384 research outputs found

    Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain.

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    Angelman syndrome (AS) is a neurological genetic disorder caused by loss of expression of the maternal copy of UBE3A in the brain. Due to brain-specific genetic imprinting at this locus, the paternal UBE3A is silenced by a long antisense transcript. Inhibition of the antisense transcript could lead to unsilencing of paternal UBE3A, thus providing a therapeutic approach for AS. However, widespread delivery of gene regulators to the brain remains challenging. Here, we report an engineered zinc finger-based artificial transcription factor (ATF) that, when injected i.p. or s.c., crossed the blood-brain barrier and increased Ube3a expression in the brain of an adult mouse model of AS. The factor displayed widespread distribution throughout the brain. Immunohistochemistry of both the hippocampus and cerebellum revealed an increase in Ube3a upon treatment. An ATF containing an alternative DNA-binding domain did not activate Ube3a. We believe this to be the first report of an injectable engineered zinc finger protein that can cause widespread activation of an endogenous gene in the brain. These observations have important implications for the study and treatment of AS and other neurological disorders

    The Formation of the Collisional Family around the Dwarf Planet Haumea

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    Haumea, a rapidly rotating elongated dwarf planet (~ 1500 km in diameter), has two satellites and is associated with a "family" of several smaller Kuiper Belt objects (KBOs) in similar orbits. All members of the Haumea system share a water ice spectral feature that is distinct from all other KBOs. The relative velocities between the Haumea family members are too small to have formed by catastrophic disruption of a large precursor body, which is the process that formed families around much smaller asteroids in the Main Belt. Here we show that all of the unusual characteristics of the Haumea system are explained by a novel type of giant collision: a graze-and-merge impact between two comparably sized bodies. The grazing encounter imparted the high angular momentum that spun off fragments from the icy crust of the elongated merged body. The fragments became satellites and family members. Giant collision outcomes are extremely sensitive to the impact parameters. Compared to the Main Belt, the largest bodies in the Kuiper Belt are more massive and experience slower velocity collisions; hence, outcomes of giant collisions are dramatically different between the inner and outer solar system. The dwarf planets in the Kuiper Belt record an unexpectedly large number of giant collisions, requiring a special dynamical event at the end of solar system formation.Comment: Accepted for publication in ApJ, 12 pages, 4 figures, 2 tables

    Preserved Grasshopper Fauna Of Knife Point Glacier, Fremont County, Wyoming, U.S.A.

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    In 1987 and 1988, samples of preserved insects were extracted from the ice of Knife Point Glacier, Fremont County, Wyoming. The glacier lies at an altitude of 3500 m a.s.l. in the Shoshone National Forest, Wind River Range, and is known to contain preserved insects. Although the glacier has undergone extensive recession in the last 50 yr, some insect deposits are still embedded at 20 to 25 cm below the surface and perhaps much deeper. The frozen deposits appear to consist entirely of grasshoppers. A few, virtually intact, specimens and body parts were in a state of preservation that allowed their identification as Spharagemon campestris McNeill and Melanoplus spretus (Walsh) or M. sanguinipes (F.). The majority of the deposits consisted of partial bodies and isolated parts, including, in order of frequency: mandibles, tibiae, tentoria, femora, wings (primarily tegmina), and cingulae/epiphalli. Deposits from various depths and locations on the glacier were radiocarbon dated at 205 + 65 to 450 + 80 yr BP. Although access to the glacier is quite difficult, the insects are better preserved than any glacial deposit documented in recent history. Thus, the state of preservation and age of the frozen deposits would suggest that additional, intensive sampling may be valuable in obtain- ing information on the ecology of grasshoppers prior to European settlement of North America

    Preserved Grasshopper Fauna Of Knife Point Glacier, Fremont County, Wyoming, U.S.A.

    Get PDF
    In 1987 and 1988, samples of preserved insects were extracted from the ice of Knife Point Glacier, Fremont County, Wyoming. The glacier lies at an altitude of 3500 m a.s.l. in the Shoshone National Forest, Wind River Range, and is known to contain preserved insects. Although the glacier has undergone extensive recession in the last 50 yr, some insect deposits are still embedded at 20 to 25 cm below the surface and perhaps much deeper. The frozen deposits appear to consist entirely of grasshoppers. A few, virtually intact, specimens and body parts were in a state of preservation that allowed their identification as Spharagemon campestris McNeill and Melanoplus spretus (Walsh) or M. sanguinipes (F.). The majority of the deposits consisted of partial bodies and isolated parts, including, in order of frequency: mandibles, tibiae, tentoria, femora, wings (primarily tegmina), and cingulae/epiphalli. Deposits from various depths and locations on the glacier were radiocarbon dated at 205 + 65 to 450 + 80 yr BP. Although access to the glacier is quite difficult, the insects are better preserved than any glacial deposit documented in recent history. Thus, the state of preservation and age of the frozen deposits would suggest that additional, intensive sampling may be valuable in obtain- ing information on the ecology of grasshoppers prior to European settlement of North America

    Can surface flux transport account for the weak polar field in cycle 23?

