bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic field dependence of the maximum adiabatic temperature change
Authors: Kuz'min M. D. , Skokov K. P. , Karpenkov D. Yu. , Moore J. D. , Richter M. , Gutfleisch O.
Published: July 2011

The field dependence of the maximum magnetocaloric ΔT-effect in ferromagnets with second-order phase transitions is studied by way of direct measurements. All studied materials are found to follow the formula ΔTmax=A(H+H0)2/3-AH02/3, where A and H0 are constants and H is the internal magnetic field. It is essential to distinguish the latter from external field Hext. The dependence of ΔTmax on Hext is qualitatively distinct, the difference being particularly pronounced in the low-field region. In the field range relevant to applications (0.1–2 T), ΔTmax follows a linear dependence on H2/3. It is proposed to use the slope of this dependence as a figure of merit of magnetic refrigerants.
Top-gate dielectric induced doping and scattering of charge carriers in epitaxial graphene
Authors: Puls Conor P. , Staley Neal E. , Moon Jeong-Sun , Robinson Joshua A. , Campbell Paul M. , Tedesco Joseph L. , Myers-Ward Rachael L. , Eddy Charles R. , Gaskill D. Kurt , Liu Ying
Published: July 2011

We show that an e-gun deposited dielectric impose severe limits on epitaxial graphene-based device performance based on Raman spectroscopy and low-temperature transport measurements. Specifically, we show from studies of epitaxial graphene Hall bars covered by SiO2 that the measured carrier density is strongly inhomogenous and predominantly induced by charged impurities at the grapheme/dielectric interface that limit mobility via Coulomb interactions. Our work emphasizes that material integration of epitaxial graphene and a gate dielectric is the next major road block towards the realization of graphene-based electronics.
Thermoelectric power factor of In2O3:Pd nanocomposite films
Authors: Gregory Otto J. , Amani Matin , Fralick Gustave C.
Published: July 2011

A nanocomposite exhibiting large thermoelectric powers and capable of operating at temperatures as high as 1100 °C in air was fabricated by embedding palladium nanoparticles into an indium oxide matrix via co-sputtering from metal and ceramic targets. Combinatorial chemistry techniques were used to systematically investigate the effect of palladium content in these nanocomposite films on thermoelectric response. Based on these rapid screening experiments, the thermoelectric properties of the most promising nanocomposites were evaluated as a function of post-deposition heat treatment at high temperatures. An n-type nanocomposite film was developed exhibiting a power factor of 4.5 × 10−4 W/m·K2 at 1000 °C in air.
Temperature dependence of the local conductance in nanocrystalline CdSe films
Authors: Toker D. , Balberg I. , Zelaya-Angel O. , Savir E. , Millo O.
Published: July 2011

We have studied the local transport properties of nanocrystalline CdSe films by conductance atomic force microscopy (C-AFM) in the temperature range of 25–300 K. Surprisingly, the conductance measured under positive AFM-tip bias for the more resistive films was found to increase with decreasing temperature (i.e., “metallic-like” behavior), whereas the opposite temperature dependence was observed for the more conductive samples consisting of larger crystallites. We explain the results by considering the crystallite-size dependence of quantum-confinement and electron delocalization, which accounts also for the current decay-rate under the application of negative tip-bias.
Microbubbles as contrast agent for in-line x-ray phase-contrast imaging
Authors: Xi Yan , Tang Rongbiao , Wang Yujie , Zhao Jun
Published: July 2011

In the present study, we investigated the potential of gas-filled microbubbles as contrast agents for in-line x-ray phase-contrast imaging (PCI) in biomedical applications. When imaging parameters are optimized, the microbubbles function as microlenses that focus the incoming x-rays to form bright spots, which can significantly enhance the image contrast. Since microbubbles have been shown to be safe contrast agents in clinical ultrasonography, this contrast-enhancement procedure for PCI may have promising utility in biomedical applications, especially when the dose of radiation is a serious concern. In this study, we performed both numerical simulations and ex vivo experiments to investigate the formation of the contrast and the effectiveness of microbubbles as contrast agents in PCI.
Dopant profile control of epitaxial emitter for silicon solar cells by low temperature epitaxy
Authors: Lai Donny , Tan Yew Heng , Gunawan Oki , He Lining , Seng Tan Chuan
Published: July 2011

We report an alternative approach to grow phosphorus-doped epitaxial silicon emitter by rapid thermal chemical vapor deposition at low temperature (T ≥ 700 °C). A power conversion efficiency (PCE) of (6.6 ± 0.3)% and a pseudo PCE of (10.2 ± 0.2)% has been achieved for the solar cell with epi-emitter grown at 700 °C, in the absence of surface texturization, antireflective coating, and back surface field enhancement, without considering front contact shading. Secondary ion mass spectroscopy revealed that lower temperature silicon epitaxy yields a more abrupt p-n junction, suggesting potential applications for radial p-n junction wire array solar cells.
Extremely high internal quantum efficiencies from AlGaN/AlN quantum wells emitting in the deep ultraviolet spectral region
Authors: Banal Ryan G. , Funato Mitsuru , Kawakami Yoichi
Published: July 2011

