bluuebunny/crossref_metadata_2025 huggingface dataset:
Distraction
Authors: Young Damon
Published: February 2013

In Distraction, the philosopher Damon Young explores distraction in our lives, and shows that distraction is not simply too many stimuli. Instead, its a confusion about what to attend to and why. If we are dying already, as Heidegger cheerily put it, then we only have so many days to invest. To commit to this job, this spouse, this leisure, this gadget means withdrawing time, energy and wherewithal from other possibilities. In an age of innumerable, intense diversions, Young argues, we need to be clearer than ever about what is important, and not be waylaid when seeking it. Drawing on the lives of luminaries like Seneca, Henri Matisse, Karl Marx, T. S. Eliot, and Henry James, Young takes us on a fascinating journey into the heart of distraction. In an engaging and witty analysis, he explores the nature of work and free time, the challenges of technology, the deceptions of politics, art as an antidote to distraction, and the importance of caring for ourselves without retreating from others. Young clarifies his subject with the work of thinkers including Nietzsche, Foucault, Heidegger, Marcuse, Bourdieu, and Schiller, but always in a lively and accessible way. Young argues that distraction is a basic impediment to freedom: the freedom to pursue a life of ones own. The opposite of distraction is a life of liberty, which takes up the challenge of existence; the struggle to flourish within the limitations of mortality. For anyone whos ever imagined a less restless, fractured life, it will be inspiring reading.
The Problem of Free Will
Authors: Iredale Mathew
Published: February 2013

Whether human choices and actions are causally determined or are in a way free is one of the trickiest questions in philosophy. Undaunted, Mathew Iredale presents a clear, comprehensive and concise introduction to the topic. What sets this book apart is its focus on the positions currently jostling for acceptance rather than on the more familiar historical debates. The book explores what it is about the free will problem that makes it so intractable and argues that the only acceptable solution must be one consistent with what science tells us about the world. It is here, maintains Iredale, that many works on free will, introductory or otherwise, fall down, by focusing only on how free will relates to determinism. He shows that there are clear areas of scientific research which are directly and significantly relevant to free will in a way that does not involve determinism. Although these areas of scientific research may not allow us to solve the problem, they do enable us to separate the more plausible ideas concerning free will from the less plausible.
β1‐adrenergic receptor antagonists signal via PDE4 translocation
Authors: Richter Wito , Mika Delphine , Blanchard Elise , Day Peter , Conti Marco
Published: February 2013

It is generally assumed that antagonists of Gs‐coupled receptors do not activate cAMP signalling, because they do not stimulate cAMP production via Gs‐protein/adenylyl cyclase activation. Here, we report a new signalling pathway whereby antagonists of β1‐adrenergic receptors (β1ARs) increase cAMP levels locally without stimulating cAMP production directly. Binding of antagonists causes dissociation of a preformed complex between β1ARs and Type‐4 cyclic nucleotide phosphodiesterases (PDE4s). This reduces the local concentration of cAMP‐hydrolytic activity, thereby increasing submembrane cAMP and PKA activity. Our study identifies receptor/PDE4 complex dissociation as a novel mechanism of antagonist action that contributes to the pharmacological properties of β1AR antagonists and might be shared by other receptor subtypes.
Design of a high-speed electrochemical scanning tunneling microscope
Authors: Yanson Y. I. , Schenkel F. , Rost M. J.
Published: February 2013

In this paper, we present a bottom-up approach to designing and constructing a high-speed electrochemical scanning tunneling microscope (EC-STM). Using finite element analysis (FEA) calculations of the frequency response of the whole mechanical loop of the STM, we analyzed several geometries to find the most stable one that could facilitate fast scanning. To test the FEA results, we conducted measurements of the vibration amplitudes using a prototype STM setup. Based on the FEA analysis and the measurement results, we identified the potentially most disturbing vibration modes that could impair fast scanning. By modifying the design of some parts of the EC-STM, we reduced the amplitudes as well as increased the resonance frequencies of these modes. Additionally, we designed and constructed an electrochemical flow-cell that allows STM imaging in a flowing electrolyte, and built a bi-potentiostat to achieve electrochemical potential control during the measurements. Finally, we present STM images acquired during high-speed imaging in air as well as in an electrochemical environment using our newly-developed EC-STM.
Sensitivity calibration of an imaging extreme ultraviolet spectrometer-detector system for determining the efficiency of broadband extreme ultraviolet sources
Authors: Fuchs S. , Rödel C. , Krebs M. , Hädrich S. , Bierbach J. , Paz A. E. , Kuschel S. , Wünsche M. , Hilbert V. , Zastrau U. , Förster E. , Limpert J. , Paulus G. G.
Published: February 2013

We report on the absolute sensitivity calibration of an extreme ultraviolet (XUV) spectrometer system that is frequently employed to study emission from short-pulse laser experiments. The XUV spectrometer, consisting of a toroidal mirror and a transmission grating, was characterized at a synchrotron source in respect of the ratio of the detected to the incident photon flux at photon energies ranging from 15.5 eV to 99 eV. The absolute calibration allows the determination of the XUV photon number emitted by laser-based XUV sources, e.g., high-harmonic generation from plasma surfaces or in gaseous media. We have demonstrated high-harmonic generation in gases and plasma surfaces providing 2.3 μW and μJ per harmonic using the respective generation mechanisms.
Modeling molecular response in uniform and non-uniform electric fields
Authors: Morris Michael , Jordan Meredith J. T.
Published: February 2013

