bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic ripples in single layer graphene
Authors: He Y. Z. , Li H. , Si P. C. , Li Y. F. , Yu H. Q. , Zhang X. Q. , Ding F. , Liew K. M. , Liu X. F.
Published: February 2011

Similar to the water wave on a pond caused by dropping a pebble, the formation of ripples is shown in a single layer graphene (SLG) when it is stroked by a C60 molecule, no matter whether the graphene is plane or corrugated. The controllable ripple in SLG is investigated by molecular dynamics simulations. Noticeable diffraction and interference of the ripples are observed. This study indicates that the ripple propagation in graphene can be used to detect defects.
Shocks, explosions, and vortices in two-dimensional homogeneous quantum magnetoplasma
Authors: Yang J. R. , Tang X. Y. , Lou S. Y.
Published: February 2011

Using the quantum hydrodynamic model for a uniform quantum magnetoplasma, and considering that the collision between ions and neutrals is dominant, a two-dimensional nonlinear system is derived. The linear dispersion relation is obtained and thus the variations of the dispersion relation with the obliqueness angle and density are discussed in detail. Shock, explosion, and vortex solutions of the nonlinear system are obtained. It is found that increasing the plasma density may enhance the strength of the shock and the width of the explosion. However, the higher the collision frequency is, the weaker the shock and the narrower the explosion will be. The temporal and spatial distributions for the vortex potential are studied. Spatially, it forms a periodic vortex street. Temporally, the vortex street may evolve in various ways owing to the arbitrary function of time.
Generation of coherent magnetic fields in sheared inhomogeneous turbulence: No need for rotation?
Authors: Leprovost Nicolas , Kim Eun-jin
Published: February 2011

Coherent magnetic fields are often believed to be generated by the combination of stretching by differential rotation and turbulent amplification of magnetic field, via the so-called α effect. The latter is known to exist in helical turbulence, which is envisioned to arise due to both rotation and convection in solar-type stars. In this contribution, a turbulent flow driven by a nonhelical inhomogeneous forcing and its kinematic dynamo action are studied for a uniform magnetic field in the background of a linear shear flow. By using a quasilinear analysis and a nonperturbative method utilizing a time-dependent wave number, turbulence property and electromotive force are computed for arbitrary shear strength. Due to the large-scale shear flow, the turbulence is highly anisotropic, as a consequence, so is the electromotive force. The latter is found to exist even without rotation due to the combined effect of shear flow and inhomogeneous forcing, containing not only the α effect but also magnetic pumping (the γ effect representing a transport of magnetic flux by turbulence). Specifically, without shear, only the magnetic pumping exists, aligned with the direction of inhomogeneity. For a weak but nonzero shear, the combined effects of shear and inhomogeneous forcing modify the structure of the magnetic pumping when the inhomogeneity is in the plane of the shear flow, the magnetic pumping becoming bidimensional in that plane. It also induces an α tensor which has nondiagonal components. When the inhomogeneity is perpendicular to the plane of the shear flow, the α effect has three nonzero diagonal components and one off-diagonal component. However, for a sufficiently strong shear, the γ and α effects are suppressed due to shear stabilization which damps turbulence. A simplified dynamo model is then proposed where a large-scale dynamo arises due to the combined effect of shear flow and inhomogeneous forcing. In particular, the growth of a large-scale axisymmetric magnetic field is demonstrated in case of an inhomogeneity which is perpendicular to the plane of the shear flow. Interesting implications of these results for the structure of magnetic fields in star with slow rotation are discussed.
Universal asymptotics of poloidal spectra of magnetic perturbations of saddle coils in tokamaks
Authors: Abdullaev S. S.
Published: February 2011

Universal and generic features of poloidal spectra of external magnetic perturbations created by a set of saddle coils in tokamak plasmas are studied in a vacuum approximation. It is found that the poloidal mode spectra with high-accuracy are described by a linear combination of three universal asymptotical formulas which depend only on the safety factor of the equilibrium plasma and the geometry of perturbation coils. The validity of these formulas is confirmed by numerical calculations of the mode spectra in the DIII-D plasma [G. L. Jackson et al., Europhys. Conf. Abstr. 27A, P–4 (2007)] and a spherical tokamak, National Spherical Tokamak Experiment [D. A. Gates, et al., Nucl. Fusion 49, 104016 (2009)], plasmas perturbed by external control coils.
InN/InGaN multiple quantum wells emitting at 1.5 μm grown by molecular beam epitaxy
Authors: Grandal J. , Pereiro J. , Bengoechea-Encabo A. , Fernández-Garrido S. , Sánchez-García M. A. , Muñoz E. , Calleja E. , Luna E. , Trampert A.
Published: February 2011

This work reports on the growth by molecular beam epitaxy and characterization of InN/InGaN multiple quantum wells (MQWs) emitting at 1.5 μm. X-ray diffraction (XRD) spectra show satellite peaks up to the second order. Estimated values of well (3 nm) and barrier (9 nm) thicknesses were derived from transmission electron microscopy and the fit between experimental data and simulated XRD spectra. Transmission electron microscopy and XRD simulations also confirmed that the InGaN barriers are relaxed with respect to the GaN template, while the InN MQWs grew under biaxial compression on the InGaN barriers. Low temperature (14 K) photoluminescence measurements reveal an emission from the InN MQWs at 1.5 μm. Measurements as a function of temperature indicate the existence of localized states, probably due to InN quantum wells’ thickness fluctuations as observed by transmission electron microscopy.
Intersubband gain without global inversion through dilute nitride band engineering
Authors: Pereira Mauro F. , Tomić Stanko
Published: February 2011

