bluuebunny/crossref_metadata_2025 huggingface dataset:
S100 Calgranulins in inflammatory arthritis
Authors: Perera Chandima , McNeil H Patrick , Geczy Carolyn L
Published: November 2009

Calgranulins comprise three proteins, S100A8 (Calgranulin A), S100A9 (Calgranulin B) and S100A12 (Calgranulin C) that are predominantly expressed by neutrophils, monocytes and activated macrophages. These S100 calcium‐binding proteins are important molecular mediators in a range of diseases, including inflammatory arthritis, atherosclerosis and microbial infections. Much of the literature has focused on the pro‐inflammatory functions of calgranulins, and this has tended to underplay important regulatory, anti‐oxidant and protective properties. S100A8 and S100A9 are particularly complex in their actions because they exert intracellular and extracellular functions, they form a heterocomplex, S100A8–A9 (calprotectin), and have actions that are independent of or dependent on heterocomplex formation. In some circumstances S100A9 appears to regulate, rather than synergize with the actions of S100A8 and vice versa. Moreover, these calgranulins also bind zinc and other divalent cations and are sensitive to post‐translational oxidative modifications, properties that also affect some functions. It is important to note that S100A8 has potent anti‐oxidant activity, which could be important in host protection. Furthermore, although the genes for S100A8 and S100A9 are induced by activation of the toll‐like receptor/interleukin‐1 pathway, their expression is enhanced by interleukin‐10 and glucocorticoids, thus suggesting a regulatory role in inflammation. On the other hand, S100A12 appears to be predominantly pro‐inflammatory, particularly by its ability to activate mast cells. Measurement of S100A12 levels may be a highly sensitive biomarker for inflammatory disease activity. This review summarizes the current understanding of the biology of calgranulins, with a focus on their pleiotropic roles in inflammatory arthritis.
Picogram material dosing of microstructures
Authors: Bedair Sarah S. , Fedder Gary K.
Published: November 2009

A solution delivery platform comprised of a suspended microcapillary connected to a microwell enables picogram solute deposition on suspended structures. Precision material placement in the capillary from a 100pl drop inkjetted into the well is achieved without the destruction of the microstructure and adjacent submicron electrostatic gaps. This method scales to smaller structures without the need for drop miniaturization. The theory behind the solute transfer in the system is developed. Three regions in the drying process are observed and match with the model. The “accumulation” region builds solute concentration in the capillary. The “solidification” region initiates the solidification of solute starting at the free end of the capillary. The “termination” region is characterized by a rapid increase in the solidification due to an increase in the well concentration near the end of the drop lifetime. The accumulation time and solidification rate dependence on concentration compare well with the model.
Why droplet dimension can be larger than, equal to, or smaller than the nanowire dimension
Authors: Mohammad S. Noor
Published: November 2009

Droplets play central roles in the nanowire (NW) growth by vapor phase mechanisms. These mechanisms include vapor-liquid-solid (VLS), vapor-solid-solid or vapor-solid (VSS), vapor-quasisolid-solid or vapor-quasiliquid-solid (VQS), oxide-assisted growth (OAG), and self-catalytic growth (SCG) mechanisms. Fundamentals of the shape, size, characteristics, and dynamics of droplets and the impacts of them on the NW growth, have been studied. The influence of growth techniques, growth parameters (e.g., growth temperature, partial pressure, gas flow rates, etc.), thermodynamic conditions, surface and interface energy, molar volume, chemical potentials, etc. have been considered on the shapes and sizes of droplets. A model has been presented to explain why droplets can be larger than, equal to, or smaller than the associated NWs. Various growth techniques have been analyzed to understand defects created in NWs. Photoluminescence characteristics have been presented to quantify the roles of droplets in the creation of NW defects. The study highlights the importance of the purity of the droplet material. It attests to the superiority of the SCG mechanism, and clarifies the differences between the VSS, VQS, VLS, and SCG mechanisms. It explains why droplets produced by some mechanisms are visible but droplets produced by some other mechanisms are not visible. It elucidates the formation mechanisms of very large and very small droplets, and discusses the ground rules for droplets creating necked NWs. It puts forth reasons to demonstrate that very large droplets may not behave as droplets.
Substrate-mediated diffusion-induced growth of single-crystal nanowires
Authors: Mohammad S. Noor
Published: November 2009

Theoretical investigations of the growth and growth rates of single-crystal nanowires (NWs) by vapor phase mechanisms have been carried out. Substrate-induced processes are assumed to dominate this growth. The modeling for growth takes adsorption, desorption, surface scattering, and diffusion into account. It takes into consideration also the retarding electric field arising from the scattering of the NW vapor species by both the substrate and the NW sidewalls. Growth characteristics under the influence of the retarding electric field have been studied. Competitive roles of adatom diffusivity and the electric field in the NW growth are elucidated. Influence of the growing NW length and the adatom impingement rate on the NW growth rate has been described. The effect of adatom collection area around each NW has been examined. The NW tapering and kinking have been explained. The fundamentals of the substrate induction and details of the growth parameters have been analyzed. The influence of foreign element catalytic agents in the vapor-liquid-solid mechanism has been presented. All these have led to the understanding and resolution of problems, controversies, and contradictions involving substrate-induced NW growths.
Judd–Ofelt analysis, frequency upconversion, and infrared photoluminescence of Ho3+-doped and Ho3+/Yb3+-codoped lead bismuth gallate oxide glasses
Authors: Zhou Bo , Pun Edwin Yue-Bun , Lin Hai , Yang Dianlai , Huang Lihui
Published: November 2009

