bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding design fluency: Motor and executive contributions
Authors: SUCHY YANA , KRAYBILL MATTHEW L. , GIDLEY LARSON JENNIFER C.
Published: October 2009

Design Fluency (DF) is typically assumed to assess planning, cognitive flexibility, and fluency in generation of visual patterns, above and beyond contributions from motor speed (Delis, Kaplan, & Kramer, 2001; Ruff, 1998). The present study examined these assumptions, as little construct validation research has been done in the past. Sixty one community-dwelling elderly participants were administered the DF, Trail Making, and Letter Fluency tests from the Delis-Kaplan Executive Function System (D-KEFS), as well as electronically administered measures of motor planning and motor sequence fluency. Hierarchical regressions were used to parse out unique variance contributions to DF performance. The results showed that generation of novel designs (i.e., the first two trials on the D-KEFS DF) relied primarily on motor planning, the ability to generate novel motor actions, and, to a lesser extent, speed of drawing with a writing implement. In contrast, generation of unique designs while switching (i.e., the third trial on the D-KEFS DF) relied primarily on visual scanning and perhaps visual-attentional resources. These findings highlight the wisdom of interpreting the switching trial of the D-KEFS DF separately. Interestingly, cognitive flexibility did not contribute to performance on any of the three D-KEFS DF trials. (JINS, 2010, 16, 26–37.)
Political party contestation over Europe in the mass media: who criticizes Europe, how, and why?
Authors: Statham Paul , Koopmans Ruud
Published: October 2009

This study examines political party contestation over Europe, its relationship to the left/right cleavage, and the nature and emergence of Euroscepticism. The analysis is based on a large original sample of parties’ claims systematically drawn from political discourses in the mass media in seven countries: Britain, France, Germany, the Netherlands, Italy, Spain, and Switzerland. It addresses questions concerning parties’ mobilized criticisms of European integration and the European Union (EU), specifically: their degree and form; their location among party families and within party systems; cross-national and diachronic trends; their substantive issue contents; whether their ‘Euro-criticism’ is more tactical or ideological; whether claims construct a cleavage; and their potential for transforming party politics. Findings show that a party’s country of origin has little explanatory power, once differences between compositions of party systems are accounted for. Also governing parties are significantly more likely to be pro-European, regardless of party-type. Regional party representatives, by contrast, are significantly more likely to be ‘Euro-critical’. Overall, we find a lop-sided ‘inverted U’ on the right of the political spectrum, but this is generated entirely by the significant, committed Euroscepticism of the British Conservatives andSchweizerische Volkspartei. There is relatively little evidence for Euroscepticism elsewhere at the core, where pro-Europeanism persists. Finally, parties’ Euro-criticism from the periphery mostly constructs substantive political and economic critiques of European integration and the EU, and is not reducible to strategic anti-systemic challenges.
Towards a post-secular political order?
Authors: Barbato Mariano , Kratochwil Friedrich
Published: October 2009

The ‘return of religion’ as a social phenomenon has aroused at least three different debates, with the first being the ‘clash of civilizations’, the second criticizing ‘modernity’, and the third focusing on the public/private distinction. This article uses Habermas’ idea of a post-secular society as a prism through which we examine the return of religion and impact on secularization. In doing so, we attempt to understand the new role of religion as a challenger of the liberal projects following the decline of communism. Against this background, section four focuses on Habermas’s central arguments in his proposal for a post-secular society. We claim that theproblematiquein Habermas’s analysis must be placed within the wider framework of an emerging global public sphere. In this context we examine the problem of religion’s place in political process and the two readings of Habermas as suggested by Simone Chambers.
Space environment of Mercury at the time of the first MESSENGER flyby: Solar wind and interplanetary magnetic field modeling of upstream conditions
Authors: Baker Daniel N. , Odstrcil Dusan , Anderson Brian J. , Arge C. Nick , Benna Mehdi , Gloeckler George , Raines Jim M. , Schriver David , Slavin James A. , Solomon Sean C. , Killen Rosemary M. , Zurbuchen Thomas H.
Published: October 2009

The first flyby of Mercury by the Mercury Surface, Space Environment, Geochemistry and Ranging (MESSENGER) spacecraft occurred on 14 January 2008. In order to provide contextual information about the solar wind (SW) properties and the interplanetary magnetic field near the planet, we have used an empirical modeling technique combined with a numerical physics‐based SW model. The Wang‐Sheeley‐Arge (WSA) method uses solar photospheric magnetic field observations (from Earth‐based instruments) in order to estimate inner heliospheric conditions out to 21.5 solar radii from the Sun. This information is then used as input to the global numerical magnetohydrodynamic model, ENLIL, which calculates SW velocity, density, temperature, and magnetic field strength and polarity throughout the inner heliosphere. The present paper shows WSA‐ENLIL conditions computed for the several week period encompassing the first flyby. This information is used in conjunction with MESSENGER magnetometer data (and the only limited available MESSENGER SW plasma data) to help understand the Mercury flyby results. The in situ spacecraft data, in turn, can also be used iteratively to improve the model accuracy for inner heliospheric “space weather” purposes. Looking to the future, we discuss how with such modeling we can estimate relatively continuously the SW properties near Mercury and at the cruise location of MESSENGER now, for upcoming flybys, and toward the time of spacecraft orbit insertion in 2011.
Scattering of near‐inertial internal waves along the Japanese coast of the Japan Sea
Authors: Igeta Yosuke , Kumaki Yutaka , Kitade Yujiro , Senjyu Tomoharu , Yamada Haruya , Watanabe Tatsuro , Katoh Osamu , Matsuyama Masaji
Published: October 2009

