bluuebunny/crossref_metadata_2025 huggingface dataset:
Anaplasma marginale(Rickettsiales: Anaplasmataceae): recent advances in defining host–pathogen adaptations of a tick-borne rickettsia
Authors: KOCAN K. M. , DE LA FUENTE J. , BLOUIN E. F. , GARCIA-GARCIA J. C.
Published: April 2005

The tick-borne intracellular pathogenAnaplasma marginale(Rickettsiales: Anaplasmataceae) develops persistent infections in cattle and tick hosts. While erythrocytes appear to be the only site of infection in cattle,A. marginaleundergoes a complex developmental cycle in ticks and transmission occurs via salivary glands during feeding. Many geographic isolates occur that vary in genotype, antigenic composition, morphology and infectivity for ticks. In this chapter we review recent research on the host–vector–pathogen interactions ofA. marginale. Major surface proteins (MSPs) play a crucial role in the interaction ofA. marginalewith host cells. The MSP1a protein, which is an adhesin for bovine erythrocytes and tick cells, is differentially regulated and affects infection and transmission ofA. marginalebyDermacentorspp. ticks. MSP2 undergoes antigenic variation and selection in cattle and ticks, and contributes to the maintenance of persistent infections. Phylogenetic studies ofA. marginalegeographic isolates usingmsp4andmsp1α provide information about the biogeography and evolution ofA. marginale:msp1α genotypes evolve under positive selection pressure. Isolates ofA. marginaleare maintained by independent transmission events and a mechanism of infection exclusion in cattle and ticks allows for only the infection of one isolate per animal. Prospects for development of control strategies by use of pathogen and tick-derived antigens are discussed. TheA. marginale/vector/host studies described herein could serve as a model for research on other tick-borne rickettsiae.
Theileria: intracellular protozoan parasites of wild and domestic ruminants transmitted by ixodid ticks
Authors: BISHOP R. , MUSOKE A. , MORZARIA S. , GARDNER M. , NENE V.
Published: April 2005

Theileriaare economically important, intra-cellular protozoa, transmitted by ixodid ticks, which infect wild and domestic ruminants. In the mammalian host, parasites infect leukocytes and erythrocytes. In the arthropod vector they develop in gut epithelial cells and salivary glands. All four intra-cellular stages ofTheileriasurvive free in the cytoplasm. The schizont stages of certainTheileriaspecies induce a unique, cancer-like, phenotype in infected host leukocytes.Theileriaundergoes an obligate sexual cycle, involving fusion of gametes in the tick gut, to produce a transiently diploid zygote. The existence of sexual recombination inT.parvahas been confirmed in the laboratory, and is presumed to contribute to the extensive polymorphism observed in field isolates. Key parameters inT. parvapopulation dynamics are the relative importance of asymptomatic carrier cattle and animals undergoing severe disease, in transmission of the parasite to ticks, and the extent of transmission by nymphs as compared to adult ticks. Tick populations differ in vector competence for specificT. parvastocks. Recombinant forms ofT.parvaandT. annulatasporozoite surface antigens induce protection against parasite challenge in cattle. In future, vaccines might be improved by inclusion of tick peptides in multivalent vaccines.
Tick immunobiology
Authors: BROSSARD M. , WIKEL S. K.
Published: April 2005

Ticks are of vast medical and veterinary public health importance due to direct damage caused by feeding and their roles in transmitting well known and emerging infectious agents. Ticks and tick-borne pathogens stimulate the immune system of the host. Those immune interactions are of importance in tick biology, pathogen transmission and control of ticks and tick-borne diseases. Both innate and specific acquired immune defenses are involved in the responses of vertebrate hosts to infestation. Ticks have evolved countermeasures to circumvent host immune defenses. This review addresses the immunobiology of the tick–host interface from the perspectives of the pharmacology of tick saliva; relationship of tick saliva to pathogen transmission; host immune responses to infestation; tick modulation of host immune defences; and genomic/proteomic strategies for studying tick salivary gland molecules.
Exploring tick saliva: from biochemistry to ‘sialomes’ and functional genomics
Authors: VALENZUELA J. G.
Published: April 2005

Tick saliva, a fluid once believed to be only relevant for lubrication of mouthparts and water balance, is now well known to be a cocktail of potent anti-haemostatic, anti-inflammatory and immunomodulatory molecules that helps these arthropods obtain a blood meal from their vertebrate hosts. The repertoire of pharmacologically active components in this cocktail is impressive as well as the number of targets they specifically affect. These salivary components change the physiology of the host at the bite site and, consequently, some pathogens transmitted by ticks take advantage of this change and become more infective. Tick salivary proteins have therefore become an attractive target to control tick-borne diseases. Recent advances in molecular biology, protein chemistry and computational biology are accelerating the isolation, sequencing and analysis of a large number of transcripts and proteins from the saliva of different ticks. Many of these newly isolated genes code for proteins with homologies to known proteins allowing identification or prediction of their function. However, most of these genes code for proteins with unknown functions therefore opening the road to functional genomic approaches to identify their biological activities and roles in blood feeding and hence, vaccine development to control tick-borne diseases.
Tick–host interactions: saliva-activated transmission
Authors: NUTTALL P. A. , LABUDA M.
Published: April 2005

