bluuebunny/crossref_metadata_2025 huggingface dataset:
Representation of the Sierra Barrier Jet in 11 years of a high‐resolution dynamical reanalysis downscaling compared with long‐term wind profiler observations
Authors: Hughes Mimi , Neiman Paul J. , Sukovich Ellen , Ralph Marty
Published: September 2012

We investigate the representation of the Sierra Barrier Jet (SBJ) in four numerical models at different resolutions, primarily documenting its representation within a high‐resolution (6 km), 11‐year WRF reanalysis downscaling (WRF‐RD). A comprehensive validation of this dynamical downscaling is undertaken during 11 cool seasons (water years 2001–2011, October to March) using available wind profiler data at Chico, CA (CCO). We identify SBJ cases in the observed CCO wind profiler data, as well as in WRF‐RD at the closest grid point. WRF‐RD's representation of the SBJ at CCO is compared with that of other reanalysis products with coarser horizontal resolutions (i.e., the North American Regional Reanalysis (NARR), the California Reanalysis downscaling, and the NCEP/NCAR Reanalysis) to assess whether downscaling is necessary to correctly capture this topographically induced low‐level jet. Detailed comparisons across California between WRF‐RD and NARR suggest downscaling is necessary: Only WRF‐RD at 6 km resolution is well‐capturing this dynamical feature. A catalog of modeled SBJ events that have significant timing overlap with observations is created and used to further assess WRF‐RD's representation of SBJ events. In addition, observation‐model comparisons of other meteorologically important variables (e.g., precipitation melting level, wind profiles, temperature, and relative humidity) are performed in order to evaluate WRF‐RD's ability to capture the dynamical evolution of the SBJ. The detailed, case‐by‐case comparisons reveal WRF‐RD accurately represents 56 percent of the 256 observed SBJ cases occurring during these 11 cool seasons, albeit with a weak wind bias that increases with jet maximum wind strength.
On the gas‐particle partitioning of soluble organic aerosol in two urban atmospheres with contrasting emissions: 2. Gas and particle phase formic acid
Authors: Liu Jiumeng , Zhang Xiaolu , Parker Eric T. , Veres Patrick R. , Roberts James M. , de Gouw Joost A. , Hayes Patrick L. , Jimenez Jose L. , Murphy Jennifer G. , Ellis Raluca A. , Huey L. Greg , Weber Rodney J.
Published: September 2012

Gas and fine particle (PM2.5) phase formic acid concentrations were measured with online instrumentation during separate one‐month studies in the summer of 2010 in Los Angeles (LA), CA, and Atlanta, GA. In both urban environments, median gas phase concentrations were on the order of a few ppbv (LA 1.6 ppbv, Atlanta 2.3 ppbv) and median particle phase concentrations were approximately tens of ng/m3 (LA 49 ng/m3, Atlanta 39 ng/m3). LA formic acid gas and particle concentrations had consistent temporal patterns; both peaked in the early afternoon and generally followed the trends in photochemical secondary gases. Atlanta diurnal trends were more irregular, but the mean diurnal profile had similar afternoon peaks in both gas and particle concentrations, suggesting a photochemical source in both cities. LA formic acid particle/gas (p/g) ratios ranged between 0.01 and 12%, with a median of 1.3%. No clear evidence that LA formic acid preferentially partitioned to particle water was observed, except on three overcast periods of suppressed photochemical activity. Application of Henry's Law to predict partitioning during these periods greatly under‐predicted particle phase formate concentrations based on bulk aerosol liquid water content (LWC) and pH estimated from thermodynamic models. In contrast to LA, formic acid partitioning in Atlanta appeared to be more consistently associated with elevated relative humidity (i.e., aerosol LWC), although p/g ratios were somewhat lower, ranging from 0.20 to 5.8%, with a median of 0.8%. Differences in formic acid gas absorbing phase preferences between these two cities are consistent with that of bulk water‐soluble organic carbon reported in a companion paper.
Micro‐topographic analysis of shell pavements formed by aeolian transport in a wind tunnel simulation
Authors: McKenna Neuman Cheryl , Li Bailiang , Nash David
Published: September 2012

Beach surfaces containing shell materials represent one end‐member of a range of environments in which armoring is the primary control on wind erosion. Unlike spheres and cylinders which have formed the basis of theoretical model formulation and much of the early work in wind tunnels, mollusc shells have complex and non‐uniform shapes which vary with their orientation. Identification of shell perimeter, height and frontal area relative to the bed area (roughness density) is therefore a formidable task, but nonetheless is essential for modeling sediment entrainment from beach surfaces. A methodology is suggested in this paper for capturing and analyzing these geospatial data, in the context of a wind tunnel simulation designed to improve understanding of the geophysical processes involved in armoring. For deposits where non‐erodible shells represent half of the volume of the parent material, the surface appears to be highly stable to wind erosion from the outset, although minor reworking of the intervening, erodible sediment does occur. In comparison, the shell coverage must increase to approximately 30% during wind erosion events in order for any given beach surface to stabilize, especially beach deposits with a low concentration of shells by volume. With suitable calibration, the Raupach shear stress partitioning model can be forced to perform well in predicting the threshold conditions for particle entrainment. However, this approach overlooks the pivotal involvement of particle impact and ricochet in the creation and sculpting of the armored bed. As a case in point, when the shells are removed from digital elevation models of armored beach surfaces formed in aeolian systems, the adjusted topography is not suggestive of the presence of coherent flow structures (e.g., horseshoe vortices and wedge shaped shelter areas) as assumed to exist in the stress partitioning approach for isolated flows. This would suggest that future work on the armoring of natural surfaces affected by wind erosion must allow for more complexity in the flow perturbation.
CADASIL Mutations and shRNA Silencing of NOTCH3 Affect Actin Organization in Cultured Vascular Smooth Muscle Cells
Authors: Tikka Saara , Ng Yan Peng , Maio Giuseppe Di , Mykkänen Kati , Siitonen Maija , Lepikhova Tatiana , Pöyhönen Minna , Viitanen Matti , Virtanen Ismo , Kalimo Hannu , Baumann Marc
Published: September 2012

