bluuebunny/crossref_metadata_2025 huggingface dataset:
A local superbasin kinetic Monte Carlo method
Authors: Fichthorn Kristen A. , Lin Yangzheng
Published: April 2013

We present a local superbasin kinetic Monte Carlo (LSKMC) method that efficiently treats multiple-time-scale problems in kinetic Monte Carlo (KMC). The method is designed to solve the small-barrier problem created by groups of recurrent free-energy minima connected by low free-energy barriers and separated from the full phase space of the system by high barriers. We propose an algorithm to detect, on the fly, groups of recurrent free-energy minima connected by low free-energy barriers and to consolidate them into “superbasins,” which we treat with rate equations and/or absorbing Markov chains. We discuss various issues involved with implementing LSKMC simulations that contain local superbasins and non-superbasin events concurrently. These issues include the time distribution of superbasin escapes and interactions between superbasin and non-superbasin states. The LSKMC method is exact, as it introduces no new approximations into conventional KMC simulations. We demonstrate various aspects of LSKMC in several examples, which indicate that significant increases in computational efficiency can be achieved using this method.
Turbulent flow characteristics in a randomly packed porous bed based on particle image velocimetry measurements
Authors: Patil Vishal A. , Liburdy James A.
Published: April 2013

An experimental study was undertaken to better understand the turbulent flow characteristics within a randomly packed porous bed. A relatively low aspect ratio bed (bed width to spherical solid phase particle diameter of 4.67) with the fluid phase refractive index matched to that of the solid phase was used to obtain time resolved particle image velocimetry data. Care was taken to assure that data were outside of the wall affected region, and results are based on detailed time dependent velocity vector maps obtained at selected pores. In particular, four pores were identified that display a range of very disparate mean flow conditions which resemble channel-like flow, impinging flow, recirculating flow, and jet like flow. Velocity data were used for a range of pore Reynolds numbers, Repore, from 418 to 3964 to determine the following turbulence measures: (i) turbulent kinetic energy components, (ii) turbulent shear production rate, (iii) integral Eulerian length and time scales, and (iv) energy spectra. The pore Reynolds number is based on the porous bed hydraulic diameter, DH = ϕDB/(1 − ϕ) where ϕ is bed porosity and DB is solid phase bead diameter and average bed interstitial velocity, Vint = VDarcy/ϕ, where VDarcy = Q/Abed, with Q being the volumetric flow rate and Abed the bed cross section normal to the flow. Results show that when scaled with the bed hydraulic diameter, DH, and average interstitial velocity, Vint, these turbulence measures all collapse for Repore, beyond approximately 2800, except that the integral scales collapse at a lower value near 1300–1800. These results show that the pore turbulence characteristics are remarkably similar from pore to pore and that scaling based on bed averaged variables like DH and Vint characterizes their magnitudes despite very different mean flow conditions.
Performance of a wing with nonuniform flexibility in hovering flight
Authors: Shoele Kourosh , Zhu Qiang
Published: April 2013

The deformability of insect wings is associated with the embedded skeleton (venation). In this paper, the aerodynamic performance of wings with nonuniform flexibility is computationally investigated. By using a two-dimensional rendition, the underlying veins are modeled as springs, and the membrane is modeled as a flexible plate. The focus is on the effects of the detailed distribution of vein flexibility upon the performance of such a wing in the generation of lift force. Specifically, we are interested in finding the importance of leading edge strengthening. Towards this end, the aerodynamic performances of three wings, a rigid wing, a flexible wing with identical veins, and a flexible wing with strengthened leading edge, are studied and compared against each other. It is shown that the flexible wing with leading edge strengthening is capable of producing significantly higher lift force without consuming more energy. This is found to be related to the stabilizing and cambering effects at the leading edge, which enhances the leading edge vortices. In addition, in contrast to the other two wings, which show sensitivity to kinematic parameters, the wing with strengthened leading edge perform well over a wide range of parameters.
Note: Generation of Raman laser beams based on a sideband injection-locking technique using a fiber electro-optical modulator
Authors: Xue H. B. , Feng Y. Y. , Wang X. J. , Chen S. , Zhou Z. Y.
Published: April 2013

Two phase-coherent Raman laser beams with a frequency offset of 6.835 GHz were generated by sideband injection-locking technique. A master diode laser was phase-modulated at 6.835 GHz by a fiber electro-optic modulator. A slave diode was injection-locked to the −1 sideband of the phase-modulated beam, and another diode was locked to the master laser carrier. This method produced stable and spatially separated Raman lasers with a large frequency shift range (>180 MHz). The relative linewidth of these two beams was ∼1 Hz, and the unwanted carrier mode was suppressed down to −24 dB. Stimulated Raman transitions and Ramsey fringes were driven by Raman lasers in a cold atomic beam.
A fluorescence based method for the quantification of surface functional groups in closed micro- and nanofluidic channels
Authors: Wang Yu , Lowe Rachel D. , Mejia Yara X. , Feindt Holger , Steltenkamp Siegfried , Burg Thomas P.
Published: April 2013

Surface analysis is critical for the validation of microfluidic surface modifications for biology, chemistry, and physics applications. However, until now quantitative analytical methods have mostly been focused on open surfaces. Here, we present a new fluorescence imaging method to directly measure the surface coverage of functional groups inside assembled microchannels over a wide dynamic range. A key advance of our work is the elimination of self-quenching to obtain a linear signal even with a high density of functional groups. This method is applied to image the density and monitor the stability of vapor deposited silane layers in bonded silicon/glass micro- and nanochannels.
Adsorption of nanoparticles and nanoparticle aggregates on membrane under gravity
Authors: Zhu Tao , Jiang Zhongying , Ma Yuqiang
Published: April 2013

