bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of thioredoxin reductase 1 inhibits migration of HEK‐293 cells
Authors: Sroka Jolanta , Antosik Agata , Czyż Jarosław , Nalvarte Ivan , Olsson Jerker M. , Spyrou Giannis , Madeja Zbigniew
Published: November 2007

Background information. TrxR (thioredoxin reductase), in addition to protecting against oxidative stress, plays a role in the redox regulation of intracellular signalling pathways controlling, among others, cell proliferation and apoptosis. The aim of the present study was to determine whether TrxR1 is involved in the regulation of cell migration.

Results. Stably transfected HEK‐293 (human embryonic kidney) cells which overexpress cytosolic TrxR1 (HEK‐TrxR15 and HEK‐TrxR11 cells) were used in the present study. We found that the stimulation of cell motility induced by PKC (protein kinase C) activators, PMA and DPhT (diphenyltin), was inhibited significantly in the HEK‐TrxR15 and HEK‐TrxR11 cells compared with control cells. The overexpression of TrxR1 also inhibited characteristic morphological changes and reorganization of the F‐actin cytoskeleton induced by PMA and DPhT. In addition, the selective activation of PKCδ by DPhT was inhibited in cells that overexpressed cytosolic TrxR1. Furthermore, rottlerin, a selective inhibitor of PKCδ, and PKCδ siRNA (small interfering RNA), suppressed the morphological changes induced by DPhT in the control cells.

Conclusions. The overexpression of TrxR1 inhibits migration of HEK‐293 cells stimulated with PMA and DPhT. Moreover, our observations suggest that this effect is mediated by the inhibition of PKCδ activation.
Influence of N on the electronic properties of GaAsN alloy films and heterostructures
Authors: Reason M. , Jin Y. , McKay H. A. , Mangan N. , Mao D. , Goldman R. S. , Bai X. , Kurdak C.
Published: November 2007

We have investigated the effects of N on the electronic properties of Si-doped GaAs1−xNx alloy films and AlGaAs∕GaAsN modulation-doped heterostructures. For bulk-like alloy films, the electron mobility is independent of free carrier concentration and arsenic species, and decreases with increasing N composition. Thus, N-related defects are the main source of scattering in the dilute nitride alloys. For AlGaAs∕GaAsN heterostructures, gated and illuminated magnetoresistance measurements reveal a two-dimensional electron gas mobility which increases with carrier concentration to a constant value. Thus, in contrast to the long-range ionized scattering sources which are dominant in N-free heterostructures, N-induced neutral scattering sources are the dominant source of scattering in AlGaAs∕GaAsN heterostructures. Finally, a decrease in free carrier concentration with increasing N composition is apparent for bulk-like films, while the free carrier concentration is independent of N composition in modulation-doped heterostructures. Since N and Si atoms are spatially separated in the modulation-doped heterostructures, N–Si defect complexes in the bulk GaAsN layers are likely acting as trapping centers.
Experimental synchronization of single-transistor-based chaotic circuits
Authors: Fortuna Luigi , Frasca Mattia
Published: November 2007

This work deals with nonautonomous chaotic circuits and, in particular, with the experimental characterization of the synchronization properties of two simple nonautonomous circuits. Two single-transistor chaotic circuits, which are among the simplest chaotic oscillators, are investigated. We studied synchronization of these circuits and found that the most appropriate technique to synchronize two single-transistor chaotic circuits is that based on the design of an inverse circuit.
Maps of the stress distributions in drying latex films
Authors: von der Ehe Kerstin , Johannsmann Diethelm
Published: November 2007

We report on spatially resolved measurements of the mechanical stress in drying polymer films. The technique is based on the deflection of a flexible membrane serving as the substrate. Assuming that the lateral tension of the membrane is the main source of its resistance to deformation, one can show that the local surface stress σf (x,y) is proportional to the vertical displacement of the membrane uz(x,y). The membrane distortion was determined by optical means. Measurements taken on drying latex dispersions revealed a maximum of film stress at the rim. The heterogeneous stress distribution often persisted after the film had become dry.
Laser-induced breakdown spectroscopy of trisilane using infrared CO2 laser pulses
Authors: Camacho J. J. , Poyato J. M. L. , Díaz L. , Santos M.
Published: November 2007

The plasma produced in trisilane (Si3H8) at room temperature and pressures ranging from 50to103Pa by laser-induced breakdown (LIB) has been investigated. The ultraviolet-visible-near infrared emission generated by high-power IR CO2 laser pulses in Si3H8 has been studied by means of optical emission spectroscopy. Optical breakdown threshold intensities in trisilane at 10.591μm for laser pulse lengths of 100ns have been measured as a function of gas pressure. The strong emission observed in the plasma region is mainly due to electronic relaxation of excited atomic H and Si and ionic fragments Si+, Si2+, and Si3+. An excitation temperature Texc=5600±300K was calculated by means of H atomic lines assuming local thermodynamic equilibrium. The physical processes leading to LIB of trisilane in the power density range 0.28GWcm−2<J<3.99GWcm−2 have been analyzed. From our experimental observations we can propose that, although the first electrons must appear via multiphoton ionization, electron cascade is the main mechanism responsible for the breakdown in trisilane.
Effect of plasma temperature on electrostatic shock generation and ion acceleration by laser
Authors: Zhang Xiaomei , Shen Baifei , Yu M. Y. , Li Xuemei , Jin Zhangying , Wang Fengchao , Wen Meng
Published: November 2007

