bluuebunny/crossref_metadata_2025 huggingface dataset:
Study Mechanism Of Action Of Krishnavajrabhraka Bhasma In Asthma
Authors: Sarda Kushal , Pandit Vijaya , Dawane Jayshree , Deshmane Gourav
Published: December 2010

Objective:

To evaluate the mechanism of action of Krishnavajrabhraka Bhasma(KVB) in chronic asthma.

Methodology:

30 animals divided into 5 groups: 1)vehicle(water) 2)vehicle(honey) 3)Low dose KVB 4)High dose KVB 5)Standard drug.Expt I:- Mast cell stabilization-On day 1, animals were sensitized with egg albumin. Treatment started from day 22 in two ways: a)Single dose b)14days. Egg albumin challenge was given at the end of the treatment. Rats were sacrificed, mesentery collected & observed for mast cell degranulation.Expt II:- Anti-inflammatory action-Croton oil was injected in the back in all rats to make a pouch. After 7 days of drug treatment, animals were sacrificed, pouch removed & weighed. Exudate was measured.

Results:

Expt.I – KVB was found to have mast cell stabilizing action in both experiments. High dose of KVB was equally effective as sodium-cromoglycate.Expt.II – High dose of KVB showed significant reduction of inflammation comparable to diclofenac.

Conclusion:

KVB has mast cell stabilizing & anti-inflammatory activity.
Peer Interactions of Preschool Children With and Without Hearing Loss
Authors: DeLuzio Joanne , Girolametto Luigi
Published: December 2010

Purpose

Little is known about the social interaction skills of children with severe to profound hearing loss (SPHL) in terms of how they manage conversational exchanges with peers. This study compared the initiation and response skills of children with SPHL with those of children with typical hearing during group play in integrated preschool programs.

Method

Two groups of 12 children were matched on a number of variables and assessed for intelligence, language, speech, and social development. All initiations, responses, and resulting interactions during 20 min of group play were transcribed and coded. Outcome measures included number and type of initiation strategies, number of responses, and length of interactions.

Results

Despite poorer speech, language, and social development, there were no significant differences in initiation and response skills measured between children with SPHL and their matched peers. The small sample size may have made differences difficult to detect; however, playmates initiated interactions less often with the children with SPHL and ignored their initiations more often than those of other children.

Conclusions

Preschool children with SPHL were excluded from interactions by their playmates. Having age-appropriate language skills did not ensure successful peer interactions. Inclusive preschool programs may consider offering classroom-wide social skills training to enhance interaction opportunities.
Working Memory Training for Children With Cochlear Implants: A Pilot Study
Authors: Kronenberger William G. , Pisoni David B. , Henning Shirley C. , Colson Bethany G. , Hazzard Lindsey M.
Published: December 2010

Purpose

This study investigated the feasibility and efficacy of a working memory training program for improving memory and language skills in a sample of 9 children who are deaf (age 7–15 years) with cochlear implants (CIs).

Method

All children completed the Cogmed Working Memory Training program on a home computer over a 5-week period. Feasibility and acceptability of the program were evaluated using parent report and measures of children’s performance on the training exercises. Efficacy measures of working memory and sentence repetition were obtained prior to training, immediately after training, and 1 month and 6 months after training.

Results

Children’s performance improved on most training exercises, and parents reported no problems with children’s hearing or understanding of the exercises. After completion of working memory training, children demonstrated significant improvement on measures of verbal and nonverbal working memory, parent-reported working memory behavior, and sentence-repetition skills. The magnitude of improvement in working memory decreased slightly at the 1-month follow-up and more substantially at 6-month follow-up. However, sentence repetition continued to show marked improvement at 6-month follow-up.

Conclusions

Working memory training may produce benefit for some memory and language skills for children with CIs, supporting the importance of conducting a large-scale, randomized clinical trial with this population.
In vacancies in InN grown by plasma-assisted molecular beam epitaxy
Authors: Reurings Floris , Tuomisto Filip , Gallinat Chad S. , Koblmüller Gregor , Speck James S.
Published: December 2010

The authors have applied positron annihilation spectroscopy to study the effect of different growth conditions on vacancy formation in In- and N-polar InN grown by plasma-assisted molecular beam epitaxy. The results suggest that the structural quality of the material and limited diffusion of surface adatoms during growth dictate the In vacancy formation in low electron-density undoped epitaxial InN, while growth conditions and thermodynamics have a less important role, contrary to what is observed in, e.g., GaN. Furthermore, the results imply that in high quality InN, the electron mobility is likely limited not by ionized point defect scattering, but rather by threading dislocations.
Self-polarization phenomenon and control of dispersion of synthetic antiferromagnetic nanoparticles for biological applications
Authors: Joisten H. , Courcier T. , Balint P. , Sabon P. , Faure-Vincent J. , Auffret S. , Dieny B.
Published: December 2010

