bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating ozone variability and instrument uncertainties from SBUV(/2), ozonesonde, Umkehr, and SAGE II measurements: Short‐term variations
Authors: Fioletov V. E. , Tarasick D. W. , Petropavlovskikh I.
Published: January 2006

Coincident ozone measurements by the Solar Backscattered Ultra Violet (SBUV) and Stratospheric Aerosol and Gas Experiment (SAGE) II instruments and by ozonesondes and the Umkehr method are used to estimate stratospheric ozone variability and standard uncertainties of these different measurements. Below 20 km over northern midlatitudes, estimated measurement uncertainties for SBUV(/2), sondes, and Umkehr are similar (∼8% for 0 to 20 km integrated ozone), although only sondes have a high vertical resolution there. From 20 to 28 km., the estimated uncertainties (4–6%) for all four measurement sources are substantially smaller than the ozone variability in winter (10–15%), but they are comparable in summer (∼5%). Above 28 km, sonde uncertainties are larger than or comparable to the ozone variability, and much larger than uncertainties of SBUV(/2), Umkehr, or SAGE II data. Umkehr measurement uncertainties at 24–32 km are about 5% and are lower than sonde uncertainties (7–13%) at these levels. SBUV(/2) data are used to evaluate differences between different types of ozonesondes, and to show that correction by total ozone measurements noticeably reduces ozonesonde uncertainties. The latitudinal dependence of ozone variability and instrument uncertainties is studied using pairs of collocated SBUV(/2) and SAGE II measurements. There is good correlation between these measurements over middle and high latitudes. Over the tropical region, the correlation coefficients are modest (about 0.5) but significant in all layers except at 28–31 km. It is noted that where ozone variability is comparable to instrument uncertainties, comparison with a climatology based on a large number of observations may provide better insight into instrument performance than intercomparison of a small number of quasi‐coincident measurements.
Alpha Particle X‐Ray Spectrometer (APXS): Results from Gusev crater and calibration report
Authors: Gellert R. , Rieder R. , Brückner J. , Clark B. C. , Dreibus G. , Klingelhöfer G. , Lugmair G. , Ming D. W. , Wänke H. , Yen A. , Zipfel J. , Squyres S. W.
Published: January 2006

The chemical composition of rocks and soils on Mars analyzed during the Mars Exploration Rover Spirit Mission was determined by X‐ray analyses with the Alpha Particle X‐Ray Spectrometer (APXS). Details of the data analysis method and the instrument calibration are presented. Measurements performed on Mars to address geometry effects and background contributions are shown. Cross calibration measurements among several instrument sensors and sources are discussed. An unintentional swap of the two flight instruments is evaluated. New concentration data acquired during the first 470 sols of rover Spirit in Gusev Crater are presented. There are two geological regions, the Gusev plains and the Columbia Hills. The plains contain soils that are very similar to previous landing sites on Mars. A meteoritic component in the soil is identified. Rocks in the plains revealed thin weathering rinds. The underlying abraded rock was classified as primitive basalt. One of these rocks contained significant Br that is probably associated with vein‐filling material of different composition. One of the trenches showed large subsurface enrichments of Mg, S, and Br. Disturbed soils and rocks in the Columbia Hills revealed different elemental compositions. These rocks are significantly weathered and enriched in mobile elements, such as P, S, Cl, or Br. Even abraded rock surfaces have high Br concentrations. Thus, in contrast to the rocks and soils in the Gusev Plains, the Columbia Hills material shows more significant evidence of ancient aqueous alteration.
Active alignment for two-beam interferometers
Authors: Kalamatianos Dimitrios , Wellstead Peter E. , Edmunds John M. , Liatsis Panos
Published: January 2006

An active control system is described for the automatic alignment of the mirrors in a two-beam interferometer. From an initial unaligned position the active control system determines the degree of misalignment and adjusts the relative mirror positions accordingly. An embodiment of the system is described for a Michelson interferometer in which one of the mirrors is mounted upon three piezoelectric transducers (PZT) arranged so that they can both tilt and retard the mirror. Laser sources and corresponding photodetectors are also incorporated such that a control system can use the PZT actuators to produce a series of mirror movements relative to the fixed mirror and give a set of two-dimensional diffraction patterns—one for each of the laser photodetectors. Amplitude and phase information is extracted from these patterns which enables the control system to align the mirrors such that the diffraction pattern maxima is at the center of the instrument central photodetector. In a further stage of the control algorithm, the alignment accuracy is refined using information from the laser photodetectors during retardation of the mirror. In this manner, the initial mirror alignment, maintaining that alignment during retardation and diagnosis of possible misalignment, become part of a single active control technology for instrument alignment.
Surface elemental analysis in ambient atmosphere using electron-induced x-ray fluorescence
Authors: Urgiles Eduardo , Toda Risaku , Wilcox Jaroslava Z.
Published: January 2006

