Effect of cell density on thrombin binding to a specific site on bovine vascular endothelial cells.

We studied thrombin binding to proliferating and confluent endothelial cells derived from bovine vascular endothelium. [125]thrombin was incubated with nonconfluent or confluent endothelial cells and both the total amount bound and the amount linked in a 77,000-dalton thrombin-cell complex were determined. Approximately 230,000 molecules of thrombin bound per cell in nonconfluent cultures compared to 12,800 molecules per cell in confluent cultures. Approximately 67,7000 thrombin molecules were bound in an apparently covalent complex, Mr = 77,000, with each cell in sparse cultures, whereas only 4,600 thrombin molecules per cell were bound in this complex with confluent cultures. Similar studies with [125I]thrombin and endothelial cells derived from bovine cornea revealed no difference either in the total amount of thrombin bound or in the amount bound in the 77,000-dalton complex using sparse or confluent cultures. When confluent vascular endothelial cultures were wounded, additional cellular binding sites for the 77,000-dalton complex with thrombin appeared within 24 h. A 237% increase in the amount of thrombin bound to these sites was induced by a wound which resulted in a 20% decrease in cell number in the monolayer. There was no significant increase in thrombin binding to other cellular sites at 24 h. These experiments provide evidence that the first change in thrombin binding after injury is an increase in the cellular sites involved in the 77,000-dalton complex, and suggest that thrombin binding to endothelial cells may be important in the vascular response to injury

Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo

Ribonucleotides are the most abundant non-canonical component of yeast genomic DNA and their persistence is associated with a distinctive mutation signature characterized by deletion of a single repeat unit from a short tandem repeat. These deletion events are dependent on DNA topoisomerase I (Top1) and are initiated by Top1 incision at the relevant ribonucleotide 3′-phosphodiester. A requirement for the re-ligation activity of Top1 led us to propose a sequential cleavage model for Top1-dependent mutagenesis at ribonucleotides. Here, we test key features of this model via parallel in vitro and in vivo analyses. We find that the distance between two Top1 cleavage sites determines the deletion size and that this distance is inversely related to the deletion frequency. Following the creation of a gap by two Top1 cleavage events, the tandem repeat provides complementarity that promotes realignment to a nick and subsequent Top1-mediated ligation. Complementarity downstream of the gap promotes deletion formation more effectively than does complementarity upstream of the gap, consistent with constraints to realignment of the strand to which Top1 is covalently bound. Our data fortify sequential Top1 cleavage as the mechanism for ribonucleotide-dependent deletions and provide new insight into the component steps of this process

Distance Metric Learning using Graph Convolutional Networks: Application to Functional Brain Networks

Evaluating similarity between graphs is of major importance in several computer vision and pattern recognition problems, where graph representations are often used to model objects or interactions between elements. The choice of a distance or similarity metric is, however, not trivial and can be highly dependent on the application at hand. In this work, we propose a novel metric learning method to evaluate distance between graphs that leverages the power of convolutional neural networks, while exploiting concepts from spectral graph theory to allow these operations on irregular graphs. We demonstrate the potential of our method in the field of connectomics, where neuronal pathways or functional connections between brain regions are commonly modelled as graphs. In this problem, the definition of an appropriate graph similarity function is critical to unveil patterns of disruptions associated with certain brain disorders. Experimental results on the ABIDE dataset show that our method can learn a graph similarity metric tailored for a clinical application, improving the performance of a simple k-nn classifier by 11.9% compared to a traditional distance metric.Comment: International Conference on Medical Image Computing and Computer-Assisted Interventions (MICCAI) 201

Abrupt climate change as an important agent of ecological change in the Northeast U.S. throughout the past 15,000 years

Author Posting. © The Author(s), 2009. 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 Quaternary Science Reviews 28 (2009): 1693-1709, doi:10.1016/j.quascirev.2009.04.005.We use a series of tests to evaluate two competing hypotheses about the association of climate and vegetation trends in the northeastern United States over the past 15 kyrs. First, that abrupt climate changes on the scale of centuries had little influence on long-term vegetation trends, and second, that abrupt climate changes interacted with slower climate trends to determine the regional sequence of vegetation phases. Our results support the second. Large dissimilarity between temporally-close fossil pollen samples indicates large vegetation changes within 500 years across >4° of latitude at ca. 13.25-12.75, 12.0-11.5, 10.5, 8.25, and 5.25 ka. The evidence of vegetation change coincides with independent isotopic and sedimentary indicators of rapid shifts in temperature and moisture balance. In several cases, abrupt changes reversed long-term vegetation trends, such as when spruce (Picea) and pine (Pinus) pollen percentages rapidly declined to the north and increased to the south at ca. 13.25-12.75 and 8.25 ka respectively. Abrupt events accelerated other long‐term trends, such as a regional increase in beech (Fagus) pollen percentages at 8.5-8.0 ka. The regional hemlock (Tsuga) decline at ca. 5.25 ka is unique among the abrupt events, and may have been induced by high climatic variability (i.e., repeated severe droughts from 5.7-2.0 ka); autoregressive ecological and evolutionary processes could have maintained low hemlock abundance until ca. 2.0 ka. Delayed increases in chestnut (Castanea) pollen abundance after 5.8 and 2.5 ka also illustrate the potential for multi-century climate variability to influence species’ recruitment as well as mortality. Future climate changes will probably also rapidly initiate persistent vegetation change, particularly by acting as broad, regional-scale disturbances.This work was supported by NSF grants to B. Shuman (EAR‐0602408; DEB‐0816731) and J. Donnelly (EAR‐0602380)

