bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple, efficient polarizable coarse-grained water model for molecular dynamics simulations
Authors: Riniker Sereina , van Gunsteren Wilfred F.
Published: March 2011

The development of coarse-grained (CG) models that correctly represent the important features of compounds is essential to overcome the limitations in time scale and system size currently encountered in atomistic molecular dynamics simulations. Most approaches reported in the literature model one or several molecules into a single uncharged CG bead. For water, this implicit treatment of the electrostatic interactions, however, fails to mimic important properties, e.g., the dielectric screening. Therefore, a coarse-grained model for water is proposed which treats the electrostatic interactions between clusters of water molecules explicitly. Five water molecules are embedded in a spherical CG bead consisting of two oppositely charged particles which represent a dipole. The bond connecting the two particles in a bead is unconstrained, which makes the model polarizable. Experimental and all-atom simulated data of liquid water at room temperature are used for parametrization of the model. The experimental density and the relative static dielectric permittivity were chosen as primary target properties. The model properties are compared with those obtained from experiment, from clusters of simple-point-charge water molecules of appropriate size in the liquid phase, and for other CG water models if available. The comparison shows that not all atomistic properties can be reproduced by a CG model, so properties of key importance have to be selected when coarse graining is applied. Yet, the CG model reproduces the key characteristics of liquid water while being computationally 1–2 orders of magnitude more efficient than standard fine-grained atomistic water models.
Determining the Bohm criterion in plasmas with two ion species
Authors: Baalrud S. D. , Hegna C. C.
Published: March 2011

A model that uniquely determines the flow speed of each ion species at the sheath edge of two ion species plasmas is developed. In this analysis, ion-ion two-stream instabilities can play an important role because they significantly enhance the friction between ion species. Two-stream instabilities arise when the difference in flow speeds between the ion species exceeds a critical value: V1−V2≡ΔV≥ΔVc. The resultant instability-enhanced friction rapidly becomes so strong that ΔV cannot significantly exceed ΔVc. Using the condition provided by ΔV=ΔVc and the generalized Bohm criterion, the speed of each ion species is uniquely determined as it leaves a quasineutral plasma and enters a sheath. Previous work [S. D. Baalrud et al., Phys. Rev. Lett. 103, 205002 (2009)] considered the cold ion limit (Ti→0), in which case ΔVc→0 and each ion species obtains a common “system” sound speed at the sheath edge. Finite ion temperatures are accounted for in this work. The result is that ΔVc depends on the density and thermal speed of each ion species; ΔVc has a minimum when the density ratio of the two ion species is near one, and becomes larger as the density ratio deviates from unity. As ΔVc increases, the speed of each ion species approaches its individual sound speed at the sheath edge.
Evolution and tailoring of plasmonic properties in Ag:ZrO2 nanocomposite films by swift heavy ion irradiation
Authors: Kumar Manish , Kulriya P. K. , Pivin J. C. , Avasthi D. K.
Published: March 2011

Ag:ZrO2 nanocomposite films have been synthesized by a sol-gel dip coating process at room temperature, followed by irradiation using swift heavy ions. The effect of electronic energy loss and fluences on the evolution and consequently on the tailoring of plasmonic properties of films has been studied. The optical study exhibits that color of films converts from transparent in pristine form into shiny yellow when films are irradiated by 100 MeV Ag ions at a fluence of 3×1012 ions/cm2. However, irradiation by 120 MeV O ions up to the fluence of 1 × 1014 ions/cm2 does not induce any coloration in films. The coloration is attributed to the evolution of plasmonic feature resulting in a surface plasmon resonance (SPR) induced absorption peak in the visible region. Increase in fluence from 3 × 1012 to 6 × 1013 ions/cm2 of 100 MeV Ag ions induces a redshift in SPR induced peak position from 434 to 487 nm. Microstructural studies confirms the conversion of Ag2O3 (in pristine films) into cubic phase of metallic Ag and the increase of average size of particles with the increasing fluence up to 6 × 1013 ions/cm2. Further increase in fluence leads to the dissolution of Ag atoms in the ZrO2 matrix.
Viscometer using drag force measurements
Authors: Noël M. H. , Semin B. , Hulin J. P. , Auradou H.
Published: March 2011

A robust and precise viscometer using the forces exerted by a laminar flow inside a small duct is presented: the force is measured on a long cylindrical sensor dipped into the flow. Two devices of respective volumes 1.4 and 0.031 ml have been realized, demonstrating that the technique is usable with small fluid volumes. Several Newtonian and non-Newtonian fluids have been tested at shear rates ranging from 0.3 to 10 s−1 for the first device and from 85 to 2550 s−1 for the second one. For Newtonian fluids, of viscosities ranging from 10−3 to 0.1 Pa s, the linear response of the device has been verified and a 90% agreement with the values provided by commercial rheometers is obtained. For non-Newtonian polymer solutions, the variation of the force with the flow velocity allows one to determine the dependence of the viscosity on the shear rate. Two shear thinning polymer solutions with a power law behavior at intermediate shear rates have been investigated and their rheological parameters have been determined.
Numerical simulations to study solar wind turbulence
Authors: Sharma R. P. , Kumar Sachin , Sharma Nidhi , Singh H. D. , Kumar Sanjay
Published: March 2011

