bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of ion orbit loss on the structure in the H-mode tokamak edge pedestal profiles of rotation velocity, radial electric field, density, and temperature
Authors: Stacey Weston M.
Published: September 2013

An investigation of the effect of ion orbit loss of thermal ions and the compensating return ion current directly on the radial ion flux flowing in the plasma, and thereby indirectly on the toroidal and poloidal rotation velocity profiles, the radial electric field, density, and temperature profiles, and the interpretation of diffusive and non-diffusive transport coefficients in the plasma edge, is described. Illustrative calculations for a high-confinement H-mode DIII-D [J. Luxon, Nucl. Fusion 42, 614 (2002)] plasma are presented and compared with experimental results. Taking into account, ion orbit loss of thermal ions and the compensating return ion current is found to have a significant effect on the structure of the radial profiles of these quantities in the edge plasma, indicating the necessity of taking ion orbit loss effects into account in interpreting or predicting these quantities.
Development of the gas puff charge exchange recombination spectroscopy (GP-CXRS) technique for ion measurements in the plasma edge
Authors: Churchill R. M. , Theiler C. , Lipschultz B. , Dux R. , Pütterich T. , Viezzer E. ,   Alcator C-Mod Team,   ASDEX Upgrade Team
Published: September 2013

A novel charge-exchange recombination spectroscopy (CXRS) diagnostic method is presented, which uses a simple thermal gas puff for its donor neutral source, instead of the typical high-energy neutral beam. This diagnostic, named gas puff CXRS (GP-CXRS), is used to measure ion density, velocity, and temperature in the tokamak edge/pedestal region with excellent signal-background ratios, and has a number of advantages to conventional beam-based CXRS systems. Here we develop the physics basis for GP-CXRS, including the neutral transport, the charge-exchange process at low energies, and effects of energy-dependent rate coefficients on the measurements. The GP-CXRS hardware setup is described on two separate tokamaks, Alcator C-Mod and ASDEX Upgrade. Measured spectra and profiles are also presented. Profile comparisons of GP-CXRS and a beam based CXRS system show good agreement. Emphasis is given throughout to describing guiding principles for users interested in applying the GP-CXRS diagnostic technique.
Exploring electrical conductivity within mesoscopic phases of semiconducting poly(3,4-ethylenedioxythiophene):poly(4-styrene-sulfonate) films by broadband dielectric spectroscopy
Authors: Papathanassiou A. N. , Sakellis I. , Grammatikakis J. , Vitoratos E. , Sakkopoulos S.
Published: September 2013

Poly(3,4-ethylenedioxythiophene): poly(4-styrene sulfonate) (PEDOT:PSS), an optically transparent organic semi-conductor, constitutes a suspension of conducting PEDOT:PSS grains, shelled by an insulating layer of PSS. While a percolation network enhances dc conductivity, structural and electrical inhomogeneity hinters electric charge flow giving rise to capacitance effects. In the present work, two distinct relaxation mechanisms are detected by Broadband Dielectric Spectroscopy. Double polarization mechanisms are predicted by bi-phase suspension dielectric theory. Within the frame of interfacial polarization, we propose a methodology to have an insight into the local conductivity of the interior of mesoscopic conducting phase.
Tandem organic photovoltaics incorporating two solution-processed small molecule donor layers
Authors: Lassiter B. E. , Zimmerman J. D. , Forrest S. R.
Published: September 2013

We develop a partially solution-processed small molecule tandem organic photovoltaic cell using an organic/inorganic interlayer structure that provides efficient charge recombination while protecting underlying layers from degradation due to attack from solvents applied during the deposition of subsequent sub-cells. Each sub-cell consists of a functionalized squaraine (fSQ) blend donor that is cast from solution, followed by evaporation of other functional layers. The first fSQ layer is cast from chloroform, while the second is cast from a tetrahydrofuran, thereby minimizing dissolution of the relatively insoluble, underlying fullerene layer that acts to protect the first donor layer. Solvent vapor annealing increases the sub-cell performance while decreasing the damage caused by spin-coating of the second fSQ layer, both of which result from increased film crystallinity that reduces the rate of solvent penetration. The tandem cell has a power conversion efficiency of 6.2% ± 0.3% and an open circuit voltage nearly equal to the sum of the constituent sub-cells.
Contragredient supersymmetric pairs
Authors: Chuah Meng-Kiat
Published: September 2013

The symmetric pairs of complex semisimple Lie algebras can be characterized by commuting involutions. We present its analogue on the contragredient Lie superalgebras, so that their symmetric pairs correspond to some commuting automorphisms. As an application, we classify the symmetric pairs of the exceptional Lie superalgebras F(4) and G(3).
Surfactant-induced stagnant zones in the Jeong-Moffatt free surface Stokes flow problem
Authors: Crowdy Darren G.
Published: September 2013

