bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical analysis of electronegative plasma in the extraction region of negative hydrogen ion sources
Authors: Kuppel S. , Matsushita D. , Hatayama A. , Bacal M.
Published: January 2011

This numerical study focuses on the physical mechanisms involved in the extraction of volume-produced H− ions from a steady state laboratory negative hydrogen ion source with one opening in the plasma electrode (PE) on which a dc-bias voltage is applied. A weak magnetic field is applied in the source plasma transversely to the extracted beam. The goal is to highlight the combined effects of the weak magnetic field and the PE bias voltage (upon the extraction process of H− ions and electrons). To do so, we focus on the behavior of electrons and volume-produced negative ions within a two-dimensional model using the particle-in-cell method. No collision processes are taken into account, except for electron diffusion across the magnetic field using a simple random-walk model at each time step of the simulation. The results show first that applying the magnetic field (without PE bias) enhances H− ion extraction, while it drastically decreases the extracted electron current. Secondly, the extracted H− ion current has a maximum when the PE bias is equal to the plasma potential, while the extracted electron current is significantly reduced by applying the PE bias. The underlying mechanism leading to the above results is the gradual opening by the PE bias of the equipotential lines towards the parts of the extraction region facing the PE. The shape of these lines is due originally to the electron trapping by the magnetic field.
Ionization in inductively coupled argon plasmas studied by optical emission spectroscopy
Authors: Lee Young-Kwang , Chung Chin-Wook
Published: January 2011

Contribution of stepwise ionization to total ionization was experimentally investigated in low-pressure inductively coupled argon plasmas. In the pressure range 3–50 mTorr, optical emission spectroscopy was employed to determine metastable fractions (metastable density relative to ground state density) by measuring the emission intensity of selected lines. The measured metastable fractions were in good agreement with the calculation, showing a dependence on the discharge pressure. The rate of stepwise ionization was estimated from the excited level densities (measurements and model predictions) and their ionization rate coefficients. It is observed that at relatively low discharge pressures (<10 mTorr) the ionization is mainly provided by the direct ionization, whereas at higher pressure the stepwise ionization is predominant with increasing absorbed power.
Polaritonic pulse and coherent X- and gamma rays from Compton (Thomson) backscattering
Authors: Apostol M. , Ganciu M.
Published: January 2011

The formation of polariton wave-packets created by high-intensity laser beams focused in plasmas is analyzed, and the velocity, energy, size, structure, stability, and electron content of such polaritonic pulses are characterized. It is shown that polaritonic pulses may transport trapped electrons with appreciable energies, provided the medium behaves as a rarefied classical plasma. The relativistic electron energy is related to the polariton group velocity, which is close to the velocity of light in this case. The plasma pulse is polarized, and the electron number in the pulse is estimated as being proportional to the square root of the laser intensity and the 3/2-power of the pulse size. It is shown that Compton (Thomson) backscattering by such polaritonic pulses of electrons may produce coherent X- and gamma rays, as a consequence of the quasirigidity of the electrons inside the polaritonic pulses and their relatively large number. The classical results of the Compton scattering are re-examined in this context, the energy of the scattered photons and their cross-section are analyzed, especially for backscattering, the great enhancement of the scattered flux of X- or gamma rays due to the coherence effect is highlighted and numerical estimates are given for some typical situations.
Defect properties of ZnO and ZnO:P microwires
Authors: Dietrich Christof P. , Brandt Matthias , Lange Martin , Kupper Johannes , Böntgen Tammo , von Wenckstern Holger , Grundmann Marius
Published: January 2011

We report on the defect properties of nominally undoped and phosphorus-doped ZnO microwires grown by carbothermal vapor phase transport. Cathodoluminescence measurements show very narrow (≈300 μeV), donorlike transitions in the UV spectral range. A recombination-line at 3.356 eV, previously assigned to phosphorus acceptors, is observed in our undoped ZnO. Thus the correlation of this recombination process and possible acceptor doping can be excluded. Hall effect measurements confirmed these findings and revealed n-type conductivity in both ZnO and high quality ZnO:P microwires.
Manipulation of diamond nanoparticles using bulk acoustic waves
Authors: Raeymaekers Bart , Pantea Cristian , Sinha Dipen N.
Published: January 2011

We investigate the manipulation of 5 nm diamond nanoparticles in a user-defined pattern on a substrate using the acoustic radiation force associated with a bulk acoustic standing wave. Both concentric and rectangular patterns are studied and the experimental results are compared with theoretical predictions. The effect of drag force acting on a nanoparticle is evaluated and limits for particle speed and particle size that can be moved by acoustic radiation force are determined. We found good agreement between our experimental results and existing theoretical models and demonstrate that nanosized particles can be manipulated effectively by means of bulk wave acoustic radiation force.
Midinfrared electroluminescence from PbTe/CdTe quantum dot light-emitting diodes
Authors: Hochreiner A. , Schwarzl T. , Eibelhuber M. , Heiss W. , Springholz G. , Kolkovsky V. , Karczewski G. , Wojtowicz T.
Published: January 2011

