bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeatability of lifetime exercise reporting
Authors: Ropponen A. , Levälahti E. , Simonen R. , Videman T. , Battié M. C.
Published: October 2010

The purpose of the study was to determine the reliability of lifetime exercise data obtained through a structured interview. Interviews were conducted in 1992–1993 and repeated in 1997 in 150 monozygotic male twins, aged 35–69 years, from the population‐based Finnish Twin Cohort. Exercise mode, frequency, duration, intensity and period of participation were solicited for each regularly performed exercise from 12 years of age to the present. Questions related to the most common exercise mode reported in the initial interview were repeated in all subjects and the entire exercise interview was repeated in a subgroup of 38 subjects. The repeatability was highest for exercise years and mean hours/week by mode for the most commonly performed exercise (Mean ICC=0.63–0.90), and for the sum of all lifetime exercises reported (Mean ICC=0.69–0.73). The lowest repeatability was found for exercise intensity (Mean Kappa=0.33–0.48). Similarly poor reliability was found for whether or not exercise was performed at a competitive level (Mean Kappa=0.25–0.63). Overall, the structured interview of lifetime exercise was most repeatable for years of exercise and mean hours/week. Thus, these exposure variables should be considered in retrospective studies of exercise effects.
A Review of the it Outsourcing Empirical Literature and Future Research Directions
Authors: Lacity Mary C , Khan Shaji , Yan Aihua , Willcocks Leslie P
Published: October 2010

An enormous amount of information has been produced about the IT outsourcing phenomenon over the last 20 years, but one has to look to the academic literature for consistent, objective, and reliable research approaches and analyses. Our review finds that, In practice, the academic literature on IT outsourcing has very much honored both rigor and relevance In the ways In which research has been conducted. Our central purpose In the review was to answer two research questions: What has the empirical academic literature found about information technology outsourcing (ITO) decisions and outcomes? What are the gaps In knowledge to consider In future ITO research? To answer these questions, we examined 164 empirical ITO articles published between 1992 and 2010 In 50 journals. Adapting a method used by Jeyaraj et al. (2006), we encapsulated this vast empirical literature on ITO In a way that was concise, meaningful, and helpful to researchers. We coded 36 dependent variables, 138 independent variables, and 741 relationships between Independent and dependent variables. By extracting the best evidence, we developed two models of outsourcing: one model addressed ITO decisions and one model addressed ITO outcomes. The model of ITO decisions includes Independent variables associated with motives to outsource, transaction attributes, client firm characteristics, and influence sources. The model of ITO outcomes includes Independent variables associated with client and supplier capabilities, relationship characteristics, contractual governance, decision characteristics, and transaction attributes. We also examined the interactions among broad categories of variables and the learning curve effects resulting from feedback loops. Overall, ITO researchers have a broad and deep understanding of ITO. However, the field continues to evolve as clients and suppliers on every inhabited continent participate actively in the global sourcing community. There is still much research yet to be done. We reviewed recent studies that have identified gaps in current knowledge and proposed future paths of research pertaining to strategic motivations, environmental influences, dynamic interactions, configurational and portfolio approaches, global destinations, emerging models, reference theory extension, and grounded theory development.
Design of a cavity ring-down spectroscopy diagnostic for negative ion rf source SPIDER
Authors: Pasqualotto R. , Alfier A. , Lotto L.
Published: October 2010

The rf source test facility SPIDER will test and optimize the source of the 1 MV neutral beam injection systems for ITER. Cavity ring-down spectroscopy (CRDS) will measure the absolute line-of-sight integrated density of negative (H− and D−) ions, produced in the extraction region of the source. CRDS takes advantage of the photodetachment process: negative ions are converted to neutral hydrogen atoms by electron stripping through absorption of a photon from a laser. The design of this diagnostic is presented with the corresponding simulation of the expected performance. A prototype operated without plasma has provided CRDS reference signals, design validation, and results concerning the signal-to-noise ratio.
Collective Thomson scattering measurements with high frequency resolution at TEXTOR
Authors: Stejner M. , Nielsen S. K. , Korsholm S. B. , Salewski M. , Bindslev H. , Furtula V. , Leipold F. , Meo F. , Michelsen P. K. , Moseev D. , Bürger A. , Kantor M. , de Baar M.
Published: October 2010

We discuss the development and first results of a receiver system for the collective Thomson scattering (CTS) diagnostic at TEXTOR with frequency resolution in the megahertz range or better. The improved frequency resolution expands the diagnostic range and utility of CTS measurements in general and is a prerequisite for measurements of ion Bernstein wave signatures in CTS spectra. The first results from the new acquisition system are shown to be consistent with theory and with simultaneous measurements by the standard receiver system.
Two color multichannel heterodyne interferometer set up for high spatial resolution electron density profile measurements in TJ-II
Authors: Pedreira P. , Esteban L. , Criado A. R. , Acedo P. , Sánchez M. , Sánchez J.
Published: October 2010

