Norwegian Atlantic Slope Current, consistent with hydraulic control of the FSC exchanges.
Nonlocal transport due to Langmuir circulation in a coastal ocean
Authors: Kukulka T. , Plueddemann A. J. , Sullivan P. P.
Published: October 2012

We present observations and simulations of large‐scale velocity structures associated with turbulent boundary layer dynamics of a coastal ocean. Special purpose acoustic Doppler current profiler measurements revealed that such structures were frequently present, in spite of complex coastal environmental conditions. Large eddy simulation results are only consistent with these observations if the Langmuir circulation (LC) effect due to wave‐current interaction is included in the model. Thus, model results indicate that the observed large‐scale velocity structures are due to LC. Based on these simulations, we examine the shift of energetics and transport from a local regime for purely shear‐driven turbulence to a nonlocal regime for turbulence with LC due to coherent large‐scale motions that span the whole water column. Without LC, turbulent kinetic energy (TKE) dissipation rates approximately balance TKE shear production, consistent with solid wall boundary layer turbulence. This stands in contrast to the LC case for which the vertical TKE transport plays a dominant role in the TKE balance. Conditional averages argue that large‐scale LC coherent velocity structures extract only a small fraction of energy from the wavefield but receive most of their energy input from the Eulerian shear. The analysis of scalar fields and Lagrangian particles demonstrates that the vertical transport is significantly enhanced with LC but that small‐scale mixing may be reduced. In the presence of LC, vertical scalar fluxes may be up gradient, violating a common assumption in oceanic boundary layer turbulence parameterizations.
Comment on “Hydrocarbon emissions characterization in the Colorado Front Range: A pilot study” by Gabrielle Pétron et al.
Authors: Levi Michael A.
Published: October 2012

Pétron et al. (2012) have recently observed and analyzed alkane concentrations in air in Colorado's Weld County and used them to estimate the volume of methane vented from oil and gas operations in the Denver‐Julesburg Basin. They conclude that “the emissions of the species we measured are most likely underestimated in current inventories”, often by large factors. However, their estimates of methane venting, and hence of other alkane emissions, rely on unfounded assumptions about the composition of vented natural gas. We show that relaxing those assumptions results in much greater uncertainty. We then exploit previously unused observations reported in Pétron et al. (2012) to constrain methane emissions without making assumptions about the composition of vented gas. This results in a new set of estimates that are consistent with current inventories but inconsistent with the estimates in Pétron et al. (2012). The analysis also demonstrates the value of the mobile air sampling method employed in Pétron et al. (2012).
Towards the use of cloud microphysical properties to simulate IASI spectra in an operational context
Authors: Faijan François , Lavanant Lydie , Rabier Florence
Published: October 2012

Capabilities and limitations of two fast radiative transfer models simulating cloudy spectra of the Infrared Atmospheric Sounding Interferometer (IASI) have been investigated in this paper. These models include a better modeling of the clouds than current operational fast forward models, such as scattering effects of the radiation in the cloud layer. An accurate simulation of the IASI spectra in the presence of ice clouds or for vertically extended clouds is a necessary step toward the use of these cloud‐affected radiances in an operational context. Through a collocation of IASI observations with an independent data set from the Lindenberg ground‐based station and the A‐Train space‐borne active instruments, this study first examines the accuracy of the fast radiative transfer models to simulate the cloudy spectra and provides some indications of confidence in the use of the cloud microphysical and optical properties. This first step shows the high sensitivity toward the cloudy inputs (crystal shapes, particle size, and cloud water content) which can reach several kelvins. It also provides a screening method to process cloudy radiances and to deal with the strong sensitivity of the fast radiative transfer model. The performance of the scattering fast radiative transfer models is then assessed in a global operational through simulations during a one week period over the globe, with the profiles of cloud variables from the ECMWF forecast used to compute the radiances. The applied screening method has reduced the standard deviation between simulated and observed spectra from 9 to 3 K.
Interannual variability of outgoing longwave radiation as observed by AIRS and CERES
Authors: Susskind Joel , Molnar Gyula , Iredell Lena , Loeb Norman G.
Published: October 2012