Particle adsorption on lipid membrane is critical to biomedical applications. Gravity effect on the process has long been ignored. A combination of the upright and inverted configuration measurements was developed to exhibit that gravity causes a particle adsorption disparity on membrane between the different heights of medium. The more homogeneous adsorption tendency of nanoparticle aggregate compared to nanoparticle under the same gravitational motive force is attributed to the larger hydrodynamic diameter induced lower concentration disparity.
Enhancement of the anomalous Hall effect in Ni thin films by artificial interface modification
Authors: Xu Jianli , Li Yufan , Hou Dazhi , Ye Li , Jin Xiaofeng
Published: April 2013

The enhancement of the anomalous Hall effect has been realized by capping one monolayer Cu on Ni thin films. This approach with artificial interface engineering is proved to be an effective way to improve spin to charge transformation and may have potential application in spintronics.
Magnetic field induced shell-to-core confinement transition in type-II semiconductor quantum wires
Authors: Macêdo R. , Costa e Silva J. , Chaves A. , Farias G. A. , Ferreira R.
Published: April 2013

We investigate the excitonic properties of a core-multishell semiconductor nanowire with type-II band mismatch, i.e., with spatially separated electrons and holes, under an external magnetic field. Our results demonstrate that, depending on the core wire radius, the carrier in the type-II band exhibits either a quantum dot-like or a quantum ring-like energy spectrum, corresponding to a carrier confinement in the core wire or in the outer shell, respectively. In the latter, a shell-to-core confinement transition can be induced by increasing the magnetic field intensity, which may lead to interesting photocurrent properties of these confining structures, tunable by the external field.
Tailoring the perpendicular exchange bias in [Pt/Co/CoO]n multilayer by tensile stress on curved substrate
Authors: Wang Y. X. , Li W. , Zhang Y. J. , Liu Y. , Liu S. S. , Zhang X. L. , Jiang Y. H. , Yang J. H.
Published: April 2013

The effects of the tensile stress on exchange bias of [Pt/Co/CoO]n multilayer are investigated by depositing the magnetic film onto the ordered curved substrate composed of a polystyrene nanosphere monolayer film. The square ratio of the loop decreases first and increases then with the reduction of tensile stress when the nanosphere size increases. The square ratio and exchange bias field are enhanced significantly when 60 nm polystyrene nanosphere arrays are chosen as the substrate, which is ascribed to the increased interfacial uncompensated antiferromagnetic spins created by the periodical knots between neighbor spheres and the formation of the entire domain wall. In addition, the easy axis of [Pt/Co/CoO]n multilayer is tailored when the CoO sublayer thickness changes, which is due to the gradual development of a tilted anisotropy. When CoO is 1.9 and 2.6 nm, the exchange coupling with tilted magnetic easy axis is obtained in the 45° direction.
Thickness dependence of the anchoring energy of a nematic cell
Authors: Ataalla R. M. S. , Barbero G. , Komitov L.
Published: April 2013

The cell gap thickness dependence of the anchoring energy strength of a nematic cell is investigated. The relaxation time of the elastic deformation of a nematic liquid crystal layer imposed by an external electric field is analyzed as a function of the thickness of the nematic layer. The measurements have been performed with conventional sandwich cells with cell gap ranging from 1 μm to 10 μm. According to our data, the anchoring energy strength is not only a characteristic of the interface substrate-nematic liquid crystal but it also depends strongly on the cell thickness.
Electrical tip-sample contact in scanning conductive torsion mode
Authors: Weber Stefan A. L. , Berger Rüdiger
Published: April 2013

We investigated the nature of the mechanical and the electrical tip-sample contact in scanning conductive torsion mode microscopy (SCTMM). Experiments on the soft conducting polymer blend of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) demonstrated that the tip-sample force and thus the danger of tip-induced sample damage can be minimized. Using current-voltage spectroscopy, we found a space-charge limited conduction behavior with no indication of a tunneling barrier. Spectroscopy and imaging experiments showed that SCTMM allows for a gentler tip-sample contact compared to conventional conductive scanning force microscopy. A gentle and well-defined contact is a prerequisite for reproducible scanning probe based conductivity measurements, in particular on soft organic materials.
Symmetry breaking induced anti-resonance in three dimensional sub-diffraction semiconducting grating
Authors: Cheng F. , Li B. H. , Han J. , Xiao H. , Gu C. Z. , Qiu X. G.
Published: April 2013

A kind of three dimensional, sub-diffraction grating with converging-diverging channel working at terahertz regime has been developed on doped silicon wafers by wet etching. By introducing a geometric asymmetry to the vertical direction of the 3D grating, an anti-resonance is observed near the resonant wavelength of the surface plasmon polariton mode. Numerical simulations reveal that the surface waves propagating on the top and bottom surfaces are decoupled due to the symmetry breaking, which results in the destructive interference of electromagnetic field and thus the anti-resonance in the spectrum. It was also found that the bulk sensitivity of the 3D structure as a terahertz sensor can reach a value up to 8818%/RIU and a figure of merit up to 50.
Large second-order optical nonlinearity in a ferroelectric molecular crystal of croconic acid with strong intermolecular hydrogen bonds
Authors: Sawada R. , Uemura H. , Sotome M. , Yada H. , Kida N. , Iwano K. , Shimoi Y. , Horiuchi S. , Okamoto H.
Published: April 2013

