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At least 1,675 records · Page 93

Amelioration of Alzheimer’s disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer’s disease

The most common age-related neurodegenerative disease is Alzheimer’s disease (AD) characterized by aggregated amyloid-β (Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles, together with loss of cholinergic neurons, synaptic alterations, and chronic inflammation within the brain. These lead to progressive impairment of cognitive function. There is evidence of innate immune activation in AD with microgliosis. Classically-activated microglia (M1 state) secrete inflammatory and neurotoxic mediators, and peripheral immune cells are recruited to inflammation sites in the brain. The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects. Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials. Treatment with immunomodulatory/anti-inflammatory agents early in the disease process, while not preventive, is able to inhibit the inflammatory consequences of both Aβ and tau aggregation. The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD. The majority of the animal studies reviewed had used transgenic models of early-onset AD. More effort needs to be given to create models of late-onset AD. The effects of a combinational therapy involving two or more of the tested pharmaceutical agents, or one of these agents given in conjunction with one of the cell-based therapies, in an aged animal model of AD would warrant investigation.

60 APPLIED LIFE SCIENCES↗

Perturbations of the optical properties of mineral dust particles by mixing with black carbon: a numerical simulation study

Field observations show that individual aerosol particles are a complex mixture of a wide variety of species, reflecting different sources and physico-chemical transformations. The impacts of individual aerosol morphology and mixing characteristics on the Earth system are not yet fully understood. Here we present a sensitivity study on climate-relevant aerosols optical properties to various approximations. Based on aerosol samples collected in various geographical locations, we have observationally constrained size, morphology and mixing, and accordingly simulated, using the discrete dipole approximation model (DDSCAT), optical properties of three aerosols types: (1) bare black carbon (BC) aggregates, (2) bare mineral dust, and (3) an internal mixture of a BC aggregate laying on top of a mineral dust particle, also referred to as polluted dust. DDSCAT predicts optical properties and their spectral dependence consistently with observations for all the studied cases. Predicted values of mass absorption, scattering and extinction coefficients (MAC, MSC, MEC) for bare BC show a weak dependence on the BC aggregate size, while the asymmetry parameter ( g ) shows the opposite behavior. The simulated optical properties of bare mineral dust present a large variability depending on the modeled dust shape, confirming the limited range of applicability of spheroids over different types and size of mineral dust aerosols, in agreement with previous modeling studies. The polluted dust cases show a strong decrease in MAC values with the increase in dust particle size (for the same BC size) and an increase of the single scattering albedo (SSA). Furthermore, particles with a radius between 180 and 300 nm are characterized by a decrease in SSA values compared to bare dust, in agreement with field observations.This paper demonstrates that observationally constrained DDSCAT simulations allow one to better understand the variability of the measured aerosol optical properties in ambient air and to define benchmark biases due to different approximations in aerosol parametrization.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Modeling dust mineralogical composition: sensitivity to soil mineralogy atlases and their expected climate impacts

Soil dust aerosols are a key component of the climate system, as they interact with short- and long-wave radiation, alter cloud formation processes, affect atmospheric chemistry and play a role in biogeochemical cycles by providing nutrient inputs such as iron and phosphorus. The influence of dust on these processes depends on its physicochemical properties, which, far from being homogeneous, are shaped by its regionally varying mineral composition. The relative amount of minerals in dust depends on the source region and shows a large geographical variability. However, many state-of-the-art Earth system models (ESMs), upon which climate analyses and projections rely, still consider dust mineralogy to be invariant. The explicit representation of minerals in ESMs is more hindered by our limited knowledge of the global soil composition along with the resulting size-resolved airborne mineralogy than by computational constraints. In this work we introduce an explicit mineralogy representation within the state-of-the-art Multiscale Online Nonhydrostatic AtmospheRe CHemistry (MONARCH) model. We review and compare two existing soil mineralogy datasets, which remain a source of uncertainty for dust mineralogy modeling and provide an evaluation of multiannual simulations against available mineralogy observations. Soil mineralogy datasets are based on measurements performed after wet sieving, which breaks the aggregates found in the parent soil. Our model predicts the emitted particle size distribution (PSD) in terms of its constituent minerals based on brittle fragmentation theory (BFT), which reconstructs the emitted mineral aggregates destroyed by wet sieving. Our simulations broadly reproduce the most abundant mineral fractions independently of the soil composition data used. Feldspars and calcite are highly sensitive to the soil mineralogy map, mainly due to the different assumptions made in each soil dataset to extrapolate a handful of soil measurements to arid and semi-arid regions worldwide. For the least abundant or more difficult-to-determine minerals, such as iron oxides, uncertainties in soil mineralogy yield differences in annual mean aerosol mass fractions of up to ~ 100 %. Although BFT restores coarse aggregates including phyllosilicates that usually break during soil analysis, we still identify an overestimation of coarse quartz mass fractions (above 2 µm in diameter). In a dedicated experiment, we estimate the fraction of dust with undetermined composition as given by a soil map, which makes up ~ 10 % of the emitted dust mass at the global scale and can be regionally larger. Changes in the underlying soil mineralogy impact our estimates of climate-relevant variables, particularly affecting the regional variability of the single-scattering albedo at solar wavelengths or the total iron deposited over oceans. All in all, this assessment represents a baseline for future model experiments including new mineralogical maps constrained by high-quality spaceborne hyperspectral measurements, such as those arising from the NASA Earth Surface Mineral Dust Source Investigation (EMIT) mission.

