bluuebunny/crossref_metadata_2025 huggingface dataset:
A mathematical model for blood flow in magnetic field
Authors: Tzirtzilakis E. E.
Published: July 2005

In the present study a mathematical model of biomagnetic fluid dynamics (BFD), suitable for the description of the Newtonian blood flow under the action of an applied magnetic field, is proposed. This model is consistent with the principles of ferrohydrodynamics and magnetohydrodynamics and takes into account both magnetization and electrical conductivity of blood. As a representative application the laminar, incompressible, three-dimensional, fully developed viscous flow of a Newtonian biomagnetic fluid (blood) in a straight rectangular duct is numerically studied under the action of a uniform or a spatially varying magnetic field. The numerical results are obtained using a finite differences numerical technique based on a pressure-linked pseudotransient method on a collocated grid. The flow is appreciably influenced by the application of the magnetic field and in particularly by the strength and the magnetic field gradient. A comparison of the derived results is also made with those obtained using the existing BFD model indicating the necessity of taking into account the electrical conductivity of blood.
Trapped-electron solitary wave structures in a magnetized plasma
Authors: Grabbe C. L.
Published: July 2005

The classic one-dimensional (1D) BGK-mode (trapped-particle) analysis is extended to 3D plasmas in which a background magnetic field is present. A theoretical analysis is made of such nonlinear states from the coupled plasma equations for a magnetized plasma, which yields a generalized BGK-like equation for trapped-particle distributions that produce this structure in the guiding-center approximation, and the resulting conditional requirement for electron trapping as a function of the electric-field components, and magnetic gradient and polarization drifts. This condition shows that the amount of trapping decreases as the angle of the electric field with respect to the background magnetic field increases, often ceasing at a critical finite angle. The full solution to the generalized BGK-type equation for the trapped-electron distribution is obtained and reduced to the extent possible, thereby extending the classic 1D solution for electron holes to that for the 3D magnetized plasmas for cylindrical symmetry. This solution is very easily generalized for the inclusion of any cross-tail drift for the case of interest. For the case that the E×B drift dominates, the solution shows that these trapped-particle modes usually are restricted to angles θ<sin−1−2B2W∕meE2, where −W is the available trapping energy for the electrons, although in rarer cases slightly higher angles for these modes may be allowed. In no case can θ be as large as sin−12−B2W∕meE2.
Magnetic reconnection in nontoroidal plasmas
Authors: Boozer Allen H.
Published: July 2005

Magnetic reconnection is a major issue in solar and astrophysical plasmas. The mathematical result that the evolution of a magnetic field with only point nulls is always locally ideal limits the nature of reconnection in nontoroidal plasmas. Here it is shown that the exponentially increasing separation of neighboring magnetic field lines, which is generic, tends to produce rapid magnetic reconnection if the length of the field lines is greater than about 20 times the exponentiation, or Lyapunov, length.
Hole drift-mobility measurements in microcrystalline silicon
Authors: Dylla T. , Finger F. , Schiff E. A.
Published: July 2005

We have measured transient photocurrents on several p-i-n solar cells based on microcrystalline silicon. For two of these samples, we were able to obtain conclusive hole drift-mobility measurements. Despite the predominant crystallinity of these samples, temperature-dependent measurements were consistent with an exponential-bandtail trapping model for transport, which is usually associated with noncrystalline materials. We estimated valence bandtail widths of about 31meV and hole band mobilities of 1–2cm2∕Vs. The measurements support mobility-edge transport for holes in these microcrystalline materials, and broaden the range of materials for which mobility-edge transport corresponds to an apparently universal band mobility of order 1cm2∕Vs.
Multiple time scale chaos in a Schmitt trigger circuit
Authors: Carroll Thomas L.
Published: July 2005

It is known that stray radio frequency signals can produce nonlinear effects that disrupt the operation of circuits, but the mechanisms by which this disruption occurs are not well known. In this paper, an emitter coupled Schmitt trigger circuit is driven with a high-frequency signal to look for disruptive effects. As the circuit makes a transition between mode locked states (period 2 and period 3, for example), there is a region of chaos in which the largest peak in the power spectrum is in between the mode-locked frequencies, and is not related to the driving frequency by an integer multiple. This chaos resembles the chaos seen during a period adding sequence, except that it contains frequencies ranging over many orders of magnitude, from the driving frequencies on the order of megahertz, down to a few hertz. It is found that only a one-transistor circuit is necessary to produce this extremely broadband chaos, and true quasiperiodicity is not seen in this circuit. The single-transistor circuit is then simulated to confirm the frequency conversion effects.
Aligned silver nanorod arrays produce high sensitivity surface-enhanced Raman spectroscopy substrates
Authors: Chaney Stephen B. , Shanmukh Saratchandra , Dluhy Richard A. , Zhao Y.-P.
Published: July 2005

Substrates consisting of silver nanorod arrays with an irregular surface lattice (i.e., random nucleation sites) and with varying rod lengths were fabricated by an oblique angle vapor deposition method. These arrays were evaluated as potential surface-enhanced Raman spectroscopy (SERS) substrates using trans-1,2-bis(4-pyridyl)ethene as a reported molecule. SERS activity was shown to depend upon the length of the nanorods. The Ag nanorods with average lengths of 508.29±44.86nm, and having aspect ratios of 5.69±1.49 exhibited the maximum SERS enhancement factors of greater than 108. Theoretical calculations indicate that this large SERS enhancement may be partially explained by the shape, density, and lateral arrangement of the Ag nanorod arrays.
Near-field measurement of spectral anisotropy and optical absorption of isolated ZnO nanorod single-quantum-well structures
Authors: Yatsui Takashi , Ohtsu Motoichi , Yoo Jinkyoung , An Sung Jin , Yi Gyu-Chul
Published: July 2005

