bluuebunny/crossref_metadata_2025 huggingface dataset:
Routhian reduction for quasi-invariant Lagrangians
Authors: Langerock B. , Cantrijn F. , Vankerschaver J.
Published: February 2010

In this paper, we describe Routhian reduction as a special case of standard symplectic reduction, also called Marsden–Weinstein reduction. We use this correspondence to present a generalization of Routhian reduction for quasi-invariant Lagrangians, i.e., Lagrangians that are invariant up to a total time derivative. We show how functional Routhian reduction can be seen as a particular instance of reduction in a quasi-invariant Lagrangian, and we exhibit a Routhian reduction procedure for the special case of Lagrangians with quasicyclic coordinates. As an application, we consider the dynamics of a charged particle in a magnetic field.
Light polarization characteristics of m-plane AlxGa1−xN films suffering from in-plane anisotropic tensile stresses
Authors: Hazu K. , Hoshi T. , Kagaya M. , Onuma T. , Chichibu S. F.
Published: February 2010

Polarization characteristics of the near-band-edge optical transitions in m-plane AlxGa1−xN epilayers suffering from anisotropic stresses were quantified. The epilayers were grown by both ammonia-source molecular beam epitaxy and metalorganic vapor phase epitaxy methods on an m-plane freestanding GaN substrate. The light polarization direction altered from E⊥c to E∥c at the AlN molar fraction, x, between 0.25 and 0.32, where E is the electric field component of the light and ⊥ and ∥ represent perpendicular and parallel, respectively. To give a quantitative explanation for the result, energies and oscillator strengths of the exciton transitions involving three separate valence bands were calculated as functions of strains using the Bir–Pikus Hamiltonian. The calculation predicted that the lowest energy transition (E1) is polarized to the m-axis normal to the surface (X3) for 0<x≤1, meaning that E1 emission is principally undetectable from the surface normal for any in-plane tensile strained AlxGa1−xN. The polarization direction of observable surface emission was predicted to alter from c-axis normal (X1) to c-axis parallel (X2) for the middle energy transition (E2) and X2 to X1 for the highest energy transition (E3) between x=0.25 and 0.32. The experimental results were consistently reproduced by the calculation.
Anomalous nonlinear response of glassy liquids: General arguments and a mode-coupling approach
Authors: Tarzia Marco , Biroli Giulio , Lefèvre Alexandre , Bouchaud Jean-Philippe
Published: February 2010

We study theoretically the nonlinear response properties of glass formers. We establish several general results, which together with the assumption of time-temperature superposition, lead to a relation between the nonlinear response and the derivative of the linear response with respect to temperature. Using results from mode-coupling theory and scaling arguments valid close to the glass transition, we obtain the frequency and temperature dependence of the nonlinear response in the α- and β-regimes. Our results demonstrate that supercooled liquids are characterized by responses to external perturbations that become increasingly nonlinear as the glass transition is approached. These results are extended to the case of inhomogeneous perturbing fields.
Size-dependent recombination dynamics in ZnO nanowires
Authors: Reparaz J. S. , Güell F. , Wagner M. R. , Hoffmann A. , Cornet A. , Morante J. R.
Published: February 2010

A deep understanding of the recombination dynamics of ZnO nanowires (NWs) is a natural step for a precise design of on-demand nanostructures based on this material system. In this work we investigate the influence of finite-size on the recombination dynamics of the neutral bound exciton around 3.365 eV for ZnO NWs with different diameters. We demonstrate that the lifetime of this excitonic transition decreases with increasing the surface-to-volume ratio due to a surface induced recombination process. Furthermore, we have observed two broad transitions around 3.341 and 3.314 eV, which were identified as surface states by studying the dependence of their life time and intensitiy with the NWs dimensions.
Electron energy band alignment at the (100)Si/MgO interface
Authors: Afanas’ev V. V. , Stesmans A. , Cherkaoui K. , Hurley P. K.
Published: February 2010

The electron energy band diagram at the (100)Si/MgO interface is characterized using internal photoemission of electrons and holes from Si into the oxide. For the as-deposited amorphous MgO the interface barriers correspond to a band gap width of 6.1 eV, i.e., much lower than the conventionally assumed bulk crystal value (7.83 eV). The annealing-induced crystallization of MgO mostly affects the energy of the valence band while the conduction band bottom retains its energy position at 3.37±0.05 eV above the top of the silicon valence band.
Optimization of the regenerator of a traveling-wave thermoacoustic refrigerator
Authors: Ueda Yuki , Mehdi Bassem Mohamed , Tsuji Kohei , Akisawa Atsushi
Published: February 2010

Numerical investigations on the performance of a traveling-wave thermoacoustic refrigerator are described. This refrigerator consists of a looped tube attached to an acoustic driver. A regenerator with many narrow flow channels is installed in the looped tube. When acoustic power is supplied by the acoustic driver to the looped tube, heat pumping occurs inside the regenerator. The coefficient of performance (COP), i.e., the ratio of cooling power to input power, of the refrigerator was calculated by varying the position, length, and flow-channel radius of the regenerator. When the three factors were simultaneously optimized, the COP was found to exceed 60% of the Carnot COP.
Terahertz dielectric response and optical conductivity of n-type single-crystal ZnO epilayers grown by metalorganic chemical vapor deposition
Authors: Zhang X. H. , Guo H. C. , Yong A. M. , Ye J. D. , Tan S. T. , Sun X. W.
Published: February 2010