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular dementia caused by mutations in NOTCH3 gene. Pathology is manifested in small- and middle-sized arteries throughout the body, though primarily in cerebral white matter. Hemodynamics is altered in CADASIL and NOTCH3 is suggested to regulate actin filament polymerization and thereby vascular tone. We analyzed NOTCH3 expression and morphology of actin cytoskeleton in genetically genuine cultured human CADASIL vascular smooth muscle cells (VSMCs) (including a cell line homozygous for p. Arg133Cys mutation) derived from different organs, and in control VSMCs with short hairpin RNA (shRNA)-silenced NOTCH3. NOTCH3 protein level was higher in VSMCs derived from adult than newborn arteries in both CADASIL and control VSMCs. CADASIL VSMCs showed altered actin cytoskeleton including increased branching and node formation, and more numerous and smaller adhesion sites than control VSMCs. Alterations in actin cytoskeleton in shRNA-silenced VSMCs were similar as in CADASIL VSMCs. Severity of the alterations in actin filaments corresponded to NOTCH3 expression level being most severe in VSMCs derived from adult cerebral arteries. These observations suggest that hypomorphic NOTCH3 activity causes alterations in actin organization in CADASIL. Furthermore, arteries from different organs have specific characteristics, which modify the effects of the NOTCH3 mutation and which is one explanation for the exceptional susceptibility of cerebral white matter arteries.
Half-metallicity in graphene nanoribbons with topological defects at edge
Authors: Bhattacharjee Joydeep
Published: September 2012

We report first principles studies of zigzag edged graphene nanoribbons (ZGNR) with one edge partially covered by topological defects. With increasing coverage of an edge by pentagons and heptagons, which are two of the simplest topological defects possible in a graphenic lattice, ZGNRs evolve from a magnetic semiconductor to a ferromagnetic metal. This evolution can be intermediated by a narrow bandgap half-metallic phase, upon suitable concentration and conformation of defects at the edge. Spin-frustration induced by topological defects lead to substantial lowering of magnetic ordering and localization of defect-states in the vicinity of the defects. Dispersion of bands constituted by the defect-states within the bandgap of the corresponding unmodified ZGNR, leads to availability of energy windows for spin-polarized electron transport. Driven primarily by exchange interactions, the energy window for transport of electrons near Fermi energy, is consistently wider and more prevalent for the minority spin, in the entire class of ZGNRs with discontinuous patches of topological defects at an edge. Such defects have been widely predicted and observed to be naturally present at the interfaces in polycrystalline graphene, and can even be formed through chemical and physical processes. Our approach thus may lead to a feasible strategy to manifest workable half-metallicity in ZGNRs without involving non-carbon dopants or functional groups.
The electrical asymmetry effect in geometrically asymmetric capacitive radio frequency plasmas
Authors: Schüngel E. , Eremin D. , Schulze J. , Mussenbrock T. , Czarnetzki U.
Published: September 2012

The electrical asymmetry effect (EAE) allows an almost ideal separate control of the mean ion energy, 〈Ei〉, and flux, Γi, at the electrodes in capacitive radio frequency discharges with identical electrode areas driven at two consecutive harmonics with adjustable phase shift, θ. In such geometrically symmetric discharges, a DC self bias is generated as a function of θ. Consequently, 〈Ei〉 can be controlled separately from Γi by adjusting the phase shift. Here, we systematically study the EAE in low pressure dual-frequency discharges with different electrode areas operated in argon at 13.56 MHz and 27.12 MHz by experiments, kinetic simulations, and analytical modeling. We find that the functional dependence of the DC self bias on θ is similar, but its absolute value is strongly affected by the electrode area ratio. Consequently, the ion energy distributions change and 〈Ei〉 can be controlled by adjusting θ, but its control range is different at both electrodes and determined by the area ratio. Under distinct conditions, the geometric asymmetry can be compensated electrically. In contrast to geometrically symmetric discharges, we find the ratio of the maximum sheath voltages to remain constant as a function of θ at low pressures and Γi to depend on θ at the smaller electrode. These observations are understood by the model. Finally, we study the self-excitation of non-linear plasma series resonance oscillations and its effect on the electron heating.
Effect of ternary mixed crystals on interface optical phonons in wurtizte InxGa1−xN/GaN quantum wells
Authors: Huang Wen-Deng , Chen Guang-De , Ren Ya-Jie
Published: September 2012

