bluuebunny/crossref_metadata_2025 huggingface dataset:
A compact time-resolved system for near infrared spectroscopy based on wavelength space multiplexing
Authors: Re Rebecca , Contini Davide , Caffini Matteo , Cubeddu Rinaldo , Spinelli Lorenzo , Torricelli Alessandro
Published: November 2010

We designed and developed a compact dual-wavelength and dual-channel time-resolved system for near-infrared spectroscopy studies of muscle and brain. The system employs pulsed diode lasers as sources, compact photomultipliers, and time-correlated single photon counting boards for detection. To exploit the full temporal and dynamic range of the acquisition technique, we implemented an approach based on wavelength space multiplexing: laser pulses at the two wavelengths are alternatively injected into the two channels by means of an optical 2×2 switch. In each detection line (i.e., in each temporal window), the distribution of photon time-of-flights at one wavelength is acquired. The proposed approach increases the signal-to-noise ratio and avoids wavelength cross-talk with respect to the typical approach based on time multiplexing. The instrument was characterized on tissue phantoms to assess its properties in terms of linearity, stability, noise, and reproducibility. Finally, it was successfully tested in preliminary in vivo measurements on muscle during standard cuff occlusion and on the brain during a motor cortex response due to hand movements.
The axial methionine ligand may control the redox reorganizations in the active site of blue copper proteins
Authors: Ando Koji
Published: November 2010

Structural and energetic reorganizations in redox reaction of type 1 copper proteins are studied by density functional and ab initio molecular orbital calculations. Model complexes of the active site with varying number of ligands, from Cu(SCH3)0/+ to Cu(SCH3)(Im)2(S(CH3)2)0/+, where Im denotes imidazole, are investigated. Following the findings of structural instability in Cu(I)(SCH3)(Im)2 and its stabilization by the addition of the axial methionine (Met) ligand model, the structure and energetics are examined as functions of the Cu–SMet distance in the range of 2.1–3.3 Å. The reorganization energies in both redox states exhibit a minimum at the Cu–SMet distance of ∼2.4 Å, whereas the ionization potential increases monotonically. The changes of reorganization energies correlate well with one of the Cu–NHis distances rather than the Cu–SCys distance. The estimated Arrhenius factor for oxidation of plastocyanin by P700+ (in photosystem I) changes by an order of magnitude when the Cu–SMet distance fluctuates between 2.4 and 3.0 Å, whereas the factor for reduction of plastocyanin by cytochrome f is nearly constant. Together with the data from our previous classical molecular dynamics simulation of solvated protein, we argue that the electron transfer rate is affected, and thus may be controlled, by the fluctuation of a weakly bound axial Met ligand. We also present the assessment of various exchange-correlation functionals, including those with the long-range correction, against the CCSD(T) reference and on the basis of a perturbative adiabatic connection model. For Cu(SCH3) and Cu(SCH3)(Im), simple correlations have been found between the reorganization energies and the amount of Hartree–Fock exchange.
Nonmonotoic fluctuation-induced interactions between dielectric slabs carrying charge disorder
Authors: Sarabadani Jalal , Naji Ali , Dean David S. , Horgan Ron R. , Podgornik Rudolf
Published: November 2010

We investigate the effect of monopolar charge disorder on the classical fluctuation-induced interactions between randomly charged net-neutral dielectric slabs and discuss various generalizations of recent results [A. Naji et al., Phys. Rev. Lett. 104, 060601 (2010)] to highly inhomogeneous dielectric systems with and without statistical disorder correlations. We shall focus on the specific case of two generally dissimilar plane-parallel slabs, which interact across vacuum or an arbitrary intervening dielectric medium. Monopolar charge disorder is considered to be present on the bounding surfaces and/or in the bulk of the slabs, may be in general quenched or annealed and may possess a finite lateral correlation length reflecting possible “patchiness” of the random charge distribution. In the case of quenched disorder, the bulk disorder is shown to give rise to an additive long-range contribution to the total force, which decays as the inverse distance between the slabs and may be attractive or repulsive depending on the dielectric constants of the slabs. By contrast, the force induced by annealed disorder in general combines with the underlying van der Waals forces in a nonadditive fashion, and the net force decays as an inverse cube law at large separations. We show, however, that in the case of two dissimilar slabs, the net effect due to the interplay between the disorder-induced and the pure van der Waals interactions can lead to a variety of unusual nonmonotonic interaction profiles between the dielectric slabs. In particular, when the intervening medium has a larger dielectric constant than the two slabs, we find that the net interaction can become repulsive and exhibit a potential barrier, while the underlying van der Waals force is attractive. On the contrary, when the intervening medium has a dielectric constant between that of the two slabs, the net interaction can become attractive and exhibit a free energy minimum, while the pure van der Waals force is repulsive. Therefore, the charge disorder, if present, can drastically alter the effective interaction between net-neutral objects.
Flux pinning properties and microstructure of SmBa2Cu3Oy thin films with systematically controlled BaZrO3 nanorods
Authors: Ozaki Toshinori , Yoshida Yutaka , Ichino Yusuke , Takai Yoshiaki , Ichinose Ataru , Matsumoto Kaname , Horii Shigeru , Mukaida Masashi , Takano Yoshihiko
Published: November 2010