The response of a molecule to an electric field E, often a model of environment, can be expressed in terms of a sum of power series expansions. We investigate the accuracy and limits of applicability of this expression using one-, two-, and three-dimensional models of the hydrogen-bonded complex, ClH:NH3. Energetic, structural, and vibrational spectroscopic characteristics are determined at first- and second-order in E and ∇E and compared with ab initio values for a range of uniform and non-uniform electric fields chosen to simulate molecular environments. It is found that even at field strengths large enough to cause dramatic structural change in the complex, energetic, structural, and vibrational spectroscopic characteristics are accurately calculated using only terms linear in E and ∇E. These results suggest that knowledge of the zero-field molecular potential energy, dipole, and quadrupole moment surfaces may be sufficient to accurately model the interaction of a molecule with a wide range of chemical environments.
Molecular noise induces concentration oscillations in chemical systems with stable node steady states
Authors: Toner D. L. K. , Grima R.
Published: February 2013

It is well known that internal or molecular noise induces concentration oscillations in chemical systems whose deterministic models exhibit damped oscillations. In this article we show, using the linear-noise approximation of the chemical master equation, that noise can also induce oscillations in systems whose deterministic descriptions admit no damped oscillations, i.e., systems with a stable node. This non-intuitive phenomenon is remarkable since, unlike noise-induced oscillations in systems with damped deterministic oscillations, it cannot be explained by noise excitation of the deterministic resonant frequency of the system. We here prove the following general properties of stable-node noise-induced oscillations for systems with two species: (i) the upper bound of their frequency is given by the geometric mean of the real eigenvalues of the Jacobian of the system, (ii) the upper bound of the Q-factor of the oscillations is inversely proportional to the distance between the real eigenvalues of the Jacobian, and (iii) these oscillations are not necessarily exhibited by all interacting chemical species in the system. The existence and properties of stable-node oscillations are verified by stochastic simulations of the Brusselator, a cascade Brusselator reaction system, and two other simple chemical systems involving auto-catalysis and trimerization. It is also shown how external noise induces stable node oscillations with different properties than those stimulated by internal noise.
Electronic structure, surface morphology, and topologically protected surface states of Sb2Te3 thin films grown on Si(111)
Authors: Plucinski L. , Herdt A. , Fahrendorf S. , Bihlmayer G. , Mussler G. , Döring S. , Kampmeier J. , Matthes F. , Bürgler D. E. , Grützmacher D. , Blügel S. , Schneider C. M.
Published: February 2013

We have performed a combined spectroscopy and microscopy study on surfaces of Sb2Te3/Si(111) thin films exposed to air and annealed under ultra-high vacuum conditions. Scanning tunneling microscopy images, with atomic resolution present in most areas of such processed surfaces, show a significant amount of impurities and defects. Scanning tunneling spectroscopy reveals the bulk band gap of ∼170 meV centered ∼65 meV above the Fermi level. This intrinsic p-type doping behavior is confirmed by high-resolution angle-resolved photoemission spectra, which show the dispersions of the lower Dirac cone and the spectral weight of the bulk valence bands crossing the Fermi level. Spin-polarized photoemission revealed up to ∼15% in-plane spin polarization for photoelectrons related to the topologically protected Dirac cone states near the Fermi level, and up to ∼40% for several states at higher binding energies. The results are interpreted using ab initio electronic structure simulations and confirm the robustness of the time-reversal symmetry protected topological surface states in Sb2Te3 in the presence of impurities and defects.
Enhancing the efficiency of SnS solar cells via band-offset engineering with a zinc oxysulfide buffer layer
Authors: Sinsermsuksakul Prasert , Hartman Katy , Bok Kim Sang , Heo Jaeyeong , Sun Leizhi , Hejin Park Helen , Chakraborty Rupak , Buonassisi Tonio , Gordon Roy G.
Published: February 2013

SnS is a promising earth-abundant material for photovoltaic applications. Heterojuction solar cells were made by vapor deposition of p-type tin(II) sulfide, SnS, and n-type zinc oxysulfide, Zn(O,S), using a device structure of soda-lime glass/Mo/SnS/Zn(O,S)/ZnO/ITO. A record efficiency was achieved for SnS-based thin-film solar cells by varying the oxygen-to-sulfur ratio in Zn(O,S). Increasing the sulfur content in Zn(O,S) raises the conduction band offset between Zn(O,S) and SnS to an optimum slightly positive value. A record SnS/Zn(O,S) solar cell with a S/Zn ratio of 0.37 exhibits short circuit current density (Jsc), open circuit voltage (Voc), and fill factor (FF) of 19.4 mA/cm2, 0.244 V, and 42.97%, respectively, as well as an NREL-certified total-area power-conversion efficiency of 2.04% and an uncertified active-area efficiency of 2.46%.
Quasimonoenergetic proton bunches generation from doped foil targets irradiated by intense lasers
Authors: Cui Yun-Qian , Wang Wei-Min , Sheng Zheng-Ming , Li Yu-Tong , Zhang Jie
Published: February 2013

