512 research outputs found

    Price Adjustment and Liquidity in a Residential Real Estate Market with an Accelerated Information Cascade

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    We examine the effect of an unannounced information event, Hurricane Katrina, on the liquidity of the residential real estate market in an area proximately located to the Mississippi Gulf Coast. Using 2SLS and Weibull techniques applied to a unique MLS data set, we test changes in liquidity in a submarkets framework. Results suggest Katrina created submarket effects with respect to the listing and sales periods of our sample and market liquidity was directly influenced by this event. We suggest that this effect was tied to information flow as owners of heavily damaged properties sought new housing in a nearby area.

    Microbial control of diatom bloom dynamics in the open ocean

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    Diatom blooms play a central role in supporting foodwebs and sequestering biogenic carbon to depth. Oceanic conditions set bloom initiation, whereas both environmental and ecological factors determine bloom magnitude and longevity. Our study reveals another fundamental determinant of bloom dynamics. A diatom spring bloom in offshore New Zealand waters was likely terminated by iron limitation, even though diatoms consumed <1/3 of the mixed-layer dissolved iron inventory. Thus, bloom duration and magnitude were primarily set by competition for dissolved iron between microbes and small phytoplankton versus diatoms. Significantly, such a microbial mode of control probably relies both upon out-competing diatoms for iron (i.e., K-strategy), and having high iron requirements (i.e., r-strategy). Such resource competition for iron has implications for carbon biogeochemistry, as, blooming diatoms fixed three-fold more carbon per unit iron than resident non-blooming microbes. Microbial sequestration of iron has major ramifications for determining the biogeochemical imprint of oceanic diatom blooms. Citation: Boyd, P. W., et al. (2012), Microbial control of diatom bloom dynamics in the open ocean, Geophys. Res. Lett., 39, L18601

    Topological Constraint Theory Analysis of Rigidity Transition in Highly Coordinate Amorphous Hydrogenated Boron Carbide

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    Topological constraint theory (TCT) has revealed itself to be a powerful tool in interpreting the behaviors of amorphous solids. The theory predicts a transition between a “rigid” overconstrained network and a “floppy” underconstrained network as a function of connectivity or average coordination number, 〈râŒȘ. The predicted results have been shown experimentally for various glassy materials, the majority of these being based on 4-fold-coordinate networks such as chalcogenide and oxide glasses. Here, we demonstrate the broader applicability of topological constraint theory to uniquely coordinated amorphous hydrogenated boron carbide (a-BC:H), based on 6-fold-coordinate boron atoms arranged into partially hydrogenated interconnected 12-vertex icosahedra. We have produced a substantial set of plasma-enhanced chemical vapor deposited a-BC:H films with a large range of densities and network coordination, and demonstrate a clear threshold in Young\u27s modulus as a function of 〈râŒȘ, ascribed to a rigidity transition. We investigate constraint counting strategies in this material and show that by treating icosahedra as “superatoms,” a rigidity transition is observed within the range of the theoretically predicted 〈râŒȘc value of 2.4 for covalent solids with bond-stretching and bond-bending forces. This experimental data set for a-BC:H is unique in that it represents a uniform change in connectivity with 〈râŒȘ and demonstrates a distinct rigidity transition with data points both above and below the transition threshold. Finally, we discuss how TCT can be applied to explain and optimize mechanical and dielectric properties in a-BC:H and related materials in the context of microelectronics applications

    The Cool Accretion Disk in ESO 243-49 HLX-1: Further Evidence of an Intermediate Mass Black Hole

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    With an inferred bolometric luminosity exceeding 10^42 erg/s, HLX-1 in ESO 243-49 is the most luminous of ultraluminous X-ray sources and provides one of the strongest cases for the existence of intermediate mass black holes. We obtain good fits to disk-dominated observations of the source with BHSPEC, a fully relativistic black hole accretion disk spectral model. Due to degeneracies in the model arising from the lack of independent constraints on inclination and black hole spin, there is a factor of 100 uncertainty in the best-fit black hole mass M. Nevertheless, spectral fitting of XMM-Newton observations provides robust lower and upper limits with 3000 Msun < M < 3 x 10^5 Msun, at 90% confidence, placing HLX-1 firmly in the intermediate-mass regime. The lower bound on M is entirely determined by matching the shape and peak energy of the thermal component in the spectrum. This bound is consistent with (but independent of) arguments based solely on the Eddington limit. Joint spectral modelling of the XMM-Newton data with more luminous Swift and Chandra observations increases the lower bound to 6000 Msun, but this tighter constraint is not independent of the Eddington limit. The upper bound on M is sensitive to the maximum allowed inclination i, and is reduced to M < 10^5 Msun if we limit i < 75 deg.Comment: 10 pages, 7 figures, accepted for publication in Ap

    Carbon‐Enriched Amorphous Hydrogenated Boron Carbide Films for Very‐Low‐k Interlayer Dielectrics