Numerical simulation of coupled equations of kinetic Alfvén wave (KAW) and ion acoustic wave is presented in the solar wind. The nonlinear dynamical equations satisfy the modified Zakharov system of equations by taking the nonadiabatic response of the background density. The ponderomotive nonlinearity is incorporated in the wave dynamics. The effect of Landau damping of KAW is taken into account. Localization of magnetic field intensity and the wavenumber spectra (perpendicular and parallel) of magnetic fluctuations are studied in solar plasmas around 1 a.u. Our results reveal the formation of damped localized structures and the steeper spectra that are in good agreement with the observations. These damped structures and steeper turbulent spectra can be responsible for plasma heating and particle acceleration in solar wind.
Ionic electrostatic excitations along biological membranes
Authors: Moradi Afshin
Published: March 2011

A theoretical analysis of ionic electrostatic excitations of a charged biological membrane is presented within the framework of the fluid theory for surface ions inside and outside the cell, in conjunction with the Poisson’s equation. General expressions of dispersion relations are obtained for electrostatic oscillations of intrinsic cellular with different shapes and symmetries.
Molecular cluster building algorithm: Electrostatic guidelines and molecular tailoring approach
Authors: Yeole Sachin D. , Gadre Shridhar R.
Published: March 2011

Nano-sized clusters of various materials are recent experimental targets, since they exhibit size-dependent physico-chemical properties. A vast amount of literature is available on the study of molecular clusters but general methods for systematic evolution of their growth are rather scarce. The present work reports a molecular cluster building algorithm based on the electrostatic guidelines, followed by ab initio investigations, enabled by the application of molecular tailoring approach. Applications of the algorithm for generating geometries and interaction energies of large molecular clusters of zinc sulfide, benzene, and water are presented.
Acoustic plate mode propagation and interaction with ultraviolet light in periodic AIN-on-sapphire structure
Authors: Chivukula Venkata , Čiplys Daumantas , Jain Rakesh , Yang Jinwei , Gaska Remis , Shur Michael
Published: March 2011

AlN overlay featuring periodic columnar structure fabricated by epitaxial lateral overgrowth technique leads to excitation of acoustic plate modes (APMs) not observed in overlays without such periodic structure. The measured velocities of acoustic plate modes propagating in AlN-on-sapphire structure were verified by numerical simulation. The APM velocity is strongly modulated by UV illumination at wavelengths from 240 to 365 nm, and the corresponding phase response is sensitive to both the UV power and the wavelength with maximum sensitivity of 3.0 ppm/(μW/cm2) at 240 nm.
An accurate symplectic calculation of the inboard magnetic footprint from statistical topological noise and field errors in the DIII-D
Authors: Punjabi Alkesh , Ali Halima
Published: March 2011

Any canonical transformation of Hamiltonian equations is symplectic, and any area-preserving transformation in 2D is a symplectomorphism. Based on these, a discrete symplectic map and its continuous symplectic analog are derived for forward magnetic field line trajectories in natural canonical coordinates. The unperturbed axisymmetric Hamiltonian for magnetic field lines is constructed from the experimental data in the DIII-D [J. L. Luxon and L. E. Davis, Fusion Technol. 8, 441 (1985)]. The equilibrium Hamiltonian is a highly accurate, analytic, and realistic representation of the magnetic geometry of the DIII-D. These symplectic mathematical maps are used to calculate the magnetic footprint on the inboard collector plate in the DIII-D. Internal statistical topological noise and field errors are irreducible and ubiquitous in magnetic confinement schemes for fusion. It is important to know the stochasticity and magnetic footprint from noise and error fields. The estimates of the spectrum and mode amplitudes of the spatial topological noise and magnetic errors in the DIII-D are used as magnetic perturbation. The discrete and continuous symplectic maps are used to calculate the magnetic footprint on the inboard collector plate of the DIII-D by inverting the natural coordinates to physical coordinates. The combination of highly accurate equilibrium generating function, natural canonical coordinates, symplecticity, and small step-size together gives a very accurate calculation of magnetic footprint. Radial variation of magnetic perturbation and the response of plasma to perturbation are not included. The inboard footprint from noise and errors are dominated by m=3, n=1 mode. The footprint is in the form of a toroidally winding helical strip. The width of stochastic layer scales as 12 power of amplitude. The area of footprint scales as first power of amplitude. The physical parameters such as toroidal angle, length, and poloidal angle covered before striking, and the safety factor all have fractal structure. The average field diffusion near the X-point for lines that strike and that do not strike differs by about three to four orders of magnitude. The magnetic footprint gives the maximal bounds on size and heat flux density on collector plate.
Low power high-performance radio frequency oscillator for driving ion traps
Authors: Jau Y.-Y. , Benito F. M. , Partner H. , Schwindt P. D. D.
Published: March 2011