We propose a scheme to generate 10 MeV-level quasimonoenergetic proton bunches using proton-doped heavy-ion targets irradiated by intense lasers via target normal sheath acceleration. The heavy substrate ions provide a long-life quasi-stable sheath field to accelerate the doped protons at the target rear and consequently a quasimonoenergetic proton bunch is produced. The scheme is demonstrated by two-dimensional particle-in-cell simulations. An exemplificative simulation with parameters of targets made by ion-implant technique, a kind of modern doping process, gives a quasimonoenergetic bunch with peak energy ∼13MeV, energy spread ∼24%, and ∼nC charge at the focused laser intensity 1020W/cm2.
In-situ observation of nickel oxidation using synchrotron based full-field transmission X-ray microscopy
Authors: Kiss Andrew M. , Harris William M. , Wang Steve , Vila-Comamala Joan , Deriy Alex , Chiu Wilson K. S.
Published: February 2013

An in situ imaging-based approach is reported to study chemical reactions using full-field transmission x-ray microscopy (TXM). Ni particles were oxidized at temperatures between 400 and 850 °C in the TXM to directly observe their morphology change while the chemical composition is monitored by x-ray absorption near edge spectroscopy. Reaction rates and activation energies are calculated from the image data. The goal of this effort is to better understand Ni oxidation in electrode materials. The approach developed will be an effective technique for directly studying chemical reactions of particles and their behavior at the nano-scale.
Homogeneous and stable p-type doping of graphene by MeV electron beam-stimulated hybridization with ZnO thin films
Authors: Song Wooseok , Kim Yooseok , Hwan Kim Sung , Youn Kim Soo , Cha Myoung-Jun , Song Inkyung , Sung Jung Dae , Jeon Cheolho , Lim Taekyung , Lee Sumi , Ju Sanghyun , Chel Choi Won , Wook Jung Min , An Ki-Seok , Park Chong-Yun
Published: February 2013

In this work, we demonstrate a unique and facile methodology for the homogenous and stable p-type doping of graphene by hybridization with ZnO thin films fabricated by MeV electron beam irradiation (MEBI) under ambient conditions. The formation of the ZnO/graphene hybrid nanostructure was attributed to MEBI-stimulated dissociation of zinc acetate dihydrate and a subsequent oxidation process. A ZnO thin film with an ultra-flat surface and uniform thickness was formed on graphene. We found that homogeneous and stable p-type doping was achieved by charge transfer from the graphene to the ZnO film.
High-pressure synthesis and in-situ high pressure x-ray diffraction study of cadmium tetraphosphide
Authors: Wang Pei , Peng Fang , Lei Li , Chen Haihua , Wang Qiming , Xu Chao , Liu Ke , Ran Xiangtian , Wang Jianghua , Tang Mingjun , Wang Wendan , Liu Jing , He Duanwei
Published: February 2013

Pure-phase polycrystalline cadmium tetraphosphide (CdP4) has been successfully synthesized under high pressures in a large volume cubic press, and the pressure–temperature (P-T) formation boundary of CdP4 from the Cd–P binary system has been determined. The equation of state of monoclinic CdP4 has also been evaluated by synchrotron-radiation angle-dispersive X-ray diffraction (ADXRD) under quasihydrostatic compression up to 26.4 GPa in a diamond-anvil cell. The ADXRD data yield a bulk modulus B0 = 94 ± 9 GPa with a pressure derivative B0′ = 8.0. The experimental data are discussed and compared to the results of first-principles calculations.
A microlens array based on polymer network liquid crystal
Authors: Xu Miao , Zhou Zuowei , Ren Hongwen , Hee Lee Seung , Wang Qionghua
Published: February 2013

Using UV light to expose a homogeneous cell containing liquid crystal (LC)/monomer mixture through a patterned photomask, we prepared a polymer network liquid crystal (PNLC) microlens array. In each microlens, the formed polymer network presents a central-symmetrical inhomogeneous morphology and LC exhibits a gradient refractive index distribution. By applying an external voltage to the cell, the gradient of the LC refractive index is changed. As a result, the focal length of the microlens can be tuned. Our PNLC microlens array has the advantages of low operating voltage, easy fabrication, and good stability. This kind of microlens array has potential applications in image processing, optical communications, and switchable 2D/3D displays.
Length dependence of carbon-doped BN nanowires: A-D Rectification and a route to potential molecular devices
Authors: Qiu M. , Liew K. M.
Published: February 2013

Based on the first-principles approach, electronic transport properties of different lengths of carbon-doped boron-nitrogen nanowires, capped with two thiols as end groups connected to Au electrodes surfaces, are investigated. The results show that rectifying performance and negative differential resistance (NDR) behaviors can be enhanced obviously by increasing the length. Analysis of Mülliken population, transmission spectra, evolutions of frontier orbitals and molecular projected self-consistent Hamiltonian of molecular orbital indicate that electronic transmission strength, charge transfer and distributions of molecular states change are the intrinsic origin of these rectifying performances and NDR behaviors.
Evaluation of field emission parameters in a copper nano-tip based diode
Authors: Kumar Singh Abhishek , Kumar Jitendra
Published: February 2013