We investigate the effect of surfactants on the problem introduced by Jeong and Moffatt [J. Fluid Mech. 241, 1–22 (1992)] to model the free surface deformation induced by two rollers beneath an infinite interface in a bath of viscous fluid. We demonstrate that the presence of surfactant dramatically affects the shape of the response curve for steady state equilibria. It is also shown that there is a well defined, albeit non-uniform, passage to the clean flow limit as the influence of the surfactant vanishes. Our analysis proceeds via a new mathematical approach to mixed boundary value problems arising in free surface Marangoni flows at infinite Péclet number in two-dimensional Stokes flows. Such problems often involve interfaces with a mixture of no-slip zones and regions where a capillary stress balance holds. By a conformal mapping technique accounting for the square root singularities inherent in such mixed boundary value problems it is shown that the latter can be transformed to the classical modified Schwarz problem of complex analysis solvable by standard methods. As a second application of the method we give a new derivation, and representation, of the solutions for steady surfactant-laden stagnant-cap bubbles in a linear strain presented by Siegel [SIAM J. Appl. Math. 59, 1998–2027 (1999)].
Cooling rate and size effects on the medium-range structure of multicomponent oxide glasses simulated by molecular dynamics
Authors: Tilocca Antonio
Published: September 2013

A set of molecular dynamics simulations were performed to investigate the effect of cooling rate and system size on the medium-range structure of melt-derived multicomponent silicate glasses, represented by the quaternary 45S5 Bioglass composition. Given the significant impact of the glass degradation on applications of these materials in biomedicine and nuclear waste disposal, bulk structural features which directly affect the glass dissolution process are of particular interest. Connectivity of the silicate matrix, ion clustering and nanosegregation, distribution of ring and chain structural patterns represent critical features in this context, which can be directly extracted from the models. A key issue is represented by the effect of the computational approach on the corresponding glass models, especially in light of recent indications questioning the suitability of conventional MD approaches (that is, involving melt-and-quench of systems containing ∼103 atoms at cooling rates of 5-10 K/ps) when applied to model these glasses. The analysis presented here compares MD models obtained with conventional and nonconventional cooling rates and system sizes, highlighting the trend and range of convergence of specific structural features in the medium range. The present results show that time-consuming computational approaches involving much lower cooling rates and/or significantly larger system sizes are in most cases not necessary in order to obtain a reliable description of the medium-range structure of multicomponent glasses. We identify the convergence range for specific properties and use them to discuss models of several glass compositions for which a possible influence of cooling-rate or size effects had been previously hypothesized. The trends highlighted here represent an important reference to obtain reliable models of multicomponent glasses and extract converged medium-range structural features which affect the glass degradation and thus their application in different fields. In addition, as a first application of the present findings, the fully converged structure of the 45S5 glass was further analyzed to shed new light on several dissolution-related features whose interpretation has been rather controversial in the past.
Effects of impact velocity on pressure-driven nanofluid
Authors: Liu Hailong , Cao Guoxin
Published: September 2013

Using molecular dynamics simulations, we investigate the pressure-driven water infiltration behavior of carbon nanotubes (CNTs), in which water molecules can infiltrate into CNTs from outside upon an external impact load. According to the direction of impact mechanical wave, the infiltration procedure can be divided into the forward stage (stage I) and the reflected stage (stage II). At the forward stage of mechanical wave, the flow behavior strongly depends on the impact velocity but it is essentially not very sensitive to the tube radius. With a higher impact velocity, the water flow has a higher transport velocity, a lower density, a weaker CNT-water interaction, a higher potential energy, and a more disordered structure shown by a wider distribution of water dipole and OH bonds orientations. At the reflected stage, due to the impact pressure effect, the water structure is significantly changed, and the flow behavior is less sensitive to the impact velocity but more sensitive to the tube radius. After the reflected wave passed the water molecules inside CNTs, the water density and potential are significantly increased, which initiates a significant change for the water structure inside CNTs, especially for small size tubes. In a small tube like (10,10), a new water conformation is created in the reflected procedure, while there is no such new structure created in a larger tube like (20,20). Due to the different structures, the behavior of the pressure-driven water flow inside CNTs is significantly different than the steady flow.
New methodology of speed-control of photovoltaic pumping system
Authors: Khiareddine A. , Ben Salah C. , Mimouni M. F.
Published: September 2013

The use of renewable energy is growing significantly in the world. In front of the growing demand for electric energy, essentially for the needs of remote, desolate, and mountainous regions, photovoltaic systems, especially water pumping systems, are beginning to emerge in large applications. In this sense, the proposed study deals with the problem of the water level regulation in the photovoltaic pumping system. To achieve this aim, a fuzzy logic controller has been developed in order to determine the reference speed needed for vectorial command of induction motor, taking into account the water level in the tank and the variation of solar irradiation. On the one hand, the energy management and control of the photovoltaic subsystem is based on voltage and current control with maximum power point tracking allowing the optimal transfer of power to the pump through two converters, a boost (DC-DC converter) and an inverter (DC-AC converter) are controlled by space vector pulse width modulation. On the other hand, the proposed study provides a comparison between a fuzzy logic controller and an algorithm controller. The latter technique is less successful than the first, but more easily implemented. The string of photovoltaic pumping is simulated under Matlab-Simulink. The results were promising, and yet they remain to be validated in practice.
Simulation of charge transport in multi-island tunneling devices: Application to disordered one-dimensional systems at low and high biases
Authors: Savaikar Madhusudan A. , Banyai Douglas , Bergstrom Paul L. , Jaszczak John A.
Published: September 2013