We report low-temperature near-field spectroscopy of isolated ZnO∕ZnMgO single-quantum-well structures (SQWs) on the end of ZnO nanorod to define their potential for nanophotonics. First, absorption spectra of isolated ZnO∕ZnMgO nanorod SQWs with the Stokes shift as small as 3meV and very sharp photoluminescent peaks indicate that the nanorod SQWs are of very high optical quality. Furthermore, we performed polarization spectroscopy of isolated ZnO SQWs, and observed valence-band anisotropy of ZnO SQWs in photoluminescence spectra directly. Since the exciton in a quantum structure is an ideal two-level system with long coherence times, our results provide criteria for designing nanophotonic devices.
Polarization mode splitting in monolithic polymer microcavities
Authors: Persano Luana , Mele Elisa , Cingolani Roberto , Pisignano Dario
Published: July 2005

We demonstrate the mode splitting of the resonant emission from a symmetric monolithic organic semiconductor microcavity. The device, realized by low-temperature reactive electron-beam evaporation and deposition of a conjugated polymer, exhibits a 100 meV polarization-induced splitting of the transmission and emission resonances for angles larger than 45°. This opens the way for the realization of novel polarized-emitting optoelectronic devices based on plastic materials.
Process development and bonding quality investigations of silicon layer stacking based on copper wafer bonding
Authors: Chen K. N. , Chang S. M. , Fan A. , Tan C. S. , Shen L. C. , Reif R.
Published: July 2005

Process development of silicon layer stacking based on copper wafer bonding, grind-back, and etch-back was applied to demonstrate a strong four-layer-stack structure. Bonded copper layers in this structure became homogeneous layers and did not show original bonding interfaces. This process can be used in three-dimensional integrated circuit applications. Voids and total bonded area after each layer stacking were investigated for the bonding quality after each layer stacking. Large wafer bows from high residual stresses result in the structure failure at the stacking of a high number of layers.
Structural characterization of zincblende Ga1−xMnxN epilayers grown by molecular beam epitaxy on (001) GaAs substrates
Authors: Fay M. W. , Han Y. , Brown P. D. , Novikov S. V. , Edmonds K. W. , Campion R. P. , Gallagher B. L. , Foxon C. T.
Published: July 2005

Zincblende p-type Ga1−xMnxN epilayers, grown with and without AlN∕GaN buffer layers using plasma-assisted molecular beam epitaxy on (001) oriented GaAs substrates, have been investigated using a variety of complementary transmission electron microscopy techniques. The epilayers were found to contain a high anisotropic density of stacking faults and microtwins. MnAs inclusions were identified at the Ga1−xMnxN∕(001)GaAs interface extending into the substrate. The use of AlN∕GaN buffer layers was found to inhibit the formation of these inclusions.
Magnetically superior and easy to handle L1-FePt nanocrystals
Authors: Yamamoto Shinpei , Morimoto Yasumasa , Ono Teruo , Takano Mikio
Published: July 2005

We report synthesis of monodisperse L10-FePt nanocrystals that are not only superior in magnetism but also easy to handle through being dispersible in solvents. Thanks to a thick SiO2 coating, the thermal treatment needed to form the L10 structure can be done even at 900°C without inducing coalescence and coarsening. The protecting shell was thereafter removed in a specific way that enabled us to recover the L10-FePt nanocrystals in a water dispersion. The SiO2-coated nanocrystals show a high coercivity of 18.5kOe at room temperature in spite of their core size of only 6.5nm in diameter, and the hysteresis loop of the water-dispersed nanocrystals, which were frozen under an external field, was almost rectangular indicating that their magnetic and structural orientation could be attained.
Patterned growth of carbon nanotubes on Si substrates without predeposition of metal catalysts
Authors: Chen Y. , Yu J.
Published: July 2005

Aligned carbon nanotubes (CNTs) can be readily synthesized on quartz or silicon-oxide-coated Si substrates using a chemical vapor deposition method, but it is difficult to grow them on pure Si substrates without predeposition of metal catalysts. We report that aligned CNTs were grown by pyrolysis of iron phthalocyanine at 1000°C on the templates created on Si substrates with simple mechanical scratching. Scanning electron microscopy and x-ray energy spectroscopy analysis revealed that the trenches and patterns created on the surface of Si substrates were preferred nucleation sites for nanotube growth due to a high surface energy, metastable surface structure, and possible capillarity effect. A two-step pyrolysis process maintained Fe as an active catalyst.
Band gap and band offset of (GaIn)(PSb) lattice matched to InP
Authors: Köhler F. , Böhm G. , Meyer R. , Amann M.-C.
Published: July 2005

Metastable (GaxIn1−x)(PySb1−y) layers were grown on (001) InP substrates by gas source molecular beam epitaxy. Low-temperature photoluminescence spectroscopy was applied to these heterostructures and revealed spatially indirect band-to-band recombination of electrons localized in the InP with holes in the (GaxIn1−x)(PySb1−y). In addition, samples with layer thicknesses larger than 100nm showed direct PL across the band gap of (GaxIn1−x)(PySb1−y). Band-gap energies and band offset energies of (GaxIn1−x)(PySb1−y) relative to InP were derived from these PL data. A strong bowing parameter was observed.
Depletion regions in the aluminum-induced layer exchange process crystallizing amorphous Si
Authors: Schneider Jens , Klein Juliane , Muske Martin , Gall Stefan , Fuhs Walther
Published: July 2005

