bluuebunny/crossref_metadata_2025 huggingface dataset:
Refined similarity hypotheses for turbulent velocity and temperature fields
Authors: Zhu Y. , Antonia R. A. , Hosokawa I.
Published: July 2002

The refined similarity hypothesis of Kolmogorov [J. Fluid Mech. 13, 82 (1962)] is extended to a scalar field. These hypotheses are tested using measurements in a circular jet and the atmospheric surface layer. Over a significant part of the inertial range, statistics of the normalized stochastic variables for velocity and temperature indicate a dependence on the separation r. This dependence is also quantified through the probability density functions of the stochastic variables and the correlation between the velocity (or temperature) increment and the local energy (or temperature) dissipation rates. Probability density functions of the stochastic variables are conditioned on the local Reynolds number Rer based on r and the local energy dissipation rate. These functions depend on Rer when the latter is small and are approximately universal when Rer is very large. This behaviour is consistent with the refined similarity hypothesis. There is however a slight difference between the shapes of the conditional probability density functions in the two flows, implying a weak dependence on the turbulence Reynolds number Rλ and flow conditions.
Study of large-coherent structures in a plane wall jet
Authors: Scibilia M. F. , Lain J.
Published: July 2002

This work concerns the interaction between a mean flow and large-scale coherent structures in a wall jet at low Reynolds numbers in the case of single and multiple modes. The Navier–Stokes equations have been used to study the evolution of the wall jet and, in particular, its kinetic energy. The nonlinear interaction problem has been solved by means of the integral method taking into account the shape assumptions and local linear theory to obtain characteristics of coherent modes in the wall jet. It has been observed that the fundamental wave in case of a single mode, extracts its energy from the mean flow. When considering the fundamental mode superposed to its first subharmonic one with a phase difference θ=0, it can be observed that there are interactions between the mean flow and these waves. Energy is extracted from the mean flow to the fundamental wave and then to its first subharmonic mode. The evolution of the thickness of the jet δ and the maximum velocity U for each dimensionless downstream coordinate is also shown with a growth of increasing of δ and decreasing of U. Initial conditions play an important role. In this work, fine-grained turbulence quantities have been neglected. Some comparisons with experimental results have been performed.
A numerical calculation of the hydraulic permeability of three-dimensional disordered fibrous media
Authors: Clague David S. , Phillips Ronald J.
Published: July 2002

Hydraulic permeabilities of polymeric membranes and gels are of interest both for calculating fluid flow rates and hindered diffusion coefficients. We have calculated hydraulic permeabilities for monomodal and bimodal, periodic and random fibrous media. Hydrodynamic interactions between fibers are calculated by applying a numerical version of slender body theory to a collection of fibers in a cubic cell many Brinkman screening lengths in dimension. Results for random media are obtained by averaging over many ensembles of fibers. To account for the surrounding medium, the line distribution of point forces along the fiber axes are replicated throughout space by using the Ewald summation technique. Results for periodic media agree with previous theoretical results up to a fiber volume fraction of 50% for parallel flow and 40% for transverse flow. Hydraulic permeabilities calculated for three-dimensional, disordered media with monomodal and bimodal distributions of fiber radius are compared with existing theories and with experimentally determined hydraulic permeabilities for a range of fiber volume fractions. Specific calculations are performed for agarose and collagen/proteoglycan gel systems, which are well described as bimodal fibrous media and are relevant to bioseparations and physiological systems, respectively.
Collapse interactions of finite-sized two-dimensional vortices
Authors: Vosbeek P. W. C. , van Geffen J. H. G. M. , Meleshko V. V. , van Heijst G. J. F.
Published: July 2002

The point vortex model predicts that a certain configuration of three point vortices leads to a collapse of these vortices to one point. Numerical simulations have been performed to investigate the effect of a finite vortex size on this two-dimensional collapse interaction. The paper presents results obtained with contour dynamics simulations of patches of uniform vorticity, and results obtained with finite difference simulations of vortices with continuous properties. In addition, the effect of viscosity and the presence of impermeable domain boundaries are investigated. The results show that the motion of finite-sized vortices is quite similar to the motion of point vortices as long as the mutual distance between the vortices is larger than their size. When the vortices are closer together their shapes start to deform and the subsequent evolution is different from that of the point vortices, and an actual collapse to one vortex does not take place.
Bifurcation analysis of double-diffusive convection with opposing horizontal thermal and solutal gradients
Authors: Xin Shihe , Le Quéré Patrick , Tuckerman Laurette S.
Published: July 2002

The onset of convection in double diffusion with equal and opposite thermal and solutal buoyancy forces is studied. Numerical linear stability analyses and integration of the full Boussinesq equations are performed in an infinite vertical fluid layer and in closed rectangular cavities bounded by rigid walls. Detailed study of the subsequent nonlinear evolution is carried out for Le=1.2 and Pr=1. In the infinite vertical layer, the onset of convection is found to correspond to a subcritical circle pitchfork bifurcation. The finite-amplitude branch of steady states in turn loses stability to traveling waves via a supercritical drift pitchfork bifurcation. In a square cavity the bifurcation is transcritical and the full branch of stable and unstable solutions is constructed. With increasing cavity aspect-ratio, we observe alternating transcritical and pitchfork bifurcations, depending on the symmetry of the most unstable eigenvector.
On the collision rate of small particles in isotropic turbulence. II. Finite inertia case
Authors: Zhou Yong , Wexler Anthony S. , Wang Lian-Ping
Published: July 2002