Although devices have been fabricated displaying interesting single-electron transport characteristics, there has been limited progress in the development of tools that can simulate such devices based on their physical geometry over a range of bias conditions up to a few volts per junction. In this work, we present the development of a multi-island transport simulator, MITS, a simulator of tunneling transport in multi-island devices that takes into account geometrical and material parameters, and can span low and high source-drain biases. First, the capabilities of MITS are demonstrated by modeling experimental devices described in the literature, and showing that the simulated device characteristics agree well with the experimental observations. Then, the results of studies of charge transport through a long one-dimensional (1D) chain of gold nano-islands on an insulating substrate are presented. Current-voltage (IV) characteristics are investigated as a function of the overall chain-length and temperature. Under high bias conditions, where temperature has a minimal effect, the IV characteristics are non-Ohmic, and do not exhibit any Coulomb staircase (CS) structures. The overall resistance of the device also increases non-linearly with increasing chain-length. For small biases, IV characteristics show clear CS structures that are more pronounced for larger chain-lengths. The Coulomb blockade and the threshold voltage (Vth) required for device switching increase linearly with the increase in chain length. With increasing temperature, the blockade effects are diminished as the abrupt increase in current at Vth is washed out and the apparent blockade decreases. Microscopic investigations demonstrate that the overall IV characteristics are a result of a complex interplay among those factors that affect the tunneling rates that are fixed a priori (island sizes, island separations, temperature, etc.), and the evolving charge state of the system, which changes as the applied source-drain bias (VSD) is changed. In a system of nano-islands with a broad distribution of sizes and inter-island spacings, the applied bias is divided across the junctions as one would expect of a voltage divider, with larger potential drops across the wider junctions and smaller drops across the narrower junctions. As a result, the tunneling resistances across these wider junctions decrease dramatically, relative to the other junctions, at high VSD thereby increasing their electron tunneling rates. IV behavior at high VSD follows a power-law scaling behavior with the exponent dependent on the length of the chain and the degree of disorder in the system.
Electronic structure and ferromagnetism of boron doped bulk and surface CdSe: By generalized gradient approximation and generalized gradient approximation plus modified Becke and Johnson calculations
Authors: Fan S. W. , Ding L. J. , Yao K. L.
Published: September 2013

Using the full potential linearized augment plane wave method with the generalized gradient approximation (GGA) and GGA plus modified Becke and Johnson (GGA+mBJ) potential, the electronic structures and ferromagnetism for the boron doped bulk and surface CdSe are investigated. Calculations show that the substitutional boron for selenium in CdSe could induce spin polarized localized states in the gap and generate local magnetic moments 3.00 μB with one dopant atom. Energy difference between the antiferromagnetic and ferromagnetic phase suggests that BSe favors the ferromagnetic ground state. Electronic structures indicate the magnetic moments mainly provided by the doped boron atoms, and carriers mediated double exchange mechanism plays crucial role in forming the ferromagnetism. Ferromagnetic boron doped CdSe (100) films could be realized by using the high energy boron ions injection to form the non-surface doped configurations. The cadmium vacancy would reduce the ferromagnetism and lead the boron doped CdSe to magnetic metallicity. Formation energy for the four high symmetry doped configurations indicates BSe could be realized by using Cd-rich condition.
Non-contact method for measurement of the microwave conductivity of graphene
Authors: Hao L. , Gallop J. , Goniszewski S. , Shaforost O. , Klein N. , Yakimova R.
Published: September 2013

We report a non-contact method for conductivity and sheet resistance measurements of monolayer and few layers graphene samples using a high Q microwave dielectric resonator perturbation technique, with the aim of fast and accurate measurement. The dynamic range of the microwave conductivity measurements makes this technique sensitive to a range of imperfections and impurities and can provide rapid non-contacting characterisation. As a demonstration of the power of the technique, we present results for graphene samples grown by three different methods with widely differing sheet resistance values.
Origins of nanostructure in amorphous polymer coatings via matrix assisted pulsed laser evaporation
Authors: Shepard Kimberly B. , Arnold Craig B. , Priestley Rodney D.
Published: September 2013

We investigate the nanostructure of sub-monolayer and monolayer amorphous polymer films deposited via Matrix Assisted Pulsed Laser Evaporation (MAPLE). The structure is quantified by analyzing the size distribution of polymer nanoglobules as a function of deposition parameters: time and polymer concentration. Two deposition regimes are observed in the early stages of MAPLE deposition, with a transition at a critical time. The observed distribution of nanoglobule sizes that is present after the critical time agrees well with prior molecular dynamics simulations of the MAPLE process. We discuss the mechanism of nanostructured coatings within the framework of the Zhigilei model.
Nanosecond optical imaging spectroscopy of an electrothermal radiofrequency plasma thruster plume
Authors: Charles C. , Dedrick J. , Boswell R. W. , O'Connell D. , Gans T.
Published: September 2013

