bluuebunny/crossref_metadata_2025 huggingface dataset:
Edge effects in some perturbations of the Gaussian unitary ensemble
Authors: Bassler K. E. , Forrester P. J. , Frankel N. E.
Published: December 2010

A bordering of Gaussian unitary ensemble matrices is considered, in which the bordered row consists of zero mean complex Gaussians N[0, σ/2] + iN[0, σ/2] off the diagonal and the real Gaussian N \documentclass[12pt]{minimal}\begin{document}$[\mu ,\sigma /\sqrt{2}]$\end{document}[μ,σ/2] on the diagonal. We compute the explicit form of the eigenvalue probability function for such matrices as well as that for matrices obtained by repeating the bordering. The correlations are in general determinantal, and in the single bordering case the explicit form of the correlation kernel is computed. In the large N limit it is shown that μ and/or σ can be tuned to induce a separation of the largest eigenvalue. This effect is shown to be controlled by a single parameter, universal correlation kernel.
Curvature function and coarse graining
Authors: Díaz-Marín Homero , Zapata José A.
Published: December 2010

A classic theorem in the theory of connections on principal fiber bundles states that the evaluation of all holonomy functions gives enough information to characterize the bundle structure (among those sharing the same structure group and base manifold) and the connection up to a bundle equivalence map. This result and other important properties of holonomy functions have encouraged their use as the primary ingredient for the construction of families of quantum gauge theories. However, in these applications often the set of holonomy functions used is a discrete proper subset of the set of holonomy functions needed for the characterization theorem to hold. We show that the evaluation of a discrete set of holonomy functions does not characterize the bundle and does not constrain the connection modulo gauge appropriately. We exhibit a discrete set of functions of the connection and prove that in the abelian case their evaluation characterizes the bundle structure (up to equivalence), and constrains the connection modulo gauge up to “local details” ignored when working at a given scale. The main ingredient is the Lie algebra valued curvature function \documentclass[12pt]{minimal}\begin{document}$F_S (A)$\end{document}FS(A) defined below. It covers the holonomy function in the sense that \documentclass[12pt]{minimal}\begin{document}$\exp {F_S (A)} = {\rm Hol}(l= \partial S , A)$\end{document}expFS(A)= Hol (l=∂S,A).
Particle-diameter dependence of the coercive field in FePt nanoparticles with a face-centered tetragonal structure
Authors: Mito M. , Komorida Y. , Silva N. J. O. , Tsuruda H. , Deguchi H. , Takagi S. , Tajiri T. , Iwamoto T. , Kitamoto Y.
Published: December 2010

It has recently been reported that, in FePt nanoparticles (NPs) protected by poly(N-vinyl-2-pyrrolidone) (PVP), which possess a particle diameter (D) near the critical size (2–3 nm) for the emergence of the face-centered tetragonal (fct) structure, the coercive field (Hc) at room temperature increases with increasing D, whereas the Hc value below 10 K increases with decreasing D. We investigated the fct-ordering parameter (S) for PVP-coated FePt NPs with three mean D values (=2.0, 2.6, and 3.4 nm) in order to gain a better insight into the unique behavior of Hc. Furthermore, the temperature dependencies of Hc, saturation magnetization (Ms), and their product (HcMs) were also investigated. The behavior of Hc at high temperature is attributed to the decrease in the magnetic switching volume (V), while the enhancement of Hc at low temperatures with decreasing D is thought to originate from the decrease in the saturation magnetization, Ms, with decreasing D. The decrease in Ms with decreasing D is related to the decrease in the fct-ordering.
Design concepts of terahertz quantum cascade lasers: Proposal for terahertz laser efficiency improvements
Authors: Kubis Tillmann , Mehrotra Saumitra Raj , Klimeck Gerhard
Published: December 2010

Conceptual disadvantages of typical resonant phonon terahertz quantum cascade lasers (THz-QCLs) are analyzed. Alternative designs and their combination within a concrete device proposal are discussed to improve the QCL performance. The improvements are (1) indirect pumping of the upper laser level, (2) diagonal optical transitions, (3) complete electron thermalization, and (4) materials with low effective electron masses. The nonequilibrium Green’s function method is applied to predict stationary electron transport and optical gain. The proposed THz-QCL shows a higher optical gain, a lower threshold current, and a higher operation temperature. Alloy disorder scattering can worsen the QCL performance.
First-principles study of metal–graphene interfaces
Authors: Gong Cheng , Lee Geunsik , Shan Bin , Vogel Eric M. , Wallace Robert M. , Cho Kyeongjae
Published: December 2010

Metal-graphene contact is a key interface in graphene-based device applications, and it is known that two types of interfaces are formed between metal and graphene. In this paper, we apply first-principles calculations to twelve metal-graphene interfaces and investigate the detailed interface atomic and electronic structures of physisorption and chemisorption interfaces. For physisorption interfaces (Ag, Al, Cu, Cd, Ir, Pt, and Au), Fermi level pinning and Pauli-exclusion-induced energy-level shifts are shown to be two primary factors determining graphene’s doping types and densities. For chemisorption interfaces (Ni, Co, Ru, Pd, and Ti), the combination of Pauli-exclusion-induced energy-level shifts and hybridized states’ repulsive interactions lead to a band gap opening with metallic gap states. For practical applications, we show that external electric field can be used to modulate graphene’s energy-levels and the corresponding control of doping or energy range of hybridization.
Study of composition dependent structural, optical, and magnetic properties of Cu-doped Zn1−xCdxS nanoparticles
Authors: Chawla Amit Kumar , Singhal Sonal , Nagar Sandeep , Gupta Hari Om , Chandra Ramesh
Published: December 2010