Internal quantum efficiencies (IQEs) as high as 69% were realized at room temperature from AlGaN/AlN quantum wells (QWs) emitting at 247 nm grown by metalorganic vapor phase epitaxy. The extremely high IQEs were achieved by examining the source–supply sequence. QWs fabricated by a continuous source–supply method have longer emission wavelengths (λ) and higher IQEs compared to QWs fabricated by modified migration enhanced epitaxy (MMEE). MMEE is an alternating source–supply method where the NH3 interruption promotes Ga evaporation. Thus, to obtain the same λ, MMEE requires a lower growth temperature than the continuous method, compromising the quality of the AlN and AlGaN layers as well as the IQE of QWs.
Spectral and spatially resolved imaging of photoluminescence in multicrystalline silicon wafers
Authors: Olsen E. , Flø A.S.
Published: July 2011

The photoluminescent properties of multicrystalline silicon wafers have been studied using hyperspectral imaging in the region 900–1700 nm. Hyperspectral imaging provides high resolution macroscopic images in both the spatial and spectral dimensions over a time frame of seconds. Energy states introduced in the bandgap of Si from crystal imperfections resulted in increased recombination of photogenerated free charge carriers. Spectral resolution in the near infrared enabled us to spatially image specific radiative recombination processes through traps in the Si bandgap. Hyperspectral imaging is a fast, non-contact, and non-destructive method, giving it potential for industrial applications.
Electrically pumped heterogeneously integrated Si/III-V evanescent lasers with micro-loop mirror reflector
Authors: Zheng Yunan , Keh-Ting Ng Doris , Wei Yongqiang , Yadong Wang , Huang Yingyan , Tu Yongming , Lee Chee-Wei , Liu Boyang , Ho Seng-Tiong
Published: July 2011

An electrically pumped heterogeneously integrated Si/AlGaInAs evanescent laser with micro-loop mirror (MLM) as high reflectors at both ends is experimentally demonstrated. Finite-difference time-domain simulation shows that 98% reflectivity can be achieved with micro-loop mirror formed by single-mode silicon-on-insulator (SOI) waveguides. The laser based on a Si/III-V hybrid gain waveguide and passive SOI MLM reflectors is fabricated and single-mode continuous-wave (CW) lasing is achieved at room temperature with a lasing threshold current density of 2.5 kA/cm2.
On the efficiency of exciton dissociation at the interface between a conjugated polymer and an electron acceptor
Authors: Wiemer M. , Nenashev A. V. , Jansson F. , Baranovskii S. D.
Published: July 2011

It is a matter of controversy why excitons can efficiently dissociate into free carriers at an intrinsic polymer/fullerene interface, despite the strong Coulomb interaction between the charges provided by the very low dielectric constant in organic materials. The effect has been ascribed to the presence of intrinsic dipoles on the polymer/fullerene interface, though assuming an unrealistically small carrier effective mass necessary for exciton dissociation. We improve the model showing that it allows realistic carrier effective masses. The dissociation probability is calculated as a function of electric field acting on the dissociating electron-hole pairs.
Stark-effect scattering in rough quantum wells
Authors: Jana Raj K. , Jena Debdeep
Published: July 2011

A scattering mechanism stemming from the Stark-shift of energy levels by electric fields due to interface roughness in semiconductor quantum wells is identified. This scattering mechanism feeds off interface roughness and electric fields and modifies the well known “sixth-power” law of electron mobility degradation. This work first treats Stark-effect scattering in rough quantum wells as a perturbation for small electric fields and then directly absorbs it into the Hamiltonian for large fields. The major result is the existence of a window of quantum well widths for which the combined roughness scattering is minimum. Carrier scattering and mobility degradation in wide quantum wells are thus expected to be equally severe as in narrow wells due to Stark-effect scattering in electric fields.
Retrieval of terahertz spectra through ultrafast electro-optic modulation
Authors: Chen Z. , Gao Y. , DeCamp M. F.
Published: July 2011

Ultrafast electro-optic modulation on a narrow band optical pulse is utilized to spectrally resolve coherent terahertz radiation. This technique requires no moving parts and has the potential to measure THz spectra with a resolution better than 10 GHz, limited by the bandwidth of the optical probe field or optical spectrometer. The dynamic range of this device is limited by the detection capabilities of an optical spectrometer, providing a highly efficient method of spectral reconstruction of both narrow band and broadband terahertz radiation.
Electromechanics of twisted graphene nanoribbons
Authors: Koskinen Pekka
Published: July 2011

Graphene nanoribbons are the flimsiest material systems in the world, and they get readily distorted. Distortion by twisting, for one, is important because it couples to ribbon’s electronic properties. In this letter, using simulations with density-functional tight-binding and revised periodic boundary conditions, I show that twisting appears almost equivalent to stretching; electronic structures in a given nanoribbon either upon twisting or upon certain stretching are quantitatively similar. This simple equivalence will provide a valuable guideline for interpreting and designing experiments with these flimsy ribbons.
Comparative study on size dependence of melting temperatures of pure metal and alloy nanoparticles
Authors: Chen C. L. , Lee J.-G. , Arakawa K. , Mori H.
Published: July 2011