The progress in the development of the atmospheric electron x-ray spectrometer (AEXS) is described. The AEXS is a surface analysis tool based on excitation of characteristic x-ray fluorescence (XRF) spectra from samples in ambient atmospheres using a focused electron beam. Operation in ambient atmospheres with moderate-to-high spatial resolution in comparison to similar instruments is obtained through the use of a thin electron-transmissive membrane to isolate the vacuum of the electron probe, obviating the need for the samples to be drawn into the probe vacuum. Our initial setup that was used for the demonstration of the ability of the transmitted electrons to excite the XRF spectra in the external atmosphere consisted of an actively pumped chamber from within which the electrons were transmitted—not a portable instrument. The AEXS instrument that has been assembled in our laboratory during the past year consists of a miniature 20 keV electron microprobe that is vacuum sealed with a thin SiN membrane and requires no active pumping—a big step towards the development of a stand-alone instrument. The microprobe has been in operation for over one year and is used for performing rapid elemental analysis of NIST and USGS traceable metal and mineral standards, with good agreement with the certified composition for samples in up to about 90 Torr cm thick external atmospheres.
Generation of vortex rings by nonstationary laser wake field
Authors: Tsintsadze N. L. , Murtaza G. , Shah H. A.
Published: January 2006

A new concept of generating quasistatic magnetic fields, vortex rings, and electron jets in an isotropic homogeneous plasma is presented. The propagation of plasma waves, generated by a relativistically intense short pulse laser, is investigated by using the kinetic model and a novel nonpotential, time-dependent ponderomotive force is derived by obtaining a hydrodynamic equation of motion. This force can in turn generate quasistatic magnetic fields, vortex rings, and electron jets. It is also shown that the vortex rings can become a means for accelerating electrons, which are initially in equilibrium. The conservation of canonical momentum circulation and the frozen-in condition for the vorticity is discussed. The excitation of the vortex waves by the modulation of the amplitude of the plasma waves is considered. These vortex waves, which generate a lower hybrid mode propagating across the generated magnetic field, are also investigated.
Diffusion of spheres in isotropic and nematic suspensions of rods
Authors: Kang Kyongok , Wilk A. , Buitenhuis J. , Patkowski A. , Dhont Jan K. G.
Published: January 2006

Diffusion of a small tracer sphere (apoferritin) in isotropic and nematic networks [of fd virus] is discussed. For a tracer sphere that is smaller than the mesh size of the network, screened hydrodynamic interactions between the sphere and the network determine its diffusion coefficient. A theory is developed for such interactions as well as their relation to the long-time self-diffusion coefficient. Fluorescence correlation spectroscopy measurements on mixtures of apoferritin and fd virus are presented. The long-time self-diffusion coefficient of apoferritin is measured as a function of the fd-virus concentration, both in the isotropic and nematic state, in directions parallel and perpendicular to the nematic director. The hydrodynamic screening length of the fd-virus network as a function of fd concentration is obtained by combining these experimental data with the theory. Surprisingly, the screening length increases with increasing concentration in nematic networks. This is due to the increase in the degree of alignment, which apparently leads to a strong increase of the screening length. Hydrodynamic screening is thus strongly diminished by alignment. A self-consistent calculation of the screening length does not work at higher concentrations, probably due to the strong variation of the typical incident flow fields over the contour of a rod.
Catalytic action of β source on x-ray emission from plasma focus
Authors: Ahmad S. , Sadiq Mehboob , Hussain S. , Shafiq M. , Zakaullah M. , Waheed A.
Published: January 2006

The influence of preionization around the insulator sleeve by a mesh-type β source (Ni6328) for the x-ray emission from a (2.3-3.9 kJ) plasma focus device is investigated. Quantrad Si p-i-n diodes along with suitable filters are employed as time-resolved x-ray detectors and a multipinhole camera with absorption filters is used for time-integrated analysis. X-ray emission in 4π geometry is measured as a function of argon and hydrogen gas filling pressures with and without β source at different charging voltages. It is found that the pressure range for the x-ray emission is broadened, x-ray emission is enhanced, and shot to shot reproducibility is improved with the β source. With argon, the CuKα emission is estimated to be 27.14 J with an efficiency of 0.7% for β source and 21.5 J with an efficiency of 0.55% without β source. The maximum x-ray yield in 4π geometry is found to be about 68.90 J with an efficiency of 1.8% for β source and 54.58 J with an efficiency of 1.4% without β source. With hydrogen, CuKα emission is 11.82 J with an efficiency of 0.32% for β source and 10.07 J with an efficiency of 0.27% without β source. The maximum x-ray yield in 4π geometry is found to be 30.20 J with an efficiency of 0.77% for β source and 25.58 J with an efficiency of 0.6% without β source. The x-ray emission with Pb insert at the anode tip without β source is also investigated and found to be reproducible and significantly high. The maximum x-ray yield is estimated to be 46.6 J in 4π geometry with an efficiency of 1.4% at 23 kV charging voltage. However, degradation of x-ray yield is observed when charging voltage exceeds 23 kV for Pb insert. From pinhole images it is observed that the x-ray emission due to the bombardment of electrons at the anode tip is dominant in both with and without β source.
Customized analog circuit design for fiber-based optical coherence microscopy
Authors: Xu Wei , Bonnema Garret T. , Gossage Kirk W. , Wade Norman H. , Medford June , Barton Jennifer K.
Published: January 2006