The effect of ternary mixed crystals on the interface optical phonons in wurtizte InxGa1−xN/GaN quantum wells is studied based on the modified random-element isodisplacement model and dielectric continuum model. The results show that the interface optical phonons appear different frequency range with different indium concentration. The frequencies of interface optical phonons in the high frequency range decrease almost linearly with increasing indium concentration and do not vary almost linearly in the low frequency range. The indium concentration has more important effect on the electron-phonon interaction in low frequency range.
Structural and dielectric properties of poly(vinylidene fluoride)–based terpolymer/copolymer blends developed on aluminum foil
Authors: Eršte A. , Chen X.-Z. , Cheng Z.-X. , Shen Q.-D. , Bobnar V.
Published: September 2012

We report structural, caloric, and dielectric properties in the blends of relaxor poly(vinylidene fluoride–trifluoroethylene–chlorofluoroethylene) terpolymer with small amount of poly(vinylidene fluoride–chlorotrifluoroethylene) copolymer, developed on aluminum surface. X-ray diffraction and differential scanning calorimetry results indicate that the copolymer additive disturbs the crystallizing process of the terpolymer. Consequently, relatively high values of the dielectric constant of ≈80, detected in terpolymer films around room temperature, decrease to ≈60 in blends. We show that addition of the copolymer does not influence the relaxor dielectric dynamics of the terpolymer and we explain the detected dielectric response by calculations that take into account the fact that in these heterogeneous systems two similar dynamic processes superimpose in the same temperature range, i.e., relaxor dynamics in the crystalline regions and a glassy transition in the amorphous matrix.
Anisotropy in the crystal growth of hexagonal ice, Ih
Authors: Rozmanov Dmitri , Kusalik Peter G.
Published: September 2012

Growth of ice crystals has attracted attention because ice and water are ubiquitous in the environment and play critical roles in natural processes. Hexagonal ice, Ih, is the most common form of ice among 15 known crystalline phases of ice. In this work we report the results of an extensive and systematic molecular dynamics study of the temperature dependence of the crystal growth on the three primary crystal faces of hexagonal ice, the basal {0001} face, the prism \documentclass[12pt]{minimal}\begin{document}$\lbrace 10\bar{1}0\rbrace$\end{document}{101¯0} face, and the secondary prism \documentclass[12pt]{minimal}\begin{document}$\lbrace 11\bar{2}0\rbrace$\end{document}{112¯0} face, utilizing the TIP4P-2005 water model. New insights into the nature of its anisotropic growth are uncovered. It is demonstrated that the ice growth is indeed anisotropic; the growth and melting of the basal face are the slowest of the three faces, its maximum growth rates being 31% and 43% slower, respectively, than those of the prism and the secondary prism faces. It is also shown that application of periodic boundary conditions can lead to varying size effect for different orientations of an ice crystal caused by the anisotropic physical properties of the crystal, and results in measurably different thermodynamic melting temperatures in three systems of similar, yet moderate, size. Evidence obtained here provides the grounds on which to clarify the current understanding of ice growth on the secondary prism face of ice. We also revisit the effect of the integration time step on the crystal growth of ice in a more thorough and systematic way. Careful evaluation demonstrates that increasing the integration time step size measurably affects the free energy of the bulk phases and shifts the temperature dependence of the growth rate curve to lower temperatures by approximately 1 K when the step is changed from 1 fs to 2 fs, and by 3 K when 3 fs steps are used. A thorough investigation of the numerical aspects of the simulations exposes important consequences of the simulation parameter choices upon the delicate dynamic balance that is involved in ice crystal growth.
Effect of photodiode angular response on surface plasmon resonance measurements in the Kretschmann-Raether configuration
Authors: Galvez F. , Monton C. , Serrano A. , Valmianski I. , de la Venta J. , Schuller Ivan K. , Garcia M. A.
Published: September 2012

We study the effect of photodiode angular response on the measurement of surface plasmon resonance (SPR) in metallic thin films using the Kretschmann-Raether configuration. The photodiode signal depends not only on the light intensity but also on the incidence angle. This implies that the photodiode sensitivity changes along the SPR curve. Consequently, the measured SPR spectrum is distorted, thus affecting fits and numerical analyses of SPR curves. We analyze the magnitude of this change, determine when it is significant, and develop a calibration method of the experimental setup which corrects for this type of spectral shape distortions.
A two-axis goniometer for low-temperature nuclear magnetic resonance measurements on single crystals
Authors: Shiroka T. , Casola F. , Mesot J. , Bachmann W. , Ott H.-R.
Published: September 2012

We report on the construction of a two-axis goniometer intended for low-temperature, single-crystal nuclear magnetic resonance (NMR) measurements. With the use of home-made and commercially available parts, our simple probe-head design achieves good sensitivity, while maintaining a high angular precision and the ability to orient samples also when cooled to liquid helium temperatures. The probe with the goniometer is adapted to be inserted into a commercial 4He-flow cryostat, which fits into a wide-bore superconducting solenoid magnet. Selected examples of NMR measurements illustrate the operation of the device.
Effect of nanopatterns on Kapitza resistance at a water-gold interface during boiling: A molecular dynamics study
Authors: Hu Han , Sun Ying
Published: September 2012