54 ENVIRONMENTAL SCIENCES↗

Evaluation of integrated assessment model hindcast experiments: a case study of the GCAM 3.0 land use module

Abstract. Hindcasting experiments (conducting a model forecast for a time period in which observational data are available) are being undertaken increasingly often by the integrated assessment model (IAM) community, across many scales of models. When they are undertaken, the results are often evaluated using global aggregates or otherwise highly aggregated skill scores that mask deficiencies. We select a set of deviation-based measures that can be applied on different spatial scales (regional versus global) to make evaluating the large number of variable–region combinations in IAMs more tractable. We also identify performance benchmarks for these measures, based on the statistics of the observational dataset, that allow a model to be evaluated in absolute terms rather than relative to the performance of other models at similar tasks. An ideal evaluation method for hindcast experiments in IAMs would feature both absolute measures for evaluation of a single experiment for a single model and relative measures to compare the results of multiple experiments for a single model or the same experiment repeated across multiple models, such as in community intercomparison studies. The performance benchmarks highlight the use of this scheme for model evaluation in absolute terms, providing information about the reasons a model may perform poorly on a given measure and therefore identifying opportunities for improvement. To demonstrate the use of and types of results possible with the evaluation method, the measures are applied to the results of a past hindcast experiment focusing on land allocation in the Global Change Assessment Model (GCAM) version 3.0. The question of how to more holistically evaluate models as complex as IAMs is an area for future research. We find quantitative evidence that global aggregates alone are not sufficient for evaluating IAMs that require global supply to equal global demand at each time period, such as GCAM. The results of this work indicate it is unlikely that a single evaluation measure for all variables in an IAM exists, and therefore sector-by-sector evaluation may be necessary.

58 GEOSCIENCES↗

An Approach to Enhance pnetCDF Performance in Environmental Modeling Applications

I/O has been considered as a bottleneck in parallel applications. The software package, pnetCDF which works with parallel file systems, was developed to address this issue and provide parallel I/O capability. This study examines the performance of a novel approach which performs data aggregation along either row or column dimension of the spatial domain, and then applies the pnetCDF parallel I/O paradigm. The test was done with three different domain sizes which represents small, moderately large and large data domains, using a small scale Community Multi-scale Air Quality model (CMAQ) mocked up code. The examination includes comparing I/O performance with traditional serial I/O technique, straight application of pnetCDF, and the data aggregation along row and column dimension before applying pnetCDF. After the comparison, “optimal” I/O configurations for this new novel approach were quantified. Data aggregation along the row dimension (pnetCDFcr) works better than along the column dimension (pnetCDFcc) although it may perform slightly worse than straight the pnetCDF method with a small number of processors. When the number of processors becomes larger, pnetCDFcr out performs pnetCDF significantly. If the number of processors keeps increasing, pnetCDF reaches a point that the performance is even worse than the serial I/O technique. This new approach has also been tested on a real application where it performs two times better than the straight pnetCDF paradigm.