The scattering of near‐inertial internal waves (NIIWs) induced at the tips of landmasses was investigated by mooring observations using current meters and thermometers in the surface layer along peninsulas and an island located along the Japanese coast of the Japan Sea during the fall of 2006. Signals of NIIWs were found in alongshore currents and in temperatures recorded near the seasonal thermocline. The signals appeared after wind stress had reached a maximum, and they lasted for more than 2 days. Relatively high current energy regions due to NIIWs were localized around the northern parts of the peninsulas and island. The phase lag of the temperature fluctuations increased in the southern regions along the eastern coasts of the peninsulas and island. The generation and propagation of NIIWs were investigated by numerical experiments that used a multilayer level model with realistic topography. Model results showed that NIIWs induced by the wind struck the tips of landmasses and scattered and that NIIWs were trapped by the coast and propagated with characteristics of coastal‐trapped waves (CTWs) and then rapidly attenuated. The CTWs had a distorted current structure at landmass tips because of periodic beam‐like current structures from the seafloor. These signals show that CTWs radiate energy away from the shore as internal waves originating from topographical scattering, which is considered to cause the rapid attenuation of the CTWs.
A randomised controlled trial of an intervention to promote early presentation of breast cancer in older women: effect on breast cancer awareness
Authors: Linsell Louise , Forbes Lindsay , Kapari Marcia , Burgess Caroline , Omar Lynne , Tucker Lorraine , Ramirez Amanda
Published: October 2009

There is virtually no evidence for the effectiveness of interventions to promote early presentation in breast cancer. We tested the efficacy of an intervention to equip older women with the knowledge, skills, confidence and motivation to detect symptoms and seek help promptly, with the aim of promoting early presentation with breast cancer symptoms. We randomised 867 women aged 67 to 70 attending for their final routine appointment on the UK NHS Breast Screening Programme to receive: a scripted ten-minute interaction with a radiographer plus a booklet; a booklet alone; or usual care. The primary outcome was whether or not a woman was breast cancer aware based on knowledge of breast cancer symptoms and age-related risk; and reported breast checking. At one month, the intervention increased the proportion who were breast cancer aware compared with usual care (interaction arm: 32.8% versus 4.1%; odds ratio 24.0, 95% confidence interval 7.7 to 73.7; booklet arm: 12.7% versus 4.1%; odds ratio 4.4, 95% confidence interval 1.6 to 12.0). At one year, the effects of the interaction plus booklet, and the booklet, on breast cancer awareness were largely sustained, although the interaction plus booklet remained much more effective. Future research will evaluate whether the intervention promotes early presentation and reduces breast cancer mortality.
FTO Genotype and the Weight Loss Benefits of Moderate Intensity Exercise
Authors: Mitchell Jonathan A. , Church Timothy S. , Rankinen Tuomo , Earnest Conrad P. , Sui Xuemei , Blair Steven N.
Published: October 2009

The fat mass and obesity‐associated (FTO) gene was genotyped for the participants in the Dose‐Response to Exercise in postmenopausal Women (DREW) trial and analyses were performed to determine whether an FTO variant was associated with adiposity and cardiorespiratory fitness (CRF) before and after 6 months of moderate intensity exercise in white women (n = 234). The A/A homozygotes for rs8050136 had a higher BMI (kg/m2) compared to C/C homozygotes at baseline (32.8 (0.6) vs. 31.0 (0.4), respectively; P < 0.05) and at follow‐up (31.9 (0.6) vs. 30.4 (0.5), respectively; P < 0.05). Weight loss occurred after exercise, but there was no significant genotype by exercise interaction over time. Exploratory analyses among women exposed to moderate intensity exercise meeting, or exceeding, the physical activity recommendation found that those homozygous A/A lost significantly more weight than the C allele carriers (−3.3 (0.7) kg vs. −1.4 (0.4) kg and −1.5 (0.5) kg, respectively; P < 0.05). CRF, defined as VO2peak (oxygen consumption), increased after exercise and the magnitude of the increase was similar for each genotype. In conclusion, women genetically predisposed to being obese experienced weight loss and CRF benefits with moderate intensity exercise, with additional weight loss observed when the women met or exceeded the physical activity recommendations.
G-protein-coupled-receptor kinases mediate TNFα-induced NF-κB signalling via direct interaction with and phosphorylation of IκBα
Authors: Patial Sonika , Luo Jiansong , Porter Katie J. , Benovic Jeffrey L. , Parameswaran Narayanan
Published: October 2009