Annealing of aluminum/amorphous silicon bilayers below the eutectic temperature of the aluminum/silicon system leads to an exchange of the layer positions and a concurrent crystallization of silicon (aluminum-induced layer exchange). This letter discusses a model for the self-limited suppression of nucleation during the process. This characteristic feature is the reason why large grain sizes can be obtained. In our experiments, we combine nucleation caused by supersaturation and undercooling. Si depletion regions around existing grains are made visible. These experiments give direct proof of the idea that the suppression of nucleation occurs by Si depletion in the aluminum-induced layer exchange process.
Controllable generation of highly stripped ions with different charges by nanosecond laser ionization of clusters at different wavelengths
Authors: Niu Dongmei , Li Haiyang , Liang Feng , Luo Xiaolin , Wen Lihua
Published: July 2005

We report an effective method to selectively produce highly charged ions by photoionization of cluster beams using commercial nanosecond Nd:yttrium–aluminum–garnet lasers at different wavelengths. He-like ions of C4+, N5+, O6+, S6+ and highly charged Xeq+(q∼19) ions are produced when cluster beams of benzene, ammonia, acetone, hydrogen sulfide, and xenon are irradiated, respectively, by 1064 nm laser with intensity of ∼1011W∕cm2. While the cluster beams are irradiated by 532 nm laser of similar intensity, the ions of the highest charge state switch to C3+, N3+, O3+, S4+ and Xe11+, respectively.
Micro-Raman and photoluminescence studies of neutron-irradiated gallium nitride epilayers
Authors: Wang R. X. , Xu S. J. , Fung S. , Beling C. D. , Wang K. , Li S. , Wei Z. F. , Zhou T. J. , Zhang J. D. , Huang Ying , Gong M.
Published: July 2005

GaN epilayers grown on sapphire substrate were irradiated with various dosages of neutrons and were characterized using Micro-Raman and photoluminescence. It was found that the A1(LO) peak in the Raman spectra clearly shifted with neutron irradiation dosage. Careful curve fitting of the Raman data was carried out to obtain the carrier concentration which was found to vary with the neutron irradiation dosage. The variation of the full width at half maximum height of the photoluminescence was consistent with the Raman results. The neutron irradiation-induced structural defects (likely to be GeGa) give rise to carrier trap centers which are responsible for the observed reduction in carrier concentration of the irradiated GaN.
Low-temperature phase of SrTiO3
Authors: Levstik A. , Filipič C. , Pirc R. , Bobnar V. , Blinc R. , Itoh M.
Published: July 2005

The linear and nonlinear dielectric properties of SrTiO3 (STO16) and SrTiO318 (STO18) are described by an order-disorder component represented by the spherical random-bond-random-field model, up until now applied only to relaxor ferroelectrics. It is shown that, due to the contribution of domain walls, the dielectric response of STO18 below Tc increases with increasing the measuring field. As similar behavior is observed in STO16 also and, furthermore, the field-cooled-zero-field-heated polarization is different from zero below 55 K, the high values of the linear dielectric constant in the low-temperature phase of STO16 are ascribed to the dynamic response of the polar clusters.
Double interference fluorescence enhancement from reflective slides: Application to bicolor microarrays
Authors: Choumane H. , Ha N. , Nelep C. , Chardon A. , Reymond G. O. , Goutel C. , Cerovic G. , Vallet F. , Weisbuch C. , Benisty H.
Published: July 2005

A technique for enhancing fluorescence from species close to a substrate is described, based on a multilayer dielectric mirror coating. For proper design, interferences bring improvements to both fluorescence excitation and collection, each about four fold. The overall improvement reaches 10 to 15 fold as compared to a standard glass slide. We apply this to so-called deoxyribonucleic acid (DNA) chips, that is to DNA hybridization assays on microarray platforms, for which two fluorophores most commonly used are cyanine dyes (Cy3™ and Cy5™). Impact of the two-color scheme is discussed. A validation method based on spin-coated fluorescent ultrathin layers is shown to accurately determine the amplification factors of the different tagging dyes.
Thermal processes in metal-coated fiber probes for near-field experiments
Authors: Ambrosio A. , Allegrini M. , Latini G. , Cacialli F.
Published: July 2005

We have used a ray optics model to calculate the optical power absorbed in the metal coating of apertured probes for scanning near-field optical microscopy. We have then introduced the absorbed power profile into the heat balance equation to calculate the temperature of the probe as a function of the distance from the apex. By comparing our results with available experimental data, we demonstrate accurate prediction of both the temperature profile along the probe, and the temperature increase per mW of power launched into the fiber (60.7 versus 60K∕mW at 25μm from the apex).
High-quality factor optical microcavities using oxide apertured micropillars
Authors: Stoltz N. G. , Rakher M. , Strauf S. , Badolato A. , Lofgreen D. D. , Petroff P. M. , Coldren L. A. , Bouwmeester D.
Published: July 2005

An oxide aperture is used to confine optical modes in a micropillar structure. This method overcomes the limitations due to sidewall scattering loss typical in semiconductor etched micropillars. High cavity quality factors (Q) up to 48 000 are determined by external Fabry–Perot cavity scanning measurements, a significantly higher value than prior work in III-V etched micropillars. Measured Q values and estimated mode volumes correspond to a maximum Purcell factor figure of merit value of 72.
True atomic resolution in liquid by frequency-modulation atomic force microscopy
Authors: Fukuma Takeshi , Kobayashi Kei , Matsushige Kazumi , Yamada Hirofumi
Published: July 2005