The paper examines spatial anomaly time series of outgoing longwave radiation (OLR) and Clear Sky OLR (OLRCLR) as determined using observations from CERES Terra and AIRS over the time period September 2002 through June 2011. We find excellent agreement of the two OLR data sets in almost every detail down to the 1° × 1° spatial grid point level. The extremely close agreement of OLR anomaly time series derived from observations by two different instruments implies high stability of both sets of results. Anomalies of global mean, and especially tropical mean, OLR are shown to be strongly correlated with an El Niño Index. These correlations explain that the recent global and tropical mean decreases in OLR over the time period studied are primarily the result of a transition from an El Niño condition at the beginning of the data record to La Niña conditions toward the end of the data period. We show that the close correlation of mean OLR anomalies with the El Niño Index can be well accounted for by temporal changes of OLR within two spatial regions, one to the east of, and one to the west of, the NOAA Niño‐4 region. Anomalies of OLR in these two spatial regions are both strongly correlated with the El Niño Index as a result of the strong anticorrelation of anomalies of cloud cover and midtropospheric water vapor in these two regions with the El Niño Index.
A numerical issue in calculating the coupled carbon and water fluxes in a climate model
Authors: Sun Ying , Gu Lianhong , Dickinson Robert E.
Published: October 2012

The Community Land Model (CLM) uses a fixed‐point iteration approach to solve the coupled photosynthesis and stomatal conductance model (A– gs). Here we demonstrate that this approach does not converge in its iterative calculation of gross primary production (GPP) and transpiration in large portions of land surface, because the coupled A– gsmodel does not always comply with a condition (the fixed‐point theorem) required by the fixed‐point approach for convergence. This iteration fails more frequently in some regions of the world than in others, leading to regionally varying uncertainty and global biases in the estimated carbon and water fluxes. Moreover, CLM applies an artificial constraint to the water vapor pressure of canopy air in its calculations ofA– gs, with an intention to prevent the ‘numerical instability’ arising from the fixed‐point approach. Our results show that this constraint reduces but does not prevent the occurrence of nonconvergence. Since this constraint is artificial, it can bias GPP and transpiration simulations. We then propose a Newton‐Raphson iteration scheme to replace the fixed‐point approach and show that this new approach can ensure convergence, does not require an artificial constraint on the atmospheric water vapor pressure, and is computationally efficient. On the other hand, the default fixed‐point treatment in CLM leads to a ∼2.7 PgCyr−1overestimation of GPP globally but with much higher regional biases (∼27%). We suggest that the current fixed‐point treatment in CLM be replaced with the Newton‐Raphson approach and that the artificial constraint on the atmospheric water vapor pressure be removed.
The determination of permafrost thawing trends from long‐term streamflow measurements with an application in eastern Siberia
Authors: Brutsaert Wilfried , Hiyama Tetsuya
Published: October 2012

Permafrost has been reported to be degrading at increasing rates over wide areas in northern regions of Eurasia and North America; the evidence has come mainly from in situ observations in the soil profile, which have limited spatial and invariably limited temporal coverage. Herein three methods are proposed to relate low river flows (or base flows) during the open water season with the rate of change of the active groundwater layer thickness resulting from permafrost thawing at the scale of the upstream river basin. As an example, the methods are tested with data from four gaging stations within the Lena River basin in eastern Siberia, one in the Upper Lena basin, and three in two of its tributaries, namely the Olyokma and the Aldan basins. The different results are mutually consistent and suggest that over the 1950–2008 period the active layer thickness has been increasing at average rates roughly of the order of 0.3 to 1 cm a−1 in the areas with discontinuous permafrost and at average rates about half as large in colder more eastern areas with continuous permafrost. These rates have not been steady but have been increasing; thus it appears that in the earlier years over the period 1950–1970, some large regions have not been undergoing active layer thickness increases and perhaps even decreases, whereas from the 1990s onward vast areas have experienced larger average layer thickness increases, especially those with continuous permafrost.
Enhanced hydrogen at the lunar poles: New insights from the detection of epithermal and fast neutron signatures
Authors: Miller R. S. , Nerurkar G. , Lawrence D. J.
Published: October 2012

