bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable and highly bright white organic light-emitting diode based on 4,4′,4″-tris(N-3-methylphenyl-N-phenyl-amino)-triphenylamine
Authors: Yang Su-Hua , Liu Mine-Huang , Su Yan-Kuin
Published: October 2006

A stable and very bright white organic light-emitting diode (WOLED) was fabricated with the structure ITO/m-MTDATA (30nm)∕NPB (30nm)/DPVBi (11nm)∕Alq3:DCJTB(50nm)∕LiF(1nm)∕Al(250nm). White light emission was achieved by combining blue and orange emissions emitted from DPVBi and Alq3:DCJTB layers, respectively. Inserting an m-MTDATA layer between ITO and NPB improved the charge balance in the recombination zone, improving the stability of the emission color of WOLED. The maximum luminance was 20590cd∕m2 at 13V with CIE coordinates of x=0.30, y=0.31. The maximum power and current efficiencies were 6.01lm∕W at 5V and 6.2cd∕A at 5V, respectively. Conversely, the WOLED without an m-MTDATA buffer layer exhibited unstable emission characteristic.
The effect of potential on the electron-trapping process of surface states in nanocrystalline TiO2 film electrode
Authors: Fu Yao , Cao Wanghe
Published: October 2006

The effect of electrode potential (U) on the electron-trapping process of surface states in nanocrystalline TiO2 film electrode was investigated by current-potential (I-U) curves and transient photocurrent spectra. A simple model, the transfer property of photogenerated carriers in alkaline electrolyte varied with U, was built up. As a result, two kinds of surface states, deep surface state OL− (Sc) formed by nonprotonic lattice oxygen ion and shallow surface state Ti–O–̈O–̈O− (So) formed by chemisorbed O2, were formed on the hydroxylated surface of TiO2 particles, which could efficiently trap the photogenerated electrons. The variation of U could remarkably change the relative position between Fermi level of TiO2 (EFn) and surface state level (ES), consequently affecting the electron-trapping probability of surface states. As U>0.4V, the more negative EFn could significantly suppress the electron-trapping process of Sc and So, improving the intensity and stability of anodic photocurrent. When U was decreased, the EFn shifted to positive direction, which resulted in the facilitative trapping process of Sc and the decrease in anodic photocurrent. As U⩽−0.4V, the EFn was more positive than the energy level of So (ESo). Therefore, So could easily trap the photogenerated electrons, and the produced cathodic current resulted in the further decrease in anodic photocurrent.
Mechanical properties of sol-gel derived BiScO3–PbTiO3 thin films by nanoindentation
Authors: Wen Hai , Wang Xiaohui , Li Longtu
Published: October 2006

The mechanical properties of sol-gel derived BiScO3–PbTiO3 (BSPT) thin films annealed at different temperatures were investigated by nanoindentation. The effects of annealing temperature on the microstructures and mechanical properties were discussed. As the annealing temperature increased from 550to800°C, the (100) orientation degree of the BSPT thin films increased from a Lotgering factor [J. Inorg. Nucl. Chem. 9, 113 (1959)] of 0.47 to 0.67, while the grain size increased from 22to54nm. Due to the grain size effect, hardness for the BSPT thin films dropped from 7.8to6.7GPa. By fitting the experiment results with a Hall-Petch equation, a probable lattice friction stress of 4.69GPa and a Hall-Petch constant of 15.35GPanm1∕2 were obtained for the BSPT thin films. Because of the combined effect of grain size and film orientation, Young’s modulus did not show a clear trend with the annealing temperature. The highest Young’s modulus was 132GPa, appearing in the sample annealed at 550°C.
Instrument design and optimization using genetic algorithms
Authors: Hölzel Robert , Bentley Phillip M. , Fouquet Peter
Published: October 2006

This article describes the design of highly complex physical instruments by using a canonical genetic algorithm (GA). The procedure can be applied to all instrument designs where performance goals can be quantified. It is particularly suited to the optimization of instrument design where local optima in the performance figure of merit are prevalent. Here, a GA is used to evolve the design of the neutron spin-echo spectrometer WASP which is presently being constructed at the Institut Laue-Langevin, Grenoble, France. A comparison is made between this artificial intelligence approach and the traditional manual design methods. We demonstrate that the search of parameter space is more efficient when applying the genetic algorithm, and the GA produces a significantly better instrument design. Furthermore, it is found that the GA increases flexibility, by facilitating the reoptimization of the design after changes in boundary conditions during the design phase. The GA also allows the exploration of “nonstandard” magnet coil geometries. We conclude that this technique constitutes a powerful complementary tool for the design and optimization of complex scientific apparatus, without replacing the careful thought processes employed in traditional design methods.
Mössbauer morphological analysis of Fe-filled multiwalled carbon nanotube samples
Authors: Ruskov T. , Spirov I. , Ritschel M. , Müller C. , Leonhardt A. , Ruskov R.
Published: October 2006