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    To reproduce the weak magnetic field on the polar caps of the Sun observed during the declining phase of cycle 23 poses a challenge to surface flux transport models since this cycle has not been particularly weak. We use a well-calibrated model to evaluate the parameter changes required to obtain simulated polar fields and open flux that are consistent with the observations. We find that the low polar field of cycle 23 could be reproduced by an increase of the meridional flow by 55% in the last cycle. Alternatively, a decrease of the mean tilt angle of sunspot groups by 28% would also lead to a similarly low polar field, but cause a delay of the polar field reversals by 1.5 years in comparison to the observations.Comment: 9 pages, 8 figures, Space Science Reviews, accepte

    Aerocapture Systems Analysis for a Titan Mission

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    Performance projections for aerocapture show a vehicle mass savings of between 40 and 80%, dependent on destination, for an aerocapture vehicle compared to an all-propulsive chemical vehicle. In addition aerocapture is applicable to multiple planetary exploration destinations of interest to NASA. The 2001 NASA In-Space Propulsion Program (ISP) technology prioritization effort identified aerocapture as one of the top three propulsion technologies for solar system exploration missions. An additional finding was that aerocapture needed a better system definition and that supporting technology gaps needed to be identified. Consequently, the ISP program sponsored an aerocapture systems analysis effort that was completed in 2002. The focus of the effort was on aerocapture at Titan with a rigid aeroshell system. Titan was selected as the initial destination for the study due to potential interest in a follow-on mission to Cassini/Huygens. Aerocapture is feasible, and the performance is adequate, for the Titan mission and it can deliver 2.4 times more mass to Titan than an all-propulsive system for the same launch vehicle

    Mobilisation of arsenic from bauxite residue (red mud) affected soils: effect of pH and redox conditions

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    The tailings dam breach at the Ajka alumina plant, western Hungary in 2010 introduced ~1 million m3 of red mud suspension into the surrounding area. Red mud (fine fraction bauxite residue) has a characteristically alkaline pH and contains several potentially toxic elements, including arsenic. Aerobic and anaerobic batch experiments were prepared using soils from near Ajka in order to investigate the effects of red mud addition on soil biogeochemistry and arsenic mobility in soil–water experiments representative of land affected by the red mud spill. XAS analysis showed that As was present in the red mud as As(V) in the form of arsenate. The remobilisation of red mud associated arsenate was highly pH dependent and the addition of phosphate to red mud suspensions greatly enhanced As release to solution. In aerobic batch experiments, where red mud was mixed with soils, As release to solution was highly dependent on pH. Carbonation of these alkaline solutions by dissolution of atmospheric CO2 reduced pH, which resulted in a decrease of aqueous As concentrations over time. However, this did not result in complete removal of aqueous As in any of the experiments. Carbonation did not occur in anaerobic experiments and pH remained high. Aqueous As concentrations initially increased in all the anaerobic red mud amended experiments, and then remained relatively constant as the systems became more reducing, both XANES and HPLC–ICP-MS showed that no As reduction processes occurred and that only As(V) species were present. These experiments show that there is the potential for increased As mobility in soil–water systems affected by red mud addition under both aerobic and anaerobic conditions

    Results from the CERN pilot CLOUD experiment

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    During a 4-week run in October–November 2006, a pilot experiment was performed at the CERN Proton Synchrotron in preparation for the Cosmics Leaving OUtdoor Droplets (CLOUD) experiment, whose aim is to study the possible influence of cosmic rays on clouds. The purpose of the pilot experiment was firstly to carry out exploratory measurements of the effect of ionising particle radiation on aerosol formation from trace H2SO4 vapour and secondly to provide technical input for the CLOUD design. A total of 44 nucleation bursts were produced and recorded, with formation rates of particles above the 3 nm detection threshold of between 0.1 and 100 cm -3 s -1, and growth rates between 2 and 37 nm h -1. The corresponding H2O concentrations were typically around 106 cm -3 or less. The experimentally-measured formation rates and htwosofour concentrations are comparable to those found in the atmosphere, supporting the idea that sulphuric acid is involved in the nucleation of atmospheric aerosols. However, sulphuric acid alone is not able to explain the observed rapid growth rates, which suggests the presence of additional trace vapours in the aerosol chamber, whose identity is unknown. By analysing the charged fraction, a few of the aerosol bursts appear to have a contribution from ion-induced nucleation and ion-ion recombination to form neutral clusters. Some indications were also found for the accelerator beam timing and intensity to influence the aerosol particle formation rate at the highest experimental SO2 concentrations of 6 ppb, although none was found at lower concentrations. Overall, the exploratory measurements provide suggestive evidence for ion-induced nucleation or ion-ion recombination as sources of aerosol particles. However in order to quantify the conditions under which ion processes become significant, improvements are needed in controlling the experimental variables and in the reproducibility of the experiments. Finally, concerning technical aspects, the most important lessons for the CLOUD design include the stringent requirement of internal cleanliness of the aerosol chamber, as well as maintenance of extremely stable temperatures (variations below 0.1 °C
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