Using a top-down approach, synthetic antiferromagnetic micro/nanoparticles usable for biological applications were prepared. These particles exhibit “superparamagneticlike” properties. Their magnetic susceptibility can be accurately controlled by the thickness of the constituting layers. When dispersed in solution, striking differences in their interactions are observed depending on their susceptibility. Above a susceptibility threshold, a phenomenon of self-polarization is observed in zero applied field, resulting in a gradual agglomeration of the particles. In contrast, below the susceptibility threshold, the particles get redispersed in zero field. This is interpreted by a self-consistent model taking into account dipolar interactions between particles and their magnetic susceptibility.
Development of a digital integrator for the KSTAR device
Authors: Seo Seong-Heon , Werner Andreas , Marquardt M.
Published: December 2010

The development of an integrator for magnetic diagnostics becomes more important as the pulse length of fusion devices gets longer and longer, especially for present-day superconducting fusion devices. A small offset in the signal can cause a significant drift in the integrator output for long pulse experiments. A lock-in amplifying digital integrator has been developed for Wendelstein 7-X (W7-X). It succeeds in suppressing the drift to a low value but requires about 100 ms for data processing. To shorten the data processing time, a Field Programmable Gate Array (FPGA) built in the digitizer is utilized. Since there is no need to transfer the data to an external computer, the integration can be done in real time. The microprocessor built in the digitizer directly transfers the data integrated in the internal FPGA into the reflective memory installed in the same compact Peripheral Component Interconnect chassis. These features result in a very compact system design. The design and the preliminary results of the digital integrator will be presented.
Distribution of structural domains in MnAs layers grown on GaAs substrates
Authors: Takagaki Y. , Lähnemann J. , Jenichen B. , Herfort J. , Herrmann C. , Jahn U.
Published: December 2010

Electron backscatter diffraction is utilized to determine the distribution of coexisting structural domains in MnAs layers prepared on GaAs substrates. In a layer grown on a GaAs(111)B substrate using solid phase epitaxy, the structural domains roughly correspond to the morphological features of the surface. The domains are, in contrast, considerably larger in size than the surface roughness when the substrate is GaAs(113)A. We examine the role of the freedom in in-plane crystalline alignment for causing such a difference using a numerical model. In a layer grown at an extraordinary high temperature (600 °C) on a GaAs(111)B substrate, (0001) and (11¯0l) orientations are interwoven. While the (0001) component is present mainly as thin flat films, a mixture of all the components forms thick elongated islands in the surrounding of the films. Consequences of such an inhomogeneity on the magnetic and electrical properties of the layer are discussed.
Quantitative analyses of oxidation states for cubic SrMnO3 and orthorhombic SrMnO2.5 with electron energy loss spectroscopy
Authors: Kobayashi S. , Tokuda Y. , Mizoguchi T. , Shibata N. , Sato Y. , Ikuhara Y. , Yamamoto T.
Published: December 2010

The oxidation state of Mn in cubic SrMnO3 and orthorhombic SrMnO2.5 was investigated by electron energy loss (EEL) spectroscopy. Change in the oxidation state of Mn produced some spectral changes in the O-K edge as well as in the Mn-L2,3 edge EEL spectra. This study demonstrated that the oxidation state of Mn and the amount of oxygen vacancies in cubic SrMnO3 and orthorhombic SrMnO2.5 could be quantified by analyzing the features of the O-K edge spectrum and the Mn L3/L2 ratio in the Mn-L2,3 edge spectrum. Our quantitative analysis showed that the spectral changes in the Mn-L2,3 edge were mainly caused by the oxidation state of Mn, whereas those in the O-K edge could be sensitive to both the oxidation state of Mn and to lattice distortions.
Electron transport properties in high-purity Ge down to cryogenic temperatures
Authors: Aubry-Fortuna V. , Dollfus P.
Published: December 2010

Electron transport in Ge at various temperatures down to 20 mK has been investigated using particle Monte Carlo simulation taking into account ionized impurity and inelastic phonon scattering. The simulations account for the essential features of electron transport at cryogenic temperature: Ohmic regime, anisotropy of the drift velocity relative to the direction of the electric field, as well as a negative differential mobility phenomenon along the ⟨111⟩ field orientation. Experimental data for the electron velocities are reproduced with a satisfactory accuracy. Examples of electron position in the real space during the simulations are given and evidence separated clouds of electrons propagating along different directions depending on the valley they belong to.
Self-field effects on instability of wave modes in a free-electron laser with background plasma
Authors: Ghazavi Atefeh , Maraghechi Behrouz , Mohsenpour Taghi
Published: December 2010

A dispersion relation for the plasma loaded free-electron laser (FEL), with a helical wiggler and an axial magnetic field is derived. The cold fluid formulation is used with self-fields of the electron beam taken into account. By solving the dispersion relation numerically the influence of self-fields on the FEL resonance and the two-stream instability is investigated. It was found that although self-fields have strong effect on the FEL resonance, their effects on the two-stream instability is much weaker.
Observation by conductive-probe atomic force microscopy of strongly inverted surface layers at the hydrogenated amorphous silicon/crystalline silicon heterojunctions
Authors: Maslova O. A. , Alvarez J. , Gushina E. V. , Favre W. , Gueunier-Farret M. E. , Gudovskikh A. S. , Ankudinov A. V. , Terukov E. I. , Kleider J. P.
Published: December 2010