Using terahertz time-domain spectroscopy, we measured the frequency dependent complex dielectric response and conductivity of n-type single-crystal ZnO epilayers with different carrier concentrations over the frequency range from 0.1 to 3.0 THz. The measured complex dielectric response and conductivity are analyzed using Drude model.
Transition temperature in the growing of poly-Si/amorphous-SiO2 by electron-beam evaporation
Authors: Jiang Shao-Ji , Wei Yu-Wei , Chen Zi-Yi , Wang He-Zhou
Published: February 2010

The transition temperature Tt in the growing of poly-Si thin film on amorphous-SiO2, which is prepared by means of electron-beam evaporation (EBE), is evaluated through both simulation and experiment method. Our results demonstrate that there is a sudden transformation in the grain size at transition temperature Tt, and this temperature is apparently influenced by the external factors like the deposition rate F and the substrate material property. Besides, the condition of grain formation at Tt primarily determines the crystallinity of poly-Si thin film, and the relationship between the crystallinity of poly-Si thin film and the transition temperature Tt is also fitted in our work. Thus according to Tt, the parameters of preparation can be predicted and be used to prepare poly-Si to satisfy the needs of the industry through the simple and low-cost EBE method.
Effect of RuCoCr-oxide intermediate layers on the growth, microstructure, and recording performance of CoCrPt–SiO2 perpendicular recording media
Authors: Srinivasan Kumar , Piramanayagam S. N. , Kay Yew Seng
Published: February 2010

The crystallographic growth, magnetic properties, microstructure, and recording performance of CoCrPt–SiO2 perpendicular magnetic recording media on RuCoCr type of intermediate layers were systematically investigated. Excellent Co (00•2) crystallographic texture with dispersion Δθ50 as low as 3.2° could be obtained on the RuCoCr as the grain isolation layer, whereas the Δθ50 on the pure Ru grain isolation layer was 3.9°. Upon injecting oxygen into the RuCoCr layer via reactive sputtering and at high sputter pressures, grain center-to-center distance as small as 5.9 nm with a distribution of about 13% was achieved. The Δθ50 deteriorated on the RuCoCr-oxide type of intermediate layers, however, it remained comparable to that on the pure Ru layers. Signal-to-noise ratio also increased on the RuCoCr-oxide grain isolation layers due to the decreased grain sizes. The effectiveness of the RuCoCr-oxide type of intermediate layers toward grain size reduction and in improving the performance of perpendicular magnetic recording media is discussed.
Luminescence, lifetime, and quantum yield studies of redispersible Eu3+-doped GdPO4 crystalline nanoneedles: Core-shell and concentration effects
Authors: Yaiphaba N. , Ningthoujam R. S. , Singh N. Shanta , Vatsa R. K. , Singh N. Rajmuhon , Dhara Sangita , Misra N. L. , Tewari R.
Published: February 2010

Crystalline nanoneedles of Eu3+-doped GdPO4 and Eu3+-doped GdPO4 covered with GdPO4 shell (core shell) have been prepared at relatively low temperature of 150 °C in ethylene glycol medium. From luminescence study, asymmetric ratio of Eu3+ emission at 612 nm (electric dipole transition) to 592 nm (magnetic dipole transition) is found to be less than one. Maximum luminescence was observed from the nanoparticles with Eu3+ concentration of 5 at. %. For a fixed concentration of Eu3+ doping, there is an improvement in emission intensity for core-shell nanoparticles compared to that for core. This has been attributed to effective removal of surface inhomogeneities around Eu3+ ions present on the surface of core as well as the passivation of inevitable surface states, defects or capping ligand (ethylene glycol) of core nanoparticles by bonding to the shell. Lifetime for D50 level of Eu3+ was found to increase three times for core-shell nanoparticles compared to that for core confirming the more Eu3+ ions with symmetry environment in core shell. For 5 at. % Eu3+-doped GdPO4, quantum yield of 19% is obtained. These nanoparticles are redispersible in water, ethanol, or chloroform and thus will be useful in biological labeling. The dispersed particles are incorporated in polymer-based films that will be useful in display devices.
Nanophononic thin-film filters and mirrors studied by picosecond ultrasonics
Authors: Lanzillotti-Kimura N. D. , Perrin B. , Fainstein A. , Jusserand B. , Lemaître A.
Published: February 2010

Optimized acoustic phonon thin-film filters are studied by picosecond ultrasonics. A broadband mirror and a color filter based on aperiodic multilayers were optimized to work in the subterahertz range, and grown by molecular beam epitaxy. Time resolved differential optical reflectivity experiments were performed with pump and probe pulses incident on opposite sides of the substrate. We provide broadband transmission curves for the phonon devices. The results are in good agreement with standard transfer matrix method simulations. In addition, we analyze the effects of the free surface and the influence of an Al capping layer on the response of the aperiodic devices.
Effect of surface roughness on thermal conductivity of silicon nanowires
Authors: Liu Ling , Chen Xi
Published: February 2010