The effect of plasma temperature on electrostatic shock generated by a circularly polarized laser pulse in overdense plasma is studied by particle-in-cell simulation. Ion reflection and transmission in the collisionless electrostatic shock (CES) are investigated analytically. As the initial ion temperature is varied, a distinct transition from the laser-driven piston scenario with all ions being reflected to the CES scenario with partial ion reflection is found. The results show that at low but finite temperatures the ions are much more accelerated than if they were cold.
Influence of fullerene dispersion on high temperature thermoelectric properties of BayCo4Sb12-based composites
Authors: Shi X. , Chen L. D. , Bai S. Q. , Huang X. Y. , Zhao X. Y. , Yao Q. , Uher C.
Published: November 2007

Ba y Co 4 Sb 12 -based composites with dispersed fullerene or barium fulleride have been synthesized by the solid state reaction and spark plasma sintering technique. When fullerene was used as a dispersed phase, a part of barium in the filled skutterudite reacted with fullerene to form barium fullerides. Most of the extended impurity aggregated to form large defects at the grain boundaries of the matrix. The thermoelectric properties of the composites were measured from room temperature to 850 K. Both the electrical conductivity and thermal conductivity decreased with increasing impurity contents. We attributed these significant reductions to enhanced grain-boundary scattering of charge carriers and phonons. A large ZT value of 1.3 was obtained in a composite with an appropriate content of fullerene dispersants.
Ferroelectric poly(vinylidene fluoride) thin films on Si substrate with the β phase promoted by hydrated magnesium nitrate
Authors: Chen Shuting , Yao Kui , Tay Francis Eng Hock , Liow Chung Lee
Published: November 2007

Solution derived poly(vinylidene fluoride) (PVDF) homopolymer thin films on silicon substrates with the addition of hydrated salt [Mg(NO3)2⋅6H2O] were systematically investigated. β phase dominant ferroelectric PVDF thin films with a remnant polarization of 77 mC∕m2 were achieved by optimizing the concentration of Mg(NO3)2⋅6H2O and the processing condition. Our experimental results and theoretical analysis indicated that the hydrogen bonds between water in the hydrated salt and the PVDF molecules result in the interchain registration of the all-trans conformation, and the hydrated salt acts as the nucleation agent and promotes the crystallization of the β phase. The obtained effective d33 was −14.5 pm∕V, tested with a laser scanning vibrometer, without taking into account the substrate clamping effect. The numerical simulation, after considering the elastic constrain of the substrate, determined that the corresponding actual d33 is −30.8 pm∕V, which is comparable to that of uniaxially stretched piezoelectric PVDF films.
Effect of pinholes in magnetic tunnel junctions
Authors: Chen Xi , Victora R. H.
Published: November 2007

The electron transport in magnetic tunnel junction containing pinholes is studied, where ferromagnetic layers make direct contact through narrow conducting channels. The transport is treated within the Landauer formalism using a tight-binding Hamiltonian. It is found that a narrow pinhole induces a resonant tunneling behavior causing a magnetoresistance that oscillates with the bias voltage. After averaging over pinholes of various shapes, the oscillation and magnitude of magnetoresistance (MR) are reduced, which can explain how barrier roughness diminishes the MR. For a pinhole of a large radius, where the number of atoms inside is much larger than 1, an enhanced MR is obtained whose value is similar to an all-metal giant magnetoresistance spin valve.
Energy transfer in porous-silicon/laser-dye composite evidenced by polarization memory of photoluminescence
Authors: Chouket A. , Elhouichet H. , Oueslati M. , Koyama H. , Gelloz B. , Koshida N.
Published: November 2007

The optical properties of nanocomposites are studied for rhodamine B (RhB) dye molecules embedded in nanoscale porous silicon (PS) and porous silica (P-silica). The samples are prepared by simple immersion of porous matrix substrates in RhB solutions. Fourier transform infrared spectroscopy suggests that RhB molecules fully penetrate into the porous matrix. Efficient photoluminescence has been observed in all experimental nanocomposites. The measurement of the polarization memory (PM) effect provides a clear evidence for the presence of an excitation energy transfer from PS to RhB molecules, in contrast to the PM behavior in RhB∕P-silica composite.
Single-electron quantum dot in Si∕SiGe with integrated charge sensing
Authors: Simmons C. B. , Thalakulam Madhu , Shaji Nakul , Klein Levente J. , Qin Hua , Blick R. H. , Savage D. E. , Lagally M. G. , Coppersmith S. N. , Eriksson M. A.
Published: November 2007

Single-electron occupation is an essential component to the measurement and manipulation of spin in quantum dots, capabilities that are important for quantum information processing. Si∕SiGe is of interest for semiconductor spin qubits, but single-electron quantum dots have not yet been achieved in this system. We report the fabrication and measurement of a top-gated quantum dot occupied by a single electron in a Si∕SiGe heterostructure. Transport through the quantum dot is directly correlated with charge sensing from an integrated quantum point contact, and this charge sensing is used to confirm single-electron occupancy in the quantum dot.
Application of photoionization models based on radiative transfer and the Helmholtz equations to studies of streamers in weak electric fields
Authors: Liu Ningyu , Célestin Sébastien , Bourdon Anne , Pasko Victor P. , Ségur Pierre , Marode Emmanuel
Published: November 2007

