bluuebunny/crossref_metadata_2025 huggingface dataset:
Tuning of a graphene-electrode work function to enhance the efficiency of organic bulk heterojunction photovoltaic cells with an inverted structure
Authors: Jo Gunho , Na Seok-In , Oh Seung-Hwan , Lee Sangchul , Kim Tae-Soo , Wang Gunuk , Choe Minhyeok , Park Woojin , Yoon Jongwon , Kim Dong-Yu , Kahng Yung Ho , Lee Takhee
Published: November 2010

We demonstrate the fabrication of inverted-structure organic solar cells (OSCs) with graphene cathodes. The graphene film used in this work was work-function-engineered with an interfacial dipole layer to reduce the work function of graphene, which resulted in an increase in the built-in potential and enhancement of the charge extraction, thereby enhancing the overall device performance. Our demonstration of inverted-structure OSCs with work-function-engineering of graphene electrodes will foster the fabrication of more advanced structure OSCs with higher efficiency.
Influence of gold nanorods size on electro-optical and dielectric properties of ferroelectric liquid crystals
Authors: Podgornov Fedor V. , Ryzhkova Anna V. , Haase Wolfgang
Published: November 2010

The influence of the gold nanorods (GNRs) diameter on the electro-optic and dielectric properties of the ferroelectric liquid crystals (FLCs) was investigated. It was shown that dispersing of GNRs in FLCs could lead to an increase of the internal electric field inside the liquid crystalline layer. This effect results in a significant decrease of the switching time and the rotational viscosity of the FLC/GNRs nanodispersions independently on the GNRs diameter. Oppositely, the relaxation frequency and the dielectric strength of the Goldstone mode strongly depend on the GNRs diameter, which can be explained by the charge transfer between the GNRs and FLC molecules.
Mixed-phase p-type silicon oxide containing silicon nanocrystals and its role in thin-film silicon solar cells
Authors: Cuony P. , Marending M. , Alexander D. T. L. , Boccard M. , Bugnon G. , Despeisse M. , Ballif C.
Published: November 2010

Lower absorption, lower refractive index, and tunable resistance are three advantages of amorphous silicon oxide containing nanocrystalline silicon grains (nc-SiOx) compared to microcrystalline silicon (μc-Si), when used as a p-type layer in μc-Si thin-film solar cells. We show that p-nc-SiOx with its particular nanostructure increases μc-Si cell efficiency by reducing reflection and parasitic absorption losses depending on the roughness of the front electrode. Furthermore, we demonstrate that the p-nc-SiOx reduces the detrimental effects of the roughness on the electrical characteristics, and significantly increases μc-Si and Micromorph cell efficiency on substrates until now considered too rough for thin-film silicon solar cells.
In situ ellipsometry study of the kinetics of hydrogen plasma interaction with a-Si:H thin films: A particular temperature-dependence
Authors: Hadjadj A. , Djellouli G. , Jbara O.
Published: November 2010

We performed H2 plasma treatment of hydrogenated amorphous silicon (a-Si:H) thin films and followed by in situ spectroscopic ellipsometry measurements the kinetics of hydrogen-induced film modifications at temperatures varying from 100 to 250 °C. The time-dependence of the H-modified layer thickness dH(t) follows an exponential relation of the form dH0[1−exp(−t/τ)]. The temperature-dependence of dH0 and τ shows a discontinuity at T=200 °C. While the activation energy of dH0 changes from 0.19 eV at T<200 °C to 0.05 eV at higher temperatures, the activation energy of τ suddenly changes from 0.15 eV to a negative value (−0.26 eV). Such a discontinuity should be linked to the thermal equilibrium temperature of undoped a-Si:H. Moreover, we found that the rate of formation of the H-modified layer rH=dH0/τ varies in inverse proportion to the etching rate, indicating a balance between hydrogen insertion and film etching at the steady state.
VO
2
multidomain heteroepitaxial growth and terahertz transmission modulation
Authors: Chen Changhong , Zhu Yanhan , Zhao Yong , Lee Joon Hwan , Wang Haiyan , Bernussi Ayrton , Holtz Mark , Fan Zhaoyang
Published: November 2010

We report the epitaxial relationship of VO2 thin-films on c-plane sapphire and their terahertz transmission modulation with temperature. The films exhibit a triple-domain structure caused by the lattice mismatch between monoclinic VO2 and sapphire hexagon. The epitaxial relationship is determined to be VO2[010]∥Al2O3[0001] and VO2(2¯02)∥Al2O3{112¯0}, with the in-plane lattice mismatch of 2.66% (tensile) along [2¯02] and the out-of-plane lattice mismatch of −2.19% (compressive). Terahertz measurements revealed that VO2 films have over fourfold change in transmission during the metal-insulator transition, indicating a strong potential for terahertz wave switching and modulation applications.
Influence of carrier dynamics on the modulation bandwidth of quantum-dot based nanocavity devices
Authors: Lorke M. , Nielsen T. R. , Mørk J.
Published: November 2010