Reducing the thermal conductivity of nanowires may enhance their already exciting efficiency of thermoelectric energy conversion. Using molecular dynamics simulations, we demonstrate that the thermal conductivity of silicon nanowires could be significantly decreased by patterning (or etching) induced roughness of the nanowire surfaces. The type, amplitude, and wavelength of the surface roughness all have profound effects, and the thermal conductivity could be reduced more when the wavelength is smaller or the amplitude is larger. Such an effect of roughness on the thermal conductivity is furthermore found to be coupled with the effects of nanowire cross-sectional size and length. Typically, the roughness effect is more prominent in longer and larger nanowires.
Optical constants of Cu(In1−xGax)5Se8 crystals
Authors: Levcenko S. , Durán L. , Gurieva G. , Alonso M. I. , Arushanov E. , Durante Rincón C. A. , León M.
Published: February 2010

Spectroscopic ellipsometry has been used to characterize the dielectric functions of bulk Cu(In1−xGax)5Se8 crystals. Spectra were measured at room temperature over the energy range 0.74–5.2 eV. The dielectric functions as well as the complex refractive index, the absorption coefficient, and the normal-incidence reflectivity have been modeled using a modification of the Adachi model. The results are in a good agreement with the experimental data over the entire range of photon energies. The model parameters (strength, threshold energy, and broadening) have been determined using the simulated annealing algorithm. The transition energies E0 and E1A are found to shift linearly to higher energies as the gallium content increases.
Organic light-emitting diodes containing multilayers of organic single crystals
Authors: Nakanotani Hajime , Adachi Chihaya
Published: February 2010

Double-heterostructure (DH) organic light-emitting diodes (OLEDs) with thick carrier transport layers based on organic single crystals have been fabricated. Although the total thickness of the organic layers (∼1.4 μm) is one order of magnitude greater than that of conventional thin-film OLEDs, a current density of 100 mA/cm2 was achieved at 19 V. The major advantage of the single crystal-based DH-OLED was that a very low applied electric field (∼104 V/cm) was required for the onset of carrier injection and transport, because of the high carrier mobilities of the single crystal layers.
Schottky barrier height and conduction mechanisms in ferroelectric bismuth titanate
Authors: Liu Fen , Ma Ying , Yang Feng , Zhou Yichun
Published: February 2010

Band structure of ferroelectric bismuth titanate is calculated by first-principles computations under the framework of density functional theory. Using the metal induced gap state model, the Schottky barrier height on Pt electrode is estimated to be as high as 1.26 eV, which indicates that the Schottky effect may not be the dominant conduction mechanism in bismuth titanate. By further comparisons with the experimental data, we conclude that the leakage current behavior of bismuth titanate films is dominated by bulk limited conduction mechanisms and can be reduced by better processing conditions or doping.
Collection of suspended particles in a drop using low frequency vibration
Authors: Whitehill James , Neild Adrian , Ng Tuck Wah , Stokes Mark
Published: February 2010

Particle collection at low frequencies has been erstwhile demonstrated with dry particles and particles floating on the liquid surface. Nevertheless, the ability to collect suspended particles in a fluid offers arguably wider usage in the context of microfluidic or “lab-on-a-chip” systems. This is demonstrated here via an approach of vibrating a droplet to form resonant shapes on the liquid-gas interface. This results in particles ranging in size from 40 to 120 μm being collected predominantly at the solid-liquid interface due to a hydrodynamic focusing mechanism that develops through multiple cycles.
Dual-mode operation of flexible piezoelectric polymer diaphragm for intracranial pressure measurement
Authors: Li Chunyan , Wu Pei-Ming , Shutter Lori A. , Narayan Raj K.
Published: February 2010

The dual-mode operation of a polyvinylidene fluoride trifluoroethylene (PVDF-TrFE) piezoelectric polymer diaphragm, in a capacitive or resonant mode, is reported as a flexible intracranial pressure (ICP) sensor. The pressure sensor using a capacitive mode exhibits a higher linearity and less power consumption than resonant mode operated pressure sensor. In contrast, the latter provides better sensitivity and easier adaption for wireless application. The metrological properties of the dual-mode ICP sensor being described are satisfactory in vitro. We propose that the piezoelectric polymer diaphragm has a promising future in intracranial pressure monitoring.
Electron spin filtering by thin GaNAs/GaAs multiquantum wells
Authors: Puttisong Y. , Wang X. J. , Buyanova I. A. , Carrére H. , Zhao F. , Balocchi A. , Marie X. , Tu C. W. , Chen W. M.
Published: February 2010

Effectiveness of the recently discovered defect-engineered spin-filtering effect is closely examined in GaNAs/GaAs multiquantum wells (QWs) as a function of QW width. In spite of narrow well widths of 3–9 nm, rather efficient spin filtering is achieved at room temperature. It leads to electron spin polarization larger than 18% and an increase in photoluminescence intensity by 65% in the 9 nm wide QWs. A weaker spin filtering effect is observed in the narrower QWs, mainly due to a reduced sheet concentration of spin-filtering defects (e.g., Gai interstitial defects).
Yellow-green light-emitting electrochemical cells with long lifetime and high efficiency
Authors: Sandström Andreas , Matyba Piotr , Edman Ludvig
Published: February 2010