Recent advances in development of photoionization models in air based on radiative transfer and Helmholtz equations open new perspectives for efficient solution of nonthermal gas discharge problems involving complex geometries. Many practical applications require accurate modeling of streamer discharges developing in weak electric fields, in which the photoionization process significantly contributes to discharge dynamics. This paper (1) reports original studies, which demonstrate the validity and accuracy of the recently proposed photoionization models for studies of streamers in weak electric fields, and (2) introduces efficient boundary conditions for the photoinization models based on radiative transfer theory.
Forward tunneling effect and metal-insulator transition in the BaTiO3 film/Si n-n heterojunction
Authors: Hao Lanzhong , Xue Qingzhong , Gao Xili , Li Qun , Zheng Qingbin , Yan Keyou
Published: November 2007

A n-n heterojunction composed of BaTiO3 film and silicon substrate was fabricated, and it shows good rectifying properties in the temperature range of 80–300K. The forward tunneling effect in the junction at low temperatures (<200K) is proved by the phenomenon that the current increases abruptly when the forward electrical voltage exceeds a high threshold (>12V). The temperature dependence of the junction resistance under a high forward field exhibits an electrical field controlled metal-insulator transition. The results were explained by using the band structure of the junction.
Globalisation, Higher Education, and Urban Growth Coalitions: Turkey's Foundation Universities and the Case of Koç University in Istanbul
Authors: Yalcintan Murat Cemal , Thornley Andy
Published: November 2007

Higher education institutions (HEIs) are not only the rising actors of the knowledge-based economy—they are also among the concrete physical structures taking part in the transformation of cities. As large physical constructions, they have the potential to affect urban form. Moreover, HEIs have also begun to act as developers and their locations have become a matter of concern for local politics. In the global era, there are a number of driving forces in the restructuring and location patterns of the HEIs in cities. The nonprofit – private foundation universities (FUs) that were introduced into the Turkish higher education (HE) system in the past decade, and in particular Koç University (KU), illustrate these issues clearly. Possible relations between globalisation and HE are presented with reference to the restructuring of the HEIs. This is related to the desire to locate at the nodes of global flows. The location of the FUs in Istanbul, Turkey, and in particular of KU, is the focus. The motivation of the actors in the process is assessed in relation to the theoretical issues. The authors present the growth coalition and local opposition that were significant in the decision-making process relating to KU.
Scotland's Social Services Spending Needs: An English View
Authors: King David , Pashley Matthew , Ball Rob
Published: November 2007

Scottish citizens enjoy 25% more spending per head on public services than English citizens, but almost nothing is known about the countries' relative needs and hence about how far this gap is defensible. We explore their spending needs for local authority services, which cover over half the spending concerned. We first compare needs for local personal social services. To do so, we take the complex formulae with which the Westminster government assesses the needs of English local authorities, and we use these formulae to assess the needs of Scottish local authorities. The formulae suggest that Scotland needs 15.3% more per head than does England. We then combine these results with those of two earlier papers exploring other local services to show that the English formulae put Scotland's per capita needs for local authority services as a whole at about 6% above England's. However, we also compare the relative needs of Scottish local authorities as assessed by the English formulae with their relative needs as assessed by the Scottish needs formulae currently used by Holyrood, and we find major differences. This suggests either that at least one country assesses needs with seriously flawed formulae, or that the two countries have different conceptions of need.
Lagoon degradation and management in Yanuca Channel on the Coral Coast of Fiji
Authors: Terry James P , Kisun Priya , Qareqare Aminiasi , Rajan Jyotishma
Published: November 2007

Yanuca Channel is a narrow marine lagoon separating a low limestone island in Cuvu Bay from the south west Viti Levu mainland in Fiji, known as the ?Coral Coast?. Historical air photographs show significant changes in the drainage configuration of the lagoon and local Fijian landowners give accounts of degrading environmental conditions in the lagoon due to sediment infilling. This investigation found several processes were responsible for the aggradation. Large
quantities of terrigenous sediments are discharged by streamwaters into the lagoon, as a consequence of the removal of estuarine mangroves and agricultural practices such as burning and grazing in adjacent catchments. A previous outlet into the bay became blocked in the 1980s after inappropriate sand mining and vegetation clearance caused accelerated coastal erosion. The altered lagoon drainage pattern has led to lagoon eutrophication and aggradation. Developed on the island is a large international resort complex; the resort causeway constructed across the lagoon to the island has a significant dam effect, impeding the flow of currents and preventing the periodic scouring of sand from the lagoon floor. Several modern and traditional management options have recently been implemented to improve lagoon conditions, through partnerships between NGOs, traditional landowners and the resort management. These include riparian reforestation and the establishment of marine protected areas to conserve coral reefs.
A new algorithm to enhance power transfer using series capacitor
Authors: Mathur H D , Arora C M , Bansal R C
Published: November 2007