We theoretically investigate the modulation response of quantum-dot based nanocavity light emitting devices. For high Purcell enhancement factors, our theory predicts the possibility of decreasing the modulation bandwidth with increasing scattering rate into the lasing quantum-dot state. This counterintuitive effect is investigated using a microscopic semiconductor model. The resulting guidelines for possible optimizations of quantum-dot based nanocavity laser devices are given.
WaterSim: A Simulation Model for Urban Water Planning in Phoenix, Arizona, USA
Authors: Gober Patricia , Wentz Elizabeth A , Lant Timothy , Tschudi Michael K , Kirkwood Craig W
Published: November 2010

WaterSim, a simulation model, was built and implemented to investigate how alternative climate conditions, rates of population growth, and policy choices interact to affect future water supply and demand conditions in Phoenix, AZ. WaterSim is a hierarchical model that represents supply from surface and groundwater sources and demand from residential, commercial, and agricultural user sectors, incorporating the rules that govern reservoirs, aquifer use, and land-use change. In this paper we: (1) report on the imperative for exploratory modeling in water-resource management, given the deep uncertainties of climate change, (2) describe the geographic context for the Phoenix case study, (3) outline the objectives and structure of WaterSim, (4) report on testing the model with sensitivity analyses and history matching, (5) demonstrate the application of the model through a series of simulation experiments, and (6) discuss the model's use for scenario planning and climate adaptation. Simulation results show there are significant challenges to Phoenix's water sustainability from climate change and rapid growth. Policies to address these challenges require difficult tradeoffs among lifestyles, groundwater sustainability, the pace of growth, and what is considered to be an appropriate level of risk of climate-induced shortage.
The Perseverance of Numerical Distance Effect in Attentional Blink
Authors: Hsu Tzu-Yu , Cheng Shih-Kuen , Hung Daisy L , Tzeng Ovid J L , Juan Chi-Hung , Tseng Philip
Published: November 2010

In a number comparison task, it is easier to respond faster when the two numbers are further apart than when they are close. This inverse relationship between the size difference and the time to judge such difference is called the numerical distance effect (NDE). In this study we investigated whether attention plays a critical role in the surfacing of NDE and the way we process Arabic numbers. In experiments 1 and 2, with an attentional blink paradigm that was designed to modulate attention, we tested whether a limited or unlimited pool of attentional resources would have an impact on the performance and trend of NDE. The results showed a dissociable effect of attention that changed the overall accuracy but not the trend of NDE. In experiment 3 we examined whether the number priming effect, another phenomenon associated with the distance-related effect, would be affected during the attentional blink period. We found the pattern of number priming effect was not affected by attentional blink. An explanation of the role of attention in number distance processing, as well as how it interacts with Arabic number representation, is discussed.
Brightness Enhancement Seen through a Tube
Authors: Spillmann Lothar , Hardy Joe , Delahunt Peter , Pinna Baingio , Werner John S
Published: November 2010

We report a fascinating phenomenon that emerges when a surface is viewed through a tube held close to one eye, with the other eye open. The disk-shaped area seen through the tube looks strikingly brighter and, when viewed on a textured background, also of higher spatial contrast than the same surface area viewed without a tube. The effect is reminiscent of a spotlight illuminating the area under consideration. We call this the ‘tube effect’. The tube effect is one of the strongest contrast illusions known to us. It requires a matching luminance that is twice as high as the reference luminance seen through the tube. Brightness ratings increase linearly with the log of the background luminance. The effect (i) produces a dark afterimage, (ii) reverses in polarity with low ambient illumination, (iii) assumes the complementary colour of the illuminant, and (iv) persists with fully dilated pupils. Potential explanations include simultaneous contrast (due to the penumbra and dark inner walls of the tube) and veiling of the surround (due to local adaptation and a lower gain factor).
A regulon conserved in monocot and dicot plants defines a functional module in antifungal plant immunity
Authors: Humphry Matt , Bednarek Paweł , Kemmerling Birgit , Koh Serry , Stein Mónica , Göbel Ulrike , Stüber Kurt , Piślewska-Bednarek Mariola , Loraine Ann , Schulze-Lefert Paul , Somerville Shauna , Panstruga Ralph
Published: November 2010

At least two components that modulate plant resistance against the fungal powdery mildew disease are ancient and have been conserved since the time of the monocot–dicot split (≈200 Mya). These components are the seven transmembrane domain containing MLO/MLO2 protein and the syntaxin ROR2/PEN1, which act antagonistically and have been identified in the monocot barley (
Hordeum vulgare
) and the dicot
Arabidopsis thaliana
, respectively. Additionally, syntaxin-interacting
N
-ethylmaleimide sensitive factor adaptor protein receptor proteins (VAMP721/722 and SNAP33/34) as well as a myrosinase (PEN2) and an ABC transporter (PEN3) contribute to antifungal resistance in both barley and/or Arabidopsis. Here, we show that these genetically defined defense components share a similar set of coexpressed genes in the two plant species, comprising a statistically significant overrepresentation of gene products involved in regulation of transcription, posttranslational modification, and signaling. Most of the coexpressed Arabidopsis genes possess a common
cis
-regulatory element that may dictate their coordinated expression. We exploited gene coexpression to uncover numerous components in Arabidopsis involved in antifungal defense. Together, our data provide evidence for an evolutionarily conserved regulon composed of core components and clade/species-specific innovations that functions as a module in plant innate immunity.
Teleportation-based realization of an optical quantum two-qubit entangling gate
Authors: Gao Wei-Bo , Goebel Alexander M. , Lu Chao-Yang , Dai Han-Ning , Wagenknecht Claudia , Zhang Qiang , Zhao Bo , Peng Cheng-Zhi , Chen Zeng-Bing , Chen Yu-Ao , Pan Jian-Wei
Published: November 2010