True atomic resolution of frequency-modulation atomic force microscopy in liquid is demonstrated. Hexagonal lattice of a cleaved (001) surface of muscovite mica is resolved in water. Nonperiodic structures such as defects and adsorbates are simultaneously imaged with the atomic-scale features of mica surface. The use of small oscillation amplitude (0.16–0.33 nm) of a force sensing cantilever allows us to obtain vertical and lateral resolutions of 2–6 and 300 pm, respectively, even with a low Q factor in water (Q=20–30).
Highly ordered self-organized dot patterns on Si surfaces by low-energy ion-beam erosion
Authors: Ziberi B. , Frost F. , Rauschenbach B. , Höche Th.
Published: July 2005

Scanning force microscopy (AFM) and high-resolution transmission electron microscopy (HRTEM) have been used to investigate the complex topography evolution of Si surfaces during low-energy ion beam erosion. Depending on ion-beam parameters, a variety of different topographies can develop on the surface. At oblique ion-incidence angles, nanodots are formed for ion energies ⩾300eV upon sample rotation. Properly chosen parameters of the broad-beam ion source result in dots possessing a very high degree of lateral ordering with a mean dot size λ∼30nm. Both, degree of ordering and size homogeneity of these nanostructures increases with erosion time leading to the most ordered self-organized patterns on Si surfaces reported thus far.
Platinum–Tin Bonded Complexes, Including a Structural Analysis of the Octahedral Tris(pyrazol-1-yl)borate Complex Pt(SnMe3)Me2{(pz)3BH-N,N',N"}
Authors: Canty Allan J. , Jin Hong , Skelton Brian W. , White Allan H.
Published: July 2005

The platinum(II) complex K[PtMe2
{(pz)3BH-N,N′}]
reacts with SnCl2Me2 to form
Pt(SnClMe2)Me2-
{(pz)3BH-N,N′
,N″}
([(pz)3BH]–=tris(pyrazol-1-yl)borate).
The closely related complex
Pt(SnMe3)Me2- {
(pz)3BH-N,N′
,N″ } has distorted octahedral geometry for
platinum with Pt–Sn 2·5727(8) Å . The Pt–N distance
trans to the SnMe3 group
[2·237(7) Å] is longer than those
trans to the Me groups [2·127(7) and
2·131(6) Å], indicating for the trimethylstannyl group a
trans influence which is higher than that for the methyl
group.
Formation of a Novel Cyclopenta[b]pyran Derivative in the Dehydrobromination of 1,10-Dibromobicyclo[8.1.0]undecane-3,8-dione
Authors: Byrne Lindsay T. , Payne Alan D. , Wege Dieter , Roemkens Christina H.
Published: July 2005

Treatment of 1,10-dibromobicyclo[8.1.0]undecane-3,8-dione (3) with
triethylamine in dichloromethane results in the formation of a deep red
compound formulated as 1,4,5,6,7,10,11,12,13,15b-decahydroazuleno-
[1′,2′-e]cyclopropa[3,4]cyclodeca[1,2-b]pyran-3,14-dione
(13) on the basis of its spectral properties.
Excavatolides N - T, New Briaran Diterpenes from the Western Australian Gorgonian Briareum excavatum
Authors: Neve Juliette E. , McCool Brian J. , Bowden Bruce F.
Published: July 2005

A Western Australian sample of the gorgonian
Briareum excavatum, collected at Rowley Shoals, afforded
one known (10) and seven new briaran diterpenes (1), (3) and (5)–(9).
Gross structures and relative stereochemistries were determined by
spectroscopic methods and by comparison of spectral data with those of
previously reported briarans. Support for a proposed conformation of the
10-membered ring (stabilized by hydrogen-bonding) to explain atypical
1H n.m.r. chemical shifts and coupling constants in (9)
was obtained from energy minimization of the proposed structure by an
ab initio density functional method.
Structural specificity conferred by a group I RNA peripheral element
Authors: Johnson Travis H. , Tijerina Pilar , Chadee Amanda B. , Herschlag Daniel , Russell Rick
Published: July 2005

Like proteins, structured RNAs must specify a native conformation that is more stable than all other possible conformations. Local structure is much more stable for RNA than for protein, so it is likely that the principal challenge for RNA is to stabilize the native structure relative to misfolded and partially folded intermediates rather than unfolded structures. Many structured RNAs contain peripheral structural elements, which surround the core elements. Although it is clear that peripheral elements stabilize structure within RNAs that contain them, it has not yet been explored whether they specifically stabilize the native states relative to alternative folds. A two-piece version of the group I intron RNA from
Tetrahymena
is used here to show that the peripheral element P5abc binds to the native conformation of the rest of the RNA 50,000 times more tightly than it binds to a long-lived misfolded conformation. Thus, P5abc stabilizes the native conformation by ≈6 kcal/mol relative to this misfolded conformation. Further, activity measurements show that for the RNA lacking P5abc, the native conformation is only marginally preferred over the misfolded conformation (<0.5 kcal/mol), indicating that the peripheral structure of this RNA is required to achieve a significant thermodynamic preference for the native state. Such “structural specificity” may be a general function of RNA peripheral domains.
DNA lesions induced by UV A1 and B radiation in human cells: Comparative analyses in the overall genome and in thep53tumor suppressor gene
Authors: Besaratinia Ahmad , Synold Timothy W. , Chen Hsiu-Hua , Chang Cheng , Xi Bixin , Riggs Arthur D. , Pfeifer Gerd P.
Published: July 2005