We report a way of tuning the flux pinning properties by controlling the size and number density of BaZrO3 (BZO) nanorods without much degradation of the superconducting properties. The BZO nanorods in REBa2Cu3Oy superconducting films are known as promising c-axis-correlated pinning centers. We fabricated SmBa2Cu3Oy (SmBCO) films with BZO nanorods by a low-temperature growth technique (LTG-SmBCO+BZO films). With decreasing substrate temperature of the upper layer Tsupper in LTG-SmBCO+BZO films, the diameter of BZO nanorods decreased and their number density increased, leading to a high matching field Bϕ. Also, the considerable upturn shifts in the irreversibility field line and plateau regions in the magnetic field dependence of critical current density Jc were observed in the range from Bϕ/3 to Bϕ. These results indicate that a Bose-glass-like state of vortices localized on BZO nanorods emerges, after overcoming the vortex glass state of vortices, which are frozen on inherent pointlike disorders within the films in this magnetic field range. With this technique, it is possible to tune the flux pinning properties.
A simple radionuclide-driven single-ion source
Authors: Montero Díez M. , Twelker K. , Fairbank W. , Gratta G. , Barbeau P. S. , Barry K. , DeVoe R. , Dolinski M. J. , Green M. , LePort F. , Müller A. R. , Neilson R. , O’Sullivan K. , Ackerman N. , Aharmin B. , Auger M. , Benitez-Medina C. , Breidenbach M. , Burenkov A. , Cook S. , Daniels T. , Donato K. , Farine J. , Giroux G. , Gornea R. , Graham K. , Hagemann C. , Hall C. , Hall K. , Hallman D. , Hargrove C. , Herrin S. , Karelin A. , Kaufman L. J. , Kuchenkov A. , Kumar K. , Lacey J. , Leonard D. S. , Mackay D. , MacLellan R. , Mong B. , Niner E. , Odian A. , Piepke A. , Pocar A. , Prescott C. Y. , Pushkin K. , Rollin E. , Rowson P. C. , Sinclair D. , Slutsky S. , Stekhanov V. , Vuilleumier J.-L. , Wichoski U. , Wodin J. , Yang L. , Yen Y.-R.
Published: November 2010

We describe a source capable of producing single barium ions through nuclear recoils in radioactive decay. The source is fabricated by electroplating G148d onto a silicon α-particle detector and vapor depositing a layer of BaF2 over it. S144m recoils from the alpha decay of G148d are used to dislodge Ba+ ions from the BaF2 layer and emit them in the surrounding environment. The simultaneous detection of an α particle in the substrate detector allows for tagging of the nuclear decay and of the Ba+ emission. The source is simple, durable, and can be manipulated and used in different environments. We discuss the fabrication process, which can be easily adapted to emit most other chemical species, and the performance of the source.
X-ray photoelectron spectroscopy study of the chemical interaction at the Pd/SiC interface
Authors: Zhang Y. , Gajjala G. , Hofmann T. , Weinhardt L. , Bär M. , Heske C. , Seelmann-Eggebert M. , Meisen P.
Published: November 2010

In order to study the chemical interaction during interface formation between Pd and SiC, Pd layers of various thicknesses were deposited on structurally disordered SiC surfaces at 800 °C. The Pd/SiC interface, which plays a crucial role for many applications such as high power electronic devices and tristructural-isotropic (TRISO) nuclear fuels, was studied in situ by x-ray photoelectron spectroscopy. We find that after Pd deposition, Si–C and Si–Si bonds are broken in favor of the formation of not only Pd–Si but also Pd–C bonds. In addition, various silicon oxycarbide bonds are observed at the SiC surface and the Pd/SiC interface. These results are not only of relevance for the long-term stability of TRISO fuels but also for a variety of other applications, including Schottky-barrier-type contacts in electronic devices.
In situ Raman spectroscopy for characterization of the domain contributions to electrical and piezoelectric responses in Pb(Zr,Ti)O3 films
Authors: Nakajima Mitsumasa , Nakaki Hiroshi , Ehara Yoshitaka , Yamada Tomoaki , Nishida Ken , Yamamoto Takashi , Osada Minoru , Funakubo Hiroshi
Published: November 2010

We employed in situ Raman spectroscopy under electric field for (100)/(001)-oriented tetragonal Pb(Ti0.61Zr0.39)O3 films with (001)-volume fraction (VC) of 35%. The increase in VC was revealed above 200 kV/cm, which resulted in the larger remanent polarization. In addition, the application of high enough field also brings a feature, i.e., large reversible change in VC with/without electric field that can quantitatively explain the enhanced piezoelectric response. These demonstrate the usefulness of in situ Raman observation to probe the domain contributions to the electrical and piezoelectric responses.
Structure dependent quantum confinement effect in hydrogen-terminated nanodiamond clusters
Authors: Jiang Jun , Sun Lian , Gao Bin , Wu Ziyu , Lu Wei , Yang Jinlong , Luo Yi
Published: November 2010