Copper nano-tip based diode structure with a gap of ∼120 nm has been fabricated by milling of a thin metallic film with a 30 kV focused gallium ion beam at a current of 100 pA. Its current-voltage characteristics measured at a pressure of ∼10−6 mbar is shown to follow the Fowler-Nordheim (F-N) field emission tunneling above ∼40 V. A simple method has been proposed to evaluate parameters like effective area (Aeff), apparent work function (ϕ), and field enhancement factor (β) of the nano-emitter. The extremely small Aeff, substantial lowering of ϕ, and high β value observed have been explained in terms of changes occurring at the emitter tip with increasing applied field. The formation of metallic nanoparticles over the substrate by local evaporation of cathode material at high currents is also demonstrated.
Nitric acid compensated aluminum oxide dielectrics with improved negative bias reliability and positive bias temperature response
Authors: Lin Chien-Chih , Hwu Jenn-Gwo
Published: February 2013

The room-temperature nitric acid (HNO3) compensation method is introduced to effectively improve the dielectric quality of ultrathin aluminum oxide (Al2O3) gate dielectrics under low thermal budget consideration. The physical properties, electrical characteristics, and temperature response of Al2O3 metal-oxide-semiconductor (MOS) devices without and with HNO3 compensation are compared. The surface roughness and interface trap density are obviously decreased by utilizing HNO3 compensation. Under negative gate bias, the leakage current, hard breakdown characteristics, and temperature-dependent reliability of the Al2O3 MOS(p) capacitors are clearly improved by HNO3 compensation. Under positive gate bias, the highly temperature-dependent current is principally dominated by generation-recombination mechanism. However, the diodes without HNO3 compensation show irregular temperature response especially at temperature above 70 °C. From Frenkel-Poole emission analysis, the oxide traps in Al2O3 without HNO3 compensation are responsible to this abnormal temperature response. These results suggest that the quality of ultrathin Al2O3 gate dielectrics can be cost-effectively improved by HNO3 compensation.
Pressure dependence of magnetic transition temperature in Li[LixMn2−x]O4 (0 ≤ x ≤ 1/3) studied by muon-spin rotation and relaxation
Authors: Mukai Kazuhiko , Andreica Daniel , Ikedo Yutaka , Nozaki Hiroshi , Månsson Martin , Amato Alex , Sugiyama Jun
Published: February 2013

In order to study a change in electrochemical, structural, and magnetic properties for lithium manganese oxide spinels Li[LixMn2−x]O4 (LMO) with 0 ≤ x ≤ 1/3, muon-spin rotation and relaxation (μSR) spectra were recorded under pressure (P) up to 2.1 GPa. At ambient P, P = 0.1 MPa, the antiferromagnetic or spin-glass-like transition temperature (Tm) at P = 0.1 MPa monotonically decreases with increasing x. On the contrary, the slope of the Tm vs. P (dTm/dP) rapidly increases from 0.9(1) K/GPa at x = 0 to 1.4 K/GPa at x = 0.1, then drops to 0.7(1) K/GPa at x = 0.15, and finally keeps constant (∼0.4 K/GPa) with further increasing x. Considering the structural change of LMO with x, the decrease in the distance between Mn ions (dMn-Mn) is likely to play an essential role for determining Tm under P. According to cyclic voltammetry on LMO, the peak current at both anodic and cathodic directions shows the maximum at x = 0.1, indicating the highest diffusivity of Li+ ions (DLi) at x = 0.1.
Efficient electron injection from solution-processed cesium stearate interlayers in organic light-emitting diodes
Authors: Wetzelaer G. A. H. , Najafi A. , Kist R. J. P. , Kuik M. , Blom P. W. M.
Published: February 2013

The electron-injection capability of solution-processed cesium stearate films in organic light-emitting diodes is investigated. Cesium stearate, which is expected to exhibit good solubility and film formation due to its long hydrocarbon chain, is synthesized using a straightforward procedure. Light-emitting diodes are fabricated using orange-, yellow-, and blue-emitting conjugated polymers, comprising a cesium stearate electron-injection layer deposited from ethanol solution. It is demonstrated that these devices perform as well as benchmark devices using vacuum-deposited barium as electron-injection layer, without loss of color purity.
Remedying magnetic hysteresis and 1/f noise for magnetoresistive sensors
Authors: Hu Jiafei , Tian Wugang , Zhao Jianqiang , Pan Mengchun , Chen Dixiang , Tian Guiyun
Published: February 2013

Thermal domain hoppings cause magnetic hysteresis and 1/f resistance noise in magnetoresistive sensors, which largely degrades their response linearity and low-frequency detection ability. In this Letter, the method of constant magnetic excitation integrated with vertical motion flux modulation was proposed to remedy magnetic hysteresis and 1/f resistance noise together. As demonstrated in experiments, the response linearity of the prototype sensor is promoted by about 10 times. Its noise level is reduced to near Johnson-Nyquist noise level, and, therefore, the low-frequency detection ability is approximately enhanced with a factor of 100.
Crack-free AlGaN for solar-blind focal plane arrays through reduced area epitaxy
Authors: Cicek E. , McClintock R. , Vashaei Z. , Zhang Y. , Gautier S. , Cho C. Y. , Razeghi M.
Published: February 2013