In recent years, there has been heightened interest in quantum teleportation, which allows for the transfer of unknown quantum states over arbitrary distances. Quantum teleportation not only serves as an essential ingredient in long-distance quantum communication, but also provides enabling technologies for practical quantum computation. Of particular interest is the scheme proposed by D. Gottesman and I. L. Chuang [(1999)
Nature
402:390–393], showing that quantum gates can be implemented by teleporting qubits with the help of some special entangled states. Therefore, the construction of a quantum computer can be simply based on some multiparticle entangled states, Bell-state measurements, and single-qubit operations. The feasibility of this scheme relaxes experimental constraints on realizing universal quantum computation. Using two different methods, we demonstrate the smallest nontrivial module in such a scheme—a teleportation-based quantum entangling gate for two different photonic qubits. One uses a high-fidelity six-photon interferometer to realize controlled-NOT gates, and the other uses four-photon hyperentanglement to realize controlled-Phase gates. The results clearly demonstrate the working principles and the entangling capability of the gates. Our experiment represents an important step toward the realization of practical quantum computers and could lead to many further applications in linear optics quantum information processing.
Biodiversity can support a greener revolution in Africa
Authors: Snapp Sieglinde S. , Blackie Malcolm J. , Gilbert Robert A. , Bezner-Kerr Rachel , Kanyama-Phiri George Y.
Published: November 2010

The Asian green revolution trebled grain yields through agrochemical intensification of monocultures. Associated environmental costs have subsequently emerged. A rapidly changing world necessitates sustainability principles be developed to reinvent these technologies and test them at scale. The need is particularly urgent in Africa, where ecosystems are degrading and crop yields have stagnated. An unprecedented opportunity to reverse this trend is unfolding in Malawi, where a 90% subsidy has ensured access to fertilization and improved maize seed, with substantive gains in productivity for millions of farmers. To test if economic and ecological sustainability could be improved, we preformed manipulative experimentation with crop diversity in a countrywide trial (
n
= 991) and at adaptive, local scales through a decade of participatory research (
n
= 146). Spatial and temporal treatments compared monoculture maize with legume-diversified maize that included annual and semiperennial (SP) growth habits in temporal and spatial combinations, including rotation, SP rotation, intercrop, and SP intercrop systems. Modest fertilizer intensification doubled grain yield compared with monoculture maize. Biodiversity improved ecosystem function further: SP rotation systems at half-fertilizer rates produced equivalent quantities of grain, on a more stable basis (yield variability reduced from 22% to 13%) compared with monoculture. Across sites, profitability and farmer preference matched: SP rotations provided twofold superior returns, whereas diversification of maize with annual legumes provided more modest returns. In this study, we provide evidence that in Africa, crop diversification can be effective at a countrywide scale, and that shrubby, grain legumes can enhance environmental and food security.
Time-dependent electron phenomena at surfaces
Authors: Muiño R. Díez , Sánchez-Portal D. , Silkin V. M. , Chulkov E. V. , Echenique P. M.
Published: November 2010

Femtosecond and subfemtosecond time scales typically rule electron dynamics at metal surfaces. Recent advance in experimental techniques permits now remarkable precision in the description of these processes. In particular, shorter time scales, smaller system sizes, and spin-dependent effects are current targets of interest. In this article, we use state-of-the-art theoretical methods to analyze these refined features of electron dynamics. We show that the screening of localized charges at metal surfaces is created locally in the attosecond time scale, while collective excitations transfer the perturbation to larger distances in longer time scales. We predict that the elastic width of the resonance in excited alkali adsorbates on ferromagnetic surfaces can depend on spin orientation in a counterintuitive way. Finally, we quantitatively evaluate the electron–electron and electron–phonon contributions to the electronic excited states widths in ultrathin metal layers. We conclude that confinement and spin effects are key factors in the behavior of electron dynamics at metal surfaces.
Rapid efficient coding of correlated complex acoustic properties
Authors: Stilp Christian E. , Rogers Timothy T. , Kluender Keith R.
Published: November 2010

Natural sounds are complex, typically changing along multiple acoustic dimensions that covary in accord with physical laws governing sound-producing sources. We report that, after passive exposure to novel complex sounds, highly correlated features initially collapse onto a single perceptual dimension, capturing covariance at the expense of unitary stimulus dimensions. Discriminability of sounds respecting the correlation is maintained, but is temporarily lost for sounds orthogonal or oblique to experienced covariation. Following extended experience, perception of variance not captured by the correlation is restored, but weighted only in proportion to total experienced covariance. A Hebbian neural network model captures some aspects of listener performance; an anti-Hebbian model captures none; but, a principal components analysis model captures the full pattern of results. Predictions from the principal components analysis model also match evolving listener performance in two discrimination tasks absent passive listening. These demonstrations of adaptation to correlated attributes provide direct behavioral evidence for efficient coding.
Helicobacter pylori
proinflammatory protein up-regulates NF-κB as a cell-translocating Ser/Thr kinase
Authors: Kim Do Jin , Park Kang-Seo , Kim Jung-Ho , Yang Sang-Hwa , Yoon Ji Young , Han Byeong-Gu , Kim Hyoun Sook , Lee Sang Jae , Jang Jun Young , Kim Kyoung Hoon , Kim Mi Jung , Song Jin-Su , Kim Hie-Joon , Park Chung-Mo , Lee Sang-Kyou , Lee Byung Il , Suh Se Won
Published: November 2010