Cu-doped Zn1−xCdxS nanoparticles were synthesized by coprecipitation technique in ice bath at 280 K. The band gap energy of Zn1−xCdxS:Cu nanoparticles can be tuned to a lower energy by increasing the Cd content, indicating the formation of the alloyed nanoparticles. The alloy structure is further supported by the systematic shifting of characteristic x-ray diffraction peaks to lower angles with increase in Cd content. Systematic copper doping induces a red shift in the energy band gap of Zn0.9Cd0.1S:Cu nanoparticles with increase in copper concentration. Cu-doped Zn0.9Cd0.1S nanoparticles were found to have ferromagnetic nature at 5 K whereas undoped particles were found to be diamagnetic. Green luminescence further proves proper doping of Cu into the ZnCdS matrix. It is believed that the green luminescence originates from the recombination between the shallow donor level (sulfur vacancy) and the t2 level of Cu2+. This method provides an inexpensive and simple procedure to produce ternary ZnCdS:Cu nanoparticles with tunable optical properties via changing Cd and/or Cu concentrations.
Determining phonon deformation potentials of hexagonal GaN with stress modulation
Authors: Lu Jun-Yong , Wang Zhi-Jia , Deng Dong-Mei , Wang Yong , Chen Kevin Jing , Lau Kei-May , Zhang Tong-Yi
Published: December 2010

In this work, phonon deformation potentials for E2H and A1(LO) phonons of epitaxial hexagonal GaN thin films grown by metalorganic chemical vapor deposition on Si (111) substrate were precisely determined with a stress modulation method, which was achieved via coin-shaped patterning of an originally flat film. By changing the size of patterned coin-shaped islands, the original biaxial stress in the flat film was reduced to different levels at the island centers, which was analyzed by finite element calculations. The proposed stress modulation method allows one to carry out a large number of Raman scattering tests, thereby leading to reliable results. With this method, the Raman biaxial pressure coefficients of E2H and A1(LO) phonons of GaN were determined to be 4.47 cm−1/GPa and 2.76 cm−1/GPa, respectively.
Size-dependent structural preferences and magnetization enhancement in 0.5Bi0.8La0.2FeO3–0.5PbTiO3
Authors: Wei T. , Liu H. M. , Zhu C. , Guo Y. J. , Liu J.-M. , Wu Y. J. , Chen X. M.
Published: December 2010

The 0.5Bi0.8La0.2FeO3–0.5PbTiO3 (BLF-PT) solid solution nanoparticles of different particle sizes are prepared using sol-gel method and characterized in terms of the size-dependent crystal structure, Raman scattering, dielectric susceptibility, and magnetism. Upon decreasing particle size, the crystal structure evolves from tetragonal symmetry to rhombohedral one, and a substantial enhancement of magnetization is observed. These size-dependent effects are reasonably explained by a simple thermodynamic scenario and first-principles calculation based on the BLF-PT multilayer model.
Inclined dislocation arrays in AlGaN/AlGaN quantum well structures emitting at 290 nm
Authors: Chang T. Y. , Moram M. A. , McAleese C. , Kappers M. J. , Humphreys C. J.
Published: December 2010

We report on the structural and optical properties of deep ultraviolet emitting AlGaN/AlGaN multiple quantum wells (MQWs) grown on (0001) sapphire by metal-organic vapor phase epitaxy using two different buffer layer structures, one containing a thin (1 μm) AlN layer combined with a GaN interlayer and the other a thick (4 μm) AlN layer. Transmission electron microscopy analysis of both structures showed inclined arrays of dislocations running through the AlGaN layers at an angle of ∼30°, originating at bunched steps at the AlN surface and terminating at bunched steps at the surface of the MQW structure. In all layers, these inclined dislocation arrays are surrounded by AlGaN with a relatively higher Ga content, consistent with plan-view cathodoluminescence maps in which the bunched surface steps are associated with longer emission wavelengths. The structure with the 4 μm-thick AlN buffer layer had a dislocation density lower by a factor of 2 (at (1.7±0.1)×109 cm−2) compared to the structure with the 1 μm thick AlN buffer layer, despite the presence of the inclined dislocation arrays.
Origin of magnetism in La and Fe doped SrTiO3−δ films
Authors: Egilmez M. , Leung G. W. , Hakimi A. M. H. R. , Blamire M. G.
Published: December 2010

We have studied the magnetic and electrical properties of LaySr1−yTi0.9Fe0.1O3−δ films for compositions where y=0, 0.2, 0.5, and 0.7. All the films exhibited room temperature ferromagnetism with a magnetic moment ranging from 0.7 μB/Fe to 0.2 μB/Fe. The SrTi0.9Fe0.1O3−δ (y=0) sample is an insulator with a small polaron like temperature dependence of resistivity. On the other hand y=0.2 and y=0.5 films exhibited a metallic type of resistivity which can be described by a power law. The largest magnetic moment was observed in the most resistive member (y=0) of the LaySr1−yTi0.9Fe0.1O3−δ family. This is in contrast to the carrier mediated magnetism models. The origin of the magnetism in highly resistive y=0 film could be attributed to the mixed valence state of Fe. On the other hand, La doped sample (y>0) exhibited features of carrier mediated magnetism as well as the mixed valence magnetism. The origin of the observed magnetism in all films has been discussed.
Ge instability and the growth of Ge epitaxial layers in nanochannels on patterned Si (001) substrates
Authors: Wang G. , Rosseel E. , Loo R. , Favia P. , Bender H. , Caymax M. , Heyns M. M. , Vandervorst W.
Published: December 2010