Linear and nonlinear optical responses in a molecular crystal, croconic acid, showing electronic-type ferroelectricity were studied by reflection and second harmonic generation spectroscopy. The second-order nonlinear susceptibility χ(2) was very large, exceeding 10−6 esu in the near-infrared region. The enhancement of χ(2) was attributed to the large dipole moment of the lowest π–π* transition and the large difference between the molecular dipole moments for the ground state and the photoexcited state. We deduced the molecular orbitals (MOs) and dipole moments responsible for the large χ(2) by comparing the experimental optical parameters and MO calculation results based upon density functional theory.
Evidence of Dirac fermions in multilayer silicene
Authors: De Padova Paola , Vogt Patrick , Resta Andrea , Avila Jose , Razado-Colambo Ivy , Quaresima Claudio , Ottaviani Carlo , Olivieri Bruno , Bruhn Thomas , Hirahara Toru , Shirai Terufusa , Hasegawa Shuji , Carmen Asensio Maria , Le Lay Guy
Published: April 2013

Multilayer silicene, the silicon analogue of multilayer graphene, grown on silver (111) surfaces, possesses a honeycomb (√3 × √3)R30° reconstruction, observed by scanning tunnelling microscopy at room temperature, past the initial formation of the dominant, 3×3 reconstructed, silicene monolayer. For a few layers silicene film we measure by synchrotron radiation photoelectron spectroscopy, a cone-like dispersion at the Brillouin zone centre due to band folding. π* and π states meet at ∼0.25 eV below the Fermi level, providing clear evidence of the presence of gapless Dirac fermions.
Composition-dependent dielectric and energy-storage properties of (Pb,La)(Zr,Sn,Ti)O3 antiferroelectric thick films
Authors: Hao Xihong , Wang Ying , Zhang Le , Zhang Liwen , An Shengli
Published: April 2013

1.8 -μm-(Pb0.97La0.02)(Zr0.95−xSnxTi0.05)O3 antiferroelectric thick films with orthorhombic (x = 0.05 and 0.25) and tetragonal (x = 0.40) structure were deposited on platinum-buffered silicon substrates by using a chemical solution way. All the films had a uniform microstructure with pure perovskite phase. With increasing x value, dielectric constant and critical electric breakdown field of the thick films were gradually increased, while their saturated polarizations were decreased. As a result, their maximum recoverable energy-storage density was increased for the thick films with larger x values. A huge recoverable energy-storage density of 56 J/cm3 was obtained in antiferroelectric thick films with x = 0.40. Moreover, a good temperature-dependent stability of the energy storage was obtained in the all films from 20 to 120 °C.
An ultra-low detection-limit optofluidic biosensor with integrated dual-channel Fabry-Pérot cavity
Authors: Liu Pengbo , Huang Hui , Cao Tun , Liu Xueyu , Qi Zhenbin , Tang Zhenan , Zhang Jinnan
Published: April 2013

A silicon-on-insulator based optofluidic biosensor with integrated dual-channel Fabry–Pérot cavity is proposed for optical differential detection. A detection limit of 5.5 × 10−8 refractive index unit is experimentally demonstrated, owing to the high quality factor of the cavity and the differential detection, which can extract the small signal for efficient amplification and greatly reduce the system noise. Moreover, the measurement system features low cost compared with that of surface-plasmon-resonance sensor and ring-resonator sensor.
Electronic structure of boron doped diamond: An x-ray spectroscopic study
Authors: Glans P.-A. , Learmonth T. , Smith K. E. , Ferro S. , De Battisti A. , Mattesini M. , Ahuja R. , Guo J.-H.
Published: April 2013

The valence and conduction band electronic structure of boron-doped diamond has been measured using soft x-ray emission and absorption spectroscopy. The experimental results reveal p-type doping in the diamond film through the appearance of states in the band-gap. Structure distortion was observed around the doping center, while the long range order of the diamond structure remains. A chemically shifted C 1s level explains why one of the absorption features seems to appear below the valence band maximum. An excitonic feature was observed in the boron-doped diamond, similar to that observed in pure diamond, indicating that the exciton binding energy remains the same upon B-doping.
Simultaneous determination of diffusion and sublimation kinetics at nanoscale: Pentaerythritol tetranitrate
Authors: Hikal Walid M. , Burnham Alan K. , Weeks Brandon L.
Published: April 2013

Many theoretical studies have been proposed to understand the mechanism of pentaerythritol tetranitrate (PETN) coarsening. Up to date, no experimental observations of diffusion have been made. We present experimental evidence of diffusion of PETN at nanoscale, as observed by UV-absorbance spectroscopy. As a result of thermal gradient, non-isothermal heating of continuous PETN nanofilms results in an initial increased absorbance at ambient temperatures indicating thickness increase due to coarsening, followed by absorbance decease due to film sublimation at relatively higher temperatures. Diffusion kinetics of PETN is measured both isothermally and non-isothermally and the results are in very good agreement.
Smearing of induced ferroelectric transition and easy imprinting of different polarization configurations in relaxor ferroelectric (Na1/2Bi1/2)1−xBaxTiO3
Authors: Craciun F. , Galassi C.
Published: April 2013

