bluuebunny/crossref_metadata_2025 huggingface dataset:
Habitability of the Phoenix landing site
Authors: Stoker Carol R. , Zent Aaron , Catling David C. , Douglas Susanne , Marshall John R. , Archer Douglas , Clark Benton , Kounaves Samuel P. , Lemmon Mark T. , Quinn Richard , Renno Nilton , Smith Peter H. , Young Suzanne M.M.
Published: June 2010

The Phoenix mission's key objective was to search for a habitable zone. Mission results are used to evaluate habitability where Phoenix landed. A habitability probability (HI) is defined as the product of probabilities for the presence of liquid water (Plw), energy (Pe), nutrients (Pch), and a benign environment (Pb). Observational evidence for the presence of liquid water (past or present) includes clean ice at a polygon boundary, chemical etching of soil grains, and carbonate minerals. The presence of surface and near subsurface ice, along with thermodynamic conditions that support melting, suggest that liquid water is theoretically possible. Presently, unfrozen water can form only in adsorbed films or saline brines but more clement conditions recur periodically due to variations in orbital parameters. Energy to drive metabolism is available from sunlight, when semitransparent soil grains provide shielding from UV radiation and chemical energy from the redox couple of perchlorate and reduced iron. Nutrient sources including C, H, N, O, P, and S compounds are supplied by known atmospheric sources or global dust. Environmental conditions are within growth tolerance for terrestrial microbes. Surface soil temperatures currently reach 260 K and are periodically much higher, the pH is 7.8 and is well buffered, and the water activity is high enough to allow growth when sufficient water is available. Computation of HI for the sites visited by landers yields Phoenix, 0.47; Meridiani, 0.23; Gusev, 0.22; Pathfinder, 0.05; Viking 1, 0.01; Viking 2, 0.07. HI for the Phoenix site is the largest of any site explored, but dissimilar measurements limit the comparisons' confidence.
An improved lunar gravity field model from SELENE and historical tracking data: Revealing the farside gravity features
Authors: Matsumoto K. , Goossens S. , Ishihara Y. , Liu Q. , Kikuchi F. , Iwata T. , Namiki N. , Noda H. , Hanada H. , Kawano N. , Lemoine F. G. , Rowlands D. D.
Published: June 2010

A new spherical harmonic solution of the lunar gravity field to degree and order 100, called SGM100h, has been developed using historical tracking data and 14.2 months of SELENE tracking data (from 20 October 2007 to 26 December 2008 plus 30 January 2009). The latter includes all usable 4‐way Doppler data collected which allowed direct observations of the farside gravity field for the first time. The new model successfully reveals farside features in free‐air gravity anomalies which are characterized by ring‐shaped structures for large impact basins and negative spots for large craters. SGM100h produces a correlation with SELENE‐derived topography as high as about 0.9, through degree 70. Comparison between SGM100h and LP100K (one of the pre‐SELENE models) shows that the large gravity errors which existed in LP100K are drastically reduced and the asymmetric error distribution between the nearside and the farside almost disappears. The gravity anomaly errors predicted from the error covariance, through degree and order 100, are 26 mGal and 35 mGal for the nearside and the farside, respectively. Owing to the 4‐way Doppler measurements the gravity coefficients below degree and order 70 are now determined by real observations with contribution factors larger than 80 percent. With the SELENE farside data coverage, it is possible to estimate the gravity field to degree and order 70 without applying any a priori constraint or regularization. SGM100h can be used for global geophysical interpretation through degree and order 70.
Heavy‐tailed travel distance in gravel bed transport: An exploratory enquiry
Authors: Hill K. M. , DellAngelo L. , Meerschaert Mark M.
Published: June 2010

Bed load transport, where particles move intermittently in frequent contact with the bed, is the dominant mode of particle transport in gravel bed rivers and streams. Complex fluid/particle and particle/particle interactions lead to a broad distribution of transport behaviors under the same set of flow conditions. In this paper, we investigate the plausibility of heavy‐tailed movements for particles in bed load transport using carefully controlled flume experiments and theoretical analysis. In our experimental setting, we find travel distances for particles of a given size follow an exponential distribution whose mean varies with grain size. Building on previous work of Stark et al. (2009), we then develop a probability model to show how heavy‐tailed distributions of travel distance can emerge from a mixture of particle sizes. Heavy‐tailed travel distance can lead to anomalous diffusion in bed load transport, modeled by fractional derivatives in the transport equation.
Electrodic voltages accompanying stimulated bioremediation of a uranium‐contaminated aquifer
Authors: Williams Kenneth H. , N'Guessan A. Lucie , Druhan Jennifer , Long Philip E. , Hubbard Susan S. , Lovley Derek R. , Banfield Jillian F.
Published: June 2010

The inability to track the products of subsurface microbial activity during stimulated bioremediation has limited its implementation. We used spatiotemporal changes in electrodic potentials (EP) to track the onset and persistence of stimulated sulfate‐reducing bacteria in a uranium‐contaminated aquifer undergoing acetate amendment. Following acetate injection, anomalous voltages approaching −900 mV were measured between copper electrodes within the aquifer sediments and a single reference electrode at the ground surface. Onset of EP anomalies correlated in time with both the accumulation of dissolved sulfide and the removal of uranium from groundwater. The anomalies persisted for 45 days after halting acetate injection. Current‐voltage and current‐power relationships between measurement and reference electrodes exhibited a galvanic response, with a maximum power density of 10 mW/m2 during sulfate reduction. We infer that the EP anomalies resulted from electrochemical differences between geochemically reduced regions and areas having higher oxidation potential. Following the period of sulfate reduction, EP values ranged from −500 to −600 mV and were associated with elevated concentrations of ferrous iron. Within 10 days of the voltage decrease, uranium concentrations rebounded from 0.2 to 0.8 μM, a level still below the background value of 1.5 μM. These findings demonstrate that EP measurements provide an inexpensive and minimally invasive means for monitoring the products of stimulated microbial activity within aquifer sediments and are capable of verifying maintenance of redox conditions favorable for the stability of bioreduced contaminants, such as uranium.
Nitrous oxide emissions from the upwelling area off Mauritania (NW Africa)
Authors: Wittke Franziska , Kock Annette , Bange Hermann W.
Published: June 2010