There has been considerable interest in virulence genes in the plasticity region of
Helicobacter pylori
, but little is known about many of these genes. JHP940, one of the virulence factors encoded by the plasticity region of
H. pylori
strain J99, is a proinflammatory protein that induces tumor necrosis factor-alpha and interleukin-8 secretion as well as enhanced translocation of NF-κB in cultured macrophages. Here we have characterized the structure and function of JHP940 to provide the framework for better understanding its role in inflammation by
H. pylori
. Our work demonstrates that JHP940 is the first example of a eukaryotic-type Ser/Thr kinase from
H. pylori
. We show that JHP940 is catalytically active as a protein kinase and translocates into cultured human cells. Furthermore, the kinase activity is indispensable for indirectly up-regulating phosphorylation of NF-κB p65 at Ser276. Our results, taken together, contribute significantly to understanding the molecular basis of the role of JHP940 in inflammation and subsequent pathogenesis caused by
H. pylori
. We propose to rename the
jhp940
gene as
ctkA
(

c

ell

t

ranslocating

k

inase

A

).
Effects of Pleistocene glaciations and rivers on the population structure of Bornean orangutans (
Pongo pygmaeus
)
Authors: Arora Natasha , Nater Alexander , van Schaik Carel P. , Willems Erik P. , van Noordwijk Maria A. , Goossens Benoit , Morf Nadja , Bastian Meredith , Knott Cheryl , Morrogh-Bernard Helen , Kuze Noko , Kanamori Tomoko , Pamungkas Joko , Perwitasari-Farajallah Dyah , Verschoor Ernst , Warren Kristin , Krützen Michael
Published: November 2010

Sundaland, a tropical hotspot of biodiversity comprising Borneo and Sumatra among other islands, the Malay Peninsula, and a shallow sea, has been subject to dramatic environmental processes. Thus, it presents an ideal opportunity to investigate the role of environmental mechanisms in shaping species distribution and diversity. We investigated the population structure and underlying mechanisms of an insular endemic, the Bornean orangutan (
Pongo pygmaeus
). Phylogenetic reconstructions based on mtDNA sequences from 211 wild orangutans covering the entire range of the species indicate an unexpectedly recent common ancestor of Bornean orangutans 176 ka (95% highest posterior density, 72–322 ka), pointing to a Pleistocene refugium. High mtDNA differentiation among populations and rare haplotype sharing is consistent with a pattern of strong female philopatry. This is corroborated by isolation by distance tests, which show a significant correlation between mtDNA divergence and distance and a strong effect of rivers as barriers for female movement. Both frequency-based and Bayesian clustering analyses using as many as 25 nuclear microsatellite loci revealed a significant separation among all populations, as well as a small degree of male-mediated gene flow. This study highlights the unique effects of environmental and biological features on the evolutionary history of Bornean orangutans, a highly endangered species particularly vulnerable to future climate and anthropogenic change as an insular endemic.
Alzheimer's disease peptide β-amyloid interacts with fibrinogen and induces its oligomerization
Authors: Ahn Hyung Jin , Zamolodchikov Daria , Cortes-Canteli Marta , Norris Erin H. , Glickman J. Fraser , Strickland Sidney
Published: November 2010

Increasing evidence supports a vascular contribution to Alzheimer's disease (AD), but a direct connection between AD and the circulatory system has not been established. Previous work has shown that blood clots formed in the presence of the β-amyloid peptide (Aβ), which has been implicated in AD, have an abnormal structure and are resistant to degradation in vitro and in vivo. In the present study, we show that Aβ specifically interacts with fibrinogen with a
K
d
of 26.3 ± 6.7 nM, that the binding site is located near the C terminus of the fibrinogen β-chain, and that the binding causes fibrinogen to oligomerize. These results suggest that the interaction between Aβ and fibrinogen modifies fibrinogen's structure, which may then lead to abnormal fibrin clot formation. Overall, our study indicates that the interaction between Aβ and fibrinogen may be an important contributor to the vascular abnormalities found in AD.
Structural identification of cation binding pockets in the plasma membrane proton pump
Authors: Ekberg Kira , Pedersen Bjørn P. , Sørensen Danny M. , Nielsen Ann K. , Veierskov Bjarke , Nissen Poul , Palmgren Michael G. , Buch-Pedersen Morten J.
Published: November 2010