The skin site at which ticks attach to their hosts to feed is the critical interface between the tick and its host, and tick-borne pathogens. This site is highly modified by the pharmacologically active molecules secreted in tick saliva. For pathogens, it is an ecologically privileged niche that many exploit. Such exploitation is referred to as saliva-activated transmission (SAT) – the indirect promotion of tick-borne pathogen transmission via the actions of bioactive tick saliva molecules on the vertebrate host. Here we review evidence for SAT and consider what are the most likely candidates for SAT factors among the tick pharmacopoeia of anti-haemostatic, anti-inflammatory and immunomodulatory molecules identified to date. SAT factors appear to differ for different pathogens and tick vector species, and possibly even depend on the vertebrate host species. Most likely we are searching for a suite of molecules that act together to overcome the redundancy in host response mechanisms. Whatever they turn out to be, the quest to identify the tick molecules that mediate SAT is an exciting one, and offers new insights to controlling ticks and tick-borne diseases.
Numerical solution of saddle point problems
Authors: Benzi Michele , Golub Gene H. , Liesen Jörg
Published: April 2005

Large linear systems of saddle point type arise in a wide variety of applications throughout computational science and engineering. Due to their indefiniteness and often poor spectral properties, such linear systems represent a significant challenge for solver developers. In recent years there has been a surge of interest in saddle point problems, and numerous solution techniques have been proposed for this type of system. The aim of this paper is to present and discuss a large selection of solution methods for linear systems in saddle point form, with an emphasis on iterative methods for large and sparse problems.
Numerical methods for large-scale nonlinear optimization
Authors: Gould Nick , Orban Dominique , Toint Philippe
Published: April 2005

Recent developments in numerical methods for solving large differentiable nonlinear optimization problems are reviewed. State-of-the-art algorithms for solving unconstrained, bound-constrained, linearly constrained and non-linearly constrained problems are discussed. As well as important conceptual advances and theoretical aspects, emphasis is also placed on more practical issues, such as software availability.
Computational chemistry from the perspective of numerical analysis
Authors: Le Bris Claude
Published: April 2005

We present the field of computational chemistry from the standpoint of numerical analysis. We introduce the most commonly used models and comment on their applicability. We briefly outline the results of mathematical analysis and then mostly concentrate on the main issues raised by numerical simulations. A special emphasis is laid on recent results in numerical analysis, recent developments of new methods and challenging open issues.
Total variation and level set methods in image science
Authors: Tsai Yen-Hsi Richard , Osher Stanley
Published: April 2005

We review level set methods and the related techniques that are common in many PDE-based image models. Many of these techniques involve minimizing the total variation of the solution and admit regularizations on the curvature of its level sets. We examine the scope of these techniques in image science, in particular in image segmentation, interpolation, and decomposition, and introduce some relevant level set techniques that are useful for this class of applications. Many of the standard problems are formulated as variational models. We observe increasing synergistic progression of new tools and ideas between the inverse problem community and the ‘imagers’. We show that image science demands multi-disciplinary knowledge and flexible, but still robust methods. That is why the level set method and total variation methods have become thriving techniques in this field.

Our goal is to survey recently developed techniques in various fields of research that are relevant to diverse objectives in image science. We begin by reviewing some typical PDE-based applications in image processing. In typical PDE methods, images are assumed to be continuous functions sampled on a grid. We will show that these methods all share a common feature, which is the emphasis on processing the level lines of the underlying image. The importance of level lines has been known for some time. See, e.g., Alvarez, Guichard, Morel and Lions (1993). This feature places our slightly general definition of the level set method for image science in context. In Section 2 we describe the building blocks of a typical level set method in the continuum setting. Each important task that we need to do is formulated as the solution to certain PDEs. Then, in Section 3, we briefly describe the finite difference methods developed to construct approximate solutions to these PDEs. Some approaches to interpolation into small subdomains of an image are reviewed in Section 4. In Section 5 we describe the Chan–Vese segmentation algorithm and two new fast implementation methods. Finally, in Section 6, we describe some new techniques developed in the level set community.
Wave field migration as a tool for estimating spatially continuous radar velocity and water content in glaciers
Authors: Bradford John H. , Harper Joel T.
Published: April 2005

Normal‐moveout velocity analysis can lead to significant overestimates of the velocity structure of temperate glaciers since most englacial reflectors approximate point scatters and violate the assumption of planar flat lying reflectors. Migration velocity analysis (MVA) is a tool that does not depend on the assumption of flat lying reflectors. MVA can provide laterally and vertically continuous velocity estimates from conventional common‐offset radar sections. In a study of temperate Bench Glacier, Alaska, we used MVA coupled with dielectric modeling to estimate the distribution of water content along a cross‐section of the glacier. We found the glacier has two layers, an upper layer with relatively low water content, and lower layer with relatively high water content. The ability to quantify hydrostratigraphy is important in understanding water storage and routing within glaciers.
Persistence of armor layers in gravel‐bed streams
Authors: Wilcock Peter R. , DeTemple Brendan T.
Published: April 2005