Midinfrared electroluminescence of epitaxial PbTe quantum dots in CdTe with emission in the 2–3 μm wavelength range is demonstrated up to room temperature. The light-emitting diode structures were grown by molecular beam epitaxy with the active PbTe quantum dots embedded in the intrinsic zone of a CdTe/CdZnTe p-i-n junction on GaAs (100) substrates. The current and temperature dependences of the electroluminescence emission are presented. The comparison with photoluminescence measurements shows that midinfrared light-emission from the diodes originates from the quantum dots.
Passive hydrodynamic synchronization of two-dimensional swimming cells
Authors: Elfring Gwynn J. , Lauga Eric
Published: January 2011

Spermatozoa flagella are known to synchronize when swimming in close proximity. We use a model consisting of two-dimensional sheets propagating transverse waves of displacement to demonstrate that fluid forces lead to such synchronization passively. Using two distinct asymptotic descriptions (small amplitude and long wavelength), we derive the synchronizing dynamics analytically for arbitrarily shaped waveforms in Newtonian fluids, and show that phase-locking will always occur for sufficiently asymmetric shapes. We characterize the effect of the geometry of the waveforms and the separation between the swimmers on the synchronizing dynamics, the final stable conformations, and the energy dissipated by the cells. For two closely swimming cells, synchronization always occurs at the in-phase or opposite-phase conformation, depending solely on the geometry of the cells. In contrast, the work done by the swimmers is always minimized at the in-phase conformation. As the swimmers get further apart, additional fixed points arise at intermediate values of the relative phase. In addition, computations for large amplitude waves using the boundary integral method reveal that the two asymptotic limits capture all the relevant physics of the problem. Our results provide a theoretical framework to address other hydrodynamic interactions phenomena relevant to populations of self-propelled organisms.
Existence of solutions for Hamiltonian field theories by the Hamilton–Jacobi technique
Authors: Bruno Danilo
Published: January 2011

The paper is devoted to prove the existence of a local solution of the Hamilton–Jacobi equation in field theory, whence the general solution of the field equations can be obtained. The solution is adapted to the choice of the submanifold where the initial data of the field equations are assigned. Finally, a technique to obtain the general solution of the field equations, starting from the given initial manifold, is deduced.
Observation of a large gate-controlled persistent photoconduction in single crystal ZnO at room temperature
Authors: Mondal Shahnewaz , Raychaudhuri A. K.
Published: January 2011

Gate-controlled enhanced photoconductivity at room temperature is reported in single crystal ZnO using moderate bias and band gap illumination. A substantial part of the enhanced photocurrent is retained over a long time as a persistent photocurrent when the illumination is removed but the gate voltage (applied with a polymer-electrolyte gate) is retained. The current on the removal of illumination shows a stretched exponential decay with time constants more than few hundreds of seconds. An explanation based on change in charge state of oxygen vacancy has been proposed.
Nonlinear development of oscillatory instability in a three-layer system under the joint action of buoyancy and thermocapillary effect
Authors: Simanovskii Ilya B. , Viviani Antonio , Dubois Frank , Legros Jean-Claude
Published: January 2011

The nonlinear development of oscillatory instability under the joint action of buoyant and thermocapillary effects in multilayer system is investigated. The nonlinear convective regimes are studied by the finite difference method. The calculations have been performed for two-dimensional flows. The interfaces are assumed to be nondeforming. Rigid heat-insulated lateral walls are considered. Transitions between the flows with different spatial structures are studied. Specific types of nonlinear flows—symmetric and asymmetric oscillations—have been found. It is shown that the oscillatory flow takes place in an interval of Grashof number values bounded both from below by the quiescent mechanical equilibrium, and from above by a convecting steady state. Cavities with different lengths are considered.
Structure of trailing vortices: Comparison between particle image velocimetry measurements and theoretical models
Authors: del Pino C. , Parras L. , Felli M. , Fernandez-Feria R.
Published: January 2011

The velocity field of the trailing vortex behind a wing at different angles of attack has been measured through the stereo particle image velocimetry technique in a water tunnel for Reynolds numbers between 20 000 and 40 000, and for several distances to the wing tip. After filtering out the vortex meandering, the radial profiles of the axial and the azimuthal velocity components and of the radial profiles of the vorticity were compared to the theoretical models for trailing vortices by [G. K. Batchelor, J. Fluid Mech. 20, 645 (1964)] and by [D. W. Moore and P. G. Saffman, Proc. R. Soc. London, Ser. A 333, 491 (1973)], whose main features are conveniently summarized. We take into account the downstream evolution of these profiles from just a fraction of the wing chord to more than ten chords. The radial profiles of the vorticity and the azimuthal velocity are shown to fit quite well to Moore and Saffman’s trailing vortex model, while Batchelor’s model does not fit so well, especially in the tails of the profiles. At the downstream distances considered, the radial profiles of the axial velocity do not adjust so well to Moore and Saffman’s model as the azimuthal velocity profiles do, but the disagreement with Batchelor’s model is quite manifested, especially at the axis. Thus, the details of the flow structure are in better agreement with the predictions of Moore and Saffman’s model. The downstream evolution of several key features of the measured velocity profiles is also in agreement with the predictions of Moore and Saffman’s model, within the dispersion of the experimental data, but up to the largest axial distance considered in this work we cannot decide if they follow the asymptotic behavior predicted by this model.
Bond-specific reaction kinetics during the oxidation of (111) Si: Effect of n-type doping
Authors: Gokce B. , Aspnes D. E. , Lucovsky G. , Gundogdu K.
Published: January 2011