(Na1/2Bi1/2)1−xBaxTiO3 ferroelectrics behave as relaxors for 0.055 < x < 0.10. Inside this region, we found peculiar features distinguishing samples with compositions x = 0.070-0.075, from others near the border: (a) smeared electric-field-induced ferroelectric-relaxor transition indicating a gradual transformation of ferroelectric domains in nanodomains; (b) easy imprinting by poling of different polarization configurations. This is consistent with former studies evidencing an almost exclusive formation of polarization along the poling electric field direction.
Temperature-dependent proximity magnetism in Pt
Authors: Lim W. L. , Ebrahim-Zadeh N. , Owens J. C. , Hentschel H. G. E. , Urazhdin S.
Published: April 2013

We study experimentally the magnetic coupling between ferromagnets separated by a thin Pt layer. The coupling remains ferromagnetic regardless of the Pt thickness and exhibits a significant dependence on temperature. We show that these results are consistent with the effects of temperature-dependent magnetism induced in Pt at the interfaces with ferromagnets. Analysis shows that the characteristic magnetization decay length in Pt increases from approximately 0.2 nm at room temperature to 0.8 nm at 25 K.
Perception of Length to Width Relations of City Squares
Authors: Nefs Harold T. , van Bilsen Arthur , Pont Sylvia C. , de Ridder Huib , Wijntjes Maarten W. A. , van Doorn Andrea J.
Published: April 2013

In this paper, we focus on how people perceive the aspect ratio of city squares. Earlier research has focused on distance perception but not so much on the perceived aspect ratio of the surrounding space. Furthermore, those studies have focused on “open” spaces rather than urban areas enclosed by walls, houses and filled with people, cars, etc. In two experiments, we therefore measured, using a direct and an indirect method, the perceived aspect ratio of five city squares in the historic city center of Delft, the Netherlands. We also evaluated whether the perceived aspect ratio of city squares was affected by the position of the observer on the square. In the first experiment, participants were asked to set the aspect ratio of a small rectangle such that it matched the perceived aspect ratio of the city square. In the second experiment, participants were asked to estimate the length and width of the city square separately. In the first experiment, we found that the perceived aspect ratio was in general lower than the physical aspect ratio. However, in the second experiment, we found that the calculated ratios were close to veridical except for the most elongated city square. We conclude therefore that the outcome depends on how the measurements are performed. Furthermore, although indirect measurements are nearly veridical, the perceived aspect ratio is an underestimation of the physical aspect ratio when measured in a direct way. Moreover, the perceived aspect ratio also depends on the location of the observer. These results may be beneficial to the design of large open urban environments, and in particular to rectangular city squares.
The Role of Binocular Disparity in Rapid Scene and Pattern Recognition
Authors: Valsecchi Matteo , Caziot Baptiste , Backus Benjamin T. , Gegenfurtner Karl R.
Published: April 2013

We investigated the contribution of binocular disparity to the rapid recognition of scenes and simpler spatial patterns using a paradigm combining backward masked stimulus presentation and short-term match-to-sample recognition. First, we showed that binocular disparity did not contribute significantly to the recognition of briefly presented natural and artificial scenes, even when the availability of monocular cues was reduced. Subsequently, using dense random dot stereograms as stimuli, we showed that observers were in principle able to extract spatial patterns defined only by disparity under brief, masked presentations. Comparing our results with the predictions from a cue-summation model, we showed that combining disparity with luminance did not per se disrupt the processing of disparity. Our results suggest that the rapid recognition of scenes is mediated mostly by a monocular comparison of the images, although we can rely on stereo in fast pattern recognition.
Nutritive value for ruminants of two herbaceous South American native legumes: Adesmia bicolor and Adesmia macrostachya
Authors: Vileta D. G. , Grosso M. , Fondevila M.
Published: April 2013

Chemical composition, in vitro fermentation and in situ degradability of the native South American legumes Adesmia bicolor and A. macrostachya were studied at vegetative (VG), flowering (FW) and seeding (SD) stages, and compared with those of alfalfa at 10% flowering (AL) in two separate studies. In A. bicolor, crude protein (CP) content was highest for FW, and FW and SD showed higher values than did AL (P < 0.05). At all stages, A. bicolor showed a lower content of neutral detergent fibre and acid detergent fibre than did AL (P < 0.05). The maximum gas production (Coefficient b) was highest for FW, and no differences were recorded between SD and AL, the lowest value being for VG (P < 0.05). The effective dry matter degradability was higher for FW and VG than for SD and AL (P < 0.05), whereas effective CP degradability tended (P = 0.077) to be higher for FW than for the other stages of A. bicolor, but no differences between FW and AL were detected. A. macrostachya had lower CP content (P < 0.001), but its VG and FW stages also had lower proportions of neutral detergent fibre, acid detergent fibre and acid detergent lignin (P < 0.01) than did AL. Chemical and fermentation parameters were affected by maturity of A. macrostachya. The effective dry matter degradability was higher for VG and FW than for SD and AL (P < 0.001), but no differences were apparent on the effective CP degradability. A. bicolor showed a high nutritive value, which was even higher than that of AL, and the maturity stage of this species did not markedly affect its nutritive value, whereas the nutritive value of A. macrostachya reduced as it matured.
Salt stress, signalling and redox control in seeds
Authors: Kranner Ilse , Seal Charlotte E.
Published: April 2013