We investigate the possibility of interconduction band gain without global inversion by engineering the conduction band effective masses so that the upper lasing subband has an effective mass considerably smaller than the lower lasing subband that could not be obtained in conventional III-V materials. We recover the expected dispersive gain shape for similar masses and contrasting results if the effective masses characterizing the relevant subbands are very different.
All-printed infrared sensor based on multiwalled carbon nanotubes
Authors: Gohier A. , Dhar A. , Gorintin L. , Bondavalli P. , Bonnassieux Y. , Cojocaru C. S.
Published: February 2011

This contribution deals with all-printed infrared sensors fabricated using multiwalled carbon nanotubes deposited on a flexible polyimide substrate. A high responsivity of up to 1.2 kV/W is achieved at room temperature in ambient air. We evidence a strong dependence of the device transduction mechanism on the surrounding atmosphere, which can be attributed to bolometric effect interference with water molecule desorption upon irradiation.
Direct current dielectric barrier discharges under voltages below the ionization potential of neutrals in electrode systems with one-dimensional nanostructures
Authors: Hou Zhongyu , Zhou Weimin , Wang Yanyan , Cai Bingchu
Published: February 2011

We experimentally investigate the characteristics of dielectric barrier discharges in an electrode system with one-dimensional nanostructures of gap size at micrometer scale. Evidence of quasistationary direct current discharges in air has been observed under the applied voltage several times lower than the first ionization potential of O2. The results qualitatively agree with the hypothesis on the ionization mechanism of stepwise inelastic collisions within a metastable pool, which is populated through field excitation and inelastic impact between the neutrals and the nanostructures.
Cross-linking effect on dielectric properties of polypropylene thin films and applications in electric energy storage
Authors: Yuan Xuepei , Chung T. C. Mike
Published: February 2011

A family of cross-linked polypropylene (x-PP) thin film dielectrics is systematically studied to understand the cross-linking effect on the dielectric properties. Evidently, the butylstyrene (BSt) cross-linkers increase both the dielectric constant (ε) and breakdown strength (E), without increasing energy loss. An x-PP dielectric, with 3.65 mol % BSt cross-linkers, exhibits a ε∼3, which is independent of a wide range of temperatures and frequencies, slim D-E hysteresis loops, high breakdown strength (E=650 MV/m), narrow breakdown distribution, and reliable energy storage capacity >5 J/cm3 (double that of state-of-the-art biaxially oriented polypropylene capacitors), without showing any increase in energy loss.
π
junction transition in InAs self-assembled quantum dot coupled with SQUID
Authors: Kim S. , Ishiguro R. , Kamio M. , Doda Y. , Watanabe E. , Tsuya D. , Shibata K. , Hirakawa K. , Takayanagi H.
Published: February 2011

We report the transport measurements on the InAs self-assembled quantum dots (SAQDs) which have a unique structural zero-dimensionality, coupled to a superconducting quantum interference device (SQUID). Owing to the SQUID geometry, we directly observe a π phase shift in the current phase relation and the negative supercurrent indicating π junction behavior by not only tuning the energy level of SAQD by back-gate but also controlling the coupling between SAQD and electrodes by side-gate. Our results inspire the future quantum information devices which can link optical, spin, and superconducting state.
Strain-tunable spin transport in ferromagnetic graphene junctions
Authors: Zhai Feng , Yang Lin
Published: February 2011

We investigate spin-dependent electronic transport through normal/strained/normal/ferromagnetic/normal graphene junctions. The substrate strain leads to opposite shifts of the K and K′ valleys and thus modulates the orbital motion of Dirac electrons. The energy dependence of this effect together with the exchange splitting can be utilized to design a strain-tunable spin filter.
Transition from patchlike to clusterlike inhomogeneity arising from hydrogen bonding in water
Authors: Swiatla-Wojcik Dorota , Szala-Bilnik Joanna
Published: February 2011

Assembling of water molecules via hydrogen bonding has been studied by molecular dynamics simulations using flexible potential model. The relationship between the number of H-bonds per molecule, nHB, the size of H-bonded nets, k, and the size of patches of four-bonded molecules, k4, has been examined for several thermodynamic states of water ranging from ambient to supercritical conditions. Two kinds of structural inhomogeneity have been found: the patchlike associated with the mean $\overline n _{{\rm HB}}$n¯ HB > 2.0 and the clusterlike for $\overline n _{\rm HB}$n¯ HB < 1.9. In compressed water up to ∼473 K patches coexist with less ordered nets, both constituting the gel-like H-bonded network. The size of patches steeply decreases with the increasing temperature and the decreasing density of water. The inhomogeneity resulting from the presence of patches disappears above 473 K. This feature is associated with the rapid increase in the fraction of unbound molecules and with the breakage of the gel-like network into a variety of H-bonded clusters leading to the clusterlike structural inhomogeneity. In contrast to the patchlike inhomogeneity an increase in temperature and a decrease in density make this kind of inhomogeneity more pronounced. A degree of connectivity of H-bonds has been characterized by a parameter Pg defined as the total fraction of molecules belonging to the H-bonded clusters of size k ≥ 5. The simulation-derived values of Pg agree well with the predictions of the random bond theory giving the explicit expression for Pg as a function of the mean nHB. Going from ambient to supercritical conditions, we have found that the patchlike inhomogeneity is connected with the very slight reduction in Pg, whereas the clusterlike inhomogeneity generates a steep linear decrease of Pg with the decreasing mean nHB. The self-diffusion coefficient calculated for the thermodynamic states of water showing the clusterlike inhomogeneity has occurred to be inversely proportional to the density. We have also found that the clusterlike inhomogeneity is associated with the linear correlation between Pg and the macroscopic properties of water: the static dielectric constant, the viscosity, and the density. The provided relationships allow one to estimate the degree of connectivity of hydrogen bonds from the measured macroscopic quantities.
An analytical model of strain isolation for stretchable and flexible electronics
Authors: Cheng H. , Wu J. , Li M. , Kim D.-H. , Kim Y.-S. , Huang Y. , Kang Z. , Hwang K. C. , Rogers J. A.
Published: February 2011