Ho 3 + -doped and Ho3+/Yb3+-codoped lead bismuth gallate (PBG) oxide glasses were prepared and their spectroscopic properties were investigated. The derived Judd–Ofelt intensity parameters (Ω2=6.81×10−20 cm2, Ω4=2.31×10−20 cm2, and Ω6=0.67×10−20 cm2) indicate a higher asymmetry and stronger covalent environment for Ho3+ sites in PBG glass compared with those in tellurite, fluoride (ZBLAN), and some other lead-contained glasses. Intense frequency upconversion emissions peaking at 547, 662, and 756 nm as well as infrared emissions at 1.20 and 2.05 μm in Ho3+/Yb3+-codoped PBG glass were observed, confirming that energy transfer between Yb3+ and Ho3+ takes place, and a two-phonon-assisted energy transfer from Yb3+ to Ho3+ ions was determined by the calculation using phonon sideband theory. The 1.20 μm emission observed was primarily due to the weak multiphonon deexcitation originated from the small phonon energy of PBG glass (∼535 cm−1). A large product of emission cross-section and measured lifetime (9.93×10−25 cm2 s) was obtained for the 1.20 μm emission and the gain coefficient dependence on wavelength with population inversion rate (P) was performed. The peak emission cross-section for 2.05 μm emission was calculated to be 4.75×10−21 cm2. The relative mechanism of Ho3+-doped and Ho3+/Yb3+-codoped PBG glasses on their spectroscopic properties was also discussed. Our results suggest that Ho3+/Yb3+-doped PBG glasses are a good potential candidate for the frequency upconversion devices and infrared amplifiers/lasers.
Lifetime of high-k gate dielectrics and analogy with strength of quasibrittle structures
Authors: Le Jia-Liang , Bažant Zdeněk P. , Bazant Martin Z.
Published: November 2009

The two-parameter Weibull distribution has been widely adopted to model the lifetime statistics of dielectric breakdown under constant voltage, but recent lifetime testing for high-k gate dielectrics has revealed a systematic departure from Weibull statistics, evocative of lifetime statistics for small quasibrittle structures under constant stress. Here we identify a mathematical analogy between the dielectric breakdown in semiconductor electronic devices and the finite-size weakest-link model for mechanical strength of quasibrittle structures and adapt a recently developed probabilistic theory of structural failure to gate dielectrics. Although the theory is general and does not rely on any particular model of local breakdown events, we show how its key assumptions can be derived from the classical dielectric breakdown model, which predicts certain scaling exponents. The theory accurately fits the observed kinked shape of the histograms of lifetime plotted in Weibull scale, as well as the measured dependence of the median lifetime on the gate area (or size), including its deviation from a power law. The theory also predicts that the Weibull modulus for breakdown lifetime increases in proportion to the thickness of the oxide layer and suggests new ideas for more effective reliability testing.
Improved crystalline properties of laser molecular beam epitaxy grown SrTiO3 by rutile TiO2 layer on hexagonal GaN
Authors: Luo W. B. , Zhu J. , Chen H. , Wang X. P. , Zhang Y. , Li Y. R.
Published: November 2009

Epitaxial SrTiO3 films were fabricated by laser molecular beam epitaxy on bare and TiO2 buffered GaN(0002), respectively. The whole deposition processes were in situ monitored by reflection high energy electron diffraction (RHEED). X-ray diffraction (XRD) was carried out to study the growth orientation and crystalline quality of STO films. The interfacial characters and epitaxial relationships were also investigated by high revolution transition electron microscope and selected area electron diffraction (SAED). According to the RHEED observation, the lowest epitaxy temperature of STO on TiO2 buffered GaN was decreased compared with the direct deposited one. The epitaxial relationship was (111)[11¯0]STO//(0002)[112¯0]GaN in both cases as confirmed by RHEED, XRD, and SAED. The full width at half maximum of ω-scan and Φ-scan of STO on TiO2 buffered GaN was reduced compared with that deposited on bare GaN, indicating that epitaxial quality of STO film is improved by inserting TiO2 layer. In summary, the lattice mismatch was reduced by inserting rutile TiO2. As a result, the crystalline temperature was reduced and enhanced epitaxial quality of STO thin film was obtained.
Terahertz spectroscopic investigation of four kinds of vitamins
Authors: Zhao Guozhong , Yu Bin , Zhang Cunlin
Published: November 2009

The terahertz spectra of four kinds of vitamins are presented. The refractive index and absorption spectra of these vitamins are obtained by the terahertz time-domain spectroscopy. The full-geometry optimizations and frequency calculations using the density functional theory are applied to obtain the structure and vibration frequencies of these vitamin molecules. The calculated vibration frequencies are compared with the experimental data. The results show that there are terahertz fingerprint absorptions for all of four kinds of vitamins. The terahertz absorbance spectra of vitamins result from not only the intramolecular vibration modes, but also the intermolecular interaction or phonon modes.
Crack evolution in bulk metallic glasses
Authors: Pauly Simon , Lee Min Ha , Kim Do Hyang , Kim Ki Buem , Sordelet Daniel J. , Eckert Jürgen
Published: November 2009