Heterojunctions made of hydrogenated amorphous silicon (a-Si:H) and crystalline silicon (c-Si) are examined by conducting probe atomic force microscopy. Conductive channels at both (n)a-Si:H/(p)c-Si and (p)a-Si:H/(n)c-Si interfaces are clearly revealed. These are attributed to two-dimension electron and hole gases due to strong inversion layers at the c-Si surface in agreement with previous planar conductance measurements. The presence of a hole gas in (p)a-Si:H/(n)c-Si structures implies a quite large valence band offset (EVc-Si−EVa-Si:H>0.25 eV).
Optical properties of large-area polycrystalline chemical vapor deposited graphene by spectroscopic ellipsometry
Authors: Nelson F. J. , Kamineni V. K. , Zhang T. , Comfort E. S. , Lee J. U. , Diebold A. C.
Published: December 2010

Spectroscopic ellipsometry was used to characterize the complex refractive index of chemical vapor deposition (CVD) graphene grown on copper foils and transferred to glass substrates. Two ellipsometers, with respective wavelength ranges extending into the ultraviolet and infrared (IR), have been used to characterize the CVD graphene optical functions. The optical absorption follows the same relation to the fine structure constant previously observed in the IR region, and displays the exciton-dominated absorption peak at ∼4.5 eV. The optical functions of CVD graphene show some differences when compared to published values for exfoliated graphene.
Influence of the interface-induced electron self-energy on the subthreshold characteristics of silicon gate-all-around nanowire transistors
Authors: Li Changsheng , Bescond Marc , Lannoo Michel
Published: December 2010

The modeling of nanoscale semiconductor devices is usually performed in a self-consistent Schrödinger–Poisson procedure. This letter reports an application of a more general approach based on the so-called GW approximation. We numerically determine the contribution due to the interface dynamic polarization and its influence on the subthreshold slope and threshold voltage. Results are given for a nanowire transistor for which the influence of the confinement and the nature of the gate oxide are analyzed. Interface-induced correlations are found to increase the subthreshold slope and decrease the threshold voltage, although the use of high-κ gate oxide reduces electrical parameter variations.
High slope efficiency liquid crystal lasers
Authors: Mowatt Carrie , Morris Stephen M. , Wilkinson Timothy D. , Coles Harry J.
Published: December 2010

In this letter, we demonstrate high slope efficiency laser emission from reflective liquid crystal laser devices with a silicon backplane. Three different cell architectures were fabricated and each resulting laser device was then characterized in terms of the excitation threshold and the slope efficiency when optically excited close to the absorption maximum of the gain medium (pyrromethene 597). By combining a high gain medium with double-pass geometry, as well as the optimum cell thickness, the results demonstrate that it is possible to reduce thresholds by 25% and achieve slope efficiencies as high as 60%.
Piezoelectric characteristic of nanocrystalline AlN films obtained by pulsed laser deposition at room temperature
Authors: Cibert C. , Dutheil P. , Champeaux C. , Masson O. , Trolliard G. , Tétard F. , Catherinot A.
Published: December 2010

Aluminum nitride (AlN) thin films were deposited at room temperature by pulsed laser deposition, and their nanostructure and piezoelectric properties were investigated as a function of fluence. For all fluences, the films were found to consist of an amorphous AlN matrix containing crystalline AlN nanoparticles with size of 6–7 nm. These nanoparticles spark off the good piezoelectric response, with d33 piezoelectric coefficients between 2.3 and 3.8 pm V−1, similar to those obtained for (002)-oriented AlN films deposited at higher temperatures. These results indicate that nanocrystalline AlN films deposited at room temperature are good candidates for integration in acoustic wave applications.
Tunnel injection In0.25Ga0.75N/GaN quantum dot light-emitting diodes
Authors: Bhattacharya Pallab , Zhang Meng , Hinckley John
Published: December 2010

Hole tunnel injection is incorporated in the design of In0.25Ga0.75N/GaN quantum dot light-emitting diodes with peak emission at λ∼500 nm. Calculations show that cold holes are uniformly injected into all five quantum dot layers in the active region. Measurements were made on devices having different thicknesses, teff, of the In0.43Al0.57N hole tunnel barrier. The best performance is exhibited by a device with teff=1.5 nm. The maximum external quantum efficiency is 0.66% at 220 A/cm2, and an efficiency droop of 20% at 360 A/cm2 is tentatively attributed to reduced Auger recombination and leakage of hot carriers.
Aging of magnetic properties in MgO films
Authors: Balcells Ll. , Beltrán J. I. , Martínez-Boubeta C. , Konstantinović Z. , Arbiol J. , Martínez B.
Published: December 2010

In this work we report on the magnetic behavior of MgO thin films prepared by sputtering. A severe aging process of the ferromagnetic properties is detected in magnetic samples exposed to ambient atmosphere. However, ferromagnetism can be successively switched on again by annealing samples in vacuum. We suggest this behavior reflects the key role played by defects in stabilizing ferromagnetism in MgO films and is likely to be closely related to the hydrogen-driven instability of V-type centers in this material.
Vacancy clustering and diffusion in heavily P doped Si
Authors: Hin Céline , Dresselhaus Mildred , Chen Gang
Published: December 2010