TNFα (tumour necrosis factor α) is a multifunctional cytokine involved in the pathophysiology of many chronic inflammatory diseases. TNFα activation of the NF-κB (nuclear factor κB) signalling pathway particularly in macrophages has been implicated in many diseases. We demonstrate in the present study that GRK2 and GRK5 (G-protein-coupled-receptor kinases 2 and 5) regulate TNFα-induced NF-κB signalling in Raw 264.7 macrophages. RNAi (RNA interference) knockdown of GRK2 or GRK5 in macrophages significantly inhibited TNFα-induced IκBα (inhibitory κBα) phosphorylation and degradation, NF-κB activation and expression of the NF-κB-regulated gene MIP1β (macrophage inflammatory protein 1β). Consistent with these results, overexpression of GRK2 or GRK5 enhanced TNFα-induced NF-κB activity. In addition, we show that GRK2 and GRK5 interacted with IκBα via the N-terminal domain of IκBα and that IκBα is a substrate for GRK2 and GRK5 in vitro. Furthermore, we also found that GRK5, but not GRK2, phosphorylated IκBα at the same amino acid residues (Ser32/Ser36) as that of IKKβ (IκB kinase β). Interestingly, associated with these results, knockdown of IKKβ in Raw 264.7 macrophages did not affect TNFα-induced IκBα phosphorylation. Taken together, these results demonstrate that both GRK2 and GRK5 are important and novel mediators of a non-traditional IκBα/NF-κB signalling pathway.
MicroRNA mir-346 targets the 5′-untranslated region of receptor-interacting protein 140 (RIP140) mRNA and up-regulates its protein expression
Authors: Tsai Nien-Pei , Lin Ya-Lun , Wei Li-Na
Published: October 2009

RIP140 (receptor-interacting protein 140) is a transcriptional co-repressor that regulates diverse genes such as those responsive to hormones and involved in metabolic processes. The expression of RIP140 is regulated by multiple hormonal activities in adipose tissue and cancer cell lines. However, it is unclear whether and how RIP140 is regulated post-transcriptionally. Using 5′RACE (rapid amplification of 5′ cDNA ends), we have identified a novel 5′ splice variant of RIP140 mRNA in mouse brain and P19 cells. A target sequence for miRNA (microRNA) mir-346 was found in the 5′UTR (5′-untranslated region) of RIP140 mRNA; this miRNA is also expressed endogenously in mouse brain and P19 cells. Gain- and loss-of-function studies demonstrated that mir-346 elevates RIP140 protein levels by facilitating association of its mRNA with the polysome fraction. Furthermore, the activity of mir346 does not require Ago-2 (Argonaute 2). The expression of mir-346 enhances the gene repressive activity of RIP140. This is the first report demonstrating post-transcriptional regulation of RIP140 mRNA, involving the enhancing effect of a specific miRNA that targets RIP140's 5′UTR.
Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition
Authors: Kirby Mark , Yu Denise M.T. , O'connor Steven , Gorrell Mark D.
Published: October 2009

DPP-4 (dipeptidyl peptidase-4) degrades the incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory polypeptide), decreasing their stimulatory effects on β-cell insulin secretion. In patients with Type 2 diabetes, meal-related GLP-1 secretion is reduced. DPP-4 inhibitors (alogliptin, saxagliptin, sitagliptin and vildagliptin) correct the GLP-1 deficiency by blocking this degradation, prolonging the incretin effect and enhancing glucose homoeostasis. DPP-4 is a member of a family of ubiquitous atypical serine proteases with many physiological functions beyond incretin degradation, including effects on the endocrine and immune systems. The role of DPP-4 on the immune system relates to its extra-enzymatic activities. The intracytosolic enzymes DPP-8 and DPP-9 are recently discovered DPP-4 family members. Although specific functions of DPP-8 and DPP-9 are unclear, a potential for adverse effects associated with DPP-8 and DPP-9 inhibition by non-selective DPP inhibitors has been posed based on a single adverse preclinical study. However, the preponderance of data suggests that such DPP-8 and DPP-9 enzyme inhibition is probably without clinical consequence. This review examines the structure and function of the DPP-4 family, associated DPP-4 inhibitor selectivity and the implications of DPP-4 inhibition in the treatment of Type 2 diabetes.
2D and 3D Representations for Feature Recognition in Time Geographical Diary Data
Authors: Vrotsou Katerina , Forsell Camilla , Cooper Matthew
Published: October 2009

Time geographical representations are becoming a common approach to analysing spatio-temporal data. Such representations appear intuitive in the process of identifying patterns and features as paths of populations form tracks through the 3D space, which can be seen converging and diverging over time. In this article, we compare 2D and 3D representations within a time geographical visual analysis tool for activity diary data. We identify a representative task and evaluate task performance between the two representations. The results show that the 3D representation has benefits over the 2D representation for feature identification but also indicate that these benefits can be lost if the 3D representation is not carefully constructed to help the user to see them.
Impedance spectroscopy investigation of conjugated polymer coated core-shell nanoparticles
Authors: Mpoukouvalas Konstantinos , Wang Jianjun , Tilch Robert , Butt Hans-Juergen , Wegner Gerhard
Published: October 2009