Optical coherence microscopy (OCM) is an interferometric method for acquiring high-resolution, depth-resolved, en face images. In this article we demonstrate a fiber-based OCM system with analog fringe generation and signal demodulation. A high power operational amplifier drives a mirrored piezoelectric stack mounted in the reference arm of the interferometer causing a displacement equal to 0.42 times the light source center wavelength. The drive signal is synchronized with the demodulation frequency of two analog lock-in amplifiers which extract the first and second harmonics of the interferometric component of the signal. Four outputs (X and Y components of first and second harmonics) are acquired with a data-acquisition board and combined to eliminate the slow phase drift in the interferometer. A sample image of carrot tap root is presented. High dynamic range images are obtained at acquisition speeds up to 40000pixels∕s.
Apparatus for reactive cluster-surface studies
Authors: Christen Wolfgang , Rademann Klaus
Published: January 2006

We present a new instrument that has been specifically designed for systematic studies of reactive cluster-surface collisions under well-defined ultrahigh-vacuum conditions. As a key feature, it incorporates a temperature-controlled, high-pressure cluster source with an unsurpassed pulse-to-pulse stability for the generation of weakly bound molecular aggregates. Impact processes can be investigated in two experimental configurations complementing one another: In the first, the exploration of intracluster reactions of accelerated, size-selected, positively or negatively charged cluster ions (1–100eV∕molecule) is accomplished, employing an inert target surface combined with angular-integrated ion detection. This arrangement uses a compact, homebuilt dual time-of-flight mass spectrometer with excellent mass resolution m∕Δm>2000 and postacceleration capabilities. In the second configuration, the detailed analysis of chemical reactions between neutral clusters and a well-defined single crystal at lower kinetic energies (0.01–1eV∕molecule) is possible. Here, the surface interaction of a seeded supersonic cluster beam is probed with angular-, time-, and velocity-resolved detection of neutral reaction products using a high-performance quadrupole mass spectrometer.
Localized microwave resonances in strained SrTiO3 thin films
Authors: Irvin Patrick , Levy Jeremy , Haeni J. H. , Schlom Darrell G.
Published: January 2006

Local frequency-dependent polar dynamics of strained SrTiO3 films grown on DyScO3 are investigated using time-resolved confocal scanning optical microscopy. Spectroscopic information is obtained with <1μm spatial resolution over the frequency range 2–4GHz. Most of the DyScO3 film is found to be spatially homogeneous, in contrast to relaxed films. A strong correlation between spatial and spectral homogeneity is revealed. In addition, resonant structures are discovered that are localized both in space and in frequency.
Magnetic relaxation studies on a single-molecule magnet by time-resolved inelastic neutron scattering
Authors: Waldmann O. , Carver G. , Dobe C. , Biner D. , Sieber A. , Güdel H. U. , Mutka H. , Ollivier J. , Chakov N. E.
Published: January 2006

Time-resolved inelastic neutron scattering measurements on an array of single-crystals of the single-molecule magnet Mn12ac are presented. The data facilitate a spectroscopic investigation of the slow relaxation of the magnetization in this compound in the time domain.
Expandable fully reflective focal-plane optics for millimeter- and submillimeter-wave array receivers
Authors: Lüthi T. , Rabanus D. , Graf U. U. , Granet C. , Murk A.
Published: January 2006

We describe a focal-plane optics for millimeter- and submillimeter-wave array receivers which are both fully reflective—thus avoiding the absorption and reflection losses of dielectric lenses—and expandable to an arbitrary number of pixels. The optics unit cell consists of two mirrors and a feedhorn optimized for near-field operation. Employing an integrated optics approach the mirror setup consists of only three mechanical parts, independent of the number of pixels, and requires no internal optical alignment. With a 345GHz 3×3-beam prototype a Gaussicity of ⩾98% and a focal-plane beam separation of 3.6 waist radii was obtained. In this article we present the optics design as well as numerical simulations and measured beam patterns.
Evidence of surface acoustic wave band gaps in the phononic crystals created on thin plates
Authors: Zhang Xinya , Jackson Ted , Lafond Emmanuel , Deymier Pierre , Vasseur Jerome
Published: January 2006

Phononic structures and acoustic band gaps based on bulk materials have been researched in length in the past decades. However, few investigations have been performed on phononic structures in thin plates to form surface acoustic wave (SAW) band gaps. In this letter, we report a new type of phononic crystals manufactured by patterning periodical air-filled holes in thin plates. We confirmed the existence of SAW band gaps in the created phononic crystals through laser ultrasonics measurements. Wide multiple SAW band gaps and special structures, such as narrow pass bands within a band gap were observed experimentally.
Mechanical characterization of suspended GaN microstructures fabricated by GaN-on-patterned-silicon technique
Authors: Yang Z. , Wang R. N. , Jia S. , Wang D. , Zhang B. S. , Lau K. M. , Chen K. J.
Published: January 2006

The mechanical properties of high-quality suspended GaN microstructures fabricated by GaN-on-patterned-silicon technique are characterized. Micro-Raman scattering is used to study the stress distribution in the GaN microstructures, and the measured results show that the stress in GaN microbeams decreases 47% when the silicon underneath the microbeams is removed. Microbeam bending test is used to measure the Young’s modulus of GaN films grown on silicon (111) substrate, yielding a Young’s modulus of 330 GPa.
Laser pulse transmission through the water breakdown plasma in laser shock peening
Authors: Wu Benxin , Shin Yung C.
Published: January 2006