A high spatial resolution two color [CO2, λ=10.6 μm/Nd:YAG (Nd:YAG denotes neodymium-doped yttrium aluminum garnet), and λ=1.064 μm] expanded-beam multichannel heterodyne interferometer has been installed on the TJ-II stellarator. Careful design of the optical system has allowed complete control on the evolution of both Gaussian beams along the interferometer, as well as the evaluation and optimization of the spatial resolution to be expected in the measurements. Five CO2 (measurement) channels and three Nd:YAG (vibration compensation) channels have been used to illuminate the plasma with a probe beam of 100 mm size. An optimum interpolation method has been applied to recover both interferometric phasefronts prior to mechanical vibration subtraction. The first results of the installed diagnostic are presented in this paper.
Knowledge-based probabilistic representations of branching ratios in chemical networks: The case of dissociative recombinations
Authors: Plessis Sylvain , Carrasco Nathalie , Pernot Pascal
Published: October 2010

Experimental data about branching ratios for the products of dissociative recombination of polyatomic ions are presently the unique information source available to modelers of natural or laboratory chemical plasmas. Yet, because of limitations in the measurement techniques, data for many ions are incomplete. In particular, the repartition of hydrogen atoms among the fragments of hydrocarbons ions is often not available. A consequence is that proper implementation of dissociative recombination processes in chemical models is difficult, and many models ignore invaluable data. We propose a novel probabilistic approach based on Dirichlet-type distributions, enabling modelers to fully account for the available information. As an application, we consider the production rate of radicals through dissociative recombination in an ionospheric chemistry model of Titan, the largest moon of Saturn. We show how the complete scheme of dissociative recombination products derived with our method dramatically affects these rates in comparison with the simplistic H-loss mechanism implemented by default in all recent models.
Shell-anchor-core structures for enhanced stability and catalytic oxygen reduction activity
Authors: Ramirez-Caballero Gustavo E. , Hirunsit Pussana , Balbuena Perla B.
Published: October 2010

Density functional theory is used to evaluate activity and stability properties of shell-anchor-core structures. The structures consist of a Pt surface monolayer and a composite core having an anchor bilayer where C atoms in the interstitial sites lock 3d metals in their locations, thus avoiding their surface segregation and posterior dissolution. The modified subsurface geometry induces less strain on the top surface, thus exerting a favorable effect on the surface catalytic activity where the adsorption strength of the oxygenated species becomes more moderate: weaker than on pure Pt(111) but stronger than on a Pt monolayer having a 3d metal subsurface. Here we analyze the effect of changing the nature of the 3d metal in the subsurface anchor bilayer, and we also test the use of a Pd monolayer instead of Pt on the surface. It is found that a subsurface constituted by two layers with an approximate composition of M2C (M=Fe, Ni, and Co) provides a barrier for the migration of subsurface core metal atoms to the surface. Consequently, an enhanced resistance against dissolution in parallel to improved oxygen reduction activity is expected, as given by the values of adsorption energies of reaction intermediates, delayed onset of water oxidation, and/or low coverage of oxygenated species at surface oxidation potentials.
The height of a static liquid column pulled out of an infinite pool
Authors: Benilov E. S. , Oron A.
Published: October 2010

We consider a solid cone whose vertex points down and dips in an infinite pool of liquid. If the cone is slowly lifted, a liquid column with its top attached to the cone is pulled out of the pool. In this paper, we compute the maximum height of the cone before the column ruptures. Two reasons for rupturing are identified. In some cases, no solution for a higher position of the cone exists. In other cases, a solution does exist, but is unstable.
Nonlinear piezoelectricity in electroelastic energy harvesters: Modeling and experimental identification
Authors: Stanton Samuel C. , Erturk Alper , Mann Brian P. , Inman Daniel J.
Published: October 2010

We propose and experimentally validate a first-principles based model for the nonlinear piezoelectric response of an electroelastic energy harvester. The analysis herein highlights the importance of modeling inherent piezoelectric nonlinearities that are not limited to higher order elastic effects but also include nonlinear coupling to a power harvesting circuit. Furthermore, a nonlinear damping mechanism is shown to accurately restrict the amplitude and bandwidth of the frequency response. The linear piezoelectric modeling framework widely accepted for theoretical investigations is demonstrated to be a weak presumption for near-resonant excitation amplitudes as low as 0.5 g in a prefabricated bimorph whose oscillation amplitudes remain geometrically linear for the full range of experimental tests performed (never exceeding 0.25% of the cantilever overhang length). Nonlinear coefficients are identified via a nonlinear least-squares optimization algorithm that utilizes an approximate analytic solution obtained by the method of harmonic balance. For lead zirconate titanate (PZT-5H), we obtained a fourth order elastic tensor component of c1111p=−3.6673×1017 N/m2 and a fourth order electroelastic tensor value of e3111=1.7212×108 m/V.
Short and intermediate range order of Ge20Se80−xTex glasses
Authors: Moharram A. H. , Hefni M. A. , Abdel-Baset A. M.
Published: October 2010