Poly(styrene) nanoparticles decorated at their surface with poly(styrene sulfonate) brushes and subsequently loaded with polypyrrole have been prepared as film-forming materials to serve as hole injection layers in organic light-emitting diodes. Thin compressed pellets of these nanoparticles have been studied by impedance spectroscopy. Measurements were carried out in the temperature range between 123.15 and 453.15 K and frequency range from 10−1 to 106 Hz. The polypyrrole volume fraction φPPy was varied as well. The film-forming nanoparticles exhibit a core-shell-type morphology with a core of electrically insulating poly(styrene) and a shell consisting of a corona of poly(styrene sulfonate) chains, which form the matrix in which the electrically conducting complex of polypyrrole and poly(styrene sulfonate) is embedded. This conducting complex exists in forms of domains with nanoscale dimensions. It is demonstrated that the charge transport in samples with φPPy [for the calculation of the polypyrrole volume fractions the poly(styrene) volume was excluded] lower than 0.52 is dominated by ionic conductivity. At higher volume fractions the charge transport is mainly electronic in nature. The fluctuation-induced tunneling model can be used to describe the temperature dependence of the dc conductivity. For a sample with φPPy of 0.52, a transition from insulating to conducting behavior at 385 K has been found. An electrical percolating behavior has been observed with a percolation threshold at φPPy of 0.65, suggesting that polypyrrole rich and poor domains are present in the poly(styrene sulfonate) matrix and indicating a “transition” from electronically insulating to conducting behavior. A detailed analysis of the impedance spectra suggests a lower limit of the conducting domains of 2.5 nm.
Phase stability of YbVO4 under pressure: In situ x-ray and Raman spectroscopic investigations
Authors: Garg Alka B. , Rao Rekha , Sakuntala T. , Wani B. N. , Vijayakumar V.
Published: October 2009

The phase stability of YbVO4 under pressure has been investigated using synchrotron based angle dispersive x-ray diffraction and Raman spectroscopic techniques up to 34.5 and 26.5 GPa, respectively. The results indicate that the compound transforms from the ambient pressure zircon structure to the scheelite structure above 5.9 GPa with 11.8% volume discontinuity. The coexistence of the two phases is observed over a large pressure range. At 15.8 GPa, the (011) peak of the scheelite phase develops asymmetry, and the pattern at further high pressures could be fitted to a fergusonite-type monoclinic structure. On reducing the pressure, the fergusonite phase reverses back to the scheelite phase; the latter phase could be recovered as a metastable phase at ambient pressure. The refined structural parameters along with the equation of state are given for various phases of YbVO4. Changes in the vibrational properties across these transitions, particularly across the scheelite↔fergusonite transition, have been investigated using Raman spectroscopy.
Charge transportation and permittivity in electron beam irradiated polymethyl methacrylate
Authors: Zheng Feihu , Zhang Yewen , Xia Junfeng , Xiao Chun , An Zhenlian
Published: October 2009

The charging phenomenon in the insulating dielectrics often occurs in the radiative environments such as in the outer space and in the nuclear reactor. Both surface charging and bulk charging have various influences on the dielectric properties. Understanding electrical properties of e-beam irradiated dielectrics is of great significance in order to maintain the stability and reliability of the related operating system. In this work, the effect of electron beam irradiation on the permittivity of polymethyl methacrylate (PMMA) samples was investigated. It was found that the variance of permittivity in e-beam irradiated PMMA is mainly determined by two factors. One is the porosity of the material. The irradiating process could increase the porosity of PMMA due to the escape of the small molecule (e.g., CO, CO2, and CH4) produced during material degradation caused by e-beam irradiation. The enhanced higher porosity corresponds to lower permittivity. The distribution of the implanted charge is the other factor that influences the permittivity. When the distribution of electric field generated by the accumulating charge is asymmetric for the middle thickness of the sample, the PMMA sample with polar groups would be subjected to extra polarization by the field, which could lead to the increase in permittivity. Combining with the model of Wakino et al. [J. Am. Ceram. Soc. 76, 2588 (1993)] on permittivity of mixture materials, the Clausius–Mosotti equation was utilized to analyze the variation in permittivity in the e-beam irradiated PMMA samples.
Optical emission spectra of chromium doped nanocrystalline zinc gallate
Authors: Dhak P. , Gayen U. K. , Mishra S. , Pramanik P. , Roy A.
Published: October 2009

Optical emission spectra of nanocrystalline zinc gallate (ZnGa2O4) and trivalent chromium ion doped zinc gallate (ZnGa2O4:Cr3+) are reported for different concentrations of the dopant ion. The measurements have been carried out over the temperature range between 77 and 296 K. The emission spectrum of nanocrystalline ZnGa2O4 shows two broad peaks. The intensity variation in these peaks, with temperature, is indicative of the effect of symmetry breaking in the electronic band structure of ZnGa2O4 in nanocrystalline samples. In addition, we find that the relative intensities of the sharp spectral lines of Cr3+ in nanocrystalline ZnGa2O4:Cr3+ are quite different from those reported for corresponding bulk samples. The spectral profiles of the so-called R1, R2, N1, and N2 lines have also been studied. The data are analyzed using crystal field theory, which includes an exchange interaction between the nearest neighbor Cr3+ pairs in ZnGa2O4. We estimate the exchange parameters for Cr3+ in nanocrystalline ZnGa2O4:Cr3+. Though, in the literature, there exist reports on optical properties of the corresponding bulk spinel, our approach and consequent results on nanocrystalline ZnGa2O4:Cr3+ are not only interesting from the physics point of view but also can be of use in nanotechnology.
Low energy cluster deposition of nanoalloys
Authors: Järvi T. T. , Kuronen A. , Nordlund K. , Albe K.
Published: October 2009