We show that the electrochemical stability window of the constituent components in light-emitting electrochemical cells (LECs), e.g., the electrolyte, should be considered in order to minimize undesired side reactions. By designing and operating LECs in accordance with straightforward principles, we demonstrate sandwich cells that turn on fast at room temperature (<2 s), and which emit significant yellow-green light (>100 cd/m2) during 25 days of uninterrupted operation at low voltage (<4 V) and high power conversion efficacy (∼6 lm/W). We further demonstrate that it is possible to attain balanced p- and n-type doping and a centered p-n junction in such planar LECs based on the conjugated polymer “superyellow.”
Anisotropic relaxation and crystallographic tilt in BiFeO3 on miscut SrTiO3 (001)
Authors: Sichel Rebecca J. , Grigoriev Alexei , Do Dal-Hyun , Baek Seung-Hyub , Jang Ho-Won , Folkman Chad M. , Eom Chang-Beom , Cai Zhonghou , Evans Paul G.
Published: February 2010

Epitaxial BiFeO3 thin films on miscut (001) SrTiO3 substrates relax via mechanisms leading to an average rotation of the crystallographic axes of the BiFeO3 layer with respect to the substrate. The angle of the rotation reaches a maximum in the plane defined by the surface normal of the film and the direction of the surface miscut. X-ray microdiffraction images show that each BiFeO3 mosaic block is rotated by a slightly different angle and contains multiple polarization domains. These effects lead to a complicated overall symmetry in BiFeO3 thin films. This relaxation mechanism can be extended to other complex oxides.
Wavelength-stable cyan and green light emitting diodes on nonpolar m-plane GaN bulk substrates
Authors: Detchprohm Theeradetch , Zhu Mingwei , Li Yufeng , Zhao Liang , You Shi , Wetzel Christian , Preble Edward A. , Paskova Tanya , Hanser Drew
Published: February 2010

We report the development of 480 nm cyan and 520 nm green light emitting diodes (LEDs) with a highly stable emission wavelength. The shift is less than 3 nm when the drive current density is changed from 0.1 to 38 A/cm2. LEDs have been obtained in GaInN-based homoepitaxy on nonpolar m-plane GaN bulk substrates. For increasing emission wavelength we find a large number of additional dislocations generated within the quantum wells (2×108 to ∼1010 cm2) and a decrease in the electroluminescence efficiency. This suggests that the strain induced generation of defects plays a significant role in the performance limitations.
High-performance surface-enhanced Raman scattering sensors based on Ag nanoparticles-coated Si nanowire arrays for quantitative detection of pesticides
Authors: Wang X. T. , Shi W. S. , She G. W. , Mu L. X. , Lee S. T.
Published: February 2010

A surface-enhanced Raman scattering (SERS) sensor made of Ag nanoparticles-coated Si nanowire (SiNW) arrays was fabricated for the quantitative detection of Carbaryl (an important nitrogen pesticide). H-terminated SiNWs were capable of reducing silver ions, leading to uniform deposition of silver nanoparticles on SiNW arrays. Such wire arrays exhibited a superior detection sensitivity of 10−17 M Rodamine 6G with high reproducibility. The sensor also enabled high sensitivity, reproducibility, and stability detection of Carbaryl. Significantly, the linear relation between the logarithmic concentrations and Raman peak intensities provided quantitative detection of Carbaryl.
Underground detector yields tantalizing hint of dark matter
Authors: Schwarzschild Bertram
Published: February 2010

The dark matter that dominates the rotation and clustering of galaxies is thought to consist of heavy, weakly interacting particles not yet known but much sought after.
Cuts to science budget moderated in Japan
Authors: Feder Toni
Published: February 2010

Even as it breathes a sigh of relief, Japan’s research community worries about the negative message the government’s attack on science conveyed to the country’s young people.
US scientists step up their efforts at diplomacy
Authors: Kramer David
Published: February 2010

With recent visits to North Korea and Cuba, US scientists are seeking interactions with their peers to open channels of communication.
Multiwave imaging and super resolution
Authors: Fink Mathias , Tanter Mickael
Published: February 2010

Interactions between different kinds of waves can yield medical images that beat the single-wave resolution limit.
The first wetting layer on a solid
Authors: Feibelman Peter J.
Published: February 2010

For decades researchers imagined that hydrogen bonding imposes a hexagonal, icelike arrangement on the first water molecules on a solid. Recent theory and experiments argue for a richer view.
Hearing music in ensembles
Authors: Deutsch Diana
Published: February 2010

Musical illusions created in the laboratory or concert hall provide insight on how the brain regroups auditory inputs.
The cytoskeleton: I-beams of the cell
Authors: Shaevitz Joshua , Nørrelykke Simon
Published: February 2010

Cells derive their structural properties from a complex and active arrangement of stiff polymers. How those proteins interact to give rise to the cell’s diverse characteristics remains a key problem in biological physics.
Down and Then Out in Bucharest: Urban Poverty, Governance, and the Politics of Place in the Postsocialist City
Authors: O'Neill Bruce
Published: February 2010