The total structure factor, S(K), have been obtained for the chalcogenide Ge20Se80−xTex (where x=0, 10, 20, and 30 at. %) glasses using x-ray diffraction in the wave vector interval 0.28≤K≤6.87 Å−1. The appearance of the first sharp diffraction peak in the structure factor indicates the presence of the intermediate range order. The radii of the first- and second-coordination shells (r1,r2) are increased linearly with Te addition. The large covalent radius of Te atom in compare with that of Se atom was behind the above linear increase. The first coordination number shows insignificant changes with Te content. The obtained values of r1/r2 ratio and the corresponding bond angle (Θ) indicate that the structural units inside the present alloys are Ge(Se1/2)4 tetrahedra connected by chains of the chalcogen atoms. Raman spectra confirm the above conclusion and in the same time exclude the existence of Ge(Te1/2)4 tetrahedra. Based on the chemical ordered network mode, Te–Te bonds are responsible for the different behavior of Te-rich (30 at. %) glass from others.
The temperature dependent anisotropy constants of epitaxially grown PrCo5+x
Authors: Patra A. K. , Eisterer M. , Biele R. , Fähler S. , Schultz L. , Neu V.
Published: October 2010

The temperature dependent anisotropy of a highly textured epitaxial Pr–Co film with a single orientation of the crystallographic c-axis along MgO[001] is investigated by measuring angle dependent hysteresis loops at various temperatures. The measured magnetization curves are compared with calculated magnetization curves, which allows for a full analysis of the temperature dependent anisotropy constants of first and second order, K1 and K2 and the determination of the saturation polarization. The analysis reveals that the Pr15.4Co84.6 film undergoes a spin reorientation transition from an easy axis anisotropy to an easy cone anisotropy at 108 K. The room temperature values of K1 and K2 measured for this Pr15.4Co84.6 film are 5.0 MJ m−3 and 0.5 MJ m−3, respectively. The difference to the bulk PrCo5 single crystal values is ascribed to the high Co content of the Pr15.4Co84.6 film.
Semipolar single component GaN on planar high index Si(11h) substrates
Authors: Ravash Roghaiyeh , Blaesing Juergen , Dadgar Armin , Krost Alois
Published: October 2010

We present metal organic vapor phase epitaxy growth of polarization reduced, single component GaN on nonpatterned Si(112), Si(113), Si(114), Si(115), and Si(116) substrates. We find that the inclination angle of GaN c-axis with respect to the surface normal depends on the angle between Si(111) and above mentioned Si(11h)-surfaces. The growth of the GaN layer is essentially performed as c-axis oriented growth on the naturally occurring Si(111) facets of these Si(11h)-surfaces. The c-axis tilt-angle of GaN crystallites depends on the Si-surface direction and increases from Si(112) to Si(116) planes. GaN layers are investigated by x-ray analysis and scanning electron microscopy.
Persistent photoconductivity in Hf–In–Zn–O thin film transistors
Authors: Ghaffarzadeh Khashayar , Nathan Arokia , Robertson John , Kim Sangwook , Jeon Sanghun , Kim Changjung , Chung U-In , Lee Je-Hun
Published: October 2010

Passivated Hf–In–Zn–O (HIZO) thin film transistors suffer from a negative threshold voltage shift under visible light stress due to persistent photoconductivity (PPC). Ionization of oxygen vacancy sites is identified as the origin of the PPC following observations of its temperature- and wavelength-dependence. This is further corroborated by the photoluminescence spectrum of the HIZO. We also show that the gate voltage can control the decay of PPC in the dark, giving rise to a memory action.
Switching and defect dynamics in multistable liquid crystal devices
Authors: Tiribocchi A. , Gonnella G. , Marenduzzo D. , Orlandini E.
Published: October 2010

We investigate the switching dynamics of multistable nematic liquid crystal devices. In particular, we identify a remarkably simple two-dimensional device which exploits hybrid alignment at the surfaces to yield a bistable response. We also consider a three-dimensional tristable nematic device with patterned anchoring, recently implemented in practice, and discuss how the director and disclination patterns change during switching.
A discretely tunable multifrequency source injection locked to a spectral-mode-filtered fiber laser comb
Authors: Ryu Han Young , Lee Sung Hun , Kim Eok Bong , Suh Ho Suhng , Moon Han Seb
Published: October 2010

We present a discretely tunable multifrequency source injection locked to an optical frequency comb (OFC) based on the spectral-mode-filtered femtosecond fiber laser. The spectral-mode-filtered OFC with a 1.5 GHz mode spacing, which is based on an femtosecond fiber laser (FSFL) with 250 MHz mode spacing, was achieved using the spectral-mode-filtering method with a Fabry–Pérot cavity. With the spectral-mode-filtered OFC as the master laser and two distributed-feedback lasers as the slave lasers, we simultaneously selected and amplified the desired modes of the OFC using the IL technique. We generated the coherent multifrequency optical source to synthesize in the frequency range from gigahertz to terahertz.
Analysis of the physical processes responsible for the degradation of deep-ultraviolet light emitting diodes
Authors: Meneghini Matteo , Barbisan Diego , Rodighiero Luca , Meneghesso Gaudenzio , Zanoni Enrico
Published: October 2010