Numerical experiments have been performed to study the geometric collision rate of heavy particles with finite inertia. The turbulent flow was generated by direct numerical integration of the full Navier-Stokes equations. The collision kernel peaked at a particle response time between the Kolmogorov and the large-eddy turnover times, implying that both the large-scale and small-scale fluid motions contribute, although in very different manners, to the collision rate. Both numerical results for frozen turbulent fields and a stochastic theory show that the collision kernel approaches the kinetic theory of Abrahamson [Chem. Eng. Sci. 30, 1371 (1975)] only at very large τp/Te, where τp is the particle response time and Te is the flow integral time scale. Our results agree with those of Sundaram and Collins [J. Fluid Mech. 335, 75 (1997)] for an evolving flow. A rapid increase of the collision kernel with the particle response time was observed for small τp/τk, where τk is the flow Kolmogorov time scale. A small inertia of τp/τk=0.5 can lead to an order of magnitude increase in the collision kernel relative to the zero-inertia particles. A scaling law for the collision kernel at small τp/τk was proposed and confirmed numerically by varying the particle size, inertial response time, and flow Reynolds number. A leading-order theory for small τp/τk was developed, showing that the enhanced collision is mainly a result of the nonuniform particle concentration that results from the interaction of heavy particles with local flow microstructures.
Dynamic molecular collision (DMC) model for rarefied gas flow simulations by the DSMC method
Authors: Tokumasu T. , Matsumoto Y.
Published: July 2002

The Dynamic Molecular Collision (DMC) model is constructed for accurate and realistic simulations of rarefied gas flows of nonpolar diatomic molecules by the Direct Simulation Monte Carlo (DSMC) method. This model is applicable for moderate temperatures (up to a few hundred K for nitrogen), where most molecules are in the vibrational ground state and the vibrational degree of freedom can be neglected. In this range, moreover, the rotational energy can be considered as a continuous one. The collisions of diatomic molecules are simulated many times by the Molecular Dynamics (MD) method at various initial conditions. The site to site potential is used as an intermolecular one. The collision cross section is developed from the database obtained by MD simulation and kinetic theory of viscosity coefficient of diatomic molecules. The probability density function of energy after collision is also developed using the database. In order to verify the DMC model, two flow fields are simulated. First, the DMC model is applied to the simulation of the translational and rotational energy distribution at the equilibrium condition and the results are compared with the Maxwell distribution. The results agree very well with each other. Second, the DMC model is applied to the simulation of the rotational relaxation through low and high Mach number normal shock wave. These results also agree very well with the experimental results of Robben and Talbot, although the upstream rotational temperature is a little lower.
Experimental study of non-Boussinesq Rayleigh–Bénard convection at high Rayleigh and Prandtl numbers
Authors: Manga Michael , Weeraratne Dayanthie
Published: July 2002

A set of experiments is performed, in which a layer of fluid is heated from below and cooled from above, in order to study convection at high Rayleigh numbers (Ra) and Prandtl numbers (Pr). The working fluid, corn syrup, has a viscosity that depends strongly on temperature. Viscosity within the fluid layer varies by a factor of 6 to 1.8×103 in the various experiments. A total of 28 experiments are performed for 104<Ra<108 and Pr sufficiently large, 103<Pr<106, that the Reynolds number (Re) is less than 1; here, values of Ra and Pr are based on material properties at the average of the temperatures at the top and bottom of the fluid layer. As Ra increases above O(105), flow changes from steady to time-dependent. As Ra increases further, large scale flow is gradually replaced by isolated rising and sinking plumes. At Ra>O(107), there is no evidence for any large scale circulation, and flow consists only of plumes. Plumes have mushroom-shaped “heads” and continuous “tails” attached to their respective thermal boundary layers. The characteristic frequency for the formation of these plumes is consistent with a Ra2/3 scaling. In the experiments at the largest Ra, the Nusselt number (Nu) is lower than expected, based on an extrapolation of the Nu–Ra relationship determined at lower Ra; at the highest Ra, Re→1, and the lower-than-expected Nu is attributed to inertial effects that reduce plume head speeds.
Propagation of waves in dusty plasmas with variable charges on dust particles
Authors: Vladimirov Sergey V.
Published: July 2002

The propagation of electromagnetic and Langmuir waves in multicomponent unmagnetized plasmas with dust particles is investigated. The effect of capture of plasma electrons and ions by the dust particles is taken into account. The recent theory proposed by Tsytovich and Havnes [Comments Plasma Phys. Controlled Fusion 15, 267 (1993)] to describe the kinetics of the capture process, as well as its perturbations, is further developed. The new wave damping due to this effect is calculated.
Nonlinear solutions of the Vlasov–Poisson equations
Authors: Karimov A. R. , Lewis H. Ralph
Published: July 2002

Based on the kinetic description, properties of collisionless unmagnetized plasma are studied. Time-dependent solutions of the nonlinear Vlasov–Poisson equations are found. Several dynamical structures of a Maxwellian type are presented.
Field emitter arrays for plasma and microwave source applications
Authors: Jensen K. L.
Published: July 2002