Laser shock peening (LSP) under a water confinement regime can produce plasma pressures on the target surface four times higher and 2–3 times longer than that under direct regime configurations. However, when the laser power density is above some threshold, a breakdown plasma occurs in water, which screens a significant amount of the incident laser pulse and therefore limits the magnitude and duration of the pressure induced on the target surface. A self-closed numerical model that can simulate the laser pulse transmission through the breakdown plasma generated in water during LSP has rarely been reported in literature. In this work, the breakdown plasma is simulated by solving an electron rate equation coupled with a Maxwell’s wave equation. The peak irradiance and duration of the laser pulse transmitted through the breakdown plasma predicted from the model can be correlated reasonably well with experimental data for 25 ns-1064 nm laser pulses. This model is then coupled with a previously developed thermal model for LSP to calculate the pressure pulse induced on the target surface. The trend of the pressure saturation and the pressure pulse duration decrease beyond some threshold laser irradiance is captured successfully by the model, and good agreements with experimental data have been obtained under a variety of LSP conditions.
ATM promotes apoptosis and suppresses tumorigenesis in response to Myc
Authors: Pusapati Raju V. , Rounbehler Robert J. , Hong SungKi , Powers John T. , Yan Mingshan , Kiguchi Kaoru , McArthur Mark J. , Wong Paul K. , Johnson David G.
Published: January 2006

Overexpression of thec-myconcogene contributes to the development of a significant number of human cancers. In response to deregulated Myc activity, the p53 tumor suppressor is activated to promote apoptosis and inhibit tumor formation. Here we demonstrate that p53 induction in response to Myc overexpression requires the ataxia-telangiectasia mutated (ATM) kinase, a major regulator of the cellular response to DNA double-strand breaks. In a transgenic mouse model overexpressing Myc in squamous epithelial tissues, inactivation ofAtmsuppresses apoptosis and accelerates tumorigenesis. Deregulated Myc expression induces DNA damage in primary transgenic keratinocytes and the formation of γH2AX and phospho-SMC1 foci in transgenic tissue. These findings suggest that Myc overexpression causes DNA damagein vivoand that the ATM-dependent response to this damage is critical for p53 activation, apoptosis, and the suppression of tumor development.
Dissection of a viral autoprotease elucidates a function of a cellular chaperone in proteolysis
Authors: Lackner T. , Thiel H.-J. , Tautz N.
Published: January 2006

Replication of positive-strand RNA viruses involves translation of polyproteins which are proteolytically processed into functional peptides. These maturation steps often involve virus-encoded autoproteases specialized in generating their own N or C termini. Nonstructural protein 2 (NS2) of the pestivirus bovine viral diarrhea virus represents such an enzyme. Bovine viral diarrhea virus NS2 creates in cis its own C terminus and thereby releases an essential viral replication factor. As a unique feature, this enzyme requires for proteolytic activity stoichiometric amounts of a cellular chaperone termed Jiv (J-domain protein interacting with viral protein) or its fragment Jiv90. To obtain insight into the structural organization of the NS2 autoprotease, the basis for its restriction to cis cleavage, as well as its activation by Jiv, we dissected NS2 into functional domains. Interestingly, an N-terminal NS2 fragment covering the active center of the protease, cleaved in trans an artificial substrate composed of a C-terminal NS2 fragment and two downstream amino acids. In the authentic NS2, the 4 C-terminal amino acids interfered with binding and cleavage of substrates offered in trans. These findings strongly suggest an intramolecular product inhibition for the NS2 autoprotease. Remarkably, the chaperone fragment Jiv90 independently interacted with protease and substrate domain and turned out to be essential for the formation of a protease/substrate complex that is required for cleavage. Thus, the function of the cell-derived protease cofactor Jiv in proteolysis is regulation of protease/substrate interaction, which ultimately results in positioning of active site and substrate peptide into a cleavage-competent conformation.
Nitric oxide regulates endocytosis by
S
-nitrosylation of dynamin
Authors: Wang Gaofeng , Moniri Nader H. , Ozawa Kentaro , Stamler Jonathan S. , Daaka Yehia
Published: January 2006

The GTPase dynamin regulates endocytic vesicle budding from the plasma membrane, but the molecular mechanisms involved remain incompletely understood. We report that dynamin, which interacts with NO synthase, is
S
-nitrosylated at a single cysteine residue (C607) after stimulation of the β
2
adrenergic receptor.
S
-nitrosylation increases dynamin self-assembly and GTPase activity and facilitates its redistribution to the membrane. A mutant protein bearing a C607A substitution does not self-assemble properly or increase its enzymatic activity in response to NO. In NO-generating cells, expression of dynamin C607A, like the GTPase-deficient dominant-negative K44A dynamin, inhibits both β
2
adrenergic receptor internalization and bacterial invasion. Furthermore, exogenous or endogenously produced NO enhances internalization of both β
2
adrenergic and epidermal growth factor receptors. Thus, NO regulates endocytic vesicle budding by
S
-nitrosylation of dynamin. Collectively, our data suggest a general NO-dependent mechanism by which the trafficking of receptors may be regulated and raise the idea that pathogenic microbes and viruses may induce
S
-nitrosylation of dynamin to facilitate cellular entry.
The methyl-CpG binding protein MBD1 is required for PML-RARα function
Authors: Villa Raffaella , Morey Lluis , Raker Veronica A. , Buschbeck Marcus , Gutierrez Arantxa , De Santis Francesca , Corsaro Massimo , Varas Florencio , Bossi Daniela , Minucci Saverio , Pelicci Pier Giuseppe , Di Croce Luciano
Published: January 2006