Streambed surfaces are typically coarsened, or armored, at low flows, but there is little evidence of their condition during floods, when significant hydraulic and ecologic disturbance occurs. Some flume experiments have been used to conclude that armor layers wash out during floods, although other experiments have produced a persistent armor layer. In the absence of clear field or flume evidence, we use a surface‐based transport model in an inverse prediction of surface grain size as a function of transport rates observed in the field. The predicted surface grain size matches that observed at low flow and indicates that low‐flow armor layers persist at large flows. In the field, transport grain size increases with transport rate, reducing or eliminating adjustments in bed surface grain size as flow and transport increase. A persistent armor layer considerably simplifies the prediction of sediment transport, hydraulic roughness, and habitat disturbance during floods.
The quasi‐biennial oscillation: Analysis using ERA‐40 data
Authors: Pascoe Charlotte L. , Gray Lesley J. , Crooks Simon A. , Juckes Martin N. , Baldwin Mark P.
Published: April 2005

The ERA‐40 data set is used to examine the equatorial quasi‐biennial oscillation (QBO). The data set extends from the ground to 0.1 hPa (∼65 km) and covers a 44‐year period (January 1958 to December 2001), including 18.5 QBO cycles. Analysis of this data set of unprecedented spatial and temporal coverage has revealed a threefold structure in height in the QBO zonal wind anomalies at the equator. In addition to the well‐known twofold structure in the lower and middle stratosphere, that is, easterlies overlying westerlies or vice versa, there is a third anomaly in the upper stratosphere. The sign of this upper stratospheric anomaly is the same as the lower stratospheric anomaly, thus forming anomalies of alternating sign throughout the depth of the equatorial stratosphere. The amplitude of this upper stratospheric anomaly is ∼10 m s−1, approximately one third of the amplitude of the lower stratospheric signal. The frequency and descent rates of the east and west QBO phases are analyzed in detail, with particular attention to any 11‐year solar cycle influence. In addition to the observed solar modulation of the duration of the QBO west phase the analysis shows a solar modulation of the mean descent rate of the easterly shear zone. The mean time required for the easterly shear zone to descend from 20 to 44 hPa is 2 months less under solar maximum conditions than under solar minimum conditions (7.4 months versus 9.7 months). This rapid descent of the easterly shear zone cuts short the west phase of the QBO in the lower stratosphere during solar maximum periods.
Large nitric acid trihydrate particles and denitrification caused by mountain waves in the Arctic stratosphere
Authors: Mann G. W. , Carslaw K. S. , Chipperfield M. P. , Davies S. , Eckermann S. D.
Published: April 2005

The contribution of stratospheric mountain waves to the formation of large nitric acid trihydrate (NAT) particles and subsequent denitrification of the Arctic polar vortex is calculated for the 1999/2000 winter using a three‐dimensional (3‐D) model. The model production mechanism involves the formation of NAT clouds with high particle number concentrations downwind of mountain wave ice clouds, as has been previously observed. These wave‐induced NAT clouds then serve as “mother clouds” for the release of low concentrations of sedimenting NAT particles, following the mechanism of Fueglistaler et al. (2002a). Our calculations show that wave‐induced NAT mother clouds can occupy up to 5–10% of the volume of air below the NAT temperature. NAT particles that have sedimented from the mother cloud bases can occupy in excess of 60% of the NAT supersaturated region. Integrated over the entire vortex at the end of the 1999/2000 simulation, it is estimated that denitrification due to this mechanism could potentially be responsible for as much as 80% of that observed. These results show that mountain waves may contribute to the occurrence of solid polar stratospheric clouds more than was previously thought and that they may play a significant role in denitrification.
Atmospheric water vapor transport associated with typical anomalous summer rainfall patterns in China
Authors: Zhou Tian‐Jun , Yu Ru‐Cong
Published: April 2005

This paper attempts to reveal the atmospheric water vapor transports associated with typical anomalous summer rainfall patterns in China. The results show that origins of water vapor supply related to anomalous rainfall patterns are different from those related to the normal monsoon rainfall. Anomalous pattern 1, with a heavier rainbelt along the middle and lower reaches of the Yangtze River valley, follows from a convergence of the tropical southwest water vapor transport with the midlatitude northeast water vapor transport; the tropical water vapor transport comes directly from the Bay of Bengal and the South China Sea but originally from the Philippine Sea. The anomalous water vapor transport is associated with a southwestward extension of the western Pacific subtropical high and a southward shift of the upper East Asian jet stream. Anomalous pattern 2, with a main rainbelt along the Huaihe River valley, is supported by the convergence of the subtropical southwest water vapor with the midlatitude water vapor transport. The subtropical branch comes directly from the South China Sea but originally from the East China Sea and the adjacent subtropical Pacific to the further east along 20–25°N. The background large‐scale circulation change includes a northwestward extension of the western Pacific subtropical high and an eastward shift of the upper jet stream. Although the cross‐equator flows including the Somali jet supply abundant water vapor for the normal condition of June, July, and August rainfall over China, the tropical water vapor transports related to typical anomalous rainfall anomalies originate from the tropical western Pacific Ocean. The northward transport of anomalous warm water vapor occurs mainly in the lower troposphere, while the transport of midlatitude cold water vapor occurs briefly in the upper troposphere.
Photolysis of sulfuric acid vapor by visible light as a source of the polar stratospheric CN layer
Authors: Mills Michael J. , Toon Owen B. , Vaida Veronica , Hintze Paul E. , Kjaergaard Henrik G. , Schofield Daniel P. , Robinson Timothy W.
Published: April 2005