The compensation of transmission line reactance by means of series compensation is an effective method increasing the power transfer capacity and thereby improving the transient stability of the power system. This paper presents a novel series compensation method to increase the power capacity of the system. The proposed method is applied to a 9-bus
power system.
The digestive adaptation of flying vertebrates: High intestinal paracellular absorption compensates for smaller guts
Authors: Caviedes-Vidal Enrique , McWhorter Todd J. , Lavin Shana R. , Chediack Juan G. , Tracy Christopher R. , Karasov William H.
Published: November 2007

Anecdotal evidence suggests that birds have smaller intestines than mammals. In the present analysis, we show that small birds and bats have significantly shorter small intestines and less small intestine nominal (smooth bore tube) surface area than similarly sized nonflying mammals. The corresponding >50% reduction in intestinal volume and hence mass of digesta carried is advantageous because the energetic costs of flight increase with load carried. But, a central dilemma is how birds and bats satisfy relatively high energy needs with less absorptive surface area. Here, we further show that an enhanced paracellular pathway for intestinal absorption of water-soluble nutrients such as glucose and amino acids may compensate for reduced small intestines in volant vertebrates. The evidence is that
l
-rhamnose and other similarly sized, metabolically inert, nonactively transported monosaccharides are absorbed significantly more in small birds and bats than in nonflying mammals. To broaden our comparison and test the veracity of our finding we surveyed the literature for other similar studies of paracellular absorption. The patterns found in our focal species held up when we included other species surveyed in our analysis. Significantly greater amplification of digestive surface area by villi in small birds, also uncovered by our analysis, may provide one mechanistic explanation for the observation of higher paracellular absorption relative to nonflying mammals. It appears that reduced intestinal size and relatively enhanced intestinal paracellular absorption can be added to the suite of adaptations that have evolved in actively flying vertebrates.
An action spectrum (290–320 nm) for TNFα protein in human skinin vivosuggests that basal-layer epidermal DNA is the chromophore
Authors: Walker Susan L. , Young Antony R.
Published: November 2007

Terrestrial solar UVB radiation (≈295–320 nm) readily induces cyclobutane pyrimidine dimers (CPDs) in human skin DNA that result in characteristic mutations associated with nonmelanoma skin cancer. The proinflammatory cytokine TNFα is important in mouse skin chemical carcinogenesis and is thought to also play a role in UVR-induced skin cancer by its immunomodulatory properties. There is somein vitroevidence that CPDs initiate the production of TNFα, and we tested this hypothesis by comparing the wavelength dependence (action spectrum) for TNFα protein induction in human skinin vivowith our earlierin vivoaction spectra for CPD induction in four different epidermal layers of human skin. Normal volunteers (n= 35) were irradiated with physiologically relevant doses of monochromatic UVB (290–320 nm), and TNFα concentration was assessed, by high-sensitivity ELISA, in exudates from skin suction blisters raised 8 h after irradiation. An action spectrum, constructed from the slopes of the dose–response curves at the different wavelengths, showed maximal efficacy at 300 nm. An excellent match was observed for TNFα and the CPD action spectrum for cells in the lower basal epidermis. These data strongly suggest that UVB-induced photodamage to DNA in the epidermal basal layer is a major trigger for TNFα production. The TNFα may originate directly from the keratinocytes in this layer or inflammatory cells that are rapidly recruited into the upper dermis (e.g., neutrophils) as a consequence of DNA photodamage to basal-layer keratinocytes.
Pulse-like and crack-like ruptures in experiments mimicking crustal earthquakes
Authors: Lu Xiao , Lapusta Nadia , Rosakis Ares J.
Published: November 2007

Theoretical studies have shown that the issue of rupture modes has important implications for fault constitutive laws, stress conditions on faults, energy partition and heat generation during earthquakes, scaling laws, and spatiotemporal complexity of fault slip. Early theoretical models treated earthquakes as crack-like ruptures, but seismic inversions indicate that earthquake ruptures may propagate in a self-healing pulse-like mode. A number of explanations for the existence of slip pulses have been proposed and continue to be vigorously debated. This study presents experimental observations of spontaneous pulse-like ruptures in a homogeneous linear-elastic setting that mimics crustal earthquakes; reveals how different rupture modes are selected based on the level of fault prestress; demonstrates that both rupture modes can transition to supershear speeds; and advocates, based on comparison with theoretical studies, the importance of velocity-weakening friction for earthquake dynamics.
Continuous inertial focusing, ordering, and separation of particles in microchannels
Authors: Di Carlo Dino , Irimia Daniel , Tompkins Ronald G. , Toner Mehmet
Published: November 2007

Under laminar flow conditions, when no external forces are applied, particles are generally thought to follow fluid streamlines. Contrary to this perspective, we observe that flowing particles migrate across streamlines in a continuous, predictable, and accurate manner in microchannels experiencing laminar flows. The migration is attributed to lift forces on particles that are observed when inertial aspects of the flow become significant. We identified symmetric and asymmetric channel geometries that provide additional inertial forces that bias particular equilibrium positions to create continuous streams of ordered particles precisely positioned in three spatial dimensions. We were able to order particles laterally, within the transverse plane of the channel, with >80-nm accuracy, and longitudinally, in regular chains along the direction of flow. A fourth dimension of rotational alignment was observed for discoidal red blood cells. Unexpectedly, ordering appears to be independent of particle buoyant direction, suggesting only minor centrifugal contributions. Theoretical analysis indicates the physical principles are operational over a range of channel and particle length scales. The ability to differentially order particles of different sizes, continuously, at high rates, and without external forces in microchannels is expected to have a broad range of applications in continuous bioparticle separation, high-throughput cytometry, and large-scale filtration systems.
Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury
Authors: Bryan Nathan S. , Calvert John W. , Elrod John W. , Gundewar Susheel , Ji Sang Yong , Lefer David J.
Published: November 2007