Size-dependent quantum confinement effect on electronic structure of hydrogen-terminated carbon nanodiamond (ND) cluster has been investigated at the hybrid density functional theory level. Large scale all-electron calculations have been carried out for ND clusters of 0.76 nm (29 carbons) to 7.3 nm (20 959 carbons) in diameter. It is demonstrated that the quantum confinement effect in these clusters shows strong structural dependence. An important structural factor, describing the ratio between the number of atoms within the inner core and outer shell of the cluster, is identified which dictates the size-dependent behavior of the electronic states. For ND clusters with diameter smaller than 1.5 nm, the core-shell ratio changes fast with the increase in cluster size, and the evolution of electronic properties does not follow conventional quantum confinement models. For ND clusters exceeding the threshold of 1.5 nm in diameter, the change in the core-shell ratio saturates and quantum confinement effect becomes visible. Electronic states within the inner core and surface show different size dependence, but a general formula is proposed and describes their structure dependent quantum confinement effects. This formula provides useful insights into quantum confinement behavior in ND clusters, and thereby leads to important physical property information. The calculated electron effective masses for core and surface states of ND clusters are in very good agreement with the experiments.
On-film tunneling resistance measurements of unpatterned magnetic tunnel junctions
Authors: Lee Sangho , Han Yoonsung , Bae Taejin , Hong Jongill , Shim Jaechul , Kim Eunsik , Sunwoo Kukhyun
Published: November 2010

We successfully measured not only the tunneling properties but also the magnetic properties of a magnetic tunnel junction without patterning the magnetic tunnel junction stack itself by the current-in-plane tunneling method. Arrays of in-line four-point-probe sets with different spacings defined on the wafer made it possible to evaluate film tunneling properties. The estimated results differed little from those estimated by the commercial instrument. The small standard deviations of measured magnetic properties prove that our method is indeed reliable. Even though the properties for a less than submicron spacing were not available, we could successfully estimate the major characteristics of magnetic tunnel junctions. Our method can be applied in any environment, even in air without any clean-room facilities, and completed in as little as a day.
Magnetic properties of La doped Bi2FeMnO6 ceramic and film
Authors: Zhao Hongyang , Kimura Hideo , Cheng Zhenxiang , Wang Xiaolin , Ozawa Kiyoshi , Nishida Takashi
Published: November 2010

We present a comprehensive study of the magnetic properties for La doped Bi2FeMnO6 (LBFM) ceramic and film which was first deposited on (100) SrTiO3 substrate by pulsed laser deposition method. The LBFM film is antiferromagnetic or weak ferrimagnetic at room temperature and it shows clear magnetic anisotropy. But it is not sure whether the spin-glass behavior is present in LBFM film because of the influence from substrate. Compared to the film, LBFM ceramic shows different magnetic properties. It has a lower TN and all the observations indicate that LBFM ceramic shows spin-glass behavior.
CdS/CdSe cosensitized oriented single-crystalline TiO2 nanowire array for solar cell application
Authors: Li Ming , Liu Yong , Wang Hai , Shen Hui , Zhao Wenxia , Huang Hong , Liang Chaolun
Published: November 2010

Vertically oriented single-crystalline TiO2 nanowires array was grown on transparent conductive oxide glass substrate, and then CdS and CdSe quantum dots (QDs) were deposited on nanowires to form a TiO2/CdS/CdSe core-shell structure films. The optical properties of films with different layers of QDs were compared. The QD sensitized solar cells (QD-SSCs) were assembled and the effect of coating cycles of QDs on the photovoltaic performance was investigated. Under optimum parameters, QD-SSCs assembled with 5 μm thick TiO2 nanowires film exhibited a short-circuit current density of 7.92 mA cm−2, an open-circuit voltage of 0.40 V, and a power conversion efficiency of 1.14%.
Magnetic field sensing with a single piezoelectric ceramic disk: Experiments and modeling
Authors: Guiffard B. , Zhang J.-W. , Guyomar D. , Garbuio L. , Cottinet P.-J. , Belouadah R.
Published: November 2010

This study reports on the magnetoelectric coupling in a single piezoelectric ceramic disk subjected to both ac and dc magnetic fields perpendicularly applied to the sample’s plane. Eddy currents are induced within the electrodes of the ceramic by ac magnetic flux via the Lenz–Faraday equation and yields Lorentz forces and stresses which are transferred to the piezoelectric ceramic. This latter transduces stress into electrical charges through electromechanical coupling in radial mode. The measured output magnetoelectric current could be successfully modeled using piezoelectric equations providing the inductively coupled voltage between the electrodes of the ceramic is taken into account. This voltage originates from the ac magnetic flux through the experimental loop, which is not a perfect short-circuit and yields two other contributions to the total current: piezoelectric current due to the induced electric field and the dielectric loop current. Radial velocity measurements confirmed the distinct contributions to the current. Thus, room temperature magnetic field detection is achievable using this single piezoelectric disk with a good sensitivity and linear response versus dc magnetic field change.
Generation of 3 GW microwave pulses in X-band from a combination of a relativistic backward-wave oscillator and a helical-waveguide compressor
Authors: Bratman V. L. , Denisov G. G. , Kolganov N. G. , Mishakin S. V. , Samsonov S. V. , Cross A. W. , He W. , Zhang L. , McStravick M. , Whyte C. G. , Young A. R. , Ronald K. , Robertson C. W. , Phelps A. D. R.
Published: November 2010

The phenomenon of passive compression of frequency-modulated (FM) pulses in a dispersive media (DM) was used to increase the peak microwave power up to the multigigawatt level. A helically corrugated waveguide was used as the DM, while a relativistic X-band backward-wave oscillator (RBWO) with a descending-during-the-pulse accelerating voltage served as a source of FM pulses. Compression of pulses down to a halfwidth of 2.2 ns accompanied by a 4.5-fold power increase up to a value of about 3.2 GW has been demonstrated.
Examinations into the contaminant-induced transport instabilities in a molecular device
Authors: Zhang Z. H. , Deng X. Q. , Tan X. Q. , Qiu M. , Pan J. B.
Published: November 2010