We present the first microphysical calculations confirming that photolysis of sulfuric acid vapor by visible light is responsible for the formation of the springtime “CN layer” observed in the polar stratosphere. Our calculations show that the recently proposed photolysis mechanism is also sufficient to explain observations of vertically increasing SO2 mixing ratios in the upper stratosphere. Such photolysis, however, does not sufficiently explain the limited observations above 40 km of vertically decreasing H2SO4 and SO3 vapor, suggesting an additional loss mechanism there. We rule out previous speculation regarding reaction of H2SO4 with O(1D) or OH as inconsistent with observations of SO2. Rather, the loss is consistent with a permanent sink for sulfur, such as H2SO4 neutralization by metals on meteoritic dust. In light of such removal, H2SO4 photolysis to SO2 gains added importance in preserving gaseous sulfur in the upper stratosphere. We also present new cross sections derived from ab initio calculations for H2SO4 absorption at visible and Lyman‐α wavelengths and evaluate their atmospheric implications. Our atmospheric model reveals that photolysis of H2SO4 by Lyman‐α radiation is responsible for up to one third of the SO2 in the mesosphere and 10% of the particles in the polar stratospheric CN layer.
Modeling the effect of the ocean‐land interface on induced electric fields during geomagnetic storms
Authors: Gilbert James L.
Published: April 2005

In this paper a model is developed for the calculation of the enhancement of geomagnetic storm electric fields near ocean‐land interfaces. The motivation for this work is the calculation of the electric fields applied to power and telecommunication conductors near the seashore. This model consists of an ocean of depth linearly increasing with distance from the shoreline and a uniformly conducting soil. With this assumption an integral equation is obtained for the electric field for exponentially rising surface magnetic fields. This equation is solved numerically and, for a special limiting case, analytically. Solutions for two different surface magnetic field time histories at the surface are obtained by taking inverse Laplace transforms. Expressions are derived for the change in the electric field when compared with the electric field at the surface of a homogeneous Earth. Numerical examples are given for the enhancement of the electric field for sudden storm commencement and electrojet magnetic field time histories.
Hamiltonian and action principle formulations of plasma physics
Authors: Morrison P. J.
Published: April 2005

Hamiltonian and action principle formulations of the basic equations of plasma physics are reviewed. Various types of Lagrangian and Poisson bracket formulations for kinetic and fluid theories are discussed, and it is described how such formulations can be used to derive and approximate physical models. Additional uses are also described. Two applications are treated in greater detail: an algorithm based on Dirac brackets for the calculation of V-states of contour dynamics and the calculation of fluctuation spectra of Vlasov theory and shear flow dynamics by methods of statistical mechanics.
Interferometric detection of acoustic waves at air-solid interface applications to non-destructive testing
Authors: Jenot F. , Ouaftouh M. , Duquennoy M. , Ourak M.
Published: April 2005

In this paper, some properties of acoustic waves at the air-solid interface are reviewed and laser-ultrasonics is used to optically excite and detect these waves. In comparison with the leaky Rayleigh wave, a large amplitude is observed for the acoustic disturbance which is composed of Scholte and lateral waves. However, it is apparent from theoretical results, taking source terms into account, that the normal displacement of these waves cannot be large in such an interface. Another explanation for the high-intensity fluctuation measured is the optical heterodyne detection of the refractive index variation induced in the fluid. This assumption is experimentally checked by probing the acoustic field parallel to the surface of the sample. The potentialities of these waves in non-destructive testing are also investigated. It is clearly shown that the transmitted, reflected, or diffracted acoustic fields provide useful information about the position or the size of structures intercepting the propagation path. Indeed, glass plate thickness or steel block position can be easily determined using a time of flight analysis. This suggests a lot of new applications in the sizing of structures where noncontact measurements on inaccessible parts would be necessary.
Quasistatic magnetic and electric fields generated in intense laser plasma interaction
Authors: Qiao Bin , Zhu Shao-ping , Zheng C. Y. , He X. T.
Published: April 2005

A self-consistent kinetic model based on relativistic Vlasov–Maxwell equations is presented for the generation of quasistatic spontaneous fields, i.e., both the quasistatic magnetic (QSM) field and the quasistatic electric (QSE) field, in intense laser plasma interaction. For the circularly polarized laser, QSM field includes two parts, the axial part Bz as well as the azimuthal Bθ; the QSE field Es, corresponding to the space-charge potential, forms a plasma density channel. For the linearly polarized laser, Bz is absent. Equations for Bz, Bθ, and Es are uniformly derived from one self-consistent model under the static-state approximation, which satisfies the conservation law of charge. The profile of the plasma density channel and the dependence of the peak QSM fields on the laser intensity are discussed. The experiment and simulation results are explained by the model. The predicted QSM and QSE fields are also observed in the three-dimensional particle simulation.
Thermal analysis, nuclear magnetic resonance spectroscopy, and impedance spectroscopy of N,N-dimethyl-pyrrolidinium iodide: An ionic solid exhibiting rotator phases
Authors: Adebahr Josefina , Seeber Aaron J. , MacFarlane Douglas R. , Forsyth Maria
Published: April 2005