We report on crack reduction for solar-blind ultraviolet detectors via the use of a reduced area epitaxy (RAE) method to regrow on patterned AlN templates. With the RAE method, a pre-deposited AlN template is patterned into isolated mesas in order to reduce the formation of cracks in the subsequently grown high Al-content AlxGa1−xN structure. By restricting the lateral dimensions of the epitaxial growth area, the biaxial strain is relaxed by the edges of the patterned squares, which resulted in ∼97% of the pixels being crack-free. After successful implementation of RAE method, we studied the optical characteristics, the external quantum efficiency, and responsivity of average pixel-sized detectors of the patterned sample increased from 38% and 86.2 mA/W to 57% and 129.4 mA/W, respectively, as the reverse bias is increased from 0 V to 5 V. Finally, we discussed the possibility of extending this approach for focal plane array, where crack-free large area material is necessary for high quality imaging.
Control of dissipation in superconducting films by magnetic stray fields
Authors: Gomez A. , Gilbert D. A. , Gonzalez E. M. , Liu Kai , Vicent J. L.
Published: February 2013

Hybrid superconducting/magnetic nanostructures on Si substrates have been built with identical physical dimensions but different magnetic configurations. By constructing arrays based on Co-dots with in-plane, out-of-plane, and vortex state magnetic configurations, the stray fields are systematically tuned. Dissipation in the mixed state of superconductors can be decreased (increased) by several orders of magnitude by decreasing (increasing) the stray magnetic fields. Furthermore, ordering of the stray fields over the entire array helps to suppress dissipation and enhance commensurability effects increasing the number of dissipation minima.
Electro-optical and lasing properties of hybrid quantum dot/quantum well material system for reconfigurable photonic devices
Authors: Thoma Jiri , Liang Baolai , Lewis Liam , Hegarty Stephen P. , Huyet Guillaume , Huffaker Diana L.
Published: February 2013

We characterize the electro-optical and lasing properties of a hybrid material consisting of multiple InAs quantum dot (QD) layers together with an InGaAs quantum well (QW) grown on a GaAs substrate. Over 40 nm Stark shift of the InGaAs QW leading to 9 dB extinction ratio was demonstrated. Lasing operation at the QD first excited state transition of 1070 nm was achieved and together with < 10 ps absorption recovery the system shows promise for high-speed mode-locked lasers and electro-modulated lasers.
Plant wilting can be caused either by the plant or by the soil
Authors: Czyż Ewa A. , Dexter Anthony R.
Published: February 2013

In this paper, plant wilting is re-analysed and re-interpreted on the basis of previously published work. Wilting is considered only in terms of the stress caused by the matric suction of the soil water. Other factors that can induce wilting, such as salinity and plant pathogens, are not considered. It is found that there is confusion around the subject for two main reasons. First, it is usually assumed that the matric suction of the pore water that exists in soil samples when they are removed from pressure plate extractors is equal to the air pressure that was applied. Second (and this is a special case of the first reason), because the soil water content when most plants wilt is very close to that remaining in soil samples on pressure plates operating with an air pressure of 1.5 MPa, it is assumed that plants wilt at a pore water suction of 1.5 MPa. These assumptions are examined here, and it is shown that neither of them is true. Published results are used for the wilting condition. The recently described double-exponential (DE) equation for soil water retention is used for cases where the water is non-equilibrated because of hydraulic cut-off. The non-equilibrated condition is appropriate for plant roots because they, like pressure plate extractors, extract water from soil by immiscible displacement. The DE equation is used to illustrate the conditions under which plant wilting can be either a plant or a soil property. It is shown how this approach can be used to estimate the pore water suction at which plants would wilt because the soil is no longer able to supply water to their roots. It is demonstrated that the commonly used, but often erroneous, value for the wilting-point suction of h = 1.5 MPa is a consequence of the fact that this is the largest value of air pressure used in pressure cell extractors. It is therefore neither a plant nor a soil property, but is an artefact of the experimental procedure. The use of the DE equation for soil water retention shows that we know only that h ≤1.5 MPa, and that h can be as small as 0.2 or 0.3 MPa. Implications for estimation of plant water availability in soils, for plant breeding, and for soil microbial activity are discussed.
ARCH domain of XPD, an anchoring platform for CAK that conditions TFIIH DNA repair and transcription activities
Authors: Abdulrahman Wassim , Iltis Izarn , Radu Laura , Braun Cathy , Maglott-Roth Anne , Giraudon Christophe , Egly Jean-Marc , Poterszman Arnaud
Published: February 2013

The xeroderma pigmentosum group D (XPD) helicase is a subunit of transcription/DNA repair factor, transcription factor II H (TFIIH) that catalyzes the unwinding of a damaged DNA duplex during nucleotide excision repair. Apart from two canonical helicase domains, XPD is composed of a 4Fe-S cluster domain involved in DNA damage recognition and a module of uncharacterized function termed the “ARCH domain.” By investigating the consequences of a mutation found in a patient with trichothiodystrophy, we show that the ARCH domain is critical for the recruitment of the cyclin-dependent kinase (CDK)-activating kinase (CAK) complex. Indeed, this mutation not only affects the interaction with the MAT1 CAK subunit, thereby decreasing the in vitro basal transcription activity of TFIIH itself and impeding the efficient recruitment of the transcription machinery on the promoter of an activated gene, but also impairs the DNA unwinding activity of XPD and the nucleotide excision repair activity of TFIIH. We further demonstrate the role of CAK in downregulating the XPD helicase activity within TFIIH. Taken together, our results identify the ARCH domain of XPD as a platform for the recruitment of CAK and as a potential molecular switch that might control TFIIH composition and play a key role in the conversion of TFIIH from a factor active in transcription to a factor involved in DNA repair.
S-nitrosylated SHP-2 contributes to NMDA receptor-mediated excitotoxicity in acute ischemic stroke
Authors: Shi Zhong-Qing , Sunico Carmen R. , McKercher Scott R. , Cui Jiankun , Feng Gen-Sheng , Nakamura Tomohiro , Lipton Stuart A.
Published: February 2013