Nitrite has emerged as an endogenous signaling molecule with potential therapeutic implications for cardiovascular disease. Steady-state levels of nitrite are derived in part from dietary sources; therefore, we investigated the effects of dietary nitrite and nitrate supplementation and deficiency on NO homeostasis and on the severity of myocardial ischemia-reperfusion (MI/R) injury. Mice fed a standard diet with supplementation of nitrite (50 mg/liter) in their drinking water for 7 days exhibited significantly higher plasma levels of nitrite, exhibited significantly higher myocardial levels of nitrite, nitroso, and nitrosyl–heme, and displayed a 48% reduction in infarct size (Inf) after MI/R. Supplemental nitrate (1 g/liter) in the drinking water for 7 days also increased blood and tissue NO products and significantly reduced Inf. A time course of ischemia-reperfusion revealed that nitrite was consumed during the ischemic phase, with an increase in nitroso/nitrosyl products in the heart. Mice fed a diet deficient in nitrite and nitrate for 7 days exhibited significantly diminished plasma and heart levels of nitrite and NO metabolites and a 59% increase in Inf after MI/R. Supplementation of nitrite in the drinking water for 7 days reversed the effects of nitrite deficiency. These data demonstrate the significant influence of dietary nitrite and nitrate intake on the maintenance of steady-state tissue nitrite/nitroso levels and illustrate the consequences of nitrite deficiency on the pathophysiology of MI/R injury. Therefore, nitrite and nitrate may serve as essential nutrients for optimal cardiovascular health and may provide a treatment modality for cardiovascular disease.
Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein–lipoxygenase fusion protein from the cyanobacterium
Anabaena
PCC 7120
Authors: Schneider Claus , Niisuke Katrin , Boeglin William E. , Voehler Markus , Stec Donald F. , Porter Ned A. , Brash Alan R.
Published: November 2007

Biological transformations of polyunsaturated fatty acids often lead to chemically unstable products, such as the prostaglandin endoperoxides and leukotriene A
4
epoxide of mammalian biology and the allene epoxides of plants. Here, we report on the enzymatic production of a fatty acid containing a highly strained bicyclic four-carbon ring, a moiety known previously only as a model compound for mechanistic studies in chemistry. Starting from linolenic acid (C18.3ω3), a dual function protein from the cyanobacterium
Anabaena
PCC 7120 forms 9
R
-hydroperoxy-C18.3ω3 in a lipoxygenase domain, then a catalase-related domain converts the 9
R
-hydroperoxide to two unstable allylic epoxides. We isolated and identified the major product as 9
R
,10
R
-epoxy-11
trans
-C18.1 containing a bicyclo[1.1.0]butyl ring on carbons 13–16, and the minor product as 9
R
,10
R
-epoxy-11
trans
,13
trans
,15
cis
-C18.ω3, an epoxide of the leukotriene A type. Synthesis of both epoxides can be understood by initial transformation of the hydroperoxide to an epoxy allylic carbocation. Rearrangement to an intermediate bicyclobutonium ion followed by deprotonation gives the bicyclobutane fatty acid. This enzymatic reaction has no parallel in aqueous or organic solvent, where ring-opened cyclopropanes, cyclobutanes, and homoallyl products are formed. Given the capability shown here for enzymatic formation of the highly strained and unstable bicyclobutane, our findings suggest that other transformations involving carbocation rearrangement, in both chemistry and biology, should be examined for the production of the high energy bicyclobutanes.
APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination
Authors: Guikema Jeroen E.J. , Linehan Erin K. , Tsuchimoto Daisuke , Nakabeppu Yusaku , Strauss Phyllis R. , Stavnezer Janet , Schrader Carol E.
Published: November 2007

Antibody class switch recombination (CSR) occurs by an intrachromosomal deletion requiring generation of double-stranded breaks (DSBs) in switch-region DNA. The initial steps in DSB formation have been elucidated, involving cytosine deamination by activation-induced cytidine deaminase and generation of abasic sites by uracil DNA glycosylase. However, it is not known how abasic sites are converted into single-stranded breaks and, subsequently, DSBs. Apurinic/apyrimidinic endonuclease (APE) efficiently nicks DNA at abasic sites, but it is unknown whether APE participates in CSR. We address the roles of the two major mammalian APEs, APE1 and APE2, in CSR. APE1 deficiency causes embryonic lethality in mice; we therefore examined CSR and DSBs in mice deficient in APE2 and haploinsufficient for APE1. We show that both APE1 and APE2 function in CSR, resulting in the DSBs necessary for CSR and thereby describing a novel in vivo function for APE2.
Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model
Authors: Hirota Keiji , Yoshitomi Hiroyuki , Hashimoto Motomu , Maeda Shinji , Teradaira Shin , Sugimoto Naoshi , Yamaguchi Tomoyuki , Nomura Takashi , Ito Hiromu , Nakamura Takashi , Sakaguchi Noriko , Sakaguchi Shimon
Published: November 2007

