Tuning the structure, stability and responsivity of polymeric arsenical nanoparticles using polythiol cross-linkers

The use of organic arsenicals in polymer chemistry and biomaterials science is limited despite the distinctive and versatile chemistry of arsenic. The interchangeable oxidation states of arsenic and the subsequent changes in chemical properties make it a promising candidate for redox-responsive materials. Thus, reversible addition–fragmentation chain transfer (RAFT) polymerization has been employed for the first time to synthesize thermoresponsive organic arsenical containing block copolymers. The polymers undergo simultaneous self-assembly and cross-linking, via the organic arsenical pendant groups, under reductive conditions (to reduce As(V) to As(III)) in the presence of polythiol reagents as cross-linkers. The formation of As–S bonds stabilizes the nanoparticles formed (Dh = 19–29 nm) and enables the stability and responsivity to oxidative stress of the particles, in aqueous and model biological solutions, to be tuned as a function of the number of thiols in the cross-linker or the [SH]/[As] stoichiometric ratio. The parent block copolymers and nanoparticles are nontoxic in vitro, and the tunable responsivity of these nanoparticles and the (bio)chemical activity of organic arsenical reagents could be advantageous for targeted drug delivery and the other bio(nano)medical applications. To the best our knowledge, this is the first time that arsenic–thiolate (As–S) bonding has been employed for stimuli-responsive cross-linking of polymeric nanoparticles

Late Holocene sea- and land-level change on the U.S. southeastern Atlantic coast

Late Holocene relative sea-level (RSL) reconstructions can be used to estimate rates of land-level (subsidence or uplift) change and therefore to modify global sea-level projections for regional conditions. These reconstructions also provide the long-term benchmark against which modern trends are compared and an opportunity to understand the response of sea level to past climate variability. To address a spatial absence of late Holocene data in Florida and Georgia, we reconstructed ~ 1.3 m of RSL rise in northeastern Florida (USA) during the past ~ 2600 years using plant remains and foraminifera in a dated core of high salt-marsh sediment. The reconstruction was fused with tide-gauge data from nearby Fernandina Beach, which measured 1.91 ± 0.26 mm/year of RSL rise since 1900 CE. The average rate of RSL rise prior to 1800 CE was 0.41 ± 0.08 mm/year. Assuming negligible change in global mean sea level from meltwater input/removal and thermal expansion/contraction, this sea-level history approximates net land-level (subsidence and geoid) change, principally from glacio-isostatic adjustment. Historic rates of rise commenced at 1850–1890 CE and it is virtually certain (P = 0.99) that the average rate of 20th century RSL rise in northeastern Florida was faster than during any of the preceding 26 centuries. The linearity of RSL rise in Florida is in contrast to the variability reconstructed at sites further north on the U.S. Atlantic coast and may suggest a role for ocean dynamic effects in explaining these more variable RSL reconstructions. Comparison of the difference between reconstructed rates of late Holocene RSL rise and historic trends measured by tide gauges indicates that 20th century sea-level trends along the U.S. Atlantic coast were not dominated by the characteristic spatial fingerprint of melting of the Greenland Ice Sheet

The Behavior of Novae Light Curves Before Eruption

In 1975, E. R. Robinson conducted the hallmark study of the behavior of classical nova light curves before eruption, and this work has now become part of the standard knowledge of novae. He made three points; that 5 out of 11 novae showed pre-eruption rises in the years before eruption, that one nova (V446 Her) showed drastic changes in the variability across eruptions, and that all but one of the novae (excepting BT Mon) have the same quiescent magnitudes before and after the outburst. This work has not been tested since it came out. We have now tested these results by going back to the original archival photographic plates and measuring large numbers of pre-eruption magnitudes for many novae using comparison stars on a modern magnitude scale. We find in particular that four out of five claimed pre-eruption rises are due to simple mistakes in the old literature, that V446 Her has the same amplitude of variations across its 1960 eruption, and that BT Mon has essentially unchanged brightness across its 1939 eruption. Out of 22 nova eruptions, we find two confirmed cases of significant pre-eruption rises (for V533 Her and V1500 Cyg), while T CrB has a deep pre-eruption dip. These events are a challenge to theorists. We find no significant cases of changes in variability across 27 nova eruptions beyond what is expected due to the usual fluctuations seen in novae away from eruptions. For 30 classical novae plus 19 eruptions from 6 recurrent novae, we find that the average change in magnitude from before the eruption to long after the eruption is 0.0 mag. However, we do find five novae (V723 Cas, V1500 Cyg, V1974 Cyg, V4633 Sgr, and RW UMi) that have significantly large changes, in that the post-eruption quiescent brightness level is over ten times brighter than the pre-eruption level.Comment: 91 pages (preprint), AJ accepte

Collapse of the North American ice saddle 14,500 years ago caused widespread cooling and reduced ocean overturning circulation