A kinetic Monte Carlo (KMC) algorithm with a vacancy source and sink has been developed to determine the equilibrium vacancy concentration (CVe) in Si1−xPx alloys. KMC results for CVe exhibit good agreement with the Lomer formula with added entropic terms to account for high P concentrations. They also highlight the role of CVe and clustering on self and impurity diffusion during thermal aging.
Effects of convection and solid wall on the diffusion in microscale convection flows
Authors: Zhang Jun , Fan Jing , Fei Fei
Published: December 2010

The diffusive transport properties in microscale convection flows are studied by using the direct simulation Monte Carlo method. The effective diffusion coefficient D∗ is computed from the mean square displacements of simulated molecules based on the Einstein diffusion equation D∗=⟨Δx2(t)⟩/2t. Two typical convection flows, namely, thermal creep convection and Rayleigh–Bénard convection, are investigated. The thermal creep convection in our simulation is in the noncontinuum regime, with the characteristic scale of the vortex varying from 1 to 100 molecular mean free paths. The diffusion is shown to be enhanced only when the vortex scale exceeds a certain critical value, while the diffusion is reduced when the vortex scale is less than the critical value. The reason for phenomenon of diffusion reduction in the noncontinuum regime is that the reduction effect due to solid wall is dominant while the enhancement effect due to convection is negligible. A molecule will lose its memory of macroscopic velocity when it collides with the walls, and thus molecules are hard to diffuse away if they are confined between very close walls. The Rayleigh–Bénard convection in our simulation is in the continuum regime, with the characteristic length of 1000 molecular mean free paths. Under such condition, the effect of solid wall on diffusion is negligible. The diffusion enhancement due to convection is shown to scale as the square root of the Péclet number in the steady convection regime, which is in agreement with previous theoretical and experimental results. In the oscillation convection regime, the diffusion is more strongly enhanced because the molecules can easily advect from one roll to its neighbor due to an oscillation mechanism.
Front-gate InGaAs-on-Insulator metal-insulator-semiconductor field-effect transistors
Authors: Urabe Yuji , Yokoyama Masafumi , Takagi Hideki , Yasuda Tetsuji , Miyata Noriyuki , Yamada Hisashi , Fukuhara Noboru , Hata Masahiko , Takenaka Mitsuru , Takagi Shinichi
Published: December 2010

We report on In0.53Ga0.47As(100)-on-insulator metal-insulator-semiconductor field-effect transistors (InGaAs-OI MISFETs) on Si wafers with standard front-gate configuration. The channel mobility of the InGaAs-OI MISFETs was higher than those for InGaAs MISFETs on bulk InP wafers. The on/off ratio was controlled over a wide range by applying a back-gate bias, which indicates the possibility of double-gate operation for higher drivability and lower power consumption.
Excitation of surface plasma waves by a density-modulated electron beam in a magnetized plasma cylinder
Authors: Gupta Ruby , Sharma Suresh C. , Prakash Ved
Published: December 2010

A density-modulated electron beam propagating through a plasma cylinder excites surface plasma waves (SPWs) via Cerenkov and fast cyclotron interaction. A nonlocal theory of this process has been developed. Numerical calculations of the growth rate and unstable mode frequencies have been carried out for the typical parameters of the SPWs. The growth rate γ (in rad/s) of the unstable wave instability increases with the modulation index Δ and has the largest value for Δ∼1 in addition to when the frequency and wave number of the modulation are comparable to that of the unstable wave. For Δ=0, γ turns out to be ∼6.06×109 rad/s for Cerenkov interaction and ∼5.47×109 rad/s for fast cyclotron interaction. The growth rate of the instability increases with the beam density and scales as one-third power of the beam density in Cerenkov interaction and is proportional to the square root of beam density in fast cyclotron interaction. The real part of the frequency of the unstable wave increases as almost the square root of the beam voltage. The results of the theory are applied to explain some of the experimental observations.
Electrostatic beams from tailored plasmas in a Penning–Malmberg trap
Authors: Weber T. R. , Danielson J. R. , Surko C. M.
Published: December 2010

In recent work, a technique was developed to extract high quality beams from single-component plasmas confined in a Penning–Malmberg trap in a 4.8 T magnetic field. In this paper, a procedure is developed to extract these beams from the confining magnetic field and then focus them to create especially tailored electrostatic beams. Electron beams are extracted from the field in two stages: they are first transported to a region of reduced field (1 mT), and then taken to zero field with a nonadiabatic, fast extraction. Once in the field-free region, the beams are focused using an Einzel lens. Experimental results and numerical simulations are presented to illustrate the extraction and focusing process. Theoretical expressions are developed to describe the modifications to the relevant beam energy and spatial distributions. Where possible, analytic expressions are presented for the case relevant here of beams with Gaussian radial profiles. Beam emittance considerations are discussed as well as prospects for further development of these techniques. Application of these techniques to provide high-quality positron beams is also discussed.
High-performance optoelectrical dual-mode memory based on spiropyran-containing polyimide
Authors: Liu Qisheng , Jiang Kejian , Wen Yongqiang , Wang Jingxia , Luo Jia , Song Yanlin
Published: December 2010