The Lunar Prospector (LP) and Lunar Reconnaissance Orbiter (LRO) orbital neutron spectroscopy data sets represent a unique comprehensive multimission lunar resource. A rigorous statistical approach has been used to (re)analyze neutron data from both missions to provide new details regarding the relationships between the individual detector data sets, as well as a new evaluation of enhanced hydrogen deposits at the lunar poles. Using the multimission epithermal neutron data set, we find water ice distributed broadly across the poles, but showing evidence for a dependence on topographical features. A footprint averaged water equivalent hydrogen (WEH) abundance of 106 ± 11 ppm at each pole, with maxima of 131 and 112 ppm at the north and south poles, respectively, is derived from the epithermal neutron data. We also report the first definitive detection of a fast neutron signature consistent with an enhanced hydrogen hypothesis. These data suggest a highly localized distribution, consistent with Shackleton Crater, corresponding to a footprint averaged WEH abundance of 194 ± 11. If confined to this crater, this abundance yields a localized deposit of ∼0.7% WEH. Details of the analysis approach are presented along with spatial distribution maps showing the intriguing enhanced hydrogen deposits at the lunar poles.
Transport‐limitations on fluvial sediment supply to the sea
Authors: Dade W. B.
Published: October 2012

The ability to understand and predict the flux and fate of sediment delivered to the sea by rivers remains an outstanding scientific challenge. Approaches to this challenge are necessarily synthetic, spanning wide ranges in spatial and temporal scales. Here a conventional sediment transport theory used by engineers and sedimentologists at reach and channel scales is applied at the basin scale. Specifically, a straightforward expression proposed by Bagnold and modified accordingly predicts the observed importance of combined wetness and steepness of a source basin as a control of sediment supply to the sea. The reasonable, key assumption underlying the application of sediment transport theory in this context is that the river‐mouth sites for which suspended‐sediment loads are reported are alluviated, and thus characterized by transport‐limited flux of sediment. This analysis also indicates the potential significance of additional, as yet poorly documented factors constraining sediment supply to the sea. These factors, some of which appear to covary systematically with climate, include river‐profile concavity, river‐mouth channel width and friction, and the characteristic size of sediment in transport.
Spreading and convective dissolution of carbon dioxide in vertically confined, horizontal aquifers
Authors: MacMinn Christopher W. , Neufeld Jerome A. , Hesse Marc A. , Huppert Herbert E.
Published: October 2012

Injection of carbon dioxide (CO2) into saline aquifers is a promising tool for reducing anthropogenic CO2 emissions. At reservoir conditions, the injected CO2 is buoyant relative to the ambient groundwater. The buoyant plume of CO2 rises toward the top of the aquifer and spreads laterally as a gravity current, presenting the risk of leakage into shallower formations via a fracture or fault. In contrast, the mixture that forms as the CO2 dissolves into the ambient water is denser than the water and sinks, driving a convective process that enhances CO2dissolution and promotes stable long‐term storage. Motivated by this problem, we study convective dissolution from a buoyant gravity current as it spreads along the top of a vertically confined, horizontal aquifer. We conduct laboratory experiments with analog fluids (water and a mixture of methanol and ethylene glycol) and compare the experimental results with simple theoretical models. Since the aquifer has a finite thickness, dissolved buoyant fluid accumulates along the bottom of the aquifer, and this mixture spreads laterally as a dense gravity current. When dissolved buoyant fluid accumulates slowly, our experiments show that the spreading of the buoyant current is characterized by a parabola‐like advance and retreat of its leading edge. When dissolved buoyant fluid accumulates quickly, the retreat of the leading edge slows as further dissolution is controlled by the slumping of the dense gravity current. We show that simple theoretical models predict this behavior in both limits, where the accumulation of dissolved buoyant fluid is either negligible or dominant. Finally, we apply one of these models to a plume of CO2 in a saline aquifer. We show that the accumulation of dissolved CO2 in the water can increase the maximum extent of the CO2 plume by several fold and the lifetime of the CO2 plume by several orders of magnitude.
Nothing but the truth
Authors: Brown Paige
Published: October 2012