We report a simple, efficient, high voltage radio frequency (RF) generator powered by a single voltage source (1.5–7 V) to resonantly drive ion traps or other capacitive loads. Our circuit is able to deliver RF voltages \documentclass[12pt]{minimal}\begin{document}$>$\end{document}> 500 Vp-p at frequencies ranging from 0.1 to 10 MHz. This RF oscillator uses low-cost, commercially available components, and can be easily assembled onto a circuit board of a few cm2. Because of its simplicity and good efficiency, this circuit is useful in applications requiring small size and low power consumption such as portable ion trap systems where the duration of operation under battery power is of concern.
Heat transfer and friction factor of discrete V-down rib roughened solar air heater ducts
Authors: Singh Sukhmeet , Chander Subhash , Saini J. S.
Published: March 2011

In this paper, results of experimental investigation on heat transfer and friction in rectangular ducts roughened with a new configuration of “discrete V-down ribs” on one broad wall are presented. The discretization of V-down rib is done by providing small symmetrical gap equal to rib height in both legs of V-shape. The rectangular duct has width-to-height ratio of 12 and the Reynolds number ranged from 3000 to 15 000. The roughened wall is uniformly heated while the remaining three walls are insulated. These boundary conditions correspond closely to those found in solar air heaters. The rib roughness has height-to-hydraulic diameter ratio of 0.043, angle of attack of 60°, and pitch-to-height ratio of 10. The relative gap position was varied from 0.20 to 0.80. The effects of gap position on Nusselt number and friction factor have been discussed and results compared with continuous V-down rib roughened duct and smooth duct under similar flow and boundary conditions to investigate the enhancement in Nusselt number and friction factor. The maximum enhancement in Nusselt number and friction factor has been obtained at relative gap position of 0.65 and is of order of 2.88 and 3.03 times of that of the smooth duct, respectively. The thermohydraulic performance of solar air heater provided with such rib roughness is considerably enhanced.
Luminescence decay dynamics of self-assembled germanium islands in silicon
Authors: Julsgaard B. , Balling P. , Hansen J. Lundsgaard , Svane A. , Larsen A. Nylandsted
Published: March 2011

The dynamics of the luminescence decay from self-assembled germanium islands embedded in crystalline silicon has been studied for temperatures varied between 16 K and room temperature. We separate the time scale for various dynamical processes by time-resolved emission spectroscopy and identify a characteristic time scale of Auger recombination processes around 10 ns largely independent on temperature, while two slower decay components appear on time scales around 1μs and 10μs, respectively, at low temperatures.
High quality tensile-strained n-doped germanium thin films grown on InGaAs buffer layers by metal-organic chemical vapor deposition
Authors: Jakomin R. , de Kersauson M. , El Kurdi M. , Largeau L. , Mauguin O. , Beaudoin G. , Sauvage S. , Ossikovski R. , Ndong G. , Chaigneau M. , Sagnes I. , Boucaud P.
Published: March 2011

We show that high quality tensile-strained n-doped germanium films can be obtained on InGaAs buffer layers using metal-organic chemical vapor deposition with isobutyl germane as germanium precursor. A tensile strain up to 0.5% is achieved, simultaneously measured by x-ray diffraction and Raman spectroscopy. The effect of tensile strain on band gap energy is directly observed by room temperature direct band gap photoluminescence.
Nonthermal effects on the ion-acoustic solitons in Lorentzian electron-ion plasmas
Authors: Jung Young-Dae , Hong Woo-Pyo
Published: March 2011

The nonthermal effects on the propagation of the ion-acoustic soliton are investigated in generalized Lorentzian electron-ion plasmas. The soliton solution of the Korteweg–de Vries equation is obtained as a function of the spectral index and modified stretched coordinate in the generalized Lorentzian plasma. It is found that the nonthermal effect on the dispersive term is found to be stronger than that on the nonlinear term. It is shown that the nonthermal effect of the Lorentzian plasma strongly suppresses the stretched coordinate of the ion-acoustic soliton. It is also shown that the nonthermal effect increases the position of the ion-acoustic soliton. In addition, the nonthermal effects on the position of the ion-acoustic soliton are found to be more important in the forward direction. It is found that the nonthermal effect strongly suppresses the amplitude of the ion-acoustic soliton in Lorentzian electron-ion plasmas. It is also found that the nonthermal effect on the amplitude of the ion-acoustic soliton is more significant in the backward direction.
Concurrent nonvolatile resistance and capacitance switching in LaAlO3
Authors: Wu S. X. , Peng H. Y. , Wu T.
Published: March 2011

We report on the correlated nonvolatile resistance and capacitance switching in Pt/LaAlO3/Nb:SrTiO3 heterostructures. The pristine devices show the typical characteristics of a Schottky junction; however, after forming, a reverse bias switches the device into a low resistance and high capacitance state while a forward bias drives it into a high resistance and low capacitance state. Our experiments suggest that both the formation of conducting filaments and the modulation of interface barrier contribute to the resistance switching. Oxygen vacancies play critical roles in determining the switching characteristics and can be controlled in the process of device fabrication.
Effect of nonadiabatic spin transfer torque on domain wall resonance frequency and mass
Authors: Jamali Mahdi , Lee Kyung-Jin , Yang Hyunsoo
Published: March 2011