We report the Ge thermal instability against surface diffusion in extremely narrow channels isolated by SiO2 and demonstrate the selective growth of strain-relaxed Ge epitaxial layers in channels as narrow as 10 nm on patterned Si (001) substrates by a combination of low temperature growth and selective recrystallization using Ge melt and regrowth during a millisecond laser anneal. Filling narrow channels at high growth temperatures is prohibited by Ge outdiffusion due to the high Ge chemical potential in such narrow channels. The Ge thermal instability depends on the channel width and a critical channel width of 50 nm is extracted from our calculation and experimental results. The Ge surface diffusion rate is dominated by the surface diffusion activation energy barrier that is significantly enhanced by the adsorbed surface hydrides. At a low temperature below 450 °C, a hydride-terminated surface is maintained which increases the Ge surface diffusion barrier and retards the outdiffusion of the Ge adatoms, providing excellent channel filling. The resulting low crystalline quality can be restored with a millisecond laser melt and regrowth.
Saturation of absorption in noble metal doped nanocomposite glass film excited by evanescent light field
Authors: Corbari Costantino , Beresna Martynas , Kazansky Peter G.
Published: December 2010

A leaky-waveguide configuration is proposed for saturable absorbers. Evanescent field interaction between the leaky-mode and the absorber layer reduces material degradation at high power levels while providing control over the interaction length and thus the modulation strength and nonsaturable losses simply by tuning the coupling angle around the resonance of the leaky-mode. This concept was applied to a sol-gel silicon-dioxide glass film doped with gold nanoparticles. Saturation of the surface plasmon resonance absorption was demonstrated with modulation depths of up to 34% achieved.
Three-dimensional microcoils as terahertz metamaterial with electric and magnetic response
Authors: Waselikowski Stefan , Kratt Kai , Badilita Vlad , Wallrabe Ulrike , Korvink Jan G. , Walther Markus
Published: December 2010

A metamaterial consisting of three-dimensional submillimeter solenoidal coils is presented. The structures have been fabricated by an automated wire-bonding technique and are characterized by terahertz time-domain spectroscopy and numerical simulations. We demonstrate the excitation of electric and magnetic resonances in the microcoils at frequencies between 0.05 and 0.6 THz. The implementation of these microstructures provides a promising route for the design of nonplanar and intrinsically chiral metamaterials for gigahertz to terahertz frequencies.
Single-electron transfer between two donors in nanoscale thin silicon-on-insulator field-effect transistors
Authors: Hamid Earfan , Moraru Daniel , Tarido Juli Cha , Miki Sakito , Mizuno Takeshi , Tabe Michiharu
Published: December 2010

We describe single-electron transfer between two donors in thin silicon-on-insulator field-effect transistors with phosphorus-doped channel. At low temperatures, single-electron tunneling through one donor can be identified in source-drain current/gate voltage measurements as a single current peak. On this peak, we observed hysteresis most likely as a signature of single-electron transfer with another donor. The origin of single-electron transfer is related to different intensities of coupling between each donor and the interface, as evidenced from simulations. It was found that donor-interface coupling is essential for the energetic transfer of a single-electron location within the two-donor system.
Photovoltage bleaching in bulk heterojunction solar cells through population of the singlet exciton
Authors: Shah H. M. , Mohite A. D. , Bansal T. , Alphenaar B. W.
Published: December 2010

The effect of illumination by a tunable light source on the open circuit voltage of a poly[2-methoxy-5-(3,7-dimethyloctyloxy)]-1,4-phenylenevinylene (MDMO-PPV): [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) bulk heterojunction solar cell is measured. Illumination at the energy of the PCBM ground state singlet exciton causes a sharp decrease in the photovoltage, while illumination at the MDMO-PPV exciton produces no change. Capacitive photocurrent spectroscopy reveals that the charge dissociated from the PCBM exciton is large despite the small photovoltage signal. This implies that polarons generated by the below gap excitation promote recombination of the above gap photoexcited charge.
Control of defect-mediated tunneling barrier heights in ultrathin MgO films
Authors: Kim D. J. , Choi W. S. , Schleicher F. , Shin R. H. , Boukari S. , Davesne V. , Kieber C. , Arabski J. , Schmerber G. , Beaurepaire E. , Jo W. , Bowen M.
Published: December 2010

The impact of oxygen vacancies on local tunneling properties across rf-sputtered MgO thin films was investigated by optical absorption spectroscopy and conducting atomic force microscopy. Adding O2 to the Ar plasma during MgO growth alters the oxygen defect populations, leading to improved local tunneling characteristics such as a lower density of current hotspots and a lower tunnel current amplitude. We discuss a defect-based potential landscape across ultrathin MgO barriers.
Hole injection and efficiency droop improvement in InGaN/GaN light-emitting diodes by band-engineered electron blocking layer
Authors: Wang C. H. , Ke C. C. , Lee C. Y. , Chang S. P. , Chang W. T. , Li J. C. , Li Z. Y. , Yang H. C. , Kuo H. C. , Lu T. C. , Wang S. C.
Published: December 2010

A graded-composition electron blocking layer (GEBL) with aluminum composition increasing along the [0001] direction was designed for c-plane InGaN/GaN light-emitting diodes (LEDs) by employing the band-engineering. The simulation results demonstrated that such GEBL can effectively enhance the capability of hole transportation across the EBL as well as the electron confinement. Consequently, the LED with GEBL grown by metal-organic chemical vapor deposition exhibited lower forward voltage and series resistance and much higher output power at high current density as compared to conventional LED. Meanwhile, the efficiency droop was reduced from 34% in conventional LED to only 4% from the maximum value at low injection current to 200 A/cm2.
Interface formation between tris(8-hydroxyquinoline) aluminum and ZnO nanowires and film
Authors: Lee Jung Han , Shin Jeong Ho , Song Jae Yong , Yi Yeonjin
Published: December 2010