A thermally stable polyimide (PI-SP) was designed as a functional material for the fabrication of memory device, and its optoelectrical dual-mode memory was studied. In an Al/PI-SP/Al device, the memory can be switched on with the negative or positive voltage with the on/off current ratios of about 104. Besides, the PI-SP can also undergo the reversibly photochromic reactions in solution or solid state with high fatigue resistance, which can serve as optical recording material. The PI-SP based device can exhibit the electrical and optical switching properties independently, while their cooperative switching properties cannot be realized simultaneously.
Diamond as a high pressure gauge up to 2.7 Mbar
Authors: Dubrovinskaia Natalia , Dubrovinsky Leonid , Caracas Razvan , Hanfland Michael
Published: December 2010

A pressure gauge is a key issue of any high pressure experiment in a diamond anvil cell (DAC). Here we present a method of in situ synthesis of microcrystals of diamond that can be further used as a pressure standard in the course of the same DAC experiment. Calibration curve of the Raman shift versus pressure is extended up to 270 GPa and experimental results are compared with those of ab initio calculations.
Current crowding effect on the ideality factor and efficiency droop in blue lateral InGaN/GaN light emitting diodes
Authors: Malyutenko V. K. , Bolgov S. S. , Podoltsev A. D.
Published: December 2010

By examining two types of lateral InGaN/GaN light emitting diodes with different contact patterns, we demonstrate that in the intermediate range of current where the space-charge region dominates in the device performance, the ideality factor (β) increases from 1.9 (current spreading design) up to 2.4 (current crowding design). This modification of β-factor could be erroneously treated as the change of free carrier recombination nature. The current crowding design is also responsible for the local overheating and heavier efficiency droop that occurs at the characteristic current 2.3 times smaller in comparison with the current spreading design.
On the widespread use of the Corrsin hypothesis in diffusion theories
Authors: Tautz R. C. , Shalchi A.
Published: December 2010

In the past four decades, several nonlinear theories have been developed to describe (i) the motion of charged test particles through a turbulent magnetized plasma and (ii) the random walk of magnetic field lines. In many such theories, the so-called Corrsin independence hypothesis has been applied to enforce analytical tractability. In this note, it is shown that the Corrsin hypothesis is part of most nonlinear diffusion theories. In some cases, the Corrsin approximation is somewhat hidden, while in other cases a different name is used for the same approach. It is shown that even the researchers who criticized the application of this hypothesis have used it in their nonlinear diffusion theories. It is hoped that the present article will eliminate the recently caused confusion about the applicability and validity of the Corrsin hypothesis.
The Shading Cue in Context
Authors: Wagemans Johan , Van Doorn Andrea J , Koenderink Jan J
Published: December 2010

The shading cue is supposed to be a major factor in monocular stereopsis. However, the hypothesis is hardly corroborated by available data. For instance, the conventional stimulus used in perception research, which involves a circular disk with monotonic luminance gradient on a uniform surround, is theoretically ‘explained’ by any quadric surface, including spherical caps or cups (the conventional response categories), cylindrical ruts or ridges, and saddle surfaces. Whereas cylindrical ruts or ridges are reported when the outline is changed from circular to square, saddle surfaces are never reported. We introduce a method that allows us to differentiate between such possible responses. We report observations on a number of variations of the conventional stimulus, including variations of shape and quality of the boundary, and contexts that allow the observer to infer illumination direction. We find strong and expected influences of outline shape, but, perhaps surprisingly, we fail to find any influence of context, and only partial influence of outline quality. Moreover, we report appreciable differences within the generic population. We trace some of the idiosyncrasies (as compared to shape from shading algorithms) of the human observer to generic properties of the environment, in particular the fact that many objects are limited in size and elliptically convex over most of their boundaries.
Interdisciplinary approaches for the management of existing and emerging human - wildlife conflicts
Authors: White Piran C. L. , Ward Alastair I.
Published: December 2010

Human–wildlife conflicts are increasing throughout the world, principally due to a combination of human population growth, increased pressure on land and natural resources and climate change. Many human–wildlife conflicts stem from differences in objectives between various stakeholder groups, especially where the wildlife in question is a resource that can be exploited for economic or cultural benefit, or where the conservation of wildlife is at odds with human population growth or development pressure. Conflicts can be exacerbated by an incomplete understanding of their causes and/or inappropriate intervention measures. Many traditional forms of intervention are also subject to increasing scrutiny and criticism from society. Here, we highlight the potential strategic benefits that can be made by an interdisciplinary approach to human–wildlife conflict situations, by integrating knowledge and understanding across the natural and social sciences. We also stress the potential tactical benefits from combining new approaches to management with more traditional ones. We emphasise the potential contribution of more recent developments in decision-making under conditions of limited data availability and uncertainty. Finally, we recommend that monitoring should play a more prominent role, both in assessing the role of stakeholder engagement in participatory decision-making and in contributing to the evidence base that will allow competing hypotheses about specific systems to be evaluated in an iterative manner.
Neurogenin3 inhibits proliferation in endocrine progenitors by inducing Cdkn1a
Authors: Miyatsuka Takeshi , Kosaka Yasuhiro , Kim Hail , German Michael S.
Published: December 2010