This paper reports an extensive analysis of the degradation of deep-ultraviolet light-emitting diodes submitted to dc stress test. The study was carried out by means of combined electrical and optical characterization techniques. Results described in the paper indicate that the following: (i) stress can induce a significant decrease in the optical power emitted by the devices; (ii) optical power decrease is more prominent at low measuring current levels, thus suggesting that degradation is related to an increase in the concentration of defects; (iii) stress induces a significant increase in the green-yellow parasitic emission of the devices; and (iv) stress causes a localized increase in the apparent charge distribution profiles in the active region of the devices. Experimental evidence collected within this work suggest that degradation is due to an increase in the defectiveness in the active layer of the devices, with subsequent worsening of their radiative efficiency.
Retinal light trapping in textured photovoltaic cells
Authors: Kravets V. G. , Grigorenko A. N.
Published: October 2010

We suggest a new structure for light trapping in solar cells which is loosely based on retina of human eye. In this design, the incident light is scattered by noble metal nanoparticles acting as amacrine retinal cells and then is guided and concentrated by conelike structures. We show that the proposed textured structure should lead to a significant enhancement of optical path of trapped light resulting in a higher degree of light conversion into electric current. The proposed design should work efficiently in direct sunlight and in cloudy weather.
Ferroelectricity in nonstoichiometric SrTiO3 films studied by ultraviolet Raman spectroscopy
Authors: Tenne D. A. , Farrar A. K. , Brooks C. M. , Heeg T. , Schubert J. , Jang H. W. , Bark C. W. , Folkman C. M. , Eom C. B. , Schlom D. G.
Published: October 2010

Homoepitaxial Sr1+xTiO3+δ films with −0.2≤x≤0.25 grown by reactive molecular-beam epitaxy on SrTiO3 (001) substrates have been studied by ultraviolet Raman spectroscopy. Nonstoichiometry for strontium-deficient compositions leads to the appearance of strong first-order Raman scattering at low temperatures, which decreases with increasing temperature and disappears at about 350 K. This indicates the appearance of a spontaneous polarization with a paraelectric-to-ferroelectric transition temperature above room temperature. Strontium-rich samples also show a strong first-order Raman signal, but the peaks are significantly broader and exhibit a less pronounced temperature dependence, indicating a stronger contribution of the disorder-activated mechanism in Raman scattering.
Low temperature electrostatic force microscopy of a deep two-dimensional electron gas using a quartz tuning fork
Authors: Hedberg J. A. , Lal A. , Miyahara Y. , Grütter P. , Gervais G. , Hilke M. , Pfeiffer L. , West K. W.
Published: October 2010

Using an ultralow temperature, high magnetic field scanning probe microscope, we have measured electric potentials of a deeply buried two-dimensional electron gas (2DEG). Relying on the capacitive coupling between the 2DEG and a resonant tip/cantilever structure, we can extract electrostatic potential information of the 2DEG from the dynamics of the oscillator. We present measurements using a quartz tuning fork oscillator and a 2DEG with a cleaved edge overgrowth structure. The sensitivity of the quartz tuning fork as force sensor is demonstrated by observation of Shubnikov–de Haas oscillations at a large tip-2DEG separation distance of more than 500 nm.
Impacts of wind farms on surface air temperatures
Authors: Baidya Roy Somnath , Traiteur Justin J.
Published: October 2010

Utility-scale large wind farms are rapidly growing in size and numbers all over the world. Data from a meteorological field campaign show that such wind farms can significantly affect near-surface air temperatures. These effects result from enhanced vertical mixing due to turbulence generated by wind turbine rotors. The impacts of wind farms on local weather can be minimized by changing rotor design or by siting wind farms in regions with high natural turbulence. Using a 25-y-long climate dataset, we identified such regions in the world. Many of these regions, such as the Midwest and Great Plains in the United States, are also rich in wind resources, making them ideal candidates for low-impact wind farms.
Structure of bacterial cellulose synthase subunit D octamer with four inner passageways
Authors: Hu Song-Qing , Gao Yong-Gui , Tajima Kenji , Sunagawa Naoki , Zhou Yong , Kawano Shin , Fujiwara Takaaki , Yoda Takanori , Shimura Daisuke , Satoh Yasuharu , Munekata Masanobu , Tanaka Isao , Yao Min
Published: October 2010

The cellulose synthesizing terminal complex consisting of subunits A, B, C, and D in
Acetobacter xylinum
spans the outer and inner cell membranes to synthesize and extrude glucan chains, which are assembled into subelementary fibrils and further into a ribbon. We determined the structures of subunit D (AxCeSD/AxBcsD) with both N- and C-terminal His
6
tags, and in complex with cellopentaose. The structure of AxCeSD shows an exquisite cylinder shape (height: ∼65 
Å
, outer diameter: ∼90 
Å
, and inner diameter: ∼25 
Å
) with a right-hand twisted dimer interface on the cylinder wall, formed by octamer as a functional unit. All N termini of the octamer are positioned inside the AxCeSD cylinder and create four passageways. The location of cellopentaoses in the complex structure suggests that four glucan chains are extruded individually through their own passageway along the dimer interface in a twisted manner. The complex structure also shows that the N-terminal loop, especially residue Lys6, seems to be important for cellulose production, as confirmed by in vivo assay using mutant cells with
axcesD
gene disruption and N-terminus truncation. Taking all results together, a model of the bacterial terminal complex is discussed.
Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones
Authors: Yuen William W. , Du Nan R. , Chan Chun H. , Silva Eduardo A. , Mooney David J.
Published: October 2010