One important aspect of stretchable electronics design is to shield the active devices from strains through insertion of a soft layer between devices and substrate. An analytical model is established, which gives linear dependence of strain isolation on the reciprocal of strain-isolation layer thickness, and the reciprocal of device and substrate stiffness. Strain isolation is also linearly proportional to the shear modulus of strain-isolation layer and square of device length.
Direct measurement of the band gap and Fermi level position at InN(112¯)
Authors: Ebert Ph. , Schaafhausen S. , Lenz A. , Sabitova A. , Ivanova L. , Dähne M. , Hong Y.-L. , Gwo S. , Eisele H.
Published: February 2011

A nonpolar stoichiometric InN(112¯0) surface freshly cleaved inside UHV was investigated by scanning tunneling microscopy and spectroscopy. Due to the absence of intrinsic surface states in the band gap, scanning tunneling spectroscopy yields directly the fundamental bulk band gap of 0.7±0.1 eV. The Fermi energy is pinned 0.3 eV below the conduction band minimum due to cleavage induced defect states. Thus, intrinsic electron accumulation can be excluded for this surface. Electron accumulation is rather an extrinsic effect due to surface contamination or material decomposition, but not an intrinsic material property of InN.
Direct writing of ferroelectric domains on the x- and y-faces of lithium niobate using a continuous wave ultraviolet laser
Authors: Steigerwald H. , Ying Y. J. , Eason R. W. , Buse K. , Mailis S. , Soergel E.
Published: February 2011

Ferroelectric domain reversal has been achieved by scanning a tightly focused, strongly absorbed ultraviolet laser beam across the x- and y-faces of lithium niobate crystals. The domains were investigated by piezoresponse force microscopy. The emergence and width of any domain was found to depend on the scanning direction of the irradiating laser beam with respect to the polar z-axis. Full width and half width domains or no domain formation at all could be achieved for scanning along specific directions. We interpret the results by a direct correlation between the local temperature gradient and the resulting polarization direction.
Photoelectron and computational studies of the copper-nucleoside anionic complexes, Cu–(cytidine) and Cu–(uridine)
Authors: Li Xiang , Ko Yeon-Jae , Wang Haopeng , Bowen Kit H. , Guevara-García Alfredo , Martínez Ana
Published: February 2011

The copper-nucleoside anions, Cu–(cytidine) and Cu–(uridine), have been generated in the gas phase and studied by both experimental (anion photoelectron spectroscopy) and theoretical (density functional calculations) methods. The photoelectron spectra of both systems are dominated by single, intense, and relatively narrow peaks. These peaks are centered at 2.63 and 2.71 eV for Cu–(cytidine) and Cu–(uridine), respectively. According to our calculations, Cu–(cytidine) and Cu–(uridine) species with these peak center [vertical detachment energy (VDE)] values correspond to structures in which copper atomic anions are bound to the sugar portions of their corresponding nucleosides largely through electrostatic interactions; the observed species are anion–molecule complexes. The combination of experiment and theory also reveal the presence of a slightly higher energy, anion–molecule complex isomer in the case of the Cu–(cytidine). Furthermore, our calculations found that chemically bond isomers of these species are much more stable than their anion–molecule complex counterparts, but since their calculated VDE values are larger than the photon energy used in these experiments, they were not observed.
Electric response of a cell of hydrogel: Role of the electrodes
Authors: Alexe-Ionescu A. L. , Atasiei R. , Dascalu C. , Freire F. C. M. , Barbero G.
Published: February 2011

We investigate the dielectric properties of hydrogel by means of the impedance spectroscopy technique. Our experimental data relevant to the frequency dependence of the real and imaginary parts of the electrical impedance of the cell indicate that, in the low frequency region (f<20 Hz), the electric response of the cell is dominated by surface effects, weakly dependent on the thickness of the sample. On the contrary, in the high frequency region (f>100 Hz), the electric response of the sample is mainly due to the bulk properties. The observed frequency dependence of the electrical impedance of the cell can be well interpreted by means of the Poisson–Nernst–Planck model taking into account the Ohmic character of the interface electrodes-hydrogel.
Tunable single mode lasing from an on-chip optofluidic ring resonator laser
Authors: Lee Wonsuk , Li Hao , Suter Jonathan D. , Reddy Karthik , Sun Yuze , Fan Xudong
Published: February 2011