Low energy deposition of metal alloy nanoclusters is studied by molecular dynamics simulations. In a previous study, two mechanisms were introduced for epitaxial alignment of elemental clusters: The heating induced by the surface energy released upon impact and the thermally activated dislocation motion. In this study, these mechanisms are shown to dominate for Cu3Ag, Cu3Au, and Cu3Ni clusters as well. The question whether the alloyed nature of the system or the initial chemical ordering of the particles influences epitaxial alignment with a substrate is discussed. Chemical ordering is shown to have a negligible effect due to disordering occurring at the initial stages of deposition.
Dwell time in graphene-based magnetic barrier nanostructures
Authors: Gong Yiyang , Guo Yong
Published: October 2009

The authors have investigated the dwell time of electrons tunneling through nonuniform magnetically modulated graphene monolayer. Two types of models, i.e., the square magnetic barrier and the δ-function magnetic barrier, are introduced to simulate the magnetic modulation realized by depositing nanoscale ferromagnetic stripes on top of the graphene monolayer. It is found that both the dwell time and the transmission probability show remarkable anisotropy that varies in different magnetically modulated configurations. Particularly, when the electrons tunnel through the graphene monolayer modulated by two antiparallelly aligned ferromagnetic stripes, the corresponding transmission probability exhibits angularly symmetric property, whereas the dwell time does not. Moreover, there exists great discrepancy of the dwell time between in the Klein tunneling region and in the resonant tunneling region, where each region corresponds to the perfect transmission peaks.
Effect of dye concentrations in blended-layer white organic light-emitting devices based on phosphorescent dyes
Authors: Pearson C. , Cadd D. H. , Petty M. C. , Hua Y. L.
Published: October 2009

The electronic and optoelectronic behavior of white organic light-emitting devices (OLEDs) based on blue (FIrpic) and red [Ir(piq)2(acac)] phosphorescent dyes doped into the same layer of a polyvinylcarbazole (PVK) host are reported. The conductivity of all the OLEDs studied appeared to be dominated by space-charge injection effects, exhibiting a current I versus voltage V dependence of the form I∝Vn, with n≈7 at applied voltages at which electroluminescence was observed. Systematic studies of the current versus voltage and light-emitting behavior of the OLEDs have identified different excitation processes for the two dyes. It is suggested that electroluminescence from the FIrpic molecules originates by direct transfer of the exciton energy from the PVK to the dye molecules, while the process of light emission from the Ir(piq)2(acac) molecules involves carrier trapping. The efficiency of the devices can be tuned, to some extent, by varying the thickness of the organic film. Luminous efficiencies and luminous power efficiencies of 8 cd A−1 and 3 lm W−1 were measured for these blended-layer OLEDs, with Commission Internationale de l’Eclairage coordinates of 0.35, 0.35.
New technique for measuring carrier mobility using a modified boxcar integrator
Authors: Wee Kyung-Ryang , Han Won-sik , Son Ho-Jin , Kang Sang Ook , Kwon Soonnam
Published: October 2009

A new technique for measuring the drift carrier mobility is described. A boxcar integrator was modified to enable a delay-time scan using simple decimal counters. The transient photocurrent was integrated repeatedly using the modified boxcar integrator. After simple signal processing, the original photocurrent was recovered with enhanced signal to noise ratios. The hole mobility of a 4,4′-bis[N-(1-naphthyl)-N-phenylamino]biphenyl (NPB) thin film was measured using the new method. The mobility of NPB under an electric field as low as 2.5×104 V cm−1 was calculated to be 5.84×10−4 cm2 V−1 s−1. This method may be a useful measurement technique when either the electric field or signal to noise ratio is very low.
Effect of magnetic geometry on transport of neutral particles locally entering confined plasma volume
Authors: Tokar M. Z.
Published: October 2009

The effect of the position where neutral particles enter the confined plasma region with closed magnetic surfaces on the radial profiles of the neutral flux and plasma density is numerically investigated. The case of elongated magnetic surfaces with X-point, in whose vicinity the metric coefficients are varying very fast with the radius of magnetic surfaces, is considered.
Mostly recovered, the LHC readies for restart
Authors: Feder Toni
Published: October 2009

The LHC will run at reduced energy until its superconducting magnets are retrained and the connections between them fixed.
Color-tuned neurons are spatially clustered according to color preference within alert macaque posterior inferior temporal cortex
Authors: Conway Bevil R. , Tsao Doris Y.
Published: October 2009

Large islands of extrastriate cortex that are enriched for color-tuned neurons have recently been described in alert macaque using a combination of functional magnetic resonance imaging (fMRI) and single-unit recording. These millimeter-sized islands, dubbed “globs,” are scattered throughout the posterior inferior temporal cortex (PIT), a swath of brain anterior to area V3, including areas V4, PITd, and posterior TEO. We investigated the micro-organization of neurons within the globs. We used fMRI to identify the globs and then used MRI-guided microelectrodes to test the color properties of single glob cells. We used color stimuli that sample the CIELUV perceptual color space at regular intervals to test the color tuning of single units, and make two observations. First, color-tuned neurons of various color preferences were found within single globs. Second, adjacent glob cells tended to have the same color tuning, demonstrating that glob cells are clustered by color preference and suggesting that they are arranged in color columns. Neurons separated by 50 μm, measured parallel to the cortical sheet, had more similar color tuning than neurons separated by 100 μm, suggesting that the scale of the color columns is <100 μm. These results show that color-tuned neurons in PIT are organized by color preference on a finer scale than the scale of single globs. Moreover, the color preferences of neurons recorded sequentially along a given electrode penetration shifted gradually in many penetrations, suggesting that the color columns are arranged according to a chromotopic map reflecting perceptual color space.
Impaired tumor growth, metastasis, angiogenesis and wound healing in annexin A1-null mice
Authors: Yi Ming , Schnitzer Jan E.
Published: October 2009