The effect of nanopatterns on Kapitza resistance of water boiling on a gold surface is examined via molecular dynamics simulations. The TIP4P-Ew potential for water, embedded-atom model for gold, and the calibrated Lennard-Jones parameters for water-gold interactions are used to accurately predict the boiling point of water and the wetting angle of water on gold. The results show that boiling of water does not affect the Kapitza resistance of the water-gold interface. The increase of the height of nanopatterns leads to a reduction of the Kapitza resistance by increasing the interaction energy per unit area at the water-gold interface. With the increase of the width-to-spacing ratio of nanopatterns, the Kapitza resistance reduces due to the decrease of the mismatch between the vibrational density of states of water and gold.
Carrier doping to the organic Mott insulator by conjugating with tetrathiafulvalene
Authors: Takahashi Y. , Nakagawa Y. , Hayakawa K. , Inabe T. , Naito T.
Published: September 2012

The electrical conductivity of the organic Mott insulator ET-F2TCNQ (ET = bis(ethylenedithio)tetrathiafulvalene, F2TCNQ = 2,5-difluoro-7,7,8,8-tetracyanoquinodimethane) crystal was found to be enhanced by conjugation with a tetrathiafulvalene (TTF) single crystal on its surface; surface sheet resistance decreased from 5 × l05 to 2 × 103 Ω/sq. The mechanism of this decrement was investigated through optical and atomic force microscopy measurements at the interface. When TTF was conjugated to the ET-F2TCNQ crystal, electron injection from TTF and complex formation between TTF and F2TCNQ occurred. Neutral ET molecules were consequently generated at the interface, and this charge doping broke the Mott insulating state.
Single photon emission in the red spectral range from a GaAs-based self-assembled quantum dot
Authors: Dusanowski Ł. , Golnik A. , Syperek M. , Nawrocki M. , Sȩk G. , Misiewicz J. , Schlereth T. W. , Schneider C. , Höfling S. , Kamp M. , Forchel A.
Published: September 2012

Low temperature micro-photoluminecence and second-order single photon correlation experiments were performed on individual self-assembled In0.47Al0.34Ga0.19As/Al0.3Ga0.7As/GaAs quantum dots emitting in the range of 680–780 nm. Emission lines originating from exciton, biexciton, and charge exciton confined in the same dot could be identified. The derived exciton fine structure splitting is ∼125 μeV, whereas the biexciton and charge exciton binding energies are ∼4 and ∼9 meV, respectively. The photon correlation statistics measured for the exciton emission exhibited a clear antibunching with the value of gX−X2(0)=0.30±0.05, confirming unambiguously that such quantum dots act as true single photon quantum emitters.
Tunable aluminium-gated single electron transistor on a doped silicon-on-insulator etched nanowire
Authors: Gonzalez-Zalba M. F. , Heiss D. , Podd G. , Ferguson A. J.
Published: September 2012

We report the fabrication and electrical characterization of an electrostatically defined aluminum-gated SET on a lightly doped SOI etched nanowire based on MOSFET structures. The tunability of the device is achieved via two sets of electrically isolated aluminum surface gates. The results demonstrate a reproducible constant charging energy of 2 meV for a large range of gate voltages as well as tunable tunneling resistance. The controllable tunnel barriers permit transport spectroscopy of subthreshhold features.
Alpha 1-antitrypsin reduces inflammation and enhances mouse pancreatic islet transplant survival
Authors: Koulmanda Maria , Bhasin Manoj , Fan Zhigang , Hanidziar Dusan , Goel Nipun , Putheti Prabhakar , Movahedi Babak , Libermann Towia A. , Strom Terry B.
Published: September 2012

The promise of islet cell transplantation cannot be fully realized in the absence of improvements in engraftment of resilient islets. The marginal mass of islets surviving the serial peritransplant insults may lead to exhaustion and thereby contribute to an unacceptably high rate of intermediate and long-term graft loss. Hence, we have studied the effects of treatment with alpha 1-antitrypsin (AAT) in a syngeneic nonautoimmune islet graft model. A marginal number of syngeneic mouse islets were transplanted into nonautoimmune diabetic hosts and islet function was analyzed in control and AAT treated hosts. In untreated controls, marginal mass islet transplants did not restore euglycemia. Outcomes were dramatically improved by short-term AAT treatment. Transcriptional profiling identified 1,184 differentially expressed transcripts in AAT-treated hosts at 3 d posttransplantation. Systems-biology–based analysis revealed AAT down-regulated regulatory hubs formed by inflammation-related molecules (e.g., TNF-α, NF-κB). The conclusions yielded by the systems-biology analysis were rigorously confirmed by QRT-PCR and immunohistology. These data suggest that short-term AAT treatment of human islet transplant recipients may be worthy of a clinical trial.
Biodiversity tracks temperature over time
Authors: Mayhew Peter J. , Bell Mark A. , Benton Timothy G. , McGowan Alistair J.
Published: September 2012