The activity of P-type plasma membrane H
+
-ATPases is modulated by H
+
and cations, with K
+
and Ca
2+
being of physiological relevance. Using X-ray crystallography, we have located the binding site for Rb
+
as a K
+
congener, and for Tb
3+
and Ho
3+
as Ca
2+
congeners. Rb
+
is found coordinated by a conserved aspartate residue in the phosphorylation domain. A single Tb
3+
ion is identified positioned in the nucleotide-binding domain in close vicinity to the bound nucleotide. Ho
3+
ions are coordinated at two distinct sites within the H
+
-ATPase: One site is at the interface of the nucleotide-binding and phosphorylation domains, and the other is in the transmembrane domain toward the extracellular side. The identified binding sites are suggested to represent binding pockets for regulatory cations and a H
+
binding site for protons leaving the pump molecule. This implicates Ho
3+
as a novel chemical tool for identification of proton binding sites.
Altered antisense-to-sense transcript ratios in breast cancer
Authors: Maruyama Reo , Shipitsin Michail , Choudhury Sibgat , Wu Zhenhua , Protopopov Alexei , Yao Jun , Lo Pang-Kuo , Bessarabova Marina , Ishkin Alex , Nikolsky Yuri , Liu X. Shirley , Sukumar Saraswati , Polyak Kornelia
Published: November 2010

Transcriptome profiling studies suggest that a large fraction of the genome is transcribed and many transcripts function independent of their protein coding potential. The relevance of noncoding RNAs (ncRNAs) in normal physiological processes and in tumorigenesis is increasingly recognized. Here, we describe consistent and significant differences in the distribution of sense and antisense transcripts between normal and neoplastic breast tissues. Many of the differentially expressed antisense transcripts likely represent long ncRNAs. A subset of genes that mainly generate antisense transcripts in normal but not cancer cells is involved in essential metabolic processes. These findings suggest fundamental differences in global RNA regulation between normal and cancer cells that might play a role in tumorigenesis.
Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood
Authors: Sanchez-Cardenas Claudia , Fontanaud Pierre , He Zhenhe , Lafont Chrystel , Meunier Anne-Cécile , Schaeffer Marie , Carmignac Danielle , Molino François , Coutry Nathalie , Bonnefont Xavier , Gouty-Colomer Laurie-Anne , Gavois Elodie , Hodson David J. , Le Tissier Paul , Robinson Iain C. A. F. , Mollard Patrice
Published: November 2010

There are well-recognized sex differences in many pituitary endocrine axes, usually thought to be generated by gonadal steroid imprinting of the neuroendocrine hypothalamus. However, the recognition that growth hormone (GH) cells are arranged in functionally organized networks raises the possibility that the responses of the network are different in males and females. We studied this by directly monitoring the calcium responses to an identical GH-releasing hormone (GHRH) stimulus in populations of individual GH cells in slices taken from male and female murine GH-eGFP pituitary glands. We found that the GH cell network responses are sexually dimorphic, with a higher proportion of responding cells in males than in females, correlated with greater GH release from male slices. Repetitive waves of calcium spiking activity were triggered by GHRH in some males, but were never observed in females. This was not due to a permanent difference in the network architecture between male and female mice; rather, the sex difference in the proportions of GH cells responding to GHRH were switched by postpubertal gonadectomy and reversed with hormone replacements, suggesting that the network responses are dynamically regulated in adulthood by gonadal steroids. Thus, the pituitary gland contributes to the sexually dimorphic patterns of GH secretion that play an important role in differences in growth and metabolism between the sexes.
Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression
Authors: Bergthaler Andreas , Flatz Lukas , Hegazy Ahmed N. , Johnson Susan , Horvath Edit , Löhning Max , Pinschewer Daniel D.
Published: November 2010

The Clone 13 (Cl13) strain of lymphocytic choriomeningitis virus is widely studied as a model of chronic systemic viral infection. Here, we used reverse genetic techniques to identify the molecular basis of Cl13 persistence and immunosuppression, the characteristics differentiating it from the closely related Armstrong strain. We found that a single-point mutation in the Cl13 polymerase was necessary and partially sufficient for viral persistence and immunosuppression. A glycoprotein mutation known to enhance dendritic cell targeting accentuated both characteristics but when introduced alone, failed to alter the phenotype of the Armstrong strain. The decisive polymerase mutation increased intracellular viral RNA load in plasmacytoid dendritic cells, which we identified as a main initial target cell type in vivo, and increased viremia in the early phase of infection. These findings establish the enhanced replicative capacity as the primary determinant of the Cl13 phenotype. Viral persistence and immunosuppression can, thus, represent a direct consequence of excessive viral replication overwhelming the host's antiviral defense.
Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Rα complexes
Authors: Elpek Kutlu G. , Rubinstein Mark P. , Bellemare-Pelletier Angelique , Goldrath Ananda W. , Turley Shannon J.
Published: November 2010