Despite 2 decades of research, no clear function for annexin A1 (AnxA1) has been established. Using AnxA1-KO mice, we show that tumor growth and metastasis are significantly decreased, whereas rodent survival and tumor necrosis are greatly increased when tumors grow in AnxA1-KO mice. Systems analysis of gene expression in these tumors specifically implicates 2 related vascular functions, angiogenesis and wound healing, in this impairment. Both tumor vascular development and wound healing are greatly retarded in KO tissues. Aortic ring assays reveal induced AnxA1 expression on sprouting endothelial cells of normal mice whereas KO aortas exhibit impaired endothelial cell sprouting that is rescued by adenoviral expression of AnxA1. Key differences in specific gene regulation may define new molecular pathways mediating angiogenesis, including a reset profile of pro- versus anti-angiogenic factors, apparently distinct for physiological versus pathological angiogenesis. These studies establish novel pro-angiogenic functions for AnxA1 in vascular endothelial cell sprouting, wound healing, and tumor growth and metastasis, thereby uncovering a new functional target for repairing damaged tissue and treating diseases such as cancer. They also provide critical new evidence that the tumor stroma and its microenvironment can greatly affect tumor progression and metastasis.
Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels
Authors: Sander Edward A. , Stylianopoulos Triantafyllos , Tranquillo Robert T. , Barocas Victor H.
Published: October 2009

The mechanical environment plays an important role in cell signaling and tissue homeostasis. Unraveling connections between externally applied loads and the cellular response is often confounded by extracellular matrix (ECM) heterogeneity. Image-based multiscale models provide a foundation for examining the fine details of tissue behavior, but they require validation at multiple scales. In this study, we developed a multiscale model that captured the anisotropy and heterogeneity of a cell-compacted collagen gel subjected to an off-axis hold mechanical test and subsequently to biaxial extension. In both the model and experiments, the ECM reorganized in a nonaffine and heterogeneous manner that depended on multiscale interactions between the fiber networks. Simulations predicted that tensile and compressive fiber forces were produced to accommodate macroscopic displacements. Fiber forces in the simulation ranged from −11.3 to 437.7 nN, with a significant fraction of fibers under compression (12.1% during off-axis stretch). The heterogeneous network restructuring predicted by the model serves as an example of how multiscale modeling techniques provide a theoretical framework for understanding relationships between ECM structure and tissue-level mechanical properties and how microscopic fiber rearrangements could lead to mechanotransductive cell signaling.
An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense
Authors: Souza-Neto Jayme A. , Sim Shuzhen , Dimopoulos George
Published: October 2009

Here, we show that the major mosquito vector for dengue virus uses the JAK-STAT pathway to control virus infection. Dengue virus infection in
Aedes aegypti
mosquitoes activates the JAK-STAT immune signaling pathway. The mosquito's susceptibility to dengue virus infection increases when the JAK-STAT pathway is suppressed through RNAi depletion of its receptor Domeless (Dome) and the Janus kinase (Hop), whereas mosquitoes become more resistant to the virus when the negative regulator of the JAK-STAT pathway, PIAS, is silenced. The JAK-STAT pathway exerts its anti-dengue activity presumably through one or several STAT-regulated effectors. We have identified, and partially characterized, two JAK-STAT pathway-regulated and infection-responsive dengue virus restriction factors (DVRFs) that contain putative STAT-binding sites in their promoter regions. Our data suggest that the JAK-STAT pathway is part of the
A. aegypti
mosquito's anti-dengue defense and may act independently of the Toll pathway and the RNAi-mediated antiviral defenses.
Kinesin's step dissected with single-motor FRET
Authors: Verbrugge Sander , Lansky Zdenek , Peterman Erwin J. G.
Published: October 2009

The motor protein Kinesin-1 drives intracellular transport along microtubules, with each of its two motor domains taking 16-nm steps in a hand-over-hand fashion. The way in which a single-motor domain moves during a step is unknown. Here, we use Förster resonance energy transfer (FRET) between fluorescent labels on both motor domains of a single kinesin. This approach allows us to resolve the relative distance between the motor domains and their relative orientation, on the submillisecond timescale, during processive stepping. We observe transitions between high and low FRET values for certain kinesin constructs, depending on the location of the labels. These results reveal that, during a step, a kinesin motor domain dwells in a well-defined intermediate position for ≈3 ms.
Adaptive landscapes and protein evolution
Authors: Carneiro Maurício , Hartl Daniel L.
Published: October 2009

The principles governing protein evolution under strong selection are important because of the recent history of evolved resistance to insecticides, antibiotics, and vaccines. One experimental approach focuses on studies of mutant proteins and all combinations of mutant sites that could possibly be intermediates in the evolutionary pathway to resistance. In organisms carrying each of the engineered proteins, a measure of protein function or a proxy for fitness is estimated. The correspondence between protein sequence and fitness is widely known as a fitness landscape or adaptive landscape. Here, we examine some empirical fitness landscapes and compare them with simulated landscapes in which the fitnesses are randomly assigned. We find that mutant sites in real proteins show significantly more additivity than those obtained from random simulations. The high degree of additivity is reflected in a summary statistic for adaptive landscapes known as the “roughness,” which for the actual proteins so far examined lies in the smallest 0.5% tail of random landscapes.
Direct evidence of 1,900 years of indigenous silver production in the Lake Titicaca Basin of Southern Peru
Authors: Schultze Carol A. , Stanish Charles , Scott David A. , Rehren Thilo , Kuehner Scott , Feathers James K.
Published: October 2009