Many scientists blame the media for sensationalising scientific findings, but new research suggests that things can go awry at all levels, from the scientific report to the press officer to the journalist.
Explaining life
Authors: Deplazes‐Zemp Anna , Biller‐Andorno Nikola
Published: October 2012

There are many different explanations of life inspired by scientific knowledge, philosophical theories or religious beliefs. Synthetic biologists would do well to take these views into account when they work to create artificial organisms and attempt to answer the question: what is life?
Protein nanotubes, channels and cages
Authors: Heddle Jonathan G. , Tame Jeremy R. H.
Published: October 2012

Proteins are the work-horses of life and excute the essential processes involved in the growth and repair of cells. These roles include all aspects of cell signalling, metabolism and repair that allow living things to exist. They are not only chemical catalysts and machine components, they are also structural components of the cell or organism, capable of self-organisation into strong supramolecular cages, fibres and meshes. How proteins are encoded genetically and how they are sythesised in vivo is now well understood, and for an increasing number of proteins, the relationship between structure and function is known in exquisite detail. The next challenge in bionanoscience is to adapt useful protein systems to build new functional structures. Well-defined natural structures with potential useful shapes are a good starting point. With this in mind, in this chapter we discuss the properties of natural and artificial protein channels, nanotubes and cages with regard to recent progress and potential future applications. Chemistries for attaching together different proteins to form superstructures are considered as well as the difficulties associated with designing complex protein structures ab initio.
Prescriptive peptide design
Authors: Ryadnov Maxim G
Published: October 2012

This chapter highlights developments in peptide design over the last years to the time of its submission, with background information covering an unlimited timeframe. An emphasis is made on prescriptive or de novo design of polypeptide sequences in relation to specific folds, topologies and functions, as seen in native systems. Therefore, the choice of reviewed designs in this chapter is biased towards biologically relevant structures that span molecular and nano- to micrometer length scales, and towards native strategies for their construction, that is self-assembly. The chapter reviews literature sourced from different databases including Web of Science and PubMed. Individual sections are arranged according to structural preferences and definitions and consequently to the types of relevant de novo designs. A section describing basic design principles provides introduction to the problem of peptide design and structure-function relationships.
Targeting alpha-helix based protein interactions; nuclear receptors as a case study
Authors: Milroy Lech-Gustav , Nieto Lidia , Brunsveld Luc
Published: October 2012

This book chapter highlights the important role played by α-helical structures in controlling protein-protein interactions (PPIs). First a brief discussion of the fundamental aspects of the α-helix structure is provided, including a word on nomenclature. Then some examples of different proteins involved in α-helical PPIs – for example Bcl-2, p53 and HIF-1α – are introduced alongside current methods for inhibiting these interactions, which typically rely on small lipophilic drug molecules, oligomeric structures or modified peptides. Next, nuclear hormone receptors will be discussed as quintessential α-helix mediated PPIs. By covering two of the most widely studied members of this intriguing protein class – the estrogen receptor (ER) and the androgen receptor (AR) – the important structural features of nuclear receptors will be discussed, and the significance of PPIs in terms of the binding of α-helical coregulator proteins highlighted. Finally, the chapter will round off with a discussion on how the principles of α-helicity have helped in the design of peptide-based and non-peptidic inhibitors of PPIs for drug discovery. In this case, the reader's attention will be mainly drawn to recent advances in the field.
Psychiatric Disorders – an Overview
Authors: Connor Kathryn M. , Michelson David
Published: October 2012