The dynamics of a magnetic domain wall in a semi circular nanowire loop is studied by an analytical model and micromagnetic simulations. We find a damped sinusoidal oscillation of the domain wall for small displacement angles around its equilibrium position under an external magnetic field in the absence of currents. By studying the effect of current induced nonadiabatic spin transfer torque on the magnetic domain wall resonance frequency and mass, a redshift is found in the resonance frequency and domain wall mass increases by increasing the ratio of nonadiabatic spin torque to adiabatic contribution above 1.
Self-assembled hexagonal double fishnets as negative index materials
Authors: Lodewijks Kristof , Verellen Niels , Van Roy Willem , Moshchalkov Victor , Borghs Gustaaf , Van Dorpe Pol
Published: March 2011

We show experimentally the use of nanosphere lithography for fabricating negative index metamaterials in the near-infrared wavelength range. We investigated a specific implementation of the widely studied double fishnet metamaterials, consisting of a gold-silica-gold layer stack perforated by a hexagonal array of round holes. Tuning of the hole diameter allows to tailor these self-assembled materials as single- or double negative metamaterials.
Metal-dispersed porous graphene for hydrogen storage
Authors: Reunchan Pakpoom , Jhi Seung-Hoon
Published: March 2011

First-principles calculations are carried out to study the role of various metal atoms on porous graphene for molecular hydrogen (H2) adsorption. The binding sites of each metal atom on porous graphene are investigated and the binding energies are determined. It is shown that H2 exhibits different adsorption characteristics onto alkaline, alkaline-earth, or transition metals in porous graphene. In particular, Ca-decorated porous graphene is investigated and found to be feasible for high-capacity hydrogen storage. Our results provide a general picture on the interactions of H2 with porous graphene decorated with various metals.
Influence of sample processing parameters on thermal boundary conductance value in an Al/AlN system
Authors: Monachon Christian , Hojeij Mohamad , Weber Ludger
Published: March 2011

The influence of sample processing parameters on the thermal boundary conductance (TBC) between aluminum and aluminum nitride has been investigated by transient thermoreflectance. An evaporated Al layer on the polished substrate yielded a TBC at ambient of roughly 47 MW m−2 K−1. The largest improvement (by a factor of 5) was obtained by plasma-etching of the substrate and subsequent evaporation of the metal layer. Electron microscopy suggests that the differences in TBC were mainly due to the (partial) elimination of the native oxide layer on the substrate. The importance of an adequate model for data extraction on measured TBC is highlighted.
Localized surface plasmon resonance of nanoporous gold
Authors: Lang Xingyou , Qian Lihua , Guan Pengfei , Zi Jian , Chen Mingwei
Published: March 2011

We report the plasmonic properties of free-standing nanoporous gold (NPG) films with an intricate bicontinuous nanostructure. Two characteristic plasmon bands of NPG have been detected in absorption spectra. One at ∼490 nm, resulting from the resonant absorption of gold films, is independent of nanopore sizes and dielectric surroundings. The other at ∼550–650 nm, arising from the excitation of localized surface plasmon resonance, shows obvious band shift with the nanopore sizes and dielectric indices of surrounding media, suggesting that NPG is a promising candidate as plasmonic sensors for organic and biologic molecule detection. This study also shines light on the underlying mechanisms of surface enhanced spectroscopy of NPG.
Direct climate effects of perennial bioenergy crops in the United States
Authors: Georgescu Matei , Lobell David B. , Field Christopher B.
Published: March 2011

Biomass-derived energy offers the potential to increase energy security while mitigating anthropogenic climate change, but a successful path toward increased production requires a thorough accounting of costs and benefits. Until recently, the efficacy of biomass-derived energy has focused primarily on biogeochemical consequences. Here we show that the biogeophysical effects that result from hypothetical conversion of annual to perennial bioenergy crops across the central United States impart a significant local to regional cooling with considerable implications for the reservoir of stored soil water. This cooling effect is related mainly to local increases in transpiration, but also to higher albedo. The reduction in radiative forcing from albedo alone is equivalent to a carbon emissions reduction of, which is six times larger than the annual biogeochemical effects that arise from offsetting fossil fuel use. Thus, in the near-term, the biogeophysical effects are an important aspect of climate impacts of biofuels, even at the global scale. Locally, the simulated cooling is sufficiently large to partially offset projected warming due to increasing greenhouse gases over the next few decades. These results demonstrate that a thorough evaluation of costs and benefits of bioenergy-related land-use change must include potential impacts on the surface energy and water balance to comprehensively address important concerns for local, regional, and global climate change.
Predicting clonal self-renewal and extinction of hematopoietic stem cells
Authors: Sieburg Hans B. , Rezner Betsy D. , Muller-Sieburg Christa E.
Published: March 2011