Archaeological excavations at a U-shaped pyramid in the northern Lake Titicaca Basin of Peru have documented a continuous 5-m-deep stratigraphic sequence of metalworking remains. The sequence begins in the first millennium AD and ends in the Spanish Colonial periodca.AD 1600. The earliest dates associated with silver production are 1960 ± 40 BP (2-sigma cal. 40 BC to AD 120) and 1870 ± 40 BP (2-sigma cal. AD 60 to 240) representing the oldest known silver smelting in South America. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) analysis of production debris indicate a complex, multistage, high temperature technology for producing silver throughout the archaeological sequence. These data hold significant theoretical implications including the following: (i) silver production occurred before the development of the first southern Andean state of Tiwanaku, (ii) the location and process of silverworking remained consistent for 1,500 years even though political control of the area cycled between expansionist states and smaller chiefly polities, and (iii) that U-shaped structures were the location of ceremonial, residential, and industrial activities.
Thrombospondin-1 is a critical effector of oncosuppressive activity of sst2 somatostatin receptor on pancreatic cancer
Authors: Laklai Hanane , Laval Séverine , Dumartin Laurent , Rochaix Philippe , Hagedorn Martin , Bikfalvi Andreas , Le Guellec Sophie , Delisle Marie-Bernadette , Schally Andrew V. , Susini Christiane , Pyronnet Stéphane , Bousquet Corinne
Published: October 2009

The somatostatin receptor subtype 2 (sst2) behaves as a tumor suppressor when expressed and stimulated by its ligand somatostatin in pancreatic cancer. We reveal a mechanism underlying oncosuppressive action of sst2, whereby this inhibitory receptor upregulates the expression of the secreted angioinhibitory factor thrombospondin-1 (TSP-1), as demonstrated in exocrine BxPC-3 and endocrine BON pancreatic cancer cells. The sst2-dependent upregulation of TSP-1 occurs through the inhibition of the PI3K pathway. It depends on transcriptional and translational events, involving a previously undescribed IRES in the 5′-UTR of TSP-1 mRNA. Chick chorioallantoic membrane was used as an in vivo model to demonstrate that TSP-1 is a critical effector of the inhibitory role of sst2 on the neoangiogenesis and oncogenesis induced by pancreatic cancer cells. TSP-1 reduced in vitro tubulogenesis of endothelial cells when grown in conditioned medium from pancreatic cancer cells expressing sst2, as compared to those expressing the control vector. TSP-1 inhibited tumor cell-induced neoangiogenesis by directly sequestering the proangiogenic factor VEGF, and inactivating the angiogenesis initiated by VEGFR2 phosphorylation in endothelial cells. Using human pancreatic tissue-microarrays, the expression of both sst2 and TSP-1 was shown to be correlated during the pancreatic neoplastic program. Both proteins are nearly undetectable in normal exocrine pancreas and in most invasive cancer lesions, but their expression is strikingly upregulated in most preinvasive cancer-adjacent lesions. The upregulation of both sst2 and TSP-1 tumor suppressors may function as an early negative feedback to restrain pancreatic carcinogenesis.
Membrane domains and flagellar pocket boundaries are influenced by the cytoskeleton in African trypanosomes
Authors: Gadelha Catarina , Rothery Stephen , Morphew Mary , McIntosh J. Richard , Severs Nicholas J. , Gull Keith
Published: October 2009

A key feature of immune evasion for African trypanosomes is the functional specialization of their surface membrane in an invagination known as the flagellar pocket (FP), the cell's sole site of endocytosis and exocytosis. The FP membrane is biochemically distinct yet continuous with those of the cell body and the flagellum. The structural features maintaining this individuality are not known, and we lack a clear understanding of how extracellular components gain access to the FP. Here, we have defined domains and boundaries on these surface membranes and identified their association with internal cytoskeletal features. The FP membrane appears largely homogeneous and uniformly involved in endocytosis. However, when endocytosis is blocked, receptor-mediated and fluid-phase endocytic markers accumulate specifically on membrane associated with four specialized microtubules in the FP region. These microtubules traverse a distinct boundary and associate with a channel that connects the FP lumen to the extracellular space, suggesting that the channel is the major transport route into the FP.
RETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
Authors: Lee KangAe , Zhang Huafeng , Qian David Z. , Rey Sergio , Liu Jun O. , Semenza Gregg L.
Published: October 2009

HIF-1 is a heterodimeric transcription factor that mediates adaptive responses to hypoxia and plays critical roles in cancer progression. Using a cell-based screening assay we have identified acriflavine as a drug that binds directly to HIF-1α and HIF-2α and inhibits HIF-1 dimerization and transcriptional activity. Pretreatment of mice bearing prostate cancer xenografts with acriflavine prevented tumor growth and treatment of mice bearing established tumors resulted in growth arrest. Acriflavine treatment inhibited intratumoral expression of angiogenic cytokines, mobilization of angiogenic cells into peripheral blood, and tumor vascularization. These results provide proof of principle that small molecules can inhibit dimerization of HIF-1 and have potent inhibitory effects on tumor growth and vascularization.
Predicted poxvirus FEN1-like nuclease required for homologous recombination, double-strand break repair and full-size genome formation
Authors: Senkevich Tatiana G. , Koonin Eugene V. , Moss Bernard
Published: October 2009