We report first-principles calculations of transport behaviors for a molecular device whose electrode surface is contaminated by various diatomic groups. It has been found that such a device demonstrates less transport variations for the contamination of the group PO or SO in the whole bias range but it shows more transport variations for contamination of the group CN, HS, or NO only under low bias, which suggests that contamination of all diatomic groups studied here always affects high-bias transport properties of a device in an extremely gentle manner.
Graphene synthesis by ion implantation
Authors: Garaj Slaven , Hubbard William , Golovchenko J. A.
Published: November 2010

We demonstrate an ion implantation method for large-scale synthesis of high quality graphene films with controllable thickness. Thermally annealing polycrystalline nickel substrates that have been ion implanted with carbon atoms results in the surface growth of graphene films whose average thickness is controlled by implantation dose. The graphene film quality, as probed with Raman and electrical measurements, is comparable to previously reported synthesis methods. The implantation synthesis method can be generalized to a variety of metallic substrates and growth temperatures, since it does not require a decomposition of chemical precursors or a solvation of carbon into the substrate.
Role of strain in polarization switching in semipolar InGaN/GaN quantum wells
Authors: Yan Qimin , Rinke Patrick , Scheffler Matthias , Van de Walle Chris G.
Published: November 2010

The effect of strain on the valence-band structure of (112¯2) semipolar InGaN grown on GaN substrates is studied. A k⋅p analysis reveals that anisotropic strain in the c-plane and shear strain are crucial for deciding the ordering of the two topmost valence bands. The shear-strain deformation potential D6 is calculated for GaN and InN using density functional theory with the Heyd–Scuseria–Ernzerhof hybrid functional [J. Heyd, G. E. Scuseria, and M. Ernzerhof, J. Chem. Phys. 124, 219906 (2006)]. Using our deformation potentials and assuming a pseudomorphically strained structure, no polarization switching is observed. We investigate the role of partial strain relaxation in the observed polarization switching.
Highly stacked and well-aligned In0.4Ga0.6As quantum dot solar cells with In0.2Ga0.8As cap layer
Authors: Sugaya T. , Furue S. , Komaki H. , Amano T. , Mori M. , Komori K. , Niki S. , Numakami O. , Okano Y.
Published: November 2010

We report In0.4Ga0.6As quantum dot (QD) solar cells with In0.2Ga0.8As cap layers, which extends the photoabsorption spectra toward a wavelength longer than those of In0.4Ga0.6As QD solar cells without cap layers. Well-aligned 50-stack In0.4Ga0.6As QD structures with In0.2Ga0.8As cap layers can be grown without using a strain balancing technique. The photoluminescence wavelength of ten-stack In0.4Ga0.6As QDs with an In0.2Ga0.8As cap layer becomes longer, as a result of the reduced strain in the QDs achieved by using the cap layer. The cell characteristics of multistacked In0.4Ga0.6As QD solar cells are improved by employing In0.2Ga0.8As cap layers.
Enhanced carbon nanotube fibers by polyimide
Authors: Fang Chao , Zhao Jingna , Jia Jingjing , Zhang Zuoguang , Zhang Xiaohua , Li Qingwen
Published: November 2010

The performance of carbon nanotube (CNT) fibers is limited by the intertube characteristics. Here we report a direct method of curing to improve mechanical properties of poly(amic acid)-infiltrated fibers. After curing at 190 °C for 60 min the fibers composed of double- and triple-walled CNTs, their strength is stably improved by 30.3%, from 1.58 to 2.06 GPa. The enhancement arises from the increase in shear stress between tube surfaces, by measuring the static frictional force of CNT fibers. Due to the existence of CNTs, the imidization temperature of polyimide drops greatly from 218 to 157 °C.
241.Reproductive performance in Clock mutant mice
Authors: Kennaway D. J. , Voultsios A. , Boden M. J.
Published: October 2010

The relationship between circadian rhythmicity and rodent reproductive cyclicity is well established, but the impact of disrupted clock gene function on reproduction has not been investigated. This study evaluated the reproductive performance of melatonin deficient and proficient mice carrying a mutation in the core circadian gene, Clock. In natural matings, melatonin deficient Clock mutant mice took 2 to 3 days longer to mate and to subsequently deliver pups than their control line. The melatonin proficient mutants (Clock-MEL) had a smaller, but still significant delay (P < 0.05). The Clock mutation resulted in smaller median litter sizes compared to the control lines (7 v. 8 pups, P < 0.05) while melatonin proficiency reversed this difference. Survival to weaning was 84% and 80% for the melatonin deficient and proficient Clock mutant lines respectively, compared to 94 to 96% for their control lines. When immature mice were subjected to a standard PMSG/HCG superovulation protocol, Clock-MEL mice had lowered fertility and significantly fewer ovulations than their control line although embryo development appeared to be only slightly affected (Table 1, see PDF file).
281.A novel scavenger receptor domain containing genes differentially expressed in the embryonic mouse testis
Authors: Sarraj M. A. , McClive P. J. , Sinclair A. H.
Published: October 2010