Field emitter arrays (FEAs) stand to strongly impact device performance when physical size, weight, power consumption, beam current, and/or high pulse repetition frequencies are an issue. FEAs are capable of instant ON/OFF performance, high brightness, high current density, large transconductance to capacitance ratio, and low voltage operation characteristics. Advanced microwave power tubes, and in particular, inductive output amplifiers, are by far the most technically challenging use to date. Other important uses include, e.g., electron sources for micropropulsion systems–Hall thrusters–and tethers for satellites, and (the most widely pursued application) field emission displays. The characteristics of field emitters that make them attractive to such applications shall be surveyed. A thorough analytical model of a field emitter array, beginning with a review of the nature of field emission and continuing with an analytical model of a single emitter and the operation of an array of emitters, shall be presented. In particular, attention shall be directed towards those features of FEAs that render them attractive as cold cathode candidates for electron beam generation. Tip characteristics, such as emission distribution, and array operation, such as space charge effects, will be analyzed in the context of the model. Finally, restricting attention to microwave applications, the performance of a tapered-helix inductive output amplifier to highlight the advantages of high frequency emission gating of the electron beam in a power tube shall be investigated.
Modeling of the stabilization of neoclassical tearing modes by localized radio frequency current drive
Authors: Yu Q. , Günter S. , Giruzzi G. , Lackner K. , Zabiego M.
Published: July 2002

Numerical modeling of the stabilization of neoclassical tearing modes by localized radio frequency (rf) current drive is presented. The bootstrap current is self-consistently calculated from the pressure evolution equation, the rf current source is obtained from the ray-tracing code and the Fokker–Planck code, and the change of the driven current profile due to the change of the magnetic island width has also been taken into account by modeling the two-dimensional transport of the fast electrons induced by the rf wave. It is found that both parallel and the perpendicular transport of the fast electrons play important roles in the stabilization, and modulated and nonmodulated rf current drive have approximately the same stabilizing effect. The neoclassical tearing modes is shown to be stabilized by a continuous rf current drive. The simulation results essentially agree with experimental observations.
Room-temperature excitons in 1.6-μm band-gap GaInAs/AlInAs quantum wells
Authors: Weiner J. S. , Chemla D. S. , Miller D. A. B. , Wood T. H. , Sivco D. , Cho A. Y.
Published: July 2002

The first observation of strong and well-resolved exciton peaks in the room-temperature absorption spectra of infrared band-gap multiple quantum well structures (MQW’s) is reported. Assignment of the optical resonances in the absorption spectra of GaInAs/AlInAs MQW’s yields the material parameters of this new heterojunction. The discontinuities of the conduction and valence bands are found to be ΔEc=0.44 eV and ΔEv=0.29 eV, respectively.
Solidification kinetics of pulsed laser melted silicon based on thermodynamic considerations
Authors: Galvin G. J. , Mayer J. W. , Peercy P. S.
Published: July 2002

The measured solidification velocities in silicon after pulsed laser melting are analyzed in terms of thermodynamic and kinetic considerations. Both interface and thermal transport limited growth regimes are observed. From the observed kinetics in the 1–6-m/s regime, the undercooling at the liquid-solid interface can be calculated. At velocities ≤6 m/s the undercooling increases with interface velocity at the rate of 15±5 deg/m/s.
Intensity discrimination through nonlinear power coupling in birefringent fibers
Authors: Vatarescu A.
Published: July 2002

The nonlinear coupling of energy between the polarization eigenmodes is shown to affect both the relative phase and amplitude ratio of a light beam propagating in a birefringent fiber. These two quantities determine the polarization state at the output. The general formalism and some specific numerical examples are presented.
Defect reduction in GaAs grown by molecular beam epitaxy using different superlattice structures
Authors: Bedair S. M. , Humphreys T. P. , El-Masry N. A. , Lo Y. , Hamaguchi N. , Lamp C. D. , Tuttle A. A. , Dreifus D. L. , Russell P.
Published: July 2002

Several superlattice structures, grown by molecular beam epitaxy, have been used to reduce the density of threading dislocations originating from the GaAs substrate. Results clearly indicate that compared to epitaxial layers grown directly on GaAs substrates, a GaAs-InxGa1−xAs superlattice (x<0.12) reduces the dislocations by approximately two orders of magnitude. Transmission electron microscopy, electron beam induced current, and etch pit density have been used to characterize the effectiveness of using superlattice buffer layers for the reduction of defects in GaAs epilayers.
Linewidth enhancement factor in InGaAsP/InP multiple quantum well lasers
Authors: Green C. A. , Dutta N. K. , Watson W.
Published: July 2002

The linewidth enhancement factor α in an InGaAsP/InP multiple quantum well (MQW) laser has been determined from the spontaneous emission spectra below threshold. It is demonstrated that the measured value of α in the MQW laser is appreciably smaller than that in a conventional double heterostructure laser as expected from theoretical calculations.
Strong 8.2 μm infrared intersubband absorption in doped GaAs/AlAs quantum well waveguides
Authors: Levine B. F. , Malik R. J. , Walker J. , Choi K. K. , Bethea C. G. , Kleinman D. A. , Vandenberg J. M.
Published: July 2002

We have measured the infrared intersubband absorption at 8.2 μm in doped GaAs/AlAs quantum well superlattices. Waveguide geometry experiments demonstrate strong absorption with 95% of the incident infrared energy being absorbed.
Highly activated shallow Ga profiles in silicon obtained by implantation and rapid thermal annealing
Authors: Harrison H. B. , Iyer S. S. , Sai-Halasz G. A. , Cohen S. A.
Published: July 2002