The UV components of sunlight (UVA and UVB) are implicated in the etiology of human skin cancer. The underlying mechanism of action for UVB carcinogenicity is well defined; however, the mechanistic involvement of UVA in carcinogenesis is not fully delineated. We investigated the genotoxicity of UVA1 versus UVB in the overall genome and in thep53tumor suppressor gene in normal human skin fibroblasts. Immuno-dot blot analysis identified thecis-syncyclobutane pyrimidine-dimer (CPD) as a distinctive UVB-induced lesion and confirmed its formation in the genomic DNA of UVA1-irradiated cells dependent on radiation dose. HPLC/tandem MS analysis showed an induction of 8-oxo-7,8-dihydro-2′-deoxyguanosine in the genomic DNA of UVA1-irradiated cells only. Mapping of DNA damages by terminal transferase-dependent PCR revealed preferential, but not identical, formation of polymerase-blocking lesions and/or strand breaks along exons 5-8 of thep53gene in UVB- and UVA1-irradiated cells. The UVB-induced lesions detected by terminal transferase-PCR were almost exclusively mapped to pyrimidine-rich sequences; however, the UVA1-induced lesions were mapped to purine- and pyrimidine-containing sequences along thep53gene. Cleavage assays with lesion-specific DNA repair enzymes coupled to ligation-mediated PCR showed preferential, but not identical, formation of CPDs along thep53gene in UVB- and UVA1-irradiated cells. Additionally, dose-dependent formation of oxidized and ring-opened purines and abasic sites was established in thep53gene in only UVA1-irradiated cells. We conclude that UVA1 induces promutagenic CPDs and oxidative DNA damage at both the genomic and nucleotide resolution level in normal human skin fibroblasts.
Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase
Authors: Hibuse Toshiyuki , Maeda Norikazu , Funahashi Tohru , Yamamoto Kaori , Nagasawa Azumi , Mizunoya Wataru , Kishida Ken , Inoue Kazuo , Kuriyama Hiroshi , Nakamura Tadashi , Fushiki Tohru , Kihara Shinji , Shimomura Iichiro
Published: July 2005

In adipocytes, hydrolysis of triglycerides results in the release of free fatty acids and glycerol. Aquaporin 7 (AQP7), a member of aquaglyceroporins, is known to permeabilize glycerol and water. We recently generated
Aqp7
-knockout (KO) mice and demonstrated that such mice have low plasma glycerol levels and impaired glycerol release in response to β3-adrenergic agonist, suggesting that AQP7 acts as a glycerol gateway molecule in adipocytes for the efficient release of glycerol
in vivo
. Although there was no difference in body weight between WT and KO mice until 10 weeks of age, here we found that KO mice developed adult-onset obesity. The body weight and fat mass increased significantly in KO mice compared with WT mice after 12 weeks of age. Adipocytes of KO mice were large and exhibited accumulation of triglycerides compared with WT mice. The KO mice developed obesity and insulin resistance even at a young age after consumption of high-fat/high-sucrose diet. We demonstrated the enhanced glycerol kinase enzymatic activity in
Aqp7
-KO and -knockdown adipocytes. A series of our results indicate that AQP7 disruption elevates adipose glycerol kinase activity, accelerates triglycerides synthesis in adipocytes, and, finally, develops obesity.
cAMP-response element-binding protein and heat-shock protein 70 additively suppress polyglutamine-mediated toxicity inDrosophila
Authors: Iijima-Ando Kanae , Wu Priscilla , Drier Eric A. , Iijima Koichi , Yin Jerry C. P.
Published: July 2005

Gene-specific expansion of polyglutamine-encoding CAG repeats can cause neurodegenerative disorders, including Huntington's disease. It is believed that part of the pathological effect of the expanded protein is due to transcriptional dysregulation. UsingDrosophilaas a model, we show that cAMP-response element-binding protein (CREB) is involved in expanded polyglutamine-induced toxicity. A mutation in theDrosophilahomolog of CREB,dCREB2, enhances lethality due to polyglutamine peptides (polyQ), and an additional copy ofdCREB2partially rescues this lethality. Neuronal expression of expanded polyQ attenuatesin vivoCRE-mediated transcription of a reporter gene. As reported previously, overexpression of heat-shock protein 70 (Hsp70) rescues polyglutamine-dependent lethality. However, it does not rescue CREB-mediated transcription. The protective effects of CREB and heat-shock protein 70 against polyQ are additive, suggesting that targeting multiple pathways may be effective for treatment of polyglutamine diseases.
Φ values in protein-folding kinetics have energetic and structural components
Authors: Merlo Claudia , Dill Ken A. , Weikl Thomas R.
Published: July 2005

Φ values are experimental measures of how the kinetics of protein folding is changed by single-site mutations. Φ values measure energetic quantities, but they are often interpreted in terms of the structures of the transition-state ensemble. Here, we describe a simple analytical model of the folding kinetics in terms of the formation of protein substructures. The model shows that Φ values have both structural and energetic components. It also provides a natural and general interpretation of “nonclassical” Φ values (i.e., <0or >1). The model reproduces the Φ values for 20 single-residue mutations in the α-helix of the protein CI2, including several nonclassical Φ values, in good agreement with experiments.
Evolution through genetically controlled allometry space
Authors: Langlade Nicolas B. , Feng Xianzhong , Dransfield Tracy , Copsey Lucy , Hanna Andrew I. , Thébaud Christophe , Bangham Andrew , Hudson Andrew , Coen Enrico
Published: July 2005