During organogenesis, the final size of mature cell populations depends on their rates of differentiation and expansion. Because transient expression of Neurogenin3 (Neurog3) in progenitor cells in the developing pancreas initiates their differentiation to mature islet cells, we examined the role of Neurog3 in cell cycle control during this process. We found that mitotically active pancreatic progenitor cells in mouse embryos exited the cell cycle after the initiation of Neurog3 expression. Transcriptome analysis demonstrated that the Neurog3-expressing cells dramatically up-regulated the mRNA encoding cyclin-dependent kinase inhibitor 1a (
Cdkn1a
). In
Neurog3
null mice, the islet progenitor cells failed to activate
Cdkn1a
expression and continued to proliferate, showing that their exit from the cell cycle requires Neurog3. Furthermore, induced transgenic expression of Neurog3 in mouse β-cells in vivo markedly decreased their proliferation, increased
Cdkn1a
levels, and eventually caused profound hyperglycemia. In contrast, in
Cdkn1a
null mice, proliferation was incompletely suppressed in the Neurog3-expressing cells. These studies reveal a crucial role for Neurog3 in regulating the cell cycle during the differentiation of islet cells and demonstrate that the subsequent down-regulation of Neurog3 allows the mature islet cell population to expand.
Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue
Authors: Iijima Norifumi , Mattei Lisa M. , Iwasaki Akiko
Published: December 2010

Monocytes patrol various tissues for signs of infection and inflammation. Inflammatory monocytes enter peripheral tissues at sites of microbial infection and differentiate into dendritic cells and macrophages. Here, we examined the importance of monocytes in primary mucosal infection with herpes simplex virus 2 (HSV-2), and demonstrate that monocyte-derived APCs are required to elicit IFN-γ secretion from effector Th1 cells to mediate antiviral protection. However, monocyte-derived APCs were dispensable for the generation of Th1 immunity and for the restimulation of memory Th1 cells during secondary viral challenge. These results demonstrate that distinct APC subsets are dedicated for CD4 T cell priming, elicitation, and memory recall responses to a given viral pathogen within the same mucosal tissue and reveal a specialized role for monocyte-derived APCs in the emergency response to infection.
A network model for plant–pollinator community assembly
Authors: Campbell Colin , Yang Suann , Albert Réka , Shea Katriona
Published: December 2010

Community assembly models, usually constructed for food webs, are an important component of our understanding of how ecological communities are formed. However, models for mutualistic community assembly are still needed, especially because these communities are experiencing significant anthropogenic disturbances that affect their biodiversity. Here, we present a unique network model that simulates the colonization and extinction process of mutualistic community assembly. We generate regional source pools of species interaction networks on the basis of statistical properties reported in the literature. We develop a dynamic synchronous Boolean framework to simulate, with few free parameters, the dynamics of new mutualistic community formation from the regional source pool. This approach allows us to deterministically map out every possible trajectory of community formation. This level of detail is rarely observed in other analytic approaches and allows for thorough analysis of the dynamical properties of community formation. As for food web assembly, we find that the number of stable communities is quite low, and the composition of the source pool influences the abundance and nature of community outcomes. However, in contrast to food web assembly, stable mutualistic communities form rapidly. Small communities with minor fluctuations in species presence/absence (self-similar limit cycles) are the most common community outcome. The unique application of this Boolean network approach to the study of mutualistic community assembly offers a great opportunity to improve our understanding of these critical communities.
Derivation of Ca
2+
signals from puff properties reveals that pathway function is robust against cell variability but sensitive for control
Authors: Thurley Kevin , Falcke Martin
Published: December 2010

Ca
2+
is a universal second messenger in eukaryotic cells transmitting information through sequences of concentration spikes. A prominent mechanism to generate these spikes involves Ca
2+
release from the endoplasmic reticulum Ca
2+
store via inositol 1,4,5-trisphosphate (IP
3
)-sensitive channels. Puffs are elemental events of IP
3
-induced Ca
2+
release through single clusters of channels. Intracellular Ca
2+
dynamics are a stochastic system, but a complete stochastic theory has not been developed yet. We formulate the theory in terms of interpuff interval and puff duration distributions because, unlike the properties of individual channels, they can be measured in vivo. Our theory reproduces the typical spectrum of Ca
2+
signals like puffs, spiking, and bursting in analytically treatable test cases as well as in more realistic simulations. We find conditions for spiking and calculate interspike interval (ISI) distributions. Signal form, average ISI and ISI distributions depend sensitively on the details of cluster properties and their spatial arrangement. In contrast to that, the relation between the average and the standard deviation of ISIs does not depend on cluster properties and cluster arrangement and is robust with respect to cell variability. It is controlled by the global feedback processes in the Ca
2+
signaling pathway (e.g., via IP
3
-3-kinase or endoplasmic reticulum depletion). That relation is essential for pathway function because it ensures frequency encoding despite the randomness of ISIs and determines the maximal spike train information content. Hence, we find a division of tasks between global feedbacks and local cluster properties that guarantees robustness of function while maintaining sensitivity of control of the average ISI.
Quantifying the biophysical characteristics of
Plasmodium-falciparum
-parasitized red blood cells in microcirculation
Authors: Fedosov D. A. , Caswell B. , Suresh S. , Karniadakis G. E.
Published: December 2010