We have performed morphological analysis of samples of Fe nanowires encapsulated into aligned multiwalled carbon nanotubes (Fe-MWCNTs) via Fe57 Mössbauer spectroscopy. The aligned Fe-MWCNTs were obtained by pyrolysis of ferrocene onto an oxidized Si substrate. Transmission Mössbauer spectroscopy (TMS) and backscattered conversion electron Mössbauer spectroscopy (CEMS) were applied in order to distinguish different Fe phases and their spatial distribution within the whole sample and along the tubes’ height. A characterization (on a large spatial scale) of the aligned CNT samples was performed by obtaining TMS spectra for selected spots positioned at different locations of the sample. While the total Fe content changes considerably from one location to another, the γ-Fe∕α-Fe phase ratio is constant onto a relatively large area. Using TMS and CEMS for all aligned Fe-MWCNT samples it is also shown that along the CNT axes, going to the top of the nanotube the relative content of the γ-Fe phase increases. Going to the opposite direction, i.e., towards the silicon substrate, the relative content of the Fe3C phase increases, which is in agreement with our previous works. The results of an additional Mössbauer spectroscopy experiment in TMS and CEMS modes performed on a nonaligned sample support the conclusion that in our case the iron phases in the channels of carbon nanotubes are spatially separated as individual nanoparticles. The relative intensity ratio of the α-Fe phase Mössbauer sextets shows good magnetic texture along the nanotubes’ axis for one of the aligned samples and the lack of such orientation for the others.
A truncated version of reduced multireference coupled-cluster method with singles and doubles and noniterative triples: Application to F2 and Ni(CO)n (n=1, 2, and 4)
Authors: Li Xiangzhu , Paldus Josef
Published: October 2006

A perturbatively truncated version of the reduced multireference coupled-cluster method with singles and doubles and noniterative triples RMR CCSD(T) is described. In the standard RMR CCSD method, the effect of all triples and quadruples that are singles or doubles relative to references spanning a chosen multireference (MR) model space is accounted for via the external corrections based on the MR CISD wave function. In the full version of RMR CCSD(T), the remaining triples are then handled via perturbative corrections as in the standard, single-reference (SR) CCSD(T) method. By using a perturbative threshold in the selection of MR CISD configuration space, we arive at the truncated version of RMR CCSD(T), in which the dimension of the MR CISD problem is significantly reduced, thus leaving more triples to be treated perturbatively. This significantly reduces the computational cost. We illustrate this approach on the F2 molecule, in which case the computational cost of the truncated version of RMR CCSD(T) is only about 10%–20% higher than that of the standard CCSD(T), while still eliminating the failure of CCSD(T) in the bond breaking region of geometries. To demonstrate the capabilities of the method, we have also used it to examine the structure and binding energy of transition metal complexes Ni(CO)n with n=1, 2, and 4. In particular, Ni(CO)2 is shown to be bent rather than linear, as implied by some earlier studies. The RMR CCSD(T) binding energy differs from the SR CCSD(T) one by 1–2kcal∕mol, while the energy barrier separating the linear and bent structures of Ni(CO)2 is smaller than 1kcal∕mol.
Effect of indium segregation on optical and structural properties of GaInNAs∕GaAs quantum wells at emission wavelength of 1.3μm
Authors: Liu H. F. , Dixit V. , Xiang N.
Published: October 2006

We studied the effect of In segregation on the optical and structural properties of GaInNAs∕GaAs quantum wells (QWs). The segregation model developed by Muraki et al. [Appl. Phys. Lett. 61, 557 (1992)] is used to calculate the composition profiles of the QWs with different segregation efficiencies of In atoms. Confinement potentials of electron and hole are then derived, from which energies of electron and hole are numerically calculated by serving the Schrödinger equation. The effects of valence band mixing and strain are included in the calculations of the energies of electron and hole. The optical transition energy of the QWs is then obtained from the energy difference of electron and hole. It is found that the blueshift in transition energy due to segregation is mainly affected by strain rather than by composition in the studied QWs. Calculations using the segregation model together with the dynamical theory of x-ray diffractions are also carried out for the segregated QWs. The results indicate that the behavior of In segregation in Ga0.65In0.35N0.015As0.985∕GaAs QW can be resolved by both photoluminescence and x-ray diffraction for the segregation coefficients larger than 0.7.
Calculation of the vibronic structure of the photodetachment spectra of CCCl− and CCBr−
Authors: Mishra Sabyashachi , Vallet Valérie , Poluyanov Leonid V. , Domcke Wolfgang
Published: October 2006

The vibronic structure of the closely spaced and strongly coupled X̃Σ+2 and ÃΠ2 states in the photodetachment spectra of CCCl− and CCBr− has been calculated by considering Σ-Π vibronic coupling together with spin-orbit coupling. The stretching modes are treated within the so-called linear-vibronic-coupling model. The vibronic and spin-orbit parameters have been determined by accurate ab initio electronic-structure calculations. While the nonrelativistic vibronic-coupling parameters are of approximately equal strength in CCCl and CCBr, the vibronic-coupling parameters of spin-orbit origin are found to be larger in the latter. The calculated photodetachment spectra of both systems are shown to exhibit a complicated vibronic structure due to strong Σ-Π vibronic coupling. The spectral envelopes of the calculated photodetachment spectra exhibit a double-hump reminiscent of strongly coupled E×e Jahn-Teller systems.
Optimal control of filamentation in air
Authors: Ackermann Roland , Salmon Estelle , Lascoux Noëlle , Kasparian Jérôme , Rohwetter Philipp , Stelmaszczyk Kamil , Li Shaohui , Lindinger Albrecht , Wöste Ludger , Béjot Pierre , Bonacina Luigi , Wolf Jean-Pierre
Published: October 2006

The authors demonstrate optimal control of the propagation of ultrashort, ultraintense (multiterawatt) laser pulses in air over distances up to 36m in a closed-loop scheme. They optimized three spectral ranges within the white-light continuum as well as the ionization efficiency. Optimization results in signal enhancements by typical factors of 2 and 1.4 for the target parameters. The optimization results in shorter pulses by reducing their chirp in the case of white-light continuum generation, while they correct the pulse from its defects and set the filamentation onset near the detector as far as air ionization is concerned.
Temperature dependence of current-voltage characteristics of Ag–La0.7Ca0.3MnO3–Pt heterostructures
Authors: Shang D. S. , Chen L. D. , Wang Q. , Zhang W. Q. , Wu Z. H. , Li X. M.
Published: October 2006