The energy level alignments at the interface between tris(8-hydroxyquinoline) aluminum (Alq3) and ZnO nanowires and thin film were studied with in situ x-ray and ultraviolet photoemission spectroscopy. The changes of work functions, highest occupied molecular orbitals, and core levels were measured with step-by-step deposition of Alq3 on each ZnO substrate. Although both substrates show similar electronic structures, a larger interface dipole is induced at the interface between Alq3 and ZnO nanowires. This results in the reduction of the electron injection barrier at the interface of Alq3/ZnO nanowires. Thus, the ZnO nanowire substrate is expected to show better performance than that of ZnO film when used as a cathode. We discussed the different interface dipole formation at each interface.
Current-driven domain wall motion across a wide temperature range in a (Ga,Mn)(As,P) device
Authors: Wang K. Y. , Edmonds K. W. , Irvine A. C. , Tatara G. , De Ranieri E. , Wunderlich J. , Olejnik K. , Rushforth A. W. , Campion R. P. , Williams D. A. , Foxon C. T. , Gallagher B. L.
Published: December 2010

Current-driven magnetic domain wall motion is demonstrated in the quaternary ferromagnetic semiconductor (Ga,Mn)(As,P) at temperatures well below the ferromagnetic transition temperature, with critical currents of the order 105 A cm−2. This is enabled by a much weaker domain wall pinning compared to (Ga,Mn)As layers grown on a strain-relaxed buffer layer. The critical current is shown to be comparable with theoretical predictions. The wide temperature range over which domain wall motion can be achieved indicates that this is a promising system for developing an improved understanding of spin-transfer torque in systems with strong spin-orbit interaction.
Nonradiative energy transfer between vertically coupled indirect and direct bandgap InAs quantum dots
Authors: Shamirzaev Timur S. , Abramkin Demid S. , Dmitriev Dmitry V. , Gutakovskii Anton K.
Published: December 2010

Nonradiative energy transfer from indirect bandgap InAs/AlAs quantum dots (QDs) to direct bandgap InAs/AlGaAs QDs was studied by steady-state and transient photoluminescence. We demonstrate that long excitonic lifetime in donor InAs/AlAs QDs allows one to extend the efficient exciton energy transfer between coupled QDs to distances up to 9 nm.
Coherent heteroepitaxy of Bi2Se3 on GaAs (111)B
Authors: Richardella A. , Zhang D. M. , Lee J. S. , Koser A. , Rench D. W. , Yeats A. L. , Buckley B. B. , Awschalom D. D. , Samarth N.
Published: December 2010

We report the heteroepitaxy of single crystal thin films of Bi2Se3 on the (111)B surface of GaAs by molecular beam epitaxy. We find that Bi2Se3 grows highly c-axis oriented, with an atomically sharp interface with the GaAs substrate. By optimizing the growth of a very thin GaAs buffer layer before growing the Bi2Se3, we demonstrate the growth of thin films with atomically flat terraces over hundreds of nanometers. Initial time-resolved Kerr rotation measurements herald opportunities for probing coherent spin dynamics at the interface between a candidate topological insulator and a large class of GaAs-based heterostructures.
Sorting receptor Rer1 controls surface expression of muscle acetylcholine receptors by ER retention of unassembled α-subunits
Authors: Valkova Christina , Albrizio Marina , Röder Ira V. , Schwake Michael , Betto Romeo , Rudolf Rüdiger , Kaether Christoph
Published: December 2010

The nicotinic acetylcholine receptor of skeletal muscle is composed of five subunits that are assembled in a stepwise manner. Quality control mechanisms ensure that only fully assembled receptors reach the cell surface. Here, we show that Rer1, a putative Golgi-ER retrieval receptor, is involved in the biogenesis of acetylcholine receptors. Rer1 is expressed in the early secretory pathway in the myoblast line C2C12 and in mouse skeletal muscle, and up-regulated during myogenesis. Upon down-regulation of Rer1 in C2C12 cells, unassembled acetylcholine receptor α-subunits escape from the ER and are transported to the plasma membrane and lysosomes, where they are degraded. As a result, the amount of fully assembled receptor at the cell surface is reduced. In vivo Rer1 knockdown and genetic inactivation of one Rer1 allele lead to significantly smaller neuromuscular junctions in mice. Our data show that Rer1 is a functionally important unique factor that controls surface expression of muscle acetylcholine receptors by localizing unassembled α-subunits to the early secretory pathway.
Finding undetected protein associations in cell signaling by belief propagation
Authors: Bailly-Bechet M. , Borgs C. , Braunstein A. , Chayes J. , Dagkessamanskaia A. , François J.-M. , Zecchina R.
Published: December 2010

External information propagates in the cell mainly through signaling cascades and transcriptional activation, allowing it to react to a wide spectrum of environmental changes. High-throughput experiments identify numerous molecular components of such cascades that may, however, interact through unknown partners. Some of them may be detected using data coming from the integration of a protein–protein interaction network and mRNA expression profiles. This inference problem can be mapped onto the problem of finding appropriate optimal connected subgraphs of a network defined by these datasets. The optimization procedure turns out to be computationally intractable in general. Here we present a new distributed algorithm for this task, inspired from statistical physics, and apply this scheme to alpha factor and drug perturbations data in yeast. We identify the role of the COS8 protein, a member of a gene family of previously unknown function, and validate the results by genetic experiments. The algorithm we present is specially suited for very large datasets, can run in parallel, and can be adapted to other problems in systems biology. On renowned benchmarks it outperforms other algorithms in the field.
Illusory motion perception in blindsight
Authors: Azzopardi Paul , Hock Howard S.
Published: December 2010