Nitrous oxide (N2O) flux densities across the ocean/atmosphere interface from the Mauritanian upwelling (16°–18.5°W, 16°–21°N) were computed with a simple upwelling model using N2O measurements from four cruises between 2006 and 2008 as well as wind data from the QuikSCAT satellite. The resulting N2O flux densities show a strong seasonality reflecting the wind‐driven seasonality of the upwelling: N2O flux densities are highest in the northern part (19.5°–21°N) and show a decreasing trend towards the south. The summer periods with no upwelling (and thus associated with no or negligible N2O flux densities) are most pronounced in the southern part (16°–17°N). The mean seasonally and regionally weighted annual N2O emissions from the Mauritanian upwelling were estimated to 1.0 Gg N. This is low compared to other major upwelling areas (Arabian Sea, off Chile) indicating that N2O emissions from the Mauritanian upwelling are a minor source of atmospheric N2O.
Sensitivity of river discharge to ENSO
Authors: Ward Philip J. , Beets Wisse , Bouwer Laurens M. , Aerts Jeroen C. J. H. , Renssen Hans
Published: June 2010

El Niño Southern Oscillation (ENSO) has significant impacts on streamflows around the world. While many studies have assessed correlations, an assessment of the magnitude of this impact is lacking, and little is known of ENSO's impact on extreme discharges. We use a daily discharge dataset to provide a global assessment of the sensitivity of annual mean and flood discharges to ENSO, and a gridded climate dataset to assess the global impact of ENSO on precipitation and temperature. We find that, on average, for the stations studied ENSO has a greater impact on annual high‐flow events than on mean annual discharge, especially in the extra‐tropics. The quantification of ENSO impacts provides relevant information for water‐management, allowing the identification of problem areas and providing a basis for risk assessments.
Modulation of mammary cancer cell migration by 15-deoxy-Δ12,14-prostaglandin J2: implications for anti-metastatic therapy
Authors: Diers Anne R. , Dranka Brian P. , Ricart Karina C. , Oh Joo Yeun , Johnson Michelle S. , Zhou Fen , Pallero Manuel A. , Bodenstine Thomas M. , Murphy-Ullrich Joanne E. , Welch Danny R. , Landar Aimee
Published: June 2010

Recently, a number of steps in the progression of metastatic disease have been shown to be regulated by redox signalling. Electrophilic lipids affect redox signalling through the post-translational modification of critical cysteine residues in proteins. However, the therapeutic potential as well as the precise mechanisms of action of electrophilic lipids in cancer cells is poorly understood. In the present study, we investigate the effect of the electrophilic prostaglandin 15d-PGJ2 (15-deoxy-Δ12,14-prostaglandin J2) on metastatic properties of breast cancer cells. 15d-PGJ2 was shown to decrease migration, stimulate focal-adhesion disassembly and cause extensive F-actin (filamentous actin) reorganization at low concentrations (0.03–0.3 μM). Importantly, these effects seem to be independent of PPARγ (peroxisome-proliferator-activated receptor γ) and modification of actin or Keap1 (Kelch-like ECH-associated protein 1), which are known protein targets of 15d-PGJ2 at higher concentrations. Interestingly, the p38 inhibitor SB203580 was able to prevent both 15d-PGJ2-induced F-actin reorganization and focal-adhesion disassembly. Taken together, the results of the present study suggest that electrophiles such as 15d-PGJ2 are potential anti-metastatic agents which exhibit specificity for migration and adhesion pathways at low concentrations where there are no observed effects on Keap1 or cytotoxicity.
Unusual organization, complexity and redundancy at the Escherichia coli hcp-hcr operon promoter
Authors: Chismon David L. , Browning Douglas F. , Farrant Gregory K. , Busby Stephen J. W.
Published: June 2010

Expression from the Escherichia coli hcp-hcr operon promoter is optimally induced during anaerobic conditions in the presence of nitrite. This expression depends on transcription activation by FNR (fumarate and nitrate reduction regulator), which binds to a target centred at position −72.5 upstream of the transcript start site. Mutational analysis was exploited to identify the corresponding −10 and −35 hexamer elements. A DNA site for NarL and NarP, located at position −104.5, plays only a minor role, whereas NsrR binding to a DNA target centred at position +6 plays a major role in induction of the hcp-hcr operon promoter. Electrophoretic mobility-shift assays show that NsrR binds to this target. The consequences of this for the kinetics of induction of the hcp-hcr operon are discussed.
Selective inhibition of ADAM12 catalytic activity through engineering of tissue inhibitor of metalloproteinase 2 (TIMP-2)
Authors: Kveiborg Marie , Jacobsen Jonas , Lee Meng-Huee , Nagase Hideaki , Wewer Ulla M. , Murphy Gillian
Published: June 2010