Temperature dependence of the current-voltage characteristics of Ag–La0.7Ca0.3MnO3–Pt heterostructures was investigated and the related current conduction mechanism was discussed. Poole-Frenkel emission and trap-controlled space charge limited current mechanisms are employed to explain the carrier transport at low and high temperature regions, respectively. Obvious hysteresis is observed only in the region dominated by space charge limited current with traps exponentially distributed in energy. This can be explained by the retention behavior of trapped carriers at the Ag∕La0.7Ca0.3MnO3 interface layer. It is proposed that the resistance switching can be optimized for device application by the electrode/film interface defect engineering.
Electrically tunable two-dimensional holographic photonic crystal fabricated by a single diffractive element
Authors: Liu Y. J. , Sun X. W.
Published: October 2006

An electrically tunable two-dimensional holographic photonic crystal was fabricated in polymer-dispersed liquid crystal using a single diffraction element, which was a specially designed photomask consisting of three diffraction gratings, which had a period of 4μm, oriented 120° relative to one another. With the photomask subjected to a collimated Ar+ laser beam operating at 514.5nm, a two-dimensional spatial light intensity pattern was created by interference of the three first order diffracted beams produced by the mask. The spatial light intensity pattern was then recorded inside a cell filled with the liquid crystal/prepolymer mixture to create a photonic crystal. The photonic crystal structures were observed under an optical microscope. It showed triangular structures with a lattice constant of about 2.50μm. The diffraction properties and electro-optic tunability were also presented.
Genetics of grain dormancy in a white wheat
Authors: Tan M.-K. , Sharp P. J. , Lu M.-Q. , Howes N.
Published: October 2006

A white-grained wheat accession, AUS1408, is a current major source of pre-harvest sprouting (PHS) tolerance in Australian breeding programs. This study has located 2 significant quantitative trait loci (QTLs) for its grain dormancy on 4AL and 5BL. Their associations with seed dormancy have been determined from population-level marker-trait associations (with 3 years of phenotype data) and confirmed by transmission/disequilibrium test on selected advanced breeding lines. The 4AL QTL was expressed in all years of testing, with phenotypic variance ranging from 5 to 15%, indicating a strong genotype × environment interaction. This QTL has been reported in wheat cultivars of diverse origin and was also found to be strongly influenced by the environment. The 5BL QTL was found to have a remarkably consistent effect on the trait at a phenotypic variance of around 10%. The successful outcome in this study was facilitated by high throughput DArT mapping, which complemented mapping with microsatellite markers for critical QTL identification. Identification of these QTLs from AUS1408 should enable sprouting tolerance derived from this source to be incorporated into advanced breeding lines, with the use of molecular markers reducing the requirement for multi-year field testing.
Loss of AP-3 function affects spontaneous and evoked release at hippocampal mossy fiber synapses
Authors: Scheuber Anita , Rudge Rachel , Danglot Lydia , Raposo Graca , Binz Thomas , Poncer Jean-Christophe , Galli Thierry
Published: October 2006

Synaptic vesicle (SV) exocytosis mediating neurotransmitter release occurs spontaneously at low intraterminal calcium concentrations and is stimulated by a rise in intracellular calcium. Exocytosis is compensated for by the reformation of vesicles at plasma membrane and endosomes. Although the adaptor complex AP-3 was proposed to be involved in the formation of SVs from endosomes, whether its function has an indirect effect on exocytosis remains unknown. Using
mocha
mice, which are deficient in functional AP-3, we identify an AP-3-dependent tetanus neurotoxin-resistant asynchronous release that can be evoked at hippocampal mossy fiber (MF) synapses. Presynaptic targeting of the tetanus neurotoxin-resistant vesicle soluble
N
-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is lost in
mocha
hippocampal MF terminals, whereas the localization of synaptobrevin 2 is unaffected. In addition, quantal release in
mocha
cultures is more frequent and more sensitive to sucrose. We conclude that lack of AP-3 results in more constitutive secretion and loss of an asynchronous evoked release component, suggesting an important function of AP-3 in regulating SV exocytosis at MF terminals.
Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d)
Authors: Shiroishi Mitsunori , Kuroki Kimiko , Rasubala Linda , Tsumoto Kouhei , Kumagai Izumi , Kurimoto Eiji , Kato Koichi , Kohda Daisuke , Maenaka Katsumi
Published: October 2006

HLA-G is a nonclassical MHC class I (MHCI) molecule that can suppress a wide range of immune responses in the maternal–fetal interface. The human inhibitory immune receptors leukocyte Ig-like receptor (LILR) B1 [also called LIR1, Ig-like transcript 2 (ILT2), or CD85j] and LILRB2 (LIR2/ILT4/CD85d) preferentially recognize HLA-G. HLA-G inherently exhibits various forms, including β2-microglobulin (β2m)-free and disulfide-linked dimer forms. Notably, LILRB1 cannot recognize the β2m-free form of HLA-G or HLA-B27, but LILRB2 can recognize the β2m-free form of HLA-B27. To date, the structural basis for HLA-G/LILR recognition remains to be examined. Here, we report the 2.5-Å resolution crystal structure of the LILRB2/HLA-G complex. LILRB2 exhibits an overlapping but distinct MHCI recognition mode compared with LILRB1 and dominantly recognizes the hydrophobic site of the HLA-G α3 domain. NMR binding studies also confirmed these LILR recognition differences on both conformed (heavy chain/peptide/β2m) and free forms of β2m. Binding studies using β2m-free MHCIs revealed differential β2m-dependent LILR-binding specificities. These results suggest that subtle structural differences between LILRB family members cause the distinct binding specificities to various forms of HLA-G and other MHCIs, which may in turn regulate immune suppression.
A common mechanism underlies stretch activation and receptor activation of TRPC6 channels
Authors: Spassova Maria A. , Hewavitharana Thamara , Xu Wen , Soboloff Jonathan , Gill Donald L.
Published: October 2006