Motion detection is typically spared in blindsight, which results from damage to the striate cortex (area V1) of the brain that is sufficient to eliminate conscious visual awareness and severely reduce sensitivity to luminance contrast, especially for high spatial and low temporal frequencies. Here we show that the discrimination of motion direction within cortically blind fields is not attributable to feature tracking (the detection of changes in position or shape), but is due instead to the detection of first-order motion energy (spatiotemporal changes in luminance). The key to this finding was a version of the line motion illusion entailing reverse-phi motion in which opposing motion directions are simultaneously cued by motion energy and changes in stimulus shape. In forced-choice tests, a blindsighted test subject selected the direction cued by shape change when the stimulus was presented in his intact field, but reliably selected the direction cued by motion energy when the same stimulus was presented in his blind field, where relevant position information was either inaccessible or invalid. Motion energy has been characterized as objectless, so reliance on motion energy detection is consistent with impaired access to shape information in blindsight. The dissociation of motion direction by visual field (cortically blind vs. intact) provides evidence that two pathways from the retina to MT/V5 (the cortical area specialized for motion perception) are functionally distinct: the retinogeniculate pathway through V1 is specialized for feature-based motion perception, whereas the retinocollicular pathway, which bypasses V1, is specialized for detecting motion energy.
Egr1 mediates p53-independent c-Myc–induced apoptosis via a noncanonical ARF-dependent transcriptional mechanism
Authors: Boone David N. , Qi Ying , Li Zhaoliang , Hann Stephen R.
Published: December 2010

c-Myc is frequently deregulated in human cancers. Although deregulated c-Myc leads to tumor growth, it also triggers apoptosis in partnership with tumor suppressors such as ARF and p53. Apoptosis induced by c-Myc is a critical fail-safe mechanism for the cell to protect against unrestrained proliferation. Despite the plethora of information on c-Myc, the molecular mechanism of how c-Myc induces both transformation and apoptosis is unclear. Oncogenic c-Myc can indirectly induce the expression of the tumor suppressor ARF, which leads to apoptosis through the stabilization of p53, but both c-Myc and ARF have apoptotic activities that are independent of p53. In cells without p53, ARF directly binds to c-Myc protein and inhibits c-Myc–induced hyperproliferation and transformation with a concomitant inhibition of canonical c-Myc target gene induction. However, ARF is an essential cofactor for p53-independent c-Myc–induced apoptosis. Here we show that ARF is necessary for c-Myc to drive transcription of a unique noncanonical target gene,
Egr1
. In contrast, c-Myc induces another family member,
Egr2
, through a canonical mechanism that is inhibited by ARF. We further demonstrate that Egr1 is essential for p53-independent c-Myc–induced apoptosis, but not ARF-independent c-Myc–induced apoptosis. Therefore, ARF binding switches the inherent activity of c-Myc from a proliferative to apoptotic protein without p53 through a unique noncanonical transcriptional mechanism. These findings also provide evidence that cofactors can differentially regulate specific transcriptional programs of c-Myc leading to different biological outcomes.
Engineered
Saccharomyces cerevisiae
capable of simultaneous cellobiose and xylose fermentation
Authors: Ha Suk-Jin , Galazka Jonathan M. , Rin Kim Soo , Choi Jin-Ho , Yang Xiaomin , Seo Jin-Ho , Louise Glass N. , Cate Jamie H. D. , Jin Yong-Su
Published: December 2010

The use of plant biomass for biofuel production will require efficient utilization of the sugars in lignocellulose, primarily glucose and xylose. However, strains of
Saccharomyces cerevisiae
presently used in bioethanol production ferment glucose but not xylose. Yeasts engineered to ferment xylose do so slowly, and cannot utilize xylose until glucose is completely consumed. To overcome these bottlenecks, we engineered yeasts to coferment mixtures of xylose and cellobiose. In these yeast strains, hydrolysis of cellobiose takes place inside yeast cells through the action of an intracellular β-glucosidase following import by a high-affinity cellodextrin transporter. Intracellular hydrolysis of cellobiose minimizes glucose repression of xylose fermentation allowing coconsumption of cellobiose and xylose. The resulting yeast strains, cofermented cellobiose and xylose simultaneously and exhibited improved ethanol yield when compared to fermentation with either cellobiose or xylose as sole carbon sources. We also observed improved yields and productivities from cofermentation experiments performed with simulated cellulosic hydrolyzates, suggesting this is a promising cofermentation strategy for cellulosic biofuel production. The successful integration of cellobiose and xylose fermentation pathways in yeast is a critical step towards enabling economic biofuel production.
Nonspecific binding limits the number of proteins in a cell and shapes their interaction networks
Authors: Johnson Margaret E. , Hummer Gerhard
Published: December 2010