The psychiatric illnesses represent, collectively, a group of brain disorders characterized by behavioural and cognitive abnormalities and dysfunction. In marked contrast to other fields of medicine where diagnosis is based on pathophysiology or etiology, few psychiatric disorders have been defined based on pathophysiologic and etiologic considerations. Rather, psychiatric diagnoses or diseases are predominantly syndromes. Developments in the field of psychopharmacology over the last 60 years have provided considerable advances for pharmacologically based approaches, which are considered the foundation of treatment for most psychiatric disorders. As such, effective treatments for schizophrenia, depression, bipolar disorder, the anxiety disorders and other debilitating psychiatric conditions are now available. While many patients may benefit from these treatments, others demonstrate only a partial response or may fail to respond altogether. Treatment response is also challenged by high rates of co-morbidity with other psychiatric and medical conditions and poor tolerability of available treatments, which impact treatment adherence. The complex nature of these disorders coupled with our limited understanding of the pathogenesis and pathophysiology of psychiatric illnesses present both challenges and opportunities for today's drug discoverers and developers.
Discovery and Clinical Data for a Novel AMPA Receptor Positive Modulator
Authors: Ward Simon E.
Published: October 2012

In this chapter, a case study of a discovery project to identify potential new clinical agents for treating the cognitive deficits of schizophrenia is presented. Specifically, a hit identification and lead optimization activity is detailed for a novel series of AMPA receptor positive allosteric modulators, which ultimately delivered a clinical development candidate. The challenges of running high-throughput screening to identify positive modulators of ion channels are discussed, along with the opportunity presented by X-ray crystallography to improve the rational basis for onward analogue design. The evolution of the screening cascade, including recombinant and native tissue assays, fluorescent and electrophysiological readouts is outlined, with particular emphasis on the relevance and predictability of in vitro assays to the downstream pharmacodynamic, behavioural and tolerability screens. Additionally, the path to build confidence in the efficacy and safety profile of the clinical candidate is discussed, in light of the generic concerns of tolerability of agents that potentiate excitatory neurotransmission.
Neurocircuitry of Anxiety Disorders: Focus on Panic Disorder and Post-traumatic Stress Disorder
Authors: Murrough James W. , Schiller Daniela , Charney, MD Dennis S.
Published: October 2012

This chapter will provide an overview of the epidemiology, clinical features and neurocircuitry of anxiety disorders with a focus on panic disorder and post-traumatic stress disorder (PTSD). Anxiety disorders are among the most common and disabling psychiatric illnesses. Ongoing basic, clinical and translational research aimed at understanding the neurobiology underlying the disorders is shedding new light on mechanisms of disease and opening up potential new avenues for much needed therapeutic discovery. Neurocircuitry models of fear learning in animals will be described in order to provide a translational basis of human neuroimaging and therapeutic studies in anxiety disorders. Findings from human pharmacological challenge studies and other clinical studies in panic disorder and PTSD will also be reviewed. Finally, the chapter concludes with a discussion of potential novel therapeutic strategies for anxiety disorders based on the findings from preclinical and clinical studies presented.
Glutamate Approaches Towards the Treatment of Mood Disorders
Authors: Jones Carrie K. , Jeffrey Conn P. , Lindsley Craig W.
Published: October 2012

Mood disorders, including both major depressive disorders (MDD) and bipolar disorders (BPD), are forms of chronic mental illness associated with alterations in normal affective response that result in profound disruptions in daily living and for which there are limited treatment options. Recent preclinical and clinical findings indicate that alterations in the signalling of the glutamatergic system may account at least in part for many of the symptoms observed in patients with mood disorders. These findings have shifted the focus of novel therapeutic development for mood disorders from traditional monoamine-based approaches to the investigation of different modulators of glutamatergic signalling as will be reviewed in this chapter.
Modulation of HPA Axis Function for Treatment of Mood Disorders
Authors: Brothers Shaun P. , Wahlestedt Claes , Nemeroff Charles B.
Published: October 2012