The physical and electrical characteristics of gallium (Ga) ion implanted 〈100〉 silicon, annealed for times of the order of seconds to several tens of seconds for temperatures in the range of 550–900 °C, are presented. It is shown that for the chosen doses of 1–6×1015/cm2 and energy of 100 keV highly electrically active p-type layers (approaching 100%) can be achieved. The highest activation being reached at temperatures below ∼650 °C with no profile distortion. For temperatures in excess of 800 °C this electrical activation decreases and significant profile movement occurs even for times as short as 2 s.
Theory of the steady-state hole drift velocity in InGaAs
Authors: Brennan Kevin
Published: July 2002

We present calculations of the steady-state hole drift velocity in Ga0.47In0.53As as a function of applied electric field based on an ensemble Monte Carlo method. The calculation uses no adjustable parameters in the determination of the scattering rates and contains the full details of the valence-band structure derived using the k*p method. It is found that the calculated values match recent experimental values within 20% in the saturated regime. The calculations are made over the applied field range of 10–250 kV/cm.
New method to relax thermal stress in GaAs grown on Si substrates
Authors: Sakai Shiro
Published: July 2002

A new method to grow stress-free GaAs on bent Si substrates is proposed and demonstrated by metalorganic chemical vapor deposition. The stress produced by the thermal expansion coefficient difference of Si and GaAs is compensated by the external mechanical strain applied in the substrate at high temperature. The photoluminescence peak energy of GaAs on Si becomes almost the same as that of the stress-free GaAs on GaAs grown by liquid phase epitaxy by applying this method.
Effect of substrate tilting on molecular beam epitaxial grown AlGaAs/GaAs lasers having very low threshold current densities
Authors: Chen H. Z. , Ghaffari A. , Morkoç H. , Yariv A.
Published: July 2002

Single quantum well, graded refractive index separate confinement heterostucture (SQW GRINSCH) lasers with well thicknesses in the range of 65–480 Å have been grown by molecular beam epitaxy (MBE) on (100) and off of (100) by 4° toward (111) A substrates. The threshold current density appears to be independent of the well thickness in the range of 65–165 Å due to the compensating effects of volume of inversion and optical confinement. Under optimum growth conditions, the tilted substrates led to lower threshold current densities, the lowest value being 93 A/cm2 for a 520-μm-long cavity laser with a 125-Å-thick well. To our knowledge, this is by far the best ever reported threshold current density obtained in a semiconductor injection laser. Deviations from optimum growth conditions drastically increased the threshold current density on (100) substrates whereas the degradation for those on the tilted substrates was much less pronounced.
Bi-Sr-Ca-Cu-oxide superconducting thin films deposited by dc magnetron sputtering
Authors: Sullivan Brian T. , Osborne N. R. , Hardy W. N. , Carolan J. F. , Yang B. X. , Michael P. J. , Parsons R. R.
Published: July 2002

Thin films of the high-temperature superconductor Bi-Sr-Ca-Cu-oxide were deposited by dc magnetron sputtering onto various substrates. Films deposited on (100) MgO substrates achieved zero resistance between 78 and 82.5 K depending upon the annealing conditions. The best films were produced with a quick post-anneal in oxygen at 870 °C followed by a slower anneal in air at the same temperature. The composition of the sputtered films was uniform within ±3% over an area 40 mm in radius, and films deposited at 15 and 40 mm from the center of deposition both exhibited high Tc transitions.
TOGA: An automated parsing technology for analyzing expression of nearly all genes
Authors: Sutcliffe J. Gregor , Foye Pamela E. , Erlander Mark G. , Hilbush Brian S. , Bodzin Leon J. , Durham Jayson T. , Hasel Karl W.
Published: July 2002

We have developed an automated, high-throughput, systematic cDNA display method called TOGA, an acronym for total gene expression analysis. TOGA utilizes 8-nt sequences, comprised of a 4-nt restriction endonuclease cleavage site and adjacent 4-nt parsing sequences, and their distances from the 3′ ends of mRNA molecules to give each mRNA species in an organism a single identity. The parsing sequences are used as parts of primer-binding sites in 256 PCR-based assays performed robotically on tissue extracts to determine simultaneously the presence and relative concentration of nearly every mRNA in the extracts, regardless of whether the mRNA has been discovered previously. Visualization of the electrophoretically separated fluorescent assay products from different extracts displayed via a Netscape browser-based graphical user interface allows the status of each mRNA to be compared among samples and its identity to be matched with sequences of known mRNAs compiled in databases.
Potent blockade of sodium channels and protection of brain tissue from ischemia by BIII 890 CL
Authors: Carter Adrian J. , Grauert Matthias , Pschorn Uwe , Bechtel Wolf Dietrich , Bartmann-Lindholm Christina , Qu Yusheng , Scheuer Todd , Catterall William A. , Weiser Thomas
Published: July 2002