Understanding evolutionary change requires phenotypic differences between organisms to be placed in a genetic context. However, there are few cases where it has been possible to define an appropriate genotypic space for a range of species. Here we address this problem by defining a genetically controlled space that captures variation in shape and size between closely related species of
Antirrhinum
. The axes of the space are based on an allometric model of leaves from an F
2
of an interspecific cross between
Antirrhinum majus
and
Antirrhinum charidemi
. Three principal components were found to capture most of the genetic variation in shape and size, allowing a three-dimensional allometric space to be defined. The contribution of individual genetic loci was determined from QTL analysis, allowing each locus to be represented as a vector in the allometric space. Leaf shapes and sizes of 18 different
Antirrhinum
taxa, encompassing a broad range of leaf morphologies, could be accurately represented as clouds within the space. Most taxa overlapped with, or were near to, at least one other species in the space, so that together they defined a largely interconnected domain of viable forms. It is likely that the pattern of evolution within this domain reflects a combination of directional selection and evolutionary tradeoffs within a high dimensional space.
Evolution of highly active enzymes by homology-independent recombination
Authors: Griswold Karl E. , Kawarasaki Yasuaki , Ghoneim Nada , Benkovic Stephen J. , Iverson Brent L. , Georgiou George
Published: July 2005

The theta-class GST enzymes hGSTT1-1 (human GSTθ-1-1) and rGSTT2-2 (rat GSTθ-2-2) share 54.3% amino acid identity and exhibit different substrate specificities. Homology-independent techniques [incremental truncation for the creation of hybrid enzymes (ITCHY) and SCRATCHY] and low-homology techniques (recombination-dependent exponential amplification PCR) were used to create libraries of chimeric enzymes containing crossovers (C/Os) at positions not accessible by DNA family shuffling. High-throughput flow cytometric screening using the fluorogenic rGSTT2-2-specific substrate 7-amino-4-chloromethyl coumarin led to the isolation of active variants with either one or two C/Os. One of these enzymes, SCR23 (83% identity to hGSTT1-1), was encoded by a gene that exchanged helices 4 and 5 of hGSTT1-1 with the corresponding sequence from rGSTT2-2. Compared with either parent, this variant was found to have an improved
k
cat
with the selection substrate and also exhibited activity for the conjugation of glutathione to ethacrynic acid, a compound that is not recognized by either parental enzyme. These results highlight the power of combinatorial homology-independent and low-homology recombination methods for the generation of unique, highly active enzymes and also suggest a possible means of enzyme “humanization.”
Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways
Authors: Zhao Chen , Denison Carilee , Huibregtse Jon M. , Gygi Steven , Krug Robert M.
Published: July 2005

IFN-α/β plays an essential role in innate immunity against viral and bacterial infection. Among the proteins induced by IFN-α/β are the ubiquitin-like ISG15 protein and its E1- (Ube1L) and E2- (UbcH8) conjugating enzymes, leading to the conjugation of ISG15 to cellular proteins. It is likely that ISG15 conjugation plays an important role in antiviral response because a human virus, influenza B virus, inhibits ISG15 conjugation. However, the biological function of ISG15 modification remains unknown, largely because only a few human ISG15 target proteins have been identified. Here we purify ISG15-modified proteins from IFN-β-treated human (HeLa) cells by using double-affinity selection and use mass spectroscopy to identify a large number (158) of ISG15 target proteins. Eight of these proteins were subjected to further analysis and verified to be ISG15 modified in IFN-β-treated cells, increasing the likelihood that most, if not all, targets identified by mass spectroscopy are bona fide ISG15 targets. Several of the targets are IFN-α/β-induced antiviral proteins, including PKR, MxA, HuP56, and RIG-I, providing a rationale for the inhibition of ISG15 conjugation by influenza B virus. Most targets are constitutively expressed proteins that function in diverse cellular pathways, including RNA splicing, chromatin remodeling/polymerase II transcription, cytoskeleton organization and regulation, stress responses, and translation. These results indicate that ISG15 conjugation impacts nuclear as well as cytoplasmic functions. By targeting a wide array of constitutively expressed proteins, ISG15 conjugation greatly extends the repertoire of cellular functions that are affected by IFN-α/β.
Dynamic assembly and sustained retention of 53BP1 at the sites of DNA damage are controlled by Mdc1/NFBD1
Authors: Bekker-Jensen Simon , Lukas Claudia , Melander Fredrik , Bartek Jiri , Lukas Jiri
Published: July 2005

53BP1 is a key component of the genome surveillance network activated by DNA double strand breaks (DSBs). Despite its known accumulation at the DSB sites, the spatiotemporal aspects of 53BP1 interaction with DSBs and the role of other DSB regulators in this process remain unclear. Here, we used real-time microscopy to study the DSB-induced redistribution of 53BP1 in living cells. We show that within minutes after DNA damage, 53BP1 becomes progressively, yet transiently, immobilized around the DSB-flanking chromatin. Quantitative imaging of single cells revealed that the assembly of 53BP1 at DSBs significantly lagged behind Mdc1/NFBD1, another DSB-interacting checkpoint mediator. Furthermore, short interfering RNA-mediated ablation of Mdc1/NFBD1 drastically impaired 53BP1 redistribution to DSBs and triggered premature dissociation of 53BP1 from these regions. Collectively, these in vivo measurements identify Mdc1/NFBD1 as a key upstream determinant of 53BP1's interaction with DSBs from its dynamic assembly at the DSB sites through sustained retention within the DSB-flanking chromatin up to the recovery from the checkpoint.
The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria
Authors: Griffin Erik E. , Graumann Johannes , Chan David C.
Published: July 2005