Sex in mammals is determined by the constitution of the sex chromosomes: two X-chromosomes results in the development of ovaries and a female phenotype, while an X and a Y chromosome result in testis development and a male phenotype. The SRY gene on the Y chromosome has been identified as the genetic switch, which initiates testis formation. The importance of SRY and the related SOX9 gene in sex determination has been well characterised in humans and mouse. Mutations in SRY and SOX9 account for approximately 20% of sex reversed XY-female patients suggesting that other genes are required for normal testis development. The mouse model was used to identify and characterise differentially expressed genes in the embryonic testis/ovary that may represent new sex determining candidates.
A suppression subtraction hybridisation screen was conducted on testes/ovaries mouse cDNA between 12.0-12.5 dpc. Differential clones were sequenced, bioinformatic analysis was performed and expression patterns verified by whole mount in situ hybridisation (WISH) on 12.5 dpc mouse partial embryos.
We identified a novel gene (B7) containing a scavenger receptor domain of unknown function. B7 was expressed in the gonads of both sexes from 11.5-12.0 dpc. From 12.5 -13.5 dpc, B7 expression was present in the testis but not in the ovary. We termed B7 Testis Expressed Scavenger Receptor (Tesr). Expression of Tesr was also seen in the mouse brain, eye, head, heart, neural arch and cartilage primordium. Furthermore, Tesr expression was analysed in the chicken embryo. Low expression was seen in the male gonads and mesonephric tubules from day 3.5-7.5. Tesr was expressed in chicken embryo's heart, notochord, neural tube, dorsal aorta and the somites at day 3.5 and 4.5.
Tesr may play a role in phagocytosis of apoptotic cells and may be involved in scavenger, adhesion, defence functions and immune responses. Another possible role for Tesr in the developing testis may be cholesterol delivery for steroidogenesis.
Nonstimulated early visual areas carry information about surrounding context
Authors: Smith Fraser W. , Muckli Lars
Published: November 2010

Even within the early sensory areas, the majority of the input to any given cortical neuron comes from other cortical neurons. To extend our knowledge of the contextual information that is transmitted by such lateral and feedback connections, we investigated how visually nonstimulated regions in primary visual cortex (V1) and visual area V2 are influenced by the surrounding context. We used functional magnetic resonance imaging (fMRI) and pattern-classification methods to show that the cortical representation of a nonstimulated quarter-field carries information that can discriminate the surrounding visual context. We show further that the activity patterns in these regions are significantly related to those observed with feed-forward stimulation and that these effects are driven primarily by V1. These results thus demonstrate that visual context strongly influences early visual areas even in the absence of differential feed-forward thalamic stimulation.
Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains
Authors: Miao Benchun , Skidan Igor , Yang Jinsheng , Lugovskoy Alexey , Reibarkh Mikhail , Long Kai , Brazell Tres , Durugkar Kulbhushan A. , Maki Jenny , Ramana C. V. , Schaffhausen Brian , Wagner Gerhard , Torchilin Vladimir , Yuan Junying , Degterev Alexei
Published: November 2010

The PI3-kinase (PI3K) pathway regulates many cellular processes, especially cell metabolism, cell survival, and apoptosis. Phosphatidylinositol-3,4,5-trisphosphate (PIP3), the product of PI3K activity and a key signaling molecule, acts by recruiting pleckstrin-homology (PH) domain-containing proteins to cell membranes. Here, we describe a new structural class of nonphosphoinositide small molecule antagonists (PITenins, PITs) of PIP3–PH domain interactions (IC
50
ranges from 13.4 to 31 μM in PIP3/Akt PH domain binding assay). PITs inhibit interactions of a number of PIP3-binding PH domains, including those of Akt and PDK1, without affecting several PIP2-selective PH domains. As a result, PITs suppress the PI3K-PDK1-Akt pathway and trigger metabolic stress and apoptosis. A PIT-1 analog displayed significant antitumor activity in vivo, including inhibition of tumor growth and induction of apoptosis. Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling.
Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders
Authors: Neasta Jérémie , Ben Hamida Sami , Yowell Quinn , Carnicella Sebastien , Ron Dorit
Published: November 2010

Alcohol addiction is a chronically relapsing disorder that includes certain maladaptive learning and memory. The serine and threonine kinase complex, mammalian target of rapamycin complex 1 (mTORC1), has been implicated in synaptic plasticity, learning, and memory by controlling protein translation. Here we show that administration of alcohol and excessive voluntary consumption of alcohol induce the activation of the mTORC1-mediated signaling pathway in the nucleus accumbens (NAc) of rodents. We further show that the protein expression levels of GluR1 and Homer, two synaptic proteins whose translation has been shown to be modulated by mTORC1, are up-regulated in the NAc of rodents with a history of excessive alcohol consumption. In addition, our results document that the Food and Drug Administration-approved inhibitor of mTORC1, rapamycin, decreases expression of alcohol-induced locomotor sensitization and place preference, as well as excessive alcohol intake and seeking in preclinical rodent models of alcohol abuse. Together, our results suggest that mTORC1 within the NAc is a contributor to molecular mechanisms underlying alcohol-drinking behaviors. Furthermore, despite its massive health and socioeconomic impact worldwide, pharmacotherapies for alcohol abuse and addiction remain limited. Our data therefore put forward the possibility that targeting the mTORC1 signaling cascade is an innovative and valuable strategy for the treatment of alcohol use and abuse disorders.
In vivo protein stabilization based on fragment complementation and a split GFP system
Authors: Lindman Stina , Hernandez-Garcia Armando , Szczepankiewicz Olga , Frohm Birgitta , Linse Sara
Published: November 2010