Nature frequently utilizes opposing factors to create a stable activator gradient to robustly control pattern formation. This study employs a biomimicry approach, by delivery of both angiogenic and antiangiogenic factors from spatially restricted zones of a synthetic polymer to achieve temporally stable and spatially restricted angiogenic zones in vivo. The simultaneous release of the two spatially separated agents leads to a spatially sharp angiogenic region that is sustained over 3 wk. Further, the contradictory action of the two agents leads to a stable level of proangiogenic stimulation in this region, in spite of significant variations in the individual release rates over time. The resulting spatially restrictive and temporally sustained profiles of active signaling allow the creation of a spatially heterogeneous and functional vasculature.
Forecasting potential global environmental costs of livestock production 2000–2050
Authors: Pelletier Nathan , Tyedmers Peter
Published: October 2010

Food systems—in particular, livestock production—are key drivers of environmental change. Here, we compare the contributions of the global livestock sector in 2000 with estimated contributions of this sector in 2050 to three important environmental concerns: climate change, reactive nitrogen mobilization, and appropriation of plant biomass at planetary scales. Because environmental sustainability ultimately requires that human activities as a whole respect critical thresholds in each of these domains, we quantify the extent to which current and future livestock production contributes to published estimates of sustainability thresholds at projected production levels and under several alternative endpoint scenarios intended to illustrate the potential range of impacts associated with dietary choice. We suggest that, by 2050, the livestock sector alone may either occupy the majority of, or significantly overshoot, recently published estimates of humanity’s “safe operating space” in each of these domains. In light of the magnitude of estimated impacts relative to these proposed (albeit uncertain) sustainability boundary conditions, we suggest that reining in growth of this sector should be prioritized in environmental governance.
Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models
Authors: Liu Huiping , Patel Manishkumar R. , Prescher Jennifer A. , Patsialou Antonia , Qian Dalong , Lin Jiahui , Wen Susanna , Chang Ya-Fang , Bachmann Michael H. , Shimono Yohei , Dalerba Piero , Adorno Maddalena , Lobo Neethan , Bueno Janet , Dirbas Frederick M. , Goswami Sumanta , Somlo George , Condeelis John , Contag Christopher H. , Gambhir Sanjiv Sam , Clarke Michael F.
Published: October 2010

To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy.
Structure, function, and folding of phosphoglycerate kinase are strongly perturbed by macromolecular crowding
Authors: Dhar Apratim , Samiotakis Antonios , Ebbinghaus Simon , Nienhaus Lea , Homouz Dirar , Gruebele Martin , Cheung Margaret S.
Published: October 2010

We combine experiment and computer simulation to show how macromolecular crowding dramatically affects the structure, function, and folding landscape of phosphoglycerate kinase (PGK). Fluorescence labeling shows that compact states of yeast PGK are populated as the amount of crowding agents (Ficoll 70) increases. Coarse-grained molecular simulations reveal three compact ensembles: C (crystal structure), CC (collapsed crystal), and Sph (spherical compact). With an adjustment for viscosity, crowded wild-type PGK and fluorescent PGK are about 15 times or more active in 200 mg/ml Ficoll than in aqueous solution. Our results suggest a previously undescribed solution to the classic problem of how the ADP and diphosphoglycerate binding sites of PGK come together to make ATP: Rather than undergoing a hinge motion, the ADP and substrate sites are already located in proximity under crowded conditions that mimic the in vivo conditions under which the enzyme actually operates. We also examine T-jump unfolding of PGK as a function of crowding experimentally. We uncover a nonmonotonic folding relaxation time vs. Ficoll concentration. Theory and modeling explain why an optimum concentration exists for fastest folding. Below the optimum, folding slows down because the unfolded state is stabilized relative to the transition state. Above the optimum, folding slows down because of increased viscosity.
Prefrontal cortex and basal ganglia contributions to visual working memory
Authors: Voytek Bradley , Knight Robert T.
Published: October 2010

Visual working memory (VWM) is a remarkable skill dependent on the brain's ability to construct and hold an internal representation of the world for later comparison with an external stimulus. The prefrontal cortex (PFC) and basal ganglia (BG) interact within a cortical and subcortical network supporting VWM. We used scalp electroencephalography in groups of patients with unilateral PFC or BG lesions to provide evidence that these regions play complementary but dissociable roles in VWM. PFC patients show behavioral and electrophysiological deficits manifested by attenuation of extrastriate attention and VWM-related neural activity only for stimuli presented to the contralesional visual field. In contrast, patients with BG lesions show behavioral and electrophysiological VWM deficits independent of the hemifield of stimulus presentation but have intact extrastriate attention activity. The results support a model wherein the PFC is critical for top-down intrahemispheric modulation of attention and VWM with the BG involved in global support of VWM processes.
In an early branching metazoan, bacterial colonization of the embryo is controlled by maternal antimicrobial peptides
Authors: Fraune Sebastian , Augustin René , Anton-Erxleben Friederike , Wittlieb Jörg , Gelhaus Christoph , Klimovich Vladimir B. , Samoilovich Marina P. , Bosch Thomas C. G.
Published: October 2010