Single mode lasing from the polydimethylsiloxane based on-chip coupled optofluidic ring resonator (OFRR) with the lasing threshold of a few μJ/mm2 is demonstrated using the Vernier effect. The single mode operation is highly stable even at high pump energy densities. The effect of the OFRR size and coupling strength on the single mode emission is investigated, showing that the excessive coupling results in incomplete side mode suppression. Tuning of the lasing wavelength is achieved by modifying the dye solution.
Ultrashort pulses characterization by nonlinear diffraction from virtual beam
Authors: Aleksandrovsky A. S. , Vyunishev A. M. , Zaitsev A. I. , Ikonnikov A. A. , Pospelov G. I.
Published: February 2011

Noncollinear frequency doubling in a random nonlinear photonic crystal of strontium tetraborate via nonlinear diffraction from virtual beam is investigated. This effect is shown to be useful for ultrashort pulses characterization in broad spectral range. Nonlinear photonic crystals of strontium tetraborate are a promising medium for ultrafast diagnostics in short-wavelength applications.
Measurement of the valence band structure in dielectric films by a focused ion beam
Authors: Uhm Han S. , Hong Young J. , Choi Eun H. , Kim Do Y.
Published: February 2011

The measured profile of the energy distribution of electrons emitted from dielectric films due to the Auger neutralization of incoming ions is rescaled to facilitate the Auger self-convolution, which illustrates the details of the valence band. As an application for this research scheme, the properties of the valence band in MgO layers are investigated in terms of the measured Auger self-convolution, indicating that the state density is a decaying function of the energy deviation from the band of ε0=7.63 eV, although a numerical calculation shows a spiky structure of the state density in the valence band.
Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth
Authors: Madeja Zofia , Yadi Hakim , Apps Richard , Boulenouar Selma , Roper Stephen J. , Gardner Lucy , Moffett Ashley , Colucci Francesco , Hemberger Myriam
Published: February 2011

The mammalian fetus represents a semiallograft within the maternal uterus yet is not rejected. This situation is particularly pronounced in species with a hemochorial type of placentation, such as humans and rodents, where maternal tissues and blood are in direct contact with fetal trophoblast and thus potentially with paternal antigens. The main polymorphic antigens responsible for graft rejection are MHC antigens. In humans the trophoblast cells invading into the decidua have a unique pattern of MHC class I expression characterized by both classical (HLA-C) and nonclassical (HLA-G and HLA-E) molecules. Whether such an unusual MHC repertoire on the surface of trophoblast is a conserved feature between species with hemochorial placentation has not been resolved. Here we demonstrate, using a range of methods, that C57BL/6 mouse trophoblast predominantly expresses only one MHC class I antigen, H2-K, at the cell surface of giant cells but lacks expression of nonclassical MHC molecules. Antigenic disparity between parental MHCs affects trophoblast-induced transformation of the uterine vasculature and, consequently, placental and fetal gowth. Maternal uterine blood vessels were more dilated, allowing for increased blood supply, in certain combinations of maternal and paternal MHC haplotypes, and these allogeneic fetuses and placentas were heavier at term compared with syngeneic controls. Thus, maternal–fetal immune interactions are instrumental to optimize reproductive success. This cross-talk has important implications for human disorders of pregnancy, such as preeclampsia and fetal growth restriction.
Brief predator sound exposure elicits behavioral and neuronal long-term sensitization in the olfactory system of an insect
Authors: Anton Sylvia , Evengaard Katarina , Barrozo Romina B. , Anderson Peter , Skals Niels
Published: February 2011

Modulation of sensitivity to sensory cues by experience is essential for animals to adapt to a changing environment. Sensitization and adaptation to signals of the same modality as a function of experience have been shown in many cases, and some of the neurobiological mechanisms underlying these processes have been described. However, the influence of sensory signals on the sensitivity of a different modality is largely unknown. In males of the noctuid moth,
Spodoptera littoralis
, the sensitivity to the female-produced sex pheromone increases 24 h after a brief preexposure with pheromone at the behavioral and central nervous level. Here we show that this effect is not confined to the same sensory modality: the sensitivity of olfactory neurons can also be modulated by exposure to a different sensory stimulus, i.e., a pulsed stimulus mimicking echolocating sounds from attacking insectivorous bats. We tested responses of preexposed male moths in a walking bioassay and recorded from neurons in the primary olfactory center, the antennal lobe. We show that brief exposure to a bat call, but not to a behaviorally irrelevant tone, increases the behavioral sensitivity of male moths to sex pheromone 24 h later in the same way as exposure to the sex pheromone itself. The observed behavioral modification is accompanied by an increase in the sensitivity of olfactory neurons in the antennal lobe. Our data provide thus evidence for cross-modal experience-dependent plasticity not only on the behavioral level, but also on the central nervous level, in an insect.
Dispensability of
Escherichia coli
’s latent pathways
Authors: Cornelius Sean P. , Lee Joo Sang , Motter Adilson E.
Published: February 2011

