bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal variations of stratospheric age spectra in the Goddard Earth Observing System Chemistry Climate Model (GEOSCCM)
Authors: Li Feng , Waugh Darryn W. , Douglass Anne R. , Newman Paul A. , Pawson Steven , Stolarski Richard S. , Strahan Susan E. , Nielsen J. Eric
Published: January 2012

The stratospheric age spectrum is the probability distribution function of the transit times since a stratospheric air parcel had last contact with a tropospheric boundary region. Previous age spectrum studies have focused on its annual mean properties. Knowledge of the age spectrum's seasonal variability is very limited. In this study, we investigate the seasonal variations of the stratospheric age spectra using the pulse tracer method in the Goddard Earth Observing System Chemistry Climate Model (GEOSCCM). The relationships between the age spectrum and the boundary impulse response (BIR) are reviewed, and a simplified method to reconstruct seasonally varying age spectra is introduced. The age spectra in GEOSCCM have strong seasonal cycles, especially in the lowermost and lower stratosphere and in the subtropical overworld. These changes reflect the seasonal evolution of the Brewer‐Dobson circulation, isentropic mixing, and transport barriers. We also investigate the seasonal and interannual variations of the BIRs. Our results clearly show that computing an ensemble of seasonally dependent BIRs is necessary in order to capture the seasonal and annual mean properties of the stratospheric age spectrum.
Upscaling sparse ground‐based soil moisture observations for the validation of coarse‐resolution satellite soil moisture products
Authors: Crow Wade T. , Berg Aaron A. , Cosh Michael H. , Loew Alexander , Mohanty Binayak P. , Panciera Rocco , de Rosnay Patricia , Ryu Dongryeol , Walker Jeffrey P.
Published: January 2012

The contrast between the point‐scale nature of current ground‐based soil moisture instrumentation and the ground resolution (typically >102 km2) of satellites used to retrieve soil moisture poses a significant challenge for the validation of data products from current and upcoming soil moisture satellite missions. Given typical levels of observed spatial variability in soil moisture fields, this mismatch confounds mission validation goals by introducing significant sampling uncertainty in footprint‐scale soil moisture estimates obtained from sparse ground‐based observations. During validation activities based on comparisons between ground observations and satellite retrievals, this sampling error can be misattributed to retrieval uncertainty and spuriously degrade the perceived accuracy of satellite soil moisture products. This review paper describes the magnitude of the soil moisture upscaling problem and measurement density requirements for ground‐based soil moisture networks. Since many large‐scale networks do not meet these requirements, it also summarizes a number of existing soil moisture upscaling strategies which may reduce the detrimental impact of spatial sampling errors on the reliability of satellite soil moisture validation using spatially sparse ground‐based observations.
Prediction and uncertainty of free convection phenomena in porous media
Authors: Xie Yueqing , Simmons Craig T. , Werner Adrian D. , Diersch Hans‐J. G.
Published: January 2012

Over the past few decades, groundwater flow and solute transport models have been commonly used to make predictions of complex, highly nonlinear, semichaotic free convective processes in various hydrogeologic settings. However, there has been much confusion in the literature about the ability of models to make reliable predictions of free convection phenomena. Particularly, different model codes and numerical schemes have been observed to give different solutions to the same problem. Attempts to match the precise nature of finger patterns in space and time have been somewhat unsuccessful. The classical notion of grid convergence appears to be nonmeaningful in the context of these processes when attempting to compare the complex fingering patterns. This study examines the predictability of a highly unstable free convective flow system by quantitatively investigating several representative plume characteristics. These characteristics include “microscopic” features such as the number of fingers and deepest plume front, and “macroscopic” features such as vertical center of solute mass, total solute mass, and solute flux through the source zone. Surprisingly, both microscopic and macroscopic variables can be estimated with a small degree of uncertainty. It is shown that the microscopic variables have slightly greater uncertainty than macroscopic variables. This indicates a greater degree of predictability in free convection systems than may have been previously thought to exist. It also suggests that a paradigm shift which analyses free convection in a stochastic rather than deterministic framework is required. This has significant consequences for model simulation and testing as well as process prediction.
Universal scaling of spontaneous imbibition for water‐wet systems
Authors: Schmid K. S. , Geiger S.
Published: January 2012

Spontaneous, counter‐current imbibition (SI) is a key mechanism in many multiphase flow processes, such as cleanup of nonaqueous phase liquids (NAPLs), bioremediation, or CO2 storage. For interpreting and upscaling laboratory SI data, and modeling and prediction purposes, scaling groups are an essential tool. The question of how to formulate a general scaling group has been debated for over 90 years. Here we propose the first scaling group that incorporates the influence of all parameters on SI that are present in the two‐phase Darcy model. The group is derived rigorously from the only known exact analytical solution for spontaneous imbibition by relating the cumulative water phase imbibed to the normalized pore volume. We show the validity of the group by applying it to 42 published SI studies for water‐oil and water‐air experiments, for a wide range of viscosity ratios, different materials, different initial water saturations, and different length‐scales. In all cases, water was the wetting phase. Our group serves as a “master equation” whose generality allows the rigorous prediction of the validity of a large number of specialized scaling groups proposed during the last 90 years. Furthermore, our results give strong evidence that the Darcy model is suitable for describing SI, and that including dynamic effects in capillary pressure is not necessary for counter‐current SI, contrary to what has been hypothesized. Two key applications of the group are discussed: First, the group can serve as the long sought after general transfer rate for imbibition used in dual‐porosity models. Second, it is the so far missing proportionality constant in imbibition‐germination models for plant seeds.
Anisotropic Rayleigh‐wave tomography of Ireland's crust: Implications for crustal accretion and evolution within the Caledonian Orogen
Authors: Polat G. , Lebedev S. , Readman P. W. , O'Reilly B. M. , Hauser F.
Published: January 2012