In the present study, the mechanisms underlying plastic deformation of a Ni-based bulk metallic glass (BMG) are explored. Based on the microstructural investigations, a model is proposed how fracture emerges in BMGs. After deformation, the glass is macroscopically more fragile indicating a decrease in the viscosity within the shear bands due to shear softening. These fluctuations of viscosity and therefore Poisson ratio between the deformed and undeformed regions appear to be the initiation sites for nanometer-scale cracks, which are aligned parallel to the applied force. Coalescence of voids is believed to form these small cracks, which eventually interconnect along the interface between the sheared and unsheared regions to form a detrimental defect resulting in fracture.
Spatially resolved investigations of the emission around 3.31 eV (A-line) from ZnO nanocrystals
Authors: Kurbanov S. S. , Panin G. N. , Kang T. W.
Published: November 2009

ZnO nanocrystals grown by chemical solution deposition were studied by means of photoluminescence and cathodoluminescence spectroscopy. A postgrown annealing treatment significantly improved the UV emission efficiency and resulted in the clear appearance of a low temperature emission band around 3.31 eV (so-called A-line). Spatially and wavelength resolved cathodoluminescence measurements revealed a spotlike distribution of the A-line emission on a nanocrystal surface. It is found that there is a strong correlation between the emission around 3.31 eV and the specklike defects on the nanocrystal surface that appeared after annealing. The origin of the A-line and the specklike defects are discussed.
Inquiry into thermodynamic behavior of hard sphere plus repulsive barrier of finite height
Authors: Zhou Shiqi , Solana J. R.
Published: November 2009

A bridge function approximation is proposed to close the Ornstein–Zernike (OZ) integral equation for fluids with purely repulsive potentials. The performance of the bridge function approximation is then tested by applying the approximation to two kinds of repulsive potentials, namely, the square shoulder potential and the triangle shoulder potential. An extensive comparison between simulation and the OZ approach is performed over a wide density range for the fluid phase and several temperatures. It is found that the agreement between the two routes is excellent for not too low temperatures and satisfactory for extremely low temperatures. Then, this globally trustworthy OZ approach is used to investigate the possible existence or not of a liquid anomaly, i.e., a liquid-liquid phase transition at low temperatures and negative values of the thermal expansion coefficient in certain region of the phase diagram. While the existence of the liquid anomaly in the square shoulder potential has been previously predicted by a traditional first-order thermodynamic perturbation theory (TPT), the present investigation indicates that the liquid-liquid phase transition disappears in the OZ approach, so that its prediction by the first-order TPT is only an artifact originating from the low temperature inadequacy of the first-order TPT. However, the OZ approach indeed predicts negative thermal expansion coefficients. The present bridge function approximation, free of adjustable parameters, is suitable to be used within the context of a recently proposed nonhard sphere perturbation scheme.
High spontaneous emission rate asymmetrically graded 480 nm InGaN/GaN quantum well light-emitting diodes
Authors: Wang Lei , Li Rui , Yang Ziwen , Li Ding , Yu Tao , Liu Ningyang , Liu Lei , Chen Weihua , Hu Xiaodong
Published: November 2009

Spontaneous emission property of an asymmetrically graded 480 nm InGaN/GaN quantum well (QW) is investigated via k⋅p theory. Comparing to rectangular QW, band profiles of the graded QW change into parabolalike due to the variation of internal piezoelectric field along the growth direction, and the spontaneous emission rates of the graded QW are three times larger than rectangular case under various carrier densities. This can be attributed to the fact that the graded QW has much larger matrix element (Me)nmσ(kt) than rectangular QW considering that the wave function overlap of the graded QW is less affected by the quantum confined Stark effect.
Tunable long-range surface plasmon polaritons taking advantage of nonlinear surface waves
Authors: Shao Weiwei , Li Lin , Liu Weiwu , Zhang Tianhao , Ma Huihui , Xu Jingjun , Tian Jianguo
Published: November 2009

We present an improved Kretschmann configuration with nonlinear dielectric as substrate, in which long-range surface plasmon polaritons (SPPs) may appear, the modes and propagation lengths are tunable. We numerically simulated the solutions of SPP modes and their propagations. The results show that the SPP propagation length can range from tens of micrometers to tens of centimeters or even longer. The configuration proposed in this letter makes a breakthrough of the intrinsic restriction in conventional Kretschmann configuration and there exist the continuous steady SPP modes also in the range of k0ε31/2>β>k0ε11/2. It allows for optimization of SPP properties and makes SPP application more flexible in practices.
A computational study of tunneling-percolation electrical transport in graphene-based nanocomposites
Authors: Hicks Jeremy , Behnam Ashkan , Ural Ant
Published: November 2009

Using a tunneling-percolation model and Monte Carlo simulations, we study the resistivity of graphene-based nanocomposites as a function of both graphene sheet and device parameters. We observe an inverse power law dependence of resistivity on device dimensions and volume fraction near the percolation threshold, and find that high aspect ratio graphene sheets result in a much lower resistivity, particularly at low sheet densities. Furthermore, we find that graphene sheet area affects nanocomposite resistivity more strongly than sheet density does. These results impart important fundamental insights for future experimental investigations and applications of graphene-based conductive nanocomposites.
Electrokinetic focusing and filtration of cells in a serpentine microchannel
Authors: Church Christopher , Zhu Junjie , Wang Gaoyan , Tzeng Tzuen-Rong J. , Xuan Xiangchun
Published: November 2009