The mitochondrial division machinery regulates mitochondrial dynamics and consists of Fis1p, Mdv1p, and Dnm1p. Mitochondrial division relies on the recruitment of the dynamin-related protein Dnm1p to mitochondria. Dnm1p recruitment depends on the mitochondrial outer membrane protein Fis1p. Mdv1p interacts with Fis1p and Dnm1p, but is thought to act at a late step during fission because Mdv1p is dispensable for Dnm1p localization. We identify the WD40 repeat protein Caf4p as a Fis1p-associated protein that localizes to mitochondria in a Fis1p-dependent manner. Caf4p interacts with each component of the fission apparatus: with Fis1p and Mdv1p through its NH2-terminal half and with Dnm1p through its COOH-terminal WD40 domain. We demonstrate that mdv1Δ yeast contain residual mitochondrial fission due to the redundant activity of Caf4p. Moreover, recruitment of Dnm1p to mitochondria is disrupted in mdv1Δ caf4Δ yeast, demonstrating that Mdv1p and Caf4p are molecular adaptors that recruit Dnm1p to mitochondrial fission sites. Our studies support a revised model for assembly of the mitochondrial fission apparatus.
It's HIP to be a hub
Authors: Vecchi Manuela , Di Fiore Pier Paolo
Published: July 2005

Many endocytic proteins shuttle between the nucleus and the cytoplasm; however, their putative function in the nucleus is unclear. Now, new data demonstrate that huntingtin interacting protein 1 (HIP1), an endocytic protein, modulates the transcriptional activity of nuclear hormone receptors. In network theory, therefore, HIP1 can be regarded as a hub connecting heterogeneous functional “territories:” a possibility with important physiological and pathological implications.
Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis
Authors: Miyaji Michihiko , Jin Zhe-Xiong , Yamaoka Shohei , Amakawa Ryuichi , Fukuhara Shirou , Sato Satoshi B. , Kobayashi Toshihide , Domae Naochika , Mimori Tsuneyo , Bloom Eda T. , Okazaki Toshiro , Umehara Hisanori
Published: July 2005

Engagement of the Fas receptor (CD95) initiates multiple signaling pathways that lead to apoptosis, such as the formation of death-inducing signaling complex (DISC), activation of caspase cascades, and the generation of the lipid messenger, ceramide. Sphingomyelin (SM) is a major component of lipid rafts, which are specialized structures that enhance the efficiency of membrane receptor signaling and are a main source of ceramide. However, the functions of SM in Fas-mediated apoptosis have yet to be clearly defined, as the responsible genes have not been identified. After cloning a gene responsible for SM synthesis, SMS1, we established SM synthase–defective WR19L cells transfected with the human Fas gene (WR/Fas-SM(−)), and cells that have been functionally restored by transfection with SMS1 (WR/Fas-SMS1). We show that expression of membrane SM enhances Fas-mediated apoptosis through increasing DISC formation, activation of caspases, efficient translocation of Fas into lipid rafts, and subsequent Fas clustering. Furthermore, WR/Fas-SMS1 cells, but not WR/Fas-SM(−) cells, showed a considerable increase in ceramide generation within lipid rafts upon Fas stimulation. These data suggest that a membrane SM is important for Fas clustering through aggregation of lipid rafts, leading to Fas-mediated apoptosis.
Aberrant T cell differentiation in the absence of Dicer
Authors: Muljo Stefan A. , Ansel K. Mark , Kanellopoulou Chryssa , Livingston David M. , Rao Anjana , Rajewsky Klaus
Published: July 2005

Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and vertebrates. To test the requirement for Dicer in cell-lineage decisions in a mammalian organism, we have generated a conditional allele of dicer-1 (dcr-1) in the mouse. Specific deletion of dcr-1 in the T cell lineage resulted in impaired T cell development and aberrant T helper cell differentiation and cytokine production. A severe block in peripheral CD8+ T cell development was observed upon dcr-1 deletion in the thymus. However, Dicer-deficient CD4+ T cells, although reduced in numbers, were viable and could be analyzed further. These cells were defective in microRNA processing, and upon stimulation they proliferated poorly and underwent increased apoptosis. Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-γ, the hallmark effector cytokine of the Th1 lineage.
Human CD1-restricted T cell recognition of lipids from pollens
Authors: Agea Elisabetta , Russano Anna , Bistoni Onelia , Mannucci Roberta , Nicoletti Ildo , Corazzi Lanfranco , Postle Anthony D. , De Libero Gennaro , Porcelli Steven A. , Spinozzi Fabrizio
Published: July 2005

Plant pollens are an important source of environmental antigens that stimulate allergic responses. In addition to acting as vehicles for foreign protein antigens, they contain lipids that incorporate saturated and unsaturated fatty acids, which are necessary in the reproduction of higher plants. The CD1 family of nonpolymorphic major histocompatibility complex–related molecules is highly conserved in mammals, and has been shown to present microbial and self lipids to T cells. Here, we provide evidence that pollen lipids may be recognized as antigens by human T cells through a CD1-dependent pathway. Among phospholipids extracted from cypress grains, phosphatidyl-choline and phosphatidyl-ethanolamine were able to stimulate the proliferation of T cells from cypress-sensitive subjects. Recognition of phospholipids involved multiple cell types, mostly CD4+ T cell receptor for antigen (TCR)αβ+, some CD4−CD8− TCRγδ+, but rarely Vα24i+ natural killer–T cells, and required CD1a+ and CD1d+ antigen presenting cell. The responding T cells secreted both interleukin (IL)-4 and interferon-γ, in some cases IL-10 and transforming growth factor-β, and could provide help for immunoglobulin E (IgE) production. Responses to pollen phospholipids were maximally evident in blood samples obtained from allergic subjects during pollinating season, uniformly absent in Mycobacterium tuberculosis–exposed health care workers, but occasionally seen in nonallergic subjects. Finally, allergic, but not normal subjects, displayed circulating specific IgE and cutaneous weal and flare reactions to phospholipids.
Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity
Authors: Liu George Y. , Essex Anthony , Buchanan John T. , Datta Vivekanand , Hoffman Hal M. , Bastian John F. , Fierer Joshua , Nizet Victor
Published: July 2005