This paper analyzes at the level of space the invention and management of homelessness in postsocialist cities. Based on more than a year of ethnographic fieldwork in a nongovernmental organization (NGO) that provides shelter space in Bucharest, Romania, this paper foregrounds the political significance of placing homeless populations to better understand neoliberal governance as a set of spatially minded practices, arguing (ultimately) that space is a key domain through which homeless populations become managed. This paper, in the end, focuses on ‘the place’ of homelessness to bring the dynamics of postsocialist liberalization into clearer relief.
Estrogen receptor–β activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFα mediated
Authors: McPherson Stephen J. , Hussain Shirin , Balanathan Preetika , Hedwards Shelley L. , Niranjan Birunthi , Grant Michael , Chandrasiri Upeksha P. , Toivanen Roxanne , Wang Yuzhuo , Taylor Renea A. , Risbridger Gail P.
Published: February 2010

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent diseases commonly treated by inhibiting androgen action. However, androgen ablation or castration fail to target androgen-independent cells implicated in disease etiology and recurrence. Mechanistically different to castration, this study shows beneficial proapoptotic actions of estrogen receptor–β (ERβ) in BPH and PCa. ERβ agonist induces apoptosis in prostatic stromal, luminal and castrate-resistant basal epithelial cells of estrogen-deficient aromatase knock-out mice. This occurs via extrinsic (caspase-8) pathways, without reducing serum hormones, and perturbs the regenerative capacity of the epithelium. TNFα knock-out mice fail to respond to ERβ agonist, demonstrating the requirement for TNFα signaling. In human tissues, ERβ agonist induces apoptosis in stroma and epithelium of xenografted BPH specimens, including in the CD133+enriched putative stem/progenitor cells isolated from BPH-1 cells in vitro. In PCa, ERβ causes apoptosis in Gleason Grade 7 xenografted tissues and androgen-independent cells lines (PC3 and DU145) via caspase-8. These data provide evidence of the beneficial effects of ERβ agonist on epithelium and stroma of BPH, as well as androgen-independent tumor cells implicated in recurrent disease. Our data are indicative of the therapeutic potential of ERβ agonist for treatment of PCa and/or BPH with or without androgen withdrawal.
Crystal structure of the bifunctional proline utilization A flavoenzyme from
Bradyrhizobium japonicum
Authors: Srivastava Dhiraj , Schuermann Jonathan P. , White Tommi A. , Krishnan Navasona , Sanyal Nikhilesh , Hura Greg L. , Tan Anmin , Henzl Michael T. , Becker Donald F. , Tanner John J.
Published: February 2010

The bifunctional proline catabolic flavoenzyme, proline utilization A (PutA), catalyzes the oxidation of proline to glutamate via the sequential activities of FAD-dependent proline dehydrogenase (PRODH) and NAD
+
-dependent Δ
1
-pyrroline-5-carboxylate dehydrogenase (P5CDH) domains. Although structures for some of the domains of PutA are known, a structure for the full-length protein has not previously been solved. Here we report the 2.1 Å resolution crystal structure of PutA from
Bradyrhizobium japonicum
, along with data from small-angle x-ray scattering, analytical ultracentrifugation, and steady-state and rapid-reaction kinetics. PutA forms a ring-shaped tetramer in solution having a diameter of 150 Å. Within each protomer, the PRODH and P5CDH active sites face each other at a distance of 41 Å and are connected by a large, irregularly shaped cavity. Kinetics measurements show that glutamate production occurs without a lag phase, suggesting that the intermediate, Δ
1
-pyrroline-5-carboxylate, is preferably transferred to the P5CDH domain rather than released into the bulk medium. The structural and kinetic data imply that the cavity serves both as a microscopic vessel for the hydrolysis of Δ
1
-pyrroline-5-carboxylate to glutamate semialdehyde and a protected conduit for the transport of glutamate semialdehyde to the P5CDH active site.
Supramolecular design of self-assembling nanofibers for cartilage regeneration
Authors: Shah Ramille N. , Shah Nirav A. , Del Rosario Lim Marc M. , Hsieh Caleb , Nuber Gordon , Stupp Samuel I.
Published: February 2010

Molecular and supramolecular design of bioactive biomaterials could have a significant impact on regenerative medicine. Ideal regenerative therapies should be minimally invasive, and thus the notion of self-assembling biomaterials programmed to transform from injectable liquids to solid bioactive structures in tissue is highly attractive for clinical translation. We report here on a coassembly system of peptide amphiphile (PA) molecules designed to form nanofibers for cartilage regeneration by displaying a high density of binding epitopes to transforming growth factor β-1 (TGFβ-1). Growth factor release studies showed that passive release of TGFβ-1 was slower from PA gels containing the growth factor binding sites. In vitro experiments indicate these materials support the survival and promote the chondrogenic differentiation of human mesenchymal stem cells. We also show that these materials can promote regeneration of articular cartilage in a full thickness chondral defect treated with microfracture in a rabbit model with or even without the addition of exogenous growth factor. These results demonstrate the potential of a completely synthetic bioactive biomaterial as a therapy to promote cartilage regeneration.
Compartmentalization by directional gene expression
Authors: Daube Shirley S. , Bracha Dan , Buxboim Amnon , Bar-Ziv Roy H.
Published: February 2010