Cytotoxic lymphocytes such as natural killer (NK) and CD8 T cells play important roles in immunosurveillance by killing virally infected or malignant cells. The homeostatic cytokine, IL-15, promotes the development, function, and survival of NK and CD8 T cells. IL-15 is normally presentedin transas a surface complex with IL-15 receptor-alpha-chain (IL-15Rα) by dendritic cells (DCs) and monocytes. Signaling by IL-15 occurs via the IL-2/IL-15 receptor β-chain (CD122) which is expressed primarily by NK1.1+cells and CD8 T cells. The use of preformed complexes of IL-15 with soluble IL-15Rα complexes to boost the effector function of CD122+cytolytic lymphocytes such as NK and CD8 T cells has recently gained considerable attention. Here we describe the impact of transient and prolonged in vivo stimulation by IL-15/IL-15Rα complexes on NK and CD8 T cells. Whereas transitory stimulation increased the number of activated NK cells and significantly enhanced their effector function, prolonged stimulation by IL-15/IL-15Rα complexes led to a marked accumulation of mature NK cells with considerably impaired activation, cytotoxicity, and proliferative activity, and an altered balance of activating and inhibitory receptors. In contrast to NK cells, CD8 T cells exhibited an activated phenotype and robust T cell receptor stimulation and effector function upon chronic stimulation with IL-15/IL-15Rα complexes. Thus, prolonged stimulation with the strong activating signal leads to a preferential accrual of mature NK cells with altered activation and diminished functional capacity. These findings point to a negative feedback mechanism to preferentially counterbalance excessive NK cell activity and may have important implications for cytokine immunotherapy.
A vesicle carrier that mediates peroxisome protein traffic from the endoplasmic reticulum
Authors: Lam Sheung Kwan , Yoda Naofumi , Schekman Randy
Published: November 2010

Pex19p, a soluble cytoplasmic transport protein, is required for the traffic of the peroxisomal membrane proteins Pex3p and Pex15p from the endoplasmic reticulum (ER) to the peroxisome. We documented Pex15p traffic from the ER using a chimeric protein containing a C-terminal glycosylation acceptor peptide. Pex15Gp expressed in wild-type yeast cells is N-glycosylated and functions properly in the peroxisome. In contrast,
pex19Δ
-mutant cells accumulate the glycoprotein Pex15Gp in the ER. We developed a cell-free preperoxisomal vesicle-budding reaction in which Pex15Gp and Pex3p are packaged into small vesicles in the presence of cytosol, Pex19p, and ATP. Secretory vesicle budding (COPII) detected by the packaging of a SNARE protein (soluble N-ethylmaleimide-sensitive attachment protein receptor) occurs in the same incubation but does not depend on Pex19p. Conversely a dominant GTPase mutant Sar1p which inhibits COPII has no effect on Pex3p packaging. Pex15Gp and Pex3p budded vesicles sediment as low-buoyant-density membranes on a Nycodenz gradient and copurify by affinity isolation using native but not Triton X-100–treated budded vesicles. ER–peroxisome transport vesicles appear to rely on a novel budding mechanism requiring Pex19p and additional unknown factors.
Mechanistic insights into cognate substrate discrimination during proofreading in translation
Authors: Hussain Tanweer , Kamarthapu Venu , Kruparani Shobha P. , Deshmukh Mandar V. , Sankaranarayanan Rajan
Published: November 2010

Editing/proofreading by aminoacyl-tRNA synthetases is an important quality control step in the accurate translation of the genetic code that removes noncognate amino acids attached to tRNA. Defects in the process of editing result in disease conditions including neurodegeneration. While proofreading, the cognate amino acids larger by a methyl group are generally thought to be sterically rejected by the editing modules as envisaged by the “Double-Sieve Model.” Strikingly using solution based direct binding studies, NMR-heteronuclear single quantum coherence (HSQC) and isothermal titration calorimetry experiments, with an editing domain of threonyl-tRNA synthetase, we show that the cognate substrate can gain access and bind to the editing pocket. High-resolution crystal structural analyses reveal that functional positioning of substrates rather than steric exclusion is the key for the mechanism of discrimination. A strategically positioned “catalytic water” molecule is excluded to avoid hydrolysis of the cognate substrate using a “RNA mediated substrate-assisted catalysis mechanism” at the editing site. The mechanistic proof of the critical role of RNA in proofreading activity is a completely unique solution to the problem of cognate-noncognate selection mechanism.
Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl
Authors: Lu Jie , Chiang Jeffrey , Iyer Rajiv R. , Thompson Eli , Kaneski Christine R. , Xu David S. , Yang Chunzhang , Chen Masako , Hodes Richard J. , Lonser Russell R. , Brady Roscoe O. , Zhuang Zhengping
Published: November 2010

Gaucher disease (GD), the most common lysosomal storage disorder of humans, is caused by mutations in the gene coding for the enzyme glucocerebrosidase (GCase). Clinical manifestations vary among patients with the three types of GD, and phenotypic heterogeneity occurs even among patients with identical mutations. To gain insight into why phenotypic heterogeneity occurs in GD, we investigated mechanisms underlying the net loss of GCase catalytic activity in cultured skin fibroblasts derived from patients with the three types of GD. The findings indicate that the loss of catalytic activity of GCase correlates with its quantitative reduction, rather than a decrease in functional capacity of mutant enzyme. Use of a proteasome inhibitor, lactacystin, resulted in increased expression of GCase, suggesting a mechanism of protein degradation in GD. Furthermore, reduced binding of GCase to TCP1 ring complex (TRiC), a regulator of correct protein folding, may result in defective maturation of nascent GCase in GD cells. Additionally, increased interaction between GCase and c-Cbl, an E3 ubiquitin ligase, may be involved in the degradation and loss of GCase in GD. The findings suggest that specific molecular mediators involved in GCase maturation and degradation could be responsible for phenotypic variation among patients with the same genotypes and that these mediators could be therapeutically targeted to increase GCase activity in patients with GD.
In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury
Authors: Nyein Michelle K. , Jason Amanda M. , Yu Li , Pita Claudio M. , Joannopoulos John D. , Moore David F. , Radovitzky Raul A.
Published: November 2010