PML-RARα induces a block of hematopoietic differentiation and acute promyelocytic leukemia. This block is based on its capacity to inactivate target genes by recruiting histone deacetylase (HDAC) and DNA methyltransferase activities. Here we report that MBD1, a member of a conserved family of proteins able to bind methylated DNA, cooperates with PML-RARα in transcriptional repression and cellular transformation. PML-RARα recruits MBD1 to its target promoter through an HDAC3-mediated mechanism. Binding of HDAC3 and MBD1 is not confined to the promoter region but instead is spread over the locus. Knock-down of HDAC3 expression by RNA interference in acute promyelocytic leukemia cells alleviates PML-RAR-induced promoter silencing. We further demonstrate that retroviral expression of dominant-negative mutants of MBD1 in hematopoietic precursors compromises the ability of PML-RARα to block their differentiation and thus restored cell differentiation. Our results demonstrate that PML-RARα functions by recruiting an HDAC3-MBD1 complex that contributes to the establishment and maintenance of the silenced chromatin state.
The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases
Authors: Simonini M. V. , Camargo L. M. , Dong E. , Maloku E. , Veldic M. , Costa E. , Guidotti A.
Published: January 2006

The association of the histone deacetylase (HDAC) inhibitor valproate (VPA) with atypical antipsychotics has become a frequent treatment strategy for schizophrenia and bipolar disorder. Because the VPA doses administered are elevated, one cannot assume that the benefits of the VPA plus antipsychotic treatment are exclusively related to the covalent modifications of nucleosomal histone tails. We compared the actions of
N
-(2-aminophenyl)-4-[
N
-(pyridin-3-yl-methoxycarbonyl)aminomethyl]benzamide derivative (MS-275), which is a potent HDAC inhibitor
in vitro
, with the actions of VPA for their ability to (
i
) increase the acetylated status of brain nucleosomal histone tail domains and (
ii
) to regulate brain histone-
RELN
and histone-

GAD
67

promoter interactions. MS-275 increases the content of acetylhistone 3 (Ac-H3) in the frontal cortex. Whereas this response peaks after a s.c. injection of 15 μmol/kg, the increase in Ac-H3 content in the hippocampus becomes significant only after an injection of 60 μmol/kg, suggesting that MS-275 is 30- to 100-fold more potent than VPA in increasing Ac-H3 in these brain regions. In contrast to VPA, MS-275, in doses up to 120 μmol/kg, fails to increase Ac-H3 content in the striatum. Chromatin immunoprecipitation shows that MS-275 increases Ac-H3-
RELN
and Ac-H3-

GAD
67

promoter interaction in the frontal cortex. These results suggest that MS-275 is a potent brain region-selective HDAC inhibitor. It is likely that, in addition to MS-275, other benzamide derivatives, such as sulpiride, are brain-region selective inhibitors of HDACs. Hence, some benzamide derivatives may express a greater efficacy than VPA as an adjunctive to antipsychotics in the treatment of epigentically induced psychiatric disorders.
The Kernel Energy Method: Application to a tRNA
Authors: Huang Lulu , Massa Lou , Karle Jerome
Published: January 2006

The Kernel Energy Method (KEM) may be used to calculate quantum mechanical molecular energy by the use of several model chemistries. Simplification is obtained by mathematically breaking a large molecule into smaller parts, called kernels. The full molecule is reassembled from calculations carried out on the kernels. KEM is as yet untested for RNA, and such a test is the purpose here. The basic kernel for RNA is a nucleotide that in general may differ from those of DNA. RNA is a single strand rather than the double helix of DNA. KEM energy has been calculated for a tRNA, whose crystal structure is known, and which contains 2,565 atoms. The energy is calculated to be
E
= –108,995.1668 (a.u.), in the Hartree–Fock approximation, using a limited basis. Interaction energies are found to be consistent with the hydrogen-bonding scheme previously found. In this paper, the range of biochemical molecules, susceptible of quantum studies by means of the KEM, have been broadened to include RNA.
Theory of the deuterium NMR of sterol–phospholipid membranes
Authors: McConnell Harden , Radhakrishnan Arun
Published: January 2006

A general theoretical model is described for the NMR spectra of mixtures of sterols and deuterium-labeled phospholipids. In the case of homogeneous membranes, the average quadrupole splittings are determined by equilibria between lipids in cholesterol–phospholipid complexes and lipids not in complexes. Chemical exchange of lipids between those in the free state and those in the complex state affects the deuterium resonance line shapes. The lifetime of a phospholipid molecule in an ergosterol–dipalmitoylphosphatidylcholine complex is estimated to be of the order of 10
–5
s on the basis of the observed line broadenings. In the vicinity of a critical point of a cholesterol–phospholipid mixture, fluctuations in the concentration of complexes also can contribute to the deuterium nuclear resonance line broadening. At the critical point, the temperature derivative of the concentration of complexes is discontinuous. There is a corresponding jump in the calculated heat capacity as well as in the temperature derivative of the deuterium NMR first moment.
Role of β-arrestin 1 in the metastatic progression of colorectal cancer
Authors: Buchanan F. Gregory , Gorden D. Lee , Matta Pranathi , Shi Qiong , Matrisian Lynn M. , DuBois Raymond N.
Published: January 2006