I/O↗

Generating porosity during olivine carbonation via dissolution channels and expansion cracks

Abstract. The olivine carbonation reaction, in which carbon dioxide is chemically incorporated to form carbonate, is central to the emerging carbon sequestration method using ultramafic rocks. The rate of this retrograde metamorphic reaction is controlled, in part, by the available reactive surface area: as the solid volume increases during carbonation, the feasibility of this method ultimately depends on the maintenance of porosity and the creation of new reactive surfaces. We conducted in situ dynamic X-ray microtomography and nanotomography experiments to image and quantify the porosity generation during olivine carbonation. We designed a sample setup that included a thick-walled cup (made of porous olivine aggregates with a mean grain size of either ∼ 5 or ∼ 80 µm) filled with loose olivine sands with grain sizes of 100–500 µm. The whole sample assembly was reacted with a NaHCO 3 aqueous solution at 200 °C, under a constant confining pressure of 13 MPa and a pore pressure of 10 MPa. Using synchrotron-based X-ray microtomography, the three-dimensional (3-D) pore structure evolution of the carbonating olivine cup was documented until the olivine aggregates became disintegrated. The dynamic microtomography data show a volume reduction in olivine at the beginning of the reaction, indicating a vigorous dissolution process consistent with the disequilibrium reaction kinetics. In the olivine cup with a grain size of ∼ 80 µm (coarse-grained cup), dissolution planes developed within 30 h, before any precipitation was observed. In the experiment with the olivine cup of ∼ 5 µm mean grain size (fine-grained cup), idiomorphic magnesite crystals were observed on the surface of the olivine sands. The magnesite shows a near-constant growth throughout the experiment, suggesting that the reaction is self-sustained. Large fractures were generated as the reaction proceeded and eventually disintegrated the aggregate after 140 h. Detailed analysis show that these are expansion cracks caused by the volume mismatch in the cup walls, between the expanding interior and the near-surface which keeps a nearly constant volume. Nanotomography images of the reacted olivine cup reveal pervasive etch pits and wormholes in the olivine grains. We interpret this perforation of the solids to provide continuous fluid access, which is likely key to the complete carbonation observed in nature. Reactions proceeding through the formation of nano- to micron-scale dissolution channels provide a viable microscale mechanism in carbon sequestration practices. For the natural peridotite carbonation, a coupled mechanism of dissolution and reaction-induced fracturing should account for the observed self-sustainability of the reaction.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Therapeutic genetic variation revealed in diverse Hsp104 homologs

The AAA+ protein disaggregase, Hsp104, increases fitness under stress by reversing stress-induced protein aggregation. Natural Hsp104 variants might exist with enhanced, selective activity against neurodegenerative disease substrates. However, natural Hsp104 variation remains largely unexplored. Here, we screened a cross-kingdom collection of Hsp104 homologs in yeast proteotoxicity models. Prokaryotic ClpG reduced TDP-43, FUS, and α-synuclein toxicity, whereas prokaryotic ClpB and hyperactive variants were ineffective. Furthermore, we uncovered therapeutic genetic variation among eukaryotic Hsp104 homologs that specifically antagonized TDP-43 condensation and toxicity in yeast and TDP-43 aggregation in human cells. We also uncovered distinct eukaryotic Hsp104 homologs that selectively antagonized α-synuclein condensation and toxicity in yeast and dopaminergic neurodegeneration in C. elegans . Surprisingly, this therapeutic variation did not manifest as enhanced disaggregase activity, but rather as increased passive inhibition of aggregation of specific substrates. By exploring natural tuning of this passive Hsp104 activity, we elucidated enhanced, substrate-specific agents that counter proteotoxicity underlying neurodegeneration.

59 BASIC BIOLOGICAL SCIENCES↗

Development, fabrication and test of a high purity silica heat shield

A highly reflective hyperpure ( 25 ppm ion impurities) slip cast fused silica heat shield material developed for planetary entry probes was successfully scaled up. Process development activities for slip casting large parts included green strength improvements, casting slip preparation, aggregate casting, strength, reflectance, and subscale fabrication. Successful fabrication of a one-half scale Saturn probe (shape and size) heat shield was accomplished while maintaining the silica high purity and reflectance through the scale-up process. However, stress analysis of this original aggregate slip cast material indicated a small margin of safety (MS. = +4%) using a factor of safety of 1.25. An alternate hyperpure material formulation to increase the strength and toughness for a greater safety margin was evaluated. The alternate material incorporates short hyperpure silica fibers into the casting slip. The best formulation evaluated has a 50% by weight fiber addition resulting in an 80% increase in flexural strength and a 170% increase in toughness over the original aggregate slip cast materials with comparable reflectance.