The geographic distribution of life on Earth supports a general pattern of increase in biodiversity with increasing temperature. However, some previous analyses of the 540-million-year Phanerozoic fossil record found a contrary relationship, with paleodiversity declining when the planet warms. These contradictory findings are hard to reconcile theoretically. We analyze marine invertebrate biodiversity patterns for the Phanerozoic Eon while controlling for sampling effort. This control appears to reverse the temporal association between temperature and biodiversity, such that taxonomic richness increases, not decreases, with temperature. Increasing temperatures also predict extinction and origination rates, alongside other abiotic and biotic predictor variables. These results undermine previous reports of a negative biodiversity-temperature relationship through time, which we attribute to paleontological sampling biases. Our findings suggest a convergence of global scale macroevolutionary and macroecological patterns for the biodiversity-temperature relationship.
History of expansion and anthropogenic collapse in a top marine predator of the Black Sea estimated from genetic data
Authors: Fontaine Michaël C. , Snirc Alodie , Frantzis Alexandros , Koutrakis Emmanuil , Öztürk Bayram , Öztürk Ayaka A. , Austerlitz Fréderic
Published: September 2012

Two major ecological transitions marked the history of the Black Sea after the last Ice Age. The first was the postglacial transition from a brackish-water to a marine ecosystem dominated by porpoises and dolphins once this basin was reconnected back to the Mediterranean Sea (
ca
. 8,000 y B.P.). The second occurred during the past decades, when overfishing and hunting activities brought these predators close to extinction, having a deep impact on the structure and dynamics of the ecosystem. Estimating the extent of this decimation is essential for characterizing this ecosystem’s dynamics and for formulating restoration plans. However, this extent is poorly documented in historical records. We addressed this issue for one of the main Black Sea predators, the harbor porpoise, using a population genetics approach. Analyzing its genetic diversity using an approximate Bayesian computation approach, we show that only a demographic expansion (at most 5,000 y ago) followed by a contemporaneous population collapse can explain the observed genetic data. We demonstrate that both the postglacial settlement of harbor porpoises in the Black Sea and the recent anthropogenic activities have left a clear footprint on their genetic diversity. Specifically, we infer a strong population reduction (∼90%) that occurred within the past 5 decades, which can therefore clearly be related to the recent massive killing of small cetaceans and to the continuing incidental catches in commercial fisheries. Our study thus provides a quantitative assessment of these demographically catastrophic events, also showing that two separate historical events can be inferred from contemporary genetic data.
Wnt ligands signal in a cooperative manner to promote foregut organogenesis
Authors: Miller Mayumi F. , Cohen Ethan David , Baggs Julie E. , Lu Min Min , Hogenesch John B. , Morrisey Edward E.
Published: September 2012

Endoderm-mesenchyme cross-talk is a central process in the development of foregut-derived organs. How signaling pathways integrate the activity of multiple ligands to guide organ development is poorly understood. We show that two Wnt ligands, Wnt2 and Wnt7b, cooperatively induce Wnt signaling without affecting the stabilization of the Wnt canonical effector β-catenin despite it being necessary for Wnt2–Wnt7b cooperativity. Wnt2–Wnt7b cooperation is specific for mesenchymal cell lineages and the combined loss of Wnt2 and Wnt7b leads to more severe developmental defects in the lung than loss of Wnt2 or Wnt7b alone. High-throughput small-molecule screens and biochemical assays reveal that the Pdgf pathway is required for cooperative Wnt2-Wnt7b signaling. Inhibition of Pdgf signaling in cell culture reduces Wnt2–Wnt7b cooperative signaling. Moreover, inhibition of Pdgf signaling in lung explant cultures results in decreased Wnt signaling and lung smooth-muscle development. These data suggest a model in which Pdgf signaling potentiates Wnt2–Wnt7b signaling to promote high levels of Wnt activity in mesenchymal progenitors that is required for proper development of endoderm-derived organs, such as the lung.
Self-regulation of the head-inducing properties of the Spemann organizer
Authors: Inui Masafumi , Montagner Marco , Ben-Zvi Danny , Martello Graziano , Soligo Sandra , Manfrin Andrea , Aragona Mariaceleste , Enzo Elena , Zacchigna Luca , Zanconato Francesca , Azzolin Luca , Dupont Sirio , Cordenonsi Michelangelo , Piccolo Stefano
Published: September 2012

The Spemann organizer stands out from other signaling centers of the embryo because of its broad patterning effects. It defines development along the anteroposterior and dorsoventral axes of the vertebrate body, mainly by secreting antagonists of growth factors. Qualitative models proposed more than a decade ago explain the organizer’s region-specific inductions (i.e., head and trunk) as the result of different combinations of antagonists. For example, head induction is mediated by extracellular inhibition of Wnt, BMP, and Nodal ligands. However, little is known about how the levels of these antagonists become harmonized with those of their targets and with the factors initially responsible for germ layers and organizer formation, including Nodal itself. Here we show that key ingredients of the head-organizer development, namely Nodal ligands, Nodal antagonists, and ADMP ligands reciprocally adjust each other’s strength and range of activity by a self-regulating network of interlocked feedback and feedforward loops. A key element in this cross-talk is the limited availability of ACVR2a, for which Nodal and ADMP must compete. By trapping Nodal extracellularly, the Nodal antagonists Cerberus and Lefty are permissive for ADMP activity. The system self-regulates because ADMP/ACVR2a/Smad1 signaling in turn represses the expression of the Nodal antagonists, reestablishing the equilibrium. In sum, this work reveals an unprecedented set of interactions operating within the organizer that is critical for embryonic patterning.
Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis
Authors: Schulz Martin Michael Peter , Reisen Felix , Zgraggen Silvana , Fischer Stephanie , Yuen Don , Kang Gyeong Jin , Chen Lu , Schneider Gisbert , Detmar Michael
Published: September 2012