Gene-knockout experiments on single-cell organisms have established that expression of a substantial fraction of genes is not needed for optimal growth. This problem acquired a new dimension with the recent discovery that environmental and genetic perturbations of the bacterium
Escherichia coli
are followed by the temporary activation of a large number of latent metabolic pathways, which suggests the hypothesis that temporarily activated reactions impact growth and hence facilitate adaptation in the presence of perturbations. Here, we test this hypothesis computationally and find, surprisingly, that the availability of latent pathways consistently offers no growth advantage and tends, in fact, to inhibit growth after genetic perturbations. This is shown to be true even for latent pathways with a known function in alternate conditions, thus extending the significance of this adverse effect beyond apparently nonessential genes. These findings raise the possibility that latent pathway activation is in fact derivative of another, potentially suboptimal, adaptive response.
Low-resolution structure of a vesicle disrupting α-synuclein oligomer that accumulates during fibrillation
Authors: Giehm Lise , Svergun Dmitri I. , Otzen Daniel E. , Vestergaard Bente
Published: February 2011

One of the major hallmarks of Parkinson disease is aggregation of the protein α-synuclein (αSN). Aggregate cytotoxicity has been linked to an oligomeric species formed at early stages in the aggregation process. Here we follow the fibrillation process of αSN in solution over time using small angle X-ray scattering and resolve four major coexisting species in the fibrillation process, namely monomer, dimer, fibril and an oligomer. By ab initio modeling to fit the data, we obtain a low-resolution structure of a symmetrical and slender αSN fibril in solution, consisting of a repeating unit with a maximal distance of 900 Å and a diameter of ∼180 
Å
. The same approach shows the oligomer to be shaped like a wreath, with a central channel and with dimensions corresponding to the width of the fibril. The structure, accumulation and decay of this oligomer is consistent with an on-pathway role for the oligomer in the fibrillation process. We propose an oligomer-driven αSN fibril formation mechanism, where the fibril is built from the oligomers. The wreath-shaped structure of the oligomer highlights its potential cytotoxicity by simple membrane permeabilization. This is confirmed by the ability of the purified oligomer to disrupt liposomes. Our results provide the first structural description in solution of a potentially cytotoxic oligomer, which accumulates during the fibrillation of αSN.
Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer
Authors: Cima Igor , Schiess Ralph , Wild Peter , Kaelin Martin , Schüffler Peter , Lange Vinzenz , Picotti Paola , Ossola Reto , Templeton Arnoud , Schubert Olga , Fuchs Thomas , Leippold Thomas , Wyler Stephen , Zehetner Jens , Jochum Wolfram , Buhmann Joachim , Cerny Thomas , Moch Holger , Gillessen Silke , Aebersold Ruedi , Krek Wilhelm
Published: February 2011

A key barrier to the realization of personalized medicine for cancer is the identification of biomarkers. Here we describe a two-stage strategy for the discovery of serum biomarker signatures corresponding to specific cancer-causing mutations and its application to prostate cancer (PCa) in the context of the commonly occurring phosphatase and tensin homolog (
PTEN
) tumor-suppressor gene inactivation. In the first stage of our approach, we identified 775
N
-linked glycoproteins from sera and prostate tissue of wild-type and
Pten
-null mice. Using label-free quantitative proteomics, we showed that
Pten
inactivation leads to measurable perturbations in the murine prostate and serum glycoproteome. Following bioinformatic prioritization, in a second stage we applied targeted proteomics to detect and quantify 39 human ortholog candidate biomarkers in the sera of PCa patients and control individuals. The resulting proteomic profiles were analyzed by machine learning to build predictive regression models for tissue
PTEN
status and diagnosis and grading of PCa. Our approach suggests a general path to rational cancer biomarker discovery and initial validation guided by cancer genetics and based on the integration of experimental mouse models, proteomics-based technologies, and computational modeling.
Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota
Authors: Kirouac Kevin N. , Ling Hong
Published: February 2011

The 8-oxo-guanine (8-oxo-G) lesion is the most abundant and mutagenic oxidative DNA damage existing in the genome. Due to its dual coding nature, 8-oxo-G causes most DNA polymerases to misincorporate adenine. Human Y-family DNA polymerase iota (polι) preferentially incorporates the correct cytosine nucleotide opposite 8-oxo-G. This unique specificity may contribute to polι’s biological role in cellular protection against oxidative stress. However, the structural basis of this preferential cytosine incorporation is currently unknown. Here we present four crystal structures of polι in complex with DNA containing an 8-oxo-G lesion, paired with correct dCTP or incorrect dATP, dGTP, and dTTP nucleotides. An exceptionally narrow polι active site restricts the purine bases in a
syn
conformation, which prevents the dual coding properties of 8-oxo-G by inhibiting
syn/anti
conformational equilibrium. More importantly, the 8-oxo-G base in a
syn
conformation is not mutagenic in polι because its Hoogsteen edge does not form a stable base pair with dATP in the narrow active site. Instead, the
syn
8-oxo-G template base forms the most stable replicating base pair with correct dCTP due to its small pyrimidine base size and enhanced hydrogen bonding with the Hoogsteen edge of 8-oxo-G. In combination with site directed mutagenesis, we show that Gln59 in the finger domain specifically interacts with the additional O
8
atom of the lesion base, which influences nucleotide selection, enzymatic efficiency, and replication stalling at the lesion site. Our work provides the structural mechanism of high-fidelity 8-oxo-G replication by a human DNA polymerase.
Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes
Authors: Cole Steven W. , Hawkley Louise C. , Arevalo Jesusa M. G. , Cacioppo John T.
Published: February 2011