Validation of the MODIS "Clear-Sky" Surface Temperature of the Greenland Ice Sheet

Surface temperatures on the Greenland Ice Sheet have been studied on the ground, using automatic weather station (AWS) data from the Greenland-Climate Network (GC-Net), and from analysis of satellite sensor data. Using Advanced Very High Frequency Radiometer (AVHRR) weekly surface temperature maps, warming of the surface of the Greenland Ice Sheet has been documented from 1981 to present. We extend and refine this record using higher-resolution Moderate-Resolution Imaging Spectroradiometer (MODIS) data from March 2000 to the present. To permit changes to be observed over time, we are developing a well-characterized monthly climate-data record (CDR) of the "clear-sky" surface temperature of the Greenland Ice Sheet using data from both the Terra and Aqua satellites. We use the MODIS ice-surface temperature (IST) algorithm. Validation of the CDR consists of several facets: 1) comparisons between the Terra and Aqua IST maps; 2) comparisons between ISTs and in-situ measurements; 3) comparisons between ISTs and AWS data; and 4) comparisons of ISTs with surface temperatures derived from other satellite instruments such as the Thermal Emission and Reflection Radiometer. In this work, we focus on 1) and 2) above. Surface temperatures on the Greenland Ice Sheet have been studied on the ground, using automatic weather station (AWS) data from the Greenland-Climate Network (GC-Net), and from analysis of satellite sensor data. Using Advanced Very High Frequency Radiometer (AVHRR) weekly surface temperature maps, warming of the surface of the Greenland Ice Sheet has been documented from 1981 to present. We extend and refine this record using higher-resolution Moderate-Resolution Imaging Spectroradiometer (MODIS) data from March 2000 to the present. To permit changes to be observed over time, we are developing a well-characterized monthly climate-data record (CDR) of the "clear-sky" surface temperature of the Greenland Ice Sheet using data from both the Terra and Aqua satellites. We use the MODIS ice-surface temperature (IST) algorithm. Validation of the CDR consists of several facets: 1) comparisons between the Terra and Aqua IST maps; 2) comparisons between ISTs and in-situ measurements; 3) comparisons between ISTs and AWS data; and 4) comparisons of ISTs with surface temperatures derived from other satellite instruments such as the Thermal Emission and Reflection Radiometer. In this work, we focus on 1) and 2) above. First we provide comparisons between Terra and Aqua swath-based ISTs at approximately 14:00 Local Solar Time, reprojected to 12.5 km polar stereographic cells. Results show good correspondence when Terra and Aqua data were acquired within 2 hrs of each other. For example, for a cell centered over Summit Camp (72.58 N, 38.5 W), the average agreement between Terra and Aqua ISTs is 0.74 K (February 2003), 0.47 K (April 2003), 0.7 K (August 2003) and 0.96 K (October 2003) with the Terra ISTs being generally lower than the Aqua ISTs. More precise comparisons will be calculated using pixel data at the swath level, and correspondence between Terra and Aqua IST is expected to be closer. (Because of cloud cover and other considerations, only a few common cloud-free swaths are typically available for each month for comparison.) Additionally, previous work comparing land-surface temperatures (LSTs) from the standard MODIS LST product and in-situ surface-temperature data at Summit Camp on the Greenland Ice Sheet show that Terra MODIS LSTs are about 3 K lower than in-situ temperatures at Summit Camp, during the winter of 2008-09. This work will be repeated using both Terra and Aqua IST pixel data (in place of LST data). In conclusion, we demonstrate that the uncertainties in the CDR will be well characterized as we work through the various facets of its validation