Rusert, E. L.↗

AgRISTARS: Foreign commodity production forecasting. The 1980 US corn and soybeans exploratory experiment

The U.S. corn and soybeans exploratory experiment is described which consisted of evaluations of two technology components of a production forecasting system: classification procedures (crop labeling and proportion estimation at the level of a sampling unit) and sampling and aggregation procedures. The results from the labeling evaluations indicate that the corn and soybeans labeling procedure works very well in the U.S. corn belt with full season (after tasseling) LANDSAT data. The procedure should be readily adaptable to corn and soybeans labeling required for subsequent exploratory experiments or pilot tests. The machine classification procedures evaluated in this experiment were not effective in improving the proportion estimates. The corn proportions produced by the machine procedures had a large bias when the bias correction was not performed. This bias was caused by the manner in which the machine procedures handled spectrally impure pixels. The simulation test indicated that the weighted aggregation procedure performed quite well. Although further work can be done to improve both the simulation tests and the aggregation procedure, the results of this test show that the procedure should serve as a useful baseline procedure in future exploratory experiments and pilot tests.

Malin, J. T.↗

Large space structure model reduction and control system design based upon actuator and sensor influence functions

A model reduction procedure based on aggregation with respect to sensor and actuator influences rather than modes is presented for large systems of coupled second-order differential equations. Perturbation expressions which can predict the effects of spillover on both the aggregated and residual states are derived. These expressions lead to the development of control system design constraints which are sufficient to guarantee, to within the validity of the perturbations, that the residual states are not destabilized by control systems designed from the reduced model. A numerical example is provided to illustrate the application of the aggregation and control system design method.

Yam, Y.↗

A brittle to ductile transition in NiAl of a critical grain size

Tensile tests have been carried out on the strongly ordered B2 aluminide NiAl at 400 C to investigate the effect of the grain size on the ductility of the material. It is found that the ductility is very low and essentially independent of the grain size for aggregates of grains larger than about 20 microns; for finer-grained aggregates, the ductility increases sharply with decreasing grain size. Thus, NiAl exhibits a critical grain size below which polycrystalline aggregates are ductile in tension. For all grain sizes, fracture occurs in a brittle manner through a combination of intergranular decohesion and transgranular cleavage.

Schulson, E. M.↗

Abrasion by aeolian particles: Earth and Mars

Estimation of the rate of aeolian abrasion of rocks on Mars requires knowledge of: (1) particle flux, (2) susceptibilities to abrasion of various rocks, and (3) wind frequencies on Mars. Fluxes and susceptibilities for a wide range of conditions were obtained in the laboratory and combined with wind data from the Viking meteorology experiment. Assuming an abundant supply of sand-sized particles, estimated rates range up to 2.1 x 10 to the minus 2 power cm of abrasion per year in the vicinity of Viking Lander 1. This rate is orders of magnitude too great to be in agreement with the inferred age of the surface based on models of impact crater flux. The discrepancy in the estimated rate of abrasion and the presumed old age of the surface cannot be explained easily by changes in climate or exhumation of ancient surfaces. The primary reason is thought to be related to the agents of abrasion. At least some sand-sized (approx. 100 micrometers) grains appear to be present, as inferred from both lander and orbiter observations. High rates of abrasion occur for all experimental cases involving sands of quartz, basalt, or ash. However, previous studies have shown that sand is quickly comminuted to silt- and clay-sized grains in the martian aeolian regime. Experiments also show that these fine grains are electrostatically charged and bond together as sand-sized aggregates. Laboratory simulations of wind abrasion involving aggregates show that at impact velocities capable of destroying sand, aggregates from a protective veneer on the target surface and can give rise to extremely low abrasion rates.

Greeley, R.↗

Mineralogy and petrology of chondrules and inclusions in the Mokoia CV3 chondrite

The inclusions and chondrules of the Mokoia CV3 chondrite are studied systematically and compared with those in the Allende meteorite. Five polished thin sections of Mokoia were examined by optical microscopy, backscattered scanning electron microscopy, and electronprobe microanalysis, and objects greater than about 100 microns in apparent diameter were measured and classified petrographically. Three major types of olivine chondrules are distinguished: igneous chondrules, which evidently crystallized from droplets of silicate melt; recrystallized chondrules, apparently metamorphosed at relatively high temperatures; and accretional aggregates, which are probably fragments of igneous chondrules. Refractory inclusions in Mokoia are generally similar to those found in Allende, although Mokoia inclusions include phyllosilicates rather than feldspathoids and melilite-rich Ca, Al-rich inclusions (CAIs) are more abundant in Allende. The small, fine-grained CAIs, which are more abundant than coarse-grained CAIs in both meteorites, are observed to represent aggregates of three distinct constituents: concentric objects, chaotic material and inclusion matrix. It is concluded that most of the CAIs probably formed during metamorphism, partial melting, and incomplete distillation of primitive dust aggregates heated in the solar nebula.