A comparative study on the size dependence of the melting temperatures of pure metal and alloy nanoparticles has been carried out. It was found that the melting temperatures of Bi-Sn, In-Sn, and Pb-Sn alloy nanoparticles decreased more rapidly with decreasing particle size than those of the constituent metal nanoparticles (Bi, In, Pb, Sn). Namely, the size dependence of the melting temperature was stronger for the alloy nanoparticles than that for the constituent metal nanoparticles. Results calculated with a thermodynamic model were in good agreement with the experimental observations.
Photoelectron spectroscopy study of band alignment at interface between Ni-InGaAs and In0.53Ga0.47As
Authors: Ivana  , Pan Jisheng , Zhang Zheng , Zhang Xingui , Guo Huaxin , Gong Xiao , Yeo Yee-Chia
Published: July 2011

The work function of Ni-InGaAs and the band alignment between Ni-InGaAs and In0.53Ga0.47As were investigated using photoelectron spectroscopy. The vacuum work function of Ni-InGaAs is obtained to be ∼5.1 eV using ultraviolet photoelectron spectroscopy (UPS). In addition, it was observed that the Fermi level of Ni-InGaAs is aligned to near conduction band of In0.53Ga0.47As at interface. For Ni-InGaAs formed on p-type In0.53Ga0.47As, this gives a Schottky contact with a hole barrier height of 0.8 ± 0.1 eV. Ni-InGaAs would form an ohmic contact on n-type In0.53Ga0.47As.
Fermi level shifting of TiO2 nanostructures during dense electronic excitation
Authors: Kumar Avesh , Jaiswal M. K. , Kanjilal D. , Joshi Rakesh K. , Mohanty T.
Published: July 2011

Scanning Kelvin probe microscopy has been used to understand the modification of work function of TiO2 with swift heavy ion irradiation. The observed increase in contact potential difference (CPD) indicates a shift in Fermi level towards the valence band, which is due to the development of defects during the bombardment of high energy heavy ions. The change in CPD values on ion irradiation is attributed to electronic excitation induced defect concentration and surface roughness.
Characterization of a junctionless diode
Authors: Yu Ran , Ferain Isabelle , Akhavan Nima Dehdashti , Razavi Pedram , Duffy Ray , Colinge Jean-Pierre
Published: July 2011

A diode has been realised using a silicon junctionless (JL) transistor. The device contains neither PN junction nor Schottky junction. The device is measured at different temperatures. The characteristics of the JL diode are essentially identical to those of a regular PN junction diode. The JL diode has an on/off current ratio of 108, an ideality factor of 1.09, and a reverse leakage current of 1 × 10−14 A at room temperature. The mechanism of the leakage current is discussed using the activation energy (EA). The turn-on voltage of the device can be tuned by JL transistor threshold voltage.
Extending the voltage window in the characterization of electrical transport of large-area molecular junctions
Authors: Katsouras Ilias , Kronemeijer Auke J. , Smits Edsger C. P. , van Hal Paul A. , Geuns Tom C. T. , Blom Paul W. M. , de Leeuw Dago M.
Published: July 2011

A large bias window is required to discriminate between different transport models in large-area molecular junctions. Under continuous DC bias, the junctions irreversibly break down at fields over 9 MV/cm. We show that, by using pulse measurements, we can reach electrical fields of 35 MV/cm before degradation. The breakdown voltage is shown to depend logarithmically on both duty cycle and pulse width. A tentative interpretation is presented based on electrolysis in the polymeric top electrode. Expanding the bias window using pulse measurements unambiguously shows that the electrical transport exhibits not an exponential but a power-law dependence on bias.
Rapid adiabatic passage in quantum dots: Influence of scattering and dephasing
Authors: Schuh K. , Jahnke F. , Lorke M.
Published: July 2011

Theoretical investigations for the realization of population inversion of semiconductor quantum dot ground-state transitions by means of adiabatic passage with chirped optical pulses are presented. While the inversion due to Rabi oscillations depends sensitively on the resonance condition, the pulse area, as well as on the absence of carrier scattering and dephasing, we find that adiabatic passage is surprisingly insensitive to the excitation conditions and carrier scattering effects. Quantum kinetic models for the interaction of quantum-dot carriers with longitudinal optical phonons are used to describe carrier scattering and dephasing in the corresponding simulations and allow to quantify the conditions to simultaneously invert an ensamble of quantum dots.
Action-Specific Effects Underwater
Authors: Witt Jessica K , Schuck Donald M , Taylor J Eric T
Published: July 2011

Action-specific effects on perception are apparent in terrestrial environments. For example, targets that require more effort to walk, jump, or throw to look farther away than when the targets require less effort. Here, we examined whether action-specific effects would generalize to an underwater environment. Instead, perception might be geometrically precise, rather than action-specific, in an environment that is novel from an evolutionary perspective. We manipulated ease to swim by giving participants swimming flippers or taking them away. Those who estimated distance while wearing the flippers judged underwater targets to be closer than did participants who had taken them off. In addition, participants with better swimming ability judged the targets to be closer than did those with worse swimming ability. These results suggest perceived distance underwater is a function of the perceiver's ability to swim to the targets.
Flashed Face Distortion Effect: Grotesque Faces from Relative Spaces
Authors: Tangen Jason M , Murphy Sean C , Thompson Matthew B
Published: July 2011