We have synthesized a new benzomorphan derivative, 2
R-
[2α,3(
S
*),6α]-1,2,3,4,5,6-hexahydro-6,11,11-trimethyl-3-[2-(phenylmethoxy)propyl]-2,6-methano-3-benzazocin-10-ol hydrochloride (BIII 890 CL), which displaced [
3
H]batrachotoxinin A-20α-benzoate from neurotoxin receptor site 2 of the Na
+
channel in rat brain synaptosomes (IC
50
= 49 nM), but exhibited only low affinity for 65 other receptors and ion channels. BIII 890 CL inhibited Na
+
channels in cells transfected with type IIA Na
+
channel α subunits and shifted steady-state inactivation curves to more negative potentials. The IC
50
value for the inactivated Na
+
channel was much lower (77 nM) than for Na
+
channels in the resting state (18 μM). Point mutations F1764A and Y1771A in transmembrane segment S6 in domain IV of the α subunit reduced the voltage- and frequency-dependent block, findings which suggest that BIII 890 CL binds to the local anesthetic receptor site in the pore. BIII 890 CL inhibited veratridine-induced glutamate release in brain slices, as well as glutamate release and neurotoxicity in cultured cortical neurons. BIII 890 CL (3–30 mg/kg s.c.) reduced lesion size in mice and rats when administered 5 min after permanent focal cerebral ischemia at doses that did not impair motor coordination. In contrast to many other agents, BIII 890 CL was neuroprotective in both cortical and subcortical regions of the rat brain. Our results demonstrate that BIII 890 CL is a potent, selective, and highly use-dependent Na
+
channel blocker that protects brain tissue from the deleterious effects of focal cerebral ischemia in rodents.
Functional studies on the role of the C-terminal domain of mammalian polo-like kinase
Authors: Jang Young-Joo , Lin Chin-Yo , Ma Sheng , Erikson Raymond L.
Published: July 2002

Mammalian polo-like kinase (Plk) acts at various stages in early and late mitosis. Plk is phosphorylated and activated in mitosis, and the proper subcellular localization of Plk is essential for mitotic regulation. We have observed that overexpression of the C-terminal domain of Plk is more effective than wild-type or kinase-defective Plk in causing mitotic delay or arrest. The specific activity of Plk with C-terminal deletions or substitution of aspartate for threonine-210 is increased severalfold relative to wild type. We show in this communication that the C-terminal domain can bind to full-length or the catalytic domain of Plk and inhibit its kinase activity, and that this binding is disrupted when threonine-210 is substituted with an aspartic acid residue. The C-terminal domain binds unphosphorylated Plk from G
2
arrested cells, but not phosphorylated Plk from mitotic cells. Green fluorescent protein–C-terminal Plk is localized at the centrosome and the midbody of transfected cells as shown previously for full-length enzyme. These and other data indicate that although the C terminus serves to regulate Plk kinase activity, the localization of the C terminus at the centrosome and other sites in transfected cells may block the correct localization of endogenous Plk.
A spliceosomal intron in
Giardia
lamblia
Authors: Nixon Julie E. J. , Wang Amy , Morrison Hilary G. , McArthur Andrew G. , Sogin Mitchell L. , Loftus Brendan J. , Samuelson John
Published: July 2002

Short introns occur in numerous protist lineages, but there are no reports of intervening sequences in the protists
Giardia lamblia
and
Trichomonas vaginalis,
which may represent the deepest known branches in the eukaryotic line of descent. We have discovered a 35-bp spliceosomal intron in a gene encoding a putative [2Fe-2S] ferredoxin of
G. lamblia
. The
Giardia
intron contains a canonical splice site at its 3′ end (AG), a noncanonical splice site at its 5′ end (CT), and a branch point sequence that fits the yeast consensus sequence of TACTAAC except for the first nucleotide (AACTAAC). We have also identified several
G. lamblia
genes with spliceosomal peptides, including homologues of eukaryote-specific spliceosomal peptides (Prp8 and Prp11), several DExH-box RNA-helicases that have homologues in eubacteria, but serve essential functions in the splicing of introns in eukaryotes, and 11 predicted archaebacteria-like Sm and like-Sm core peptides, which coat small nuclear RNAs. Phylogenetic analyses show the
Giardia
Sm core peptides are the products of multiple, ancestral gene duplications followed by divergence, but they retain strong similarity to Sm and like-Sm peptides of other eukaryotes. Although we have documented only a single intron in
Giardia
, it likely has other introns and fully functional, spliceosomal machinery. If introns were added during eukaryotic evolution (the introns-late hypothesis), then these results push back the date of this event before the branching of
G. lamblia
.
Carbon nanotube atomic force microscopy tips: Direct growth by chemical vapor deposition and application to high-resolution imaging
Authors: Cheung Chin Li , Hafner Jason H. , Lieber Charles M.
Published: July 2002

Carbon nanotubes are potentially ideal atomic force microscopy probes because they can have diameters as small as one nanometer, have robust mechanical properties, and can be specifically functionalized with chemical and biological probes at the tip ends. This communication describes methods for the direct growth of carbon nanotube tips by chemical vapor deposition (CVD) using ethylene and iron catalysts deposited on commercial silicon-cantilever-tip assemblies. Scanning electron microscopy and transmission electron microscopy measurements demonstrate that multiwalled nanotube and single-walled nanotube tips can be grown by predictable variations in the CVD growth conditions. Force-displacement measurements made on the tips show that they buckle elastically and have very small (≤ 100 pN) nonspecific adhesion on mica surfaces in air. Analysis of images recorded on gold nanoparticle standards shows that these multi- and single-walled carbon nanotube tips have radii of curvature of 3–6 and 2–4 nm, respectively. Moreover, the nanotube tip radii determined from the nanoparticle images are consistent with those determined directly by transmission electron microscopy imaging of the nanotube ends. These molecular-scale CVD nanotube probes have been used to image isolated IgG and GroES proteins at high-resolution.
Sequence conservation at human and mouse orthologous common fragile regions,
FRA3B
/
FHIT
and
Fra14A2
/
Fhit
Authors: Shiraishi Takeshi , Druck Teresa , Mimori Koshi , Flomenberg Jacob , Berk Lori , Alder Hansjuerg , Miller Webb , Huebner Kay , Croce Carlo M.
Published: July 2002