A single hematopoietic stem cell (HSC) can generate a clone, consisting of daughter HSCs and differentiated progeny, which can sustain the hematopoietic system of multiple hosts for a long time. At the same time, this massive expansion potential must be restrained to prevent abnormal, leukemic proliferation. We used an interdisciplinary approach, combining transplantation assays with mathematical and computational methods, to systematically analyze the proliferative potential of individual HSCs. We show that all HSC clones examined have an intrinsically limited life span. Daughter HSCswithina clone behaved synchronously in transplantation assays and eventually exhausted at the same time. These results indicate that each HSC is programmed to have a finite life span. This program and the memory of the life span of the mother HSC are inherited by all daughter HSCs. In contrast, there was extensive heterogeneity in life spansbetweenindividual HSC clones, ranging from 10 to almost 60 mo. We used model-based machine learning to develop a mathematical model that efficiently predicts the life spans of individual HSC clones on the basis of a few initial measurements of donor type cells in blood. Computer simulations predict that the probability of self-renewal decays with a logistic kinetic over the life span of a normal HSC clone. Other decay functions lead to either graft failure or leukemic proliferation. We propose that dynamical fate probabilities are a crucial condition that leads to self-limiting clonal proliferation.
Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice
Authors: Mochizuki Takatoshi , Arrigoni Elda , Marcus Jacob N. , Clark Erika L. , Yamamoto Mihoko , Honer Michael , Borroni Edilio , Lowell Bradford B. , Elmquist Joel K. , Scammell Thomas E.
Published: March 2011

Narcolepsy is caused by a loss of orexin/hypocretin signaling, resulting in chronic sleepiness, fragmented non-rapid eye movement sleep, and cataplexy. To identify the neuronal circuits underlying narcolepsy, we produced a mouse model in which a loxP-flanked gene cassette disrupts production of the orexin receptor type 2 (OX2R; also known as HCRTR2), but normal OX2R expression can be restored by Cre recombinase. Mice lacking OX2R signaling had poor maintenance of wakefulness indicative of sleepiness and fragmented sleep and lacked any electrophysiological response to orexin-A in the wake-promoting neurons of the tuberomammillary nucleus. These defects were completely recovered by crossing them with mice that express Cre in the female germline, thus globally deleting the transcription-disrupter cassette. Then, by using an adeno-associated viral vector coding for Cre recombinase, we found that focal restoration of OX2R in neurons of the tuberomammillary nucleus and adjacent parts of the posterior hypothalamus completely rescued the sleepiness of these mice, but their fragmented sleep was unimproved. These observations demonstrate that the tuberomammillary region plays an essential role in the wake-promoting effects of orexins, but orexins must stabilize sleep through other targets.
Platonic and Archimedean geometries in multicomponent elastic membranes
Authors: Vernizzi Graziano , Sknepnek Rastko , Olvera de la Cruz Monica
Published: March 2011

Large crystalline molecular shells, such as some viruses and fullerenes, buckle spontaneously into icosahedra. Meanwhile multicomponent microscopic shells buckle into various polyhedra, as observed in many organelles. Although elastic theory explains one-component icosahedral faceting, the possibility of buckling into other polyhedra has not been explored. We show here that irregular and regular polyhedra, including some Archimedean and Platonic polyhedra, arise spontaneously in elastic shells formed by more than one component. By formulating a generalized elastic model for inhomogeneous shells, we demonstrate that coassembled shells with two elastic components buckle into polyhedra such as dodecahedra, octahedra, tetrahedra, and hosohedra shells via a mechanism that explains many observations, predicts a new family of polyhedral shells, and provides the principles for designing microcontainers with specific shapes and symmetries for numerous applications in materials and life sciences.
Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing
Authors: Melo Sonia , Villanueva Alberto , Moutinho Catia , Davalos Veronica , Spizzo Riccardo , Ivan Cristina , Rossi Simona , Setien Fernando , Casanovas Oriol , Simo-Riudalbas Laia , Carmona Javier , Carrere Jordi , Vidal August , Aytes Alvaro , Puertas Sara , Ropero Santiago , Kalluri Raghu , Croce Carlo M. , Calin George A. , Esteller Manel
Published: March 2011

MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at the posttranscriptional level and are critical for many cellular pathways. The disruption of miRNAs and their processing machineries also contributes to the development of human tumors. A common scenario for miRNA expression in carcinogenesis is emerging that shows that impaired miRNA production and/or down-regulation of these transcripts occurs in many neoplasms. Several of these lost miRNAs have tumor-suppressor features, so strategies to restore their expression globally in malignancies would be a welcome addition to the current therapeutic arsenal against cancer. Herein, we show that the small molecule enoxacin, a fluoroquinolone used as an antibacterial compound, enhances the production of miRNAs with tumor suppressor functions by binding to the miRNA biosynthesis protein TAR RNA-binding protein 2 (TRBP). The use of enoxacin in human cell cultures and xenografted, orthotopic, and metastatic mouse models reveals a TRBP-dependent and cancer-specific growth-inhibitory effect of the drug. These results highlight the key role of disrupted miRNA expression patterns in tumorigenesis, and suggest a unique strategy for restoring the distorted microRNAome of cancer cells to a more physiological setting.
Synthesis-enabled functional group deletions reveal key underpinnings of amphotericin B ion channel and antifungal activities
Authors: Palacios Daniel S. , Dailey Ian , Siebert David M. , Wilcock Brandon C. , Burke Martin D.
Published: March 2011