Cohen, R. E.↗

Petrography and classification of Ca, Al-rich and olivine-rich inclusions in the Allende CV3 chondrite

The results of a detailed, systematic petrographic survey of Ca, Al-rich and olivine-rich inclusions in the Allende CV3 chondrite are reported, and a new classification system based on clearly defined and readily applied petrographic criteria is presented. Most Allende inclusions are aggregates containing one or more of three distinct constituents: (1) rimmed concentric objects enriched in Al- and Ti-rich oxide minerals and various amounts of Ca-rich silicates; (2) porous, 'fine-grained' chaotic material enriched in Ca-rich silicates, especially clinopyroxenes and garnets; and (3) porous, 'fine-grained', mafic inclusion matrix, enriched in olivine, pyroxene, and feldspathoids. Two texturally distinct varieties of inclusions consist primarily of inclusion matrix: unrimmed olivine aggregates and rimmed olivine aggregates. Ca, Al-rich inclusions are classified on the basis of the size and abundance of their constituent concentric objects. Some fundamental relationships among Allende inclusions that previusly have not been emphasized are discussed.

Kormacki, A. S.↗

Saturn ring particles as dynamic ephemeral bodies

Although Saturn's rings are within the Roche zone, the accretion of centimeter-sized particles into large aggregates many meters in diameter occurs readily, on a time scale of weeks. These aggregates are disrupted when tidal stresses exceed their very low strengths; thus most of the mass of the ring system is continually processed through a population of large 'dynamic ephemeral bodies', which are continually forming and disintegrating. These large aggregates are not at all like the idealized ice spheres often used in modeling Saturn's ring dynamics. Their coefficient of restitution is low, hence they form a monolayer in the ring plane. The optically observable characteristics of the rings are dominated by the swarm of centimeter-sized particles.

Davis, D. R.↗

Mineral chemistry and origin of spinel-rich inclusions in the Allende CV3 chondrite

The present electron probe microanalysis of 20 spinel-rich inclusions in Allende indicates that the mineralogy of spinel-rich Allende inclusions is similar to that of fine grained Ca, Al-rich inclusions (CAIs) in ALH-77003 and rims on coarse grained CAIs in Allende. The mineralogy, mineral chemistry, and bulk chemistry of the inclusions indicate that they are not primitive aggregates of crystalline nebular condensates, but rather aggregates of minute concentric objects that are presently interpreted to be a fractionated distillation residue that lost Ca, Si-rich partial melt. It is suggested that interstellar dust aggregates were melted or distilled into Allende inclusions by aerodynamic drag heating, in regions of the nebula where the dust/gas ratio was so enhanced that the local oxygen fugacity was raised by several order of magnitude and liquids became thermodynamically stable.

Kornacki, A. S.↗

Interstellar fossil Mg-26 and its possible relationship to excess meteoritic Mg-26

A plausible scenario is advanced for explainig a linear correlation found in some solar system solids between their Mg-26/Mg-24 isotopic ratios and their Al/Mg elemental abundance ratios. This scenario involves three stages: (1) the mechanical aggregation of an average ensemble of Al-bearing dust particles that is postulated to be modestly enriched in the Al/Mg abundance ratio because the aggregated particles themselves are; (2) the extraction, perhaps but not necessarily by hot distillation, of almost all Mg, leaving an aggregate with a large Al/Mg ratio and a large Mg-26 excess; and (3) the uptake of normal ambient Mg by the resulting hot Al-rich solid as it cools in Mg-rich vapor. A linear correlation in solids between their Mg-26/Mg-24 isotopic ratio and their aluminum enrichment may be a fossil correlation inherited from interstellar dust.

Clayton, Donald D.↗

Scattering by fluffy grains

There are indications (Greenberg et al., 1988), that fluffy (i.e., porous) particles are responsible for the observed 3.4 and 10 micron emissions of comet Halley. The absorption characteristics of small particles both solid and fluffy are needed in order to explain the Halley emissions. How isolated small solid particles react to an external radiation field is well known - the Rayleigh approximation. How these same small particles emit when assembled as fluffy aggregates in another question. To what degree are the emission spectra of isolated and aggregated particles comparable. In order to quantify the assertion that fluffy particles produce the observed Halley infrared emission features, the authors are performing calculations to determine the effect of porosity on the absorption characteristics of aggregates of interstellar grain-type particles. The calculations are based on an integral representation of the scattered electromagnetic field. Results are given with application to comet Halley.

Hage, J. I.↗