We describe a novel face distortion effect resulting from the fast-paced presentation of eye-aligned faces. When cycling through the faces on a computer screen, each face seems to become a caricature of itself and some faces appear highly deformed, even grotesque. The degree of distortion is greatest for faces that deviate from the others in the set on a particular dimension (eg if a person has a large forehead, it looks particularly large). This new method of image presentation, based on alignment and speed, could provide a useful tool for investigating contrastive distortion effects and face adaptation.
Order by disorder in the antiferromagnetic Ising model on an elastic triangular lattice
Authors: Shokef Yair , Souslov Anton , Lubensky T. C.
Published: July 2011

Geometrically frustrated materials have a ground-state degeneracy that may be lifted by subtle effects, such as higher-order interactions causing small energetic preferences for ordered structures. Alternatively, ordering may result from entropic differences between configurations in an effect termed order by disorder. Motivated by recent experiments in a frustrated colloidal system in which ordering is suspected to result from entropy, we consider in this paper the antiferromagnetic Ising model on a deformable triangular lattice. We calculate the displacements exactly at the microscopic level and, contrary to previous studies, find a partially disordered ground state of randomly zigzagging stripes. Each such configuration is deformed differently and thus has a unique phonon spectrum with distinct entropy, lifting the degeneracy at finite temperature. Nonetheless, due to the free-energy barriers between the ground-state configurations, the system falls into a disordered glassy state.
Quantitative dissection of the simple repression input–output function
Authors: Garcia Hernan G. , Phillips Rob
Published: July 2011

We present a quantitative case study of transcriptional regulation in which we carry out a systematic dialogue between theory and measurement for an important and ubiquitous regulatory motif in bacteria, namely, that of simple repression. This architecture is realized by a single repressor binding site overlapping the promoter. From the theory point of view, this motif is described by a single gene regulation function based upon only a few parameters that are convenient theoretically and accessible experimentally. The usual approach is turned on its side by using the mathematical description of these regulatory motifs as a predictive tool to determine the number of repressors in a collection of strains with a large variation in repressor copy number. The predictions and corresponding measurements are carried out over a large dynamic range in both expression fold change (spanning nearly four orders of magnitude) and repressor copy number (spanning about two orders of magnitude). The predictions are tested by measuring the resulting level of gene expression and are then validated by using quantitative immunoblots. The key outcomes of this study include a systematic quantitative analysis of the limits and validity of the input–output relation for simple repression, a precise determination of the in vivo binding energies for DNA–repressor interactions for several distinct repressor binding sites, and a repressor census for Lac repressor in
Escherichia coli
.
Predicting stochastic systems by noise sampling, and application to the El Niño-Southern Oscillation
Authors: Chekroun Mickaël David , Kondrashov Dmitri , Ghil Michael
Published: July 2011

Interannual and interdecadal prediction are major challenges of climate dynamics. In this article we develop a prediction method for climate processes that exhibit low-frequency variability (LFV). The method constructs a nonlinear stochastic model from past observations and estimates a path of the “weather” noise that drives this model over previous finite-time windows. The method has two steps: (
i
) select noise samples—or “snippets”—from the past noise, which have forced the system during short-time intervals that resemble the LFV phase just preceding the currently observed state; and (
ii
) use these snippets to drive the system from the current state into the future. The method is placed in the framework of pathwise linear-response theory and is then applied to an El Niño–Southern Oscillation (ENSO) model derived by the empirical model reduction (EMR) methodology; this nonlinear model has 40 coupled, slow, and fast variables. The domain of validity of this forecasting procedure depends on the nature of the system’s pathwise response; it is shown numerically that the ENSO model’s response is linear on interannual time scales. As a result, the method’s skill at a 6- to 16-month lead is highly competitive when compared with currently used dynamic and statistic prediction methods for the Niño-3 index and the global sea surface temperature field.
Reductive evolution of proteomes and protein structures
Authors: Wang Minglei , Kurland Charles G. , Caetano-Anollés Gustavo
Published: July 2011

The lengths of orthologous protein families in Eukarya are almost double the lengths found in Bacteria and Archaea. Here we examine protein structures in 745 genomes and show that protein length differences between superkingdoms arise as much shorter prokaryotic nondomain linker sequences. Eukaryotic, bacterial, and archaeal linkers are 250, 86, and 73 aa residues in length, respectively, whereas folded domain sequences are 281, 280, and 256 residues, respectively. Cryptic domains match linkers (
P
< 0.0001) with probabilities ranging between 0.022 and 0.042; accordingly, they do not affect length estimates significantly. Linker sequences support intermolecular binding within proteomes and they are probably enriched in intrinsically disordered regions as well. Reductively evolved linker sequence lengths in growth rate maximized cells should be proportional to proteome diversity. By using total in-frame coding capacity of a genome [i.e., coding sequence (CDS)] as a reliable measure of proteome diversity, we find linker lengths of prokaryotes clearly evolve in proportion to CDS values, whereas those of eukaryotes are more randomly larger than expected. Domain lengths scarcely change over the entire range of CDS values. Thus, the protein linkers of prokaryotes evolve reductively whereas those of eukaryotes do not.
T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications
Authors: Lluis Frederic , Ombrato Luigi , Pedone Elisa , Pepe Stefano , Merrill Bradley J. , Cosma Maria Pia
Published: July 2011