Amphotericin B is the archetype for small molecules that form transmembrane ion channels. However, despite extensive study for more than five decades, even the most basic features of this channel structure and its contributions to the antifungal activities of this natural product have remained unclear. We herein report that a powerful series of functional group-deficient probes have revealed many key underpinnings of the ion channel and antifungal activities of amphotericin B. Specifically, in stark contrast to two leading models, polar interactions between mycosamine and carboxylic acid appendages on neighboring amphotericin B molecules are not required for ion channel formation, nor are these functional groups required for binding to phospholipid bilayers. Alternatively, consistent with a previously unconfirmed third hypothesis, the mycosamine sugar is strictly required for promoting a direct binding interaction between amphotericin B and ergosterol. The same is true for cholesterol. Synthetically deleting this appendage also completely abolishes ion channel and antifungal activities. All of these results are consistent with the conclusion that a mycosamine-mediated direct binding interaction between amphotericin B and ergosterol is required for both forming ion channels and killing yeast cells. The enhanced understanding of amphotericin B function derived from these synthesis-enabled studies has helped set the stage for the more effective harnessing of the remarkable ion channel-forming capacity of this prototypical small molecule natural product.
Three-dimensional colloidal crystals in liquid crystalline blue phases
Authors: Ravnik Miha , Alexander Gareth P. , Yeomans Julia M. , Žumer Slobodan
Published: March 2011

Applications for photonic crystals and metamaterials put stringent requirements on the characteristics of advanced optical materials, demanding tunability, high Q factors, applicability in visible range, and large-scale self-assembly. Exploiting the interplay between structural and optical properties, colloidal lattices embedded in liquid crystals (LCs) are promising candidates for such materials. Recently, stable two-dimensional colloidal configurations were demonstrated in nematic LCs. However, the question as to whether stable 3D colloidal structures can exist in an LC had remained unanswered. We show, by means of computer modeling, that colloidal particles can self-assemble into stable, 3D, periodic structures in blue phase LCs. The assembly is based on blue phases providing a 3D template of trapping sites for colloidal particles. The particle configuration is determined by the orientational order of the LC molecules: Specifically, face-centered cubic colloidal crystals form in type-I blue phases, whereas body-centered crystals form in type-II blue phases. For typical particle diameters (approximately 100 nm) the effective binding energy can reach up to a few 100 
k
B
T
, implying robustness against mechanical stress and temperature fluctuations. Moreover, the colloidal particles substantially increase the thermal stability range of the blue phases, for a factor of two and more. The LC-supported colloidal structure is one or two orders of magnitude stronger bound than, e.g., water-based colloidal crystals.
Reassessing optimal neural population codes with neurometric functions
Authors: Berens Philipp , Ecker Alexander S. , Gerwinn Sebastian , Tolias Andreas S. , Bethge Matthias
Published: March 2011

Cortical circuits perform the computations underlying rapid perceptual decisions within a few dozen milliseconds with each neuron emitting only a few spikes. Under these conditions, the theoretical analysis of neural population codes is challenging, as the most commonly used theoretical tool—Fisher information—can lead to erroneous conclusions about the optimality of different coding schemes. Here we revisit the effect of tuning function width and correlation structure on neural population codes based on ideal observer analysis in both a discrimination and a reconstruction task. We show that the optimal tuning function width and the optimal correlation structure in both paradigms strongly depend on the available decoding time in a very similar way. In contrast, population codes optimized for Fisher information do not depend on decoding time and are severely suboptimal when only few spikes are available. In addition, we use the neurometric functions of the ideal observer in the classification task to investigate the differential coding properties of these Fisher-optimal codes for fine and coarse discrimination. We find that the discrimination error for these codes does not decrease to zero with increasing population size, even in simple coarse discrimination tasks. Our results suggest that quite different population codes may be optimal for rapid decoding in cortical computations than those inferred from the optimization of Fisher information.
Synthesis and receptor profiling ofStemonaalkaloid analogues reveal a potent class of sigma ligands
Authors: Frankowski Kevin J. , Setola Vincent , Evans Jon M. , Neuenswander Ben , Roth Bryan L. , Aubé Jeffrey
Published: March 2011

Reported biological activities ofStemonanatural products, such as antitussive activity, inspired the development of synthetic methods to access several alkaloids within this family and in so doing develop a general route to the core skeleta shared by the class of natural products. The chemistry was subsequently adapted to afford a series of analogue sets bearing simplified, diverseStemona-inspired skeleta. Over 100 of these analogues were subjected to general G protein-coupled receptor profiling along with the known antitussive compound, neostenine; this led to the identification of hit compounds targeting several receptor types. The particularly rich hit subset for sigma receptors was expanded with two focused library sets, which resulted in the discovery of a fully synthetic, potent chemotype of sigma ligands. This collaborative effort combined the development of synthetic methods with extensive, flexible screening resources and exemplifies the role of natural products in bioactivity mining.
Spatial effects on species persistence and implications for biodiversity
Authors: Bertuzzo Enrico , Suweis Samir , Mari Lorenzo , Maritan Amos , Rodríguez-Iturbe Ignacio , Rinaldo Andrea
Published: March 2011