To clarify the biological rationale for social regulation of gene expression, this study sought to identify the specific immune cell types that are transcriptionally sensitive to subjective social isolation (loneliness). Using reference distributions for the expression of each human gene in each major leukocyte subtype, we mapped the cellular origin of transcripts found to be differentially expressed in the circulating immune cells from chronically lonely individuals. Loneliness-associated genes derived primarily from plasmacytoid dendritic cells, monocytes, and, to a lesser extent, B lymphocytes. Those dynamics reflected per-cell changes in the expression of inducible genes and related more strongly to the subjective experience of loneliness than to objective social network size. Evolutionarily ancient myeloid antigen-presenting cells appear to have evolved a transcriptional sensitivity to socioenvironmental conditions that may allow them to shift basal gene expression profiles to counter the changing microbial threats associated with hostile vs. affine social conditions.
Model for the regulation of
Arabidopsis thaliana
leaf margin development
Authors: Bilsborough Gemma D. , Runions Adam , Barkoulas Michalis , Jenkins Huw W. , Hasson Alice , Galinha Carla , Laufs Patrick , Hay Angela , Prusinkiewicz Przemyslaw , Tsiantis Miltos
Published: February 2011

Biological shapes are often produced by the iterative generation of repeated units. The mechanistic basis of such iteration is an area of intense investigation. Leaf development in the model plant Arabidopsis is one such example where the repeated generation of leaf margin protrusions, termed serrations, is a key feature of final shape. However, the regulatory logic underlying this process is unclear. Here, we use a combination of developmental genetics and computational modeling to show that serration development is the morphological read-out of a spatially distributed regulatory mechanism, which creates interspersed activity peaks of the growth-promoting hormone auxin and the CUP-SHAPED COTYLEDON2 (CUC2) transcription factor. This mechanism operates at the growing leaf margin via a regulatory module consisting of two feedback loops working in concert. The first loop relates the transport of auxin to its own distribution, via polar membrane localization of the PINFORMED1 (PIN1) efflux transporter. This loop captures the potential of auxin to generate self-organizing patterns in diverse developmental contexts. In the second loop, CUC2 promotes the generation of PIN1-dependent auxin activity maxima while auxin represses CUC2 expression. This CUC2-dependent loop regulates activity of the conserved auxin efflux module in leaf margins to generate stable serration patterns. Conceptualizing leaf margin development via this mechanism also helps to explain how other developmental regulators influence leaf shape.
Intramembrane cavitation as a unifying mechanism for ultrasound-induced bioeffects
Authors: Krasovitski Boris , Frenkel Victor , Shoham Shy , Kimmel Eitan
Published: February 2011

The purpose of this study was to develop a unified model capable of explaining the mechanisms of interaction of ultrasound and biological tissue at both the diagnostic nonthermal, noncavitational (<100 mW·cm
−2
) and therapeutic, potentially cavitational (>100 mW·cm
−2
) spatial peak temporal average intensity levels. The cellular-level model (termed “bilayer sonophore”) combines the physics of bubble dynamics with cell biomechanics to determine the dynamic behavior of the two lipid bilayer membrane leaflets. The existence of such a unified model could potentially pave the way to a number of controlled ultrasound-assisted applications, including CNS modulation and blood–brain barrier permeabilization. The model predicts that the cellular membrane is intrinsically capable of absorbing mechanical energy from the ultrasound field and transforming it into expansions and contractions of the intramembrane space. It further predicts that the maximum area strain is proportional to the acoustic pressure amplitude and inversely proportional to the square root of the frequency (

) and is intensified by proximity to free surfaces, the presence of nearby microbubbles in free medium, and the flexibility of the surrounding tissue. Model predictions were experimentally supported using transmission electron microscopy (TEM) of multilayered live-cell goldfish epidermis exposed in vivo to continuous wave (CW) ultrasound at cavitational (1 MHz) and noncavitational (3 MHz) conditions. Our results support the hypothesis that ultrasonically induced bilayer membrane motion, which does not require preexistence of air voids in the tissue, may account for a variety of bioeffects and could elucidate mechanisms of ultrasound interaction with biological tissue that are currently not fully understood.
Modeling aqueous solvation with semi-explicit assembly
Authors: Fennell Christopher J. , Kehoe Charles W. , Dill Ken A.
Published: February 2011

We describe a computational solvation model called semi-explicit assembly (SEA). SEA water captures much of the physics of explicit-solvent models but with computational speeds approaching those of implicit-solvent models. We use an explicit-water model to precompute properties of water solvation shells around simple spheres, then assemble a solute’s solvation shell by combining the shells of these spheres. SEA improves upon implicit-solvent models of solvation free energies by accounting for local solute curvature, accounting for near-neighbor nonadditivities, and treating water’s dipole as being asymmetrical with respect to positive or negative solute charges. SEA does not involve parameter fitting, because parameters come from the given underlying explicit-solvation model. SEA is about as accurate as explicit simulations as shown by comparisons against four different homologous alkyl series, a set of 504 varied solutes, solutes taken retrospectively from two solvation-prediction events, and a hypothetical polar-solute series, and SEA is about 100-fold faster than Poisson–Boltzmann calculations.
The influence of volume exclusion by chromatin on the time required to find specific DNA binding sites by diffusion
Authors: Isaacson S. A. , McQueen D. M. , Peskin Charles S.
Published: February 2011