The coalescence of basic biochemical reactions into compartments is a major hallmark of a living cell. Using surface-bound DNA and a transcription reaction, we investigate the conditions for boundary-free compartmentalization. The DNA self-organizes into a dense and ordered phase with coding sequences aligned at well-defined distances and orientation relative to the surface, imposing directionality on transcription. Unique to the surface in comparison to dilute homogeneous DNA solution, the reaction slows down early, is inhibited with increased DNA density, is favorable for surface-oriented promoters, and is robust against DNA condensation. We interpret these results to suggest that macromolecules (RNA polymerase and RNA), but not solutes (ions and nucleotides), are partitioned between immobilized DNA and the reservoir. Without any physical barrier, a nonequilibrium directional DNA transaction forms macromolecular gradients that define a compartment, thus offering a boundary-free approach to the assembly of a synthetic cell.
Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure
Authors: Boutaud Olivier , Moore Kevin P. , Reeder Brandon J. , Harry David , Howie Alexander J. , Wang Shuhe , Carney Clare K. , Masterson Tina S. , Amin Taneem , Wright David W. , Wilson Michael T. , Oates John A. , Roberts L. Jackson
Published: February 2010

Hemoproteins, hemoglobin and myoglobin, once released from cells can cause severe oxidative damage as a consequence of heme redox cycling between ferric and ferryl states that generates radical species that induce lipid peroxidation. We demonstrate in vitro that acetaminophen inhibits hemoprotein-induced lipid peroxidation by reducing ferryl heme to its ferric state and quenching globin radicals. Severe muscle injury (rhabdomyolysis) is accompanied by the release of myoglobin that becomes deposited in the kidney, causing renal injury. We previously showed in a rat model of rhabdomyolysis that redox cycling between ferric and ferryl myoglobin yields radical species that cause severe oxidative damage to the kidney. In this model, acetaminophen at therapeutic plasma concentrations significantly decreased oxidant injury in the kidney, improved renal function, and reduced renal damage. These findings also provide a hypothesis for potential therapeutic applications for acetaminophen in diseases involving hemoprotein-mediated oxidative injury.
Development and the evolvability of human limbs
Authors: Young Nathan M. , Wagner Günter P. , Hallgrímsson Benedikt
Published: February 2010

The long legs and short arms of humans are distinctive for a primate, the result of selection acting in opposite directions on each limb at different points in our evolutionary history. This mosaic pattern challenges our understanding of the relationship of development and evolvability because limbs are serially homologous and genetic correlations should act as a significant constraint on their independent evolution. Here we test a developmental model of limb covariation in anthropoid primates and demonstrate that both humans and apes exhibit significantly reduced integration between limbs when compared to quadrupedal monkeys. This result indicates that fossil hominins likely escaped constraints on independent limb variation via reductions to genetic pleiotropy in an ape-like last common ancestor (LCA). This critical change in integration among hominoids, which is reflected in macroevolutionary differences in the disparity between limb lengths, facilitated selection for modern human limb proportions and demonstrates how development helps shape evolutionary change.
Neutrophil spontaneous death is mediated by down-regulation of autocrine signaling through GPCR, PI3Kγ, ROS, and actin
Authors: Xu Yuanfu , Loison Fabien , Luo Hongbo R.
Published: February 2010

Neutrophil spontaneous apoptosis plays a crucial role in neutrophil homeostasis and the resolution of inflammation. We previously established Akt deactivation as a key mediator of this tightly regulated cellular death program. Nevertheless, the molecular mechanisms governing the diminished Akt activation were not characterized. Here, we report that Akt deactivation during the course of neutrophil spontaneous death was a result of reduced PtdIns(3,4,5)P3 level. The phosphatidylinositol lipid kinase activity of PI3Kγ, but not class IA PI3Ks, was significantly reduced during neutrophil death. The production of PtdIns(3,4,5)P3 in apoptotic neutrophils was mainly maintained by autocrinely released chemokines that elicited PI3Kγ activation via G protein–coupled receptors. Unlike in other cell types, serum-derived growth factors did not provide any survival advantage in neutrophils. PI3Kγ, but not class IA PI3Ks, was negatively regulated by gradually accumulated ROS in apoptotic neutrophils, which suppressed PI3Kγ activity by inhibiting an actin-mediated positive feedback loop. Taken together, these results provide insight into the mechanism of neutrophil spontaneous death and reveal a cellular pathway that regulates PtdIns(3,4,5)P3/Akt in neutrophils.
Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration
Authors: Ferris Andrea L. , Wu Xiaolin , Hughes Christina M. , Stewart Claudia , Smith Steven J. , Milne Thomas A. , Wang Gang G. , Shun Ming-Chieh , Allis C. David , Engelman Alan , Hughes Stephen H.
Published: February 2010