It has been suggested that delayed DNA replication underlies
fragility at common human fragile sites, but specific sequences
responsible for expression of these inducible fragile sites have not
been identified. One approach to identify such cis-acting sequences
within the large nonexonic regions of fragile sites would be to
identify conserved functional elements within orthologous fragile sites
by interspecies sequence comparison. This study describes a comparison
of orthologous fragile regions, the human
FRA3B
/
FHIT
and the murine
Fra14A2
/
Fhit
locus. We sequenced over
600 kbp of the mouse
Fra14A2
, covering the region
orthologous to the fragile epicenter of
FRA3B
, and
determined the
Fhit
deletion break points in a mouse
kidney cancer cell line (RENCA). The murine
Fra14A2
locus, like the human
FRA3B
, was characterized by a high
AT content. Alignment of the two sequences showed that this fragile
region was stable in evolution despite its susceptibility to mitotic
recombination on inhibition of DNA replication. There were also several
unusual highly conserved regions (HCRs). The positions of predicted
matrix attachment regions (MARs), possibly related to replication
origins, were not conserved. Of known fragile region landmarks, five
cancer cell break points, one viral integration site, and one
aphidicolin break cluster were located within or near HCRs. Thus,
comparison of orthologous fragile regions has identified highly
conserved sequences with possible functional roles in maintenance of
fragility.
Identification of a protein secretory pathway for the secretion of heat-labile enterotoxin by an enterotoxigenic strain of
Escherichia coli
Authors: Tauschek Marija , Gorrell Rebecca J. , Strugnell Richard A. , Robins-Browne Roy M.
Published: July 2002

Enterotoxigenic
Escherichia coli
(ETEC) is an enteric pathogen that causes cholera-like diarrhea in humans and animals. ETEC secretes a heat-labile enterotoxin (LT), which resembles cholera toxin, but the actual mechanism of LT secretion is presently unknown. We have identified a previously unrecognized type II protein secretion pathway in the prototypic human ETEC strain, H10407 (serotype O78:H11). The genes for this pathway are absent from
E. coli
K-12, although examination of the K-12 genome suggests that it probably once possessed them. The secretory pathway bears significant homology at the amino acid level to the type II protein secretory pathway required by
Vibrio cholerae
for the secretion of cholera toxin. With this in mind, we determined whether the homologous pathway of
E. coli
H10407 played a role in the secretion of LT. To this end, we inactivated the pathway by inserting a kanamycin-resistance gene into one of the genes (
gspD
) of the type II secretion pathway by homologous recombination. LT secretion by
E. coli
H10407 and the
gspD
mutant was assayed by enzyme immunoassay, and its biological activity was assessed by using Y-1 adrenal cells. This investigation showed that the protein secretory pathway is functional and necessary for the secretion of LT by ETEC. Our findings have revealed the mechanism for the secretion of LT by ETEC, which previously was unknown, and provide further evidence of close biological similarities of the LT and cholera toxin.
Interactions between thalamic and cortical rhythms during semantic memory recall in human
Authors: Slotnick Scott D. , Moo Lauren R. , Kraut Michael A. , Lesser Ronald P. , Hart John
Published: July 2002

Human scalp electroencephalographic rhythms, indicative of cortical population synchrony, have long been posited to reflect cognitive processing. Although numerous studies employing simultaneous thalamic and cortical electrode recording in nonhuman animals have explored the role of the thalamus in the modulation of cortical rhythms, direct evidence for thalamocortical modulation in human has not, to our knowledge, been obtained. We simultaneously recorded from thalamic and scalp electrodes in one human during performance of a cognitive task and found a spatially widespread, phase-locked, low-frequency rhythm (7–8 Hz) power decrease at thalamus and scalp during semantic memory recall. This low-frequency rhythm power decrease was followed by a spatially specific, phase-locked, fast-rhythm (21–34 Hz) power increase at thalamus and occipital scalp. Such a pattern of thalamocortical activity reflects a plausible neural mechanism underlying semantic memory recall that may underlie other cognitive processes as well.
Trypanosoma brucei
CTP synthetase: A target for the treatment of African sleeping sickness
Authors: Hofer Anders , Steverding Dietmar , Chabes Andrei , Brun Reto , Thelander Lars
Published: July 2002

The drugs in clinical use against African sleeping sickness are
toxic, costly, or inefficient. We show that
Trypanosoma
brucei
, which causes this disease, has very low levels of CTP,
which are due to a limited capacity for
de novo
synthesis and the lack of salvage pathways. The CTP synthetase
inhibitors 6-diazo-5-oxo-
l
-norleucine (DON) and
α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin)
reduced the parasite CTP levels even further and inhibited trypanosome
proliferation
in vitro
and in
T.
brucei-
infected mice. In mammalian cells, DON mainly inhibits
de novo
purine biosynthesis, a pathway lacking in
trypanosomes. We could rescue DON-treated human and mouse fibroblasts
by the addition of the purine base hypoxanthine to the growth medium.
For treatment of sleeping sickness, we propose the use of CTP
synthetase inhibitors alone or in combination with appropriate
nucleosides or bases.
TAR RNA loop: A scaffold for the assembly of a regulatory switch in HIV replication
Authors: Richter Sara , Ping Yueh-Hsin , Rana Tariq M.
Published: July 2002