The Irish landmass, now at the western extremity of the Eurasian Plate, was formed in the Caledonian Orogeny during the Palaeozoic assembly of Pangea. The associated closure of the Iapetus Ocean is recorded in the NE–SW structural trends that dominate the tectonic set‐up of Ireland today. The deep‐crustal dynamics of the orogeny and the effect on the crust of the subsequent extension and magmatism in the North Atlantic are debated. Fabrics within deep crustal rocks preserve a record of deformation during and after the continental collisions. Here, we measured Rayleigh‐wave phase velocities using seismograms recorded by permanent and temporary intermediate‐band stations in Ireland and inverted the data for phase‐velocity maps, including azimuthal anisotropy. The observed isotropic phase‐velocity heterogeneity reflects moderate crustal thickness and seismic velocity variations across Ireland. Anisotropy of Rayleigh waves at 10–20 s periods shows a NE–SW fast‐propagation direction and is largest (up to 2%) at a 15 s period, at which Rayleigh waves sample primarily the middle and lower crust. The NE–SW trend of the deep‐crustal anisotropic fabric is parallel to tectonic trends, in particular the Iapetus Suture Zone, which indicates that suture‐parallel flow in the middle and lower crust accommodated the continental collision. The apparent preservation of the Caledonian‐age fabric also shows that the deep crust of the Eurasian margin in Ireland was neither stretched by the NW–SE extension associated with the opening of the North Atlantic, nor modified significantly by the Cenozoic magmatism in the region.
Genome sequence and genetic linkage analysis of Shiitake mushroom Lentinula edodes
Authors: Yip Pui Ying , Wong Kin Sing , Li Lei , Huang Qian Li , Kwan Hoi Shan , Au Chun Hang , Wong Man Chun , Qin Jing , Kwok Iris Sze Wai , Nong Wen Yan , Chum Winnie Wing Yan
Published: January 2012

Lentinula edodes (Shiitake/Xianggu) is an important cultivated mushroom. Understanding the genomics and functional genomics of L. edodes allows us to improve its cultivation and quality. Genome sequence is a key to develop molecular genetic markers for breeding and genetic manipulation. We sequenced the genome of L. edodes monokaryon L54A using Roche 454 and ABI SOLiD genome sequencing. Sequencing reads of about 1400Mb were de novo assembled into a 40.2 Mb genome sequence. We compiled the genome sequence into a searchable database with which we have been annotating the genes and analyzing the metabolic pathways. In addition, we have been using many molecular techniques to analyze genes differentially expressed during development. Gene ortholog groups of L. edodes genome sequence compared across genomes of several fungi including mushrooms identified gene families unique to mushroom-forming fungi. We used a mapping population of haploid basidiospores of dikaryon L54 for genetic linkage analysis. High-quality variations such as single nucleotide polymorphisms, insertions, and deletions of the mapping population formed a high-density genetic linkage map. We compared the linkage map to the L. edodes L54A genome sequence and located selected quantitative trait loci. The Shiitake community will benefit from these resources for genetic studies and breeding.
Ro52/SSA sensitizes cells to death receptor‐induced apoptosis by down‐regulating c‐FLIP(L)
Authors: Zhang Jing , Fang Lei , Zhu Xuguo , Qiao Yiting , Yu Mei , Wang Lu , Chen Yuan , Yin Wu , Hua Zi‐Chun
Published: January 2012

Ro52/SSA is an autoantigen that presents in patients with SS (Sjögren's syndrome) and SLE (systemic lupus erythematosus). It increases cell death and redistributes itself to apoptotic blebs, but its pro‐apoptotic function has not been completely identified. Overexpression of Ro52/SSA promoted cell apoptosis induced by DR (death receptor) in caspase‐8‐dependent manner. Ro52/SSA expression down‐regulated c‐FLIP(L) [cellular (Fas‐associated death domain)‐like interleukin 1β‐converting enzyme‐inhibitory protein long form] expression, and Ro52/SSA siRNAs (small interfering RNAs) increased c‐FLIP(L) production, indicating that Ro52/SSA plays a role in c‐FLIP(L) regulation. Ro52/SSA negatively regulated c‐FLIP(L) transcriptional level probably by suppressing NF‐κB (nuclear factor κB) signalling. The data suggest that Ro52/SSA is involved in DR‐mediated apoptosis by regulating c‐FLIP(L).
Reconstruction of Periparotid Defects Using Temporoparietal Fascia Flap with Layered Acellular Human Dermal Allograft
Authors: Winstead Johnathan M. , Olson Garth T. , Frodel John L.
Published: January 2012