N,N-dimethyl-pyrrolidinium iodide has been investigated using differential scanning calorimetry, nuclear magnetic resonance (NMR) spectroscopy, second moment calculations, and impedance spectroscopy. This pyrrolidinium salt exhibits two solid-solid phase transitions, one at 373K having an entropy change, ΔS, of 38Jmol−1K−1 and one at 478K having ΔS of 5.7Jmol−1K−1. The second moment calculations relate the lower temperature transition to a homogenization of the sample in terms of the mobility of the cations, while the high temperature phase transition is within the temperature region of isotropic tumbling of the cations. At higher temperatures a further decrease in the H1 NMR linewidth is observed which is suggested to be due to diffusion of the cations.
Oxygen pressure measurement using singlet oxygen emission
Authors: Khalil Gamal E. , Chang Alvin , Gouterman Martin , Callis James B. , Dalton Larry R. , Turro Nicholas J. , Jockusch Steffen
Published: April 2005

Pressure sensitive paint (PSP) provides a visualization of two-dimensional pressure distributions on airfoil and model automobile surfaces. One type of PSP utilizes platinum tetra(pentafluorophenyl)porphine (PtTFPP) dissolved in a fluoro-polymer film. Since the intense 650nm triplet emission of PtTFPP is quenched by ground state oxygen, it is possible to measure two-dimensional oxygen concentration from the 650nm emission intensity using a Stern–Volmer-type relationship. This article reports an alternative luminescence method to measure oxygen concentration based on the porphyrin-sensitized 1270nm singlet oxygen emission, which can be imaged with an InGaAs near infrared camera. This direct measurement of oxygen emission complements and further validates the oxygen measurement based on PtTFPP phosphorescence quenching. Initial success at obtaining a negative correlation between the 650nm PtTFPP emission and the 1270nm O2 emission in solution led us to additional two-dimensional film studies using surfaces coated with PtTFPP, MgTFPP, and H2TFPP in polymers in a pressure and temperature controlled chamber.
A suitable plane transmission line at 900MHz rf fields for E. coli DNA studies
Authors: Belloni F. , Nassisi V. , Alifano P. , Monaco C. , Talà A. , Tredici M. , Rainò A.
Published: April 2005

Utilizing a suitable irradiating transmission line chamber, the effects of 900MHz radio frequency fields on DNA mutability and repair in Escherichia coli strains were investigated. The transmission line was very versatile and able to easily apply different field values. In this experiment the maximum electric and magnetic fields were 66V∕m and 260nT, respectively, in the absence of cell plates. Slight decrease in spontaneous mutability to erythromycin resistance was demonstrated in mismatch-repair proficient bacteria exposed to the radio frequency electromagnetic field (RF-EMF) during their growth on solid medium. The anti-mutagenic effect of the RF-EMF was much more impressive at the level of a hypermutagenic cytosine repeat, whose stability is strongly dependent on the activity of the mismatch repair system. In contrast, in mismatch repair-defective background RF-EMF neither affected the general DNA mutability nor the stability of the cytosine repeat, suggesting that the anti-mutagenic effect of the 900MHz RF-EMF might be due to an improved efficiency of the mismatch repair system.
Direct measurement of forces during scanning tunneling microscopy imaging of silicon pn junctions
Authors: Park Jeong Young , Phaneuf R. J. , Ogletree D. F. , Salmeron M.
Published: April 2005

We investigated the forces acting between tip and surface during scanning tunneling microscopy (STM) imaging of a silicon pn junction. Using a conductive and stiff atomic force microscopy (AFM) cantilever, the current between the tip and sample, and the normal force (or lever bending) were measured independently. This method allows us to use either AFM or STM, depending on the feedback signal. By comparing topographic images of the pn junction acquired in contact AFM mode with the STM images, large variations of STM topography and normal force across the junction could be observed. We find that at reverse bias the tip presses against the surface to draw the set-point current, while it is in noncontact tunneling regime at the forward bias. The current measured as a function of tip-sample distance shows a strong dependence on polarity of the bias in the p,n, and inverted regions, consistent with the force measurements during constant current STM mode.
Surface preparation of Si(001) substrate using low-pH HF solution
Authors: Morita Yukinori , Nishizawa Masayasu
Published: April 2005

We prepared atomically flat Si(001) surfaces that have well-ordered step-and-terrace structures using a low-pH (pH<1) HF solution (LPH) and subsequent low-temperature (750°⁢C) annealing in H2. The flattening was attributed to the enhanced migration of Si atoms on the LPH-treated surface because anisotropic etching is suppressed by the low concentration of OH ions. The reduction in the H2 annealing temperature to below the decomposition temperature of Si oxide enabled us to form an atomically flat Si(001) surface in a window area surrounded by a thick device isolation oxide.
Current-controlled nanotube growth and zone refinement
Authors: Jensen K. , Mickelson W. , Han W. , Zettl A.
Published: April 2005