Replication of HIV requires the Tat protein, which activates elongation of RNA polymerase II transcription at the HIV-1 promoter by interacting with the cyclin T1 (CycT1) subunit of the positive transcription elongation factor complex b (P-TEFb). The transactivation domain of Tat binds directly to the CycT1 subunit of P-TEFb and induces loop sequence-specific binding of P-TEFb onto nascent HIV-1 trans-activation responsive region (TAR) RNA. We used systematic RNA–protein photocross-linking, Western blot analysis, and protein footprinting to show that residues 252–260 of CycT1 interact with one side of the TAR RNA loop and enhance interaction of Tat residue K50 to the other side of the loop. Our results show that TAR RNA provides a scaffold for two protein partners to bind and assemble a regulatory switch in HIV replication. RNA-mediated assembly of RNA–protein complexes could be a general mechanism for stable ribonucleoprotein complex formation and a key step in regulating other cellular processes and viral replication.
Location and properties of metal-binding sites on the human prion protein
Authors: Jackson Graham S. , Murray Ian , Hosszu Laszlo L. P. , Gibbs Nicholas , Waltho Jonathan P. , Clarke Anthony R. , Collinge John
Published: July 2002

Although a functional role in copper binding has been suggested for the prion protein, evidence for binding at affinities characteristic of authentic metal-binding proteins has been lacking. By presentation of copper(II) ions in the presence of the weak chelator glycine, we have now characterized two high-affinity binding sites for divalent transition metals within the human prion protein. One is in the N-terminal octapeptide-repeat segment and has a
K
d
for copper(II) of 10
−14
M, with other metals (Ni
2+
, Zn
2+
, and Mn
2+
) binding three or more orders of magnitude more weakly. However, NMR and fluorescence data reveal a previously unreported second site around histidines 96 and 111, a region of the molecule known to be crucial for prion propagation. The
K
d
for copper(II) at this site is 4 × 10
−14
M, whereas nickel(II), zinc(II), and manganese(II) bind 6, 7, and 10 orders of magnitude more weakly, respectively, regardless of whether the protein is in its oxidized α-helical (α-PrP) or reduced β-sheet (β-PrP) conformation. A role for prion protein (PrP) in copper metabolism or transport seems likely and disturbance of this function may be involved in prion-related neurotoxicity.
Physical basis of two-tone interference in hearing
Authors: Jülicher Frank , Andor Daniel , Duke Thomas
Published: July 2002

The cochlea uses active amplification to capture faint sounds. It has been proposed that the amplifier comprises a set of self-tuned critical oscillators: each hair cell contains a force-generating dynamical system that is maintained at the threshold of an oscillatory instability, or Hopf bifurcation. While the active response to a pure tone provides frequency selectivity, exquisite sensitivity, and wide dynamic range, its intrinsic nonlinearity causes tones of different frequency to interfere with one another in the cochlea. Here we determine the response to two tones, which provides a framework for understanding how the ear processes the more complex sounds of speech and music. Our calculations of two-tone suppression and the spectrum of distortion products generated by a critical oscillator accord with experimental observations of basilar membrane motion and the nervous response. We discuss how the response of a set of self-tuned oscillators, covering a range of characteristic frequencies, represents the structure of a complex sound. The frequency components of the stimulus can be inferred from the timing of neural spikes elicited by the vibrating hair cells. Passive prefiltering by the basilar membrane improves pitch discrimination by reducing interference between tones. Our analysis provides a general framework for examining the relation between the physical nature of the peripheral detection apparatus and psychophysical phenomena such as the sensation of dissonance and auditory illusions.
Worldwide DNA sequence variation in a 10-kilobase noncoding region on human chromosome 22
Authors: Zhao Zhongming , Jin Li , Fu Yun-Xin , Ramsay Michele , Jenkins Trefer , Leskinen Elina , Pamilo Pekka , Trexler Maria , Patthy Laszlo , Jorde Lynn B. , Ramos-Onsins Sebastian , Yu Ning , Li Wen-Hsiung
Published: July 2002

Human DNA sequence variation data are useful for studying the
origin, evolution, and demographic history of modern humans and the
mechanisms of maintenance of genetic variability in human populations,
and for detecting linkage association of disease. Here, we report
worldwide variation data from a ≈10-kilobase noncoding autosomal
region. We identified 75 variant sites in 64 humans (128 sequences) and
463 variant sites among the human, chimpanzee, and orangutan sequences.
Statistical tests suggested that the region is selectively neutral. The
average nucleotide diversity (π) across the region was 0.088% among
all of the human sequences obtained, 0.085% among African sequences,
and 0.082% among non-African sequences, supporting the view of a low
nucleotide diversity (≈0.1%) in humans. The comparable π value in
non-Africans to that in Africans indicates no severe bottleneck during
the evolution of modern non-Africans; however, the possibility of a
mild bottleneck cannot be excluded because non-Africans showed
considerably fewer variants than Africans. The present and two previous
large data sets all show a strong excess of low frequency variants in
comparison to that expected from an equilibrium population, indicating
a relatively recent population expansion. The mutation rate was
estimated to be 1.15 × 10
−9
per nucleotide per year.
Estimates of the long-term effective population size