Excision of lesions in the periparotid area can leave a sizable concavity of the preauricular area with skeletonization of the mandible. To achieve the bulk necessary to fill this defect, we propose using a composite graft. Acellular human dermal allograft provides the thickness of the graft, and the temporoparietal fascia flap provides blood supply to the dermal graft. Our hypothesis is that vascularization of the graft will promote greater ingrowth of native tissue and prevent breakdown and absorption of the graft. Four representative patients are described.
Coherently controlled molecular junctions
Authors: Peskin Uri , Galperin Michael
Published: January 2012

Within a generic model, we discuss the possibility of coherent control of charge fluxes in unbiased molecular junctions. The control is induced by resonances between the Rabi frequency due to a pumping laser field and internal characteristic frequencies of pre-designed molecular donor-bridge-acceptor complexes. Two models are considered: a coherently controlled molecular charge pump and a molecular switch. The study generalizes previous consideration of light induced current [M. Galperin and A. Nitzan, Phys. Rev. Lett. 95, 206802 (2005)10.1103/PhysRevLett.95.206802] and of a molecular electron pump [R. Volkovich and U. Peskin, Phys. Rev. B 83, 033403 (2011)10.1103/PhysRevB.83.033403] and accounts for the coherently driven charge transport in an unbiased molecular junction with symmetric coupling to leads. Numerical examples demonstrate the feasibility of the control mechanism for realistic junctions parameters.
Semiclassical glory analyses in the time domain for the H + D2(vi = 0, ji = 0) → HD(vf = 3, jf = 0) + D reaction
Authors: Shan Xiao , Connor J. N. L.
Published: January 2012

We make the first application of semiclassical (SC) techniques to the plane-wavepacket formulation of time-domain (T-domain) scattering. The angular scattering of the state-to-state reaction, H + D2(vi = 0, ji = 0) → HD(vf = 3, jf = 0) + D, is analysed, where v and j are vibrational and rotational quantum numbers, respectively. It is proved that the forward-angle scattering in the T-domain, which arises from a delayed mechanism, is an example of a glory. The SC techniques used in the T-domain are: An integral transitional approximation, a semiclassical transitional approximation, a uniform semiclassical approximation (USA), a primitive semiclassical approximation and a classical semiclassical approximation. Nearside-farside (NF) scattering theory is also employed, both partial wave and SC, since a NF analysis provides valuable insights into oscillatory structures present in the full scattering pattern. In addition, we incorporate techniques into the SC theory called “one linear fit” and “two linear fits”, which allow the derivative of the quantum deflection function, ${\tilde \Theta^\prime} ( J )$Θ̃′(J), to be estimated when $\tilde \Theta \left( J \right)$Θ̃J exhibits undulations as a function of J, the total angular momentum variable. The input to our SC analyses is numerical scattering (S) matrix data, calculated from accurate quantum collisional calculations for the Boothroyd–Keogh–Martin–Peterson potential energy surface No. 2, in the energy domain (E-domain), from which accurate S matrix elements in the T-domain are generated. In the E-domain, we introduce a new technique, called “T-to-E domain SC analysis.” It half-Fourier transforms the E-domain accurate quantum scattering amplitude to the T-domain, where we carry out a SC analysis; this is followed by an inverse half-Fourier transform of the T-domain SC scattering amplitude back to the E-domain. We demonstrate that T-to-E USA differential cross sections (DCSs) agree well with exact quantum DCSs at forward angles, for energies where a direct USA analysis in the E-domain fails.
Growth of a Pt film on non-reduced ceria: A density functional theory study
Authors: Loffreda David , Delbecq Françoise
Published: January 2012

The growth of platinum on non-reduced CeO2 (111) surface is studied by means of calculations based on the density functional theory. Particles of increasing size are formed on the oxide surface by incorporating the platinum atoms one by one until multilayer films are obtained. The main conclusion is that platinum atoms tend to maximize the number of metallic bonds and to approach the situation of the bulk, hence preferring films to particles, particles to isolated atoms, and a three-dimensional growth to a two-dimensional one. The supported particles and the films exhibit a contraction of the Pt–Pt distances, with respect to those of the Pt bulk, in order to match the ceria lattice. The density of states projected on the film surface platinum atoms shows important differences in shape and energy (lower d-band center) compared to the Pt(111) reference surface, which could be the major reason for the observed changes in catalytic reactivity when deposited particles are compared with single crystal surfaces.
Tungsten monocarbide, WC: Pure rotational spectrum and 13C hyperfine interaction
Authors: Wang Fang , Steimle Timothy C.
Published: January 2012