We describe methods by which the growth of a single carbon nanotube (CNT) can be precisely controlled by an electrical current. In one method a CNT is grown to a predetermined geometry inside another nanotube, which serves as a reaction chamber. Another method allows a preexisting marginal-quality multiwall CNT to be zone refined into a higher-quality multiwall CNT by driving a catalytic bead down the length of the nanotube. In both methods, the speed of nanotube formation is adjustable, and the growth can be stopped and restarted at will.
Line-defect–waveguide laser integrated with a point defect in a two-dimensional photonic crystal slab
Authors: Sugitatsu Atsushi , Asano Takashi , Noda Susumu
Published: April 2005

We realize an active two-dimensional (2D) photonic crystal laser with a combination of line defects and point defects. Based on a line-defect–waveguide laser in a 2D photonic crystal slab, we observe laser emission from the point defect at the waveguide mode-edge frequency when there is a frequency mismatch with the point-defect mode. This phenomenon is due to the wide-field distribution at the waveguide mode edge and its distortion by the adjacent point defect. Numerical calculations estimate the emission efficiency and are in good agreement with experimental results.
Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice
Authors: Xu Aimin , Lam Michael C. , Chan Kok Weng , Wang Yu , Zhang Jialiang , Hoo Ruby L. C. , Xu Jian Yu , Chen Baoying , Chow Wing-Sun , Tso Annette W. K. , Lam Karen S. L.
Published: April 2005

Angiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly expressed in adipose tissue and liver. Several recent studies demonstrated that ANGPTL4 is the target gene of peroxisome proliferation activators, the agonists of which are widely used as the antidiabetic and lipid-lowering drugs. Here we provide evidence that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. Adenovirus-mediated expression of ANGPTL4 potently decreased blood glucose and improved glucose tolerance, whereas it induced hyperlipidemia, fatty liver, and hepatomegaly in C57 mice. In db/db diabetic mice, ANGPTL4 treatment reduced hyperglycemia to a normal level, and markedly alleviated glucose intolerance and hyperinsulinemia.
Ex vivo
studies on primary rat hepatocytes revealed that ANGPTL4 significantly decreased hepatic glucose production and enhanced insulin-mediated inhibition of gluconeogenesis. Serum levels of ANGPTL4 in human subjects inversely correlated with plasma glucose concentrations and HOMA IR, the homeostasis model assessment of insulin resistance. In patients with type 2 diabetes, serum levels of ANGPTL4 were significantly lower than those in healthy subjects, suggesting that the decreased ANGPTL4 could be a causative factor of this disease. These results collectively indicate that ANGPTL4 exerts distinct effects on glucose and lipid metabolism, and that its beneficial effect on glucose homeostasis might be useful for the treatment of diabetes.
Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors
Authors: Codina Anna , Love James D. , Li Yun , Lazar Mitchell A. , Neuhaus David , Schwabe John W. R.
Published: April 2005

SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and NCoR (nuclear receptor corepressor) are transcriptional corepressors that play an essential role in the regulation of development and metabolism. This role is achieved, in part, through the recruitment of a key histone deacetylase (HDAC3), which is itself indispensable for cell viability. The assembly of HDAC3 with the deacetylase activation domain (DAD) of SMRT and NCoR is required for activation of the otherwise inert deacetylase. The DAD comprises an N-terminal DAD-specific motif and a C-terminal SANT (SWI3/ADA2/NCoR/TFIIIB)-like domain. We report here the solution structure of the DAD from SMRT, which reveals a four-helical structure. The DAD differs from the SANT (and MYB) domains in that (
i
) it has an additional N-terminal helix and (
ii
) there is a notable hydrophobic groove on the surface of the domain. Structure-guided mutagenesis, combined with interaction assays, showed that residues in the vicinity of the hydrophobic groove are required for interaction with (and hence activation of) HDAC3. Importantly, one surface-exposed lysine is required for activation of HDAC3, but not for interaction. This lysine may play a uniquely important role in the mechanism of activating HDAC3.
Evidence of singularities for a family of contour dynamics equations
Authors: Córdoba Diego , Fontelos Marco A. , Mancho Ana M. , Rodrigo Jose L.
Published: April 2005

In this work, we show evidence of the existence of singularities developing in finite time for a class of contour dynamics equations depending on a parameter 0 < α ≤ 1. The limiting case α → 0 corresponds to 2D Euler equations, and α = 1 corresponds to the surface quasi-geostrophic equation. The singularity is point-like, and it is approached in a self-similar manner.
The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E
2
Authors: Mohn Claudia E. , Fernandez-Solari Javier , De Laurentiis Andrea , Prestifilippo Juan Pablo , de la Cal Carolina , Funk Richard , Bornstein Stefan R. , McCann Samuel M. , Rettori Valeria
Published: April 2005