The heterochromatin barrier must be overcome to generate induced pluripotent stem cells and cell fusion-mediated reprogrammed hybrids. Here, we show that the absence of T-cell factor 3 (Tcf3), a repressor of β-catenin target genes, strikingly and rapidly enhances the efficiency of neural precursor cell (NPC) reprogramming. Remarkably, Tcf3
−/−
ES cells showed a genome-wide increase in AcH3 and decrease in H3K9me3 and can reprogram NPCs after fusion greatly. In addition, during reprogramming of NPCs into induced pluripotent stem cells, the silencing of Tcf3 increased AcH3 and decreased the number of H3K9me3-positive heterochromatin foci early and long before reactivation of the endogenous stem cell genes. In conclusion, our data suggest that Tcf3 functions as a repressor of the reprogramming potential of somatic cells.
Orphan nuclear transcription factor TR3/Nur77 regulates microvessel permeability by targeting endothelial nitric oxide synthase and destabilizing endothelial junctions
Authors: Zhao Dezheng , Qin Liuliang , Bourbon Pierre-Marie , James Lauralee , Dvorak Harold F. , Zeng Huiyan
Published: July 2011

Low-level basal vascular permeability (BVP) provides nutrients to normal tissues, and increased vascular permeability is characteristic of inflammation and cancer. We recently reported that VEGF-A, a potent vascular permeabilizing and angiogenic factor, exerts much of its angiogenic activity by up-regulating expression of TR3/Nur77, an orphan nuclear transcription factor, in vascular endothelial cells (EC). To determine whether TR3/Nur77 had a more general role in regulating vascular permeability, we found that histamine, serotonin, and platelet-activating factor, small molecule vascular permeabilizing agents, also increased TR3/Nur77 expression acutely in EC. BVP and the acute vascular hyperpermeability (AVH) induced by these vascular permeabilizing factors were greatly decreased in Nur77
−/−
mice, and both BVP and AVH correlated with Nur77 expression levels in several different mouse strains. BVP and AVH were enhanced in transgenic mice in which Nur77 was selectively overexpressed in vascular EC, whereas both were suppressed in mice overexpressing dominant-negative Nur77. Chronic vascular hyperpermeability (CVH) was induced long before the onset of angiogenesis in a modified, in vivo Matrigel assay that included PT67 cells packaging retroviruses expressing Nur77-sense, whereas inclusion of cells packaging viruses expressing Nur77-antisense prevented VEGF-A–induced CVH. TR3/Nur77 modulated vascular permeability by increasing endothelial nitric-oxide synthase expression and by downregulating several EC junction proteins that maintain vascular homeostasis. Both functions required TR3/Nur77 transcriptional activity. Taking these data together, TR3/Nur77 is up-regulated by several vascular permeabilizing agents and has critical roles in mediating BVP, AVH, and CVH.
Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle defects in mice by dietary and genetic strategies
Authors: Selesniemi Kaisa , Lee Ho-Joon , Muhlhauser Ailene , Tilly Jonathan L.
Published: July 2011

Increased meiotic spindle abnormalities and aneuploidy in oocytes of women of advanced maternal ages lead to elevated rates of infertility, miscarriage, and trisomic conceptions. Despite the significance of the problem, strategies to sustain oocyte quality with age have remained elusive. Here we report that adult female mice maintained under 40% caloric restriction (CR) did not exhibit aging-related increases in oocyte aneuploidy, chromosomal misalignment on the metaphase plate, meiotic spindle abnormalities, or mitochondrial dysfunction (aggregation, impaired ATP production), all of which occurred in oocytes of age-matched ad libitum-fed controls. The effects of CR on oocyte quality in aging females were reproduced by deletion of the metabolic regulator, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Thus, CR during adulthood or loss of PGC-1α function maintains female germline chromosomal stability and its proper segregation during meiosis, such that ovulated oocytes of aged female mice previously maintained on CR or lacking PGC-1α are comparable to those of young females during prime reproductive life.
Separating intrinsic from extrinsic fluctuations in dynamic biological systems
Authors: Hilfinger Andreas , Paulsson Johan
Published: July 2011

From molecules in cells to organisms in ecosystems, biological populations fluctuate due to the intrinsic randomness of individual events and the extrinsic influence of changing environments. The combined effect is often too complex for effective analysis, and many studies therefore make simplifying assumptions, for example ignoring either intrinsic or extrinsic effects to reduce the number of model assumptions. Here we mathematically demonstrate how two identical and independent reporters embedded in a shared fluctuating environment can be used to identify intrinsic and extrinsic noise terms, but also how these contributions are qualitatively and quantitatively different from what has been previously reported. Furthermore, we show for which classes of biological systems the noise contributions identified by dual-reporter methods correspond to the noise contributions predicted by correct stochastic models of either intrinsic or extrinsic mechanisms. We find that for broad classes of systems, the extrinsic noise from the dual-reporter method can be rigorously analyzed using models that ignore intrinsic stochasticity. In contrast, the intrinsic noise can be rigorously analyzed using models that ignore extrinsic stochasticity only under very special conditions that rarely hold in biology. Testing whether the conditions are met is rarely possible and the dual-reporter method may thus produce flawed conclusions about the properties of the system, particularly about the intrinsic noise. Our results contribute toward establishing a rigorous framework to analyze dynamically fluctuating biological systems.
Bioluminescence resonance energy transfer (BRET) imaging of protein–protein interactions within deep tissues of living subjects
Authors: Dragulescu-Andrasi Anca , Chan Carmel T. , De Abhijit , Massoud Tarik F. , Gambhir Sanjiv S.
Published: July 2011