Protein stabilization was achieved through in vivo screening based on the thermodynamic linkage between protein folding and fragment complementation. The split GFP system was found suitable to derive protein variants with enhanced stability due to the correlation between effects of mutations on the stability of the intact chain and the effects of the same mutations on the affinity between fragments of the chain. PGB1 mutants with higher affinity between fragments 1 to 40 and 41 to 56 were obtained by in vivo screening of a library of the 1 to 40 fragments against wild-type 41 to 56 fragments. Colonies were ranked based on the intensity of green fluorescence emerging from assembly and folding of the fused GFP fragments. The DNA from the brightest fluorescent colonies was sequenced, and intact mutant PGB1s corresponding to the top three sequences were expressed, purified, and analyzed for stability toward thermal denaturation. The protein sequence derived from the top fluorescent colony was found to yield a 12 °C increase in the thermal denaturation midpoint and a free energy of stabilization of -8.7 kJ/mol at 25 °C. The stability rank order of the three mutant proteins follows the fluorescence rank order in the split GFP system. The variants are stabilized through increased hydrophobic effect, which raises the free energy of the unfolded more than the folded state; as well as substitutions, which lower the free energy of the folded more than the unfolded state; optimized van der Waals interactions; helix stabilization; improved hydrogen bonding network; and reduced electrostatic repulsion in the folded state.
Exposing malaria in-host diversity and estimating population diversity by capture-recapture using massively parallel pyrosequencing
Authors: Juliano Jonathan J. , Porter Kimberly , Mwapasa Victor , Sem Rithy , Rogers William O. , Ariey Frédéric , Wongsrichanalai Chansuda , Read Andrew , Meshnick Steven R.
Published: November 2010

Malaria infections commonly contain multiple genetically distinct variants. Mathematical and animal models suggest that interactions among these variants have a profound impact on the emergence of drug resistance. However, methods currently used for quantifying parasite diversity in individual infections are insensitive to low-abundance variants and are not quantitative for variant population sizes. To more completely describe the in-host complexity and ecology of malaria infections, we used massively parallel pyrosequencing to characterize malaria parasite diversity in the infections of a group of patients. By individually sequencing single strands of DNA in a complex mixture, this technique can quantify uncommon variants in mixed infections. The in-host diversity revealed by this method far exceeded that described by currently recommended genotyping methods, with as many as sixfold more variants per infection. In addition, in paired pre- and posttreatment samples, we show a complex milieu of parasites, including variants likely up-selected and down-selected by drug therapy. As with all surveys of diversity, sampling limitations prevent full discovery and differences in sampling effort can confound comparisons among samples, hosts, and populations. Here, we used ecological approaches of species accumulation curves and capture-recapture to estimate the number of variants we failed to detect in the population, and show that these methods enable comparisons of diversity before and after treatment, as well as between malaria populations. The combination of ecological statistics and massively parallel pyrosequencing provides a powerful tool for studying the evolution of drug resistance and the in-host ecology of malaria infections.
Nicotinic acid adenine dinucleotide phosphate regulates skeletal muscle differentiation via action at two-pore channels
Authors: Aley Parvinder K. , Mikolajczyk Anna M. , Munz Barbara , Churchill Grant C. , Galione Antony , Berger Felicitas
Published: November 2010

Calcium signaling is essential for the differentiation of many cell types, including skeletal muscle cells, but its mechanisms remain elusive. Here we demonstrate a crucial role for nicotinic acid adenine dinucleotide phosphate (NAADP) signaling in skeletal muscle differentiation. Although the inositol trisphosphate pathway may have a partial role to play in this process, the ryanodine signaling cascade is not involved. In both skeletal muscle precursors and C2C12, cells interfering with NAADP signaling prevented differentiation, whereas promoting NAADP signaling potentiated differentiation. Moreover, siRNA knockdown of two-pore channels, the target of NAADP, attenuated differentiation. The data presented here strongly suggest that in myoblasts, NAADP acts at acidic organelles on the recently discovered two-pore channels to promote differentiation.
Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate
Authors: Arwert Esther N. , Lal Rohit , Quist Sven , Rosewell Ian , van Rooijen Nico , Watt Fiona M.
Published: November 2010

In mammalian epidermis, integrin expression is normally confined to the basal proliferative layer that contains stem cells. However, in epidermal hyperproliferative disorders and tumors, integrins are also expressed by suprabasal cells, with concomitant up-regulation of Erk mitogen-activated protein kinase (MAPK) signaling. In transgenic mice, expression of activated MAPK kinase 1 (MEK1) in the suprabasal, nondividing, differentiated cell layers (InvEE transgenics) results in epidermal hyperproliferation and skin inflammation. We now demonstrate that wounding induces benign tumors (papillomas and keratoacanthomas) in InvEE mice. By generating chimeras between InvEE mice and mice that lack the MEK1 transgene, we demonstrate that differentiating, nondividing cells that express MEK1 stimulate adjacent transgene-negative cells to divide and become incorporated into the tumor mass. Dexamethasone treatment inhibits tumor formation, suggesting that inflammation is involved. InvEE skin and tumors express high levels of IL1α; treatment with an IL1 receptor antagonist delays tumor onset and reduces incidence. Depletion of γδ T cells and macrophages also reduces tumor incidence. Because a hallmark of cancer is uncontrolled proliferation, it is widely assumed that tumors arise only from dividing cells. In contrast, our studies show that differentiated epidermal cells can initiate tumor formation without reacquiring the ability to divide and that they do so by triggering an inflammatory infiltrate.
Mechanism of 2-oxoglutarate signaling by the
Synechococcus elongatus
P
II
signal transduction protein
Authors: Fokina Oleksandra , Chellamuthu Vasuki-Ranjani , Forchhammer Karl , Zeth Kornelius
Published: November 2010