The disintegrin and metalloprotease ADAM12 has important functions in normal physiology as well as in diseases, such as cancer. Little is known about how ADAM12 confers its pro-tumorigenic effect; however, its proteolytic capacity is probably a key component. Thus selective inhibition of ADAM12 activity may be of great value therapeutically and as an investigative tool to elucidate its mechanisms of action. We have previously reported the inhibitory profile of TIMPs (tissue inhibitor of metalloproteinases) against ADAM12, demonstrating in addition to TIMP-3, a unique ADAM-inhibitory activity of TIMP-2. These findings strongly suggest that it is feasible to design a TIMP mutant selectively inhibiting ADAM12. With this purpose, we characterized the molecular determinants of the ADAM12–TIMP complex formation as compared with known molecular requirements for TIMP-mediated inhibition of ADAM17/TACE (tumour necrosis factor α-converting enzyme). Kinetic analysis using a fluorescent peptide substrate demonstrated that the molecular interactions of N-TIMPs (N-terminal domains of TIMPs) with ADAM12 and TACE are for the most part comparable, yet revealed strikingly unique features of TIMP-mediated ADAM12 inhibition. Intriguingly, we found that removal of the AB-loop in N-TIMP-2, which is known to impair its interaction with TACE, resulted in increased affinity to ADAM12. Importantly, using a cell-based epidermal growth factor-shedding assay, we demonstrated for the first time an inhibitory activity of TIMPs against the transmembrane ADAM12-L (full-length ADAM12), verifying the distinctive inhibitory abilities of N-TIMP-2 and engineered N-TIMP-2 mutants in a cellular environment. Taken together, our findings support the idea that a distinctive ADAM12 inhibitor with future therapeutic potential can be designed.
An optical counting technique with vertical hydrodynamic focusing for biological cells
Authors: Chiavaroli Stefano , Newport David , Woulfe Bernie
Published: June 2010

A barrier in scaling laboratory processes into automated microfluidic devices has been the transfer of laboratory based assays: Where engineering meets biological protocol. One basic requirement is to reliably and accurately know the distribution and number of biological cells being dispensed. In this study, a novel optical counting technique to efficiently quantify the number of cells flowing into a microtube is presented. REH, B-lymphoid precursor leukemia, are stained with a fluorescent dye and frames of moving cells are recorded using a charge coupled device (CCD) camera. The basic principle is to calculate the total fluorescence intensity of the image and to divide it by the average intensity of a single cell. This method allows counting the number of cells with an uncertainty ±5%, which compares favorably to the standard biological methodology, based on the manual Trypan Blue assay, which is destructive to the cells and presents an uncertainty in the order of 20%. The use of a microdevice for vertical hydrodynamic focusing, which can reduce the background noise of out of focus cells by concentrating the cells in a thin layer, has further improved the technique. Computational fluid dynamics (CFD) simulation and confocal laser scanning microscopy images have shown an 82% reduction in the vertical displacement of the cells. For the flow rates imposed during this study, a throughput of 100–200 cells/s is achieved.
Interlaced P3M algorithm with analytical and ik-differentiation
Authors: Neelov Alexey , Holm Christian
Published: June 2010

The interlacing technique of Hockney and Eastwood is extended to the particle-particle, particle-mesh (P3M) algorithm with analytical and ik-differentiation that computes the approximate Coulomb forces between N point particles in a periodic box. Interlacing means that one makes two separate computations of the reciprocal-space Ewald force, using two grids shifted with respect to each other by half of the diagonal of the grid subcell, and then takes the average of the two forces. The resulting algorithms compare favorably against their own noninterlaced versions and against the interlaced smooth particle-mesh Ewald algorithm. In our tests, the accuracy of the interlaced P3M methods was usually more than an order of magnitude higher than that of the other particle-mesh algorithms with the same parameter values. This accuracy gain can be converted into a speedup if the parameters of the algorithm are changed. Interlacing allows one to increase the grid spacing by up to a factor of 2 while keeping the same accuracy. A priori error estimates for the new algorithms are constructed, and the removal of the spurious self-force term is discussed. The success of interlacing is shown to be due to the fact that it suppresses the aliasing effects in the forces. It should be easy to incorporate the interlaced P3M algorithms into an existing simulation package, since this only requires a minor modification of the particle-mesh Ewald part of the code.
A numerical study of thermocapillary migration of a small liquid droplet on a horizontal solid surface
Authors: Nguyen Huy-Bich , Chen Jyh-Chen
Published: June 2010

In the present study, the transient thermocapillary migration of a small liquid droplet on a horizontal solid surface is numerically investigated. The droplet has a large static contact angle and a high aspect ratio of the maximum height of the droplet to its footprint. The Navier–Stokes and energy equations for both the droplet and surrounding air are solved through the finite element method. The evolution of the isotherms, the flow fields and the contact angle hysteresis are presented. Two asymmetric thermocapillary vortices appear inside the droplet. The variation of the size of the thermocapillary vortex during the migration process causes the speed of the droplet to first increase significantly, and then decrease gradually to approach a constant value. The higher imposed temperature gradient causes the droplet velocity to reach its maximal value earlier and have a higher final speed. If the static contact angle of the droplet is less than (or higher) than 90°, the droplet speed is lower (or higher) since the net thermocapillary momentum in the horizontal direction is diminished (or enhanced) by the presence of capillary force. The present results for the migration velocity and the contact angle hysteresis for a squalane droplet are also in good agreement with the previous experimental results.
WindFloat: A floating foundation for offshore wind turbines
Authors: Roddier Dominique , Cermelli Christian , Aubault Alexia , Weinstein Alla
Published: June 2010