The adrenal cortex is a major stress organ in mammals that reacts rapidly to a multitude of external and internal stressors. Adrenocorticotropin (ACTH) is the main stimulator of the adrenal cortex, activating corticosteroid synthesis and secretion. We evaluated the mechanism of action of ACTH on adrenals of male rats, preserving the architecture of the gland
in vitro
. We demonstrated that both sodium nitroprusside (NP), a nitric oxide (NO) donor, and ACTH stimulate corticosterone release. NO mediated the acute response to ACTH because Nω-nitro-
l
-arginine methyl ester, a NO synthase inhibitor, and hemoglobin, a NO scavenger, blocked the stimulation of corticosterone release induced by ACTH. NP stimulated prostaglandin E release, which in turn stimulated corticosterone release from the adrenal. Additionally, indomethacin, which inhibits cyclooxygenase, and thereby, prostaglandin release, prevented corticosterone release from the adrenal induced by both NP and ACTH, demonstrating that prostaglandins mediate acute corticosterone release. Corticosterone content in adrenals after incubation with ACTH or NP was lower than in control glands, indicating that any
de novo
synthesis of corticosterone during this period was not sufficient to keep up with the release of the stored hormone. The release induced by ACTH or NP depleted the corticosterone content in the adrenal by ≈40% compared with the content of glands incubated in buffer. The mechanism of rapid release is as follows: NO produced by NO synthase activation by ACTH activates cyclooxygenase, which generates PGE
2
, which in turn releases corticosterone stored in microvesicles and other organelles.
Phosphorylation of p66Shc and forkhead proteins mediates Aβ toxicity
Authors: Smith Wanli W. , Norton Darrell D. , Gorospe Myriam , Jiang Haibing , Nemoto Shino , Holbrook Nikki J. , Finkel Toren , Kusiak John W.
Published: April 2005

Excessive accumulation of amyloid β-peptide (Aβ) plays an early and critical role in synapse and neuronal loss in Alzheimer's Disease (AD). Increased oxidative stress is one of the mechanisms whereby Aβ induces neuronal death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc in Aβ toxicity. Treatment of cells and primary neuronal cultures with Aβ caused apoptotic death and induced p66Shc phosphorylation at Ser36. Ectopic expression of a dominant-negative SEK1 mutant or chemical JNK inhibition reduced Aβ-induced JNK activation and p66Shc phosphorylation (Ser36), suggesting that JNK phosphorylates p66Shc. Aβ induced the phosphorylation and hence inactivation of forkhead transcription factors in a p66Shc-dependent manner. Ectopic expression of p66ShcS36A or antioxidant treatment protected cells against Aβ-induced death and reduced forkhead phosphorylation, suggesting that p66Shc phosphorylation critically influences the redox regulation of forkhead proteins and underlies Aβ toxicity. These findings underscore the potential usefulness of JNK, p66Shc, and forkhead proteins as therapeutic targets for AD.
p90Rsk is not involved in cytostatic factor arrest in mouse oocytes
Authors: Dumont Julien , Umbhauer Muriel , Rassinier Pascale , Hanauer André , Verlhac Marie-Hélène
Published: April 2005

Vertebrate oocytes arrest in metaphase of the second meiotic division (MII), where they maintain a high cdc2/cyclin B activity and a stable, bipolar spindle because of cytostatic factor (CSF) activity. The Mos–MAPK pathway is essential for establishing CSF. Indeed, oocytes from the mos−/− strain do not arrest in MII and activate without fertilization, as do Xenopus laevis oocytes injected with morpholino oligonucleotides directed against Mos. In Xenopus oocytes, p90Rsk (ribosomal S6 kinase), a MAPK substrate, is the main mediator of CSF activity. We show here that this is not the case in mouse oocytes. The injection of constitutively active mutant forms of Rsk1 and Rsk2 does not induce a cell cycle arrest in two-cell mouse embryos. Moreover, these two mutant forms do not restore MII arrest after their injection into mos−/− oocytes. Eventually, oocytes from the triple Rsk (1, 2, 3) knockout present a normal CSF arrest. We demonstrate that p90Rsk is not involved in the MII arrest of mouse oocytes.
Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis
Authors: Sahlender Daniela A. , Roberts Rhys C. , Arden Susan D. , Spudich Giulietta , Taylor Marcus J. , Luzio J. Paul , Kendrick-Jones John , Buss Folma
Published: April 2005

Myosin VI plays a role in the maintenance of Golgi morphology and in exocytosis. In a yeast 2-hybrid screen we identified optineurin as a binding partner for myosin VI at the Golgi complex and confirmed this interaction in a range of protein interaction studies. Both proteins colocalize at the Golgi complex and in vesicles at the plasma membrane. When optineurin is depleted from cells using RNA interference, myosin VI is lost from the Golgi complex, the Golgi is fragmented and exocytosis of vesicular stomatitis virus G-protein to the plasma membrane is dramatically reduced. Two further binding partners for optineurin have been identified: huntingtin and Rab8. We show that myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane and overexpression of constitutively active Rab8-Q67L recruits myosin VI onto Rab8-positive structures. These results show that optineurin links myosin VI to the Golgi complex and plays a central role in Golgi ribbon formation and exocytosis.
Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression
Authors: Halaschek-Wiener Julius , Khattra Jaswinder S. , McKay Sheldon , Pouzyrev Anatoli , Stott Jeff M. , Yang George S. , Holt Robert A. , Jones Steven J.M. , Marra Marco A. , Brooks-Wilson Angela R. , Riddle Donald L.
Published: April 2005