Focusing cells into a single stream is usually a necessary step prior to counting and separating them in microfluidic devices such as flow cytometers and cell sorters. This work presents a sheathless electrokinetic focusing of yeast cells in a planar serpentine microchannel using dc-biased ac electric fields. The concurrent pumping and focusing of yeast cells arise from the dc electrokinetic transport and the turn-induced ac/dc dielectrophoretic motion, respectively. The effects of electric field (including ac to dc field ratio and ac field frequency) and concentration (including buffer concentration and cell concentration) on the cell focusing performance were studied experimentally and numerically. A continuous electrokinetic filtration of E. coli cells from yeast cells was also demonstrated via their differential electrokinetic focusing in a serpentine microchannel.
Atmospheric pressure argon plasma jet using a cylindrical piezoelectric transformer
Authors: Kim Hyun , Brockhaus Albrecht , Engemann Jürgen
Published: November 2009

A low-voltage atmospheric pressure nonthermal argon plasma jet using a circular piezoelectric transducer is proposed. An Ar plasma flame is generated at an input voltage of 87 V. The consumed power is 2 W. The electrical and optical properties of the jet are analyzed. In particular, the transient Ar discharge ignition and evolution including the so-called plasma bullet phenomenon is examined temporally resolved with the aid of a fast camera. It is found that four discharge phases can be identified, designated as ignition, extension, self-propagation, and attenuation. The plasma bullet is launched while the electric field in the discharge space is decreasing. The average bullet velocity is 23 km/s.
Comparison of large-scale amplitude modulation in turbulent boundary layers, pipes, and channel flows
Authors: Mathis Romain , Monty Jason P. , Hutchins Nicholas , Marusic Ivan
Published: November 2009

Recent investigations by Monty et al. [J. Fluid Mech. 632, 431 (2009)] showed that important modal differences exist between channels/pipes and boundary layers, mainly in the largest energetic scales. In addition, Mathis et al. [J. Fluid Mech. 628, 311 (2009)] recently reported and quantified a nonlinear scale interaction in zero-pressure gradient turbulent boundary layers, whereby the large-scale motion amplitude modulates the small-scale motions. In this study, a comparison of this modulation effect of the streamwise velocity component is undertaken for all three flows for matched Reynolds number and measurement conditions. Despite the different large-scale phenomena in these internal and external wall-bounded flows, the results show that their amplitude modulation influence remains invariant in the inner region with some differences appearing in the outer region.
Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant model
Authors: Bernhardt W. M. , Gottmann U. , Doyon F. , Buchholz B. , Campean V. , Schödel J. , Reisenbuechler A. , Klaus S. , Arend M. , Flippin L. , Willam C. , Wiesener M. S. , Yard B. , Warnecke C. , Eckardt K.-U.
Published: November 2009

Long-term survival of renal allografts depends on the chronic immune response and is probably influenced by the initial injury caused by ischemia and reperfusion. Hypoxia-inducible transcription factors (HIFs) are essential for adaptation to low oxygen. Normoxic inactivation of HIFs is regulated by oxygen-dependent hydroxylation of specific prolyl-residues by prolyl-hydroxylases (PHDs). Pharmacological inhibition of PHDs results in HIF accumulation with subsequent activation of tissue-protective genes. We examined the effect of donor treatment with a specific PHD inhibitor (FG-4497) on graft function in the Fisher–Lewis rat model of allogenic kidney transplantation (KTx). Orthotopic transplantation of the left donor kidney was performed after 24 h of cold storage. The right kidney was removed at the time of KTx (acute model) or at day 10 (chronic model). Donor animals received a single dose of FG-4497 (40 mg/kg i.v.) or vehicle 6 h before donor nephrectomy. Recipients were followed up for 10 days (acute model) or 24 weeks (chronic model). Donor preconditioning with FG-4497 resulted in HIF accumulation and induction of HIF target genes, which persisted beyond cold storage. It reduced acute renal injury (serum creatinine at day 10: 0.66 ± 0.20 vs. 1.49 ± 1.36 mg/dL;
P
< 0.05) and early mortality in the acute model and improved long-term survival of recipient animals in the chronic model (mortality at 24 weeks: 3 of 16 vs. 7 of 13 vehicle-treated animals;
P
< 0.05). In conclusion, pretreatment of organ donors with FG-4497 improves short- and long-term outcomes after allogenic KTx. Inhibition of PHDs appears to be an attractive strategy for organ preservation that deserves clinical evaluation.
Phytoplankton, not allochthonous carbon, sustains herbivorous zooplankton production
Authors: Brett Michael T. , Kainz Martin J. , Taipale Sami J. , Seshan Hari
Published: November 2009