It is known that a higher concentration of free carriers leads to a higher oxide growth rate in the thermal oxidation of silicon. However, the role of electrons and holes in oxidation chemistry is not clear. Here, we report real-time second-harmonic-generation data on the oxidation of H-terminated (111)Si that reveal that high concentrations of electrons increase the chemical reactivity of the outer-layer Si-Si back bonds relative to the Si-H up bonds. However, the thicknesses of the natural oxides of all samples stabilize near 1 nm at room temperature, regardless of the chemical kinetics of the different bonds.
Modeling drag reduction and meniscus stability of superhydrophobic surfaces comprised of random roughness
Authors: Samaha Mohamed A. , Vahedi Tafreshi Hooman , Gad-el-Hak Mohamed
Published: January 2011

Previous studies dedicated to modeling drag reduction and stability of the air-water interface on superhydrophobic surfaces were conducted for microfabricated coatings produced by placing hydrophobic microposts/microridges arranged on a flat surface in aligned or staggered configurations. In this paper, we model the performance of superhydrophobic surfaces comprised of randomly distributed roughness (e.g., particles or microposts) that resembles natural superhydrophobic surfaces, or those produced via random deposition of hydrophobic particles. Such fabrication method is far less expensive than microfabrication, making the technology more practical for large submerged bodies such as submarines and ships. The present numerical simulations are aimed at improving our understanding of the drag reduction effect and the stability of the air-water interface in terms of the microstructure parameters. For comparison and validation, we have also simulated the flow over superhydrophobic surfaces made up of aligned or staggered microposts for channel flows as well as streamwise or spanwise ridges configurations for pipe flows. The present results are compared with theoretical and experimental studies reported in the literature. In particular, our simulation results are compared with work of Sbragaglia and Prosperetti, and good agreement has been observed for gas fractions up to about 0.9. The numerical simulations indicate that the random distribution of surface roughness has a favorable effect on drag reduction, as long as the gas fraction is kept the same. This effect peaks at about 30% as the gas fraction increases to 0.98. The stability of the meniscus, however, is strongly influenced by the average spacing between the roughness peaks, which needs to be carefully examined before a surface can be recommended for fabrication. It was found that at a given maximum allowable pressure, surfaces with random post distribution produce less drag reduction than those made up of staggered posts.
Fully complementary metal-oxide-semiconductor compatible nanoplasmonic slot waveguides for silicon electronic photonic integrated circuits
Authors: Zhu Shiyang , Liow T. Y. , Lo G. Q. , Kwong D. L.
Published: January 2011

Horizontal Al/SiO2/Si/SiO2/Al nanoplasmonic slot waveguides with the SiO2 width at each side of ∼15 nm and the Si core width of ∼136–43 nm were fabricated using a fully silicon complementary metal-oxide-semiconductor compatible technology. The propagation losses were measured to be ∼1.07–1.63 dB/μm at the telecommunication wavelength of 1550 nm, in agreement with those predicted from numerical simulation. A simple tapered coupler with length of ∼0.3–1 μm provides a high coupling efficiency of ∼−0.6–−1.5 dB between the plasmonic waveguide and the conventional Si dielectric waveguide. The plasmonic slot waveguide can achieve a low-loss ultracompact bend. A direct 90° bend was demonstrated to have the pure bending loss as low as ∼0.2–0.4 dB. The losses of propagation, coupling, and bending depend weakly on wavelength in the c-band. These results demonstrate the potential for seamless integration of functional plasmonic devices in existing silicon electronic photonic integrated circuits.
A spin-filter device based on armchair graphene nanoribbons
Authors: Saffarzadeh A. , Farghadan R.
Published: January 2011

The coherent spin-polarized electron transport through a zigzag-edge graphene flake (ZGF), sandwiched between two semi-infinite armchair graphene nanoribbons, is investigated by means of Landauer–Buttiker formalism. To study the edge magnetism of the ZGF, we use the half-filled Hubbard model within the Hartree–Fock approximation. The results show that the junction acts as a spin filter with high degree of spin polarization in the absence of magnetic electrodes and external fields. By applying a gate voltage the spin-filtering efficiency of this device can be effectively controlled and the spin polarization can reach values as high as 90%.
Effect of annealing temperature on microstructural evolution and electrical properties of sol-gel processed ZrO2/Si films
Authors: Hwang Soo Min , Lee Seung Muk , Park Kyung , Lee Myung Soo , Joo Jinho , Lim Jun Hyung , Kim Hyoungsub , Yoon Jae Jin , Kim Young Dong
Published: January 2011