Overproduction of nitric oxide (NO) can cause neuronal damage, contributing to the pathogenesis of several neurodegenerative diseases and stroke (i.e., focal cerebral ischemia). NO can mediate neurotoxic effects at least in part via protein S-nitrosylation, a reaction that covalently attaches NO to a cysteine thiol (or thiolate anion) to form an S-nitrosothiol. Recently, the tyrosine phosphatase Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) and its downstream pathways have emerged as important mediators of cell survival. Here we report that in neurons and brain tissue NO can S-nitrosylate SHP-2 at its active site cysteine, forming S-nitrosylated SHP-2 (SNO–SHP-2). We found that NMDA exposure in vitro and transient focal cerebral ischemia in vivo resulted in increased levels of SNO–SHP-2. S-Nitrosylation of SHP-2 inhibited its phosphatase activity, blocking downstream activation of the neuroprotective physiological ERK1/2 pathway, thus increasing susceptibility to NMDA receptor-mediated excitotoxicity. These findings suggest that formation of SNO–SHP-2 represents a key chemical reaction contributing to excitotoxic damage in stroke and potentially other neurological disorders.
Using state-trace analysis to dissociate the functions of the human hippocampus and perirhinal cortex in recognition memory
Authors: Staresina Bernhard P. , Fell Juergen , Dunn John C. , Axmacher Nikolai , Henson Richard N.
Published: February 2013

A recurring issue in neuroscience concerns evidence as to whether two or more brain regions implement qualitatively different functions. Here we introduce the application of state-trace analysis to measures of neural activity, illustrating how this analysis can furnish compelling evidence for qualitatively different functions, even when the precise “neurometric” mapping between function and brain measure is unknown. In doing so, we address a long-standing debate about the brain systems supporting human memory: whether the hippocampus and the perirhinal cortex, two key components of the medial temporal lobe memory system, provide qualitatively different contributions to recognition memory. An alternative account has been that both regions support a single shared function, such as memory strength, with the apparent dissociations obtained by previous neuroimaging studies merely reflecting different, nonlinear neurometric mappings across regions. To adjudicate between these scenarios, we analyze intracranial electroencephalographic data obtained directly from human hippocampus and perirhinal cortex during a recognition paradigm and apply state-trace analysis to responses evoked by the retrieval cue as a function of different types of memory judgment. Assuming only that the neurometric mapping in each region is monotonic, any unidimensional theory (such as the memory-strength account) will produce a monotonic state trace. Critically, results showed a nonmonotonic state trace; that is, activity levels in the two regions did not show the same relative ordering across memory conditions. This nonmonotonic state trace demonstrates that there are at least two different functions implemented across the hippocampus and perirhinal cortex, allowing formal rejection of a single-process account of medial temporal lobe contributions to recognition memory.
Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions
Authors: Peng Jia , Li Qinglei , Wigglesworth Karen , Rangarajan Adithya , Kattamuri Chandramohan , Peterson Randall T. , Eppig John J. , Thompson Thomas B. , Matzuk Martin M.
Published: February 2013

Significance

Although genetic studies have uncovered critical functions of GDF9 and BMP15 in female reproduction, many genetic and physiologic data for these ligands remain perplexing. Here we establish that mouse and human GDF9:BMP15 heterodimers are the most biopotent regulators of ovarian granulosa cell functions. Moreover, GDF9:BMP15 heterodimers require a unique signaling complex that includes the type 2 receptor BMPR2, an ALK4/5/7 type 1 kinase receptor, and an ALK6 type 1 co-receptor. GDF9:BMP15 binding to this complex stimulates phosphorylation of SMAD2/3. Our findings explain intraspecies and interspecies functions of these oocyte-synthesized proteins and have key implications for the regulation of female fertility.
Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad
Authors: Buller Andrew R. , Townsend Craig A.
Published: February 2013

Significance

The structure–function relationship of proteases is central to our understanding of biochemistry. Nature has evolved at least 23 independent solutions to this problem, using an acylation mechanism. We examined the structures of these proteases, using a new framework to characterize the geometric relationships within each active site. This analysis revealed the orientation of the base determines the stereochemistry of catalysis and elucidated why threonine does not substitute for serine in the catalytic triad. These observations explain how the absolute stereostructures of natural protease inhibitors prevent off-target inhibition and serve as boundary conditions to enzyme design.
Conservation and divergence in the transcriptional programs of the human and mouse immune systems
Authors: Shay Tal , Jojic Vladimir , Zuk Or , Rothamel Katherine , Puyraimond-Zemmour David , Feng Ting , Wakamatsu Ei , Benoist Christophe , Koller Daphne , Regev Aviv ,   the ImmGen Consortium
Published: February 2013