Identifying protein–protein interactions (PPIs) is essential for understanding various disease mechanisms and developing new therapeutic approaches. Current methods for assaying cellular intermolecular interactions are mainly used for cells in culture and have limited use for the noninvasive assessment of small animal disease models. Here, we describe red light-emitting reporter systems based on bioluminescence resonance energy transfer (BRET) that allow for assaying PPIs both in cell culture and deep tissues of small animals. These BRET systems consist of the recently developed
Renilla reniformis
luciferase (RLuc) variants RLuc8 and RLuc8.6, used as BRET donors, combined with two red fluorescent proteins, TagRFP and TurboFP635, as BRET acceptors. In addition to the native coelenterazine luciferase substrate, we used the synthetic derivative coelenterazine-
v
, which further red-shifts the emission maxima of
Renilla
luciferases by 35 nm. We show the use of these BRET systems for ratiometric imaging of both cells in culture and deep-tissue small animal tumor models and validate their applicability for studying PPIs in mice in the context of rapamycin-induced FK506 binding protein 12 (FKBP12)-FKBP12 rapamycin binding domain (FRB) association. These red light-emitting BRET systems have great potential for investigating PPIs in the context of drug screening and target validation applications.
A neural basis for real-world visual search in human occipitotemporal cortex
Authors: Peelen Marius V. , Kastner Sabine
Published: July 2011

Mammals are highly skilled in rapidly detecting objects in cluttered natural environments, a skill necessary for survival. What are the neural mechanisms mediating detection of objects in natural scenes? Here, we use human brain imaging to address the role of top-down preparatory processes in the detection of familiar object categories in real-world environments. Brain activity was measured while participants were preparing to detect highly variable depictions of people or cars in natural scenes that were new to the participants. The preparation to detect objects of the target category, in the absence of visual input, evoked activity patterns in visual cortex that resembled the response to actual exemplars of the target category. Importantly, the selectivity of multivoxel preparatory activity patterns in object-selective cortex (OSC) predicted target detection performance. By contrast, preparatory activity in early visual cortex (V1) was negatively related to search performance. Additional behavioral results suggested that the dissociation between OSC and V1 reflected the use of different search strategies, linking OSC preparatory activity to relatively abstract search preparation and V1 to more specific imagery-like preparation. Finally, whole-brain searchlight analyses revealed that, in addition to OSC, response patterns in medial prefrontal cortex distinguished the target categories based on the search cues alone, suggesting that this region may constitute a top-down source of preparatory activity observed in visual cortex. These results indicate that in naturalistic situations, when the precise visual characteristics of target objects are not known in advance, preparatory activity at higher levels of the visual hierarchy selectively mediates visual search.
Critical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis
Authors: Herrero Lara J. , Nelson Michelle , Srikiatkhachorn Anon , Gu Ran , Anantapreecha Surapee , Fingerle-Rowson Günter , Bucala Richard , Morand Eric , Santos Leilani L. , Mahalingam Suresh
Published: July 2011

Arthrogenic alphaviruses, such as Ross River virus (RRV), chikungunya, Sindbis, mayaro and o'nyong-nyong viruses circulate endemically worldwide, frequently causing outbreaks of polyarthritis. The exact mechanisms of how alphaviruses induce polyarthritis remain ill defined, although macrophages are known to play a key role. Macrophage migration inhibitory factor (MIF) is an important cytokine involved in rheumatoid arthritis pathogenesis. Here, we characterize the role of MIF in alphavirus–induced arthritides using a mouse model of RRV-induced arthritis, which has many characteristics of RRV disease in humans. RRV-infected WT mice developed severe disease associated with up-regulated MIF expression in serum and tissues, which corresponded to severe inflammation and tissue damage. MIF-deficient (MIF−/−) mice developed mild disease accompanied by a reduction in inflammatory infiltrates and muscle destruction in the tissues, despite having viral titers similar to WT mice. In addition, reconstitution of MIF into MIF−/−mice exacerbated RRV disease and treatment of mice with MIF antagonist ameliorated disease in WT mice. Collectively, these findings suggest that MIF plays a critical role in determining the clinical severity of alphavirus–induced musculoskeletal disease and may provide a target for the development of antiviral pharmaceuticals. The prospect being that early treatment with MIF-blocking pharmaceuticals may curtail the debilitating arthritis associated with alphaviral infections.
Observing Majorana bound states of Josephson vortices in topological superconductors
Authors: Grosfeld Eytan , Stern Ady
Published: July 2011