P
II
proteins control key processes of nitrogen metabolism in bacteria, archaea, and plants in response to the central metabolites ATP, ADP, and 2-oxoglutarate (2-OG), signaling cellular energy and carbon and nitrogen abundance. This metabolic information is integrated by P
II
and transmitted to regulatory targets (key enzymes, transporters, and transcription factors), modulating their activity. In oxygenic phototrophs, the controlling enzyme of arginine synthesis,
N
-acetyl-glutamate kinase (NAGK), is a major P
II
target, whose activity responds to 2-OG via P
II
. Here we show structures of the
Synechococcus elongatus
P
II
protein in complex with ATP, Mg
2+
, and 2-OG, which clarify how 2-OG affects P
II
–NAGK interaction. P
II
trimers with all three sites fully occupied were obtained as well as structures with one or two 2-OG molecules per P
II
trimer. These structures identify the site of 2-OG located in the vicinity between the subunit clefts and the base of the T loop. The 2-OG is bound to a Mg
2+
ion, which is coordinated by three phosphates of ATP, and by ionic interactions with the highly conserved residues K58 and Q39 together with B- and T-loop backbone interactions. These interactions impose a unique T-loop conformation that affects the interactions with the P
II
target. Structures of P
II
trimers with one or two bound 2-OG molecules reveal the basis for anticooperative 2-OG binding and shed light on the intersubunit signaling mechanism by which P
II
senses effectors in a wide range of concentrations.
Social and genetic interactions drive fitness variation in a free-living dolphin population
Authors: Frère Celine H. , Krützen Michael , Mann Janet , Connor Richard C. , Bejder Lars , Sherwin William B.
Published: November 2010

The evolutionary forces that drive fitness variation in species are of considerable interest. Despite this, the relative importance and interactions of genetic and social factors involved in the evolution of fitness traits in wild mammalian populations are largely unknown. To date, a few studies have demonstrated that fitness might be influenced by either social factors or genes in natural populations, but none have explored how the combined effect of social and genetic parameters might interact to influence fitness. Drawing from a long-term study of wild bottlenose dolphins in the eastern gulf of Shark Bay, Western Australia, we present a unique approach to understanding these interactions. Our study shows that female calving success depends on both genetic inheritance and social bonds. Moreover, we demonstrate that interactions between social and genetic factors also influence female fitness. Therefore, our study represents a major methodological advance, and provides critical insights into the interplay of genetic and social parameters of fitness.
Hardy-Littlewood-Sobolev inequalities via fast diffusion flows
Authors: Carlen Eric A. , Carrillo José A. , Loss Michael
Published: November 2010

We give a simple proof of the
λ
 = 
d
 - 2 cases of the sharp Hardy-Littlewood-Sobolev inequality for
d
≥3, and the sharp Logarithmic Hardy-Littlewood-Sobolev inequality for
d
 = 2 via a monotone flow governed by the fast diffusion equation.
Versatile solution for growing thin films of conducting polymers
Authors: D’Arcy Julio M. , Tran Henry D. , Tung Vincent C. , Tucker-Schwartz Alexander K. , Wong Rain P. , Yang Yang , Kaner Richard B.
Published: November 2010

The method employed for depositing nanostructures of conducting polymers dictates potential uses in a variety of applications such as organic solar cells, light-emitting diodes, electrochromics, and sensors. A simple and scalable film fabrication technique that allows reproducible control of thickness, and morphological homogeneity at the nanoscale, is an attractive option for industrial applications. Here we demonstrate that under the proper conditions of volume, doping, and polymer concentration, films consisting of monolayers of conducting polymer nanofibers such as polyaniline, polythiophene, and poly(3-hexylthiophene) can be produced in a matter of seconds. A thermodynamically driven solution-based process leads to the growth of transparent thin films of interfacially adsorbed nanofibers. High quality transparent thin films are deposited at ambient conditions on virtually any substrate. This inexpensive process uses solutions that are recyclable and affords a new technique in the field of conducting polymers for coating large substrate areas.
Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer
Authors: Su Feng , Kozak Kathy R. , Imaizumi Satoshi , Gao Feng , Amneus Malaika W. , Grijalva Victor , Ng Carey , Wagner Alan , Hough Greg , Farias-Eisner Gina , Anantharamaiah G. M. , Van Lenten Brian J. , Navab Mohamad , Fogelman Alan M. , Reddy Srinivasa T. , Farias-Eisner Robin
Published: November 2010

We examined whether reduced levels of Apolipoprotein A-I (apoA-I) in ovarian cancer patients are causal in ovarian cancer in a mouse model. Mice expressing a human apoA-I transgene had (i) increased survival (P< 0.0001) and (ii) decreased tumor development (P< 0.01), when compared with littermates, following injection of mouse ovarian epithelial papillary serous adenocarcinoma cells (ID-8 cells). ApoA-I mimetic peptides reduced viability and proliferation of ID8 cells andcis-platinum–resistant human ovarian cancer cells, and decreased ID-8 cell-mediated tumor burden in C57BL/6J mice when administered subcutaneously or orally. Serum levels of lysophosphatidic acid, a well-characterized modulator of tumor cell proliferation, were significantly reduced (>50% compared with control mice,P< 0.05) in mice that received apoA-I mimetic peptides (administered either subcutaneously or orally), suggesting that binding and removal of lysophosphatidic acid is a potential mechanism for the inhibition of tumor development by apoA-I mimetic peptides, which may serve as a previously unexplored class of anticancer agents.
Neural signatures of strategic types in a two-person bargaining game
Authors: Bhatt Meghana A. , Lohrenz Terry , Camerer Colin F. , Montague P. Read
Published: November 2010