Early embryos of many organisms develop outside the mother and are immediately confronted with myriads of potential colonizers. How these naive developmental stages control and shape the bacterial colonization is largely unknown. Here we show that early embryonic stages of the basal metazoan
Hydra
are able to control bacterial colonization by using maternal antimicrobial peptides. Antimicrobial peptides of the periculin family selecting for a specific bacterial colonization during embryogenesis are produced in the oocyte and in early embryos. If overexpressed in hydra ectodermal epithelial cells, periculin1a drastically reduces the bacterial load, indicating potent antimicrobial activity. Unexpectedly, transgenic polyps also revealed that periculin, in addition to bactericidal activity, changes the structure of the bacterial community. These findings delineate a role for antimicrobial peptides both in selecting particular bacterial partners during development and as important components of a “be prepared” strategy providing transgenerational protection.
Long-running German panel survey shows that personal and economic choices, not just genes, matter for happiness
Authors: Headey Bruce , Muffels Ruud , Wagner Gert G.
Published: October 2010

Psychologists and economists take contradictory approaches to research on what psychologists call happiness or subjective well-being, and economists call subjective utility. A direct test of the most widely accepted psychological theory, set-point theory, shows it to be flawed. Results are then given, using the economists’ newer “choice approach”—an approach also favored by positive psychologists—which yields substantial payoffs in explaining long-term changes in happiness. Data come from the German Socio-Economic Panel (1984–2008), a unique 25-y prospective longitudinal survey. This dataset enables direct tests of theories explaining long-term happiness.
Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by
O
6
-alkylguanine adducts in
Escherichia coli
Authors: Mazon Gerard , Philippin Gaëlle , Cadet Jean , Gasparutto Didier , Modesti Mauro , Fuchs Robert P.
Published: October 2010

O
6
-alkylG adducts are highly mutagenic due to their capacity to efficiently form
O
6
-alkylG:T mispairs during replication, thus triggering G→A transitions. Mutagenesis is largely prevented by repair strategies such as reversal by alkyltransferases or excision by nucleotide excision repair (NER). Moreover, methyl-directed mismatch repair (MMR) is known to trigger sensitivity to methylating agents via a mechanism that involves recognition by MutS of the
O
6
-mG:T replication intermediates. We wanted to investigate the mechanism by which MMR controls the genotoxicity of environmentally relevant
O
6
-alkylG adducts formed by ethylene oxide and propylene oxide. Recently, the alkyltransferase-like gene
ybaZ
(eATL) was shown to enhance repair of these slightly larger
O
6
-alkylG adducts by NER. We analyzed the toxicity and mutagenesis induced by these
O
6
-alkylG adducts using single-adducted plasmid probes. We show that the eATL gene product prevents MMR-mediated attack of the
O
6
-alkylG:T replication intermediate for the larger alkyl groups but not for methyl. In vivo data are compatible with the occurrence of repeated cycles of MMR attack of the
O
6
-alkylG:T intermediate. In addition, in vitro, the eATL protein efficiently prevents binding of MutS to the
O
6
-alkylG:T mispairs formed by the larger alkyl groups but not by methyl. In conclusion, eATL not only enhances the efficiency of repair of these larger adducts by NER, it also shields these adducts from MMR-mediated toxicity.
Endocytosis is required for Toll signaling and shaping of the Dorsal/NF-κB morphogen gradient during
Drosophila
embryogenesis
Authors: Lund Viktor K. , DeLotto Yvonne , DeLotto Robert
Published: October 2010

Dorsoventral cell fate in the
Drosophila
embryo is specified by activation of the Toll receptor, leading to a ventral-to-dorsal gradient across nuclei of the NF-κB transcription factor Dorsal. Toll receptor has been investigated genetically, molecularly, and immunohistologically, but much less is known about its dynamics in living embryos. Using live imaging of fluorescent protein chimeras, we find that Toll is recruited from the plasma membrane to Rab5
+
early endosomes. The distribution of a constitutively active form of Toll, Toll
10b
, is shifted from the plasma membrane to early endosomes. Inhibition of endocytosis on the ventral side of the embryo attenuates Toll signaling ventrally and causes Dorsal to accumulate on the dorsal side of the embryo, essentially inverting the dorsal/ventral axis. Conversely, enhancing endocytosis laterally greatly potentiates Toll signaling locally, altering the shape of the Dorsal gradient. Photoactivation and fluorescence recovery after photobleaching studies reveal that Toll exhibits extremely limited lateral diffusion within the plasma membrane, whereas Toll is highly compartmentalized in endosomes. When endocytosis is blocked ventrally, creating an ectopic dorsal signaling center, Toll is preferentially endocytosed at the ectopic signaling center. We propose that Toll signals from an endocytic compartment rather than the plasma membrane. Our studies reveal that endocytosis plays a pivotal role in the spatial regulation of Toll receptor activation and signaling and in the correct shaping of the nuclear Dorsal concentration gradient.
Initiation context modulates autoregulation of eukaryotic translation initiation factor 1 (eIF1)
Authors: Ivanov Ivaylo P. , Loughran Gary , Sachs Matthew S. , Atkins John F.
Published: October 2010