This report shows that interleukin (IL) 17–producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR) 6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor β and IL-6 additionally need IL-1 and neutralization of interferon (IFN) γ and IL-4 for CCR6 expression. Forced expression of RORγt, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1β, IL-17, or tumor necrosis factor α, and is suppressed by IFN-γ or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA.
The SBML discrete stochastic models test suite
Authors: Evans Thomas W. , Gillespie Colin S. , Wilkinson Darren J.
Published: November 2007

Motivation: Stochastic simulation is a very important tool for mathematical modelling. However, it is difficult to check the correctness of a stochastic simulator, since any two realizations from a single model will typically be different.

Results: We have developed a test suite of stochastic models that have been solved either analytically or using numerical methods. This allows the accuracy of stochastic simulators to be tested against known results. The test suite is already being used by a number of stochastic simulator developers.

Availability: The latest version of the test suite can be obtained from http://www.calibayes.ncl.ac.uk/Resources/dsmts/ and is licensed under GNU Lesser General Public License.

Contact:  D.J.Wilkinson@ncl.ac.uk
Spatial considerations for the Dakhla stock of Octopus vulgaris: indicators, patterns, and fisheries interactions
Authors: Faraj Abdelmalek , Bez Nicolas
Published: November 2007

Faraj, A., and Bez, N. 2007. Spatial considerations for the Dakhla stock of Octopus vulgaris: indicators, patterns, and fisheries interactions. – ICES Journal of Marine Science, 64: 1820–1828. The common octopus (Octopus vulgaris) is the target species of the cephalopod fishery that exploits two stocks, Dakhla and Cap Blanc, off southern Morocco (26°N 21°N), an area commonly referred to as the Saharan Bank. Octopusvulgaris is also one of the most abundant demersal species in this highly productive area, and plays a key role in the upwelling ecosystem. Spatial patterns of the main phases of the Octopus vulgaris life cycle of the Dakhla stock are described, using trawl surveys carried out twice a year from 1998 to 2003. Using geostatistics and spatial indicators, mature females and juveniles are analysed and mapped to characterize the main features of the spawning and recruitment phases. There are clear distinctions between the spatial patterns of the spawning and recruitment phases: juveniles are more coastal, less spatially dispersed, more anisotropically distributed, and more patchy. Our results suggest that the spatial pattern of the Octopus vulgaris Dakhla stock is different from that of the same species in other ecosystems such as the Mediterranean. GIS reveals that the spawning–stock biomass is globally more accessible to the industrial fleet than to the artisanal one, a finding contrary to contemporary thinking and with important resource management implications.
Improving the quantitative estimation of trawling impacts from sidescan-sonar and underwater-video imagery
Authors: Smith C. J. , Banks A. C. , Papadopoulou K-N.
Published: November 2007

Smith, C. J., Banks, A. C., and Papadopoulou, K.-N. 2007. Improving the quantitative estimation of trawling impacts from sidescan-sonar and underwater-video imagery. – ICES Journal of Marine Science, 64: 1692–1701. The techniques of sidescan sonar and towed, underwater-video sled were assessed as rapid-assessment methodologies for investigating trawl impacts on the substratum. Sidescan sonar is able to image a swathe of ∼200 m with a resolution of ∼20 cm at a speed of 2–3 knots, and marks of trawl doors could be observed. The towed video system imaged a swathe of 1–2 m with a resolution of 1–2 cm at a speed of ∼1 knot, and trawl-door marks, scrape marks, local bioturbation features, and fauna could be observed. Multiple tows using both methodologies were carried out in two areas in Heraklion Bay, Crete. One area, experimentally trawled, was 80–90 m deep and characterized by mixed, maerly sediments; the other was a commercial trawl lane ∼200 m deep characterized by silty-clay sediment. Descriptions of the types of trawling feature and impacts caused by trawling were made for both areas. Images were analysed from the commercial deeper trawling ground for area assessment. For sidescan-sonar records, direction of trawling and trawl-mark density by category were estimated at periodic intervals along the track. For video, categories for trawl-mark density and level of bioturbation were estimated, along with the density of the crinoid Leptometra phalangium. Using geo-referenced positioning for each data point, area maps were constructed for each of the parameters, and correlations were tested between the different datasets. The use of the assessment techniques (characteristics, data usage, mapping, complementarity) in relation to trawling-impact studies is discussed, as well as possibilities for the use of the resulting data for management.
Introduction. Carbon-based electronics: fundamentals and device applications
Authors: Nicholas Robin J , Mainwood Alison , Eaves Laurence
Published: November 2007

Carbon-based materials offer a number of exciting possibilities for both new science and applications. Many of these are based on the novel band structure of graphene, by which solids mimic the properties of relativisitic fermions and which offers the potential for high speed nanoscale electronics. When sheets of graphene are rolled up to make carbon nanotubes, further interesting properties are found; for example, both semiconducting and metallic nanotubes able to be produced. The novel properties of these new materials, together with the already remarkable properties of diamond itself, are discussed by a series of experts who came together in May 2007 to discuss and debate the potential for future development.
MAKER: An easy-to-use annotation pipeline designed for emerging model organism genomes
Authors: Cantarel Brandi L. , Korf Ian , Robb Sofia M.C. , Parra Genis , Ross Eric , Moore Barry , Holt Carson , Sánchez Alvarado Alejandro , Yandell Mark
Published: November 2007