Much of the knowledge about cell differentiation and function in the immune system has come from studies in mice, but the relevance to human immunology, diseases, and therapy has been challenged, perhaps more from anecdotal than comprehensive evidence. To this end, we compare two large compendia of transcriptional profiles of human and mouse immune cell types. Global transcription profiles are conserved between corresponding cell lineages. The expression patterns of most orthologous genes are conserved, particularly for lineage-specific genes. However, several hundred genes show clearly divergent expression across the examined cell lineages, and among them, 169 genes did so even with highly stringent criteria. Finally, regulatory mechanisms—reflected by regulators’ differential expression or enrichedcis-elements—are conserved between the species but to a lower degree, suggesting that distinct regulation may underlie some of the conserved transcriptional responses.
ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43
Authors: Arnold Eveline S. , Ling Shuo-Chien , Huelga Stephanie C. , Lagier-Tourenne Clotilde , Polymenidou Magdalini , Ditsworth Dara , Kordasiewicz Holly B. , McAlonis-Downes Melissa , Platoshyn Oleksandr , Parone Philippe A. , Da Cruz Sandrine , Clutario Kevin M. , Swing Debbie , Tessarollo Lino , Marsala Martin , Shaw Christopher E. , Yeo Gene W. , Cleveland Don W.
Published: February 2013

Significance

Mutations in the RNA binding protein TDP-43 cause amyotrophic lateral sclerosis and frontotemporal dementia. Through expressing disease-causing mutants in mice and genome-wide RNA splicing analyses, mutant TDP-43 is shown to retain normal or enhanced activity for facilitating splicing of some RNA targets, but “loss-of-function” for others. These splicing changes, as well as age-dependent, mutant-dependent lower motor neuron disease, occur without loss of nuclear TDP-43 or accumulation of insoluble aggregates of TDP-43.
The Tuscan Committee of National Liberation: new directions in research, archives and editions of sources
Authors: Mencarelli Paolo
Published: February 2013

Historians agree that the liberation of Florence (11 August 1944) was a key moment in the war in Italy for political, rather than military, reasons. This was the case, above all, because the Allies found for the first time, in a city of great international importance, an administration that at both city and provincial level was an expression of the antifascist forces. The parties as well as the organisations had, it transpired, worked to create the foundations of popular self-government during the struggle against the Germans and the Fascists and, in particular, during the months immediately preceding the Liberation. It was in Florence itself that, confronted with such a demonstration of the maturity and organisation of the Resistance, the Allied forces were compelled to rethink their relationship with the various partisan and antifascist forces. The difference between Florence and Rome was such that the Allies had, at the very least, to acknowledge the institutional and social ambitions of the Resistance movement and the desire of the partisans to change the way the country would be run after the war. These aspirations were a key aspect of the Resistance in Florence and Tuscany and, as the Allies discovered, the partisans in the North shared these same hopes and ambitions.
Who Does Dot Respond to the Agricultural Resource Management Survey and Does It Matter?
Authors: Weber Jeremy G. , Clay Dawn Marie
Published: February 2013

The Agricultural Resource Management Survey is the primary annual source of information on U.S. farms, but in a typical year one‐third of sampled farms do not respond. We use Census of Agriculture data to study nonresponse to the survey and how it affects estimates in two econometric models. Despite larger farms responding less, the coefficients estimated from the respondent subsample always fall inside confidence intervals based on draws from the full sample of respondents and nonrespondents. Although nonresponse bias can vary by application, the findings suggest that bias is unlikely to undermine conclusions based on econometrics using respondent data.
Uromyces appendiculatus in Honduras: Pathogen Diversity and Host Resistance Screening
Authors: Acevedo Maricelis , Steadman James R. , Rosas Juan C.
Published: February 2013

Bean rust, caused by the fungus Uromyces appendiculatus, is a major constraint for common bean production worldwide. Virulence of U. appendiculatus collected from wild and cultivated Phaseolus spp. was examined in 28 locations across Honduras. Host accessions representing wild and domesticated Phaseolus spp. collected at the same sampling locations were evaluated for resistance against U. appendiculatus. In total, 91 pathotypes were identified from 385 U. appendiculatus isolates according to their virulence on each of the 12 host differentials. No significant difference in pathogen total virulence, measured as the mean disease score, was found between locations. However, significant differences were found in pathotype virulence among isolates collected from different Phaseolus spp. within a location. Moreover, when locations were compared on the basis of pathotype occurrence and frequency, differences among locations were evident. No two locations had the same pathotype composition. The most common pathotype was virulent on 9 of the 12 differential lines. A high number of resistant accessions were identified in Phaseolus coccineus and P. lunatus. Although most wild P. vulgaris accessions were highly susceptible, rust resistance was observed in P. vulgaris landraces collected from farmer's fields. Thirty-two (52%) of the accessions screened showed intermediate to high levels of resistance and, of those, 16% were P. coccineus accessions. Our findings support the hypothesis that interaction of U. appendiculatus in host populations composed of diverse Phaseolus spp. and genotypes has favored highly diverse and virulent pathotypes, creating a center for virulence diversity of the pathogen in Honduras. The high percentage of intermediate and highly resistant accessions identified in the present study supports the strategy of collecting plants from the center of diversity of a pathogen or in locations with high incidence of disease and pathogen diversity to maximize the probability of identifying new sources of resistance.
The Usefulness of Fungicide Mixtures and Alternation for Delaying the Selection for Resistance in Populations of Mycosphaerella graminicola on Winter Wheat: A Modeling Analysis
Authors: Hobbelen P. H. F. , Paveley N. D. , Oliver R. P. , van den Bosch F.
Published: February 2013