This manuscript summarizes the feasibility study conducted for the WindFloat technology. The WindFloat is a three-legged floating foundation for multimegawatt offshore wind turbines. It is designed to accommodate a wind turbine, 5 MW or larger, on one of the columns of the hull with minimal modifications to the nacelle and rotor. Potential redesign of the tower and of the turbine control software can be expected. Technologies for floating foundations for offshore wind turbines are evolving. It is agreed by most experts that the offshore wind industry will see a significant increase in activity in the near future. Fixed offshore turbines are limited in water depth to ∼30–50 m. Market transition to deeper waters is inevitable, provided that suitable technologies can be developed. Despite the increase in complexity, a floating foundation offers the following distinct advantages: Flexibility in site location; access to superior wind resources further offshore; ability to locate in coastal regions with limited shallow continental shelf; ability to locate further offshore to eliminate visual impacts; an integrated hull, without a need to redesign the transition piece between the tower and the submerged structure for every project; simplified offshore installation procedures. Anchors are significantly cheaper to install than fixed foundations and large diameter towers. This paper focuses first on the design basis for wind turbine floating foundations and explores the requirements that must be addressed by design teams in this new field. It shows that the design of the hull for a large wind turbine must draw on the synergies with oil and gas offshore platform technology, while accounting for the different design requirements and functionality of the wind turbine. This paper describes next the hydrodynamic analysis of the hull, as well as ongoing work consisting of coupling hull hydrodynamics with wind turbine aerodynamic forces. Three main approaches are presented: The numerical hydrodynamic model of the platform and its mooring system; wave tank testing of a scale model of the platform with simplified aerodynamic simulation of the wind turbine; FAST, an aeroservoelastic software package for wind turbine analysis with the ability to be coupled to the hydrodynamic model. Finally, this paper focuses on the structural engineering that was performed as part of the feasibility study conducted for qualification of the technology. Specifically, the preliminary scantling is described and the strength and fatigue analysis methodologies are explained, focusing on the following aspects: The coupling between the wind turbine and the hull and the interface between the hydrodynamic loading and the structural response.
Rotation dependence of a phase delay between plasma edge electron density and temperature fields due to a fast rotating, resonant magnetic perturbation field
Authors: Stoschus H. , Schmitz O. , Frerichs H. , Jakubowski M. W. , Unterberg B. , Abdullaev S. S. , Clever M. , Coenen J. W. , Kruezi U. , Schega D. , Samm U. ,   TEXTOR Research Team
Published: June 2010

Measurements of the plasma edge electron density ne and temperature Te fields during application of a fast rotating, resonant magnetic perturbation (RMP) field show a characteristic modulation of both, ne and Te coherent to the rotation frequency of the RMP field. A phase delay Φ between the ne(t) and Te(t) waveforms is observed and it is demonstrated that this phase delay Φ is a function of the radius with Φ(r) depending on the relative rotation of the RMP field and the toroidal plasma rotation. This provides for the first time direct experimental evidence for a rotation dependent damping of the external RMP field in the edge layer of a resistive high-temperature plasma which breaks down at low rotation and high resonant field amplitudes.
A refined hydrogen bond potential for flexible protein models
Authors: Enciso Marta , Rey Antonio
Published: June 2010

One of the major disadvantages of coarse-grained hydrogen bond potentials, for their use in protein folding simulations, is the appearance of abnormal structures when these potentials are used in flexible chain models, and no other geometrical restrictions or energetic contributions are defined into the system. We have efficiently overcome this problem, for chains of adequate size in a relevant temperature range, with a refined coarse-grained hydrogen bond potential. With it, we have been able to obtain nativelike α-helices and β-sheets in peptidic systems, and successfully reproduced the competition between the populations of these secondary structure elements by the effect of temperature and concentration changes. In this manuscript we detail the design of the interaction potential and thoroughly examine its applicability in energetic and structural terms, considering factors such as chain length, concentration, and temperature.
Narrow-escape times for diffusion in microdomains with a particle-surface affinity: Mean-field results
Authors: Oshanin G. , Tamm M. , Vasilyev O.
Published: June 2010

We analyze the mean time tapp that a randomly moving particle spends in a bounded domain (sphere) before it escapes through a small window in the domain’s boundary. A particle is assumed to diffuse freely in the bulk until it approaches the surface of the domain where it becomes weakly adsorbed, and then wanders diffusively along the boundary for a random time until it desorbs back to the bulk, etc. Using a mean-field approximation, we define tapp analytically as a function of the bulk and surface diffusion coefficients, the mean time it spends in the bulk between two consecutive arrivals to the surface and the mean time it wanders on the surface within a single round of the surface diffusion.
Thin films of polymer blends for controlled drug delivery deposited by matrix-assisted pulsed laser evaporation
Authors: Paun Irina Alexandra , Ion Valentin , Moldovan Antoniu , Dinescu Maria
Published: June 2010

We demonstrate the use of matrix-assisted pulsed laser evaporation technique for incorporating drugs (indomethacin) within thin films of polymer blends, to be used as biodegradable implants that deliver drugs in a controlled manner. For irradiation at fluences up to 1 J/cm2, the films show excellent surface morphology and the chemical structure of all constituent polymers within the blend is well preserved. The optical characteristics of the films are assessed by spectroscopic ellipsometry. The presence of the drug within the polymeric films is confirmed by its specific absorption at 319 nm.
Influence of positive bias stress on N2O plasma improved InGaZnO thin film transistor
Authors: Tsai Chih-Tsung , Chang Ting-Chang , Chen Shih-Ching , Lo Ikai , Tsao Shu-Wei , Hung Ming-Chin , Chang Jiun-Jye , Wu Chen-Yi , Huang Chun-Yao
Published: June 2010