We have developed a portable and easily configurable genome annotation pipeline called MAKER. Its purpose is to allow investigators to independently annotate eukaryotic genomes and create genome databases. MAKER identifies repeats, aligns ESTs and proteins to a genome, produces ab initio gene predictions, and automatically synthesizes these data into gene annotations having evidence-based quality indices. MAKER is also easily trainable: Outputs of preliminary runs are used to automatically retrain its gene-prediction algorithm, producing higher-quality gene-models on subsequent runs. MAKER’s inputs are minimal, and its outputs can be used to create a GMOD database. Its outputs can also be viewed in the Apollo Genome browser; this feature of MAKER provides an easy means to annotate, view, and edit individual contigs and BACs without the overhead of a database. As proof of principle, we have used MAKER to annotate the genome of the planarian Schmidtea mediterranea and to create a new genome database, SmedGD. We have also compared MAKER’s performance to other published annotation pipelines. Our results demonstrate that MAKER provides a simple and effective means to convert a genome sequence into a community-accessible genome database. MAKER should prove especially useful for emerging model organism genome projects for which extensive bioinformatics resources may not be readily available.
A de novo designed protein–protein interface
Authors: Huang Po‐Ssu , Love John J. , Mayo Stephen L.
Published: November 2007

As an approach to both explore the physical/chemical parameters that drive molecular self‐assembly and to generate novel protein oligomers, we have developed a procedure to generate protein dimers from monomeric proteins using computational protein docking and amino acid sequence design. A fast Fourier transform‐based docking algorithm was used to generate a model for a dimeric version of the 56‐amino‐acid β1 domain of streptococcal protein G. Computational amino acid sequence design of 24 residues at the dimer interface resulted in a heterodimer comprised of 12‐fold and eightfold variants of the wild‐type protein. The designed proteins were expressed, purified, and characterized using analytical ultracentrifugation and heteronuclear NMR techniques. Although the measured dissociation constant was modest (∼300 μM), 2D‐[1H,15N]‐HSQC NMR spectra of one of the designed proteins in the absence and presence of its binding partner showed clear evidence of specific dimer formation.
Requirements for peptidyl‐prolyl isomerization activity: A comprehensive mutational analysis of the substrate‐binding cavity of FK506‐binding protein 12
Authors: Ikura Teikichi , Ito Nobutoshi
Published: November 2007

Peptidyl‐prolyl isomerase (PPIase) activity is exhibited by many proteins belonging to the PPIase family. However, the catalytic mechanism of this activity remains to be completely elucidated. Here, we selected human FK506‐binding protein 12 (FKBP12) as the model PPIase and investigated the nature of amino acid residues essential for the activity. The crystal structures of several complexes of PPIase with short peptides revealed that the residues Asp37, Arg42, Phe46, Val55, Trp59, and Tyr82 in the substrate‐binding cavity of FKBP12 appear to play key roles in the PPIase activity. Each of these six residues was substituted by 20 common amino acid residues. The activity of each mutant protein was measured using a peptide analog by the chymotrypsin digestion assay and then compared with wild‐type FKBP12. It was found that site‐specific interactions by the side chains of amino acid residues constituting the substrate‐binding cavity were not essential for the PPIase activity, although the 37th, 55th, and 82nd amino acid residues significantly contributed to the activity. This suggests that the PPIase activity requires only the hydrophobic cavity that captures the Pro‐containing peptide.
Tuberculin reactivity and allergic disorders in schoolchildren, Okinawa, Japan
Authors: Miyake Y. , Arakawa M. , Tanaka K. , Sasaki S. , Ohya Y.
Published: November 2007

Background
Bacillus Calmette‐Guérin (BCG) vaccination triggers a T‐helper type 1 response. Whether BCG vaccination and positive tuberculin reactivity are preventive against allergic disorders remains controversial.

Objective
The current cross‐sectional study investigated the relationship of BCG vaccination and tuberculin reactivity with the prevalence of allergic disorders using data from the Ryukyus Child Health Study (RYUCHS).

Methods
Subjects were 5717 schoolchildren aged 8–11 years in Okinawa, Japan. The RYUCHS collected information on symptoms of allergic disorders and potential confounding factors. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Data on BCG vaccination and tuberculin tests were obtained from school records. Allowance was made for grade, sex, sibship size, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level.

Results
No measurable relationship was found between BCG vaccination in infants and the prevalence of allergic disorders. Among 5567 BCG‐vaccinated children, positive tuberculin reactivity (induration 10 mm) in the first grade was independently associated with a decreased prevalence of wheeze, asthma, and atopic eczema: the multivariate odds ratios for wheeze, asthma, and atopic eczema were 0.80 (95% confidence interval [CI], 0.67–0.94), 0.78 (95% CI, 0.64–0.95), and 0.77 (95% CI, 0.62–0.95), respectively. The inverse associations were more pronounced in children with a negative parental allergic history than in those with a positive parental allergic history. There was no significant relationship between tuberculin reactivity and allergic rhinoconjunctivitis.