The J = 1 → 2 pure rotational transitions in the X3Δ1(v = 0) state of 186W12C and 184W12C were recorded using a pump/probe microwave optical double resonance (PPMODR) technique and analyzed to give fine structure parameters. The field-free [17.6]2← X3Δ1 (1, 0) bands of the W13C isotopologues were recorded using laser induced fluorescence and analyzed to produce the 13C(I = 1/2) magnetic hyperfine parameter. Bonding in the [17.6]2(v = 1) and X3Δ1(v = 0) states is discussed and a comparison of the experimentally determined properties of the X3Δ1(v = 0) state with those predicted as a prelude to the electron electric dipole moment (eEDM) measurements [J. Lee, E. R. Meyer, R. Paudel, J. L. Bohn, and A. E. Leanhardt, J. Mod. Opt. 56, 2005 (2009)10.1080/09500340903349930] is given.
Product angular distributions in the ultraviolet photodissociation of N2O
Authors: McBane George C. , Schinke Reinhard
Published: January 2012

The angular distribution of products from the ultraviolet photodissociation of nitrous oxide yielding O(1D) and N2(\documentclass[12pt]{minimal}\begin{document}$X\,{}^{1}\Sigma _g^+$\end{document}XΣg+1) was investigated using classical trajectory calculations. The calculations modeled absorption only to the 2 1A′ electronic state but used surface-hopping techniques to model nonadiabatic transitions to the ground electronic state late in the dissociation. Observed values of the anisotropy parameter β, which decrease as the product N2 rotational quantum number j increases, could be well reproduced. The relatively low observed β values arise principally from nonaxial recoil due to the very strong bending forces present in the excited state. In the main part of the product rotational distribution near 203 nm, an unusual dynamical effect produces the decrease in β with increasing j; nonaxial recoil effects remain approximately constant while higher j product molecules arise from parent molecules that had their transition dipole moments aligned more closely along the molecular axis. In both low and high j tails of the rotational distribution, the variations in β with j are caused by changes in the extent of nonaxial recoil. In the high-j tail, additional torque present on the ground state potential energy surface following nonadiabatic transitions causes both the additional rotational excitation and the lower β values.
Transport properties of the rough hard sphere fluid
Authors: Kravchenko Olga , Thachuk Mark
Published: January 2012

Results are presented of a systematic study of the transport properties of the rough hard sphere fluid. The rough hard sphere fluid is a simple model consisting of spherical particles that exchange linear and angular momenta, and energy upon collision. This allows a study of the sole effect of particle rotation upon fluid properties. Molecular dynamics simulations have been used to conduct extensive benchmark calculations of self-diffusion, shear and bulk viscosity, and thermal conductivity coefficients. As well, the validity of several kinetic theory equations have been examined at various levels of approximation as a function of density and translational-rotational coupling. In particular, expressions from Enskog theory using different numbers of basis sets in the representation of the distribution function were tested. Generally Enskog theory performs well at low density but deviates at larger densities, as expected. The dependence of these expressions upon translational-rotational coupling was also examined. Interestingly, even at low densities, the agreement with simulation results was sometimes not even qualitatively correct. Compared with smooth hard sphere behaviour, the transport coefficients can change significantly due to translational-rotational coupling and this effect becomes stronger the greater the coupling. Overall, the rough hard sphere fluid provides an excellent model for understanding the effects of translational-rotational coupling upon transport coefficients.
Model for a transformer-coupled toroidal plasma source
Authors: Rauf Shahid , Balakrishna Ajit , Chen Zhigang , Collins Ken
Published: January 2012

A two-dimensional fluid plasma model for a transformer-coupled toroidal plasma source is described. Ferrites are used in this device to improve the electromagnetic coupling between the primary coils carrying radio frequency (rf) current and a secondary plasma loop. Appropriate components of the Maxwell equations are solved to determine the electromagnetic fields and electron power deposition in the model. The effect of gas flow on species transport is also considered. The model is applied to 1 Torr Ar/NH3 plasma in this article. Rf electric field lines form a loop in the vacuum chamber and generate a plasma ring. Due to rapid dissociation of NH3, NHx+ ions are more prevalent near the gas inlet and Ar+ ions are the dominant ions farther downstream. NH3 and its by-products rapidly dissociate into small fragments as the gas flows through the plasma. With increasing source power, NH3 dissociates more readily and NHx+ ions are more tightly confined near the gas inlet. Gas flow rate significantly influences the plasma characteristics. With increasing gas flow rate, NH3 dissociation occurs farther from the gas inlet in regions with higher electron density. Consequently, more NH4+ ions are produced and dissociation by-products have higher concentrations near the outlet.
Significantly improved piezoelectric thermal stability of cellular polypropylene films by high pressure fluorination and post-treatments
Authors: An Zhenlian , Mao Mingjun , Cang Jun , Zhang Yewen , Zheng Feihu
Published: January 2012