The pathogenicity of
Plasmodium falciparum
(
Pf
) malaria results from the stiffening of red blood cells (RBCs) and its ability to adhere to endothelial cells (cytoadherence). The dynamics of Pf-parasitized RBCs is studied by three-dimensional mesoscopic simulations of flow in cylindrical capillaries in order to predict the flow resistance enhancement at different parasitemia levels. In addition, the adhesive dynamics of
Pf
-RBCs is explored for various parameters revealing several types of cell dynamics such as firm adhesion, very slow slipping along the wall, and intermittent flipping. The parasite inside the RBC is modeled explicitly in order to capture phenomena such as “hindered tumbling” motion of the RBC and the sudden transition from firm RBC cytoadherence to flipping on the endothelial surface. These predictions are in quantitative agreement with recent experimental observations, and thus the three-dimensional modeling method presented here provides new capabilities for guiding and interpreting future in vitro and in vivo studies of malaria.
Posttranscriptional gene silencing in nuclei
Authors: Hoffer Paul , Ivashuta Sergey , Pontes Olga , Vitins Alexa , Pikaard Craig , Mroczka Andrew , Wagner Nicholas , Voelker Toni
Published: December 2010

In plants, small interfering RNAs (siRNAs) with sequence homology to transcribed regions of genes can guide the sequence-specific degradation of corresponding mRNAs, leading to posttranscriptional gene silencing (PTGS). The current consensus is that siRNA-mediated PTGS occurs primarily in the cytoplasm where target mRNAs are localized and translated into proteins. However, expression of an inverted-repeat double-stranded RNA corresponding to the soybean
FAD2-1A
desaturase intron is sufficient to silence
FAD2-1
, implicating nuclear precursor mRNA (pre-mRNA) rather than cytosolic mRNA as the target of PTGS. Silencing
FAD2-1
using intronic or 3′-UTR sequences does not affect transcription rates of the target genes but results in the strong reduction of target transcript levels in the nucleus. Moreover, siRNAs corresponding to pre-mRNA–specific sequences accumulate in the nucleus. In Arabidopsis, we find that two enzymes involved in PTGS, Dicer-like 4 and RNA-dependent RNA polymerase 6, are localized in the nucleus. Collectively, these results demonstrate that siRNA-directed RNA degradation can take place in the nucleus, suggesting the need for a more complex view of the subcellular compartmentation of PTGS in plants.
Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear
Authors: Bok Jinwoong , Raft Steven , Kong Kyoung-Ah , Koo Soo Kyung , Dräger Ursula C. , Wu Doris K.
Published: December 2010

Vertebrate hearing and balance are based in complex asymmetries of inner ear structure. Here, we identify retinoic acid (RA) as an extrinsic signal that acts directly on the ear rudiment to affect its compartmentalization along the anterior-posterior axis. A rostrocaudal wave of RA activity, generated by tissues surrounding the nascent ear, induces distinct responses from anterior and posterior halves of the inner ear rudiment. Prolonged response to RA by posterior otic tissue correlates with
Tbx1
transcription and formation of mostly nonsensory inner ear structures. By contrast, anterior otic tissue displays only a brief response to RA and forms neuronal elements and most sensory structures of the inner ear.
Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat
Authors: Schulz Tim J. , Huang Tian Lian , Tran Thien T. , Zhang Hongbin , Townsend Kristy L. , Shadrach Jennifer L. , Cerletti Massimiliano , McDougall Lindsay E. , Giorgadze Nino , Tchkonia Tamara , Schrier Denis , Falb Dean , Kirkland James L. , Wagers Amy J. , Tseng Yu-Hua
Published: December 2010

Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1
+
/CD45
−
/Mac1
−
; referred to as Sca-1
+
progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1
+
cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.
Family level phylogenies reveal modes of macroevolution in RNA viruses
Authors: Kitchen Andrew , Shackelton Laura A. , Holmes Edward C.
Published: December 2010