The TRP family of ion channels transduce an extensive range of chemical and physical signals. TRPC6 is a receptor-activated nonselective cation channel expressed widely in vascular smooth muscle and other cell types. We report here that TRPC6 is also a sensor of mechanically and osmotically induced membrane stretch. Pressure-induced activation of TRPC6 was independent of phospholipase C. The stretch responses were blocked by the tarantula peptide, GsMTx-4, known to specifically inhibit mechanosensitive channels by modifying the external lipid-channel boundary. The GsMTx-4 peptide also blocked the activation of TRPC6 channels by either receptor-induced PLC activation or by direct application of diacylglycerol. The effects of the peptide on both stretch- and diacylglycerol-mediated TRPC6 activation indicate that the mechanical and chemical lipid sensing by the channel has a common molecular mechanism that may involve lateral-lipid tension. The mechanosensing properties of TRPC6 channels highly expressed in smooth muscle cells are likely to play a key role in regulating myogenic tone in vascular tissue.
Establishment of stable cell lines of
Drosophila
germ-line stem cells
Authors: Niki Yuzo , Yamaguchi Takafumi , Mahowald Anthony P.
Published: October 2006

Each
Drosophila
ovariole has three independent sets of stem cells: germ-line stem cells (GSCs) and escort stem cells, located at the anterior tip of the germarium, and somatic stem cells (SSCs), located adjacent to the newly formed 16-cell cysts. Decapentaplegic (Dpp) is required to maintain the anterior stem cells, whereas Hedgehog is required for maintenance and cell division of the SCCs. In an effort to establish a new
in vitro
system to analyze intrinsic and extrinsic factors regulating the division and differentiation of GSCs of
Drosophila
, we tested various culture conditions for growing GSCs, derived from
bag of marbles
(
bam
) mutant ovaries. We have shown that
bam
−
GSCs can be maintained and promoted to divide
in vitro
in media containing Dpp. These cells retain the morphological features of GSCs, i.e., expression of Vasa and Nanos and spectrosomes, even after several months of culture. Somatic cells are induced to grow in culture by the presence of sonic Hedgehog. The somatic cells produce Dpp. GSCs associate with the somatic cells via DE-cadherin, features that are also prominent at the niche of a normal germarium. Finally, we have established stable cell cultures consisting of GSCs and sheets of somatic cells, which are dependent on the addition of fly extract. A somatic cell line, lacking GSCs, has also been established. These cells are thought to be descendants of SCCs. Our
in vitro
system may provide the opportunity to manipulate GSCs genetically and to analyze the interaction of germ-line stem cells and soma.
Angiogenesis-independent tumor growth mediated by stem-like cancer cells
Authors: Sakariassen Per Ø. , Prestegarden Lars , Wang Jian , Skaftnesmo Kai-Ove , Mahesparan Rupavathana , Molthoff Carla , Sminia Peter , Sundlisæter Eirik , Misra Anjan , Tysnes Berit Bølge , Chekenya Martha , Peters Hans , Lende Gabriel , Kalland Karl Henning , Øyan Anne M. , Petersen Kjell , Jonassen Inge , van der Kogel Albert , Feuerstein Burt G. , Terzis A. Jorge A. , Bjerkvig Rolf , Enger Per Øyvind
Published: October 2006

In this work, highly infiltrative brain tumors with a stem-like phenotype were established by xenotransplantation of human brain tumors in immunodeficient nude rats. These tumors coopted the host vasculature and presented as an aggressive disease without signs of angiogenesis. The malignant cells expressed neural stem cell markers, showed a migratory behavior similar to normal human neural stem cells, and gave rise to tumors
in vivo
after regrafting. Serial passages in animals gradually transformed the tumors into an angiogenesis-dependent phenotype. This process was characterized by a reduction in stem cells markers. Gene expression profiling combined with high throughput immunoblotting analyses of the angiogenic and nonangiogenic tumors identified distinct signaling networks in the two phenotypes. Furthermore, proinvasive genes were up-regulated and angiogenesis signaling genes were down-regulated in the stem-like tumors. In contrast, proinvasive genes were down-regulated in the angiogenesis-dependent tumors derived from the stem-like tumors. The described angiogenesis-independent tumor growth and the uncoupling of invasion and angiogenesis, represented by the stem-like cancer cells and the cells derived from them, respectively, point at two completely independent mechanisms that drive tumor progression. This article underlines the need for developing therapies that specifically target the stem-like cell pools in tumors.
Radiolabeled somatostatin receptor antagonists are preferable to agonists forin vivopeptide receptor targeting of tumors
Authors: Ginj Mihaela , Zhang Hanwen , Waser Beatrice , Cescato Renzo , Wild Damian , Wang Xuejuan , Erchegyi Judit , Rivier Jean , Mäcke Helmut R. , Reubi Jean Claude
Published: October 2006