Nanosecond optical imaging spectroscopy is employed to investigate the spatio-temporal dynamics of the plasma plume expanding from a 4.2 mm-diameter, 20 mm-long cylindrical capacitively coupled electrothermal radiofrequency (rf) driven thruster using 10 W of power at 12.50 MHz and an argon pressure of 1.5 Torr. On-axis, the plume exhibits four distinct peaks of optical emission intensity within the rf period. The plume has a spherical shape with a transient radial extension (during half of the rf cycle) at the thruster exit plane due to an rf current to ground when the grounded electrode acts as an anode.
Metabolic responses of horses and ponies to high and low glycaemic feeds: implications for laminitis
Authors: Bailey S. R. , Bamford N. J.
Published: September 2013

Equine laminitis is the painful condition resulting from disruption of the laminar bonds within the foot. Understanding the dietary triggers may facilitate strategies to prevent laminitis in susceptible animals. The purpose of this review is to examine how dietary factors may lead to insulin resistance and/or excessive insulin production from the pancreas, and why certain breeds or types of horses are more predisposed to this form of laminitis than others. Understanding these relationships will be very important when considering appropriate feeds and the dietary countermeasures necessary for preventing this condition. It is important to note the breed type when considering the likely metabolic effects of dietary carbohydrate, because there are major differences between the Thoroughbred/Standardbred type and some other breeds of horses and ponies. Ponies and certain breeds of horses produce excessive amounts of insulin in response to dietary carbohydrates and this may lead to the development of the three main features of the equine metabolic syndrome, namely obesity, insulin resistance and laminitis. Relative glycaemic index or glycaemic load may be useful in predicting peak plasma insulin (with due consideration for breed type), but carbohydrates such as starch and fructans may have particularly marked effects on insulin sensitivity. Although it is normal for ponies and certain horse breeds to be relatively insulin resistant, it may be possible to reduce the likelihood of exacerbating insulin resistance in obese animals with careful dietary modification. This may help to some extent in reducing hyperinsulinaemia and thereby reducing the risk of laminitis.
Comparative sensitivities of larval stages of the cane toad, Rhinella marina, and the striped marsh frog, Limnodynastes peronii, to atrazine
Authors: Siddiqua Khurshida Akter , Alquezar Ralph , Wilson Scott Paton
Published: September 2013

Variations in larval sensitivities to atrazine were determined in the Australian native striped marsh frog, Limnodynastes peronii, and the introduced cane toad, Rhinella marina. The static acute test design involved six nominal concentrations of atrazine, including control, solvent control, 3, 6, 12, and 24 mg L–1. Gosner stages 22–23 as hatchlings, stages 25–26, 28–29, and 32–33 as premetamorphic, 36–37 as prometamorphic and 40–41 as metamorphic climax stages of cane toads and the first four sets of Gosner stages of striped marsh frogs were exposed to atrazine treatments for 96 h. Results showed that late larval stages were more sensitive than early stages and different premetamorphic stages showed variations in sensitivities in both test species. The striped marsh frog showed a stronger concentration- and stage-dependent response and greater sensitivity to atrazine than the cane toad. In both experimental species, Gosner stages 28–29 showed better concentration-dependent increase in sensitivities to atrazine compared with other larval stages. It can be concluded that inter- and intra-species variations in sensitivities to atrazine may occur in Australian anurans and native species may show greater sensitivity to acute concentrations of atrazine than the introduced cane toad.
Sensorimotor structure of
Drosophila
larva phototaxis
Authors: Kane Elizabeth A. , Gershow Marc , Afonso Bruno , Larderet Ivan , Klein Mason , Carter Ashley R. , de Bivort Benjamin L. , Sprecher Simon G. , Samuel Aravinthan D. T.
Published: September 2013

Significance

Small animals such as
Drosophila
provide an opportunity to understand the neural circuitry for complex behaviors from sensory input to motor output without gaps. Here, we define the algorithms for
Drosophila
larva phototaxis (i.e., the maps between sensory input and motor output) by quantifying the movements of individual animals responding to a battery of illumination conditions. Surprisingly, the distinct rules that define different components of the overall photosensory response begin to segregate at the first synapses after the photoreceptor cells. These results lay the foundation for mapping the circuits for phototaxis in the compact nervous system of the larva by first elucidating the algorithms that define behavior and then mapping these algorithms to specific circuit pathways.
Wnt signaling potentiates nevogenesis
Authors: Pawlikowski Jeff S. , McBryan Tony , van Tuyn John , Drotar Mark E. , Hewitt Rachael N. , Maier Andrea B. , King Ayala , Blyth Karen , Wu Hong , Adams Peter D.
Published: September 2013

Significance

Human benign nevi (moles) are clonal neoplasms that rarely progress to melanoma because their cells (melanocytes) are arrested in a viable but nonproliferating state (senescence). However, at low frequency, nevus melanocytes do progress to melanoma. Consequently, it is important to understand the factors that determine nevus formation and progression to melanoma. We present evidence that repression of a proliferation-promoting cell signaling pathway (Wnt signaling pathway) contributes to senescence of melanocytes in vitro. However, Wnt signaling remains active in some senescent human melanocytes in nevi, and activation of Wnt signaling leads to a delay in melanocyte senescence in a mouse model. We suggest that activated Wnt signaling in human nevi delays senescence to promote nevus formation, and thereafter, persistent Wnt signaling might undermine senescence-mediated tumor suppression.
Electromagnetically driven westward drift and inner-core superrotation in Earth’s core
Authors: Livermore Philip W. , Hollerbach Rainer , Jackson Andrew
Published: September 2013