A fungicide resistance model (reported and tested previously) was amended to describe the development of resistance in Mycosphaerella graminicola populations in winter wheat (Triticum aestivum) crops in two sets of fields, connected by spore dispersal. The model was used to evaluate the usefulness of concurrent, alternating, or mixture use of two high-resistance-risk fungicides as resistance management strategies. We determined the effect on the usefulness of each strategy of (i) fitness costs of resistance, (ii) partial resistance to fungicides, (iii) differences in the dose-response curves and decay rates between fungicides, and (iv) different frequencies of the double-resistant strain at the start of a treatment strategy. Parameter values for the quinine outside inhibitor pyraclostrobin were used to represent two fungicides with differing modes of action. The effectiveness of each strategy was quantified as the maximum number of growing seasons that disease was effectively controlled in both sets of fields. For all scenarios, the maximum effective lives achieved by the use of the strategies were in the order mixtures ≥ alternation ≥ concurrent use. Mixtures were of particular benefit where the pathogen strain resistant to both modes of action incurred a fitness penalty or was present at a low initial frequency.
Strains of Pseudomonas syringae pv. syringae from Pea Are Phylogenetically and Pathogenically Diverse
Authors: Martín-Sanz Alberto , de la Vega Marcelino Pérez , Murillo Jesús , Caminero Constantino
Published: February 2013

Pseudomonas syringae pv. syringae causes extensive yield losses in the pea crop worldwide, although there is little information on its host specialization and its interactions with pea. A collection of 88 putative P. syringae pv. syringae strains (including 39 strains isolated from pea) was characterized by repetitive polymerase chain reaction (rep-PCR), multilocus sequence typing (MLST), and syrB amplification and evaluated for pathogenicity and virulence. rep-PCR data grouped the strains from pea into two groups (1B and 1C) together with strains from other hosts; a third group (1A) was formed exclusively with strains isolated from non-legume species. MLST data included all strains from pea in the genomospecies 1 of P. syringae pathovars defined in previous studies; they were distributed in the same three groups defined by rep-PCR. The inoculations performed in two pea cultivars showed that P. syringae pv. syringae strains from groups 1A and 1C were less virulent than strains from group 1B, suggesting a possible pathogenic specialization in this group. This study shows the existence of genetically and pathogenically distinct P. syringae pv. syringae strain groups from pea, which will be useful for the diagnostic and epidemiology of this pathogen and for disease resistance breeding.
Efficient Gene Knockout in the Maize Pathogen Setosphaeria turcica Using Agrobacterium tumefaciens-Mediated Transformation
Authors: Xue Chunsheng , Wu Dongliang , Condon Bradford J. , Bi Qing , Wang Weiwei , Turgeon B. Gillian
Published: February 2013

Setosphaeria turcica, a hemibiotrophic pathogenic dothideomycete, is the causal agent of Northern Leaf Blight of maize, which periodically causes significant yield losses worldwide. To explore molecular mechanisms of fungal pathogenicity and virulence to the host, an efficient targeted gene knockout transformation system using Agrobacterium tumefaciens was established with field collected strains. The starting materials, incubation time, induction medium type, Agrobacterium cell density, and method of co-incubation were optimized for deletion of 1,3,8-trihydroxynaphthalene reductase, a gene in the melanin biosynthesis pathway, as a test case. Four additional genes were deleted in two different S. turcica field isolates to confirm robustness of the method. One of these mutant strains was reduced in virulence compared with the wild-type strain when inoculated on susceptible maize. Transformation efficiency was ≈20 ± 3 transformants per 1× 106 germlings and homologous recombination efficiency was 33.3 to 100%.
Multiple scales of selection influence the evolutionary emergence of novel pathogens
Authors: Park Miran , Loverdo Claude , Schreiber Sebastian J. , Lloyd-Smith James O.
Published: February 2013

When pathogens encounter a novel environment, such as a new host species or treatment with an antimicrobial drug, their fitness may be reduced so that adaptation is necessary to avoid extinction. Evolutionary emergence is the process by which new pathogen strains arise in response to such selective pressures. Theoretical studies over the last decade have clarified some determinants of emergence risk, but have neglected the influence of fitness on evolutionary rates and have not accounted for the multiple scales at which pathogens must compete successfully. We present a cross-scale theory for evolutionary emergence, which embeds a mechanistic model of within-host selection into a stochastic model for emergence at the population scale. We explore how fitness landscapes at within-host and between-host scales can interact to influence the probability that a pathogen lineage will emerge successfully. Results show that positive correlations between fitnesses across scales can greatly facilitate emergence, while cross-scale conflicts in selection can lead to evolutionary dead ends. The local genotype space of the initial strain of a pathogen can have disproportionate influence on emergence probability. Our cross-scale model represents a step towards integrating laboratory experiments with field surveillance data to create a rational framework to assess emergence risk.