Targeting neuroendocrine tumors expressing somatostatin receptor subtypes (sst) with radiolabeled somatostatin agonists is an established diagnostic and therapeutic approach in oncology. While agonists readily internalize into tumor cells, permitting accumulation of radioactivity, radiolabeled antagonists do not, and they have not been considered for tumor targeting. The macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was coupled to two potent somatostatin receptor-selective peptide antagonists [NH2-CO-c(DCys-Phe-Tyr-DAgl8(Me,2-naphthoyl)-Lys-Thr-Phe-Cys)-OH (sst3-ODN-8) and a sst2-selective antagonist (sst2-ANT)], for labeling with111/natIn.111/natIn-DOTA-sst3-ODN-8 and111/natIn-DOTA–[4-NO2-Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH2] (111/natIn-DOTA-sst2-ANT) showed high sst3- and sst2-binding affinity, respectively. They did not trigger sst3or sst2internalization but prevented agonist-stimulated internalization.111In-DOTA-sst3-ODN-8 and111In-DOTA-sst2-ANT were injected intravenously into mice bearing sst3- and sst2-expressing tumors, and their biodistribution was monitored. In the sst3-expressing tumors, strong accumulation of111In-DOTA-sst3-ODN-8 was observed, peaking at 1 h with 60% injected radioactivity per gram of tissue and remaining at a high level for >72 h. Excess of sst3-ODN-8 blocked uptake. As a control, the potent agonist111In-DOTA–[1-Nal3]-octreotide, with strong sst3-binding and internalization properties showed a much lower and shorter-lasting uptake in sst3-expressing tumors. Similarly,111In-DOTA-sst2-ANT was injected into mice bearing sst2-expressing tumors. Tumor uptake was considerably higher than with the highly potent sst2-selective agonist111In-diethylenetriaminepentaacetic acid–[Tyr3,Thr8]-octreotide (111In-DTPA-TATE). Scatchard plots showed that antagonists labeled many more sites than agonists. Somatostatin antagonist radiotracers therefore are preferable over agonists for thein vivotargeting of sst3- or sst2-expressing tumors. Antagonist radioligands for other peptide receptors need to be evaluated in nuclear oncology as a result of this paradigm shift.
Hypersensitivity to oxygen and shortened lifespan in a
Drosophila
mitochondrial complex II mutant
Authors: Walker David W. , Hájek Petr , Muffat Julien , Knoepfle Dan , Cornelison Stephanie , Attardi Giuseppe , Benzer Seymour
Published: October 2006

Oxidative stress is implicated as a major cause of aging and age-related diseases, such as Parkinson's and Alzheimer's, as well as ischemia-reperfusion injury in stroke. The mitochondrial electron transport chain is the principal source of reactive oxygen species within cells. Despite considerable medical interest, the molecular mechanisms that regulate reactive oxygen species formation within the mitochondrion remain poorly understood. Here, we report the isolation and characterization of a
Drosophila
mutant with a defect in subunit b of succinate dehydrogenase (SDH; mitochondrial complex II). The
sdhB
mutant is hypersensitive to oxygen and displays hallmarks of a progeroid syndrome, including early-onset mortality and age-related behavioral decay. Pathological analysis of the flight muscle, which is amongst the most highly energetic tissues in the animal kingdom, reveals structural abnormalities in the mitochondria. Biochemical analysis shows that, in the mutant, there is a complex II-specific respiratory defect and impaired complex II-mediated electron transport, although the other respiratory complexes remain functionally intact. The complex II defect is associated with an increased level of mitochondrial hydrogen peroxide production, suggesting a possible mechanism for the observed sensitivity to elevated oxygen concentration and the decreased lifespan of the mutant fly.
Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch
Authors: Giuriato Sylvie , Ryeom Sandra , Fan Alice C. , Bachireddy Pavan , Lynch Ryan C. , Rioth Matthew J. , van Riggelen Jan , Kopelman Andrew M. , Passegué Emmanuelle , Tang Flora , Folkman Judah , Felsher Dean W.
Published: October 2006

The targeted inactivation of oncogenes offers a rational therapeutic approach for the treatment of cancer. However, the therapeutic inactivation of a single oncogene has been associated with tumor recurrence. Therefore, it is necessary to develop strategies to override mechanisms of tumor escape from oncogene dependence. We report here that the targeted inactivation of MYC is sufficient to induce sustained regression of hematopoietic tumors in transgenic mice, except in tumors that had lost p53 function. p53 negative tumors were unable to be completely eliminated, as demonstrated by the kinetics of tumor cell elimination revealed by bioluminescence imaging. Histological examination revealed that upon MYC inactivation, the loss of p53 led to a deficiency in thrombospondin-1 (TSP-1) expression, a potent antiangiogenic protein, and the subsequent inability to shut off angiogenesis. Restoration of p53 expression in these tumors re-established TSP-1 expression. This permitted the suppression of angiogenesis and subsequent sustained tumor regression upon MYC inactivation. Similarly, the restoration of TSP-1 alone in p53 negative tumors resulted in the shut down of angiogenesis and led to sustained tumor regression upon MYC inactivation. Hence, the complete regression of tumor mass driven by inactivation of the MYC oncogene requires the p53-dependent induction of TSP-1 and the shut down of angiogenesis. Notably, overexpression of TSP-1 alone did not influence tumor growth. Therefore, the combined inactivation of oncogenes and angiogenesis may be a more clinically effective treatment of cancer. We conclude that angiogenesis is an essential component of oncogene addiction.
Multiple reflections and Fresnel absorption in an actual 3D keyhole during deep penetration laser welding
Authors: Jin Xiangzhong , Berger Peter , Graf Thomas
Published: October 2006