Lymphangiogenesis plays an important role in promoting cancer metastasis to sentinel lymph nodes and beyond and also promotes organ transplant rejection. We used human lymphatic endothelial cells to establish a reliable three-dimensional lymphangiogenic sprouting assay with automated image acquisition and analysis for inhibitor screening. This high-content phenotype-based assay quantifies sprouts by automated fluorescence microscopy and newly developed analysis software. We identified signaling pathways involved in lymphangiogenic sprouting by screening the Library of Pharmacologically Active Compounds (LOPAC)1280collection of pharmacologically relevant compounds. Hit characterization revealed that mitogen-activated protein kinase kinase (MEK) 1/2 inhibitors substantially block lymphangiogenesis in vitro and in vivo. Importantly, the drug class of statins, for the first time, emerged as potent inhibitors of lymphangiogenic sprouting in vitro and of corneal and cutaneous lymphangiogenesis in vivo. This effect was mediated by inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and subsequently the isoprenylation of Rac1. Supplementation with the enzymatic products of HMG-CoA reductase functionally rescued lymphangiogenic sprouting and the recruitment of Rac1 to the plasma membrane.
Singular orientations and faceted motion of dislocations in body-centered cubic crystals
Authors: Kang Keonwook , Bulatov Vasily V. , Cai Wei
Published: September 2012

Dislocation mobility is a fundamental material property that controls strength and ductility of crystals. An important measure of dislocation mobility is its Peierls stress, i.e., the minimal stress required to move a dislocation at zero temperature. Here we report that, in the body-centered cubic metal tantalum, the Peierls stress as a function of dislocation orientation exhibits fine structure with several singular orientations of high Peierls stress—stress spikes—surrounded by vicinal plateau regions. While the classical Peierls-Nabarro model captures the high Peierls stress of singular orientations, an extension that allows dislocations to bend is necessary to account for the plateau regions. Our results clarify the notion of dislocation kinks as meaningful only for orientations within the plateau regions vicinal to the Peierls stress spikes. These observations lead us to propose a Read-Shockley type classification of dislocation orientations into three distinct classes—special, vicinal, and general—with respect to their Peierls stress and motion mechanisms. We predict that dislocation loops expanding under stress at sufficiently low temperatures, should develop well defined facets corresponding to two special orientations of highest Peierls stress, the screw and the M111 orientations, both moving by kink mechanism. We propose that both the screw and the M111 dislocations are jointly responsible for the yield behavior of BCC metals at low temperatures.
Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*
Authors: Carrer Michele , Liu Ning , Grueter Chad E. , Williams Andrew H. , Frisard Madlyn I. , Hulver Matthew W. , Bassel-Duby Rhonda , Olson Eric N.
Published: September 2012

Obesity and metabolic syndrome are associated with mitochondrial dysfunction and deranged regulation of metabolic genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional coactivator that regulates metabolism and mitochondrial biogenesis through stimulation of nuclear hormone receptors and other transcription factors. We report that the
PGC-1β
gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which counterbalance the metabolic actions of PGC-1β. Mice genetically lacking miR-378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Among the many targets of these miRNAs, carnitine
O
-acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and MED13, a component of the Mediator complex that controls nuclear hormone receptor activity, are repressed by miR-378 and miR-378*, respectively, and are elevated in the livers of miR-378/378* KO mice. Consistent with these targets as contributors to the metabolic actions of miR-378 and miR-378*, previous studies have implicated carnitine
O
-acetyltransferase and MED13 in metabolic syndrome and obesity. Our findings identify miR-378 and miR-378* as integral components of a regulatory circuit that functions under conditions of metabolic stress to control systemic energy homeostasis and the overall oxidative capacity of insulin target tissues. Thus, these miRNAs provide potential targets for pharmacologic intervention in obesity and metabolic syndrome.
Structural basis for activation of the complement system by component C4 cleavage
Authors: Kidmose Rune T. , Laursen Nick S. , Dobó József , Kjaer Troels R. , Sirotkina Sofia , Yatime Laure , Sottrup-Jensen Lars , Thiel Steffen , Gál Péter , Andersen Gregers R.
Published: September 2012

An essential aspect of innate immunity is recognition of molecular patterns on the surface of pathogens or altered self through the lectin and classical pathways, two of the three well-established activation pathways of the complement system. This recognition causes activation of the MASP-2 or the C1s serine proteases followed by cleavage of the protein C4. Here we present the crystal structures of the 203-kDa human C4 and the 245-kDa C4⋅MASP-2 substrate⋅enzyme complex. When C4 binds to MASP-2, substantial conformational changes in C4 are induced, and its scissile bond region becomes ordered and inserted into the protease catalytic site in a manner canonical to serine proteases. In MASP-2, an exosite located within the CCP domains recognizes the C4 C345C domain 60 Å from the scissile bond. Mutations in C4 and MASP-2 residues at the C345C–CCP interface inhibit the intermolecular interaction and C4 cleavage. The possible assembly of the huge in vivo enzyme–substrate complex consisting of glycan-bound mannan-binding lectin, MASP-2, and C4 is discussed. Our own and prior functional data suggest that C1s in the classical pathway of complement activated by, e.g., antigen–antibody complexes, also recognizes the C4 C345C domain through a CCP exosite. Our results provide a unified structural framework for understanding the early and essential step of C4 cleavage in the elimination of pathogens and altered self through two major pathways of complement activation.
Roll up nanowire battery from silicon chips
Authors: Vlad Alexandru , Reddy Arava Leela Mohana , Ajayan Anakha , Singh Neelam , Gohy Jean-François , Melinte Sorin , Ajayan Pulickel M.
Published: September 2012