Laser cooling of a diatomic molecule

It has been roughly three decades since laser cooling techniques produced ultracold atoms, leading to rapid advances in a vast array of fields. Unfortunately laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for many applications. For example, heteronuclear molecules possess permanent electric dipole moments which lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures make ultracold molecules attractive candidates for use in quantum simulation of condensed matter systems and quantum computation. Also ultracold molecules may provide unique opportunities for studying chemical dynamics and for tests of fundamental symmetries. Here we experimentally demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using an optical cycling scheme requiring only three lasers, we have observed both Sisyphus and Doppler cooling forces which have substantially reduced the transverse temperature of a SrF molecular beam. Currently the only technique for producing ultracold molecules is by binding together ultracold alkali atoms through Feshbach resonance or photoassociation. By contrast, different proposed applications for ultracold molecules require a variety of molecular energy-level structures. Our method provides a new route to ultracold temperatures for molecules. In particular it bridges the gap between ultracold temperatures and the ~1 K temperatures attainable with directly cooled molecules (e.g. cryogenic buffer gas cooling or decelerated supersonic beams). Ultimately our technique should enable the production of large samples of molecules at ultracold temperatures for species that are chemically distinct from bialkalis.Comment: 10 pages, 7 figure

A Climate-Data Record of the "Clear-Sky" Surface Temperature of the Greenland Ice Sheet

We are developing a climate-data record (CDR of daily "clear-sky" ice-surface temperature (IST) of the Greenland Ice Sheet, from 1982 to the present using Advanced Very High Resolution Radiometer (AVHRR) (1982 - present) and Moderate-Resolution Imaging Spectroradiometer (MODIS) data (2000 - present) at a resolution of approximately 5 km. The CDR will be continued in the National Polar-orbiting Operational Environmental Satellite System Visible/Infrared Imager Radiometer Suite era. Two algorithms remain under consideration. One algorithm under consideration is based on the split-window technique used in the Polar Pathfinder dataset (Fowler et al., 2000 & 21007). Another algorithm under consideration, developed by Comiso (2006), uses a single channel of AVHRR data (channel 4) in conjunction with meteorological-station data to account for atmospheric effects and drift between AVHRR instruments. Known issues being addressed in the production of the CDR are: tune-series bias caused by cloud cover (surface temperatures can be different under clouds vs. clear areas) and cross-calibration in the overlap period between AVHRR instruments, and between AVHRR and MODIS instruments. Because of uncertainties, mainly due to clouds (Stroeve & Steffen, 1998; Wang and Key, 2005; Hall et al., 2008 and Koenig and Hall, submitted), time-series of satellite 1S'1" do not necessarily correspond to actual surface temperatures. The CDR will be validated by comparing results with automatic-,",eather station (AWS) data and with satellite-derived surface-temperature products. Regional "clear-sky" surface temperature increases in the Arctic, measured from AVHRR infrared data, range from 0.57+/-0.02 deg C (Wang and Key, 2005) to 0.72+/-0.10 deg C (Comiso, 2006) per decade since the early 1980s. Arctic warming has important implications for ice-sheet mass balance because much of the periphery of the Greenland Ice Sheet is already near 0 deg C during the melt season, and is thus vulnerable to rapid melting if temperatures continue to increase. Reference

Climate forcing of unprecedented intense-hurricane activity in the last 2000 years

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Earth's Future 3 (2015): 49–65, doi:10.1002/2014EF000274.How climate controls hurricane variability has critical implications for society is not well understood. In part, our understanding is hampered by the short and incomplete observational hurricane record. Here we present a synthesis of intense-hurricane activity from the western North Atlantic over the past two millennia, which is supported by a new, exceptionally well-resolved record from Salt Pond, Massachusetts (USA). At Salt Pond, three coarse grained event beds deposited in the historical interval are consistent with severe hurricanes in 1991 (Bob), 1675, and 1635 C.E., and provide modern analogs for 32 other prehistoric event beds. Two intervals of heightened frequency of event bed deposition between 1400 and 1675 C.E. (10 events) and 150 and 1150 C.E. (23 events), represent the local expression of coherent regional patterns in intense-hurricane–induced event beds. Our synthesis indicates that much of the western North Atlantic appears to have been active between 250 and 1150 C.E., with high levels of activity persisting in the Caribbean and Gulf of Mexico until 1400 C.E. This interval was one with relatively warm sea surface temperatures (SSTs) in the main development region (MDR). A shift in activity to the North American east coast occurred ca. 1400 C.E., with more frequent severe hurricane strikes recorded from The Bahamas to New England between 1400 and 1675 C.E. A warm SST anomaly along the western North Atlantic, rather than within the MDR, likely contributed to the later active interval being restricted to the east coast.Funding was provided by US National Science Foundation (awards 0903020 and 1356708), the Risk Prediction Initiative at the Bermuda Institute for Ocean Sciences (BIOS), US Department of Energy National Institute for Climate Change Research, National Oceanic and Atmospheric Administration (award NA11OAR431010), and the Dalio Explore Fund