In laser welding experiments of glass, keyhole shapes are observed by two high-speed cameras from two perpendicular directions. From the obtained keyhole pictures, it can be seen that in medium- and low-speed laser penetration welding, the main distortion of the keyhole is not the section metamorphosis from rotational symmetry, but the bending of its centre line. Based on such a keyhole photograph, the keyhole profiles and its centre line are determined by the method of polynomial fitting. Then, under the assumption of a circular cross section at each depth of the keyhole, the behaviour of the laser beam in the keyhole is analysed by tracing a ray of light using geometrical optics theory; the Fresnel absorption and multiple reflections in the keyhole are systematically studied, and the laser intensities absorbed on the keyhole walls are calculated. The absorbed laser intensity is not distributed uniformly on the keyhole wall. The keyhole wall absorbs laser intensity mainly on the half-part of the keyhole wall near the front wall. Because of the high absorptivity of the glass, Fresnel absorption from the first incidence of a laser beam plays a dominant role in the final laser intensity distribution on the keyhole wall, multiple reflections have some minor effects on the intensity distribution on the bottom part of the keyhole.
Arabidopsis thaliana RGXT1 and RGXT2 Encode Golgi-Localized (1,3)-α-d-Xylosyltransferases Involved in the Synthesis of Pectic Rhamnogalacturonan-II
Authors: Egelund Jack , Petersen Bent Larsen , Motawia Mohammed Saddik , Damager Iben , Faik Ahmed , Olsen Carl Erik , Ishii Tadashi , Clausen Henrik , Ulvskov Peter , Geshi Naomi
Published: October 2006

Two homologous plant-specific Arabidopsis thaliana genes, RGXT1 and RGXT2, belong to a new family of glycosyltransferases (CAZy GT-family-77) and encode cell wall (1,3)-α-d-xylosyltransferases. The deduced amino acid sequences contain single transmembrane domains near the N terminus, indicative of a type II membrane protein structure. Soluble secreted forms of the corresponding proteins expressed in insect cells showed xylosyltransferase activity, transferring d-xylose from UDP-α-d-xylose to l-fucose. The disaccharide product was hydrolyzed by α-xylosidase, whereas no reaction was catalyzed by β-xylosidase. Furthermore, the regio- and stereochemistry of the methyl xylosyl-fucoside was determined by nuclear magnetic resonance to be an α-(1,3) linkage, demonstrating the isolated glycosyltransferases to be (1,3)-α-d-xylosyltransferases. This particular linkage is only known in rhamnogalacturonan-II, a complex polysaccharide essential to vascular plants, and is conserved across higher plant families. Rhamnogalacturonan-II isolated from both RGXT1 and RGXT2 T-DNA insertional mutants functioned as specific acceptor molecules in the xylosyltransferase assay. Expression of RGXT1- and RGXT2-enhanced green fluorescent protein constructs in Arabidopsis revealed that both fusion proteins were targeted to a Brefeldin A–sensitive compartment and also colocalized with the Golgi marker dye BODIPY TR ceramide, consistent with targeting to the Golgi apparatus. Taken together, these results suggest that RGXT1 and RGXT2 encode Golgi-localized (1,3)-α-d-xylosyltransferases involved in the biosynthesis of pectic rhamnogalacturonan-II.
NPS6, Encoding a Nonribosomal Peptide Synthetase Involved in Siderophore-Mediated Iron Metabolism, Is a Conserved Virulence Determinant of Plant Pathogenic Ascomycetes
Authors: Oide Shinichi , Moeder Wolfgang , Krasnoff Stuart , Gibson Donna , Haas Hubertus , Yoshioka Keiko , Turgeon B. Gillian
Published: October 2006

NPS6, encoding a nonribosomal peptide synthetase, is a virulence determinant in the maize (Zea mays) pathogen Cochliobolus heterostrophus and is involved in tolerance to H2O2. Deletion of NPS6 orthologs in the rice (Oryza sativa) pathogen, Cochliobolus miyabeanus, the wheat (Triticum aestivum) pathogen, Fusarium graminearum, and the Arabidopsis thaliana pathogen, Alternaria brassicicola, resulted in reduced virulence and hypersensitivity to H2O2. Introduction of the NPS6 ortholog from the saprobe Neurospora crassa to the Δnps6 strain of C. heterostrophus restored wild-type virulence to maize and tolerance to H2O2, demonstrating functional conservation in filamentous ascomycete phytopathogens and saprobes. Increased sensitivity to iron depletion was identified as a conserved phenotype of Δnps6 strains. Exogenous application of iron enhanced the virulence of Δnps6 strains of C. heterostrophus, C. miyabeanus, F. graminearum, and A. brassicicola to each host. NPS6 is responsible for the biosynthesis of extracellular siderophores by C. heterostrophus, F. graminearum, and A. brassicicola. Application of the extracellular siderophore of A. brassicicola restored wild-type virulence of the ΔAbnps6 strain to Arabidopsis. It is proposed that the role of extracellular siderophores in fungal virulence to plants is to supply an essential nutrient, iron, to their producers in planta and not to act as phytotoxins, depriving their hosts of iron.
Management of cutaneous angiomyolipoma and its association with tuberous sclerosis
Authors: DEBLOOM James R. , FRIEDRICHS Amanda , SWICK Brian L. , WHITAKER Duane C.
Published: October 2006

Although typically presenting renally, angiomyolipomas can rarely present in the skin. The tumors are composed of an admixture of blood vessels, smooth muscle and adipose tissue and are often seen in the setting of tuberous sclerosis. We describe a case of angiomyolipoma presenting on the thigh of a 50‐year‐old white female. This is the 17th reported case of cutaneous angiomyolipoma. As with all previously described cases, our patient did not present with the stigmata of tuberous sclerosis. Angiomyolipoma should be considered within the differential for subcutaneous nodules and work‐up for tuberous sclerosis should not be pursued when presenting in the skin.
Meta‐analysis: anti‐viral therapy of hepatitis C virus‐related liver disease in renal transplant patients
Authors: FABRIZI F. , LUNGHI G. , DIXIT V. , MARTIN P.
Published: October 2006

Background

The efficacy and safety of interferon‐based therapy in renal transplant recipients with hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue.