Here we report an approach to roll out Li-ion battery components from silicon chips by a continuous and repeatable etch-infiltrate-peel cycle. Vertically aligned silicon nanowires etched from recycled silicon wafers are captured in a polymer matrix that operates as Li
+
gel-electrolyte and electrode separator and peeled off to make multiple battery devices out of a single wafer. Porous, electrically interconnected copper nanoshells are conformally deposited around the silicon nanowires to stabilize the electrodes over extended cycles and provide efficient current collection. Using the above developed process we demonstrate an operational full cell 3.4 V lithium-polymer silicon nanowire (LIPOSIL) battery which is mechanically flexible and scalable to large dimensions.
Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development
Authors: Galindo-Villegas Jorge , García-Moreno Diana , de Oliveira Sofia , Meseguer José , Mulero Victoriano
Published: September 2012

How fish larvae are protected from infection before the maturation of adaptive immunity, a process which may take up to several weeks in most species, has long been a matter of speculation. Using a germ-free model, we show that colonization by commensals in newly hatched zebrafish primes neutrophils and induces several genes encoding proinflammatory and antiviral mediators, increasing the resistance of larvae to viral infection. Commensal microbe recognition was found to be mediated mainly through a TLR/MyD88 signaling pathway, and professional phagocytes were identified as the source of these immune mediators. However, the induction of proinflammatory and antiviral genes, but not of antimicrobial effector genes, also required the covalent modification of histone H3 at gene promoters. Interestingly, chromatin modifications were not altered by commensal microbes or hatching. Taken together, our results demonstrate that gene-specific chromatin modifications are associated with the protection of zebrafish larvae against infectious agents before adaptive immunity has developed and prevent pathologies associated with excessive inflammation during development.
The structure of the yeast NADH dehydrogenase (Ndi1) reveals overlapping binding sites for water- and lipid-soluble substrates
Authors: Iwata Momi , Lee Yang , Yamashita Tetsuo , Yagi Takao , Iwata So , Cameron Alexander D. , Maher Megan J.
Published: September 2012

Bioenergy is efficiently produced in the mitochondria by the respiratory system consisting of complexes I–V. In various organisms, complex I can be replaced by the alternative NADH-quinone oxidoreductase (NDH-2), which catalyzes the transfer of an electron from NADH via FAD to quinone, without proton pumping. The Ndi1 protein from
Saccharomyces cerevisiae
is a monotopic membrane protein, directed to the matrix. A number of studies have investigated the potential use of Ndi1 as a therapeutic agent against complex I disorders, and the NDH-2 enzymes have emerged as potential therapeutic targets for treatments against the causative agents of malaria and tuberculosis. Here we present the crystal structures of Ndi1 in its substrate-free, NAD
+
- and ubiquinone- (UQ2) complexed states. The structures reveal that Ndi1 is a peripheral membrane protein forming an intimate dimer, in which packing of the monomeric units within the dimer creates an amphiphilic membrane-anchor domain structure. Crucially, the structures of the Ndi1–NAD
+
and Ndi1–UQ2 complexes show overlapping binding sites for the NAD
+
and quinone substrates.
Reproductive clonality of pathogens: A perspective on pathogenic viruses, bacteria, fungi, and parasitic protozoa
Authors: Tibayrenc Michel , Ayala Francisco J.
Published: September 2012

We propose that clonal evolution in micropathogens be defined as restrained recombination on an evolutionary scale, with genetic exchange scarce enough to not break the prevalent pattern of clonal population structure, a definition already widely used for all kinds of pathogens, although not clearly formulated by many scientists and rejected by others. The two main manifestations of clonal evolution are strong linkage disequilibrium (LD) and widespread genetic clustering (“near-clading”). We hypothesize that this pattern is not mainly due to natural selection, but originates chiefly from in-built genetic properties of pathogens, which could be ancestral and could function as alternative allelic systems to recombination genes (“clonality/sexuality machinery”) to escape recombinational load. The clonal framework of species of pathogens should be ascertained before any analysis of biomedical phenotypes (phylogenetic character mapping). In our opinion, this model provides a conceptual framework for the population genetics of any micropathogen.
Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs
Authors: Adams Drew J. , Dai Mingji , Pellegrino Giovanni , Wagner Bridget K. , Stern Andrew M. , Shamji Alykhan F. , Schreiber Stuart L.
Published: September 2012