A post-treatment using N2O-plasma is applied to enhance the electrical characteristics of amorphous indium gallium zinc oxide thin film transistors. Improvements in the field-effect mobility and the subthreshold swing demonstrate that interface states were passivated after N2O-plasma treatment, and a better stability under positive gate-bias stress was obtained in addition. The degradation of mobility, resulted from bias stress, reduces from 6.1% (untreated devices) to 2.6% (N2O-plasma treated devices). Nevertheless, a strange hump characteristic occurs in transfer curve during bias stress, inferring that a parasitic transistor had been caused by the gate-induced electrical field.
Photocurrent characteristics of two-dimensional-electron-gas-based AlGaN/GaN metal-semiconductor-metal photodetectors
Authors: Huang Y. , Chen D. J. , Lu H. , Shi H. B. , Han P. , Zhang R. , Zheng Y. D.
Published: June 2010

Photocurrent response characteristics of two-dimensional-electron-gas-based AlGaN/GaN metal-semiconductor-metal (MSM) photodetectors were investigated by changing the frequency of incident light signals. At low chopper frequencies, the contribution to the photocurrent is mainly from the GaN bulk layer at 5 V bias, as expected. With increasing chopper frequency, a peak response at 361 nm wavelength becomes more and more pronounced and dominates gradually the photocurrent spectrum, indicating that this peak response has a much less frequency dependence and a faster response rate than the spectral response from the GaN bulk layer. This peak response is attributed to the contribution of photoelectrons generated in the two-dimensional electron gas (2DEG) channel according to simulation results of electrical field distribution and analysis of carrier transport in the 2DEG-based AlGaN/GaN heterostructure. This characteristic makes the 2DEG-based MSM photodetectors a large potential to develop high-speed ultraviolet optoelectronic integrated devices with AlGaN/GaN high electron mobility transistors.
Thermodynamic analysis of moisture absorption phenomena in high-permittivity oxides as gate dielectrics of advanced complementary-metal-oxide-semiconductor devices
Authors: Zhao Yi , Kita Koji , Toriumi Akira
Published: June 2010

The moisture absorption phenomena in high-permittivity (k) oxides were analyzed from the view point of the thermodynamic process. The Gibbs free energy change (ΔG) in the moisture absorption reactions were calculated with the thermodynamic data of oxides, water (H2O), and hydroxides. It was found from the calculation results that the moisture absorption is a common phenomenon in high-k oxides, especially in rare earth oxides. The results also show that lanthanum oxide (La2O3) has the largest moisture-absorption-reaction speed among main candidates for high-k gate oxides. Doping a second oxide could be a direct and effective method to enhance the moisture resistance of La2O3 films.
Hot carrier injection from nanometer-thick silicon-on-insulator films measured by optical second-harmonic generation
Authors: Lei Ming , Price J. , Downer M. C.
Published: June 2010

Time-dependent electrostatic field-induced second-harmonic (TD-EFISH) generation is used to probe optically excited hot carrier injection (HCI) from silicon-on-insulator (SOI) films as thin as 2 nm into both native oxide and buried oxide (BOX), without device fabrication. The two HCI processes induce TD-EFISH signals of opposite sign, at different rates, whereby they are distinguished straightforwardly. HCI at the SOI/BOX interface is dominated by two-photon injection into HF defect induced traps created during SOI thinning. The results demonstrate that SHG can noninvasively and quantitatively characterize HCI, a key determinant of SOI device reliability.
Structure, function, and self-assembly of single network gyroid (
I
4
1
32) photonic crystals in butterfly wing scales
Authors: Saranathan Vinodkumar , Osuji Chinedum O. , Mochrie Simon G. J. , Noh Heeso , Narayanan Suresh , Sandy Alec , Dufresne Eric R. , Prum Richard O.
Published: June 2010

Complex three-dimensional biophotonic nanostructures produce the vivid structural colors of many butterfly wing scales, but their exact nanoscale organization is uncertain. We used small angle X-ray scattering (SAXS) on single scales to characterize the 3D photonic nanostructures of five butterfly species from two families (Papilionidae, Lycaenidae). We identify these chitin and air nanostructures as single network gyroid (
I
4
1
32) photonic crystals. We describe their optical function from SAXS data and photonic band-gap modeling. Butterflies apparently grow these gyroid nanostructures by exploiting the self-organizing physical dynamics of biological lipid-bilayer membranes. These butterfly photonic nanostructures initially develop within scale cells as a core-shell double gyroid (
Ia3d
), as seen in block-copolymer systems, with a pentacontinuous volume comprised of extracellular space, cell plasma membrane, cellular cytoplasm, smooth endoplasmic reticulum (SER) membrane, and intra-SER lumen. This double gyroid nanostructure is subsequently transformed into a single gyroid network through the deposition of chitin in the extracellular space and the degeneration of the rest of the cell. The butterflies develop the thermodynamically favored double gyroid precursors as a route to the optically more efficient single gyroid nanostructures. Current approaches to photonic crystal engineering also aim to produce single gyroid motifs. The biologically derived photonic nanostructures characterized here may offer a convenient template for producing optical devices based on biomimicry or direct dielectric infiltration.
Lack of lacto/neolacto-glycolipids enhances the formation of glycolipid-enriched microdomains, facilitating B cell activation
Authors: Togayachi Akira , Kozono Yuko , Ikehara Yuzuru , Ito Hiromi , Suzuki Nami , Tsunoda Yuki , Abe Sumie , Sato Takashi , Nakamura Kyoko , Suzuki Minoru , Goda Hatsumi M. , Ito Makoto , Kudo Takashi , Takahashi Satoru , Narimatsu Hisashi
Published: June 2010