Cellular polypropylene (PP) films were fluorinated under a high pressure of 13 bar of the F2/N2 mixture and were post-treated by nitrous oxide and isothermal crystallization. The fluorinated and post-treated PP films after being expanded and corona charged exhibit a significantly improved piezoelectric thermal stability. After annealing at 70 °C for 151 h or at 90 °C for 224 h, the piezoelectric d33 value of the fluorinated and post-treated piezoelectric sample still retains 58% or 45% of its initial d33 value, while the corresponding value of the virgin piezoelectric sample has decreased to 29% or 15% of the initial value. Chemical composition analysis of the cross section of the fluorinated and post-treated film by energy-dispersive x-ray spectroscopy indicates that the internal layers have been fluorinated, in spite of a lower degree of fluorination compared with the fluorinated surface layer. Short-circuit and open-circuit TSD current measurements reveal that the fluorinated internal layers, like the fluorinated surface layer, also have very deep charge traps, although there probably is a difference in density of the deep traps between them. The deeply trapped charge on the internal layers of the fluorinated and post-treated piezoelectric sample is responsible for its significantly improved piezoelectric thermal stability.
Theoretical approach to evaluating beryllium oxide as a gate dielectric considering electromagnetics and thermal stability
Authors: Yum J. H. , Bersuker G. , Oh J. , Banerjee S. K.
Published: January 2012

The effectiveness of an atomic layer deposited beryllium oxide (BeO) barrier layer has been investigated through physical and electrical analysis as a way to control the interfacial layer on Si and III-V substrates recently. In this paper, a theoretical model is suggested to find the most promising gate dielectric based on electromagnetic interactions between the channel carrier and atoms in the gate dielectric, as well as the structural stability of the gate dielectric. Using this model, Al2O3, BeO, SiO2, and HfO2 were evaluated as gate dielectrics for Si and III-V metal oxide semiconductor devices.
Short circuit current improvement in planar heterojunction organic solar cells by multijunction charge transfer
Authors: Wang J. C. , Shi S. Q. , Leung C. W. , Lau S. P. , Wong K. Y. , Chan P. K. L.
Published: January 2012

A multijunction structure was applied on an organic photovoltaic (OPV) device for broadening the absorption spectrum and enhancing the power conversion efficiency through charge transfer process. By inserting the tris[4-(2-thienyl)]amine (TTPA) into a boron subphthalocyanine chloride (SubPc)/C60 OPV device, the short circuit current density (Jsc) showed a 47.5% increases from 3.05 to 4.50 mA/cm2 in the bilayer planar heterojunction device, while the open circuit voltage (Voc) remained constant. Based on the single junction (TTPA/SubPc) device and photoluminescence absorption results, we confirmed both TTPA/SubPc and SubPc/C60 junctions are contributing to the exciton dissociation process hence the efficiency enhancement.
Comparison of scanning tunneling microscope-light emission and photoluminescence from porphyrin films using ultra-high vacuum scanning tunneling microscopy
Authors: Nishitani Ryusuke , Liu Hongwen , Iwasaki Hiroshi
Published: January 2012

In order to study the interaction between molecules and photon fields, including plasmonic and external laser fields, we have carried out in situ measurements of photoluminescence (PL) from porphyrin molecules on Au substrates with and without a scanning tunneling microscope (STM) tip. Measurements were performed in a ultra-high vacuum scanning tunneling microscope chamber during irradiation by a He-Cd laser with incident power varying in the 10−3 to 10−7 W range. At an incident power of around 10−7 W, the spectra depend strongly on the presence of STM tip, which is associated with STM light emission from molecules. We estimated the ratio of quantum efficiency of scanning tunneling microscope-induced light emission (STML) from molecules to PL on the basis of the STML/PL intensity ratio observed experimentally at a laser power of 7.5 × 10−8 W, with the use of a 40 μm laser beam diameter and an effective area of 2 nm for STML. The estimated quantum efficiency for an electron in STML is roughly 1010 times larger than that for one photon of PL. This anomalous enhancement will be discussed on the basis of plasmon-enhanced light emission from molecules in a STM nano-cavity.
Calculation of self-diffusion coefficients in diamond
Authors: Zhang Baohua , Wu Xiaoping
Published: January 2012

In the light of recently reported pressure-volume-temperature relationships in diamond, we show that the self-diffusion coefficient of diamond as a function of temperature and pressure can be satisfactory reproduced in terms of the bulk elastic and expansivity data by means of a thermodynamical model that interconnects the parameters of point defects to the bulk properties. Our calculated self-diffusion coefficients are in good agreement with the experimental ones when the uncertainties are taken into account.
Trisomy of the G protein-coupled K+channel gene,Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice
Authors: Cooper Ayelet , Grigoryan Gayane , Guy-David Liora , Tsoory Michael M. , Chen Alon , Reuveny Eitan
Published: January 2012

G protein-activated inwardly rectifying K+ channels (GIRK) generate slow inhibitory postsynaptic potentials in the brain via Gi/oprotein-coupled receptors. GIRK2, a GIRK subunit, is widely abundant in the brain and has been implicated in various functions and pathologies, such as learning and memory, reward, motor coordination, and Down syndrome. Down syndrome, the most prevalent cause of mental retardation, results from the presence of an extra maternal chromosome 21 (trisomy 21), which comprises theKcnj6gene (GIRK2). The present study examined the behaviors and cellular physiology properties in mice harboring a single trisomy of theKcnj6gene.Kcnj6triploid mice exhibit deficits in hippocampal-dependent learning and memory, altered responses to rewards, hampered depotentiation, a form of excitatory synaptic plasticity, and have accentuated long-term synaptic depression. Collectively the findings suggest that triplication ofKcnj6gene may play an active role in some of the abnormal neurological phenotypes found in Down syndrome.
Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA
Authors: Jung Hea-Jin , Coffinier Catherine , Choe Youngshik , Beigneux Anne P. , Davies Brandon S. J. , Yang Shao H. , Barnes Richard H. , Hong Janet , Sun Tao , Pleasure Samuel J. , Young Stephen G. , Fong Loren G.
Published: January 2012