Within the nuclei of eukaryotic cells, the density of chromatin is nonuniform. We study the influence of this nonuniform density, which we derive from microscopic images [Schermelleh L, et al. (2008)
Science
320:1332–1336], on the diffusion of proteins within the nucleus, under the hypothesis that chromatin density is proportional to an effective potential that tends to exclude the diffusing protein from regions of high chromatin density. The constant of proportionality, which we call the volume exclusivity of chromatin, is a model parameter that we can tune to study the influence of such volume exclusivity on the random time required for a diffusing particle to find its target. We consider randomly chosen binding sites located in regions of low (20th–30th percentile) chromatin density, and we compute the median time to find such a binding site by a protein that enters the nucleus at a randomly chosen nuclear pore. As the volume exclusivity of chromatin increases from zero, we find that the median time needed to reach the target binding site at first decreases to a minimum, and then increases again as the volume exclusivity of chromatin increases further. Random permutation of the voxel values of chromatin density abolishes the minimum, thus demonstrating that the speedup seen with increasing volume exclusivity at low to moderate volume exclusivity is dependent upon the spatial structure of chromatin within the nucleus.
Overexpression of BCL2 enhances survival of human embryonic stem cells during stress and obviates the requirement for serum factors
Authors: Ardehali Reza , Inlay Matthew A. , Ali Shah R. , Tang Chad , Drukker Micha , Weissman Irving L.
Published: February 2011

The promise of pluripotent stem cells as a research and therapeutic tool is partly undermined by the technical challenges of generating and maintaining these cells in culture. Human embryonic stem cells (hESCs) are exquisitely sensitive to culture conditions, and require constant signaling by growth factors and cell–cell and cell–matrix interactions to prevent apoptosis, senescence, and differentiation. Previous work from our laboratory demonstrated that overexpression of the prosurvival gene
BCL2
in mouse embryonic stem cells overrode the requirement of serum factors and feeder cells to maintain mESCs in culture. To determine whether this prosurvival gene could similarly protect hESCs, we generated hESC lines that constitutively or inducibly express
BCL2
. We find that
BCL2
overexpression significantly decreases dissociation-induced apoptosis, resulting in enhanced colony formation from sorted single cells, and enhanced embryoid body formation. In addition, BCL2-hESCs exhibit normal growth in the absence of serum, but require basic fibroblast growth factor to remain undifferentiated. Furthermore, they maintain their pluripotency markers, form teratomas in vivo, and differentiate into all three germ layers. Our data suggest that the BCL2 signaling pathway plays an important role in inhibiting hESC apoptosis, such that its overexpression in hESCs offers both a survival benefit in conditions of stress by resisting apoptosis and obviates the requirement for serum or a feeder layer for maintenance.
Antarctic and Arctic populations of the ciliate
Euplotes nobilii
show common pheromone-mediated cell-cell signaling and cross-mating
Authors: Di Giuseppe Graziano , Erra Fabrizio , Dini Fernando , Alimenti Claudio , Vallesi Adriana , Pedrini Bill , Wüthrich Kurt , Luporini Pierangelo
Published: February 2011

Wild-type strains of the protozoan ciliate
Euplotes
collected from different locations on the coasts of Antarctica, Tierra del Fuego and the Arctic were taxonomically identified as the morpho-species
Euplotes nobilii
, based on morphometric and phylogenetic analyses. Subsequent studies of their sexual interactions revealed that mating combinations of Antarctic and Arctic strains form stable pairs of conjugant cells. These conjugant pairs were isolated and shown to complete mutual gene exchange and cross-fertilization. The biological significance of this finding was further substantiated by demonstrating that close homology exists among the three-dimensional structures determined by NMR of the water-borne signaling pheromones that are constitutively secreted into the extracellular space by these interbreeding strains, in which these molecules trigger the switch between the growth stage and the sexual stage of the life cycle. The fact that Antarctic and Arctic
E. nobilii
populations share the same gene pool and belong to the same biological species provides new support to the biogeographic model of global distribution of eukaryotic microorganisms, which had so far been based exclusively on studies of morphological and phylogenetic taxonomy.
Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells
Authors: Chanson Lea , Brownfield Douglas , Garbe James C. , Kuhn Irene , Stampfer Martha R. , Bissell Mina J. , LaBarge Mark A.
Published: February 2011

Loss of organization is a principle feature of cancers; therefore it is important to understand how normal adult multilineage tissues, such as bilayered secretory epithelia, establish and maintain their architectures. The self-organization process that drives heterogeneous mixtures of cells to form organized tissues is well studied in embryology and with mammalian cell lines that were abnormal or engineered. Here we used a micropatterning approach that confined cells to a cylindrical geometry combined with an algorithm to quantify changes of cellular distribution over time to measure the ability of different cell types to self-organize relative to each other. Using normal human mammary epithelial cells enriched into pools of the two principal lineages, luminal and myoepithelial cells, we demonstrated that bilayered organization in mammary epithelium was driven mainly by lineage-specific differential E-cadherin expression, but that P-cadherin contributed specifically to organization of the myoepithelial layer. Disruption of the actomyosin network or of adherens junction proteins resulted in either prevention of bilayer formation or loss of preformed bilayers, consistent with continual sampling of the local microenvironment by cadherins. Together these data show that self-organization is an innate and reversible property of communities of normal adult human mammary epithelial cells.
Analysis of cellular and behavioral responses to imiquimod reveals a unique itch pathway in transient receptor potential vanilloid 1 (TRPV1)-expressing neurons
Authors: Kim Se-Jeong , Park Goon Ho , Kim Donghoon , Lee Jaekwang , Min Hyejung , Wall Estelle , Lee C. Justin , Simon Melvin I. , Lee Sung Joong , Han Sang-Kyou
Published: February 2011