Abiotic stresses, including salt stress, can impair electron transport chains, thereby increasing the production of reactive oxygen species (ROS). An excess of ROS can damage macromolecular and cellular structure, but ROS are also key components of signalling networks, through which they regulate developmental processes. Surprisingly little is known about the effects of salt stress upon seeds given their pivotal role in plant reproduction and dispersal. This review provides information on tolerance mechanisms and redox control in relation to seed metabolism and performance. First, the effects of salt stress throughout the seed life cycle are discussed, comprising salt effects on the mother plant and its implications on seed development, salt uptake upon seed imbibition and effects on seed germination. Then, responses to elevated salt concentrations are discussed according to a recently proposed triphasic seed stress model comprising the phases alarm, resistance and exhaustion. Implications of redox control in seeds on the physiological, biochemical and molecular level are considered and the review concludes with a perspective on future research in relation to salt stress and seed biology.
Insulin-like growth factor and insulin-like growth factor-binding proteins in the bovine uterus throughout the oestrous cycle
Authors: Costello Lisa M. , O'Boyle Padraic , Diskin Michael G. , Hynes Ailish C. , Morris Dermot G.
Published: April 2013

The aims of the present study were to assess several components of the insulin-like growth factor (IGF) system in bovine uterine flushings across different days of the oestrous cycle and to examine the relationship between the IGF system and systemic progesterone concentrations. Uterine flushings and plasma were collected from cows on Days 3, 7, 11 and 15 of the oestrous cycle. The IGF-1 concentration was more than 5-fold higher in the uterus compared with plasma on Days 7 and 11 of the cycle, with values similar on Days 3 and 15. Similarly, uterine concentrations of IGF-binding protein (IGFBP)-2 and IGFBP-3 were up to 10- and 4-fold higher than in plasma, respectively, suggesting synthesis and/or transportation of the IGFBPs into the uterus. In addition, concentrations of IGFBP-2 and IGFBP-3 were higher in the uterine horns, ipsilateral to the corpus luteum, on Day 15. This difference could indicate a local controlling mechanism with progesterone possibly playing a role in regulating the concentration of IGFBPs between the uterine horns. There was no significant relationship between systemic progesterone concentrations and IGFBP concentrations on Day 7 of the oestrous cycle. The present study shows that uterine concentrations of IGFBPs are cycle stage specific and also suggests IGF-dependent and -independent functions for IGFBPs during a time of major change in the developing embryo.
Nontoxic radioactive
Listeria
at
is a highly effective therapy against metastatic pancreatic cancer
Authors: Quispe-Tintaya Wilber , Chandra Dinesh , Jahangir Arthee , Harris Matthew , Casadevall Arturo , Dadachova Ekaterina , Gravekamp Claudia
Published: April 2013

No significant improvement in therapy of pancreatic cancer has been reported over the last 25 y, underscoring the urgent need for new alternative therapies. Here, we coupled a radioisotope,
188
Rhenium, to an attenuated (at) live
Listeria monocytogenes
(
Listeria
at
) using
Listeria
-binding antibodies, thus creating a unique radioactive
Listeria
at
(RL). We then demonstrated in a highly metastatic pancreatic mouse tumor model (Panc-02) that RL delivered radioactivity to the metastases and less abundantly to primary tumors in vivo, without harming normal cells. This result was possible because
Listeria
at
was efficiently cleared by the immune system in normal tissues but not in the heavily immune-suppressed microenvironment of metastases and primary tumor. Multiple treatments with low doses of the RL resulted in a dramatic decrease in the number of metastases (∼90%) compared with control groups in the Panc-02 model. This is the first report of using live attenuated bacteria delivering a highly radioactive payload to the metastases, resulting in killing tumor cells in vivo without harming normal cells. The nontoxic RL treatment is attractive for clinical development as a therapy to prevent pancreatic cancer recurrence and metastases.
Generic theory for channel sinuosity
Authors: Lazarus Eli D. , Constantine José Antonio
Published: April 2013

Sinuous patterns traced by fluid flows are a ubiquitous feature of physical landscapes on Earth, Mars, the volcanic floodplains of the Moon and Venus, and other planetary bodies. Typically discussed as a consequence of migration processes in meandering rivers, sinuosity is also expressed in channel types that show little or no indication of meandering. Sinuosity is sometimes described as “inherited” from a preexisting morphology, which still does not explain where the inherited sinuosity came from. For a phenomenon so universal as sinuosity, existing models of channelized flows do not explain the occurrence of sinuosity in the full variety of settings in which it manifests, or how sinuosity may originate. Here we present a generic theory for sinuous flow patterns in landscapes. Using observations from nature and a numerical model of flow routing, we propose that flow resistance (representing landscape roughness attributable to topography or vegetation density) relative to surface slope exerts a fundamental control on channel sinuosity that is effectively independent of internal flow dynamics. Resistance-dominated surfaces produce channels with higher sinuosity than those of slope-dominated surfaces because increased resistance impedes downslope flow. Not limited to rivers, the hypothesis we explore pertains to sinuosity as a geomorphic pattern. The explanation we propose is inclusive enough to account for a wide variety of sinuous channel types in nature, and can serve as an analytical tool for determining the sinuosity a landscape might support.
Pre-Miocene birth of the Yangtze River
Authors: Zheng Hongbo , Clift Peter D. , Wang Ping , Tada Ryuji , Jia Juntao , He Mengying , Jourdan Fred
Published: April 2013