High-permittivity (k) ZrO2/Si(100) films were fabricated by a sol-gel technique and the microstructural evolution with the annealing temperature (Ta) was correlated with the variation of their electrical performance. With increasing Ta, the ZrO2 films crystallized into a tetragonal (t) phase which was maintained until 700 °C at nanoscale thicknesses. Although the formation of the t-ZrO2 phase obviously enhanced the k value of the ZrO2 dielectric layer, the maximum capacitance in accumulation was decreased by the growth of a low-k interfacial layer (IL) between ZrO2 and Si with increasing Ta. On the other hand, the gate leakage current was remarkably depressed with increasing Ta probably due to the combined effects of the increased IL thickness, optical band gap of ZrO2, and density of ZrO2 and decreased remnant organic components.
All That is Landscape is Melted into Air: The ‘Aerography’ of Ethereal Space
Authors: Olwig Kenneth R
Published: January 2011

‘Aerography’ is an imagined scholarly discipline that is intended to raise questions concerning ‘unthought elemental and metaphysical assumptions in recent human geographies’. How, for example, would unexamined contemporary disciplinary assumptions change if geography were less ostensibly geocentric and more focused on the space of the aerosphere? This is an aerography of the role of aether and theater in the transformation of landscape's meaning away from that of an earthly polity and its place to that of a natural scenic space, helping to pave the way for geography conceptualized as spatial science.
Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress
Authors: Aggarwal Monika , Sommers Joshua A. , Shoemaker Robert H. , Brosh Robert M.
Published: January 2011

Modulation of DNA repair proteins by small molecules has attracted great interest. An in vitro helicase activity screen was used to identify molecules that modulate DNA unwinding by Werner syndrome helicase (WRN), mutated in the premature aging disorder Werner syndrome. A small molecule from the National Cancer Institute Diversity Set designated NSC 19630 [1-(propoxymethyl)-maleimide] was identified that inhibited WRN helicase activity but did not affect other DNA helicases [Bloom syndrome (BLM), Fanconi anemia group J (FANCJ), RECQ1, RecQ, UvrD, or DnaB). Exposure of human cells to NSC 19630 dramatically impaired growth and proliferation, induced apoptosis in a WRN-dependent manner, and resulted in elevated γ-H2AX and proliferating cell nuclear antigen (PCNA) foci. NSC 19630 exposure led to delayed S-phase progression, consistent with the accumulation of stalled replication forks, and to DNA damage in a WRN-dependent manner. Exposure to NSC 19630 sensitized cancer cells to the G-quadruplex–binding compound telomestatin or a poly(ADP ribose) polymerase (PARP) inhibitor. Sublethal dosage of NSC 19630 and the chemotherapy drug topotecan acted synergistically to inhibit cell proliferation and induce DNA damage. The use of this WRN helicase inhibitor molecule may provide insight into the importance of WRN-mediated pathway(s) important for DNA repair and the replicational stress response.
Mercury reduction and complexation by natural organic matter in anoxic environments
Authors: Gu Baohua , Bian Yongrong , Miller Carrie L. , Dong Wenming , Jiang Xin , Liang Liyuan
Published: January 2011

Mercuric Hg(II) species form complexes with natural dissolved organic matter (DOM) such as humic acid (HA), and this binding is known to affect the chemical and biological transformation and cycling of mercury in aquatic environments. Dissolved elemental mercury, Hg(0), is also widely observed in sediments and water. However, reactions between Hg(0) and DOM have rarely been studied in anoxic environments. Here, under anoxic dark conditions we show strong interactions between reduced HA and Hg(0) through thiolate ligand-induced oxidative complexation with an estimated binding capacity of ~3.5 μmol Hg/g HA and a partitioning coefficient >10
6
mL/g. We further demonstrate that Hg(II) can be effectively reduced to Hg(0) in the presence of as little as 0.2 mg/L reduced HA, whereas production of Hg(0) is inhibited by complexation as HA concentration increases. This dual role played by DOM in the reduction and complexation of mercury is likely widespread in anoxic sediments and water and can be expected to significantly influence the mercury species transformations and biological uptake that leads to the formation of toxic methylmercury.
Absence of keratin 8 confers a paradoxical microflora-dependent resistance to apoptosis in the colon
Authors: Habtezion Aida , Toivola Diana M. , Asghar M. Nadeem , Kronmal Greg S. , Brooks Jacqueline D. , Butcher Eugene C. , Omary M. Bishr
Published: January 2011

Keratin 8 (K8) is a major intermediate filament protein present in enterocytes and serves an antiapoptotic function in hepatocytes. K8-null mice develop colonic hyperplasia and colitis that are reversed after antibiotic treatment. To investigate the pathways that underlie the mechanism of colonocyte hyperplasia and the normalization of the colonic phenotype in response to antibiotics, we performed genome-wide microarray analysis. Functional annotation of genes that are differentially regulated in K8
−/−
and K8
+/+
isolated colon crypts (colonocytes) identified apoptosis as a major altered pathway. Exposure of K8
−/−
colonocytes or colon organ (“organoid”) cultures, but not K8
−/−
small intestine organoid cultures, to apoptotic stimuli showed, surprisingly, that they are resistant to apoptosis compared with their wild-type counterparts. This resistance is not related to inflammation per se because T-cell receptor α-null (TCR-α
−/−
) and wild-type colon cultures respond similarly upon induction of apoptosis. Following antibiotic treatment, K8
−/−
colonocytes and organ cultures become less resistant to apoptosis and respond similarly to the wild-type colonocytes. Antibiotics also normalize most differentially up-regulated genes, including survivin and β4-integrin. Treatment of K8
−/−
mice with anti–β4-integrin antibody up-regulated survivin, and induced phosphorylation of focal adhesion kinase with decreased activation of caspases. Therefore, unlike the proapoptotic effect of K8 mutation or absence in hepatocytes, lack of K8 confers resistance to colonocyte apoptosis in a microflora-dependent manner.
Masking the 5′ terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex
Authors: Machlin Erica S. , Sarnow Peter , Sagan Selena M.
Published: January 2011