Lamins A and C, alternatively spliced products of the
LMNA
gene, are key components of the nuclear lamina. The two isoforms are found in similar amounts in most tissues, but we observed an unexpected pattern of expression in the brain. Western blot and immunohistochemistry studies showed that lamin C is abundant in the mouse brain, whereas lamin A and its precursor prelamin A are restricted to endothelial cells and meningeal cells and are absent in neurons and glia. Prelamin A transcript levels were low in the brain, but this finding could not be explained by alternative splicing. In lamin A-only knockin mice, where alternative splicing is absent and all the output of the gene is channeled into prelamin A transcripts, large amounts of lamin A were found in peripheral tissues, but there was very little lamin A in the brain. Also, in knockin mice expressing exclusively progerin (a toxic form of prelamin A found in Hutchinson–Gilford progeria syndrome), the levels of progerin in the brain were extremely low. Further studies showed that prelamin A expression, but not lamin C expression, is down-regulated by a brain-specific microRNA, miR-9. Expression of miR-9 in cultured cells reduced lamin A expression, and this effect was abolished when the miR-9–binding site in the prelamin A 3′ UTR was mutated. The down-regulation of prelamin A expression in the brain could explain why mouse models of Hutchinson–Gilford progeria syndrome are free of central nervous system pathology.
Exclusive recognition of sarcosine in water and urine by a cavitand-functionalized silicon surface
Authors: Biavardi Elisa , Tudisco Cristina , Maffei Francesca , Motta Alessandro , Massera Chiara , Condorelli Guglielmo G. , Dalcanale Enrico
Published: January 2012

A supramolecular approach for the specific detection of sarcosine, recently linked to the occurrence of aggressive prostate cancer forms, has been developed. A hybrid active surface was prepared by the covalent anchoring on Si substrates of a tetraphosphonate cavitand as supramolecular receptor and it was proven able to recognize sarcosine from its nonmethylated precursor, glycine, in water and urine. The entire complexation process has been investigated in the solid state, in solution, and at the solid–liquid interface to determine and weight all the factors responsible of the observed specificity. The final outcome is a Si-based active surface capable of binding exclusively sarcosine. The complete selectivity of the cavitand-decorated surface under these stringent conditions represents a critical step forward in the use of these materials for the specific detection of sarcosine and related metabolites in biological fluids.
Insights into cis-autoproteolysis reveal a reactive state formed through conformational rearrangement
Authors: Buller Andrew R. , Freeman Michael F. , Wright Nathan T. , Schildbach Joel F. , Townsend Craig A.
Published: January 2012

ThnT is a pantetheine hydrolase from the DmpA/OAT superfamily involved in the biosynthesis of the β-lactam antibiotic thienamycin. We performed a structural and mechanistic investigation into the cis-autoproteolytic activation of ThnT, a process that has not previously been subject to analysis within this superfamily of enzymes. Removal of the γ-methyl of the threonine nucleophile resulted in a rate deceleration that we attribute to a reduction in the population of the reactive rotamer. This phenomenon is broadly applicable and constitutes a rationale for the evolutionary selection of threonine nucleophiles in autoproteolytic systems. Conservative substitution of the nucleophile (T282C) allowed determination of a 1.6-Å proenzyme ThnT crystal structure, which revealed a level of structural flexibility not previously observed within an autoprocessing active site. We assigned the major conformer as a nonreactive state that is unable to populate a reactive rotamer. Our analysis shows the system is activated by a structural rearrangement that places the scissile amide into an oxyanion hole and forces the nucleophilic residue into a forbidden region of Ramachandran space. We propose that conformational strain may drive autoprocessing through the destabilization of nonproductive states. Comparison of our data with previous reports uncovered evidence that many inactivated structures display nonreactive conformations. For penicillin and cephalosporin acylases, this discrepancy between structure and function may be resolved by invoking the presence of a hidden conformational state, similar to that reported here for ThnT.
Kinesin-2 family in vertebrate ciliogenesis
Authors: Zhao Chengtian , Omori Yoshihiro , Brodowska Katarzyna , Kovach Peter , Malicki Jarema
Published: January 2012