The development of fluvial systems in East Asia is closely linked to the evolving topography following India–Eurasia collision. Despite this, the age of the Yangtze River system has been strongly debated, with estimates ranging from 40 to 45 Ma, to a more recent initiation around 2 Ma. Here, we present40Ar/39Ar ages from basalts interbedded with fluvial sediments from the lower reaches of the Yangtze together with detrital zircon U–Pb ages from sand grains within these sediments. We show that a river containing sediments indistinguishable from the modern river was established before ∼23 Ma. We argue that the connection through the Three Gorges must postdate 36.5 Ma because of evaporite and lacustrine sedimentation in the Jianghan Basin before that time. We propose that the present Yangtze River system formed in response to regional extension throughout eastern China, synchronous with the start of strike–slip tectonism and surface uplift in eastern Tibet and fed by strengthened rains caused by the newly intensified summer monsoon.
Drosophila
ORB protein in two mushroom body output neurons is necessary for long-term memory formation
Authors: Pai Tsung-Pin , Chen Chun-Chao , Lin Hui-Hao , Chin An-Lun , Lai Jason Sih-Yu , Lee Pei-Tseng , Tully Tim , Chiang Ann-Shyn
Published: April 2013

Memory is initially labile and gradually consolidated over time through new protein synthesis into a long-lasting stable form. Studies of odor-shock associative learning in
Drosophila
have established the mushroom body (MB) as a key brain structure involved in olfactory long-term memory (LTM) formation. Exactly how early neural activity encoded in thousands of MB neurons is consolidated into protein-synthesis–dependent LTM remains unclear. Here, several independent lines of evidence indicate that changes in two MB vertical lobe V3 (MB-V3) extrinsic neurons are required and contribute to an extended neural network involved in olfactory LTM: (
i
) inhibiting protein synthesis in MB-V3 neurons impairs LTM; (
ii
) MB-V3 neurons show enhanced neural activity after spaced but not massed training; (
iii
) MB-V3 dendrites, synapsing with hundreds of MB α/β neurons, exhibit dramatic structural plasticity after removal of olfactory inputs; (
iv
) neurotransmission from MB-V3 neurons is necessary for LTM retrieval; and (
v
) RNAi-mediated down-regulation of oo18 RNA-binding protein (involved in local regulation of protein translation) in MB-V3 neurons impairs LTM. Our results suggest a model of long-term memory formation that includes a systems-level consolidation process, wherein an early, labile olfactory memory represented by neural activity in a sparse subset of MB neurons is converted into a stable LTM through protein synthesis in dendrites of MB-V3 neurons synapsed onto MB α lobes.
Single-molecule analysis of combinatorial epigenomic states in normal and tumor cells
Authors: Murphy Patrick J. , Cipriany Benjamin R. , Wallin Christopher B. , Ju Chan Yang , Szeto Kylan , Hagarman James A. , Benitez Jaime J. , Craighead Harold G. , Soloway Paul D.
Published: April 2013

Proper placement of epigenetic marks on DNA and histones is fundamental to normal development, and perturbations contribute to a variety of disease states. Combinations of marks act together to control gene expression; therefore, detecting their colocalization is important, but because of technical challenges, such measurements are rarely reported. Instead, measurements of epigenetic marks are typically performed one at a time in a population of cells, and their colocalization is inferred by association. Here, we describe a single-molecule analytical approach that can perform direct detection of multiple epigenetic marks simultaneously and use it to identify mechanisms coordinating placement of three gene silencing marks, trimethylated histone H3 lysine 9, lysine 27 (H3K9me3, H3K27me3), and cytosine methylation (mC), in the normal and cancer genome. We show that H3K9me3 and mC are present together on individual chromatin fragments in mouse embryonic stem cells and that half of the H3K9me3 marks require mC for their placement. In contrast, mC and H3K27me3 coincidence is rare, and in fact, mC antagonizes H3K27me3 in both embryonic stem cells and primary mouse fibroblasts, indicating this antagonism is shared among primary cells. However, upon immortalization or tumorigenic transformation of mouse fibroblasts, mC is required for complete H3K27me3 placement. Importantly, in human promyelocytic cells, H3K27me3 is also dependent on mC. Because aberrant placement of gene silencing marks at tumor suppressor genes contributes to tumor progression, the improper dependency of H3K27me3 by mC in immortalized cells is likely to be fundamental to cancer. Our platform can enable other studies involving coordination of epigenetic marks and leverage efforts to discover disease biomarkers and epigenome-modifying drugs.
Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
Authors: Michelucci Alessandro , Cordes Thekla , Ghelfi Jenny , Pailot Arnaud , Reiling Norbert , Goldmann Oliver , Binz Tina , Wegner André , Tallam Aravind , Rausell Antonio , Buttini Manuel , Linster Carole L. , Medina Eva , Balling Rudi , Hiller Karsten
Published: April 2013