Hepatitis C virus subverts liver-specific microRNA, miR-122, to upregulate viral RNA abundance in both infected cultured cells and in the liver of infected chimpanzees. These findings have identified miR-122 as an attractive antiviral target. Thus, it is imperative to know whether a distinct functional complex exists between miR-122 and the viral RNA versus its normal cellular target mRNAs. Toward this goal, effects on viral RNA abundance of mutated miR-122 duplex molecules, bound at each of the two target sites in the viral genome, were compared to effects on microRNA- or siRNA-mediated regulation of reporter target mRNAs. It was found that miR-122 formed an unusual microRNA complex with the viral RNA that is distinct from miR-122 complexes with reporter mRNAs. Notably, miR-122 forms an oligomeric complex in which one miR-122 molecule binds to the 5′ terminus of the hepatitis C virus (HCV) RNA with 3′ overhanging nucleotides, masking the 5′ terminal sequences of the HCV genome. Furthermore, specific internal nucleotides as well as the 3′ terminal nucleotides in miR-122 were absolutely required for maintaining HCV RNA abundance but not for microRNA function. Both miR-122 molecules utilize similar internal nucleotides to interact with the viral genome, creating a bulge and tail in the miR-122 molecules, revealing tandemly oriented oligomeric RNA complexes. These findings suggest that miR-122 protects the 5′ terminal viral sequences from nucleolytic degradation or from inducing innate immune responses to the RNA terminus. Finally, this remarkable microRNA-mRNA complex could be targeted with compounds that inactivate miR-122 or interfere with this unique RNA structure.
Listeria monocytogenes
exploits cystic fibrosis transmembrane conductance regulator (CFTR) to escape the phagosome
Authors: Radtke Andrea L. , Anderson Kelsi L. , Davis Michael J. , DiMagno Matthew J. , Swanson Joel A. , O'Riordan Mary X.
Published: January 2011

Virulence of the intracellular pathogen
Listeria monocytogenes
(
Listeria
) requires escape from the phagosome into the host cytosol, where the bacteria replicate. Phagosomal escape is a multistep process characterized by perforation, which is dependent on the pore-forming toxin listeriolysin O (LLO), followed by rupture. The contribution of host factors to
Listeria
phagosomal escape is incompletely defined. Here we show that the cystic fibrosis transmembrane conductance regulator (CFTR) facilitates
Listeria
cytosolic entry. CFTR inhibition or mutation suppressed
Listeria
vacuolar escape in culture, and inhibition of CFTR in wild-type mice before oral inoculation of
Listeria
markedly decreased systemic infection. We provide evidence that high chloride concentrations may facilitate
Listeria
vacuolar escape by enhancing LLO oligomerization and lytic activity. We propose that CFTR transiently increases phagosomal chloride concentration after infection, potentiating LLO pore formation and vacuole lysis. Our studies suggest that
Listeria
exploits mechanisms of cellular ion homeostasis to escape the phagosome and emphasize host ion-channel function as a key parameter of bacterial virulence.
Translocation of surface-localized effectors in type III secretion
Authors: Akopyan Karen , Edgren Tomas , Wang-Edgren Helen , Rosqvist Roland , Fahlgren Anna , Wolf-Watz Hans , Fallman Maria
Published: January 2011

Pathogenic
Yersinia
species suppress the host immune response by using a plasmid-encoded type III secretion system (T3SS) to translocate virulence proteins into the cytosol of the target cells. T3SS-dependent protein translocation is believed to occur in one step from the bacterial cytosol to the target-cell cytoplasm through a conduit created by the T3SS upon target cell contact. Here, we report that T3SS substrates on the surface of
Yersinia pseudotuberculosis
are translocated into target cells. Upon host cell contact, purified YopH coated on
Y. pseudotuberculosis
was specifically and rapidly translocated across the target-cell membrane, which led to a physiological response in the infected cell. In addition, translocation of externally added YopH required a functional T3SS and a specific translocation domain in the effector protein. Efficient, T3SS-dependent translocation of purified YopH added in vitro was also observed when using coated
Salmonella typhimurium
strains, which implies that T3SS-mediated translocation of extracellular effector proteins is conserved among T3SS-dependent pathogens. Our results demonstrate that polarized T3SS-dependent translocation of proteins can be achieved through an intermediate extracellular step that can be reconstituted in vitro. These results indicate that translocation can occur by a different mechanism from the assumed single-step conduit model.
Oxytocin promotes human ethnocentrism
Authors: De Dreu Carsten K. W. , Greer Lindred L. , Van Kleef Gerben A. , Shalvi Shaul , Handgraaf Michel J. J.
Published: January 2011