The central feature of standard eukaryotic translation initiation is small ribosome subunit loading at the 5′ cap followed by its 5′ to 3′ scanning for a start codon. The preferred start is an AUG codon in an optimal context. Elaborate cellular machinery exists to ensure the fidelity of start codon selection. Eukaryotic initiation factor 1 (eIF1) plays a central role in this process. Here we show that the translation of eIF1 homologs in eukaryotes from diverse taxa involves initiation from an AUG codon in a poor context. Using human eIF1 as a model, we show that this poor context is necessary for an autoregulatory negative feedback loop in which a high level of eIF1 inhibits its own translation, establishing that variability in the stringency of start codon selection is used for gene regulation in eukaryotes. We show that the stringency of start codon selection (preferential utilization of optimal start sites) is increased to a surprising degree by overexpressing eIF1. The capacity for the cellular level of eIF1 to impact initiation through the variable stringency of initiation codon selection likely has significant consequences for the proteome in eukaryotes.
Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization
Authors: Hou Jianghui , Renigunta Aparna , Yang Jing , Waldegger Siegfried
Published: October 2010

Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. The paracellular pathway in the collecting duct of the kidney is a predominant route for transepithelial chloride reabsorption that determines the extracellular NaCl content and the blood pressure. However, the molecular mechanisms underlying the paracellular chloride reabsorption in the collecting duct are not understood. Here we showed that in mouse kidney collecting duct cells, claudin-4 functioned as a Cl
–
channel. A positively charged lysine residue at position 65 of claudin-4 was critical for its anion selectivity. Claudin-4 was observed to interact with claudin-8 using several criteria. In the collecting duct cells, the assembly of claudin-4 into TJ strands required its interaction with claudin-8. Depletion of claudin-8 resulted in the loss of paracellular chloride conductance, through a mechanism involving its recruitment of claudin-4 during TJ assembly. Together, our data show that claudin-4 interacts with claudin-8 and that their association is required for the anion-selective paracellular pathway in the collecting duct, suggesting a mechanism for coupling chloride reabsorption with sodium reabsorption in the collecting duct.
Surprising flexibility in a conserved Hox transcription factor over 550 million years of evolution
Authors: Heffer Alison , Shultz Jeffrey W. , Pick Leslie
Published: October 2010

Although metazoan body plans are remarkably diverse, the structure and function of many embryonic regulatory genes are conserved because large changes would be detrimental to development. However, the
fushi tarazu
(
ftz
) gene has changed dramatically during arthropod evolution from
Hox
-like to a pair-rule segmentation gene in
Drosophila
. Changes in both expression and protein sequence contributed to this new function:
ftz
expression switched from
Hox
-like to stripes and changes in Ftz cofactor interaction motifs led to loss of homeotic and gain of segmentation potential. Here, we reconstructed
ftz
changes in a rigorous phylogenetic context. We found that
ftz
did not simply switch from
Hox
-like to segmentation function; rather,
ftz
is remarkably labile, having undergone multiple changes in sequence and expression. The segmentation LXXLL motif was stably acquired in holometabolous insects after the appearance of striped expression in early insect lineages. The homeotic YPWM motif independently degenerated multiple times. These “degen-YPWMs” showed varying degrees of homeotic potential when expressed in
Drosophila,
suggesting variable loss of
Hox
function in different arthropods. Finally, the intensity of
ftz Hox
-like expression decreased to marginal levels in some crustaceans. We propose that decreased expression levels permitted
ftz
variants to arise and persist in populations without disadvantaging organismal development. This process, in turn, allowed evolutionary transitions in protein function, as weakly expressed “hopeful gene variants” were coopted into alternative developmental pathways. Our findings show that variation of a pleiotropic transcription factor is more extensive than previously imagined, suggesting that evolutionary plasticity may be widespread among regulatory genes.
Correction of respiratory disorders in a mouse model of Rett syndrome
Authors: Abdala Ana P. L. , Dutschmann Mathias , Bissonnette John M. , Paton Julian F. R.
Published: October 2010

Rett syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked gene that encodes the transcription factor methyl-CpG-binding protein 2 (MeCP2). A major debilitating phenotype in affected females is frequent apneas, and heterozygousMecp2-deficient female mice mimic the human respiratory disorder. GABA defects have been demonstrated in the brainstem of Mecp2-deficient mice. Here, using an intact respiratory network, we show that apnea in RTT mice is characterized by excessive excitatory activity in expiratory cranial and spinal nerves. Augmenting GABA markedly improves the respiratory phenotype. In addition, a serotonin 1a receptor agonist that depresses expiratory neuron activity also reduces apnea, corrects the irregular breathing pattern, and prolongs survival in MeCP2 null males. Combining a GABA reuptake blocker with a serotonin 1a agonist in heterozygous females completely corrects their respiratory defects. The results indicate that GABA and serotonin 1a receptor activity are candidates for treatment of the respiratory disorders in Rett syndrome.
Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes
Authors: Colombo Sergio L. , Palacios-Callender Miriam , Frakich Nanci , De Leon Joel , Schmitt Christoph A. , Boorn Leanne , Davis Nicola , Moncada Salvador
Published: October 2010