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    A longstanding challenge in ultralarge‐scale integration has been the continued improvement in low‐dielectric‐constant (low‐k) interlayer dielectric materials and other specialized layers in back‐end‐of‐the‐line interconnect fabrication. Modeled after the success of carbon‐containing organosilicate materials, carbon‐enriched amorphous hydrogenated boron carbide (a‐BxC:Hy) films are grown by plasma‐enhanced chemical vapor deposition from ortho‐carborane and methane. These films contain more extraicosahedral sp3 hydrocarbon groups than nonenriched a‐BxC:Hy films, as revealed by FTIR and NMR spectroscopy, and also exhibit lower dielectric constants than their nonenriched counterparts, notably due to low densities combined with a low distortion and orientation contribution to the total polarizability. Films with dielectric constant as low as 2.5 are reported with excellent electrical stability (leakage current of 10−9 A cm−2 at 2 MV cm−1 and breakdown voltage of >6 MV cm−1), good thermal conductivity of 0.31 ± 0.03 W m−1 K−1, and high projected Young’s modulus of 12 ± 3 GPa. These properties rival those of leading SiOC:H materials, and position a‐BxC:Hy as an important complement to traditional Si‐based materials to meet the complex needs of next‐generation interconnect fabrication.Carbon‐enriched amorphous hydrogenated boron carbide films are demonstrated with dielectric constant (k) as low as 2.5—attributed to low densities combined with network‐rigidifying CH2 bridging groups—as well as excellent electrical, thermal, and mechanical properties, rivaling those of state‐of‐the‐art silicon‐based low‐k dielectric materials.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141869/1/aelm201700116_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141869/2/aelm201700116.pd

    Drug discovery for male subfertility using high-throughput screening:a new approach to an unsolved problem

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    STUDY QUESTIONCan pharma drug discovery approaches be utilized to transform investigation into novel therapeutics for male infertility?SUMMARY ANSWERHigh-throughput screening (HTS) is a viable approach to much-needed drug discovery for male factor infertility.WHAT IS KNOWN ALREADYThere is both huge demand and a genuine clinical need for new treatment options for infertile men. However, the time, effort and resources required for drug discovery are currently exorbitant, due to the unique challenges of the cellular, physical and functional properties of human spermatozoa and a lack of appropriate assay platform.STUDY DESIGN, SIZE, DURATIONSpermatozoa were obtained from healthy volunteer research donors and subfertile patients undergoing IVF/ICSI at a hospital-assisted reproductive techniques clinic between January 2012 and November 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSA HTS assay was developed and validated using intracellular calcium ([Ca2+]i) as a surrogate for motility in human spermatozoa. Calcium fluorescence was detected using a Flexstation microplate reader (384-well platform) and compared with responses evoked by progesterone, a compound known to modify a number of biologically relevant behaviours in human spermatozoa. Hit compounds identified following single point drug screen (10 ÎŒM) of an ion channel-focussed library assembled by the University of Dundee Drug Discovery Unit were rescreened to ensure potency using standard 10 point half-logarithm concentration curves, and tested for purity and integrity using liquid chromatography and mass spectrometry. Hit compounds were grouped by structure activity relationships and five representative compounds then further investigated for direct effects on spermatozoa, using computer-assisted sperm assessment, sperm penetration assay and whole-cell patch clamping.MAIN RESULTS AND THE ROLE OF CHANCEOf the 3242 ion channel library ligands screened, 384 compounds (11.8%) elicited a statistically significant increase in calcium fluorescence, with greater than 3× median absolute deviation above the baseline. Seventy-four compounds eliciting ≄50% increase in fluorescence in the primary screen were rescreened and evaluated further, resulting in 48 hit compounds that produced a concentration-dependent increase in [Ca2+]i. Sperm penetration studies confirmed in vitro exposure to two hit compounds (A and B) resulted in significant improvement in functional motility in spermatozoa from healthy volunteer donors (A: 1 cm penetration index 2.54, 2 cm penetration index 2.49; P &lt; 0.005 and B: 1 cm penetration index 2.1, 2 cm penetration index 2.6; P &lt; 0.005), but crucially, also in patient samples from those undergoing fertility treatment (A: 1 cm penetration index 2.4; P = 0.009, 2 cm penetration index 3.6; P = 0.02 and B: 1 cm penetration index 2.2; P = 0.0004, 2 cm penetration index 3.6; P = 0.002). This was primarily as a result of direct or indirect CatSper channel action, supported by evidence from electrophysiology studies of individual sperm.LIMITATIONS, REASONS FOR CAUTIONIncrease and fluxes in [Ca2+]i are fundamental to the regulation of sperm motility and function, including acrosome reaction. The use of calcium signalling as a surrogate for sperm motility is acknowledged as a potential limitation in this study.WIDER IMPLICATIONS OF THE FINDINGSWe conclude that HTS can robustly, efficiently, identify novel compounds that increase [Ca2+]i in human spermatozoa and functionally modify motility, and propose its use as a cornerstone to build and transform much-needed drug discovery for male infertility.</p

    Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.

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    The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens

    Langmuir films of layered nanomaterials: edge interactions and cell culture applications

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    The application of nanomaterials in technology is limited by challenges in their processing into macroscopic structures with reliable and scalable methods. Herein, it is demonstrated that using scalable fabrication methods such as liquid-phase exfoliation it is possible to produce dispersions of a wide variety of layered nanomaterials, including the first demonstration of boron nitride, with controllable and standardised size and thickness scaling. These can be used as-produced for Langmuir deposition, to create single layer films with tuneable density. Of particular importance, we show that the difference in edge chemistry of these materials dictates the film formation process, and therefore can be used to provide a generic fabrication methodology that is demonstrated for various layered nanomaterials, including graphene, boron nitride and transition metal dichalcogenides. We show that this leads to controllable cancer cell growth on graphene substrates with different edge densities but comparable surface coverage, which can be produced on a statistically relevant cell study amount. This opens up pathways for the generic fabrication of a range of layered nanomaterial films for various applications, towards a commercially viable film fabrication technology
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