The differentiation of cilia is mediated by kinesin-driven transport. As the function of kinesins in vertebrate ciliogenesis is poorly characterized, we decided to determine the role of kinesin-2 family motors—heterotrimeric kinesin-II and the homodimeric Kif17 kinesin—in zebrafish cilia. We report that
kif17
is largely dispensable for ciliogenesis;
kif17
homozygous mutant animals are viable and display subtle morphological defects of olfactory cilia only. In contrast to that, the
kif3b
gene, encoding a heterotrimeric kinesin subunit, is necessary for cilia differentiation in most tissues, although exceptions exist, and include photoreceptors and a subset of hair cells. Cilia of these cell types persist even in
kif3b
/
kif17
double mutants. Although we have not observed a functional redundancy of
kif3b
and
kif17
,
kif17
is able to substitute for
kif3b
in some cilia. In contrast to
kif3b
/
kif17
double mutants, simultaneous interference with
kif3b
and
kif3c
leads to the complete loss of photoreceptor and hair cell cilia, revealing redundancy of function. This is in agreement with the idea that Kif3b and Kif3c motor subunits form complexes with Kif3a, but not with each other. Interestingly,
kif3b
mutant photoreceptor cilia differentiate with a delay, suggesting that
kif3c
, although redundant with
kif3b
at later stages of differentiation, is not active early in photoreceptor ciliogenesis. Consistent with that, the overexpression of
kif3c
in
kif3b
mutants rescues early photoreceptor cilia defects. These data reveal unexpected diversity of functional relationships between vertebrate ciliary kinesins, and show that the repertoire of kinesin motors changes in some cilia during their differentiation.
Conserved role for the Dachshund protein with
Drosophila
Pax6 homolog Eyeless in insulin expression
Authors: Okamoto Naoki , Nishimori Yuka , Nishimura Takashi
Published: January 2012

Members of the insulin family peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. The
Drosophila
genome encodes seven insulin-like peptide genes,
dilp1–7,
and the most prominent
dilps
(
dilp2
,
dilp3,
and
dilp5
) are expressed in brain neurosecretory cells known as “insulin-producing cells” (IPCs). Although these
dilps
are expressed in the same cells, the expression of each
dilp
is regulated independently. However, the molecular mechanisms that regulate the expression of individual
dilps
in the IPCs remain largely unknown. Here, we show that Dachshund (Dac), which is a highly conserved nuclear protein, is a critical transcription factor that specifically regulates
dilp5
expression. Dac was strongly expressed in IPCs throughout development.
dac
loss-of-function analyses revealed a severely reduced
dilp5
expression level in young larvae. Dac interacted physically with the
Drosophila
Pax6 homolog Eyeless (Ey), and these proteins synergistically promoted
dilp5
expression. In addition, the mammalian homolog of Dac, Dach1/2, facilitated the promoting action of Pax6 on the expression of islet hormone genes in cultured mammalian cells. These observations indicate the conserved role of Dac/Dach in controlling insulin expression in conjunction with Ey/Pax6.
How Christians reconcile their personal political views and the teachings of their faith: Projection as a means of dissonance reduction
Authors: Ross Lee D. , Lelkes Yphtach , Russell Alexandra G.
Published: January 2012

The present study explores the dramatic projection of one's own views onto those of Jesus among conservative and liberal American Christians. In a large-scale survey, the relevant views that each group attributed to a contemporary Jesus differed almost as much as their own views. Despite such dissonance-reducing projection, however, conservatives acknowledged the relevant discrepancy with regard to “fellowship” issues (e.g., taxation to reduce economic inequality and treatment of immigrants) and liberals acknowledged the relevant discrepancy with regard to “morality” issues (e.g., abortion and gay marriage). However, conservatives also claimed that a contemporary Jesus would be even more conservative than themselves on the former issues whereas liberals claimed that Jesus would be even more liberal than themselves on the latter issues. Further reducing potential dissonance, liberal and conservative Christians differed markedly in the types of issues they claimed to be more central to their faith. A concluding discussion considers the relationship between individual motivational processes and more social processes that may underlie the present findings, as well as implications for contemporary social and political conflict.
Antibody directs properdin-dependent activation of the complement alternative pathway in a mouse model of abdominal aortic aneurysm
Authors: Zhou Hui-fang , Yan Huimin , Stover Cordula M. , Fernandez Tamara Montes , Rodriguez de Cordoba Santiago , Song Wen-Chao , Wu Xiaobo , Thompson Robert W. , Schwaeble Wilhelm J. , Atkinson John P. , Hourcade Dennis E. , Pham Christine T. N.
Published: January 2012

Abdominal aortic aneurysm (AAA) is a complex inflammatory vascular disease. There are currently limited treatment options for AAA when surgery is inapplicable. Therefore, insights into molecular mechanisms underlying AAA pathogenesis may reveal therapeutic targets that could be manipulated pharmacologically or biologically to halt disease progression. Using an elastase-induced AAA mouse model, we previously established that the complement alternative pathway (AP) plays a critical role in the development of AAA. However, the mechanism by which complement AP is initiated remains undefined. The complement protein properdin, traditionally viewed as a positive regulator of the AP, may also initiate complement activation by binding directly to target surfaces. In this study, we sought to determine whether properdin serves as a focal point for the initiation of the AP complement activation in AAA. Using a properdin loss of function mutation in mice and a mutant form of the complement factor B protein that produces a stable, properdin-free AP C3 convertase, we show that properdin is required for the development of elastase-induced AAA in its primary role as a convertase stabilizer. Unexpectedly, we find that, in AAA, natural IgG antibodies direct AP-mediated complement activation. The absence of IgG abrogates C3 deposition in elastase-perfused aortic wall and protects animals from AAA development. We also determine that blockade of properdin activity prevents aneurysm formation. These results indicate that an innate immune response to self-antigens activates the complement system and initiates the inflammatory cascade in AAA. Moreover, the study suggests that properdin-targeting strategies may halt aneurysmal growth.
Regulation of inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) by reversible lysine acetylation
Authors: Zhang Chunfen , Majerus Philip W. , Wilson Monita P.
Published: January 2012