Blast-induced traumatic brain injury is the most prevalent military injury in Iraq and Afghanistan, yet little is known about the mechanical effects of blasts on the human head, and still less is known about how personal protective equipment affects the brain’s response to blasts. In this study we investigated the effect of the Advanced Combat Helmet (ACH) and a conceptual face shield on the propagation of stress waves within the brain tissue following blast events. We used a sophisticated computational framework for simulating coupled fluid–solid dynamic interactions and a three-dimensional biofidelic finite element model of the human head and intracranial contents combined with a detailed model of the ACH and a conceptual face shield. Simulations were conducted in which the unhelmeted head, head with helmet, and head with helmet and face shield were exposed to a frontal blast wave with incident overpressure of 10 atm. Direct transmission of stress waves into the intracranial cavity was observed in the unprotected head and head with helmet simulations. Compared to the unhelmeted head, the head with helmet experienced slight mitigation of intracranial stresses. This suggests that the existing ACH does not significantly contribute to mitigating blast effects, but does not worsen them either. By contrast, the helmet and face shield combination impeded direct transmission of stress waves to the face, resulting in a delay in the transmission of stresses to the intracranial cavity and lower intracranial stresses. This suggests a possible strategy for mitigating blast waves often associated with military concussion.
Cation-π interaction regulates ligand-binding affinity and signaling of integrin α4β7
Authors: Pan YouDong , Zhang Kun , Qi JunPeng , Yue Jiao , Springer Timothy A. , Chen JianFeng
Published: November 2010

Integrin α4β7mediates rolling and firm adhesion of leucocytes, two of the critical steps in leukocyte migration and tissue specific homing. Affinity of α4β7for ligand is dynamically regulated by three interlinked metal ion-binding sites in β7-subunit I domain. In this study, we found that Phe185 (F185), a highly conserved aromatic residue in β7-subunit, links the specificity-determining loop and the synergistic metal ion-binding site (SyMBS) through cation-π interaction. Mutations of F185 that disrupted the SyMBS cation-F185 interaction led to deficient firm cell adhesion mediated by high affinity α4β7, and only slightly affected rolling adhesion mediated by low affinity α4β7. Disruption of SyMBS cation-F185 interaction induced partial extension of integrin ectodomain and separation of cytoplasmic tails, and impaired α4β7-mediated bidirectional signaling. In addition, loss of SyMBS cation-F185 interaction increased paxillin expression and promoted paxillin-integrin binding, leading to deficient cell spreading. Furthermore, integrin α4β7-mediated cell migration was decreased by the abolishment of SyMBS cation-F185 interaction. Thus, these findings reveal a cation-π interaction playing vital roles in the regulation of integrin affinity, signaling, and biological functions.
Luminescent nanocrystal stress gauge
Authors: Choi Charina L. , Koski Kristie J. , Olson Andrew C. K. , Alivisatos A. Paul
Published: November 2010

Microscale mechanical forces can determine important outcomes ranging from the site of material fracture to stem cell fate. However, local stresses in a vast majority of systems cannot be measured due to the limitations of current techniques. In this work, we present the design and implementation of the CdSe-CdS core-shell tetrapod nanocrystal, a local stress sensor with bright luminescence readout. We calibrate the tetrapod luminescence response to stress and use the luminescence signal to report the spatial distribution of local stresses in single polyester fibers under uniaxial strain. The bright stress-dependent emission of the tetrapod, its nanoscale size, and its colloidal nature provide a unique tool that may be incorporated into a variety of micromechanical systems including materials and biological samples to quantify local stresses with high spatial resolution.
The role of age and inhibitory efficiency in working memory processing and storage components
Authors: Blair Mervin , Vadaga Kiran K. , Shuchat Joni , Li Karen Z. H.
Published: November 2010

In this study, we examined the extent to which inhibitory efficiency accounted for age-related decline in the processing and storage components of working memory. Older and younger adults performed a sequential task, which served as an index of deletion-type inhibition (the ability to suppress no-longer-relevant information). The reading span task was used to measure working memory components by examining processing accuracy, processing time, and end-word recall of sentences presented. Reduced inhibitory efficiency, which was poorer in older adults, predicted age-related decline in recall, over and above the effects of processing speed. Similar results were observed for processing accuracy, although the age effect in this component was marginal. These results highlight the important role of deletion-type inhibition in explaining age-related decline in working memory performance, particularly in the storage component, and extend previous research by examining this relationship at a componential level.
Setting the spindle's compass
Authors: Short Ben
Published: November 2010

Two control points determine the orientation of epidermal cell divisions.
Defects in nuclear pore assembly lead to activation of an Aurora B–mediated abscission checkpoint
Authors: Mackay Douglas R. , Makise Masaki , Ullman Katharine S.
Published: November 2010