Terrestrial organic matter inputs have long been thought to play an important role in aquatic food web dynamics. Results from recent whole lake
13
C addition experiments suggest terrestrial particulate organic carbon (t-POC) inputs account for a disproportionate portion of zooplankton production. For example, several studies concluded that although t-POC only represented ≈20% of the flux of particulate carbon available to herbivorous zooplankton, this food source accounted for ≈50% of the C incorporated by zooplankton. We tested the direct dietary impact of t-POC (from the leaves of riparian vegetation) and various phytoplankton on
Daphnia magna
somatic growth, reproduction, growth efficiency, and lipid composition. By itself, t-POC was a very poor quality resource compared to cryptophytes, diatoms, and chlorophytes, but t-POC had similar food quality compared to cyanobacteria. Small additions of high quality
Cryptomonas ozolinii
to t-POC-dominated diets greatly increased
Daphnia
growth and reproduction. When offered alone, t-POC resulted in a
Daphnia
growth efficiency of 5 ± 1%, whereas 100%
Cryptomonas
and
Scenedesmus obliquus
diets resulted in growth efficiencies of 46 ± 8% (± SD) and 36 ± 3%, respectively. When offered in a 50:50 mixed diet with
Cryptomonas
or
Scenedesmus
, the t-POC fraction resulted in a partial growth efficiency of 22 ± 9% and 15 ± 6%, respectively.
Daphnia
that obtained 80% of their available food from t-POC assimilated 84% of their fatty acids from the phytoplankton component of their diet. Overall, our results suggest
Daphnia
selectively allocate phytoplankton-derived POC and lipids to enhance somatic growth and reproduction, while t-POC makes a minor contribution to zooplankton production.
Political partisanship influences perception of biracial candidates' skin tone
Authors: Caruso Eugene M. , Mead Nicole L. , Balcetis Emily
Published: November 2009

People tend to view members of their own political group more positively than members of a competing political group. In this article, we demonstrate that political partisanship influences people's visual representations of a biracial political candidate's skin tone. In three studies, participants rated the representativeness of photographs of a hypothetical (Study 1) or real (Barack Obama; Studies 2 and 3) biracial political candidate. Unbeknownst to participants, some of the photographs had been altered to make the candidate's skin tone either lighter or darker than it was in the original photograph. Participants whose partisanship matched that of the candidate they were evaluating consistently rated the lightened photographs as more representative of the candidate than the darkened photographs, whereas participants whose partisanship did not match that of the candidate showed the opposite pattern. For evaluations of Barack Obama, the extent to which people rated lightened photographs as representative of him was positively correlated with their stated voting intentions and reported voting behavior in the 2008 Presidential election. This effect persisted when controlling for political ideology and racial attitudes. These results suggest that people's visual representations of others are related to their own preexisting beliefs and to the decisions they make in a consequential context.
A nonparametric view of network models and Newman–Girvan and other modularities
Authors: Bickel Peter J. , Chen Aiyou
Published: November 2009

Prompted by the increasing interest in networks in many fields, we present an attempt at unifying points of view and analyses of these objects coming from the social sciences, statistics, probability and physics communities. We apply our approach to the Newman–Girvan modularity, widely used for “community” detection, among others. Our analysis is asymptotic but we show by simulation and application to real examples that the theory is a reasonable guide to practice.
Two- and three-dimensional folding of thin film single-crystalline silicon for photovoltaic power applications
Authors: Guo Xiaoying , Li Huan , Yeop Ahn Bok , Duoss Eric B. , Hsia K. Jimmy , Lewis Jennifer A. , Nuzzo Ralph G.
Published: November 2009

Fabrication of 3D electronic structures in the micrometer-to-millimeter range is extremely challenging due to the inherently 2D nature of most conventional wafer-based fabrication methods. Self-assembly, and the related method of self-folding of planar patterned membranes, provide a promising means to solve this problem. Here, we investigate self-assembly processes driven by wetting interactions to shape the contour of a functional, nonplanar photovoltaic (PV) device. A mechanics model based on the theory of thin plates is developed to identify the critical conditions for self-folding of different 2D geometrical shapes. This strategy is demonstrated for specifically designed millimeter-scale silicon objects, which are self-assembled into spherical, and other 3D shapes and integrated into fully functional light-trapping PV devices. The resulting 3D devices offer a promising way to efficiently harvest solar energy in thin cells using concentrator microarrays that function without active light tracking systems.
Structural determinant for switching between the polymerase and exonuclease modes in the PCNA-replicative DNA polymerase complex
Authors: Nishida Hirokazu , Mayanagi Kouta , Kiyonari Shinichi , Sato Yuichi , Oyama Takuji , Ishino Yoshizumi , Morikawa Kosuke
Published: November 2009

Proliferating cell nuclear antigen (PCNA) is responsible for the processivity of DNA polymerase. We determined the crystal structure of
Pyrococcus furiosus
DNA polymerase (PfuPol) complexed with the cognate monomeric PCNA, which allowed us to construct a convincing model of the polymerase-PCNA ring interaction, with unprecedented configurations of the two molecules. Electron microscopic analyses indicated that this complex structure exists in solution. Our structural study revealed that an interaction occurs between a stretched loop of PCNA and the PfuPol Thumb domain, in addition to the authentic PCNA-polymerase recognition site (PIP box). Comparisons of the present structure with the previously reported structures of polymerases complexed with DNA, suggested that the second interaction plays a crucial role in switching between the polymerase and exonuclease modes, by inducing a PCNA-polymerase complex configuration that favors synthesis over editing. This putative mechanism for fidelity control of replicative DNA polymerases is supported by experiments, in which mutations at the second interaction site caused enhancements in the exonuclease activity in the presence of PCNA.
Synchronous extinction of North America's Pleistocene mammals
Authors: Faith J. Tyler , Surovell Todd A.
Published: November 2009