Lens epithelium-derived growth factor (LEDGF) fusion proteins can direct HIV-1 DNA integration to novel sites in the host genome. The C terminus of LEDGF contains an integrase binding domain (IBD), and the N terminus binds chromatin. LEDGF normally directs integrations to the bodies of expressed genes. Replacing the N terminus of LEDGF with chromatin binding domains (CBDs) from other proteins changes the specificity of HIV-1 DNA integration. We chose two well-characterized CBDs: the plant homeodomain (PHD) finger from ING2 and the chromodomain from heterochromatin binding protein 1α (HP1α). The ING2 PHD finger binds H3K4me3, a histone mark that is associated with the transcriptional start sites of expressed genes. The HP1α chromodomain binds H3K9me2,3, histone marks that are widely distributed throughout the genome. A fusion protein in which the ING2 PHD finger was linked to the LEDGF IBD directed integrations near the start sites of expressed genes. A similar fusion protein in which the HP1α chromodomain was linked to the LEDGF IBD directed integrations to sites that differed from both the PHD finger fusion–directed and LEDGF-directed integration sites. The ability to redirect HIV-1 DNA integration may help solve the problems associated with the activation of oncogenes when retroviruses are used in gene therapy.
Structure of
Vibrio cholerae
ToxT reveals a mechanism for fatty acid regulation of virulence genes
Authors: Lowden Michael J. , Skorupski Karen , Pellegrini Maria , Chiorazzo Michael G. , Taylor Ronald K. , Kull F. Jon
Published: February 2010

Cholera is an acute intestinal infection caused by the bacterium
Vibrio cholerae
. In order for
V. cholerae
to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 Å resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid,
cis
-palmitoleate. The finding that
cis
-palmitoleic acid reduces TCP and CT expression in
V. cholerae
and prevents ToxT from binding to DNA in vitro provides a direct link between the host environment of
V. cholerae
and regulation of virulence gene expression.
Predicting strength and function for promoters of the
Escherichia coli
alternative sigma factor,
σ
E
Authors: Rhodius Virgil A. , Mutalik Vivek K.
Published: February 2010

Sequenced bacterial genomes provide a wealth of information but little understanding of transcriptional regulatory circuits largely because accurate prediction of promoters is difficult. We examined two important issues for accurate promoter prediction: (1) the ability to predict promoter strength and (2) the sequence properties that distinguish between active and weak/inactive promoters. We addressed promoter prediction using natural core promoters recognized by the well-studied alternative sigma factor,
Escherichia coli
σ
E
, as a representative of group 4 
σ
s, the largest
σ
group. To evaluate the contribution of sequence to promoter strength and function, we used modular position weight matrix models comprised of each promoter motif and a penalty score for suboptimal motif location. We find that a combination of select modules is moderately predictive of promoter strength and that imposing minimal motif scores distinguished active from weak/inactive promoters. The combined -35/-10 score is the most important predictor of activity. Our models also identified key sequence features associated with active promoters. A conserved “AAC” motif in the -35 region is likely to be a general predictor of function for promoters recognized by group 4 
σ
s. These results provide valuable insights into sequences that govern promoter strength, distinguish active and inactive promoters for the first time, and are applicable to both in vivo and in vitro measures of promoter strength.
Apurinic/apyrimidinic endonuclease APE1 is required for PACAP-induced neuroprotection against global cerebral ischemia
Authors: Stetler R. Anne , Gao Yanqin , Zukin R. Suzanne , Vosler Peter S. , Zhang Lili , Zhang Feng , Cao Guodong , Bennett Michael V. L. , Chen Jun
Published: February 2010

Inducible DNA repair via the base-excision repair pathway is an important prosurvival mechanism activated in response to oxidative DNA damage. Elevated levels of the essential base-excision repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor-1 correlate closely with neuronal survival against ischemic insults, depending on the CNS region, protective treatments, and degree of insult. However, the precise mechanisms by which this multifunctional protein affords protection and is activated by upstream signaling pathways in postischemic neurons are not well delineated. Here we show that intracerebral administration of pituitary adenylate cyclase-activating polypeptide (PACAP), an endogenously occurring small neuropeptide, induces expression of APE1 in hippocampal neurons. Induction of APE1 expression requires PKA- and p38-dependent phosphorylation of cAMP response-element binding and activating transcription factor 2, which leads to transactivation of the APE1 promoter. We further show that PACAP markedly reduces oxidative DNA stress and hippocampal CA1 neuronal death following transient global ischemia. These effects occurred, at least in part, via enhanced APE1 expression. Furthermore, the DNA repair function of APE1 was required for PACAP-mediated neuroprotection. Thus, induction of DNA repair enzymes may be a unique strategy for neuroprotection against hippocampal injury.
Disruption of the
Lcn2
gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis
Authors: Berger Thorsten , Cheung Carol C. , Elia Andrew J. , Mak Tak W.
Published: February 2010