In a previous study, we demonstrated that β1,3-
N
-acetylglucosaminyltransferase 5 (
B3gnt5
) is a lactotriaosylceramide (Lc
3
Cer) synthase that synthesizes a precursor structure for lacto/neolacto-series glycosphingolipids (GSLs) in in vitro experiments. Here, we generated
B3gnt5
-deficient (
B3gnt5
−/−
) mice to investigate the in vivo biological functions of lacto/neolacto-series GSLs. In biochemical analyses, lacto/neolacto-series GSLs were confirmed to be absent and no Lc
3
Cer synthase activity was detected in the tissues of these mice. These results demonstrate that β3GnT5 is the sole enzyme synthesizing Lc
3
Cer in vivo. Ganglioside GM1, known as a glycosphingolipid-enriched microdomain (GEM) marker, was found to be up-regulated in
B3gnt5
−/−
B cells by flow cytometry and fluorescence microscopy. However, no difference in the amount of GM1 was observed by TLC-immunoblotting analysis. The GEM-stained puncta on the surface of
B3gnt5
−/−
resting B cells were brighter and larger than those of WT cells. These results suggest that structural alteration of GEM occurs in
B3gnt5
−/−
B cells. We next examined whether BCR signaling-related proteins, such as BCR, CD19, and the signaling molecule Lyn, had moved into or out of the GEM fraction. In
B3gnt5
−/−
B cells, these molecules were enriched in the GEM fraction or adjacent fraction. Moreover,
B3gnt5
−/−
B cells were more sensitive to the induction of intracellular phosphorylation signals on BCR stimulation and proliferated more vigorously than WT B cells. Together, these results suggest that lacto/neolacto-series GSLs play an important role in clustering of GEMs and tether-specific proteins, such as BCR, CD19, and related signaling molecules to the GEMs.
Common biosynthetic origins for polycyclic tetramate macrolactams from phylogenetically diverse bacteria
Authors: Blodgett Joshua A. V. , Oh Dong-Chan , Cao Shugeng , Currie Cameron R. , Kolter Roberto , Clardy Jon
Published: June 2010

A combination of small molecule chemistry, biosynthetic analysis, and genome mining has revealed the unexpected conservation of polycyclic tetramate macrolactam biosynthetic loci in diverse bacteria. Initially our chemical analysis of a
Streptomyces
strain associated with the southern pine beetle led to the discovery of frontalamides A and B, two previously undescribed members of this antibiotic family. Genome analyses and genetic manipulation of the producing organism led to the identification of the frontalamide biosynthetic gene cluster and several biosynthetic intermediates. The biosynthetic locus for the frontalamides’ mixed polyketide/amino acid structure encodes a hybrid polyketide synthase nonribosomal peptide synthetase (PKS-NRPS), which resembles iterative enzymes known in fungi. No such mixed iterative PKS-NRPS enzymes have been characterized in bacteria. Genome-mining efforts revealed strikingly conserved frontalamide-like biosynthetic clusters in the genomes of phylogenetically diverse bacteria ranging from proteobacteria to actinomycetes. Screens for environmental actinomycete isolates carrying frontalamide-like biosynthetic loci led to the isolation of a number of positive strains, the majority of which produced candidate frontalamide-like compounds under suitable growth conditions. These results establish the prevalence of frontalamide-like gene clusters in diverse bacterial types, with medicinally important
Streptomyces
species being particularly enriched.
Structure of the Rift Valley fever virus nucleocapsid protein reveals another architecture for RNA encapsidation
Authors: Raymond Donald D. , Piper Mary E. , Gerrard Sonja R. , Smith Janet L.
Published: June 2010

Rift Valley fever virus (RVFV) is a negative-sense RNA virus (genus
Phlebovirus
, family
Bunyaviridae
) that infects livestock and humans and is endemic to sub-Saharan Africa. Like all negative-sense viruses, the segmented RNA genome of RVFV is encapsidated by a nucleocapsid protein (N). The 1.93-Å crystal structure of RVFV N and electron micrographs of ribonucleoprotein (RNP) reveal an encapsidated genome of substantially different organization than in other negative-sense RNA virus families. The RNP polymer, viewed in electron micrographs of both virus RNP and RNP reconstituted from purified N with a defined RNA, has an extended structure without helical symmetry. N-RNA species of ∼100-kDa apparent molecular weight and heterogeneous composition were obtained by exhaustive ribonuclease treatment of virus RNP, by recombinant expression of N, and by reconstitution from purified N and an RNA oligomer. RNA-free N, obtained by denaturation and refolding, has a novel all-helical fold that is compact and well ordered at both the N and C termini. Unlike N of other negative-sense RNA viruses, RVFV N has no positively charged surface cleft for RNA binding and no protruding termini or loops to stabilize a defined N-RNA oligomer or RNP helix. A potential protein interaction site was identified in a conserved hydrophobic pocket. The nonhelical appearance of phlebovirus RNP, the heterogeneous ∼100-kDa N-RNA multimer, and the N fold differ substantially from the RNP and N of other negative-sense RNA virus families and provide valuable insights into the structure of the encapsidated phlebovirus genome.
Endogenous antibodies promote rapid myelin clearance and effective axon regeneration after nerve injury
Authors: Vargas Mauricio E. , Watanabe Junryo , Singh Simar J. , Robinson William H. , Barres Ben A.
Published: June 2010