Significance

Seismic probing of the earth’s deep interior has shown that the inner core, the solid core of our planet, rotates slightly faster (i.e., eastward) than the rest of the earth. Quite independently, observations of the geomagnetic field provide evidence of westward-drifting features at the edge of the liquid outer core. This paper describes a computer model that suggests that the geomagnetic field itself may provide a link between them: The associated electromagnetic torque currently is westward in the outermost outer core, whereas an equal and opposite torque is applied to the inner core. Decadal changes in the geomagnetic field may cause fluctuations in both these effects, consistent with recent observations of a quasi-oscillatory inner-core rotation rate.
Localizing transcripts to single cells suggests an important role of uncultured deltaproteobacteria in the termite gut hydrogen economy
Authors: Rosenthal Adam Z. , Zhang Xinning , Lucey Kaitlyn S. , Ottesen Elizabeth A. , Trivedi Vikas , Choi Harry M. T. , Pierce Niles A. , Leadbetter Jared R.
Published: September 2013

Significance

Most environments host a poorly understood microbial diversity. In recent years, work on gene inventories and metagenomics has revealed much about the microbial species and metabolic genes that may be present in situ; however, connecting microbial species with environmental function has lagged. Here a combination of emerging single-cell and other approaches revealed the gut microbes that may catalyze a key activity in their termite hosts. The results implicate a previously unappreciated deltaproteobacterium living on a gut protist.
Isotropic band gaps and freeform waveguides observed in hyperuniform disordered photonic solids
Authors: Man Weining , Florescu Marian , Williamson Eric Paul , He Yingquan , Hashemizad Seyed Reza , Leung Brian Y. C. , Liner Devin Robert , Torquato Salvatore , Chaikin Paul M. , Steinhardt Paul J.
Published: September 2013

Recently, disordered photonic media and random textured surfaces have attracted increasing attention as strong light diffusers with broadband and wide-angle properties. We report the experimental realization of an isotropic complete photonic band gap (PBG) in a 2D disordered dielectric structure. This structure is designed by a constrained optimization method, which combines advantages of both isotropy due to disorder and controlled scattering properties due to low-density fluctuations (hyperuniformity) and uniform local topology. Our experiments use a modular design composed of Al
2
O
3
walls and cylinders arranged in a hyperuniform disordered network. We observe a complete PBG in the microwave region, in good agreement with theoretical simulations, and show that the intrinsic isotropy of this unique class of PBG materials enables remarkable design freedom, including the realization of waveguides with arbitrary bending angles impossible in photonic crystals. This experimental verification of a complete PBG and realization of functional defects in this unique class of materials demonstrate their potential as building blocks for precise manipulation of photons in planar optical microcircuits and has implications for disordered acoustic and electronic band gap materials.
Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes
Authors: Drexler Jan Felix , Geipel Andreas , König Alexander , Corman Victor M. , van Riel Debby , Leijten Lonneke M. , Bremer Corinna M. , Rasche Andrea , Cottontail Veronika M. , Maganga Gael D. , Schlegel Mathias , Müller Marcel A. , Adam Alexander , Klose Stefan M. , Borges Carneiro Aroldo José , Stöcker Andreas , Franke Carlos Roberto , Gloza-Rausch Florian , Geyer Joachim , Annan Augustina , Adu-Sarkodie Yaw , Oppong Samuel , Binger Tabea , Vallo Peter , Tschapka Marco , Ulrich Rainer G. , Gerlich Wolfram H. , Leroy Eric , Kuiken Thijs , Glebe Dieter , Drosten Christian
Published: September 2013

Significance

Hepatitis B virus (HBV) is the prototype hepadnavirus; 40% of humans have current or past infection. In a global investigation of viral diversity in bats, we discovered three unique hepadnavirus species. The relatedness of these viruses to HBV suggests that bats might constitute ancestral sources of primate hepadnaviruses. Infection patterns in bats resembled human infection with HBV. After resurrection from bat tissues, pseudotyped viruses carrying surface proteins of one bat hepadnavirus could infect human liver cells. HBV vaccination is probably not protective against these viruses, but viral replication could be blocked by a reverse transcriptase inhibitor used as an anti-HBV drug in humans. The potential of bat hepadnaviruses to infect humans should be considered in programs aimed at eradicating HBV.
Actin-related protein2/3 complex regulates tight junctions and terminal differentiation to promote epidermal barrier formation
Authors: Zhou Kang , Muroyama Andrew , Underwood Julie , Leylek Rebecca , Ray Samriddha , Soderling Scott H. , Lechler Terry
Published: September 2013

Significance

This study used a genetic approach to probe the function of the F-actin nucleating Arp2/3 complex in skin development. Although the Arp2/3 complex was expected to be involved in morphogenesis and cell adhesion, loss of its activity did not result in architectural problems in the epidermis. However, Arp2/3 was essential for epidermal function. We revealed two unexpected functions for the Arp2/3 complex in the epidermis that are critical for tissue physiology: tight junction assembly/function and the regulation of YAP activity.
Disrupting the clustering of GABAAreceptor α2 subunits in the frontal cortex leads to reduced γ-power and cognitive deficits
Authors: Hines Rochelle M. , Hines Dustin J. , Houston Catriona M. , Mukherjee Jayanta , Haydon Philip G. , Tretter Verena , Smart Trevor G. , Moss Stephen J.
Published: September 2013