Multicellular organisms, from
Caenorhabditis elegans
to humans, have roughly the same number of protein encoding genes. We show that the need to prevent disease-causing nonspecific interactions between proteins provides a simple physical reason why organism complexity is not reflected in the number of distinct proteins. By collective evolution of the amino acid sequences of protein binding interfaces we estimate the degree of misbinding as a function of the number of distinct proteins. Protein interaction energies are calculated with an empirical, residue-specific energy function tuned for protein binding. We show that the achievable energy gap favoring specific over nonspecific binding decreases with protein number in a power-law fashion. From the fraction of proteins involved in nonspecific complexes as a function of increasing protein number and decreasing energy gap, we predict the limits these binding requirements place on the number of different proteins that can function effectively in a given cellular compartment. Remarkably, the optimization of binding interfaces favors networks in which a few proteins have many partners, and most proteins have few partners, consistent with a scale-free network topology. We conclude that nonspecific binding adds to the evolutionary pressure to develop scale-free protein–protein interaction networks.
Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer
Authors: Hayakawa Yoku , Hirata Yoshihiro , Nakagawa Hayato , Sakamoto Kei , Hikiba Yohko , Kinoshita Hiroto , Nakata Wachiko , Takahashi Ryota , Tateishi Keisuke , Tada Motohisa , Akanuma Masao , Yoshida Haruhiko , Takeda Kohsuke , Ichijo Hidenori , Omata Masao , Maeda Shin , Koike Kazuhiko
Published: December 2010

Mitogen-activated protein kinase (MAPK) pathways regulate multiple cellular functions and are highly active in many types of human cancers. Apoptosis signal-regulating kinase 1 (ASK1) is an upstream MAPK involved in apoptosis, inflammation, and carcinogenesis. This study investigated the role of ASK1 in the development of gastric cancer. In human gastric cancer specimens, we observed increased ASK1 expression, compared to nontumor epithelium. Using a chemically induced murine gastric tumorigenesis model, we observed increased tumor ASK1 expression, and ASK1 knockout mice had both fewer and smaller tumors than wild-type (WT) mice. ASK1 siRNA inhibited cell proliferation through the accumulation of cells in G1 phase of the cell cycle, and reduced cyclin D1 expression in gastric cancer cells, whereas these effects were uncommon in other cancer cells. ASK1 overexpression induced the transcription of cyclin D1, through AP-1 activation, and ASK1 levels were regulated by cyclin D1, via the Rb–E2F pathway. Exogenous ASK1 induced cyclin D1 expression, followed by elevated expression of endogenous ASK1. These results indicate an autoregulatory mechanism of ASK1 in the development of gastric cancer. Targeting this positive feedback loop, ASK1 may present a potential therapeutic target for the treatment of advanced gastric cancer.
Vaccination inducing broad and improved cross protection against multiple subtypes of influenza A virus
Authors: Song Jae-Min , Van Rooijen Nico , Bozja Jadranka , Compans Richard W. , Kang Sang-Moo
Published: December 2010

Development of an influenza vaccine that provides broadly cross-protective immunity has been a scientific challenge for more than half a century. This study presents an approach to overcome strain-specific protection by supplementing conventional vaccines with virus-like particles (VLPs) containing the conserved M2 protein (M2 VLPs) in the absence of adjuvants. We demonstrate that an inactivated influenza vaccine supplemented with M2 VLPs prevents disease symptoms without showing weight loss and confers complete cross protection against lethal challenge with heterologous influenza A viruses including the 2009 H1N1 pandemic virus as well as heterosubtypic H3N2 and H5N1 influenza viruses. Cross-protective immunity was long-lived, for more than 7 mo. Immune sera from mice immunized with M2 VLP supplemented vaccine transferred cross protection to naive mice. Dendritic and macrophage cells were found to be important for this cross protection mediated by immune sera. The results provide evidence that supplementation of seasonal influenza vaccines with M2 VLPs is a promising approach for overcoming the limitation of strain-specific protection by current vaccines and developing a universal influenza A vaccine.
Formation of benzene in the interstellar medium
Authors: Jones Brant M. , Zhang Fangtong , Kaiser Ralf I. , Jamal Adeel , Mebel Alexander M. , Cordiner Martin A. , Charnley Steven B.
Published: December 2010

Polycyclic aromatic hydrocarbons and related species have been suggested to play a key role in the astrochemical evolution of the interstellar medium, but the formation mechanism of even their simplest building block—the aromatic benzene molecule—has remained elusive for decades. Here we demonstrate in crossed molecular beam experiments combined with electronic structure and statistical calculations that benzene (C
6
H
6
) can be synthesized via the barrierless, exoergic reaction of the ethynyl radical and 1,3-butadiene, C
2
H + H
2
CCHCHCH
2
 → C
6
H
6
 + H, under single collision conditions. This reaction portrays the simplest representative of a reaction class in which aromatic molecules with a benzene core can be formed from acyclic precursors via barrierless reactions of ethynyl radicals with substituted 1,3-butadiene molecules. Unique gas-grain astrochemical models imply that this low-temperature route controls the synthesis of the very first aromatic ring from acyclic precursors in cold molecular clouds, such as in the Taurus Molecular Cloud. Rapid, subsequent barrierless reactions of benzene with ethynyl radicals can lead to naphthalene-like structures thus effectively propagating the ethynyl-radical mediated formation of aromatic molecules in the interstellar medium.
Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice
Authors: Amenta Alison R. , Yilmaz Atilgan , Bogdanovich Sasha , McKechnie Beth A. , Abedi Mehrdad , Khurana Tejvir S. , Fallon Justin R.
Published: December 2010