Natural ecosystems are characterized by striking diversity of form and functions and yet exhibit deep symmetries emerging across scales of space, time, and organizational complexity. Species-area relationships and species-abundance distributions are examples of emerging patterns irrespective of the details of the underlying ecosystem functions. Here we present empirical and theoretical evidence for a new macroecological pattern related to the distributions of local species persistence times, defined as the time spans between local colonizations and extinctions in a given geographic region. Empirical distributions pertaining to two different taxa, breeding birds and herbaceous plants, analyzed in a framework that accounts for the finiteness of the observational period exhibit power-law scaling limited by a cutoff determined by the rate of emergence of new species. In spite of the differences between taxa and spatial scales of analysis, the scaling exponents are statistically indistinguishable from each other and significantly different from those predicted by existing models. We theoretically investigate how the scaling features depend on the structure of the spatial interaction network and show that the empirical scaling exponents are reproduced once a two-dimensional isotropic texture is used, regardless of the details of the ecological interactions. The framework developed here also allows to link the cutoff time scale with the spatial scale of analysis, and the persistence-time distribution to the species-area relationship. We conclude that the inherent coherence obtained between spatial and temporal macroecological patterns points at a seemingly general feature of the dynamical evolution of ecosystems.
Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells
Authors: Antonyak Marc A. , Li Bo , Boroughs Lindsey K. , Johnson Jared L. , Druso Joseph E. , Bryant Kirsten L. , Holowka David A. , Cerione Richard A.
Published: March 2011

Tumor progression involves the ability of cancer cells to communicate with each other and with neighboring normal cells in their microenvironment. Microvesicles (MV) derived from human cancer cells have received a good deal of attention because of their ability to participate in the horizontal transfer of signaling proteins between cancer cells and to contribute to their invasive activity. Here we show that MV may play another important role in oncogenesis. In particular, we demonstrate that MV shed by two different human cancer cells, MDAMB231 breast carcinoma cells and U87 glioma cells, are capable of conferring onto normal fibroblasts and epithelial cells the transformed characteristics of cancer cells (e.g., anchorage-independent growth and enhanced survival capability) and that this effect requires the transfer of the protein cross-linking enzyme tissue transglutaminase (tTG). We further demonstrate that tTG is not sufficient to transform fibroblasts but rather that it must collaborate with another protein to mediate the transforming actions of the cancer cell-derived MV. Proteomic analyses of the MV derived from MDAMB231 and U87 cells indicated that both these vesicle preparations contained the tTG-binding partner and cross-inking substrate fibronectin (FN). Moreover, we found that tTG cross-links FN in MV from cancer cells and that the ensuing MV-mediated transfers of cross-linked FN and tTG to recipient fibroblasts function cooperatively to activate mitogenic signaling activities and to induce their transformation. These findings highlight a role for MV in the induction of cellular transformation and identify tTG and FN as essential participants in this process.
Sonic hedgehog signaling is decoded by calcium spike activity in the developing spinal cord
Authors: Belgacem Yesser H. , Borodinsky Laura N.
Published: March 2011

Evolutionarily conserved hedgehog proteins orchestrate the patterning of embryonic tissues, and dysfunctions in their signaling can lead to tumorigenesis. In vertebrates, Sonic hedgehog (Shh) is essential for nervous system development, but the mechanisms underlying its action remain unclear. Early electrical activity is another developmental cue important for proliferation, migration, and differentiation of neurons. Here we demonstrate the interplay between Shh signaling and Ca
2+
dynamics in the developing spinal cord. Ca
2+
imaging of embryonic spinal cells shows that Shh acutely increases Ca
2+
spike activity through activation of the Shh coreceptor Smoothened (Smo) in neurons. Smo recruits a heterotrimeric GTP-binding protein-dependent pathway and engages both intracellular Ca
2+
stores and Ca
2+
influx. The dynamics of this signaling are manifested in synchronous Ca
2+
spikes and inositol triphosphate transients apparent at the neuronal primary cilium. Interaction of Shh and electrical activity modulates neurotransmitter phenotype expression in spinal neurons. These results indicate that electrical activity and second-messenger signaling mediate Shh action in embryonic spinal neurons.
Binge alcohol drinking is associated with GABAAα2-regulated Toll-like receptor 4 (TLR4) expression in the central amygdala
Authors: Liu Juan , Yang Andrew R. , Kelly Timothy , Puche Adam , Esoga Chioma , June Harry L. , Elnabawi Ahmed , Merchenthaler Istvan , Sieghart Werner , June Harry L. , Aurelian Laure
Published: March 2011

Binge drinking (blood-alcohol levels ≥ 0.08 g% in a 2-h period), is a significant public health burden in need of improved treatment. Gene therapy may offer beneficial alternatives to current psychosocial and pharmacotherapeutic interventions, but identification of the target genes is a clinical challenge. We report that a GABAAα2 siRNA vector (pHSVsiLA2) infused into the central nucleus of the amygdala (CeA) of alcohol-preferring (P) rats caused profound and selective reduction of binge drinking associated with inhibition of α2 expression, decreased GABAAreceptor density, and inhibition of Toll-like receptor 4 (TLR4). CeA infusion of a TLR4 siRNA vector (pHSVsiLTLR4a) also inhibited binge drinking, but neither vector functioned when infused into the ventral pallidum. Binge drinking was inhibited by a GABAAα1 siRNA vector (pHSVsiLA1) infused into the ventral pallidum, unrelated to TLR4. The vectors did not alter sucrose intake and a scrambled siRNA vector was negative. The data indicate that GABAAα2-regulated TLR4 expression in the CeA contributes to binge drinking and may be a key early neuroadaptation in excessive drinking.
High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses
Authors: Sun Yipeng , Qin Kun , Wang Jingjing , Pu Juan , Tang Qingdong , Hu Yanxin , Bi Yuhai , Zhao Xueli , Yang Hanchun , Shu Yuelong , Liu Jinhua
Published: March 2011