Human ethnocentrism—the tendency to view one's group as centrally important and superior to other groups—creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate “love drug” or “cuddle chemical” and suggest that oxytocin has a role in the emergence of intergroup conflict and violence.
Thyrotrophin receptor signaling dependence of Braf-induced thyroid tumor initiation in mice
Authors: Franco Aime T. , Malaguarnera Roberta , Refetoff Samuel , Liao Xiao-Hui , Lundsmith Emma , Kimura Shioko , Pritchard Catrin , Marais Richard , Davies Terry F. , Weinstein Lee S. , Chen Min , Rosen Neal , Ghossein Ronald , Knauf Jeffrey A. , Fagin James A.
Published: January 2011

Mutations of
BRAF
are found in ∼45% of papillary thyroid cancers and are enriched in tumors with more aggressive properties. We developed mice with a thyroid-specific knock-in of oncogenic
Braf
(

LSL-Braf
V600E
/TPO-Cre

) to explore the role of endogenous expression of this oncoprotein on tumor initiation and progression. In contrast to other
Braf
-induced mouse models of tumorigenesis (i.e., melanomas and lung), in which knock-in of

Braf
V600E

induces mostly benign lesions, Braf-expressing thyrocytes become transformed and progress to invasive carcinomas with a very short latency, a process that is dampened by treatment with an allosteric MEK inhibitor. These mice also become profoundly hypothyroid due to deregulation of genes involved in thyroid hormone biosynthesis and consequently have high TSH levels. To determine whether TSH signaling cooperates with oncogenic Braf in this process, we first crossed

LSL-Braf
V600E
/TPO-Cre

with
TshR
knockout mice. Although oncogenic Braf was appropriately activated in thyroid follicular cells of these mice, they had a lower mitotic index and were not transformed. Thyroid-specific deletion of the
Gsα
gene in

LSL-Braf
V600E
/TPO-Cre/Gnas-E1
fl/fl

mice also resulted in an attenuated cancer phenotype, indicating that the cooperation of TshR with oncogenic Braf is mediated in part by cAMP signaling. Once tumors were established in mice with wild-type
TshR
, suppression of TSH did not revert the phenotype. These data demonstrate the key role of TSH signaling in Braf-induced papillary thyroid cancer initiation and provide experimental support for recent observations in humans pointing to a strong association between TSH levels and thyroid cancer incidence.
The
Drosophila
Myc gene,
diminutive
, is a positive regulator of the
Sex-lethal
establishment promoter,
Sxl-Pe
Authors: Kappes Gretchen , Deshpande Girish , Mulvey Brett B. , Horabin Jamila I. , Schedl Paul
Published: January 2011

The binary switch gene
Sex-lethal
(
Sxl
) controls sexual identity in
Drosophila
. When activated,
Sxl
imposes female identity, whereas male identity ensues by default when the gene is off. The decision to activate
Sxl
is controlled by an X chromosome counting system that regulates the
Sxl
establishment promoter,
Sxl-Pe
. The counting system depends upon the twofold difference in the gene dose of a series of X-linked transcription factors or numerators. Because of this difference in dose, early female embryos express twice the amount of these transcription factors, and the cumulative action of these transcription factors turns on
Sxl-Pe
. Here we show that the
Drosophila
Myc gene
diminutive
is an X-linked numerator.
Kinetics and mechanistic analysis of an extremely rapid carbon dioxide fixation reaction
Authors: Huang Deguang , Makhlynets Olga V. , Tan Lay Ling , Lee Sonny C. , Rybak-Akimova Elena V. , Holm R. H.
Published: January 2011

Carbon dioxide may react with free or metal-bound hydroxide to afford products containing bicarbonate or carbonate, often captured as ligands bridging two or three metal sites. We report the kinetics and probable mechanism of an extremely rapid fixation reaction mediated by a planar nickel complex [Ni
II
(NNN)(OH)]
1-
containing a tridentate 2,6-pyridinedicarboxamidate pincer ligand and a terminal hydroxide ligand. The minimal generalized reaction is M-OH + CO
2
 → M-OCO
2
H; with variant M, previous rate constants are ≲10
3
 M
-1
 s
-1
in aqueous solution. For the present bimolecular reaction, the (extrapolated) rate constant is 9.5 × 10
5
 M
-1
 s
-1
in N,N′-dimethylformamide at 298 K, a value within the range of
k
cat
/
K

M

≈10
5
–10
8
 M
-1
 s
-1
for carbonic anhydrase, the most efficient catalyst of CO
2
fixation reactions. The enthalpy profile of the fixation reaction was calculated by density functional theory. The initial event is the formation of a weak precursor complex between the Ni-OH group and CO
2
, followed by insertion of a CO
2
oxygen atom into the Ni-OH bond to generate a four center Ni(
η
2
-OCO
2
H) transition state similar to that at the zinc site in carbonic anhydrase. Thereafter, the Ni-OH bond detaches to afford the Ni(
η
1
-OCO
2
H) fragment, after which the molecule passes through a second, lower energy transition state as the bicarbonate ligand rearranges to a conformation very similar to that in the crystalline product. Theoretical values of metric parameters and activation enthalpy are in good agreement with experimental values [Δ
H
‡
 = 3.2(5) kcal/mol].
Linking functional diversity and social actor strategies in a framework for interdisciplinary analysis of nature's benefits to society
Authors: Díaz Sandra , Quétier Fabien , Cáceres Daniel M. , Trainor Sarah F. , Pérez-Harguindeguy Natalia , Bret-Harte M. Syndonia , Finegan Bryan , Peña-Claros Marielos , Poorter Lourens
Published: January 2011