Aim

To evaluate efficacy and safety of antiviral therapy with interferon (interferon alone or interferon plus ribavirin) in renal transplant patients with hepatitis C by performing a systematic review of the literature with a meta‐analysis of clinical trials.

Methods

The primary outcomes were sustained virological response (as a measure of efficacy) and/or drop‐out rate (as a measure of tolerability). We used the random‐effects model of DerSimonian and Laird, with heterogeneity and sensitivity analysis.

Results

We identified 12 clinical trials (102 unique patients); there was one controlled study. The summary estimate for sustained virological response and drop‐out rate was 18.0% (95% CI 7.0–29.0%) and 35.0% (95% CI 20–50%), respectively. The most frequent side‐effect requiring interruption of treatment was graft dysfunction (n = 28; 71.7%). Meta‐regression analysis showed an inverse and significant association between reference year and drop‐out logit rate (P = 0.012); an inverse link between sustained virological response logit rate and frequency of hepatitis C virus genotype 1 (P = 0.067) and cirrhosis (P = 0.08) was found, even if no statistical significance was reached. No publication bias was observed.

Conclusions

Interferon‐based therapy of hepatitis C has poor tolerance and safety after renal transplant. The optimal treatment of hepatitis C after renal transplant requires additional agents or alternative therapeutic approaches.
Genomic organisation and regulation of murine alpha haemoglobin stabilising protein by erythroid Kruppel‐like factor
Authors: Keys Janelle R. , Tallack Michael R. , Hodge Denise J. , Cridland Simon O. , David Rakesh , Perkins Andrew C.
Published: October 2006

Alpha haemoglobin stabilising protein (AHSP) binds free α‐globin chains and plays an important role in the protection of red cells, particularly during β‐thalassaemia. Murine ASHP was discovered as a GATA‐1 target gene and human AHSP is directly regulated by GATA‐1. More recently, AHSP was rediscovered as a highly erythroid Kruppel‐like factor (EKLF) ‐dependent transcript. We have determined the organisation of the murine AHSP gene and compared it to orthologs. There are two CACC box elements in the proximal promoter. The proximal element is absolutely conserved, but does not bind EKLF as it is not a canonical binding site. In rodents, the distal element contains a 3 bp insertion that disrupts the typical EKLF binding consensus region. Nevertheless, EKLF binds this atypical site by gel mobility shift assay, specifically occupies the AHSP promoter in vivo in a chromatin immunoprecipitation assay, and transactivates AHSP through this CACC site in promoter–reporter assays. Our results suggest EKLF can occupy CACC elements in vivo that are not predictable from the consensus binding site inferred from structural studies. We also propose that absence of AHSP in EKLF‐null red cells exacerbates the toxicity of free α‐globin chains, which exist because of the defect in β‐globin gene activation.
Analysis of the Klebsiella pneumoniae ntrB gene by site‐directed in vitro mutagenesis
Authors: MacFarlane S. A. , Merrick M. J.
Published: October 2006

A number of in‐frame insertion and deletion mutations have been constructed in vitro in the Klebsiella pneumoniae ntrB gene and the effects of each mutant NtrB protein on NtrC activity have been assessed after reintroduction of the ntrB mutation into the glnA ntrBC operon. These experiments suggest that the phosphorylation of NtrC catalysed by NtrB not only makes NtrC competent as a transcriptional activator but also improves the DNA‐binding properties and hence the negative control functions of NtrC. The variety of NtrB phenotypes obtained suggest a structure/function model for the protein.
A gene fusion approach to the study of pullulanase export and secretion in Eschenchia coli
Authors: D'Enfert C. , Pugsley A.P.
Published: October 2006

A series of fusions between the gene for the Klebsiella pneumoniae secreted lipoprotein pullulanase (pulA) and the genes for cytoplasmic β‐galactosidase (lacZ) or periplasmic alkaline phosphatase (phoA) were created by transposon mutagenesis using mini‐Mudlt1681 or TnphoA, respectively. The hybrid genes were expressed in Escherichia coli K‐12 with or without the K. pneumoniae genes that promote pullulanase secretion in E. coli. We characterized seven different pulA‐lacZ gene fusions encoding hybrid polypeptides containing from 14 to c. 1060 residues of pro‐pullulanase. All but the smallest hybrid were fatty acylated and were toxic to producing cells, causing the accumulation of precursors of other exported proteins. Four different pulA‐phoA gene fusions encoded hybrids with alkallne phosphatase activity. All four hybrids were fatty acylated, but were not toxic. Although the hybrids were apparently membrane‐associated, they were not secreted into the medium either by E. coli carrying pullulanase secretion genes or by K. pneumoniae. Immunofluorescence tests indicated that the pullulanase secretion genes promoted the localization of one of these hybrids to the outer face of the E. coli outer membrane, which may have important implications for the design of live vaccine. strains and of immobilized enzymes.
Transcriptional activation of the Klebsiella pneumoniae nitrogenase promoter may involve DNA loop formation
Authors: Buck M. , Cannon W. , Woodcock J.
Published: October 2006