In recent years there has been an intensive search for Majorana fermion states in condensed matter systems. Predicted to be localized on cores of vortices in certain nonconventional superconductors, their presence is known to render the exchange statistics of bulk vortices non-Abelian. Here we study the equations governing the dynamics of phase solitons (fluxons) in a Josephson junction in a topological superconductor. We show that the fluxon will bind a localized zero energy Majorana mode and will consequently behave as a non-Abelian anyon. The low mass of the fluxon, as well as its experimentally observed quantum mechanical wave-like nature, will make it a suitable candidate for vortex interferometry experiments demonstrating non-Abelian statistics. We suggest two experiments that may reveal the presence of the zero mode carried by the fluxon. Specific experimental realizations will be discussed as well.
Apoptosis inhibitor of macrophage (AIM) is required for obesity-associated recruitment of inflammatory macrophages into adipose tissue
Authors: Kurokawa Jun , Nagano Hiromichi , Ohara Osamu , Kubota Naoto , Kadowaki Takashi , Arai Satoko , Miyazaki Toru
Published: July 2011

Infiltration of inflammatory macrophages into adipose tissues with the progression of obesity triggers insulin resistance and obesity-related metabolic diseases. We recently reported that macrophage-derived apoptosis inhibitor of macrophage (AIM) protein is increased in blood in line with obesity progression and is incorporated into adipocytes, thereby inducing lipolysis in adipose tissue. Here we show that such a response is required for the recruitment of adipose tissue macrophages. In vitro, AIM-dependent lipolysis induced an efflux of palmitic and stearic acids from 3T3-L1 adipocytes, thereby stimulating chemokine production in adipocytes via activation of toll-like receptor 4 (TLR4). In vivo administration of recombinant AIM toTLR4-deficient (TLR4−/−) mice resulted in induction of lipolysis without chemokine production in adipose tissues. Consistently, mRNA levels for the chemokines that affect macrophages were far lower inAIM-deficient (AIM−/−) than in wild-type (AIM+/+) obese adipose tissue. This reduction in chemokine production resulted in a marked prevention of inflammatory macrophage infiltration into adipose tissue in obeseAIM−/−mice, although these mice showed more advanced obesity thanAIM+/+mice on a high-fat diet. Diminished macrophage infiltration resulted in decreased inflammation locally and systemically in obeseAIM−/−mice, thereby protecting them from insulin resistance and glucose intolerance. These results indicate that the increase in blood AIM is a critical event for the initiation of macrophage recruitment into adipose tissue, which is followed by insulin resistance. Thus, AIM suppression might be therapeutically applicable for the prevention of obesity-related metabolic disorders.
Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability
Authors: Pant Vinod , Xiong Shunbin , Iwakuma Tomoo , Quintás-Cardama Alfonso , Lozano Guillermina
Published: July 2011

Mdm2 and Mdm4 are homologous RING domain-containing proteins that negatively regulate the tumor suppressor p53 under physiological and stress conditions. The RING domain of Mdm2 encodes an E3-ubiquitin ligase that promotes p53 degradation. In addition, Mdm2 and Mdm4 interact through their respective RING domains. The in vivo significance of Mdm2-Mdm4 heterodimerization in regulation of p53 function is unknown. In this study, we generated an
Mdm4
conditional allele lacking the RING domain to investigate its role in Mdm2 and p53 regulation. Our results demonstrate that homozygous deletion of the Mdm4 RING domain results in prenatal lethality. Mechanistically, Mdm2-Mdm4 heterodimerization is critical for inhibiting lethal p53 activation during early embryogenesis. However, Mdm2-Mdm4 interaction is dispensable for regulating p53 activity as well as the stability of Mdm2 and p53 at later stages of development. We propose that Mdm4 is a key cofactor of Mdm2 that inhibits p53 activity primarily during early embryogenesis but is dispensable for regulating p53 and Mdm2 stability in the adult mouse.
Reconciling anthropogenic climate change with observed temperature 1998–2008
Authors: Kaufmann Robert K. , Kauppi Heikki , Mann Michael L. , Stock James H.
Published: July 2011

Given the widely noted increase in the warming effects of rising greenhouse gas concentrations, it has been unclear why global surface temperatures did not rise between 1998 and 2008. We find that this hiatus in warming coincides with a period of little increase in the sum of anthropogenic and natural forcings. Declining solar insolation as part of a normal eleven-year cycle, and a cyclical change from an El Nino to a La Nina dominate our measure of anthropogenic effects because rapid growth in short-lived sulfur emissions partially offsets rising greenhouse gas concentrations. As such, we find that recent global temperature records are consistent with the existing understanding of the relationship among global surface temperature, internal variability, and radiative forcing, which includes anthropogenic factors with well known warming and cooling effects.
Inequality, communication, and the avoidance of disastrous climate change in a public goods game
Authors: Tavoni Alessandro , Dannenberg Astrid , Kallis Giorgos , Löschel Andreas
Published: July 2011

International efforts to provide global public goods often face the challenges of coordinating national contributions and distributing costs equitably in the face of uncertainty, inequality, and free-riding incentives. In an experimental setting, we distribute endowments unequally among a group of people who can reach a fixed target sum through successive money contributions, knowing that if they fail, they will lose all their remaining money with 50% probability. In some treatments, we give players the option to communicate intended contributions. We find that inequality reduces the prospects of reaching the target but that communication increases success dramatically. Successful groups tend to eliminate inequality over the course of the game, with rich players signaling willingness to redistribute early on. Our results suggest that coordination-promoting institutions and early redistribution from richer to poorer nations are both decisive for the avoidance of global calamities, such as disruptive climate change.
Molecular determinants for selective recognition of antidepressants in the human serotonin and norepinephrine transporters
Authors: Andersen Jacob , Stuhr-Hansen Nicolai , Zachariassen Linda , Toubro Søren , Hansen Stinna M. R. , Eildal Jonas N. N. , Bond Andrew D. , Bøgesø Klaus P. , Bang-Andersen Benny , Kristensen Anders S. , Strømgaard Kristian
Published: July 2011

Inhibitors of the serotonin transporter (SERT) and norepinephrine transporter (NET) are widely used in the treatment of major depressive disorder. Although SERT/NET selectivity is a key determinant for the therapeutic properties of these drugs, the molecular determinants defining SERT/NET selectivity are poorly understood. In this study, the structural basis for selectivity of the SERT selective inhibitor citalopram and the structurally closely related NET selective inhibitor talopram is delineated. A systematic structure-activity relationship study allowed identification of the substituents that control activity and selectivity toward SERT and NET and revealed a common pattern showing that SERT and NET have opposite preference for the stereochemical configuration of these inhibitors. Mutational analysis of nonconserved SERT/NET residues within the central substrate binding site was performed to determine the molecular basis for inhibitor selectivity. Changing only five residues in NET to the complementary residues in SERT transferred a SERT-like affinity profile for
R
- and
S
-citalopram into NET, showing that the selectivity of these compounds is determined by amino acid differences in the central binding site of the transporters. In contrast, the activity of
R
- and
S
-talopram was largely unaffected by any mutations within the central substrate binding site of SERT and NET and in the outer vestibule of NET, suggesting that citalopram and talopram bind to distinct sites on SERT and NET. Together, these findings provide important insight into the molecular basis for SERT/NET selectivity of antidepressants, which can be used to guide rational development of unique transporter inhibitors with fine-tuned transporter selectivity.
Small-molecule inhibitor binding to an
N
-acyl-homoserine lactone synthase
Authors: Chung Jiwoung , Goo Eunhye , Yu Sangheon , Choi Okhee , Lee Jeehyun , Kim Jinwoo , Kim Hongsup , Igarashi Jun , Suga Hiroaki , Moon Jae Sun , Hwang Ingyu , Rhee Sangkee
Published: July 2011

Quorum sensing (QS) controls certain behaviors of bacteria in response to population density. In Gram-negative bacteria, QS is often mediated by
N
-acyl-
l
-homoserine lactones (acyl-HSLs). Because QS influences the virulence of many pathogenic bacteria, synthetic inhibitors of acyl-HSL synthases might be useful therapeutically for controlling pathogens. However, rational design of a potent QS antagonist has been thwarted by the lack of information concerning the binding interactions between acyl-HSL synthases and their ligands. In the Gram-negative bacterium
Burkholderia glumae
, QS controls virulence, motility, and protein secretion and is mediated by the binding of
N
-octanoyl-
l
-HSL (C8-HSL) to its cognate receptor, TofR. C8-HSL is synthesized by the acyl-HSL synthase TofI. In this study, we characterized two previously unknown QS inhibitors identified in a focused library of acyl-HSL analogs. Our functional and X-ray crystal structure analyses show that the first inhibitor, J8-C8, binds to TofI, occupying the binding site for the acyl chain of the TofI cognate substrate, acylated acyl-carrier protein. Moreover, the reaction byproduct, 5′-methylthioadenosine, independently binds to the binding site for a second substrate,
S
-adenosyl-
l
-methionine. Closer inspection of the mode of J8-C8 binding to TofI provides a likely molecular basis for the various substrate specificities of acyl-HSL synthases. The second inhibitor, E9C-3oxoC6, competitively inhibits C8-HSL binding to TofR. Our analysis of the binding of an inhibitor and a reaction byproduct to an acyl-HSL synthase may facilitate the design of a new class of QS-inhibiting therapeutic agents.
The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires endosomal sorting complex responsible for transport (ESCRT) function
Authors: Giordano Francesca , Simoes Sabrina , Raposo Graça
Published: July 2011

The function of signaling receptors is tightly controlled by their intracellular trafficking. One major regulatory mechanism within the endo-lysosomal system required for receptor localization and down-regulation is protein modification by ubiquitination and downstream interactions with the endosomal sorting complex responsible for transport (ESCRT) machinery. Whether and how these mechanisms operate to regulate endosomal sorting of mammalian G protein-coupled receptors (GPCRs) remains unclear. Here, we explore the involvement of ubiquitin and ESCRTs in the trafficking of OA1, a pigment cell-specific GPCR, target of mutations in Ocular Albinism type 1, which localizes intracellularly to melanosomes to regulate their biogenesis. Using biochemical and morphological methods in combination with overexpression and inactivation approaches we show that OA1 is ubiquitinated and that its intracellular sorting and down-regulation requires functional ESCRT components. Depletion or overexpression of subunits of ESCRT-0, -I, and -III markedly inhibits OA1 degradation with concomitant retention within the modified endosomal system. Our data further show that OA1 ubiquitination is uniquely required for targeting to the intralumenal vesicles of multivesicular endosomes, thereby regulating the balance between down-regulation and delivery to melanosomes. This study highlights the role of ubiquitination and the ESCRT machinery in the intracellular trafficking of mammalian GPCRs and has implications for the physiopathology of ocular albinism type 1.