Despite advances in understanding the patterns and processes of microevolution in RNA viruses, little is known about the determinants of viral diversification at the macroevolutionary scale. In particular, the processes by which viral lineages assigned as different “species” are generated remain largely uncharacterized. To address this issue, we use a robust phylogenetic approach to analyze patterns of lineage diversification in five representative families of RNA viruses. We ask whether the process of lineage diversification primarily occurs when viruses infect new host species, either through cross-species transmission or codivergence, and which are defined here as analogous to allopatric speciation in animals, or by acquiring new niches within the same host species, analogous to sympatric speciation. By mapping probable primary host species onto family level viral phylogenies, we reveal a strong clustering among viral lineages that infect groups of closely related host species. Although this is consistent with lineage diversification within individual hosts, we argue that this pattern more likely represents strong biases in our knowledge of viral biodiversity, because we also find that better-sampled human viruses rarely cluster together. Hence, although closely related viruses tend to infect related host species, it is unlikely that they often infect the same host species, such that evolutionary constraints hinder lineage diversification within individual host species. We conclude that the colonization of new but related host species may represent the principle mode of macroevolution in RNA viruses.
Reversing cocaine-induced synaptic potentiation provides enduring protection from relapse
Authors: Moussawi Khaled , Zhou Wenhua , Shen Haowei , Reichel Carmela M. , See Ronald E. , Carr David B. , Kalivas Peter W.
Published: December 2010

Cocaine addiction remains without an effective pharmacotherapy and is characterized by an inability of addicts to inhibit relapse to drug use. Vulnerability to relapse arises from an enduring impairment in cognitive control of motivated behavior, manifested in part by dysregulated synaptic potentiation and extracellular glutamate homeostasis in the projection from the prefrontal cortex to the nucleus accumbens. Here we show in rats trained to self-administer cocaine that the enduring cocaine-induced changes in synaptic potentiation and glutamate homeostasis are mechanistically linked through group II metabotropic glutamate receptor signaling. The enduring cocaine-induced changes in measures of cortico-accumbens synaptic and glial transmission were restored to predrug parameters for at least 2 wk after discontinuing chronic treatment with the cystine prodrug,N-acetylcysteine.N-acetylcysteine produced these changes by inducing an enduring restoration of nonsynaptic glutamatergic tone onto metabotropic glutamate receptors. The long-lasting pharmacological restoration of cocaine-induced glutamatergic adaptations by chronicN-acetylcysteine also caused enduring inhibition of cocaine-seeking in an animal model of relapse. These data mechanistically link nonsynaptic glutamate to cocaine-induced adaptations in excitatory transmission and demonstrate a mechanism to chronically restore prefrontal to accumbens transmission and thereby inhibit relapse in an animal model.
Critical coordination of innate immune defense against
Toxoplasma gondii
by dendritic cells responding via their Toll-like receptors
Authors: Hou Baidong , Benson Alicia , Kuzmich Lili , DeFranco Anthony L. , Yarovinsky Felix
Published: December 2010

Toll-like receptors (TLRs) play an important role in host defense against a variety of microbial pathogens. We addressed the mechanism by which TLRs contribute to host defense against the lethal parasite
Toxoplasma gondii
by using mice with targeted inactivation of the TLR adaptor protein myeloid differentiation primary response gene 88 (MyD88) in different innate cell types. Lack of MyD88 in dendritic cells (DCs), but not in macrophages or neutrophils, resulted in high susceptibility to the
T. gondii
infection. In the mice deficient in MyD88 in DCs, the early IL-12 response by DCs was ablated, the IFN-γ response by natural killer cells was delayed, and the recruited inflammatory monocytes were incapable of killing the
T. gondii
parasites. The T-cell response, although attenuated in these mice, was sufficient to eradicate the parasite during the chronic stage, provided that defects in DC activation were compensated by IL-12 treatment early after infection. These results demonstrate a central role of DCs in orchestrating the innate immune response to an intracellular pathogen and establish that defects in pathogen recognition by DCs can predetermine sensitivity to infection.
Herbivorous ecomorphology and specialization patterns in theropod dinosaur evolution
Authors: Zanno Lindsay E. , Makovicky Peter J.
Published: December 2010

Interpreting key ecological parameters, such as diet, of extinct organisms without the benefit of direct observation or explicit fossil evidence poses a formidable challenge for paleobiological studies. To date, dietary categorizations of extinct taxa are largely generated by means of modern analogs; however, for many species the method is subject to considerable ambiguity. Here we present a refined approach for assessing trophic habits in fossil taxa and apply the method to coelurosaurian dinosaurs—a clade for which diet is particularly controversial. Our findings detect 21 morphological features that exhibit statistically significant correlations with extrinsic fossil evidence of coelurosaurian herbivory, such as stomach contents and a gastric mill. These traits represent quantitative, extrinsically founded proxies for identifying herbivorous ecomorphology in fossils and are robust despite uncertainty in phylogenetic relationships among major coelurosaurian subclades. The distribution of these features suggests that herbivory was widespread among coelurosaurians, with six major subclades displaying morphological evidence of the diet, and that contrary to previous thought, hypercarnivory was relatively rare and potentially secondarily derived. Given the potential for repeated, independent evolution of herbivory in Coelurosauria, we also test for repetitive patterns in the appearance of herbivorous traits within sublineages using rank concordance analysis. We find evidence for a common succession of increasing specialization to herbivory in the subclades Ornithomimosauria and Oviraptorosauria, perhaps underlain by intrinsic functional and/or developmental constraints, as well as evidence indicating that the early evolution of a beak in coelurosaurians correlates with an herbivorous diet.