The management and manipulation of our own social image in the minds of others requires difficult and poorly understood computations. One computation useful in social image management is strategic deception: our ability and willingness to manipulate other people's beliefs about ourselves for gain. We used an interpersonal bargaining game to probe the capacity of players to manage their partner's beliefs about them. This probe parsed the group of subjects into three behavioral types according to their revealed level of strategic deception; these types were also distinguished by neural data measured during the game. The most deceptive subjects emitted behavioral signals that mimicked a more benign behavioral type, and their brains showed differential activation in right dorsolateral prefrontal cortex and left Brodmann area 10 at the time of this deception. In addition, strategic types showed a significant correlation between activation in the right temporoparietal junction and expected payoff that was absent in the other groups. The neurobehavioral types identified by the game raise the possibility of identifying quantitative biomarkers for the capacity to manipulate and maintain a social image in another person's mind.
Formation of μ-/κ-opioid receptor heterodimer is sex-dependent and mediates female-specific opioid analgesia
Authors: Chakrabarti Sumita , Liu Nai-Jiang , Gintzler Alan R.
Published: November 2010

Sexually dimorphic nociception and opioid antinociception is very pervasive but poorly understood. We had demonstrated that spinal morphine antinociception in females, but not males, requires the concomitant activation of spinal μ- and κ-opioid receptors (MOR and KOR, respectively). This finding suggests an interrelationship between MOR and KOR in females that is not manifest in males. Here, we show that expression of a MOR/KOR heterodimer is vastly more prevalent in the spinal cord of proestrous vs. diestrous females and vs. males. Cross-linking experiments in combination with in vivo pharmacological analyses indicate that heterodimeric MOR/KOR utilizes spinal dynorphin 1–17 as a substrate and is likely to be the molecular transducer for the female-specific KOR component of spinal morphine antinociception. The activation of KOR within the heterodimeric MOR/KOR provides a mechanism for recruiting spinal KOR-mediated antinociception without activating the concomitant pronociceptive functions that monomeric KOR also subserves. Spinal cord MOR/KOR heterodimers represent a unique pharmacological target for female-specific pain control.
Method to measure strong protein–protein interactions in lipid bilayers using a steric trap
Authors: Hong Heedeok , Blois Tracy M. , Cao Zheng , Bowie James U.
Published: November 2010

Measuring high affinity protein–protein interactions in membranes is extremely challenging because there are limitations to how far the interacting components can be diluted in bilayers. Here we show that a steric trap can be employed for stable membrane interactions. We couple dissociation to a competitive binding event so that dissociation can be driven by increasing the affinity or concentration of the competitor. The steric trap design used here links monovalent streptavidin binding to dissociation of biotinylated partners. Application of the steric trap method to the well-characterized glycophorin A transmembrane helix (GpATM) reveals a dimer that is dramatically stabilized by 4–5 kcal/mol in palmitoyloleoylphosphatidylcholine bilayers compared to detergent. We also find larger effects of mutations at the dimer interface in bilayers compared to detergent suggesting that the dimer is more organized in a membrane environment. The high affinity we measure for GpATM in bilayers indicates that a membrane vesicle many orders of magnitude larger than a bacterial cell would be required to measure the dissociation constant using traditional dilution methods. Thus, steric trapping can open new biological systems to experimental scrutiny in natural bilayer environments.
Physiologically relevant and portable tandem ubiquitin-binding domain stabilizes polyubiquitylated proteins
Authors: Tyrrell An , Flick Karin , Kleiger Gary , Zhang Hongwei , Deshaies Raymond J. , Kaiser Peter
Published: November 2010

Ubiquitylation of proteins can be a signal for a variety of cellular processes beyond the classical role in proteolysis. The different signaling functions of ubiquitylation are thought to rely on ubiquitin-binding domains (UBDs). Several distinct UBD families are known, but their functions are not understood in detail, and mechanisms for interpretation and transmission of the ubiquitin signals remain to be discovered. One interesting example of the complexity of ubiquitin signaling is the
Saccharomyces cerevisiae
transcription factor Met4, which is regulated by a single lysine-48 linked polyubiquitin chain that can directly repress activity of Met4 or induce degradation by the proteasome. Here we show that ubiquitin signaling in Met4 is controlled by its tandem UBD regions, consisting of a previously recognized ubiquitin-interacting motif and a novel ubiquitin-binding region, which lacks homology to known UBDs. The tandem arrangement of UBDs is required to protect ubiquitylated Met4 from degradation and enables direct inactivation of Met4 by ubiquitylation. Interestingly, protection from proteasomes is a portable feature of UBDs because a fusion of the tandem UBDs to the classic proteasome substrate Sic1 stabilized Sic1 in vivo in its ubiquitylated form. Using the well-defined Sic1 in vitro ubiquitylation system we demonstrate that the tandem UBDs inhibit efficient polyubiquitin chain elongation but have no effect on initiation of ubiquitylation. Importantly, we show that the nonproteolytic regulation enabled by the tandem UBDs is critical for ensuring rapid transcriptional responses to nutritional stress, thus demonstrating an important physiological function for tandem ubiquitin-binding domains that protect ubiquitylated proteins from degradation.