Despite its clinical importance, the mechanisms that mediate or generate itch are poorly defined. The identification of pruritic compounds offers insight into understanding the molecular and cellular basis of itch. Imiquimod (IQ) is an agonist of Toll-like receptor 7 (TLR7) used to treat various infectious skin diseases such as genital warts, keratosis, and basal cell carcinoma. Itch is reportedly one of the major side effects developed during IQ treatments. We found that IQ acts as a potent itch-evoking compound (pruritogen) in mice via direct excitation of sensory neurons. Combined studies of scratching behavior, patch-clamp recording, and Ca
2+
response revealed the existence of a unique intracellular mechanism, which is independent of TLR7 as well as different from the mechanisms exploited by other well-characterized pruritogens. Nevertheless, as for other pruritogens, IQ requires the presence of transient receptor potential vanilloid 1 (TRPV1)-expressing neurons for itch-associated responses. Our data provide evidence supporting the hypothesis that there is a specific subset of TRPV1-expressing neurons that is equipped with diverse intracellular mechanisms that respond to histamine, chloroquine, and IQ.
MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer
Authors: Boeri Mattia , Verri Carla , Conte Davide , Roz Luca , Modena Piergiorgio , Facchinetti Federica , Calabrò Elisa , Croce Carlo M. , Pastorino Ugo , Sozzi Gabriella
Published: February 2011

The efficacy of computed tomography (CT) screening for early lung cancer detection in heavy smokers is currently being tested by a number of randomized trials. Critical issues remain the frequency of unnecessary treatments and impact on mortality, indicating the need for biomarkers of aggressive disease. We explored microRNA (miRNA) expression profiles of lung tumors, normal lung tissues and plasma samples from cases with variable prognosis identified in a completed spiral-CT screening trial with extensive follow-up. miRNA expression patterns significantly distinguished: (
i
) tumors from normal lung tissues, (
ii
) tumor histology and growth rate, (
iii
) clinical outcome, and (
iv
) year of lung cancer CT detection. Interestingly, miRNA profiles in normal lung tissues also displayed remarkable associations with clinical features, suggesting the influence of a permissive microenvironment for tumor development. miRNA expression analyses in plasma samples collected 1–2 y before the onset of disease, at the time of CT detection and in disease-free smokers enrolled in the screening trial, resulted in the generation of miRNA signatures with strong predictive, diagnostic, and prognostic potential (area under the ROC curve ≥ 0.85). These signatures were validated in an independent cohort from a second randomized spiral-CT trial. These results indicate a role for miRNAs in lung tissues and plasma as molecular predictors of lung cancer development and aggressiveness and have theoretical and clinical implication for lung cancer management.
PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice
Authors: Okazaki Taku , Okazaki Il-mi , Wang Jian , Sugiura Daisuke , Nakaki Fumio , Yoshida Taku , Kato Yu , Fagarasan Sidonia , Muramatsu Masamichi , Eto Tomoo , Hioki Kyoji , Honjo Tasuku
Published: February 2011

Stimulatory and inhibitory co-receptors play fundamental roles in the regulation of the immune system. We describe a new mouse model of spontaneous autoimmune disease. Activation-induced cytidine deaminase–linked autoimmunity (aida) mice harbor a loss-of-function mutation in the gene encoding lymphocyte activation gene 3 (LAG-3), an inhibitory co-receptor. Although LAG-3 deficiency alone did not induce autoimmunity in nonautoimmune-prone mouse strains, it induced lethal myocarditis in BALB/c mice deficient for the gene encoding the inhibitory co-receptor programmed cell death 1 (PD-1). In addition, LAG-3 deficiency alone accelerated type 1 diabetes mellitus in nonobese diabetic mice. These results demonstrate that LAG-3 acts synergistically with PD-1 and/or other immunoregulatory genes to prevent autoimmunity in mice.
Photoacoustic and spectroscopic characterization of the ablation process in orthogonal double-pulse configuration
Authors: Sobral H , Sánchez-Aké C , Sanginés R , Alvarez-Zauco E , Jiménez-Durán K
Published: February 2011

A photoacoustic technique was used as an alternative method to monitor the crater volume and its role in the emission line intensification in double-pulse pre-ablation configuration. The crater volume was measured using confocal microscopy and correlated with the changes in the photoacoustic signal. Laser emission spectroscopy was used to characterize the emission enhancement as a function of the delay between lasers and the first pulse energy. Optimum delay was found to be in the microsecond timescale corresponding to the maximum of the crater volume and the largest change between the single- and the double-pulse photoacoustic signals. Only a slight intensification was detected with increasing first pulse energy above the first pulse ablation threshold; however, the crater volume did not significantly change and the possible involved mechanisms are discussed.