The current understanding of how molecular targets within the HPA axis can be used as modulation points for novel therapeutics to treat mood disorders and anxiety is summarized. Dysregulation of the HPA axis has long been implicated in playing a seminal role in the pathogenesis of mood disorders, and most specifically major depression. However, with few exceptions, the development of modulators of the HPA axis, such as CRF1 receptor, glucocorticoid (GC) or mineralcorticoid (MC) receptor antagonists to treat mood disorders either have been relatively unstudied or thus far lack efficacy. One notable exception reviewed here is mifepristone, a GC receptor antagonist that has shown promising results in a number of clinical trials. We also focus on non-classical targets within the HPA axis that also represent tractable therapeutic targets such as the CRF binding protein, arginine vasopressin, other neuropeptide receptors and novel targets identified by genetic studies. Additional clinical trials with a focus on disorders shown to dysregulate CRF and the HPA axis such as psychotic depression or major depression with early life trauma will likely yield important novel information about the patient subtypes likely to respond to such novel therapeutic approaches.
Neuropeptide Receptors: Novel Therapeutic Targets for Depression and Anxiety Disorders
Authors: Chaki Shigeyuki , Kanuma Kosuke
Published: October 2012

Numerous neuropeptides have recently attracted interest as novel targets for drug discovery for the treatment of depression and anxiety based on the important roles that these proteins play in regulating stress responses. Neuropeptides exert their effects through specific receptors, most of which belong to the G-protein coupled receptor superfamily. A series of neurochemical and behavioural studies utilizing pharmacological tools and genetically engineered animals have elucidated the role of each receptor subtype in depression and anxiety. In addition, clinical studies have been conducted using selective antagonists for several receptor subtypes. In particular, neuropeptides that regulate two important stress-related pathways, HPA axis activity and reward activity, are of interest as novel approaches for the treatment of depression and anxiety.
Pharmacotherapies for Drug Addiction
Authors: Gipson C. D. , Kalivas P. W.
Published: October 2012

Various pharmacotherapies in drug addiction have been developed to target two primary neurobiological processes of addiction: 1) dopaminergic and opioid systems found to be involved in the rewarding effects of various drugs of abuse and 2) the enduring neuroplasticity mediating the vulnerability to relapse that largely includes glutamatergic mechanisms. Drug development is a costly, slow process and, thus far, pharmacotherapeutic treatment of drug addiction is not highly efficacious. Issues of compliance to both behavioural and pharmacological treatment remain of primary concern, and indeed reduce the efficacy of treatments developed thus far. Tools to improve compliance and treatment efficacy, including pharmacogenetics, hold promise but are novel and the full extent of their clinical utility has not yet been shown. In this chapter, we will discuss the current state of pharmacotherapy in addiction, as well as the various targets that have been identified as having a role in drug use and relapse.
Emerging Research towards the Understanding and Treatment of Autism
Authors: Wang Paul , Hammond Rebecca , Postma Friso , Healy Aileen
Published: October 2012

Autism and Autism Spectrum Disorders (ASD) are neurodevelopmental disorders affecting social skills, communication and behaviour. The prevalence of ASD is now recognized to be approximately 1:100. Although autism etiology is still largely undefined, there is convincing evidence of a familial effect. Significant research efforts are focused on defining genetic etiologies resulting from DNA mutations. This area of research has provoked several theories of autism etiology. One prevailing hypothesis suggests multiple DNA mutations converge on a few molecular pathways that regulate neuronal development and synapse formation to cause autism. Recent scientific findings define the regulation of synaptic protein synthesis as one critical pathway that is altered in several single-gene disorders associated with ASD. Defining the molecular neuropathophysiology underlying autism enables the development of effective therapies to treat the core symptoms of autism. Mechanism-based approaches are currently being tested in human trials. Clinical development of new therapies for autism faces significant challenges including the lack of validated outcome measures for efficacy. Identification of molecular and neurobehavioural biomarkers would directly address some of the clinical challenges faced in treating this heterogeneous patient population and speed development of novel therapeutics.