We have identified longevity-associated genes in a long-lived Caenorhabditis elegans daf-2 (insulin/IGF receptor) mutant using serial analysis of gene expression (SAGE), a method that efficiently quantifies large numbers of mRNA transcripts by sequencing short tags. Reduction of daf-2 signaling in these mutant worms leads to a doubling in mean lifespan. We prepared C. elegans SAGE libraries from 1, 6, and 10-d-old adult daf-2 and from 1 and 6-d-old control adults. Differences in gene expression between daf-2 libraries representing different ages and between daf-2 versus control libraries identified not only single genes, but whole gene families that were differentially regulated. These gene families are part of major metabolic pathways including lipid, protein, and energy metabolism, stress response, and cell structure. Similar expression patterns of closely related family members emphasize the importance of these genes in aging-related processes. Global analysis of metabolism-associated genes showed hypometabolic features in mid-life daf-2 mutants that diminish with advanced age. Comparison of our results to recent microarray studies highlights sets of overlapping genes that are highly conserved throughout evolution and thus represent strong candidate genes that control aging and longevity.
Identification of functional transcription factor binding sites using closely related Saccharomyces species
Authors: Doniger Scott W. , Huh Juyoung , Fay Justin C.
Published: April 2005

Comparative genomics provides a rapid means of identifying functional DNA elements by their sequence conservation between species. Transcription factor binding sites (TFBSs) may constitute a significant fraction of these conserved sequences, but the annotation of specific TFBSs is complicated by the fact that these short, degenerate sequences may frequently be conserved by chance rather than functional constraint. To identify intergenic sequences that function as TFBSs, we calculated the probability of binding site conservation between Saccharomyces cerevisiae and its two closest relatives under a neutral model of evolution. We found that this probability is <5% for 134 of 163 transcription factor binding motifs, implying that we can reliably annotate binding sites for the majority of these transcription factors by conservation alone. Although our annotation relies on a number of assumptions, mutations in five of five conserved Ume6 binding sites and three of four conserved Ndt80 binding sites show Ume6- and Ndt80-dependent effects on gene expression. We also found that three of five unconserved Ndt80 binding sites show Ndt80-dependent effects on gene expression. Together these data imply that although sequence conservation can be reliably used to predict functional TFBSs, unconserved sequences might also make a significant contribution to a species' biology.
Retroviruses and yeast retrotransposons use overlapping sets of host genes
Authors: Irwin Becky , Aye Michael , Baldi Pierre , Beliakova-Bethell Nadejda , Cheng Henry , Dou Yimeng , Liou Willy , Sandmeyer Suzanne
Published: April 2005

A collection of 4457 Saccharomyces cerevisiae mutants deleted for nonessential genes was screened for mutants with increased or decreased mobilization of the gypsylike retroelement Ty3. Of these, 64 exhibited increased and 66 decreased Ty3 transposition compared with the parental strain. Genes identified in this screen were grouped according to function by using GOnet software developed as part of this study. Gene clusters were related to chromatin and transcript elongation, translation and cytoplasmic RNA processing, vesicular trafficking, nuclear transport, and DNA maintenance. Sixty-six of the mutants were tested for Ty3 proteins and cDNA. Ty3 cDNA and transposition were increased in mutants affected in nuclear pore biogenesis and in a subset of mutants lacking proteins that interact physically or genetically with a replication clamp loader. Our results suggest that nuclear entry is linked mechanistically to Ty3 cDNA synthesis but that host replication factors antagonize Ty3 replication. Some of the factors we identified have been previously shown to affect Ty1 transposition and others to affect retroviral budding. Host factors, such as these, shared by distantly related Ty retroelements and retroviruses are novel candidates for antiviral targets.
Unfolding crystallins: The destabilizing role of a β‐hairpin cysteine in βB2‐crystallin by simulation and experiment
Authors: Macdonald James T. , Purkiss Andrew G. , Smith Myron A. , Evans Paul , Goodfellow Julia M. , Slingsby Christine
Published: April 2005

The thermodynamic and kinetic stabilities of the eye lens family of βγ‐crystallins are important factors in the etiology of senile cataract. They control the chance of proteins unfolding, which can lead to aggregation and loss of transparency. βB2‐Crystallin orthologs are of low stability and comprise two typical βγ‐crystallin domains, although, uniquely, the N‐terminal domain has a cysteine in one of the conserved folded β‐hairpins. Using high‐temperature (500 K) molecular dynamics simulations with explicit solvent on the N‐terminal domain of rodent βB2‐crystallin, we have identified in silico local flexibility in this folded β‐hairpin. We have shown in vitro using two‐domain human βB2‐crystallin that replacement of this cysteine with a more usual aromatic residue (phenylalanine) results in a gain in conformational stability and a reduction in the rate of unfolding. We have used principal components analysis to visualize and cluster the coordinates from eight separate simulated unfolding trajectories of both the wild‐type and the C50F mutant N‐terminal domains. These data, representing fluctuations around the native well, show that although the mutant and wild‐type appear to behave similarly over the early time period, the wild type appears to explore a different region of conformational space. It is proposed that the advantage of having this low‐stability cysteine may be correlated with a subunit‐exchange mechanism that allows βB2‐crystallin to interact with a range of other β‐crystallin subunits.