The enzyme inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) catalyzes the rate-limiting step in the formation of higher phosphorylated forms of inositol in mammalian cells. Because it sits at a key regulatory point in the inositol metabolic pathway, its activity is likely to be regulated. We have previously shown that ITPK1 is phosphorylated, a posttranslational modification used by cells to regulate enzyme activity. We show here that ITPK1 is modified by acetylation of internal lysine residues. The acetylation sites, as determined by mass spectrometry, were found to be lysines 340, 383, and 410, which are all located on the surface of this protein. Overexpression of the acetyltransferases CREB-binding protein or p300 resulted in the acetylation of ITPK1, whereas overexpression of mammalian silent information regulator 2 resulted in the deacetylation of ITPK1. Functionally, ITPK1 acetylation regulates its stability. CREB-binding protein dramatically decreased the half-life of ITPK1. We further found that ITPK1 acetylation down-regulated its enzyme activity. HEK293 cells stably expressing acetylated ITPK1 had reduced levels of the higher phosphorylated forms of inositol, compared with the levels seen in cells expressing unacetylated ITPK1. These results demonstrate that lysine acetylation alters both the stability as well as the activity of ITPK1 in cells.
Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina
Authors: Yu Yufei , Santos Laura M. , Mattiace Linda A. , Costa Manoel L. , Ferreira Luciano C. , Benabou Kelly , Kim Ana H. , Abrahams John , Bennett Michael V. L. , Rozental Renato
Published: January 2012

Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide.
Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential
Authors: Ng Ashley P. , Kauppi Maria , Metcalf Donald , Di Rago Ladina , Hyland Craig D. , Alexander Warren S.
Published: January 2012

Hematopoietic progenitor cells are the progeny of hematopoietic stem cells that coordinate the production of precise numbers of mature blood cells of diverse functional lineages. Identification of cell-surface antigen expression associated with hematopoietic lineage restriction has allowed prospective isolation of progenitor cells with defined hematopoietic potential. To clarify further the cellular origins of megakaryocyte commitment, we assessed the in vitro and in vivo megakaryocyte and platelet potential of defined progenitor populations in the adult mouse bone marrow. We show that megakaryocytes arise from CD150
+
bipotential progenitors that display both platelet- and erythrocyte-producing potential in vivo and that can develop from the Flt3
−
fraction of the pregranulocyte-macrophage population. We define a bipotential erythroid-megakaryocyte progenitor population, the CD150
+
CD9
lo
endoglin
lo
fraction of Lin
−
cKit
+
IL7 receptor alpha
−
FcγRII/III
lo
Sca1
−
cells, which contains the bulk of the megakaryocyte colony-forming capacity of the bone marrow, including bipotential megakaryocyte-erythroid colony-forming capacity, and can generate both erythrocytes and platelets efficiently in vivo. This fraction is distinct from the CD150
+
CD9
hi
endoglin
lo
fraction, which contains bipotential precursors with characteristics of increased megakaryocytic maturation, and the CD150
+
CD9
lo
endoglin
hi
fraction, which contains erythroid lineage-committed cells. Finally, we demonstrate that bipotential erythroid-megakaryocyte progenitor and CD150
+
CD9
hi
endoglin
lo
cells are TPO-responsive and that the latter population specifically expands in the recovery from thrombocytopenia induced by anti-platelet serum.
Modeling hepatitis C virus infection using human induced pluripotent stem cells
Authors: Schwartz Robert E. , Trehan Kartik , Andrus Linda , Sheahan Timothy P. , Ploss Alexander , Duncan Stephen A. , Rice Charles M. , Bhatia Sangeeta N.
Published: January 2012

Human pathogens impact patient health through a complex interplay with the host, but models to study the role of host genetics in this process are limited. Human induced pluripotent stem cells (iPSCs) offer the ability to produce host-specific differentiated cells and thus have the potential to transform the study of infectious disease; however, no iPSC models of infectious disease have been described. Here we report that hepatocyte-like cells derived from iPSCs support the entire life cycle of hepatitis C virus, including inflammatory responses to infection, enabling studies of how host genetics impact viral pathogenesis.
Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses
Authors: Pica Natalie , Hai Rong , Krammer Florian , Wang Taia T. , Maamary Jad , Eggink Dirk , Tan Gene S. , Krause Jens C. , Moran Thomas , Stein Cheryl R. , Banach David , Wrammert Jens , Belshe Robert B. , García-Sastre Adolfo , Palese Peter
Published: January 2012

After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk-specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk-specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay.