Coordinated analysis of delayed sprites with high-speed images and remote electromagnetic fields

Simultaneous measurements of high-altitude optical emissions and magnetic fields produced by sprite-associated lightning discharges enable a close examination of the link between low-altitude lightning processes and high-altitude sprite processes. We report results of the coordinated analysis of high-speed sprite video and wideband magnetic field measurements recorded simultaneously at Yucca Ridge Field Station and Duke University. From June to August 2005, sprites were detected following 67 lightning strokes, all of which had positive polarity. Our data showed that 46% of the 83 discrete sprite events in these sequences initiated more than 10 ms after the lightning return stroke, and we focus on these delayed sprites in this work. All delayed sprites were preceded by continuing current moments that averaged at least 11 kA km between the return stroke and sprites. The total lightning charge moment change at sprite initiation varied from 600 to 18,600 C km, and the minimum value to initiate long-delayed sprites ranged from 600 for 15 ms delay to 2000 C km for more than 120 ms delay. We numerically simulated electric fields at altitudes above these lightning discharges and found that the maximum normalized electric fields are essentially the same as fields that produce short-delayed sprites. Both estimated and simulation-predicted sprite initiation altitudes indicate that long-delayed sprites generally initiate around 5 km lower than short-delayed sprites. The simulation results also reveal that slow (5-20 ms) intensifications in continuing current can play a major role in initiating delayed sprites. Copyright 2008 by the American Geophysical Union.

Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation.

The folate pathway plays a crucial role in the regeneration and repair of the adult CNS after injury. Here, we have shown in rodents that such repair occurs at least in part through DNA methylation. In animals with combined spinal cord and sciatic nerve injury, folate-mediated CNS axon regeneration was found to depend on injury-related induction of the high-affinity folate receptor 1 (Folr1). The activity of folate was dependent on its activation by the enzyme dihydrofolate reductase (Dhfr) and a functional methylation cycle. The effect of folate on the regeneration of afferent spinal neurons was biphasic and dose dependent and correlated closely over its dose range with global and gene-specific DNA methylation and with expression of both the folate receptor Folr1 and the de novo DNA methyltransferases. These data implicate an epigenetic mechanism in CNS repair. Folic acid and possibly other nontoxic dietary methyl donors may therefore be useful in clinical interventions to promote brain and spinal cord healing. If indeed the benefit of folate is mediated by epigenetic mechanisms that promote endogenous axonal regeneration, this provides possible avenues for new pharmacologic approaches to treating CNS injuries.

Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.

Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18 influence susceptibility to S. aureus sepsis in A/J mice. We then used two candidate gene selection strategies to identify genes on these three chromosomes associated with S. aureus susceptibility, and targeted genes identified by both gene selection strategies. First, we used whole genome transcription profiling to identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr. 18) genes on our three chromosomes of interest that are differentially expressed between S. aureus-infected A/J and C57BL/6J. Second, we identified two significant quantitative trait loci (QTL) for survival post-infection on chr. 18 using N(2) backcross mice (F(1) [C18A]xC57BL/6J). Ten genes on chr. 18 (March3, Cep120, Chmp1b, Dcp2, Dtwd2, Isoc1, Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two significant QTL regions and were also identified by the expression array selection strategy. Using real-time PCR, 6 of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8, and Seh1l) showed significantly different expression levels between S. aureus-infected A/J and C57BL/6J. For two (Tnfaip8 and Seh1l) of these 6 genes, siRNA-mediated knockdown of gene expression in S. aureus-challenged RAW264.7 macrophages induced significant changes in the cytokine response (IL-1 beta and GM-CSF) compared to negative controls. These cytokine response changes were consistent with those seen in S. aureus-challenged peritoneal macrophages from CSS 18 mice (which contain A/J chromosome 18 but are otherwise C57BL/6J), but not C57BL/6J mice. These findings suggest that two genes, Tnfaip8 and Seh1l, may contribute to susceptibility to S. aureus in A/J mice, and represent promising candidates for human genetic susceptibility studies.

Indication of electron neutrino appearance from an accelerator-produced off-axis muon neutrino beam.

The T2K experiment observes indications of ν(μ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Δm(23)(2)| = 2.4×10(-3)  eV(2), sin(2)2θ(23) = 1 and sin(2)2θ(13) = 0, the expected number of such events is 1.5±0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2θ(13) < 0.28(0.34) for δ(CP) = 0 and a normal (inverted) hierarchy.

A Politics of the Unspeakable: The Differend of Israel

Israel's establishment in 1948 in former British-Mandate Palestine as a Jewish country and as a liberal democracy is commonly understood as a form of response to the Holocaust of WWII. Zionist narratives frame Israel's establishment not only as a response to the Holocaust, but also as a return to the Jewish people's original homeland after centuries of wandering in exile. Debates over Israel's policies, particularly with regard to Palestinians and to the country's non-Jewish population, often center on whether Israel's claims to Jewish singularity are at the expense of principles of liberal democracy, international law and universal human rights. In this dissertation, I argue that Israel's emphasis on Jewish singularity can be understood not as a violation of humanism's universalist frameworks, but as a symptom of the violence inherent to these frameworks and to the modern liberal rights-bearing subject on which they are based. Through an analysis of my fieldwork in Israel (2005-2008), I trace the relation between the figures of "Jew" and "Israeli" in terms of their historical genealogies and in contemporary Israeli contexts. Doing so makes legible how European modernity and its concepts of sovereignty, liberalism, the human, and subjectivity are based on a metaphysics of presence that defines the human through a displacement of difference. This displaced difference is manifest in affective expression. This dissertation shows how the figure of the Jew in relation to Israel reveals sexual difference as under erasure by the suppression of alterity in humanism's configuration of man, woman, and animal, and suggests a political subject unable to be sovereign or fully represented in language.

Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference.

Beta-arrestins bind to activated G protein-coupled receptor kinase-phosphorylated receptors, which leads to their desensitization with respect to G proteins, internalization via clathrin-coated pits, and signaling via a growing list of "scaffolded" pathways. To facilitate the discovery of novel adaptor and signaling roles of beta-arrestins, we have developed and validated a generally applicable interfering RNA approach for selectively suppressing beta-arrestins 1 or 2 expression by up to 95%. Beta-arrestin depletion in HEK293 cells leads to enhanced cAMP generation in response to beta(2)-adrenergic receptor stimulation, markedly reduced beta(2)-adrenergic receptor and angiotensin II receptor internalization and impaired activation of the MAP kinases ERK 1 and 2 by angiotensin II. This approach should allow discovery of novel signaling and regulatory roles for the beta-arrestins in many seven-membrane-spanning receptor systems.

Ecological homogenization of urban USA

A visually apparent but scientifically untested outcome of land-use change is homogenization across urban areas, where neighborhoods in different parts of the country have similar patterns of roads, residential lots, commercial areas, and aquatic features. We hypothesize that this homogenization extends to ecological structure and also to ecosystem functions such as carbon dynamics and microclimate, with continental-scale implications. Further, we suggest that understanding urban homogenization will provide the basis for understanding the impacts of urban land-use change from local to continental scales. Here, we show how multi-scale, multidisciplinary datasets from six metropolitan areas that cover the major climatic regions of the US (Phoenix, AZ; Miami, FL; Baltimore, MD; Boston, MA; Minneapolis-St Paul, MN; and Los Angeles, CA) can be used to determine how household and neighborhood characteristics correlate with land-management practices, land-cover composition, and landscape structure and ecosystem functions at local, regional, and continental scales. © The Ecological Society of America.

Convergent Surface Water Distributions in U.S. Cities

Earth's surface is rapidly urbanizing, resulting in dramatic changes in the abundance, distribution and character of surface water features in urban landscapes. However, the scope and consequences of surface water redistribution at broad spatial scales are not well understood. We hypothesized that urbanization would lead to convergent surface water abundance and distribution: in other words, cities will gain or lose water such that they become more similar to each other than are their surrounding natural landscapes. Using a database of more than 1 million water bodies and 1 million km of streams, we compared the surface water of 100 US cities with their surrounding undeveloped land. We evaluated differences in areal (A WB) and numeric densities (N WB) of water bodies (lakes, wetlands, and so on), the morphological characteristics of water bodies (size), and the density (D C) of surface flow channels (that is, streams and rivers). The variance of urban A WB, N WB, and D C across the 100 MSAs decreased, by 89, 25, and 71%, respectively, compared to undeveloped land. These data show that many cities are surface water poor relative to undeveloped land; however, in drier landscapes urbanization increases the occurrence of surface water. This convergence pattern strengthened with development intensity, such that high intensity urban development had an areal water body density 98% less than undeveloped lands. Urbanization appears to drive the convergence of hydrological features across the US, such that surface water distributions of cities are more similar to each other than to their surrounding landscapes. © 2014 The Author(s).

Assessing the homogenization of urban land management with an application to US residential lawn care.

Changes in land use, land cover, and land management present some of the greatest potential global environmental challenges of the 21st century. Urbanization, one of the principal drivers of these transformations, is commonly thought to be generating land changes that are increasingly similar. An implication of this multiscale homogenization hypothesis is that the ecosystem structure and function and human behaviors associated with urbanization should be more similar in certain kinds of urbanized locations across biogeophysical gradients than across urbanization gradients in places with similar biogeophysical characteristics. This paper introduces an analytical framework for testing this hypothesis, and applies the framework to the case of residential lawn care. This set of land management behaviors are often assumed--not demonstrated--to exhibit homogeneity. Multivariate analyses are conducted on telephone survey responses from a geographically stratified random sample of homeowners (n = 9,480), equally distributed across six US metropolitan areas. Two behaviors are examined: lawn fertilizing and irrigating. Limited support for strong homogenization is found at two scales (i.e., multi- and single-city; 2 of 36 cases), but significant support is found for homogenization at only one scale (22 cases) or at neither scale (12 cases). These results suggest that US lawn care behaviors are more differentiated in practice than in theory. Thus, even if the biophysical outcomes of urbanization are homogenizing, managing the associated sustainability implications may require a multiscale, differentiated approach because the underlying social practices appear relatively varied. The analytical approach introduced here should also be productive for other facets of urban-ecological homogenization.

Copper signaling axis as a target for prostate cancer therapeutics.

Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for prostate cancer cell function as we observed only modest effects of chelation strategies on the growth of these cells in vitro. With the goal of exploiting prostate cancer cell proclivity for copper uptake, we developed a "conditional lethal" screen to identify compounds whose cytotoxic actions were manifested in a copper-dependent manner. Emerging from this screen was a series of dithiocarbamates, which, when complexed with copper, induced reactive oxygen species-dependent apoptosis of malignant, but not normal, prostate cells. One of the dithiocarbamates identified, disulfiram (DSF), is an FDA-approved drug that has previously yielded disappointing results in clinical trials in patients with recurrent prostate cancer. Similarly, in our studies, DSF alone had a minimal effect on the growth of prostate cancer tumors when propagated as xenografts. However, when DSF was coadministered with copper, a very dramatic inhibition of tumor growth in models of hormone-sensitive and of castrate-resistant disease was observed. Furthermore, we determined that prostate cancer cells express high levels of CTR1, the primary copper transporter, and additional chaperones that are required to maintain intracellular copper homeostasis. The expression levels of most of these proteins are increased further upon treatment of androgen receptor (AR)-positive prostate cancer cell lines with androgens. Not surprisingly, robust CTR1-dependent uptake of copper into prostate cancer cells was observed, an activity that was accentuated by activation of AR. Given these data linking AR to intracellular copper uptake, we believe that dithiocarbamate/copper complexes are likely to be effective for the treatment of patients with prostate cancer whose disease is resistant to classical androgen ablation therapies.

In vivo visualization of abdominal malignancies with acoustic radiation force elastography.

The utility of acoustic radiation force impulse (ARFI) imaging for real-time visualization of abdominal malignancies was investigated. Nine patients presenting with suspicious masses in the liver (n = 7) or kidney (n = 2) underwent combined sonography/ARFI imaging. Images were acquired of a total of 12 tumors in the nine patients. In all cases, boundary definition in ARFI images was improved or equivalent to boundary definition in B-mode images. Displacement contrast in ARFI images was superior to echo contrast in B-mode images for each tumor. The mean contrast for suspected hepatocellular carcinomas (HCCs) in B-mode images was 2.9 dB (range: 1.5-4.2) versus 7.5 dB (range: 3.1-11.9) in ARFI images, with all HCCs appearing more compliant than regional cirrhotic liver parenchyma. The mean contrast for metastases in B-mode images was 3.1 dB (range: 1.2-5.2) versus 9.3 dB (range: 5.7-13.9) in ARFI images, with all masses appearing less compliant than regional non-cirrhotic liver parenchyma. ARFI image contrast (10.4 dB) was superior to B-mode contrast (0.9 dB) for a renal mass. To our knowledge, we present the first in vivo images of abdominal malignancies in humans acquired with the ARFI method or any other technique of imaging tissue elasticity.

In vivo guidance and assessment of liver radio-frequency ablation with acoustic radiation force elastography.

The initial results from clinical trials investigating the utility of acoustic radiation force impulse (ARFI) imaging for use with radio-frequency ablation (RFA) procedures in the liver are presented. To date, data have been collected from 6 RFA procedures in 5 unique patients. Large displacement contrast was observed in ARFI images of both pre-ablation malignancies (mean 7.5 dB, range 5.7-11.9 dB) and post-ablation thermal lesions (mean 6.2 dB, range 5.1-7.5 dB). In general, ARFI images provided superior boundary definition of structures relative to the use of conventional sonography alone. Although further investigations are required, initial results are encouraging and demonstrate the clinical promise of the ARFI method for use in many stages of RFA procedures.

Biological and physical interactions on a tropical island coral reef: Transport and retention processes on moorea, French Polynesia

The Moorea Coral Reef Long Term Ecological Research project funded by the US National Science Foundation includes multidisciplinary studies of physical processes driving ecological dynamics across the fringing reef, back reef, and fore reef habitats of Moorea, French Polynesia. A network of oceanographic moorings and a variety of other approaches have been used to investigate the biological and biogeochemical aspects of water transport and retention processes in this system. There is evidence to support the hypothesis that a low-frequency counterclockwise flow around the island is superimposed on the relatively strong alongshore currents on each side of the island. Despite the rapid flow and flushing of the back reef, waters over the reef display chemical and biological characteristics distinct from those offshore. The patterns include higher nutrient and lower dissolved organic carbon concentrations, distinct microbial community compositions among habitats, and reef assemblages of zooplankton that exhibit migration behavior, suggesting multigenerational residence on the reef. Zooplankton consumption by planktivorous fish on the reef reflects both retention of reef-associated taxa and capture by the reef community of resources originating offshore. Coral recruitment and population genetics of reef fishes point to retention of larvae within the system and high recruitment levels from local adult populations. The combined results suggest that a broad suite of physical and biological processes contribute to high retention of externally derived and locally produced organic materials within this island coral reef system. © 2013 by The Oceanography Society. All rights reserved.

Adiantumshastense, a new species of maidenhair fern from California.

A new species of Adiantum is described from California. This species is endemic to northern California and is currently known only from Shasta County. We describe its discovery after first being collected over a century ago and distinguish it from Adiantumjordanii and Adiantumcapillus-veneris. It is evergreen and is sometimes, but not always, associated with limestone. The range of Adiantumshastense Huiet & A.R.Sm., sp. nov., is similar to several other Shasta County endemics that occur in the mesic forests of the Eastern Klamath Range, close to Shasta Lake, on limestone and metasedimentary substrates.