G protein-coupled receptor ligand-dependent transactivation of growth factor receptors has been implicated in human cancer cell proliferation, migration, and cell survival. For example, prostaglandin E
2
(PGE
2
)-induced transactivation of the EGF receptor (EGFR) in colorectal carcinoma cells is mediated by means of a c-Src-dependent mechanism and regulates cell proliferation and migration. Recent evidence indicates that β-arrestin 1 may act as an important mediator in G protein-coupled receptor-induced activation of c-Src. Whether β-arrestin 1 serves a functional role in these events is, however, unknown. We investigated the effects of PGE
2
on colorectal cancer cells expressing WT and mutant β-arrestin 1. Here we report that PGE
2
induces the association of a prostaglandin E receptor 4/β-arrestin 1/c-Src signaling complex resulting in the transactivation of the EGFR and downstream Akt (PKB) signaling. The interaction of β-arrestin 1 and c-Src is critical for the regulation of colorectal carcinoma cell migration
in vitro
as well as metastatic spread of disease to the liver
in vivo
. These results show that the prostaglandin E/β-arrestin 1/c-Src signaling complex is a crucial step in PGE
2
-mediated transactivation of the EGFR and may play a pivotal role in tumor metastasis. Furthermore, our data implicate a functional role for β-arrestin 1 as a mediator of cellular migration and metastasis.
Inactivation of PU.1 in adult mice leads to the development of myeloid leukemia
Authors: Metcalf Donald , Dakic Aleksandar , Mifsud Sandra , Di Rago Ladina , Wu Li , Nutt Stephen
Published: January 2006

Genetically primed adult C57BL mice were deleted of exon 5 of the gene encoding the transcription factor PU.1 by IFN activation of Cre recombinase. After a 13-week delay, conditionally deleted (
PU.1
-/-
) mice began dying of myeloid leukemia, and 95% of the mice surviving from early postinduction death developed transplantable myeloid leukemia whose cells were deleted of PU.1 and uniformly Gr-1 positive. The leukemic cells formed autonomous colonies in semisolid culture with varying clonal efficiency, but colony formation was enhanced by IL-3 and sometimes by granulocyte-macrophage colony-stimulating factor. Nine of 13 tumors analyzed had developed a capacity for autocrine IL-3 or granulocyte-macrophage colony-stimulating factor production, and there was evidence of rearrangement of the
IL-3
gene. Acquisition of autocrine growth-factor production and autonomous growth appeared to be major events in the transformation of conditionally deleted
PU.1
-/-
cells to fully developed myeloid leukemic populations.
Olig2
+
neuroepithelial motoneuron progenitors are not multipotent stem cells
in vivo
Authors: Mukouyama Yoh-suke , Deneen Benjamin , Lukaszewicz Agnès , Novitch Bennett G. , Wichterle Hynek , Jessell Thomas M. , Anderson David J.
Published: January 2006

Neurons and glia are thought to arise from multipotent and self-renewing stem cells, which comprise the majority of neuroepithelial cells in the ventricular zone (VZ) of the early embryonic CNS. However, this idea remains to be tested rigorously, because CNS stem cells have been identified only by using
in vitro
assays, from which their abundance
in vivo
cannot be directly inferred. In the hematopoietic system, stem cells are characterized by using prospective isolation and direct
in vivo
transplantation. Here we have used this approach to ask whether most VZ progenitors behave as stem cells
in vivo
. The best-studied region of the embryonic CNS for addressing this problem is, arguably, the ventral spinal cord, within which progenitors in the motoneuron progenitor (pMN) domain sequentially generate motoneurons (MNs) and oligodendrocyte precursors (OPs). Virtually all VZ cells in pMN express the transcription factor Olig2. If most of these cells are stem cells, then they should maintain neurogenic potential, even at later, gliogenic stages. To test this hypothesis, we have prospectively isolated Olig2
+
cells from murine embryonic day (E)9.5 and E13.5 spinal cord and directly transplanted them to E2 chick spinal cord. Transplanted E9.5 cells generate both neurons, including MNs and OPs, whereas E13.5 cells generate. The observation that most Olig2
+
progenitors do not maintain neurogenic potential into the period of gliogenesis argues that they do not self-renew. These results do not support the commonly held view that most neuroepithelial cells in the embryonic CNS VZ are stem cells
in vivo
.
Simultaneous molecular imaging of redox reactions monitored by Overhauser-enhanced MRI with
14
N- and
15
N-labeled nitroxyl radicals
Authors: Utsumi Hideo , Yamada Ken-ichi , Ichikawa Kazuhiro , Sakai Kiyoshi , Kinoshita Yuichi , Matsumoto Shingo , Nagai Mika
Published: January 2006