The late Pleistocene witnessed the extinction of 35 genera of North American mammals. The last appearance dates of 16 of these genera securely fall between 12,000 and 10,000 radiocarbon years ago (≈13,800–11,400 calendar years B.P.), although whether the absence of fossil occurrences for the remaining 19 genera from this time interval is the result of sampling error or temporally staggered extinctions is unclear. Analysis of the chronology of extinctions suggests that sampling error can explain the absence of terminal Pleistocene last appearance dates for the remaining 19 genera. The extinction chronology of North American Pleistocene mammals therefore can be characterized as a synchronous event that took place 12,000–10,000 radiocarbon years B.P. Results favor an extinction mechanism that is capable of wiping out up to 35 genera across a continent in a geologic instant.
Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans
Authors: Rodrigues Sarina M. , Saslow Laura R. , Garcia Natalia , John Oliver P. , Keltner Dacher
Published: November 2009

Oxytocin, a peptide that functions as both a hormone and neurotransmitter, has broad influences on social and emotional processing throughout the body and the brain. In this study, we tested how a polymorphism (rs53576) of the oxytocin receptor relates to two key social processes related to oxytocin: empathy and stress reactivity. Compared with individuals homozygous for the G allele of rs53576 (GG), individuals with one or two copies of the A allele (AG/AA) exhibited lower behavioral and dispositional empathy, as measured by the “Reading the Mind in the Eyes” Test and an other-oriented empathy scale. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals, as determined by heart rate response during a startle anticipation task and an affective reactivity scale. Our results provide evidence of how a naturally occurring genetic variation of the oxytocin receptor relates to both empathy and stress profiles.
Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin
Authors: Carroll Joseph , Baraas Rigmor C. , Wagner-Schuman Melissa , Rha Jungtae , Siebe Cory A. , Sloan Christina , Tait Diane M. , Thompson Summer , Morgan Jessica I. W. , Neitz Jay , Williams David R. , Foster David H. , Neitz Maureen
Published: November 2009

Missense mutations in the cone opsins have been identified as a relatively common cause of red/green color vision defects, with the most frequent mutation being the substitution of arginine for cysteine at position 203 (C203R). When the corresponding cysteine is mutated in rhodopsin, it disrupts proper folding of the pigment, causing severe, early onset retinitis pigmentosa. While the C203R mutation has been associated with loss of cone function in color vision deficiency, it is not known what happens to cones expressing this mutant opsin. Here, we used high-resolution retinal imaging to examine the cone mosaic in two individuals with genes encoding a middle-wavelength sensitive (M) pigment with the C203R mutation. We found a significant reduction in cone density compared to normal and color-deficient controls, accompanying disruption in the cone mosaic in both individuals, and thinning of the outer nuclear layer. The C203R mosaics were different from that produced by another mutation (LIAVA) previously shown to disrupt the cone mosaic. Comparison of these mosaics provides insight into the timing and degree of cone disruption and has implications for the prospects for restoration of vision loss associated with various cone opsin mutations.
Regulation of hippocampal H3 histone methylation by acute and chronic stress
Authors: Hunter Richard G. , McCarthy Katharine J. , Milne Thomas A. , Pfaff Donald W. , McEwen Bruce S.
Published: November 2009

The hippocampal formation is a brain region noted for its plasticity in response to stressful events and adrenal steroid hormones. Recent work has shown that chromatin remodeling in various brain regions, including the hippocampus, is associated with the effects of stress in a variety of models. We chose to examine the effects of stress, stress duration, corticosterone administration, and fluoxetine treatment on the levels of hippocampal histone H3 methylation at lysines 4, 9, and 27, marks associated, respectively, with active transcription, heterochromatin formation, and transcriptional repression. We found that acute stress increased the levels of H3K9 tri-methylation (H3K9me3) in the dentate gyrus (DG) and CA1, while it reduced levels of H3K9 mono-methylation (H3K9me1) and H3K27 tri-methylation (H3K27me3) in the same regions, and had no effect on levels of H3K4 tri-methylation (H3K4me3). Seven days of restraint stress reduced levels of H3K4me3 in the CA1 and H3K27me3 in the DG and CA1, while increasing basal levels of H3K9me3. Chronic restraint stress (CRS) for 21 days mildly increased levels of H3K4me3 and reduced H3K9me3 levels in the DG. Treatment with fluoxetine during CRS reversed the decrease in DG H3K9me3, but had no effect on the other marks. These results show a complex, surprisingly rapid, and regionally specific pattern of chromatin remodeling within hippocampus produced by stress and anti-depressant treatment that may open an avenue of understanding the interplay of stress and hippocampal gene expression, and reveal the outlines of a potential chromatin stress response that may be diminished or degraded by chronic stress.
The transmembrane inner ear (Tmie) protein is essential for normal hearing and balance in the zebrafish
Authors: Gleason Michelle R. , Nagiel Aaron , Jamet Sophie , Vologodskaia Maria , López-Schier Hernán , Hudspeth A. J.
Published: November 2009