Golden color imparted by carotenoid pigments is the eponymous feature of the human pathogen Staphylococcus aureus. Here we demonstrate a role of this hallmark phenotype in virulence. Compared with the wild-type (WT) bacterium, a S. aureus mutant with disrupted carotenoid biosynthesis is more susceptible to oxidant killing, has impaired neutrophil survival, and is less pathogenic in a mouse subcutaneous abscess model. The survival advantage of WT S. aureus over the carotenoid-deficient mutant is lost upon inhibition of neutrophil oxidative burst or in human or murine nicotinamide adenine dinucleotide phosphate oxidase–deficient hosts. Conversely, heterologous expression of the S. aureus carotenoid in the nonpigmented Streptococcus pyogenes confers enhanced oxidant and neutrophil resistance and increased animal virulence. Blocking S. aureus carotenogenesis increases oxidant sensitivity and decreases whole-blood survival, suggesting a novel target for antibiotic therapy.
A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms II
Authors: Kaloshin Vadim , Hunt Brian
Published: July 2005

We continue the previous article’s discussion of bounds, for prevalent diffeomorphisms of smooth compact manifolds, on the growth of the number of periodic points and the decay of their hyperbolicity as a function of their period

n
n

. In that article we reduced the main results to a problem, for certain families of diffeomorphisms, of bounding the measure of parameter values for which the diffeomorphism has (for a given period

n
n

) an almost periodic point that is almost nonhyperbolic. We also formulated our results for

1
1

-dimensional endomorphisms on a compact interval. In this article we describe some of the main techniques involved and outline the rest of the proof. To simplify notation, we concentrate primarily on the

1
1

-dimensional case.
On 3-graded Lie algebras, Jordan pairs and the canonical kernel function
Authors: de Oliveira M.
Published: July 2005

We present several embedding results for

3
3

-graded Lie algebras and KKT algebras that are generated by two homogeneous elements of degrees

1
1

and

−
1

-1

. We also propose the canonical kernel function for a “universal Bergman kernel” which extends the usual Bergman kernel on a bounded symmetric domain to a group-valued function or, in terms of formal series, to an element in the formal completion of the universal enveloping algebra of the free

3
3

-graded Lie algebra in a pair of generators.
On approximation of locally compact groups by finite algebraic systems
Authors: Glebsky L. , Gordon E.
Published: July 2005

We discuss the approximability of locally compact groups by finite semigroups and finite quasigroups (latin squares). We show that if a locally compact group

G
G

is approximable by finite semigroups, then it is approximable by finite groups, and thus many important groups are not approximable by finite semigroups. This result implies, in particular, the impossibility to simulate the field of reals in computers by finite associative rings. We show that a locally compact group is approximable by finite quasigroups iff it is unimodular.
The CB1 receptor antagonist rimonabant reverses the diet‐induced obesity phenotype through the regulation of lipolysis and energy balance
Authors: Jbilo Omar , Ravinet‐Trillou Christine , Arnone Michèle , Buisson Isabelle , Bribes Estelle , Péleraux Annick , Pénarier Géraldine , Soubrié Philippe , Le Fur Gérard , Galiègue Sylvaine , Casellas Pierre
Published: July 2005

We investigated the molecular events involved in the long‐lasting reduction of adipose mass by the selective CB1 antagonist, SR141716. Its effects were assessed at the transcriptional level both in white (WAT) and brown (BAT) adipose tissues in a diet‐induced obesity model in mice. Our data clearly indicated that SR141716 reversed the phenotype of obese adipocytes at both macroscopic and genomic levels. First, oral treatment with SR141716 at 10 mg/kg/d for 40 days induced a robust reduction of obesity, as shown by the 50% decrease in adipose mass together with a major restoration of white adipocyte morphology similar to lean animals. Second, we found that the major alterations in gene expression levels induced by obesity in WAT and BAT were mostly reversed in SR141716‐treated obese mice. Importantly, the transcriptional patterns of treated obese mice were similar to those obtained in the CB1 receptor knockout mice fed a high‐fat regimen and which are resistant to obesity, supporting a CB1 receptor‐mediated process. Functional analysis of these modulations indicated that the reduction of adipose mass by the molecule resulted from an enhanced lipolysis through the induction of enzymes of the β‐oxidation and TCA cycle, increased energy expenditure, mainly through futile cycling (calcium and substrate), and a tight regulation of glucose homeostasis. These changes accompanied a significant cellular remodeling and contributed to a reduction of the obesity‐related inflammatory status. In addition to a transient reduction of food consumption, increases of both fatty acid oxidation and energy expenditure induced by the molecule summate leading to a sustained weight loss. Altogether, these data strongly indicate that the endocannabinoid system has a major role in the regulation of energy metabolism.