Based largely on studies in xenograft models, lipocalin-2 (Lcn2) has been implicated in the progression of multiple types of human tumors, including breast cancer. Here we examine the role of Lcn2 in mammary tumorigenesis and lung metastasis using an in vivo molecular genetics approach. We crossed a well-characterized transgenic mouse model of breast cancer, the MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mouse, with two independent gene-targeted Lcn2
−/−
mouse strains of the 129/Ola or C57BL/6 genetic background. The onset and progression of mammary tumor development and lung metastasis in the female progeny of these crosses were monitored over a 20-week period. Female Lcn2
−/−
MMTV-PyMT mice of the 129/Ola background (Lcn2
−/−
PyMT
129
) showed delayed onset of mammary tumors, and both Lcn2
−/−
PyMT
129
mice and Lcn2
−/−
MMTV-PyMT mice of the C57BL/6 background (Lcn2
−/−
PyMT
B6
) exhibited significant decreases in multiplicity and tumor burden (∼2- to 3-fold), as measured by total tumor weight and volume. At the molecular level, mammary tumors derived from Lcn2
−/−
PyMT
B6
females showed reduced matrix metalloproteinase-9 (MMP-9) activity and a lack of high molecular weight MMP activity. However, although increased MMP-9 activity has been linked to tumor progression, neither Lcn2
−/−
PyMT
B6
nor Lcn2
−/−
PyMT
129
female mice showed a reduction in lung metastases compared to Lcn2
+/+
PyMT controls. Our results demonstrate, using an in vivo animal model approach, that Lcn2 is a potent inducer of mammary tumor growth but not a significant promoter of lung metastasis.
Proliferation of aneuploid human cells is limited by a p53-dependent mechanism
Authors: Thompson Sarah L. , Compton Duane A.
Published: February 2010

Most solid tumors are aneuploid, and it has been proposed that aneuploidy is the consequence of an elevated rate of chromosome missegregation in a process called chromosomal instability (CIN). However, the relationship of aneuploidy and CIN is unclear because the proliferation of cultured diploid cells is compromised by chromosome missegregation. The mechanism for this intolerance of nondiploid genomes is unknown. In this study, we show that in otherwise diploid human cells, chromosome missegregation causes a cell cycle delay with nuclear accumulation of the tumor suppressor p53 and the cyclin kinase inhibitor p21. Deletion of the p53 gene permits the accumulation of nondiploid cells such that CIN generates cells with aneuploid genomes that resemble many human tumors. Thus, the p53 pathway plays an important role in limiting the propagation of aneuploid human cells in culture to preserve the diploid karyotype of the population. These data fit with the concordance of aneuploidy and disruption of the p53 pathway in many tumors, but the presence of aneuploid cells in some normal human and mouse tissues indicates that there are known exceptions to the involvement of p53 in aneuploid cells and that tissue context may be important in how cells respond to aneuploidy.
Autonomous right-screw rotation of growth cone filopodia drives neurite turning
Authors: Tamada Atsushi , Kawase Satoshi , Murakami Fujio , Kamiguchi Hiroyuki
Published: February 2010

The direction of neurite elongation is controlled by various environmental cues. However, it has been reported that even in the absence of any extrinsic directional signals, neurites turn clockwise on two-dimensional substrates. In this study, we have discovered autonomous rotational motility of the growth cone, which provides a cellular basis for inherent neurite turning. We have developed a technique for monitoring three-dimensional motility of growth cone filopodia and demonstrate that an individual filopodium rotates on its own longitudinal axis in the right-screw direction from the viewpoint of the growth cone body. We also show that the filopodial rotation involves myosins Va and Vb and may be driven by their spiral interactions with filamentous actin. Furthermore, we provide evidence that the unidirectional rotation of filopodia causes deflected neurite elongation, most likely via asymmetric positioning of the filopodia onto the substrate. Although the growth cone itself has been regarded as functionally symmetric, our study reveals the asymmetric nature of growth cone motility.
Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
Authors: Schilte Clémentine , Couderc Thérèse , Chretien Fabrice , Sourisseau Marion , Gangneux Nicolas , Guivel-Benhassine Florence , Kraxner Anton , Tschopp Jürg , Higgs Stephen , Michault Alain , Arenzana-Seisdedos Fernando , Colonna Marco , Peduto Lucie , Schwartz Olivier , Lecuit Marc , Albert Matthew L.
Published: February 2010

Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. As viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type I interferon (IFN) in CHIKV pathogenesis. Based on human studies and mouse experimentation, we show that CHIKV does not directly stimulate type I IFN production in immune cells. Instead, infected nonhematopoietic cells sense viral RNA in a Cardif-dependent manner and participate in the control of infection through their production of type I IFNs. Although the Cardif signaling pathway contributes to the immune response, we also find evidence for a MyD88-dependent sensor that is critical for preventing viral dissemination. Moreover, we demonstrate that IFN-α/β receptor (IFNAR) expression is required in the periphery but not on immune cells, as IFNAR−/−→WT bone marrow chimeras are capable of clearing the infection, whereas WT→IFNAR−/− chimeras succumb. This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV.
Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I
Authors: Puel Anne , Döffinger Rainer , Natividad Angels , Chrabieh Maya , Barcenas-Morales Gabriela , Picard Capucine , Cobat Aurélie , Ouachée-Chardin Marie , Toulon Antoine , Bustamante Jacinta , Al-Muhsen Saleh , Al-Owain Mohammed , Arkwright Peter D. , Costigan Colm , McConnell Vivienne , Cant Andrew J. , Abinun Mario , Polak Michel , Bougnères Pierre-François , Kumararatne Dinakantha , Marodi László , Nahum Amit , Roifman Chaim , Blanche Stéphane , Fischer Alain , Bodemer Christine , Abel Laurent , Lilic Desa , Casanova Jean-Laurent
Published: February 2010

Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-γ, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1β, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-β, tumor necrosis factor [α], or transforming growth factor β). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.