Duchenne muscular dystrophy (DMD) is caused by mutations in dystrophin and the subsequent disruption of the dystrophin-associated protein complex (DAPC). Utrophin is a dystrophin homolog expressed at high levels in developing muscle that is an attractive target for DMD therapy. Here we show that the extracellular matrix protein biglycan regulates utrophin expression in immature muscle and that recombinant human biglycan (rhBGN) increases utrophin expression in cultured myotubes. Systemically delivered rhBGN up-regulates utrophin at the sarcolemma and reduces muscle pathology in the mdx mouse model of DMD. RhBGN treatment also improves muscle function as judged by reduced susceptibility to eccentric contraction-induced injury. Utrophin is required for the rhBGN therapeutic effect. Several lines of evidence indicate that biglycan acts by recruiting utrophin protein to the muscle membrane. RhBGN is well tolerated in animals dosed for as long as 3 months. We propose that rhBGN could be a therapy for DMD.
The Pim protein kinases regulate energy metabolism and cell growth
Authors: Beharry Zanna , Mahajan Sandeep , Zemskova Marina , Lin Ying-Wei , Tholanikunnel Baby G. , Xia Zuping , Smith Charles D. , Kraft Andrew S.
Published: December 2010

The serine/threonine Pim kinases are overexpressed in solid cancers and hematologic malignancies and promote cell growth and survival. Here, we find that a novel Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked the rapamycin-sensitive mammalian target of rapamycin (mTORC1) activity by stimulating the phosphorylation and thus activating the mTORC1 negative regulator AMP-dependent protein kinase (AMPK). Mouse embryonic fibroblasts (MEFs) deficient for all three Pim kinases [triple knockout (TKO) MEFs] demonstrated activated AMPK driven by elevated ratios of AMP∶ATP relative to wild-type MEFs. Consistent with these findings, TKO MEFs were found to grow slowly in culture and have decreased rates of protein synthesis secondary to a diminished amount of 5′-cap–dependent translation. Pim-3 expression alone in TKO MEFs was sufficient to reverse AMPK activation, increase protein synthesis, and drive MEF growth similar to wild type. Pim-3 expression was found to markedly increase the protein levels of both c-Myc and the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), enzymes capable of regulating glycolysis and mitochondrial biogenesis, which were diminished in TKO MEFs. Overexpression of PGC-1α in TKO MEFs elevated ATP levels and inhibited the activation of AMPK. These results demonstrate the Pim kinase-mediated control of energy metabolism and thus regulation of AMPK activity. We identify an important role for Pim-3 in modulating c-Myc and PGC-1α protein levels and cell growth.
Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand
Authors: Li Jau-Yi , Tawfeek Hesham , Bedi Brahmchetna , Yang Xiaoying , Adams Jonathan , Gao Kristy Y. , Zayzafoon Majd , Weitzmann M. Neale , Pacifici Roberto
Published: December 2010

The bone loss induced by ovariectomy (ovx) has been linked to increased production of osteoclastogenic cytokines by bone marrow cells, including T cells and stromal cells (SCs). It is presently unknown whether regulatory interactions between these lineages contribute to the effects of ovx in bone, however. Here, we show that the T-cell costimulatory molecule CD40 ligand (CD40L) is required for ovx to expand SCs; promote osteoblast proliferation and differentiation; regulate the SC production of the osteoclastogenic factors macrophage colony-stimulating factor, receptor activator of nuclear factor-κB ligand, and osteoprotegerin; and up-regulate osteoclast formation. CD40L is also required for ovx to activate T cells and stimulate their production of TNF. Accordingly, ovx fails to promote bone loss and increase bone resorption in mice depleted of T cells or lacking CD40L. Therefore, cross-talk between T cells and SCs mediated by CD40L plays a pivotal role in the disregulation of osteoblastogenesis and osteoclastogenesis induced by ovx.
DRD2/AKT1interaction on D2 c-AMP independent signaling, attentional processing, and response to olanzapine treatment in schizophrenia
Authors: Blasi Giuseppe , Napolitano Francesco , Ursini Gianluca , Taurisano Paolo , Romano Raffaella , Caforio Grazia , Fazio Leonardo , Gelao Barbara , Di Giorgio Annabella , Iacovelli Luisa , Sinibaldi Lorenzo , Popolizio Teresa , Usiello Alessandro , Bertolino Alessandro
Published: December 2010

The D2/AKT1/GSK-3β signaling pathway has been involved in the downstream intracellular effects of dopamine, in the pathophysiology of cognitive deficits and related brain activity in schizophrenia, as well as in response to treatment with antipsychotics. Polymorphisms in the D2 (DRD2rs1076560) and AKT1 (AKT1rs1130233) genes have been associated with their respective protein expression and with higher-order cognition and brain function, including attention. Given the strong potential for their relationship, we investigated the interaction of these polymorphisms on multiple molecular and in vivo phenotypes associated with this signaling pathway. We measured AKT1 and GSK-3β proteins and phosphorylation in human peripheral blood mononuclear cells, functional MRI cingulate response during attentional control, behavioral accuracy during sustained attention, and response to 8 wk of treatment with olanzapine in a total of 190 healthy subjects and 66 patients with schizophrenia. In healthy subjects, we found that the interaction between the T allele ofDRD2rs1076560 and the A allele ofAKT1rs1130233 was associated with reduced AKT1 protein levels and reduced phosphorylation of GSK-3β, as well as with altered cingulate response and reduced behavioral accuracy during attentional processing. On the other hand, interaction of these two alleles was associated with greater improvement of Positive and Negative Syndrome Scale scores in patients with schizophrenia after treatment with olanzapine. The present results indicate that these functional polymorphisms are epistatically associated with multiple phenotypes of relevance to schizophrenia. Our results also lend support to further investigation of this downstream molecular pathway in the etiology and treatment of this disorder.
Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining
Authors: Fnu Sheema , Williamson Elizabeth A. , De Haro Leyma P. , Brenneman Mark , Wray Justin , Shaheen Montaser , Radhakrishnan Krishnan , Lee Suk-Hee , Nickoloff Jac A. , Hromas Robert
Published: December 2010