Little is known about the proteins that mediate mechanoelectrical transduction, the process by which acoustic and accelerational stimuli are transformed by hair cells of the inner ear into electrical signals. In our search for molecules involved in mechanotransduction, we discovered a line of deaf and uncoordinated zebrafish with defective hair-cell function. The hair cells of mutant larvae fail to incorporate fluorophores that normally traverse the transduction channels and their ears lack microphonic potentials in response to vibratory stimuli. Hair cells in the posterior lateral lines of mutants contain numerous lysosomes and have short, disordered hair bundles. Their stereocilia lack two components of the transduction apparatus, tip links and insertional plaques. Positional cloning revealed an early frameshift mutation in
tmie
, the zebrafish ortholog of the mammalian gene
transmembrane inner ear
. The mutant line therefore affords us an opportunity to investigate the role of the corresponding protein in mechanoelectrical transduction.
Language typology, task complexity and the development of L2 lexicalization patterns for describing motion events
Authors: Cadierno Teresa , Robinson Peter
Published: November 2009

The present paper focuses on the acquisition of L2 constructions for the expression of motion from a typological (Cadierno, 2008; Talmy, 1985, 1991, 2000) and a psycholinguistic perspective with implications for pedagogy (Robinson, 2003a, 2007; Robinson & Gilabert, 2007a, 2007b). Specifically, we report the results of a cross-linguistic study which examined the extent to which the manipulation of pedagogic tasks in terms of cognitive complexity can facilitate the development of target-like lexicalization patterns and appropriate L2 ways of thinking-for-speaking for the expression of motion by adult L2 learners with typologically similar and typologically different L1s and L2s, i.e., Danish vs. Japanese L1 learners of English. The results of the study show that level of L2 proficiency, assessed using a cloze test, predicts more target-like reference to L2 motion across both L1 groups. Typological similarity between the L1 (Danish) and L2 (English) results in greater use of motion constructions incorporating mention of ground of motion compared to their use by Japanese L1 speakers. More cognitively complex tasks lead to production of more target-like lexicalization patterns, but also only for speakers of the typologically similar L1, Danish.
Kinesin 9 family members perform separate functions in the trypanosome flagellum
Authors: Demonchy Raphaël , Blisnick Thierry , Deprez Caroline , Toutirais Géraldine , Loussert Céline , Marande William , Grellier Philippe , Bastin Philippe , Kohl Linda
Published: November 2009

Numerous eukaryote genome projects have uncovered a variety of kinesins of unknown function. The kinesin 9 family is limited to flagellated species. Our phylogenetic experiments revealed two subfamilies: KIF9A (including Chlamydomonas reinhardtii KLP1) and KIF9B (including human KIF6). The function of KIF9A and KIF9B was investigated in the protist Trypanosoma brucei that possesses a single motile flagellum. KIF9A and KIF9B are strongly associated with the cytoskeleton and are required for motility. KIF9A is localized exclusively in the axoneme, and its depletion leads to altered motility without visible structural modifications. KIF9B is found in both the axoneme and the basal body, and is essential for the assembly of the paraflagellar rod (PFR), a large extra-axonemal structure. In the absence of KIF9B, cells grow abnormal flagella with excessively large blocks of PFR-like material that alternate with regions where only the axoneme is present. The functional diversity of the kinesin 9 family illustrates the capacity for adaptation of organisms to suit specific cytoskeletal requirements.
δ-EF1 is a negative regulator of Ihh in the developing growth plate
Authors: Bellon Ellen , Luyten Frank P. , Tylzanowski Przemko
Published: November 2009

Indian hedgehog (Ihh) regulates proliferation and differentiation of chondrocytes in the growth plate. Although the biology of Ihh is currently well documented, its transcriptional regulation is poorly understood. δ-EF1 is a two-handed zinc finger/homeodomain transcriptional repressor. Targeted inactivation of mouse δ-EF1 leads to skeletal abnormalities including disorganized growth plates, shortening of long bones, and joint fusions, which are reminiscent of defects associated with deregulation of Ihh signaling. Here, we show that the absence of δ-EF1 results in delayed hypertrophic differentiation of chondrocytes and increased cell proliferation in the growth plate. Further, we demonstrate that δ-EF1 binds to the putative regulatory elements in intron 1 of Ihh in vitro and in vivo, resulting in down-regulation of Ihh expression. Finally, we show that δ-EF1 haploinsufficiency leads to a postnatal increase in trabecular bone mass associated with enhanced Ihh expression. In summary, we have identified δ-EF1 as an in vivo negative regulator of Ihh expression in the growth plate.
New PI(4,5)P2- and membrane proximal integrin–binding motifs in the talin head control β3-integrin clustering
Authors: Saltel Frédéric , Mortier Eva , Hytönen Vesa P. , Jacquier Marie-Claude , Zimmermann Pascale , Vogel Viola , Liu Wei , Wehrle-Haller Bernhard
Published: November 2009