Conclusions
The findings suggest that positive tuberculin reactivity may be inversely associated with the prevalence of wheeze, asthma, and atopic eczema, but not allergic rhinoconjunctivitis, especially among Japanese children without a parental allergic history.
Peroxisome proliferator activated receptor γ is not necessary for the development of LPS‐induced tolerance in macrophages
Authors: Zingarelli Basilia , Fan Hongkuan , Ashton Sarah , Piraino Giovanna , Mangeshkar Prajakta , Cook James A.
Published: November 2007

Peroxisome proliferator activated receptor‐γ (PPARγ) has been reported to exert anti‐inflammatory properties in endotoxic shock and sepsis. One phenomenon that alters the inflammatory response to endotoxin [lipopolysaccharide (LPS)] is endotoxin tolerance, which is caused by previous exposure to endotoxin. Here, we investigate whether changes in endogenous PPARγ function regulate this phenomenon using three different models of LPS‐induced tolerance in macrophages. In a first in vitro model, previous LPS exposure of murine J774.2 macrophages suppressed tumour necrosis factor‐α (TNF‐α) release in response to subsequent LPS challenge. Treatment of J774.2 cells with the PPARγ inhibitor GW9662 did not alter tolerance induction because these cells were still hyporesponsive to the secondary LPS challenge. In a second ex vivo model, primary rat peritoneal macrophages from LPS‐primed rats exhibited suppression of thromboxane B2 and TNF‐α production, while maintaining nitrite production in response to in vitro LPS challenge. Pretreatment of rats with the PPARγ inhibitor GW9662 in vivo failed to alter the tolerant phenotype of these primary macrophages. In a third ex vivo model, primary peritoneal macrophages with conditional deletion of PPARγ were harvested from LPS‐primed Cre‐lox mice (Cre+/+ PPARγ−/−) and exhibited significant suppression of TNF‐α production in response to in vitro LPS challenge. Furthermore, both LPS‐primed PPARγ‐deficient Cre+/+ PPARγ−/− mice and wild‐type Cre−/− PPARγ+/+ mice exhibited reduced plasma TNF‐α levels in response to a high dose of LPS in vivo. These data demonstrate that PPARγ does not play a role in the LPS‐induced tolerant phenotype in macrophages.
Is it the injection device or the anxiety experienced that causes pain during dental local anaesthesia?
Authors: KUSCU OZGUR ONDER , AKYUZ SERAP
Published: November 2007

Aim.  The aim of this study was to investigate the influence of anxiety and type of dental injection, a plastic syringe or an electronic computerized device, on the pain perceived by children.

Design.  Two dental injectors, a computerized device (Wand®, Milestone Scientific, Livingston, NJ, USA) and a traditional plastic syringe, were compared. Forty‐one children, aged 9–13 years, who had registered for treatment in Marmara University, Istanbul, Turkey, were included in the study. Both anxious and non‐anxious children were included in the study group. The Children's Fear Survey Schedule–Dental Subscale, Facial Image Scale, Spielberger's State Anxiety Index for Children, and heart rates were used to determine the anxiety levels. Participants were assigned to interventions by using random allocation. The first appointment was designed as an introductive familiarization session and injections were administered in the second and third sessions, with one or the other injector. The visual analogue scale was used for pain measurement after injections.

Results.  No significant differences in injection pain scores were observed between the Wand and traditional plastic injector. Higher levels of pre‐injection anxiety were found to be related to more severe pain reports by the children.

Conclusions.  Anxiety plays an important role in the pain reaction of children, and was found to be more determinative in pain perception than the injection devices preferred.
Pharmacokinetics of tramadol, and its metabolite O‐desmethyl‐tramadol, in cats
Authors: PYPENDOP B. H. , ILKIW J. E.
Published: November 2007

Tramadol is an analgesic agent and is used in dogs and cats. Tramadol exerts its action through interactions with opioid, serotonin and adrenergic receptors. The opioid effect of tramadol is believed to be, at least in part, related to its metabolite, O‐desmethyl‐tramadol. The pharmacokinetics of tramadol and O‐desmethyl‐tramadol were examined after intravenous (i.v.) and oral administration of tramadol to six cats. A two‐compartment model (with first‐order absorption in the central compartment for the oral administration) with elimination from the central compartment best described the disposition of tramadol in cats. After i.v. administration, the apparent volume of distribution of the central compartment, the apparent volume of distribution at steady‐state, the clearance, and the terminal half‐life (mean ± SEM) were 1553 ± 118 mL/kg, 3103 ± 132 mL/kg, 20.8 ± 3.2 mL/min/kg, and 134 ± 18 min, respectively. Systemic availability and terminal half‐life after oral administration were 93 ± 7% and 204 ± 8 min, respectively. O‐desmethyl‐tramadol rapidly appeared in plasma following tramadol administration and had terminal half‐lives of 261 ± 28 and 289 ± 19 min after i.v. and oral tramadol administration, respectively. The rate of formation of O‐desmethyl‐tramadol estimated from a model including both tramadol and O‐desmethyl‐tramadol was 0.014 ± 0.003/min and 0.004 ± 0.0008/min after i.v. and oral tramadol administration, respectively.