MRI has provided significant clinical utility in the diagnosis of diseases and will become a powerful tool to assess phenotypic changes in genetically engineered animals. Overhauser enhanced MRI (OMRI), which is a double resonance technique, creates images of free radical distributions in small animals by enhancing the water proton signal intensity by means of the Overhauser effect. Several studies have demonstrated noninvasive assessment of reactive oxygen species generation in small animals by using low frequency electron spin resonance (ESR) spectroscopy/imaging and nitroxyl radicals.
In vivo
ESR signal intensities of nitroxyl radicals decrease with time after injection; and the decreases are enhanced by reactive oxygen species, generated in oxidative disease models in a site-specific manner. In this study, we show images of nitroxyl radicals with different isotopes by changing the external magnetic field for ESR irradiation between
14
N and
15
N nuclei in field-cycled OMRI. OMRI simultaneously obtained dual images of two individual chemical processes. Oxidation and reduction were monitored in a rate-dependent manner at nanometer scale by labeling membrane-permeable and -impermeable nitroxyl radicals with
14
N and
15
N nuclei. Phantom objects containing ascorbic acid-encapsulated liposomes with membrane-permeable radicals but not membrane-impermeable ones show a time-dependent decrease of the OMRI image intensity. The pharmacokinetics in mice was assessed with OMRI after radical administration. This OMRI technique with dual probes should offer significant applicability to nanometer scale molecular imaging and simultaneous assessment of independent processes in gene-modified animals. Thus, it may become a powerful tool to clarify mechanisms of disease and to monitor pharmaceutical therapy.
Variable molecular clocks in hominoids
Authors: Elango Navin , Thomas James W. ,   NISC Comparative Sequencing Program§, Yi Soojin V.
Published: January 2006

Generation time is an important determinant of a neutral molecular clock. There are several human-specific life history traits that led to a substantially longer generation time in humans than in other hominoids. Indeed, a long generation time is considered an important trait that distinguishes humans from their closest relatives. Therefore, humans may exhibit a significantly slower molecular clock as compared to other hominoids. To investigate this hypothesis, we performed a large-scale analysis of lineage-specific rates of single-nucleotide substitutions among hominoids. We found that humans indeed exhibit a significant slowdown of molecular evolution compared to chimpanzees and other hominoids. However, the amount of fixed differences between humans and chimpanzees appears extremely small, suggesting a very recent evolution of human-specific life history traits. Notably, chimpanzees also exhibit a slower rate of molecular evolution compared to gorillas and orangutans in the regions analyzed.
Cancer-specific mutations in
PIK3CA
are oncogenic
in vivo
Authors: Bader Andreas G. , Kang Sohye , Vogt Peter K.
Published: January 2006

The
PIK3CA
gene, coding for the catalytic subunit p110α of class IA phosphatidylinositol 3-kinases (PI3Ks), is frequently mutated in human cancer. Mutated p110α proteins show a gain of enzymatic function
in vitro
and are oncogenic in cell culture. Here, we show that three prevalent mutants of p110α, E542K, E545K, and H1047R, are oncogenic
in vivo
. They induce tumors in the chorioallantoic membrane of the chicken embryo and cause hemangiosarcomas in the animal. These tumors are marked by increased angiogenesis and an activation of the Akt pathway. The target of rapamycin inhibitor RAD001 blocks tumor growth induced by the H1047R p110α mutant. The
in vivo
oncogenicity of PIK3CA mutants in an avian species strongly suggests a critical role for these mutated proteins in human malignancies.
Effects of Galanthus nivalis agglutinin (GNA) expressed in tomato leaves on larvae of the tomato moth Lacanobia oleracea (Lepidoptera: Noctuidae) and the effect of GNA on the development of the endoparasitoid Meteorus gyrator (Hymenoptera: Braconidae)
Authors: Wakefield M.E. , Bell H.A. , Fitches E.C. , Edwards J.P. , Gatehouse A.M.R.
Published: January 2006

The effect of ingestion of transgenic tomato leaves expressing the plant lectin Galanthus nivalis agglutinin (GNA) on development of larvae of Lacanobia oleracea (Linnaeus) was studied under laboratory conditions. When L. oleracea larvae were fed on tomato line 14.1H, expressing approximately 2.0% GNA, significant increases in the mean larval weight and in the amount of food consumed were found. This resulted in an overall reduction in the mean development time to the pupal stage of approximately 7 days. A significant increase in the percentage survival to the adult moth was also recorded when newly hatched larvae were reared on transgenic tomato leaves (72%) compared to larvae reared on untransformed leaves (40%). The effects of ingestion of GNA by L. oleracea larvae, via artificial diet or the leaves of transgenic tomato or potato plants, on the subsequent development of its solitary endoparasitoid Meteorus gyrator (Thunberg) was also studied. No significant effects on the life cycle parameters of M. gyrator developing in L. oleracea fed on GNA-containing diets were observed. Experiments with transgenic potato plants indicated that the stadium of the host larvae at parasitism had a greater influence on M. gyrator development than the presence of GNA. Potential GNA-binding glycoproteins were detected in the gut and body tissues of larval M. gyrator. Despite detection in host tissues, GNA could not be detected in adult M. gyrator and therefore it is likely that at the time of pupation M. gyrator are able to void the GNA in the meconial pellet.
The effect of bait design on bait consumption in termites (Isoptera: Rhinotermitidae)
Authors: Evans T.A. , Gleeson P.V.
Published: January 2006

The efficacy of baiting as a pest control method relies on the bait appealing to the pest species. In the case of wood-eating termites, bait stations should be designed to encourage termite presence and to maximize their consumption of bait matrix in order to expedite control in minimal time. A field experiment examined the effect of bait size (one large bait or four small baits of equivalent total size, with commensurate inspection and replacement schedules), compaction (tightly rolled or loosely folded) and composition (paper only or paper plus wood) on termite presence and on untreated bait paper removal rates over four months. All three factors were significant, with bait size the most important factor, followed by compaction and then composition. The least effective baits were small, compacted (rolled) paper-only baits with monthly inspections; these had the highest abandonment rate (70%) and had the least paper removed (mean of 24 g). The most effective baits were large, folded paper-plus-wood baits with inspections at two months; these had the lowest abandonment rate (20%) and had the highest paper removal (mean of 112 g). The more than four-fold difference between these baits types demonstrates that bait efficacy can be altered considerably merely by changing bait design without adding new ingredients to the bait matrix.
Molecular methods for assessing insect parasitism
Authors: Greenstone M.H.
Published: January 2006