Immunoresponsive gene 1 (
Irg1
) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify
Irg1
as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of
cis
-aconitate, a tricarboxylic acid cycle intermediate. Using a gain-and-loss-of-function approach in both mouse and human immune cells, we found
Irg1
expression levels correlating with the amounts of itaconic acid, a metabolite previously proposed to have an antimicrobial effect. We purified IRG1 protein and identified its
cis
-aconitate decarboxylating activity in an enzymatic assay. Itaconic acid is an organic compound that inhibits isocitrate lyase, the key enzyme of the glyoxylate shunt, a pathway essential for bacterial growth under specific conditions. Here we show that itaconic acid inhibits the growth of bacteria expressing isocitrate lyase, such as
Salmonella enterica
and
Mycobacterium tuberculosis
. Furthermore,
Irg1
gene silencing in macrophages resulted in significantly decreased intracellular itaconic acid levels as well as significantly reduced antimicrobial activity during bacterial infections. Taken together, our results demonstrate that IRG1 links cellular metabolism with immune defense by catalyzing itaconic acid production.
Limits in decision making arise from limits in memory retrieval
Authors: Giguère Gyslain , Love Bradley C.
Published: April 2013

Some decisions, such as predicting the winner of a baseball game, are challenging in part because outcomes are probabilistic. When making such decisions, one view is that humans stochastically and selectively retrieve a small set of relevant memories that provides evidence for competing options. We show that optimal performance at test is impossible when retrieving information in this fashion, no matter how extensive training is, because limited retrieval introduces noise into the decision process that cannot be overcome. One implication is that people should be more accurate in predicting future events when trained on idealized rather than on the actual distributions of items. In other words, we predict the best way to convey information to people is to present it in a distorted, idealized form. Idealization of training distributions is predicted to reduce the harmful noise induced by immutable bottlenecks in people’s memory retrieval processes. In contrast, machine learning systems that selectively weight (i.e., retrieve) all training examples at test should not benefit from idealization. These conjectures are strongly supported by several studies and supporting analyses. Unlike machine systems, people’s test performance on a target distribution is higher when they are trained on an idealized version of the distribution rather than on the actual target distribution. Optimal machine classifiers modified to selectively and stochastically sample from memory match the pattern of human performance. These results suggest firm limits on human rationality and have broad implications for how to train humans tasked with important classification decisions, such as radiologists, baggage screeners, intelligence analysts, and gamblers.
Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation
Authors: Kawasaki Norihito , Vela Jose Luis , Nycholat Corwin M. , Rademacher Christoph , Khurana Archana , van Rooijen Nico , Crocker Paul R. , Kronenberg Mitchell , Paulson James C.
Published: April 2013

Invariant natural killer T (iNKT) cells induce a protective immune response triggered by foreign glycolipid antigens bound to CD1d on antigen-presenting cells (APCs). A limitation of using glycolipid antigens to stimulate immune responses in human patients has been the inability to target them to the most effective APCs. Recent studies have implicated phagocytic CD169+macrophages as major APCs in lymph nodes for priming iNKT cells in mice immunized with glycolipid antigen in particulate form. CD169 is known as sialoadhesin (Sn), a macrophage-specific adhesion and endocytic receptor of the siglec family that recognizes sialic acid containing glycans as ligands. We have recently developed liposomes decorated with glycan ligands for CD169/Sn suitable for targeted delivery to macrophages via CD169/Sn-mediated endocytosis. Here we show that targeted delivery of a lipid antigen to CD169+macrophages in vivo results in robust iNKT cell activation in liver and spleen using nanogram amounts of antigen. Activation of iNKT cells is abrogated inCd169−/−mice and is macrophage-dependent, demonstrating that targeting CD169+macrophages is sufficient for systemic activation of iNKT cells. When pulsed with targeted liposomes, human monocyte–derived dendritic cells expressing CD169/Sn activated human iNKT cells, demonstrating the conservation of the CD169/Sn endocytic pathway capable of presenting lipid antigens to iNKT cells.
Rhomboid domain-containing protein 3 is a negative regulator of TLR3-triggered natural killer cell activation
Authors: Liu Juan , Liu Shuxun , Xia Meng , Xu Sheng , Wang Chunmei , Bao Yan , Jiang Minghong , Wu Yue , Xu Tian , Cao Xuetao
Published: April 2013

Rhomboid domain-containing protein 3 (Rhbdd3), which belongs to a family of proteins with rhomboid domain, is widely expressed in immune cells; however, the roles of the Rhbdd members, including Rhbdd3, in immunity remain unknown. Natural killer (NK) cells are critical for host immune defense and also can mediate inflammatory diseases such as hepatitis. Although much is known about how NK cells are activated, the detailed mechanisms for negative regulation of NK cell activation remain to be fully understood. Using
Rhbdd3
-
deficient mice, we reveal that Rhbdd3, selectively up-regulated in NK cells upon Toll-like receptor 3 (TLR3) stimulation, negatively regulates TLR3-mediated NK cell activation in a feedback manner. Rhbdd3 inhibits TLR3-triggered IFN-γ and granzyme B expression of NK cells in cell–cell contact dependence of accessory cells such as dendritic cells and Kupffer cells. Rhbdd3 interacts with DNAX activation protein of 12 kDa and promotes its degradation, inhibiting MAPK activation in TLR3-triggered NK cells. Furthermore, Rhbdd3 plays a critical role in attenuating TLR3-triggered acute inflammation by controlling NK cell activation and accumulation in liver and disrupting NK cell–Kupffer cell interaction. Therefore, Rhbdd3 is a feedback inhibitor of TLR3-triggered NK cell activation. Our study outlines a mechanism for the negative regulation of NK cell activation and also provides clues for the function of the rhomboid proteins in immunity.
Aurora kinase inhibitors reveal mechanisms of HURP in nucleation of centrosomal and kinetochore microtubules
Authors: Wu Jiun-Ming , Chen Chiung-Tong , Coumar Mohane Selvaraj , Lin Wen-Hsin , Chen Zi-Jie , Hsu John T.-A. , Peng Yi-Hui , Shiao Hui-Yi , Lin Wen-Hsing , Chu Chang-Ying , Wu Jian-Sung , Lin Chih-Tsung , Chen Ching-Ping , Hsueh Ching-Cheng , Chang Kai-Yen , Kao Li-Pin , Huang Chi-Ying F. , Chao Yu-Sheng , Wu Su-Ying , Hsieh Hsing-Pang , Chi Ya-Hui
Published: April 2013