Transcriptional activation of nitrogen fixation genes by Nrt A in Klebsiella pneumoniae requires an upstream Nif A binding site. We now report that the introduction of haif turns of the DNA helix into the DNA separating the upstream NifA binding site from the downstream promoter element of the nifH promoter decreases Nif A‐mediated activation to a greater extent than does the introduction of full helical turns. Reducing the spacing between the upstream and downstream elements of the nifH promoter also results in a promoter down phenotype. Introduction of a tight protein‐binding site, the lac operator, between the upstream and downstream promoter elements did not render activation of the nifH promoter sensitive to occupancy of this site by the lac repressor. These findings indicate that NifA‐mediated activation of transcription requires that NifA is bound upstream, and to the correct face of the DNA helix, in order to interact with downstream transcription factors. This implies that the interaction is brought about by the formation of a DNA loop between upstream and downstream promoter elements rather than by NifA sliding downstream.

The authors wish to thank Ray Dixon, Martin Drummond, Mike Merrick, and John Postgate for their constructive comments on the manuscript, and Beryl Scutt for typing the manuscript.
Nucleotide sequence and transcriptional startpoint of the glpT gene of Escherichia coli: extensive sequence homology of the glycerol‐3‐phosphate transport protein with components of the hexose‐6‐phosphate transport system
Authors: Eiglmeier K. , Boos W. , Cole S. T.
Published: October 2006

The nucleotide sequences of the glpT gene of Escherichia coli and its regulatory region have been elucidated and the primary structure of the glycerot‐3‐phosphate transport protein deduced. Extensive amino acid sequence homology was found with two other cytoplasmic membrane proteins: the functionally related hexose‐6‐phosphate transport protein, and the UHPC protein involved in regulating hexose‐6‐phosphate uptake. Although no significant amino acid sequence homology was found with other transport proteins, such as the arabinose, citrate, glucose, melibiose, lactose or xylose transporters, all of these proteins share a common secondary structure arrangement with the GLP T protein as they apparently contain twelve membrane‐spanning alpha‐helical segments. The promoter for glpT was located by transcript mapping and shown to overlap a site to which cata‐bolite activator protein binds in vitro. These findings indicate how catabolite repression may be mediated but do not explain its physiological significance in glycerol metabolism.
The use of DNA probes identifying restriction‐fragment‐length polymorphisms to examine the Mycobacterium avium complex
Authors: McFadden J. J. , Butcher P. D. , Thompson J. , Chiodini R. , Hermon‐Taylor J.
Published: October 2006

DNA probes were used to identify restriction‐fragment‐length polymorphisms (RFLPs) in DNA samples, demonstrating that the Mycobacterium avium complex could be clearly divided Into M. avium and Mycobacterium intracellulare strains. Less than 2% DNA base substitution was found between M. avium strains, whereas the M. intracellulare strains had greater than 15% base substitution. The Johne's disease bacillus, Mycobacterium paratubercuiosis (American type strain), was found to be distinguishable from the M. avium complex serotypes examined. Strain 18 was found to be identical to M. avium. The rat leprosy bacillus, Mycobacterium lepraemurium, was found to be very closely related, but not identical, to M. avium.
Effects of deletions in the spacer region of the rrnB operon on the transcription of the large ribosomal RNAs from Escherichia coli
Authors: Szymkowiak C. , Wagner R.
Published: October 2006

A series of deletions was constructed within the spacer region of the genes for the 16S and 23S RNA on plasmids bearing the rrnB operon. The accumulation and synthesis rates for the 16S and 23S RNAs were determined from normal growing cells and maxicells after transformation with the mutated plasmids. A marked difference In the transcription efficiency of the plasmid‐encoded ribosomal 16S and 23S RNAs was observed with cells carrying plasmids, where a sequence motif analogous to the antitermination recognition sequence (Box A) had been deleted. The overall synthesis rate of ribosomal RNAs of such cells was not altered, however, indicating that the difference in transcription rates from the plasmid genes is compensated by altered transcription rates of the corresponding chromosomal genes. In addition, the accumulation of various tRNA species encoded on rRNA operons and non rRNA operons was quantitated and compared. From these results we infer that the regulation of ribosomal RNA transcription does not only occur at the promoter sites but sequence regions possibly involved in antitermination within the operon are crucial for a coordinated synthesis of all ribosomal RNAs.
A plasmid‐encoded gas vesicle protein gene in a halophilic archaebacterium
Authors: DasSarma S. , Damerval T. , Jones J. G. , Marsac N. Tandeau de
Published: October 2006

The halophilic archaebacterium, Halobacterium halobium, displays spontaneous and revertible genetic variability for the gas vesicle phenotype (Vac) at frequencies as high as 0.5 to 5%. To investigate the mechanism of these high‐frequency mutations, we have cloned a gas vesicle protein gene (gvpA) from the Vac+ wild‐type H. halobium strain, NRC‐1, and determined its nucleotide sequence, transcription start site, and genomic location. The gene sequence predicts that the gas vesicle protein has a molecular weight of 9156 and is relatively hydrophobic except for a hydrophilic C‐terminal region. Northern hybridization analysis shows that the gene is transcribed into a 350‐nucleotide mRNA, and primer extension analysis indicates that transcription begins 20 nucleotides upstream of the ATG start codon. Southern hybridization analysis shows that the gene is encoded by a large H. halobium plasmid. We discuss potential mechanisms for genetic variability of the Vac phenotype and identify sequences in the gvpA promoter region which may function as signals for transcription in H. halobium.