Correct assembly of nuclear pore complexes (NPCs), which directly and indirectly control nuclear environment and architecture, is vital to genomic regulation. We previously found that nucleoporin 153 (Nup153) is required for timely progression through late mitosis. In this study, we report that disruption of Nup153 function by either small interfering RNA–mediated depletion or expression of a dominant-interfering Nup153 fragment results in dramatic mistargeting of the pore basket components Tpr and Nup50 in midbody-stage cells. We find a concomitant appearance of aberrantly localized active Aurora B and an Aurora B–dependent delay in abscission. Depletion of Nup50 is also sufficient to increase the number of midbody-stage cells and, likewise, triggers distinctive mislocalization of Aurora B. Together, our results suggest that defects in nuclear pore assembly, and specifically the basket structure, at this time of the cell cycle activate an Aurora B–mediated abscission checkpoint, thereby ensuring that daughter cells are generated only when fully formed NPCs are present.
Robust control of mitotic spindle orientation in the developing epidermis
Authors: Poulson Nicholas D. , Lechler Terry
Published: November 2010

Progenitor cells must balance self-amplification and production of differentiated progeny during development and homeostasis. In the epidermis, progenitors divide symmetrically to increase surface area and asymmetrically to promote stratification. In this study, we show that individual epidermal cells can undergo both types of division, and therefore, the balance is provided by the sum of individual cells’ choices. In addition, we define two control points for determining a cell’s mode of division. First is the expression of the mouse Inscuteable gene, which is sufficient to drive asymmetric cell division (ACD). However, there is robust control of division orientation as excessive ACDs are prevented by a change in the localization of NuMA, an effector of spindle orientation. Finally, we show that p63, a transcriptional regulator of stratification, does not control either of these processes. These data have uncovered two important regulatory points controlling ACD in the epidermis and allow a framework for analysis of how external cues control this important choice.
Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells
Authors: Takayama Naoya , Nishimura Satoshi , Nakamura Sou , Shimizu Takafumi , Ohnishi Ryoko , Endo Hiroshi , Yamaguchi Tomoyuki , Otsu Makoto , Nishimura Ken , Nakanishi Mahito , Sawaguchi Akira , Nagai Ryozo , Takahashi Kazutoshi , Yamanaka Shinya , Nakauchi Hiromitsu , Eto Koji
Published: November 2010

Human (h) induced pluripotent stem cells (iPSCs) are a potentially abundant source of blood cells, but how best to select iPSC clones suitable for this purpose from among the many clones that can be simultaneously established from an identical source is not clear. Using an in vitro culture system yielding a hematopoietic niche that concentrates hematopoietic progenitors, we show that the pattern of c-MYC reactivation after reprogramming influences platelet generation from hiPSCs. During differentiation, reduction of c-MYC expression after initial reactivation of c-MYC expression in selected hiPSC clones was associated with more efficient in vitro generation of CD41a+CD42b+ platelets. This effect was recapitulated in virus integration-free hiPSCs using a doxycycline-controlled c-MYC expression vector. In vivo imaging revealed that these CD42b+ platelets were present in thrombi after laser-induced vessel wall injury. In contrast, sustained and excessive c-MYC expression in megakaryocytes was accompanied by increased p14 (ARF) and p16 (INK4A) expression, decreased GATA1 expression, and impaired production of functional platelets. These findings suggest that the pattern of c-MYC expression, particularly its later decline, is key to producing functional platelets from selected iPSC clones.
Plexin-A4–semaphorin 3A signaling is required for Toll-like receptor– and sepsis-induced cytokine storm
Authors: Wen Haitao , Lei Yu , Eun So-Young , P.-Y. Ting Jenny
Published: November 2010

Plexins and semaphorins are ligand–receptor pairs that serve as guidance molecules in the nervous system and play some roles in immunity. Plexins are similar to the Toll-like receptors (TLRs) in their evolutionary conservation from flies to mammals. By studying plexin-A4–deficient (Plxna4−/−) innate immune cells, in this study we show a novel influence of plexin-A4 on TLR signaling. Plxna4−/− cells exhibit defective inflammatory cytokine production upon activation by a spectrum of TLR agonists and bacteria. Plexin-A4 is required for TLR-induced activation of the small guanosine triphosphate hydrolase (GTPase) Rac1 (ras-related C3 botulinum toxin substrate 1). Rac1 activation is accompanied by JNK (c-Jun N-terminal kinase) and NF-κB activation, culminating in TLR-induced binding of NF-κB and AP-1 to the promoters of inflammatory cytokines. Plxna4−/− mice are remarkably resistant to TLR agonist–induced inflammation and polymicrobial peritonitis caused by cecal ligation and puncture. Administration of a ligand of plexin-A4, Sema3A (semaphorin 3A), exacerbates the cytokine storm caused by TLR agonists and bacterial sepsis. TLR engagement can induce Sema3A expression, thus completing an autocrine loop. These findings expand the role of plexins to TLR signaling and suggest plexin-A4 and Sema3A as new intervention points for treating sepsis.
Quasiregular mappings of polynomial type in ℝ²
Authors: Fletcher Alastair , Goodman Dan
Published: November 2010

Complex dynamics deals with the iteration of holomorphic functions. As is well known, the first functions to be studied which gave non-trivial dynamics were quadratic polynomials, which produced beautiful computer generated pictures of Julia sets and the Mandelbrot set. In the same spirit, this article aims to study the dynamics of the simplest non-trivial quasiregular mappings. These are mappings inR2\mathbb {R}^{2}which are a composition of a quadratic polynomial and an affine stretch.