N
e

by various statistical methods were
similar to those in other studies. The age of the most recent common
ancestor was estimated to be ≈1.29 million years ago among all of the
sequences obtained and ≈634,000 years ago among the non-African
sequences, providing the first evidence from a noncoding autosomal
region for ancient human histories, even among non-Africans.
Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud
Authors: Karihaloo Anil , Karumanchi S. Ananth , Barasch Jonathan , Jha Vivekanand , Nickel Christian Hans , Yang Jun , Grisaru Silviu , Bush Kevin T. , Nigam Sanjay , Rosenblum Norman D. , Sukhatme Vikas P. , Cantley Lloyd G.
Published: July 2002

Endostatin (ES) inhibits endothelial cell migration and has been found to bind to glypicans (Gpcs) on both endothelial cells and renal epithelial cells. We examined the possibility that ES might regulate epithelial cell morphogenesis. The addition of ES to cultured epithelial cells causes an inhibition of both hepatocyte growth factor- and epidermal growth factor-dependent process formation and migration. In contrast, ES does not inhibit epidermal growth factor-dependent morphogenesis in renal epithelial cells derived from Gpc-3 −/mice, whereas expression of Gpc-1 in these cells reconstitutes ES responsiveness. Gpc-3 −/mice have been shown to display enhanced ureteric bud (UB) branching early in development, and cultured UB cells release ES into the media, suggesting that ES binding to Gpcs may regulate UB branching. The addition of ES inhibits branching of the explanted UB, whereas a neutralizing Ab to ES enhances UB outgrowth and branching. Thus, local expression of ES at the tips of the UB may play a role in the regulation of UB arborization.
Dynamic copy choice: Steady state between murine leukemia virus polymerase and polymerase-dependent RNase H activity determines frequency of
in vivo
template switching
Authors: Hwang Carey K. , Svarovskaia Evguenia S. , Pathak Vinay K.
Published: July 2002

We recently proposed a dynamic copy-choice model for retroviral recombination in which a steady state between the rates of polymerization and RNA degradation determines the frequency of reverse transcriptase (RT) template switching. The relative contributions of polymerase-dependent and polymerase-independent RNase H activities during reverse transcription and template switching
in vivo
have not been determined. We developed an
in vivo
trans-complementation assay in which direct repeat deletion through template switching reconstitutes a functional green fluorescent protein gene in a retroviral vector. Complementation in trans between murine leukemia virus Gag-Pol proteins lacking polymerase and RNase H activities restored viral replication. Because only polymerase-independent RNase H activity is present in this cell line, the relative roles of polymerase-dependent and -independent RNase H activities in template switching could be determined. We also analyzed double mutants possessing polymerase and RNase H mutations that increased and decreased template switching, respectively. The double mutants exhibited low template switching frequency, indicating that the RNase H mutations were dominant. Trans-complementation of the double mutants with polymerase-independent RNase H did not restore the high template switching frequency, indicating that polymerase-dependent RNase H activity was essential for the increased frequency of template switching. Additionally, trans-complementation of RNase H mutants in the presence and absence of hydroxyurea, which slows the rate of reverse transcription, showed that hydroxyurea increased template switching only when polymerase-dependent RNase H activity was present. This is, to our knowledge, the first demonstration of polymerase-dependent RNase H activity
in vivo
. These results provide strong evidence for a dynamic association between the rates of DNA polymerization and polymerase-dependent RNase H activity, which determines the frequency of
in vivo
template switching.
Mullerian-inhibiting substance regulates NF–κB signaling in the prostatein vitroandin vivo
Authors: Segev Dorry L. , Hoshiya Yasunori , Hoshiya Makiko , Tran Trinh T. , Carey Jennifer L. , Stephen Antonia E. , MacLaughlin David T. , Donahoe Patricia K. , Maheswaran Shyamala
Published: July 2002

Mullerian-inhibiting substance (MIS) is a member of the transforming growth factor β superfamily, a class of molecules that regulates growth, differentiation, and apoptosis in many cells. MIS type II receptor in the Mullerian duct is temporally and spatially regulated during development and becomes restricted to the most caudal ends that fuse to form the prostatic utricle. In this article, we have demonstrated MIS type II receptor expression in the normal prostate, human prostate cancer cell lines, and tissue derived from patients with prostate adenocarcinomas. MIS induced NF–κB DNA binding activity and selectively up-regulated the immediate early geneIEX-1Sin both androgen-dependent and independent human prostate cancer cellsin vitro. Dominant negative IκBα expression ablated both MIS-induced increase of IEX-1S mRNA and inhibition of growth, indicating that activation of NF–κB signaling was required for these processes. Androgen also induced NF–κB DNA binding activity in prostate cancer cells but without induction of IEX-1S mRNA, suggesting that MIS-mediated increase in IEX-1S was independent of androgen-mediated signaling. Administration of MIS to male mice induced IEX-1S mRNA in the prostatein vivo, suggesting that MIS may function as an endogenous hormonal regulator of NF–κB signaling and growth in the prostate gland.