Collapse of ice sheets can cause significant sea level rise and widespread climate change. We examine the climatic response to meltwater generated by the collapse of the Cordilleran-Laurentide ice saddle (North America) ~14.5 thousand years ago (ka) using a high-resolution drainage model coupled to an ocean-atmosphere-vegetation general circulation model. Equivalent to 7.26 m global mean sea level rise in 340 years, the meltwater caused a 6 sverdrup weakening of Atlantic Meridional Overturning Circulation (AMOC) and widespread Northern Hemisphere cooling of 1–5°C. The greatest cooling is in the Atlantic sector high latitudes during Boreal winter (by 5–10°C), but there is also strong summer warming of 1–3°C over eastern North America. Following recent suggestions that the saddle collapse was triggered by the Bølling warming event at ~14.7–14.5 ka, we conclude that this robust submillennial mechanism may have initiated the end of the warming and/or the Older Dryas cooling through a forced AMOC weakening

Response of a climate model to tidal mixing parameterization under present day and last glacial maximum conditions

Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Ocean Modelling 19 (2007): 125-137, doi:10.1016/j.ocemod.2007.06.009.Experiments with a climate model were conducted under present day and last glacial maximum conditions in order to examine the model’s response to a vertical mixing scheme based on internal tide energy dissipation. The increase in internal tide energy flux caused by a 120 m reduction in sea level had the expected effect on diffusivity values, which were higher under lower sea level conditions. The impact of this vertical diffusivity change on the Atlantic meridional overturning is not straightforward and no clear relationship between diffusivity and overturning is found. There exists a weak positive correlation between overturning and changes to the power consumed by vertical mixing. Most of the climatic response generated by sea level change was not related to alterations in the internal tide energy flux but rather to the direct change in sea level itself.Funding received from CFCAS through the CLIVAR and Polar Climate Stability Research networks. SRJ was supported by the U.S. National Science Foundation under Grant No. OCE-0241061

Concentrations and Sources of Organic Carbon Aerosol in the Free Troposphere over North America

Aircraft measurements of water-soluble organic carbon (WSOC) aerosol over NE North America during summer 2004 (ITCT-2K4) are simulated with a global chemical transport model (GEOS-Chem) to test our understanding of the sources of organic carbon (OC) aerosol in the free troposphere (FT). Elevated concentrations were observed in plumes from boreal fires in Alaska and Canada. WSOC aerosol concentrations outside of these plumes average 0.9 ± 0.9 μg C m−3 in the FT (2–6 km). The corresponding model value is 0.7 ± 0.6 μg C m−3, including 42% from biomass burning, 36% from biogenic secondary organic aerosol (SOA), and 22% from anthropogenic emissions. Previous OC aerosol observations over the NW Pacific in spring 2001 (ACE-Asia) averaged 3.3 ± 2.8 μg C m−3 in the FT, compared to a model value of 0.3 ± 0.3 μg C m−3. WSOC aerosol concentrations in the boundary layer (BL) during ITCT-2K4 are consistent with OC aerosol observed at the IMPROVE surface network. The model is low in the boundary layer by 30%, which we attribute to secondary formation at a rate comparable to primary anthropogenic emission. Observed WSOC aerosol concentrations decrease by a factor of 2 from the BL to the FT, as compared to a factor of 10 decrease for sulfate, indicating that most of the WSOC aerosol in the FT originates in situ. Despite reproducing mean observed WSOC concentrations in the FT to within 25%, the model cannot account for the variance in the observations (R = 0.21). Covariance analysis of FT WSOC aerosol with other measured chemical variables suggests an aqueous-phase mechanism for SOA generation involving biogenic precursors.Earth and Planetary SciencesEngineering and Applied Science

Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration

Huntington's disease (HD) is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt) protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%–4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to co-immunoprecipitate with full-length Htt from mouse brain. These studies demonstrate that high-throughput screening for protein interactions combined with genetic validation in a model organism is a powerful approach for identifying novel candidate modifiers of polyglutamine toxicity

Cross-Modal Object Recognition Is Viewpoint-Independent

BACKGROUND: Previous research suggests that visual and haptic object recognition are viewpoint-dependent both within- and cross-modally. However, this conclusion may not be generally valid as it was reached using objects oriented along their extended y-axis, resulting in differential surface processing in vision and touch. In the present study, we removed this differential by presenting objects along the z-axis, thus making all object surfaces more equally available to vision and touch. METHODOLOGY/PRINCIPAL FINDINGS: Participants studied previously unfamiliar objects, in groups of four, using either vision or touch. Subsequently, they performed a four-alternative forced-choice object identification task with the studied objects presented in both unrotated and rotated (180 degrees about the x-, y-, and z-axes) orientations. Rotation impaired within-modal recognition accuracy in both vision and touch, but not cross-modal recognition accuracy. Within-modally, visual recognition accuracy was reduced by rotation about the x- and y-axes more than the z-axis, whilst haptic recognition was equally affected by rotation about all three axes. Cross-modal (but not within-modal) accuracy correlated with spatial (but not object) imagery scores. CONCLUSIONS/SIGNIFICANCE: The viewpoint-independence of cross-modal object identification points to its mediation by a high-level abstract representation. The correlation between spatial imagery scores and cross-modal performance suggest that construction of this high-level representation is linked to the ability to perform spatial transformations. Within-modal viewpoint-dependence appears to have a different basis in vision than in touch, possibly due to surface occlusion being important in vision but not touch