Cell proliferation is accompanied by an increase in the utilization of glucose and glutamine. The proliferative response is dependent on a decrease in the activity of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdh1 which controls G1-to-S-phase transition by targeting degradation motifs, notably the KEN box. This occurs not only in cell cycle proteins but also in the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), as we have recently demonstrated in cells in culture. We now show that APC/C-Cdh1 controls the proliferative response of human T lymphocytes. Moreover, we have found that glutaminase 1 is a substrate for this ubiquitin ligase and appears at the same time as PFKFB3 in proliferating T lymphocytes. Glutaminase 1 is the first enzyme in glutaminolysis, which converts glutamine to lactate, yielding intermediates for cell proliferation. Thus APC/C-Cdh1 is responsible for the provision not only of glucose but also of glutamine and, as such, accounts for the critical step that links the cell cycle with the metabolic substrates essential for its progression.
Three-dimensional tracking of single mRNA particles in
Saccharomyces cerevisiae
using a double-helix point spread function
Authors: Thompson Michael A. , Casolari Jason M. , Badieirostami Majid , Brown Patrick O. , Moerner W. E.
Published: October 2010

Optical imaging of single biomolecules and complexes in living cells provides a useful window into cellular processes. However, the three-dimensional dynamics of most important biomolecules in living cells remains essentially uncharacterized. The precise subcellular localization of mRNA-protein complexes plays a critical role in the spatial and temporal control of gene expression, and a full understanding of the control of gene expression requires precise characterization of mRNA transport dynamics beyond the optical diffraction limit. In this paper, we describe three-dimensional tracking of single mRNA particles with 25-nm precision in the
x
and
y
dimensions and 50-nm precision in the
z
dimension in live budding yeast cells using a microscope with a double-helix point spread function. Two statistical methods to detect intermittently confined and directed transport were used to quantify the three-dimensional trajectories of mRNA for the first time, using
ARG3
mRNA as a model. Measurements and analysis show that the dynamics of
ARG3
mRNA molecules are mostly diffusive, although periods of non-Brownian confinement and directed transport are observed. The quantitative methods detailed in this paper can be broadly applied to the study of mRNA localization and the dynamics of diverse other biomolecules in a wide variety of cell types.
Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities
Authors: Merkel Tod J. , Perera Pin-Yu , Kelly Vanessa K. , Verma Anita , Llewellyn Zara N. , Waldmann Thomas A. , Mosca Joseph D. , Perera Liyanage P.
Published: October 2010

Bioterrorism poses a daunting challenge to global security and public health in the 21st century.
Variola major
virus, the etiological agent of smallpox, and
Bacillus anthracis
, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. Although licensed vaccines are available for both smallpox and anthrax, because of inadequacies associated with each of these vaccines, serious concerns remain as to the deployability of these vaccines, especially in the aftermath of a bioterror attack involving these pathogens. We have developed a single vaccine (Wyeth/IL-15/PA) using the licensed Wyeth smallpox vaccine strain that is efficacious against both smallpox and anthrax due to the integration of immune-enhancing cytokine IL-15 and the protective antigen (PA) of
B. anthracis
into the Wyeth vaccinia virus. Integration of IL-15 renders Wyeth vaccinia avirulent in immunodeficient mice and enhances anti-vaccinia immune responses. Wyeth/IL-15/PA conferred sterile protection against a lethal challenge of
B. anthracis
Ames strain spores in rabbits. A single dose of Wyeth/IL-15/PA protected 33% of the vaccinated A/J mice against a lethal spore challenge 72 h later whereas a single dose of licensed anthrax vaccine protected only 10%. Our dual vaccine Wyeth/IL-15/PA remedies the inadequacies associated with the licensed vaccines, and the inherent ability of Wyeth vaccinia virus to be lyophilized without loss of potency makes it cold-chain independent, thus simplifying the logistics of storage, stockpiling, and field delivery in the event of a bioterror attack involving smallpox or anthrax.
A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota
Authors: Chinen Takatoshi , Volchkov Pavel Y. , Chervonsky Alexander V. , Rudensky Alexander Y.
Published: October 2010

Suppression mediated by regulatory T cells (T reg cells) represents a unique, cell-extrinsic mechanism of in-trans negative regulation that restrains multiple types of immune cells. The loss of T reg cells leads to fatal, highly aggressive, and widespread immune-mediated lesions. This severe autoimmunity may be driven by commensal microbiota, the largest source of non-self ligands activating the innate and adaptive immune systems. Alternatively, T reg cells may primarily restrain T cells with a diverse self–major histocompatibility complex (MHC)–restricted T cell receptor repertoire independently of commensal microbiota. In this study, we demonstrate that in germ-free (GF) mice, ablation of the otherwise fully functional T reg cells resulted in a systemic autoimmune lympho- and myeloproliferative syndrome and tissue inflammation comparable with those in T reg cell–ablated conventional mice. Importantly, there were two exceptions: in GF mice deprived of T reg cells, the inflammation in the small intestine was delayed, whereas exocrine pancreatitis was markedly accelerated compared with T reg cell–ablated conventional mice. These findings suggest that the main function of T reg cells is restraint of self-MHC–restricted T cell responsiveness, which, regardless of the presence of commensal microbiota, poses a threat of autoimmunity.