The crucial role of biodiversity in the links between ecosystems and societies has been repeatedly highlighted both as source of wellbeing and as a target of human actions, but not all aspects of biodiversity are equally important to different ecosystem services. Similarly, different social actors have different perceptions of and access to ecosystem services, and therefore, they have different wants and capacities to select directly or indirectly for particular biodiversity and ecosystem characteristics. Their choices feed back onto the ecosystem services provided to all parties involved and in turn, affect future decisions. Despite this recognition, the research communities addressing biodiversity, ecosystem services, and human outcomes have yet to develop frameworks that adequately treat the multiple dimensions and interactions in the relationship. Here, we present an interdisciplinary framework for the analysis of relationships between functional diversity, ecosystem services, and human actions that is applicable to specific social environmental systems at local scales. We connect the mechanistic understanding of the ecological role of diversity with its social relevance: ecosystem services. The framework permits connections between functional diversity components and priorities of social actors using land use decisions and ecosystem services as the main links between these ecological and social components. We propose a matrix-based method that provides a transparent and flexible platform for quantifying and integrating social and ecological information and negotiating potentially conflicting land uses among multiple social actors. We illustrate the applicability of our framework by way of land use examples from temperate to subtropical South America, an area of rapid social and ecological change.
Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange
Authors: Katan-Khaykovich Yael , Struhl Kevin
Published: January 2011

Nucleosome deposition occurs on newly synthesized DNA during DNA replication and on transcriptionally active genes via nucleosome-remodeling complexes recruited by activator proteins and elongating RNA polymerase II. It has been long believed that histone deposition involves stable H3–H4 tetramers, such that newly deposited nucleosomes do not contain H3 and H4 molecules with their associated histone modifications from preexisting nucleosomes. However, biochemical analyses and recent experiments in mammalian cells have raised the idea that preexisting H3–H4 tetramers might split into dimers, resulting in mixed nucleosomes composed of “old” and “new” histones. It is unknown to what extent different genomic loci might utilize such a mechanism and under which circumstances. Here, we address whether tetramer splitting occurs in a locus-specific manner by using sequential chromatin immunoprecipitation of mononucleosomes from yeast cells containing two differentially tagged versions of H3 that are expressed “old” and “new” histones. At many genomic loci, we observe little or no nucleosomal cooccupancy of old and new H3, indicating that tetramer splitting is generally infrequent. However, cooccupancy is detected at highly active genes, which have a high rate of histone exchange. Thus, DNA replication largely results in nucleosomes bearing exclusively old or new H3–H4, thereby precluding the acquisition of new histone modifications based on preexisting modifications within the same nucleosome. In contrast, tetramer splitting, dimer exchange, and nucleosomes with mixed H3–H4 tetramers occur at highly active genes, presumably linked to rapid histone exchange associated with robust transcription.
Arabidopsis
decuple mutant reveals the importance of SnRK2 kinases in osmotic stress responses in vivo
Authors: Fujii Hiroaki , Verslues Paul E. , Zhu Jian-Kang
Published: January 2011

Osmotic stress associated with drought or salinity is a major factor that limits plant productivity. Protein kinases in the SNF1-related protein kinase 2 (SnRK2) family are activated by osmotic stress, suggesting that the kinases are involved in osmotic stress signaling. However, due to functional redundancy, their contribution to osmotic stress responses remained unclear. In this report, we constructed an
Arabidopsis
line carrying mutations in all 10 members of the SnRK2 family. The decuple mutant
snrk2.1/2/3/4/5/6/7/8/9/10
grew poorly under hyperosmotic stress conditions but was similar to the wild type in culture media in the absence of osmotic stress. The mutant was also defective in gene regulation and the accumulation of abscisic acid (ABA), proline, and inositol 1,4,5-trisphosphate under osmotic stress. In addition, analysis of mutants defective in the ABA-activated SnRK2s (
snrk2.2/3/6
) and mutants defective in the rest of the SnRK2s (
snrk2.1/4/5/7/8/9/10
) revealed that SnRK2s are a merging point of ABA-dependent and -independent pathways for osmotic stress responses. These results demonstrate critical functions of the SnRK2s in mediating osmotic stress signaling and tolerance.
Unexpected protective role for Toll-like receptor 3 in the arterial wall
Authors: Cole Jennifer E. , Navin Tina J. , Cross Amanda J. , Goddard Michael E. , Alexopoulou Lena , Mitra Anuja T. , Davies Alun H. , Flavell Richard A. , Feldmann Marc , Monaco Claudia
Published: January 2011