Poxviruses encode many if not all of the proteins required for viral genome replication in the cytoplasm of the host cell. In this context, we investigated the function of the vaccinia virus G5 protein because it belongs to the FEN1-like family of nucleases and is conserved in all poxviruses. A vaccinia virus G5 deletion mutant was severely impaired, as the yield of infectious virus was reduced by approximately two orders of magnitude. The mutant virions contained an apparently normal complement of proteins but appeared spherical rather than brick-shaped and contained no detectable DNA. The inability of G5 with substitutions of the predicted catalytic aspartates to complement the deletion mutant suggested that G5 functions as a nuclease during viral DNA replication. Although the amount of viral DNA produced in the absence of G5 was similar to that made by wild-type virus, the mean size was approximately one-fourth of the genome length. Experiments with transfected plasmids showed that G5 was required for double-strand break repair by homologous recombination, suggesting a similar role during vaccinia virus genome replication.
A selective contribution of the RIG-I-like receptor pathway to type I interferon responses activated by cytosolic DNA
Authors: Choi Myoung Kwon , Wang ZhiChao , Ban Tatsuma , Yanai Hideyuki , Lu Yan , Koshiba Ryuji , Nakaima Yukana , Hangai Sho , Savitsky David , Nakasato Makoto , Negishi Hideo , Takeuchi Osamu , Honda Kenya , Akira Shizuo , Tamura Tomohiko , Taniguchi Tadatsugu
Published: October 2009

The activation of the innate immune responses by DNA exposed within the cytosol has gained much attention and, in this context, several cytosolic DNA sensors have been identified. However, previous studies revealed the operation of redundant and complex mechanisms and it still remains to be clarified how the DNA-mediated evocation of diverse innate immune responses can be achieved. Here we show that two RIG-I-like receptors (RLRs), RIG-I and MDA5, known as cytosolic RNA receptors, nonredundantly function as cytosolic DNA receptors that lead to the selective activation of type I IFN genes. We demonstrate that overexpression of otherwise IFN-inducible RIG-I or MDA5 in IFN signal-deficient cells results in a marked enhancement of type I IFN gene induction upon cytosolic DNA stimulation, while in their absence the induction is impaired. Interestingly, the DNA-mediated induction of other cytokine genes was barely affected by the absence of RLRs. Indeed, unlike the RNA-RLR pathway that activates the transcription factors IRF3 and NF-κB, the DNA-RLR pathway is primarily responsible for the IRF3 activation critical for type I IFN gene transcription, illustrating a deliberate divergence of the DNA signaling pathways. Expectedly, the RLR pathway also contributes to intricate innate immune responses against infection by a DNA virus. Our study may provide insights into the complexity of host defense mechanisms that thwart immune evasion by DNA-containing pathogens.
Monkey drumming reveals common networks for perceiving vocal and nonvocal communication sounds
Authors: Remedios Ryan , Logothetis Nikos K. , Kayser Christoph
Published: October 2009

Salient sounds such as those created by drumming can serve as means of nonvocal acoustic communication in addition to vocal sounds. Despite the ubiquity of drumming across human cultures, its origins and the brain regions specialized in processing such signals remain unexplored. Here, we report that an important animal model for vocal communication, the macaque monkey, also displays drumming behavior, and we exploit this finding to show that vocal and nonvocal communication sounds are represented by overlapping networks in the brain's temporal lobe. Observing social macaque groups, we found that these animals use artificial objects to produce salient periodic sounds, similar to acoustic gestures. Behavioral tests confirmed that these drumming sounds attract the attention of listening monkeys similarly as conspecific vocalizations. Furthermore, in a preferential looking experiment, drumming sounds influenced the way monkeys viewed their conspecifics, suggesting that drumming serves as a multimodal signal of social dominance. Finally, by using high-resolution functional imaging we identified those brain regions preferentially activated by drumming sounds or by vocalizations and found that the representations of both these communication sounds overlap in caudal auditory cortex and the amygdala. The similar behavioral responses to drumming and vocal sounds, and their shared neural representation, suggest a common origin of primate vocal and nonvocal communication systems and support the notion of a gestural origin of speech and music.
Resolving the paradox of Singapore English hor
Authors: Kim Chonghyuck , Wee Lionel
Published: October 2009

In this paper, we present paradoxical properties of the discourse particle hor in Singapore English and attempt to resolve them. Hor has been described as an attenuator of illocutionary force, which is used to convert statements and commands into questions and requests. We provide a new observation that it can also be used as a booster of illocutionary force to make strong statements and demands. We claim that these paradoxical properties are consequences of hor’s nature to mark a nonstandard discourse context in which there is an asymmetry in epistemic or deontic authority between speaker and hearer vis-à-vis a proposition. In a context where epistemic / deontic authority for a proposition lies with the speaker, hor serves as a booster of illocutionary force. In a context where such authority rests with the hearer, hor serves as an attenuator.