Degenerating myelin inhibits axon regeneration and is rapidly cleared after peripheral (PNS) but not central nervous system (CNS) injury. To better understand mechanisms underlying rapid PNS myelin clearance, we tested the potential role of the humoral immune system. Here, we show that endogenous antibodies are required for rapid and robust PNS myelin clearance and axon regeneration. B-cell knockout JHD mice display a significant delay in macrophage influx, myelin clearance, and axon regeneration. Rapid clearance of myelin debris is restored in mutant JHD mice by passive transfer of antibodies from naïve WT mice or by an anti-PNS myelin antibody, but not by delivery of nonneural antibodies. We demonstrate that degenerating nerve tissue is targeted by preexisting endogenous antibodies that control myelin clearance by promoting macrophage entrance and phagocytic activity. These results demonstrate a role for immunoglobulin (Ig) in clearing damaged self during healing and suggest that the immune-privileged status of the CNS may contribute to failure of CNS myelin clearance and axon regeneration after injury.
Fgf-9
is required for angiogenesis and osteogenesis in long bone repair
Authors: Behr Björn , Leucht Philipp , Longaker Michael T. , Quarto Natalina
Published: June 2010

Bone healing requires a complex interaction of growth factors that establishes an environment for efficient bone regeneration. Among these, FGFs have been considered important for intrinsic bone-healing capacity. In this study, we analyzed the role of
Fgf-9
in long bone repair. One-millimeter unicortical defects were created in tibias of

Fgf-9
+/−

and wild-type mice. Histomorphometry revealed that half-dose gene of
Fgf-9
markedly reduced bone regeneration as compared with wild-type. Both immunohistochemistry and RT-PCR analysis revealed markedly decreased levels of proliferating cell nuclear antigen (PCNA), Runt-related transcription factor 2 (Runx2), osteocalcin, Vega-a, and platelet endothelial cell adhesion molecule 1 (PECAM-1) in

Fgf-9
+/−

defects. μCT angiography indicated dramatic impairment of neovascularization in

Fgf-9
+/−

mice as compared with controls. Treatment with FGF-9 protein promoted angiogenesis and successfully rescued the healing capacity of

Fgf-9
+/−

mice. Importantly, although other pro-osteogenic factors [
Fgf-2
,
Fgf-18
, and bone morphogenic protein 2 (
Bmp-2
)] still were present in

Fgf-9
+/−

mice, they could not compensate for the haploinsufficiency of the
Fgf-9
gene. Therefore, endogenous
Fgf-9
seems to play an important role in long bone repair. Taken together our data suggest a unique role for
Fgf-9
in bone healing, presumably by initiating angiogenesis through Vegf-a. Moreover, this study further supports the embryonic phenotype previously observed in the developing limb, thus promoting the concept that healing processes in adult organisms may recapitulate embryonic skeletal development.
Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom
Coprinopsis cinerea
(
Coprinus cinereus
)
Authors: Stajich Jason E. , Wilke Sarah K. , Ahrén Dag , Au Chun Hang , Birren Bruce W. , Borodovsky Mark , Burns Claire , Canbäck Björn , Casselton Lorna A. , Cheng C.K. , Deng Jixin , Dietrich Fred S. , Fargo David C. , Farman Mark L. , Gathman Allen C. , Goldberg Jonathan , Guigó Roderic , Hoegger Patrick J. , Hooker James B. , Huggins Ashleigh , James Timothy Y. , Kamada Takashi , Kilaru Sreedhar , Kodira Chinnapa , Kües Ursula , Kupfer Doris , Kwan H.S. , Lomsadze Alexandre , Li Weixi , Lilly Walt W. , Ma Li-Jun , Mackey Aaron J. , Manning Gerard , Martin Francis , Muraguchi Hajime , Natvig Donald O. , Palmerini Heather , Ramesh Marilee A. , Rehmeyer Cathy J. , Roe Bruce A. , Shenoy Narmada , Stanke Mario , Ter-Hovhannisyan Vardges , Tunlid Anders , Velagapudi Rajesh , Vision Todd J. , Zeng Qiandong , Zolan Miriam E. , Pukkila Patricia J.
Published: June 2010

The mushroom
Coprinopsis cinerea
is a classic experimental model for multicellular development in fungi because it grows on defined media, completes its life cycle in 2 weeks, produces some 10
8
synchronized meiocytes, and can be manipulated at all stages in development by mutation and transformation. The 37-megabase genome of
C. cinerea
was sequenced and assembled into 13 chromosomes. Meiotic recombination rates vary greatly along the chromosomes, and retrotransposons are absent in large regions of the genome with low levels of meiotic recombination. Single-copy genes with identifiable orthologs in other basidiomycetes are predominant in low-recombination regions of the chromosome. In contrast, paralogous multicopy genes are found in the highly recombining regions, including a large family of protein kinases (FunK1) unique to multicellular fungi. Analyses of P450 and hydrophobin gene families confirmed that local gene duplications drive the expansions of paralogous copies and the expansions occur in independent lineages of Agaricomycotina fungi. Gene-expression patterns from microarrays were used to dissect the transcriptional program of dikaryon formation (mating). Several members of the FunK1 kinase family are differentially regulated during sexual morphogenesis, and coordinate regulation of adjacent duplications is rare. The genomes of
C. cinerea
and
Laccaria bicolor
, a symbiotic basidiomycete, share extensive regions of synteny. The largest syntenic blocks occur in regions with low meiotic recombination rates, no transposable elements, and tight gene spacing, where orthologous single-copy genes are overrepresented. The chromosome assembly of
C. cinerea
is an essential resource in understanding the evolution of multicellularity in the fungi.
Nucleobase-mediated general acid-base catalysis in the Varkud satellite ribozyme
Authors: Wilson Timothy J. , Li Nan-Sheng , Lu Jun , Frederiksen John K. , Piccirilli Joseph A. , Lilley David M. J.
Published: June 2010