H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health. The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort. To evaluate the potential public risk of the reassortant viruses derived from these viruses, we used reverse genetics to generate 127 H9 reassortants derived from an avian H9N2 and a pandemic H1N1 virus, and evaluated their compatibility, replication ability, and virulence in mice. These hybrid viruses showed high genetic compatibility and more than half replicated to a high titer in vitro. In vivo studies of 73 of 127 reassortants revealed that all viruses were able to infect mice without prior adaptation and 8 reassortants exhibited higher pathogenicity than both parental viruses. All reassortants with higher virulence than parental viruses contained the PA gene from the 2009 pandemic virus, revealing the important role of the PA gene from the H1N1/2009 virus in generating a reassortant virus with high public health risk. Analyses of the polymerase activity of the 16 ribonucleoprotein combinations in vitro suggested that the PA of H1N1/2009 origin also enhanced polymerase activity. Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin.
Rational development of a strategy for modifying the aggregatibility of proteins
Authors: Tan Zhongping , Shang Shiying , Danishefsky Samuel J.
Published: March 2011

The conversion of peptide and proteins from their soluble state into well-organized aggregates, together with the accompanied oxidation of methionine residue, presents a significant challenge to human health, to the manufacture of protein therapeutics, and to the synthesis of proteins and glycoproteins. Despite their fundamental importance, little is known about the molecular basis of these two side reactions and their control. Here, using chemical peptide synthesis, we further confirmed the importance of the balance between hydrophobic interactions and electrostatic repulsive forces in inducing and inhibiting aggregation and methionine oxidation. Most importantly, through extending the established principle, we are able to effectively stabilize the problematic peptide fragment through the attachment of cleavable arginine tags. Future applications of our approach are expected to facilitate the synthesis and study of difficult peptides, proteins, and glycoproteins and will provide more opportunities for the optimization of protein biopharmaceuticals and for the development of cell-permeable biomolecules.
Generation Difficulty and Memory for Source
Authors: Nieznański Marek
Published: March 2011

The role of the word predictability from sentence context for reality monitoring and external source monitoring was examined in two experiments. In a reality-monitoring task, discrimination of an internal source was better in the hard than in the easy condition. It is probable that extra cognitive operations engaged during word generation in the hard condition were effective cues for reality-monitoring judgements. In contrast, in an external source-monitoring task (recognition memory of item's colour), the hard condition resulted in worse source memory for generated words than did the easy condition. This result is consistent both with an item–context trade-off hypothesis and a processing hypothesis. Greater effort involved at the time of generation might limit resources available for encoding of an external source. It is also possible that for generated words, the hard condition promoted conceptual processing instead of perceptual processing; therefore the item's colour was not effectively encoded.
Cdk-mediated phosphorylation of the Kvβ2 auxiliary subunit regulates Kv1 channel axonal targeting
Authors: Vacher Hélène , Yang Jae-Won , Cerda Oscar , Autillo-Touati Amapola , Dargent Bénédicte , Trimmer James S.
Published: March 2011

Kv1 channels are concentrated at specific sites in the axonal membrane, where they regulate neuronal excitability. Establishing these distributions requires regulated dissociation of Kv1 channels from the neuronal trafficking machinery and their subsequent insertion into the axonal membrane. We find that the auxiliary Kvβ2 subunit of Kv1 channels purified from brain is phosphorylated on serine residues 9 and 31, and that cyclin-dependent kinase (Cdk)–mediated phosphorylation at these sites negatively regulates the interaction of Kvβ2 with the microtubule plus end–tracking protein EB1. Endogenous Cdks, EB1, and Kvβ2 phosphorylated at serine 31 are colocalized in the axons of cultured hippocampal neurons, with enrichment at the axon initial segment (AIS). Acute inhibition of Cdk activity leads to intracellular accumulation of EB1, Kvβ2, and Kv1 channel subunits within the AIS. These studies reveal a new regulatory mechanism for the targeting of Kv1 complexes to the axonal membrane through the reversible Cdk phosphorylation-dependent binding of Kvβ2 to EB1.
Mitochondrial reactive oxygen species drive proinflammatory cytokine production
Authors: Naik Edwina , Dixit Vishva M.
Published: March 2011

High levels of reactive oxygen species (ROS) are observed in chronic human diseases such as neurodegeneration, Crohn’s disease, and cancer. In addition to the presence of oxidative stress, these diseases are also characterized by deregulated inflammatory responses, including but not limited to proinflammatory cytokine production. New work exploring the mechanisms linking ROS and inflammation find that ROS derived from mitochondria act as signal-transducing molecules that provoke the up-regulation of inflammatory cytokine subsets via distinct molecular pathways.