Significance

In mitosis, microtubules extend and shrink before the bilateral attachment is established. However, which molecules regulate this activity for spindle formation is not fully elucidated. Using two in-house developed small molecules that target the Aurora kinases, we show that hepatoma up-regulated protein (HURP) is highly dynamic, trafficking between centrosome and kinetochore driven by Aurora A-dependent phosphorylation and protein phosphatase 1/2A-associated dephosphorylation. These compounds demonstrate a spatial hierarchical preference of HURP in the attachment of microtubules extending from the mother to the daughter centrosome. These findings help explain the biology of mitosis and may lead to the development of anticancer compounds.
Specificity of RppH-dependent RNA degradation in
Bacillus subtilis
Authors: Hsieh Ping-kun , Richards Jamie , Liu Quansheng , Belasco Joel G.
Published: April 2013

Bacterial RNA degradation often begins with conversion of the 5′-terminal triphosphate to a monophosphate, creating a better substrate for subsequent ribonuclease digestion. For example, in
Bacillus subtilis
and related organisms, removal of the gamma and beta phosphates of primary transcripts by the RNA pyrophosphohydrolase RppH triggers rapid 5′-exonucleolytic degradation by RNase J. However, the basis for the selective targeting of a subset of cellular RNAs by this pathway has remained largely unknown. Here we report that purified
B. subtilis
RppH requires at least two unpaired nucleotides at the 5′ end of its RNA substrates and prefers three or more. The second of these 5′-terminal nucleotides must be G, whereas a less strict preference for a purine is evident at the third position, and A is slightly favored over G at the first position. The same sequence requirements are observed for RppH-dependent mRNA degradation in
B. subtilis
cells. By contrast, a parallel pathway for 5′-end–dependent RNA degradation in that species appears to involve an alternative phosphate-removing enzyme that is relatively insensitive to sequence variation at the first three positions.
Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation
Authors: Jurado Kellie A. , Wang Hao , Slaughter Alison , Feng Lei , Kessl Jacques J. , Koh Yasuhiro , Wang Weifeng , Ballandras-Colas Allison , Patel Pratiq A. , Fuchs James R. , Kvaratskhelia Mamuka , Engelman Alan
Published: April 2013

Integration is essential for HIV-1 replication, and the viral integrase (IN) protein is an important therapeutic target. Allosteric IN inhibitors (ALLINIs) that engage the IN dimer interface at the binding site for the host protein lens epithelium-derived growth factor (LEDGF)/transcriptional coactivator p75 are an emerging class of small molecule antagonists. Consistent with the inhibition of a multivalent drug target, ALLINIs display steep antiviral dose–response curves ex vivo. ALLINIs multimerize IN protein and concordantly block its assembly with viral DNA in vitro, indicating that the disruption of two integration-associated functions, IN catalysis and the IN-LEDGF/p75 interaction, determines the multimode mechanism of ALLINI action. We now demonstrate that ALLINI potency is unexpectedly accounted for during the late phase of HIV-1 replication. The compounds promote virion IN multimerization and, reminiscent of class II IN mutations, block the formation of the electron-dense viral core and inhibit reverse transcription and integration in subsequently infected target cells. Mature virions are recalcitrant to ALLINI treatment, and compound potency during virus production is independent of the level of LEDGF/p75 expression. We conclude that cooperative multimerization of IN by ALLINIs together with the inability for LEDGF/p75 to effectively engage the virus during its egress from cells underscores the multimodal mechanism of ALLINI action. Our results highlight the versatile nature of allosteric inhibitors to primarily inhibit viral replication at a step that is distinct from the catalytic requirement for the target enzyme. The vulnerability of IN to small molecules during the late phase of HIV-1 replication unveils a pharmacological Achilles’ heel for exploitation in clinical ALLINI development.
TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity
Authors: Decressac Mickael , Mattsson Bengt , Weikop Pia , Lundblad Martin , Jakobsson Johan , Björklund Anders
Published: April 2013

Significance

This study shows that neurodegenerative changes induced by α-synuclein in midbrain dopamine neurons in vivo can be blocked through activation of the autophagy-lysosome pathway. Using an adeno-associated virus model of Parkinson disease to overexpress α-synuclein in the substantia nigra, we show that genetic [transcription factor EB (TFEB) and Beclin-1 overexpression] or pharmacological (rapalog) manipulations that enhance autophagy protect nigral neurons from α-synuclein toxicity, but inhibiting autophagy exacerbates α-synuclein toxicity. The results provide a mechanistic link between α-synuclein toxicity and impaired TFEB function, and identify TFEB as a target for therapies aimed at neuroprotection and disease modification in Parkinson disease.