Determining insect parasitism rates is problematic due to the small size and lack of useful distinguishing morphological characters of many parasitoid taxa. To solve this problem, entomologists have employed one of four general methods to detect parasitoid protein or nucleic acid markers: serological assay; random amplified polymorphic DNA–polymerase chain reaction “RAPD-PCR” allozyme electrophoresis; or specific PCR. Serological methods, especially with monoclonal antibodies, are unrivalled for specificity, enabling discrimination at the stage as well as species level. However, they have not found favour with many workers, possibly due to complexity and expense. RAPD–PCR has been widely used, but can only be recommended for restricted applications because of its poor reproducibility. Allozyme electrophoresis provides reproducible detection and discrimination of closely related species. Specific-PCR is highly specific and reproducible, and also has the shortest latency for detection, usually 24 h or less after parasitization. The substantial existing literature on allozyme electrophoresis and specific PCR is used to support recommendations on what are apt to be fruitful enzyme systems or genomic regions for detecting and discriminating parasitoids in untried parasitoid–host assemblages.
Midgut proteases of the cardamom shoot and capsule borer Conogethes punctiferalis (Lepidoptera: Pyralidae) and their interaction with aprotinin
Authors: Josephrajkumar A. , Chakrabarty R. , Thomas G.
Published: January 2006

Protease inhibitors cause mortality in a range of insects, and transgenic plants expressing protease inhibitors have been protected against pest attack, particularly internal feeders that are not amenable to control by conventional means. A study of luminal proteases in Conogethes punctiferalis Guenée was performed to identify potential targets for proteinaceous biopesticides, such as protease inhibitors. The midgut protease profile of the gut lumen from C. punctiferalis was studied to determine the conditions for optimal protein hydrolysis. Optimum conditions for peptidase activity were found to be in 50 mm Tris-HCl, pH 10 containing 20 mm CaCl2; incubation for 30 min at 40°C. Four synthetic substrates, i.e. benzoyl-arg-p-nitroanilide, benzoyl-tyr-p-nitroanilide, succinyl-ala-ala-pro-leu-p-nitroanilide (SAAPLpNA) and leu-p-nitroanilide were hydrolysed by C. punctiferalis gut proteases in Tris-HCl buffer pH 10. Trypsin and elastase-like chymotrypsin were the prominent digestive proteases, and age-related modulation of midgut proteases existed for trypsin, chymotrypsin, elastase-like chymotrypsin and leucine aminopeptidase. Serine protease inhibitors such as aprotinin, soybean trypsin inhibitor and phenylmethanesulfonyl fluoride inhibited peptidase activity. Some metal ions such as Ca2+, Mg2+, Pb2+ and Co2+ enhanced BApNA-ase activity whereas others like Mn2+, Zn2+, Cu2+, Fe2+ and Hg2+ were inhibitory at 6 mm concentration. Trypsin and elastase-like chymotrypsin were significantly inhibited by 94% and 29%, respectively, by aprotinin (150 nm) under in vitro conditions. A possible incorporation of protease inhibitors into transgenic plants is discussed.
Biological effects of fruit and vegetables
Authors: Dragsted Lars O. , Krath Britta , Ravn-Haren Gitte , Vogel Ulla B. , Vinggaard Anne Marie , Jensen Per Bo , Loft Steffen , Rasmussen Salka E. , Sandstrom BrittMarie , Pedersen Anette
Published: January 2006

A strong and persistent effect of plant-derived foods on the prevention of lifestyle diseases has emerged from observational studies. Several groups of constituents in plants have been identified as potentially health promoting in animal studies, including cholesterol-lowering factors, antioxidants, enzyme inducers, apoptosis inducers etc. In human intervention studies the dose levels achieved tend to be lower than the levels found to be effective in animals and sampling from target organs is often not possible. A controlled dietary human intervention study was performed with forty-three volunteers, providing 600 g fruit and vegetables/d or in the controls a carbohydrate-rich drink to balance energy intake. Surrogate markers of oxidative damage to DNA, protein and lipids, enzymic defence and lipid metabolism were determined in blood and urine. It was found that a high intake of fruit and vegetables tends to increase the stability of lipids towards oxidative damage. Markers of oxidative enzymes indicate a steady increase in glutathione peroxidase (GPX1) activity in erythrocytes during intervention with fruit and vegetables but there is no effect on GPX1 transcription levels in leucocytes. No change occurs in glutathione-conjugating or -reducing enzyme activities in erythrocytes or plasma, and there are no effects on the transcription of genes involved in phase 2 enzyme induction or DNA repair in leucocytes. Fruit and vegetable intake decreases the level of total cholesterol and LDL-cholesterol, but does not affect sex hormones. In conclusion, it has been shown that total cholesterol and LDL-cholesterol, markers of peripheral lipid oxidation, and erythrocyte GPX1 activity are affected by high intakes of fruit and vegetables. This finding provides support for a protective role of dietary fruit and vegetables against CVD.