Integrin-dependent adhesion sites consist of clustered integrins that transmit mechanical forces and provide signaling required for cell survival and morphogenesis. Despite their importance, the regulation of integrin clustering by the cytoplasmic adapter protein talin (Tal) and phosphatidylinositol (PI)-4,5-biphosphate (PI(4,5)P2) lipids nor their dynamic coupling to the actin cytoskeleton is fully understood. By using a Tal-dependent integrin clustering assay in intact cells, we identified a PI(4,5)P2-binding basic ridge spanning across the F2 and F3 domains of the Tal head that regulates integrin clustering. Clustering requires a new PI(4,5)P2-binding site in F2 and is negatively regulated by autoinhibitory interactions between F3 and the Tal rod (Tal-R). The release of the Tal-R exposes a new β3-integrin–binding site in F3, enabling interaction with a membrane proximal acidic motif, which involves the formation of salt bridges between K316 and K324 with E726 and D723, respectively. This interaction shields the β-integrin tail from reassociation with its α subunit, thereby maintaining the integrin in a substrate-binding and clustering-competent form.
Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock
Authors: Busik Julia V. , Tikhonenko Maria , Bhatwadekar Ashay , Opreanu Madalina , Yakubova Nafissa , Caballero Sergio , Player Danny , Nakagawa Takahiko , Afzal Aqeela , Kielczewski Jennifer , Sochacki Andrew , Hasty Stephanie , Calzi Sergio Li , Kim Sungjin , Duclas Shane K. , Segal Mark S. , Guberski Dennis L. , Esselman Walter J. , Boulton Michael E. , Grant Maria B.
Published: November 2009

The present epidemic of diabetes is resulting in a worldwide increase in cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences in the retina as being responsible for development of this diabetic complication. However, the contribution of circulating cells in maintenance, repair, and dysfunction of the vasculature is now becoming appreciated. Diabetic individuals have fewer endothelial progenitor cells (EPCs) in their circulation and these cells have diminished migratory potential, which contributes to their decreased reparative capacity. Using a rat model of type 2 diabetes, we show that the decrease in EPC release from diabetic bone marrow is caused by bone marrow neuropathy and that these changes precede the development of diabetic retinopathy. In rats that had diabetes for 4 mo, we observed a dramatic reduction in the number of nerve terminal endings in the bone marrow. Denervation was accompanied by increased numbers of EPCs within the bone marrow but decreased numbers in circulation. Furthermore, denervation was accompanied by a loss of circadian release of EPCs and a marked reduction in clock gene expression in the retina and in EPCs themselves. This reduction in the circadian peak of EPC release led to diminished reparative capacity, resulting in the development of the hallmark feature of diabetic retinopathy, acellular retinal capillaries. Thus, for the first time, diabetic retinopathy is related to neuropathy of the bone marrow. This novel finding shows that bone marrow denervation represents a new therapeutic target for treatment of diabetic vascular complications.
Both XPD alleles contribute to the phenotype of compound heterozygote xeroderma pigmentosum patients
Authors: Ueda Takahiro , Compe Emmanuel , Catez Philippe , Kraemer Kenneth H. , Egly Jean-Marc
Published: November 2009

Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in the rare recessive genetic disorder xeroderma pigmentosum (XP). Many XP patients are compound heterozygotes with a “causative” XPD point mutation R683W and different second mutant alleles, considered “null alleles.” However, there is marked clinical heterogeneity (including presence or absence of skin cancers or neurological degeneration) in these XPD/R683W patients, thus suggesting a contribution of the second allele. Here, we report XP patients carrying XPD/R683W and a second XPD allele either XPD/Q452X, /I455del, or /199insPP. We performed a systematic study of the effect of these XPD mutations on several enzymatic functions of TFIIH and found that each mutation exhibited unique biochemical properties. Although all the mutations inhibited the nucleotide excision repair (NER) by disturbing the XPD helicase function, each of them disrupted specific molecular steps during transcription: XPD/Q452X hindered the transactivation process, XPD/I455del disturbed RNA polymerase II phosphorylation, and XPD/199insPP inhibited kinase activity of the cdk7 subunit of TFIIH. The broad range and severity of clinical features in XP patients arise from a broad set of deficiencies in NER and transcription that result from the combination of mutations found on both XPD alleles.
Targeted Surveillance to Identify Children Colonized with Vancomycin-Resistant Enterococcus in the Pediatric Intensive Care Unit
Authors: Milstone Aaron M. , Maragakis Lisa L. , Carroll Karen C. , Perl Trish M.
Published: November 2009

Performing admission surveillance cultures is a resource-intensive strategy to identify asymptomatic patients with vancomycin-resistant Enterococcus (VRE) colonization. We measured VRE prevalence among children admitted to the pediatric intensive care unit. Targeted surveillance captured 94% of VRE-colonized children and may be an effective strategy to identify VRE carriers and facilitate pediatric infection prevention strategies.
Effects of colored noise on stochastic resonance in a tumor cell growth system
Authors: Wang Can-Jun
Published: November 2009

The phenomenon of stochastic resonance (SR) in the tumor cell growth model subjected to colored noise with a weakly periodic signal is investigated by using the theory of signal-to-noise ratio (SNR) in the adiabatic limit. The effects of the noise parameters (the multiplicative noise intensity D, the additive noise intensity α, the cross-correlated strength λ and the correlation time τ1, τ2 and τ3) are analyzed by numerical calculation. It is found that the existence of a maximum in the R
SNR–α plot, R
SNR–λ plot and R
SNR–D plot is the identifying characteristic of the SR phenomenon. The two peaks appear in the SNR-α curves simultaneously with the amplitude A increasing.