Piperlongumine is a naturally occurring small molecule recently identified to be toxic selectively to cancer cells in vitro and in vivo. This compound was found to elevate cellular levels of reactive oxygen species (ROS) selectively in cancer cell lines. The synthesis of 80 piperlongumine analogs has revealed structural modifications that retain, enhance, and ablate key piperlongumine-associated effects on cells, including elevation of ROS, cancer cell death, and selectivity for cancer cells over nontransformed cell types. Structure/activity relationships suggest that the electrophilicity of the C2-C3 olefin is critical for the observed effects on cells. Furthermore, we show that analogs lacking a reactive C7-C8 olefin can elevate ROS to levels observed with piperlongumine but show markedly reduced cell death, suggesting that ROS-independent mechanisms, including cellular cross-linking events, may also contribute to piperlongumine’s induction of apoptosis. In particular, we have identified irreversible protein glutathionylation as a process associated with cellular toxicity. We propose a mechanism of action for piperlongumine that may be relevant to other small molecules having two sites of reactivity, one with greater and the other with lesser electrophilicity.
The constructional motivation of indefinite generics in Modern Greek
Authors: Marmaridou Sophia
Published: September 2012

This paper argues for the discoursal motivation of constructions and the constructional motivation of a Modern Greek indefinite article, by focusing on generics and some other nominal constructions in Modern Greek containing the indefinite determiner enas/mia/ena (“a/an”, masc./fem./ neut. respectively). Moreover, it illustrates the cross-linguistic relevance of Construction Grammar. A family of indefinite nominal constructions is identified, including the Indefinite Generic Construction, the Indefinite Proper Noun Construction, the Indefinite Predicate Nominal Construction, and the Proverbial Indefinite Construction, which is further shown to be primed by specific pragmatic and discoursal features. On the basis of the proposed analysis, and consistently with established views on semantic change (Traugott 1989), I suggest that the expressivity and the discoursal characterization associated with this family of indefinite constructions in Modern Greek motivate the partial de-semanticization of the indefinite determiner, its synchronic variability (after Hoffmann & Trousdale 2011) and, ultimately, its function as an article in the language.
Endogenous Jurisprudential Regimes
Authors: Pang Xun , Friedman Barry , Martin Andrew D. , Quinn Kevin M.
Published: September 2012

Jurisprudential regime theory is a legal explanation of decision-making on the U.S. Supreme Court that asserts that a key precedent in an area of law fundamentally restructures the relationship between case characteristics and the outcomes of future cases. In this article, we offer a multivariate multiple change-point probit model that can be used to endogenously test for the existence of jurisprudential regimes. Unlike the previously employed methods, our model does so by estimating the locations of many possible change-points along with structural parameters. We estimate the model using Markov chain Monte Carlo methods, and use Bayesian model comparison to determine the number of change-points. Our findings are consistent with jurisprudential regimes in the Establishment Clause and administrative law contexts. We find little support for hypothesized regimes in the areas of free speech and search-and-seizure. The Bayesian multivariate change-point model we propose has broad potential applications to studying structural breaks in either regular or irregular time-series data about political institutions or processes.
Necrotrophic Pathogens Use the Salicylic Acid Signaling Pathway to Promote Disease Development in Tomato
Authors: Rahman Taha Abd El , Oirdi Mohamed El , Gonzalez-Lamothe Rocio , Bouarab Kamal
Published: September 2012

Plants use different immune pathways to combat pathogens. The activation of the jasmonic acid (JA)-signaling pathway is required for resistance against necrotrophic pathogens; however, to combat biotrophic pathogens, the plants activate mainly the salicylic acid (SA)-signaling pathway. SA can antagonize JA signaling and vice versa. NPR1 (noninducible pathogenesis-related 1) is considered a master regulator of SA signaling. NPR1 interacts with TGA transcription factors, ultimately leading to the activation of SA-dependent responses. SA has been shown to promote disease development caused by the necrotrophic pathogen Botrytis cinerea through NPR1, by suppressing the expression of two JA-dependent defense genes, proteinase inhibitors I and II. We show here that the transcription factor TGA1.a contributes to disease development caused by B. cinerea in tomato by suppressing the expression of proteinase inhibitors I and II. Finally, we present evidence that the SA-signaling pathway contributes to disease development caused by another necrotrophic pathogen, Alternaria solani, in tomato. Disease development promoted by SA through NPR1 requires the TGA1.a transcription factor. These data highlight how necrotrophs manipulate the SA-signaling pathway to promote their disease in tomato.
Poisson's ratio over two centuries: challenging hypotheses
Authors: Greaves G. Neville
Published: September 2012

This article explores Poisson's ratio, starting with the controversy concerning its magnitude and uniqueness in the context of the molecular and continuum hypotheses competing in the development of elasticity theory in the nineteenth century, moving on to its place in the development of materials science and engineering in the twentieth century, and concluding with its recent re-emergence as a universal metric for the mechanical performance of materials on any length scale. During these episodes France lost its scientific pre-eminence as paradigms switched from mathematical to observational, and accurate experiments became the prerequisite for scientific advance. The emergence of the engineering of metals followed, and subsequently the invention of composites—both somewhat separated from the discovery of quantum mechanics and crystallography, and illustrating the bifurcation of technology and science. Nowadays disciplines are reconnecting in the face of new scientific demands. During the past two centuries, though, the shape versus volume concept embedded in Poisson's ratio has remained invariant, but its application has exploded from its origins in describing the elastic response of solids and liquids, into areas such as materials with negative Poisson's ratio, brittleness, glass formation, and a re-evaluation of traditional materials. Moreover, the two contentious hypotheses have been reconciled in their complementarity within the hierarchical structure of materials and through computational modelling.