The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored in recent years. The capacity of about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles to TLRs, in particular to TLR2 and TLR4, in immune and cardiovascular disease. Using human and murine systems, we have investigated the consequence of TLR3 signaling in vascular disease. We compared the responses of human atheroma-derived smooth muscle cells (AthSMC) and control aortic smooth muscle cells (AoSMC) to various TLR ligands. AthSMC exhibited a specific increase in TLR3 expression and TLR3-dependent functional responses. Intriguingly, exposure to dsRNA in vitro and in vivo induced increased expression of both pro- and anti-inflammatory genes in vascular cells and tissues. Therefore, we sought to assess the contribution of TLR3 signaling in vivo in mechanical and hypercholesterolemia-induced arterial injury. Surprisingly, neointima formation in a perivascular collar-induced injury model was reduced by the systemic administration of the dsRNA analog Poly(I:C) in a TLR3-dependent manner. Furthermore, genetic deletion of TLR3 dramatically enhanced the development of elastic lamina damage after collar-induced injury. Accordingly, deficiency of TLR3 accelerated the onset of atherosclerosis in hypercholesterolemic ApoE
−/−
mice. Collectively, our data describe a protective role for TLR signaling in the vessel wall.
A CD133-related gene expression signature identifies an aggressive glioblastoma subtype with excessive mutations
Authors: Yan Xiaowei , Ma Li , Yi Danielle , Yoon Jae-geun , Diercks Alan , Foltz Gregory , Price Nathan D. , Hood Leroy E. , Tian Qiang
Published: January 2011

Cancer cells are heterogeneous and, it has been proposed, fall into at least two classes: the tumor-initiating cancer stem cells (CSC) and the more differentiated tumor cells. The transmembrane protein CD133 has been widely used to isolate putative CSC populations in several cancer types, but its validity as a CSC marker and hence its clinical ramifications remain controversial. Here, we conducted transcriptomic profiling of sorted CD133
+
and CD133
−
cells from human glioblastoma multiforme (GBM) and, by subtractive analysis, established a CD133 gene expression signature composed of 214 differentially expressed genes. Extensive computational comparisons with a compendium of published gene expression profiles reveal that the CD133 gene signature transcriptionally resembles human ES cells and in vitro cultured GBM stem cells, and this signature successfully distinguishes GBM from lower-grade gliomas. More importantly, the CD133 gene signature identifies an aggressive subtype of GBM seen in younger patients with shorter survival who bear excessive genomic mutations as surveyed through the Cancer Genome Atlas Network GBM mutation spectrum. Furthermore, the CD133 gene signature distinguishes higher-grade breast and bladder cancers from their lower-grade counterparts. Our systematic analysis provides molecular and genetic support for the stem cell-like nature of CD133
+
cells and an objective means for evaluating cancer aggressiveness.
Cellular and molecular events in the localization of diabetogenic T cells to islets of Langerhans
Authors: Calderon Boris , Carrero Javier A. , Miller Mark J. , Unanue Emil R.
Published: January 2011

Understanding the entry of autoreactive T cells to their target organ is important in autoimmunity because this entry initiates the inflammatory process. Here, the events that lead to specific localization of diabetogenic CD4 T cells into islets of Langerhans resulting in diabetes were examined. This was evaluated in two models, one in which T cells specific for a hen-egg white lysozyme (HEL) peptide were injected into mice expressing HEL on β cells and the other using T cells in the nonobese diabetic mouse strain, which develops spontaneous diabetes. Only T cells specific for β-cell antigens localized in islets within the first hours after their injection and were found adherent to intraislet dendritic cells (DCs). DCs surrounded blood vessels with dendrites reaching into the vessels. Localization of antigen-specific T cells did not require chemokine receptor signaling but involved class II histocompatibility and intercellular adhesion molecule 1 molecules. We found no evidence for nonspecific localization of CD4 T cells into normal noninflamed islets. Thus, the anatomy of the islet of Langerhans permits the specific localization of diabetogenic T cells at a time when there is no inflammation in the islets.
Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular response
Authors: Calderon Boris , Carrero Javier A. , Miller Mark J. , Unanue Emil R.
Published: January 2011

In an accompanying paper, we find specific localization of diabetogenic T cells only to islets of Langerhans bearing the specific antigen. Instrumental in the specific localization was the presence of intraislet dendritic cells bearing the β-cell-peptide-MHC complex. Here, we report that the entry of diabetogenic CD4 T cells very rapidly triggered inflammatory gene expression changes in islets and vessels by up-regulating chemokines and adhesion molecules. Vascular cell adhesion molecule-1 (VCAM-1) expression was notable in blood vessels, as was intercellular adhesion molecule-1 (ICAM-1). ICAM-1 was also found on β-cells. These expression changes induced the entry of nonspecific T cells that otherwise did not localize to the islets. In contrast to the entry of diabetogenic CD4 T cells, the entrance of nonspecific T cells required a chemokine response and VCAM-1 expression by the islets. IFN-γ was important for the early gene expression changes in the islets. By microarray analysis, we detected up-regulation of a group of IFN-inducible genes as early as 8 h post–T-cell transfer. These studies establish that entry of diabetogenic T cells induces a state of receptivity of islets to subsequent immunological insults.