Existing evidence suggests that the Varkud satellite (VS) ribozyme accelerates the cleavage of a specific phosphodiester bond using general acid-base catalysis. The key functionalities are the nucleobases of adenine 756 in helix VI of the ribozyme, and guanine 638 in the substrate stem loop. This results in a bell-shaped dependence of reaction rate on pH, corresponding to groups with p
K
a
 = 5.2 and 8.4. However, it is not possible from those data to determine which nucleobase is the acid, and which the base. We have therefore made substrates in which the 5′ oxygen of the scissile phosphate is replaced by sulfur. This labilizes the leaving group, removing the requirement for general acid catalysis. This substitution restores full activity to the highly impaired A756G ribozyme, consistent with general acid catalysis by A756 in the unmodified ribozyme. The pH dependence of the cleavage of the phosphorothiolate-modified substrates is consistent with general base catalysis by nucleobase at position 638. We conclude that cleavage of the substrate by the VS ribozyme is catalyzed by deprotonation of the 2′-O nucleophile by G638 and protonation of the 5′-O leaving group by A756.
Trans
locus inhibitors limit concomitant polysaccharide synthesis in the human gut symbiont
Bacteroides fragilis
Authors: Chatzidaki-Livanis Maria , Weinacht Katja G. , Comstock Laurie E.
Published: June 2010

Bacteroides
is an abundant genus of bacteria of the human intestinal microbiota.
Bacteroides
species synthesize a large number of capsular polysaccharides (PS), a biological property not shared with closely related oral species, suggesting importance for intestinal survival.
Bacteroides fragilis
, for example, synthesizes eight capsular polysaccharides per strain, each of which phase varies via inversion of the promoters located upstream of seven of the eight polysaccharide biosynthesis operons. In a single cell, many of these polysaccharide loci promoters can be simultaneously oriented on for transcription of the downstream biosynthesis operons. Here, we demonstrate that despite the promoter orientations, concomitant transcription of multiple polysaccharide loci within a cell is inhibited. The proteins encoded by the second gene of each of these eight loci, collectively designated the UpxZ proteins, inhibit the synthesis of heterologous polysaccharides. These unique proteins interfere with the ability of UpxY proteins encoded by other polysaccharide loci to function in transcriptional antitermination of their respective operon. The eight UpxZs have different inhibitory spectra, thus establishing a hierarchical regulatory network for polysaccharide synthesis. Limitation of concurrent polysaccharide synthesis strongly suggests that these bacteria evolved this property as an evasion-type mechanism to avoid killing by polysaccharide-targeting factors in the ecosystem.
Preferential localization of IgG memory B cells adjacent to contracted germinal centers
Authors: Aiba Yuichi , Kometani Kohei , Hamadate Megumi , Moriyama Saya , Sakaue-Sawano Asako , Tomura Michio , Luche Hervé , Fehling Hans Jörg , Casellas Rafael , Kanagawa Osami , Miyawaki Atsushi , Kurosaki Tomohiro
Published: June 2010

It has long been presumed that after leaving the germinal centers (GCs), memory B cells colonize the marginal zone or join the recirculating pool. Here we demonstrate the preferential localization of nitrophenol-chicken γ-globulin-induced CD38+IgG1+memory B cells adjacent to contracted GCs in the spleen. The memory B cells in this region proliferated after secondary immunization, a response that was abolished by depletion of CD4+T cells. We also found that these IgG1+memory B cells could present antigen on their surface, and that this activity was required for their activation. These results implicate this peri-GC region as an important site for survival and reactivation of memory B cells.
Overcoming cancer cell resistance to Smac mimetic induced apoptosis by modulating cIAP-2 expression
Authors: Petersen Sean L. , Peyton Michael , Minna John D. , Wang Xiaodong
Published: June 2010

Smac mimetics target cancer cells in a TNFα-dependent manner, partly via proteasome degradation of cellular inhibitor of apoptosis 1 (cIAP1) and cIAP2. Degradation of cIAPs triggers the release of receptor interacting protein kinase (RIPK1) from TNF receptor I (TNFR1) to form a caspase-8 activating complex together with the adaptor protein Fas-associated death domain (FADD). We report here a means through which cancer cells mediate resistance to Smac mimetic/TNFα-induced apoptosis and corresponding strategies to overcome such resistance. These human cancer cell lines evades Smac mimetic-induced apoptosis by up-regulation of cIAP2, which although initially degraded, rebounds and is refractory to subsequent degradation. cIAP2 is induced by TNFα via NF-κB and modulation of the NF-κB signal renders otherwise resistant cells sensitive to Smac mimetics. In addition, other signaling pathways, including phosphatidyl inositol-3 kinase (PI3K), have the potential to concurrently regulate cIAP2. Using the PI3K inhibitor, LY294002, cIAP2 up-regulation was suppressed and resistance to Smac mimetics-induced apoptosis was also overcome.