Significance

Schizophrenia is a condition characterized by interrelated symptoms including psychosis and hallucinations, decreased emotional expression and motivation, and cognitive impairments. Recent studies have shown that γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the brain, contributes to the cognitive symptoms of schizophrenia. However, the details of this alteration are not understood. GABA signaling can exert powerful control on groups of neurons, acting as regulated on–off switches for brain activity. In the brains of patients with schizophrenia, an alteration in the typical on–off patterns is observed. We generated an animal model for symptoms of schizophrenia by altering the accumulation of specific types of GABA receptors. These animals show both behavioral and brain activity changes that are reminiscent of patients with schizophrenia.
Regulated structural transitions unleash the chaperone activity of αB-crystallin
Authors: Peschek Jirka , Braun Nathalie , Rohrberg Julia , Back Katrin Christiane , Kriehuber Thomas , Kastenmüller Andreas , Weinkauf Sevil , Buchner Johannes
Published: September 2013

Significance

The small heat shock protein αB-crystallin functions as an archetypical and ubiquitous molecular chaperone. It is an integral part of the cellular proteostasis system and associated with human diseases such as Alzheimer's disease, myopathy, cataract, and multiple sclerosis. The molecular architecture of αB-crystallin follows an intriguing construction plan characterized by a dynamic oligomer equilibrium. Here, we exploited phosphorylation mimetics as a tool to switch the protein to an activated functional state by a shift in the conformational ensemble. Using cryo-EM and image processing, we defined the structures of the activated αB-crystallin ensemble. Biochemical analysis revealed that, on activation, the N-terminal regions gain flexibility and solvent accessibility. This allows enhancing the activity of αB-crystallin and promoting its cooperation with the Hsp70 system.
High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations
Authors: Chen Alan A. , García Angel E.
Published: September 2013

Significance

We report atomistic simulations describing the spontaneous folding of three RNA tetraloops from the unfolded state to within 1–3 Å of their experimentally determined structures. These common and highly stable motifs serve as building blocks for large structured RNA molecules. This success is caused by the reparameterization of the energy function used to describe the interatomic interactions, which was obtained by calibrating the energy function to reproduce known thermodynamic and kinetic measurements of RNA monomers and dimers. In particular, the accurate recapitulation of the characteristic loop configurations responsible for the thermodynamic hyperstability of these motifs represents a significant milestone to the accurate description of RNA tertiary structure using unbiased all-atom molecular dynamics simulations.
XPLN is an endogenous inhibitor of mTORC2
Authors: Khanna Nidhi , Fang Yimin , Yoon Mee-Sup , Chen Jie
Published: September 2013

Significance

Mammalian target of rapamycin complex 2 (mTORC2) controls a wide range of cellular and developmental processes and is a potential target for therapeutic strategies against a range of human diseases. Here we identify XPLN (e
x
change factor found in
p
latelets,
l
eukemic, and
n
euronal tissues) as an endogenous inhibitor of mTORC2 and show that XPLN negatively regulates cell survival and skeletal myoblast differentiation by inhibiting mTORC2 and subsequently the Ser/Thr kinase Akt. This XPLN action requires its N terminus and is independent of its canonical activity as a guanine nucleotide exchange factor. Our findings provide a molecular understanding of mTORC2 regulation and uncover XPLN as a potentially important player in many aspects of biology and diseases involving mTORC2 and Akt.
TP53
suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients
Authors: Caceres Gisela , McGraw Kathy , Yip Bon Ham , Pellagatti Andrea , Johnson Joseph , Zhang Ling , Liu Kenian , Zhang Lan Min , Fulp William J. , Lee Ji-Hyun , Al Ali Najla H. , Basiorka Ashley , Smith Larry J. , Daugherty F. Joseph , Littleton Neil , Wells Richard A. , Sokol Lubomir , Wei Sheng , Komrokji Rami S. , Boultwood Jacqueline , List Alan F.
Published: September 2013

Significance

The hypoplastic anemia characteristic of del(5q) myelodysplastic syndrome (MDS) arises from ribosomal protein insufficiency, resulting in erythroid-specific activation of p53. We found that suppression of p53 by cenersen, an antisense oligonucleotide, markedly improved erythroid colony formation in primary MDS specimens assessed by two-stage colony formation assay. Erythropoietic rescue significantly correlated with the magnitude of reduction in nuclear p53. In addition, in a cohort of eight lower-risk, lenalidomide-refractory del(5q) MDS patients treated with lenalidomide and dexamethasone, a glucocorticoid receptor-dependent antagonist of p53, transfusion independence was restored in five of eight patients, accompanied by in vivo expansion of erythroid precursors without clonal suppression. These results suggest inhibition of p53 may be a unique therapeutic strategy in patients with lenalidomide-resistant del(5q) MDS.
Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus
Authors: Scobey Trevor , Yount Boyd L. , Sims Amy C. , Donaldson Eric F. , Agnihothram Sudhakar S. , Menachery Vineet D. , Graham Rachel L. , Swanstrom Jesica , Bove Peter F. , Kim Jeeho D. , Grego Sonia , Randell Scott H. , Baric Ralph S.
Published: September 2013

Significance

The identification of a novel, emerging human coronavirus with ∼50% mortality, designated Middle East respiratory syndrome coronavirus (MERS-CoV), emphasizes the importance of the rapid development of reagents that can be used to (
i
) characterize the replication and pathogenesis of emerging pathogens and (
ii
) develop therapeutics for treatment. In this report, we describe the development of a cassette-based infectious cDNA clone of MERS-CoV and verify that it functions similarly to the wild-type isolate in terms of replication, protein and RNA expression, and spike attachment protein processing. We also show that the virus replicates preferentially in differentiated primary lung cells.
Template-constrained macrocyclic peptides prepared from native, unprotected precursors
Authors: Lawson Kenneth V. , Rose Tristan E. , Harran Patrick G.
Published: September 2013

Significance

Cyclic peptides and peptidomimetics are valuable tools in biomedical research. This paper describes chemistry to convert linear, unmodified peptides directly into stable, templated macrocycles. The ring-closing reaction is an allylic substitution catalyzed by palladium(0). It requires no tailored amino acid residues or protecting groups. It proceeds rapidly at room temperature and largely independent of product-ring size and composition. The catalysis shows broad scope and predictable chemoselectivity while engaging functional groups native to peptides. These methods could be applied broadly and have special utility for those attempting to perturb biological systems with unique small molecules.
DNA cloning: A personal view after 40 years
Authors: Cohen Stanley N.
Published: September 2013

In November 1973, my colleagues A. C. Y. Chang, H. W. Boyer, R. B. Helling, and I reported in PNAS that individual genes can be cloned and isolated by enzymatically cleaving DNA molecules into fragments, linking the fragments to an autonomously replicating plasmid, and introducing the resulting recombinant DNA molecules into bacteria. A few months later, Chang and I reported that genes from unrelated bacterial species can be combined and propagated using the same approach and that interspecies recombinant DNA molecules can produce a biologically functional protein in a foreign host. Soon afterward, Boyer’s laboratory and mine published our collaborative discovery that even genes from animal cells can be cloned in bacteria. These three PNAS papers quickly led to the use of DNA cloning methods in multiple areas of the biological and chemical sciences. They also resulted in a highly public controversy about the potential hazards of laboratory manipulation of genetic material, a decision by Stanford University and the University of California to seek patents on the technology that Boyer and I had invented, and the application of DNA cloning methods for commercial purposes. In the 40 years that have passed since publication of our findings, use of DNA cloning has produced insights about the workings of genes and cells in health and disease and has altered the nature of the biotechnology and biopharmaceutical industries. Here, I provide a personal perspective of the events that led to, and followed, our report of DNA cloning.
Why abundant tropical tree species are phylogenetically old
Authors: Wang Shaopeng , Chen Anping , Fang Jingyun , Pacala Stephen W.
Published: September 2013

Significance

Neutral population models assume that competing species are ecologically equivalent and predict several properties of extant ecosystems. Ecological aspects of neutral models have been tested repeatedly, with a special focus on tropical trees, but their macroevolutionary predictions have received little attention. We show that neutral models predict flat or humped relationships between a species’ abundance and phylogenetic age. In contrast, abundances and ages of Panamanian tree species are positively correlated. Similar correlations have been reported for other groups and explained by deterministic niche theories. However, we show that neutral models predict positive age–abundance relationships with the addition of speciation rates that vary among lineages.
Active output state of the
Synechococcus
Kai circadian oscillator
Authors: Paddock Mark L. , Boyd Joseph S. , Adin Dawn M. , Golden Susan S.
Published: September 2013

Significance

For circadian clocks to modulate a daily cycle of metabolic and behavioral processes, temporal information must be transmitted to output pathways. In cyanobacteria, the circadian oscillator is composed of three Kai proteins that mediate cyclic phosphorylation of KaiC. We determined that a specific phosphostate of KaiC promotes genome-wide circadian output responses. A model that includes temporal feedback control of this KaiC phosphostate can accurately simulate key features of observed output responses of the two major contrasting promoter types. This study provides a unique perspective on the complex regulatory output responses of circadian oscillators.
Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis
Authors: Wang Yan , Quagliarini Fabiana , Gusarova Viktoria , Gromada Jesper , Valenzuela David M. , Cohen Jonathan C. , Hobbs Helen H.
Published: September 2013

Significance

Here we show that ANGPTL8 plays a major role in the trafficking of triglycerides to peripheral tissues in response to food intake in mice. Circulating triglycerides are predominantly delivered to skeletal muscle and heart during fasting and are partitioned to adipose tissue upon refeeding. The postprandial increase in triglyceride delivery to adipose tissue is abolished in mice lacking ANGPTL8; consequently, the mice fail to replenish triglyceride stores in adipose tissue. Despite major alterations in triglyceride metabolism, no defects in glucose metabolism were detected in
Angptl8

−/−

mice. The finding that plasma triglyceride levels are lower in
Angptl8

+/−

mice suggests that even partial inhibition of ANGPTL8 may provide therapeutic benefit for treatment of dyslipidemia.
HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice
Authors: Horwitz Joshua A. , Halper-Stromberg Ariel , Mouquet Hugo , Gitlin Alexander D. , Tretiakova Anna , Eisenreich Thomas R. , Malbec Marine , Gravemann Sophia , Billerbeck Eva , Dorner Marcus , Büning Hildegard , Schwartz Olivier , Knops Elena , Kaiser Rolf , Seaman Michael S. , Wilson James M. , Rice Charles M. , Ploss Alexander , Bjorkman Pamela J. , Klein Florian , Nussenzweig Michel C.
Published: September 2013

Significance

Treatment of HIV-1 infection in humans is achieved using combinations of highly effective antiretroviral therapy (ART) drugs to potently suppress viral replication and prevent the emergence of drug-resistant viruses. However, ART drugs must be taken indefinitely owing to rapid return of viremia upon termination of treatment. Highly potent broadly neutralizing antibodies (bNAbs) present a new potential therapeutic modality in the treatment of HIV-1 infection. Because of their comparatively longer half-lives relative to ART drugs and their ability to eliminate infected cells, bNAbs may alleviate some aspects of the lifelong treatment adherence burden of ART. Here we show that lowering the initial viral load with ART enables single bNAbs to effectively control an established HIV-1 infection in humanized mice.
Endothelin-2 signaling in the neural retina promotes the endothelial tip cell state and inhibits angiogenesis
Authors: Rattner Amir , Yu Huimin , Williams John , Smallwood Philip M. , Nathans Jeremy
Published: September 2013

Significance

Two distinct and interconvertible types of endothelial cells are present during blood vessel growth: tip cells at the growing front of the vascular network and stalk cells behind the front. In the present study, overexpression of Endothelin-2, a peptide previously implicated in the control of blood pressure, is shown to promote the tip cell fate and arrest vascular growth within the mouse retina. Genetic experiments show that this effect requires Endothelin receptor A expression in the neural retina, implying the existence of a retina-derived regulator of vascular growth and development that is under Endothelin control.
Enhanced group II intron retrohoming in magnesium-deficient
Escherichia coli
via selection of mutations in the ribozyme core
Authors: Truong David M. , Sidote David J. , Russell Rick , Lambowitz Alan M.
Published: September 2013

Significance

Mobile group II introns are bacterial retrotransposons. They consist of an autocatalytic intron RNA (“ribozyme”) and an intron-encoded reverse transcriptase and were likely ancestors of spliceosomal introns and retroelements in eukaryotes. Although active in bacteria, group II introns function inefficiently in eukaryotes, where lower Mg
2+
concentrations decrease their ribozyme activity and constitute a natural barrier to group II intron proliferation within nuclear genomes. By using an
Escherichia coli
Mg
2+
-transport mutant, we selected mutations near the intron RNA’s active site that enhance group II intron function at low Mg
2+
concentrations. Our results have implications for ribozyme mechanisms, evolution, and biotechnology.
Programmed cell death 1 inhibits inflammatory helper T-cell development through controlling the innate immune response
Authors: Rui Yuxiang , Honjo Tasuku , Chikuma Shunsuke
Published: September 2013

Significance

Programmed cell death 1 (PD-1) is a membrane receptor that transmits inhibitory signals on leucocytes. Lack of PD-1 in mice results in various autoimmune diseases, which have been believed to be caused by the activation of T lymphocytes without inhibition. The current study reveals that PD-1 inhibits T-lymphocyte–mediated autoimmunity through regulating macrophage function. PD-1 deficiency only in innate immune cells caused dysregulated macrophage responses against mycobacterial adjuvant and enhanced production of IL-6, a proinflammatory cytokine, leading to the development of inflammatory autoreactive helper T cells and the exacerbation of experimental autoimmune encephalomyelitis. The lymphocyte extrinsic regulation of PD-1 provides a unique perspective on the maintenance of the immune self-tolerance and the understanding of the development of autoimmune diseases.
Posture verbs
Authors: Viberg Åke
Published: September 2013

From a typological perspective, the verbs of sitting, standing and lying have been described relatively extensively. Against this background, the present paper provides a contrastive study of the lexical semantics of the Swedish posture verbs sitta ‘sit’, stå ‘stand’ and ligga ‘lie’ based on the Multilingual Parallel Corpus (MPC), which contains extracts from Swedish novels and their published translations into English, German, French and Finnish. Since the corpus is a very rich data source, the study is focused on the use of posture verbs as locative verbs. It turns out that it is possible to arrange the languages along a continuum with respect to the use of posture verbs versus the copula to describe the location of inanimate objects. In Finnish the copula dominates completely, in English there is more of a balance (in this kind of written text), whereas the posture verbs dominate in German and Swedish. French stands out as a completely different type in this comparison, since the copula is used very little and posture verbs hardly at all. Actually, there is a tension in French between the use of a small number of verbs with a general locative meaning as translations and the use of a large variety of reflexive verbs and resultative constructions with past participles (e.g. être fixé ‘be attached’) which convey fine-grained information about the placement. Among the languages that use posture verbs as locative predicates, there is a general similarity with respect to the factors that condition the choice between lie and stand, whereas even closely related Germanic languages differ with respect to the semantic factors that condition the choice of sit as a locative predicate.