Given its significant role in the maintenance of genomic stability, histone methylation has been postulated to regulate DNA repair. Histone methylation mediates localization of 53BP1 to a DNA double-strand break (DSB) during homologous recombination repair, but a role in DSB repair by nonhomologous end-joining (NHEJ) has not been defined. By screening for histone methylation after DSB induction by ionizing radiation we found that generation of dimethyl histone H3 lysine 36 (H3K36me2) was the major event. Using a novel human cell system that rapidly generates a single defined DSB in the vast majority of cells, we found that the DNA repair protein Metnase (also SETMAR), which has a SET histone methylase domain, localized to an induced DSB and directly mediated the formation of H3K36me2 near the induced DSB. This dimethylation of H3K36 improved the association of early DNA repair components, including NBS1 and Ku70, with the induced DSB, and enhanced DSB repair. In addition, expression of JHDM1a (an H3K36me2 demethylase) or histone H3 in which K36 was mutated to A36 or R36 to prevent H3K36me2 formation decreased the association of early NHEJ repair components with an induced DSB and decreased DSB repair. Thus, these experiments define a histone methylation event that enhances DNA DSB repair by NHEJ.
Vibrio cholerae
anaerobic induction of virulence gene expression is controlled by thiol-based switches of virulence regulator AphB
Authors: Liu Zhi , Yang Menghua , Peterfreund Gregory L. , Tsou Amy M. , Selamoglu Nur , Daldal Fevzi , Zhong Zengtao , Kan Biao , Zhu Jun
Published: December 2010

Bacterial pathogens have evolved sophisticated signal transduction systems to coordinately control the expression of virulence determinants. For example, the human pathogen
Vibrio cholerae
is able to respond to host environmental signals by activating transcriptional regulatory cascades. The host signals that stimulate
V. cholerae
virulence gene expression, however, are still poorly understood. Previous proteomic studies indicated that the ambient oxygen concentration plays a role in
V. cholerae
virulence gene expression. In this study, we found that under oxygen-limiting conditions, an environment similar to the intestines,
V. cholerae
virulence genes are highly expressed. We show that anaerobiosis enhances dimerization and activity of AphB, a transcriptional activator that is required for the expression of the key virulence regulator TcpP, which leads to the activation of virulence factor production. We further show that one of the three cysteine residues in AphB, C
235
, is critical for oxygen responsiveness, as the AphB
C235S
mutant can activate virulence genes under aerobic conditions in vivo and can bind to
tcpP
promoters in the absence of reducing agents in vitro. Mass spectrometry analysis suggests that under aerobic conditions, AphB is modified at the C
235
residue. This modification is reversible between oxygen-rich aquatic environments and oxygen-limited human hosts, suggesting that
V. cholerae
may use a thiol-based switch mechanism to sense intestinal signals and activate virulence.
E2f binding-deficientRb1protein suppresses prostate tumor progression in vivo
Authors: Sun Huifang , Wang Yanqing , Chinnam Meenalakshmi , Zhang Xiaojing , Hayward Simon W. , Foster Barbara A. , Nikitin Alexander Y. , Wills Marcia , Goodrich David W.
Published: December 2010

Mutational inactivation of theRB1tumor suppressor gene initiates retinoblastoma and other human cancers.RB1protein (pRb) restrains cell proliferation by binding E2f transcription factors and repressing the expression of cell cycle target genes. It is presumed that loss of pRb/E2f interaction accounts for tumor initiation, but this has not been directly tested.RB1mutation is a late event in other human cancers, suggesting a role in tumor progression as well as initiation. It is currently unknown whetherRB1mutation drives tumor progression and, if so, whether loss of pRb/E2f interaction is responsible. We have characterized tumorigenesis in mice expressing a mutant pRb that is specifically deficient in binding E2f. In endocrine tissue, the mutant pRb has no detectable effect on tumorigenesis. In contrast, it significantly delays progression to invasive and lethal prostate cancer. Tumor delay is associated with induction of a senescence response. We conclude that the pRb/E2f interaction is critical for preventing tumor initiation, but that pRb can use additional context-dependent mechanisms to restrain tumor progression.
Microfossils in calculus demonstrate consumption of plants and cooked foods in Neanderthal diets (Shanidar III, Iraq; Spy I and II, Belgium)
Authors: Henry Amanda G. , Brooks Alison S. , Piperno Dolores R.
Published: December 2010

The nature and causes of the disappearance of Neanderthals and their apparent replacement by modern humans are subjects of considerable debate. Many researchers have proposed biologically or technologically mediated dietary differences between the two groups as one of the fundamental causes of Neanderthal disappearance. Some scenarios have focused on the apparent lack of plant foods in Neanderthal diets. Here we report direct evidence for Neanderthal consumption of a variety of plant foods, in the form of phytoliths and starch grains recovered from dental calculus of Neanderthal skeletons from Shanidar Cave, Iraq, and Spy Cave, Belgium. Some of the plants are typical of recent modern human diets, including date palms (
Phoenix
spp.), legumes, and grass seeds (Triticeae), whereas others are known to be edible but are not heavily used today. Many of the grass seed starches showed damage that is a distinctive marker of cooking. Our results indicate that in both warm eastern Mediterranean and cold northwestern European climates, and across their latitudinal range, Neanderthals made use of the diverse plant foods available in their local environment and transformed them into more easily digestible foodstuffs in part through cooking them, suggesting an overall sophistication in Neanderthal dietary regimes.