bluuebunny/crossref_metadata_2025 huggingface dataset:
Refractive indices of semiconductor films measured by waveguide cutoff spectroscopy
Authors: Morasca S. , Sordo B. , De Bernardi C. , Meliga M.
Published: July 2002

It is shown that by measuring the cutoff wavelengths of supported modes in waveguides it is possible to determine accurately the refractive index of the guiding layer. This method has been applied to InGaAsP/InP waveguides, and their refractive indices are obtained with accuracy to the third decimal place.
Be+/P+ and Be+/As+ dual implantations into AlxGa1−xAs
Authors: Yamahata Shoji , Adachi Sadao
Published: July 2002

Dual implantations of Be+/P+ (Be+ and P+ ions) and Be+/As+ (Be+ and As+ ions) into Al0.3 Ga0.7 As are carried out, and electrical properties of the implanted layers are evaluated by Hall-effect measurements. Improved electrical activity is observed for the dual implant compared with the single implant. In particular, in the case of the Be+/P+ dual implant, apparent hole concentration becomes nearly twice as high as that of the Be+ single implant at annealing temperatures above 650 °C. The dual implantation technique also greatly suppresses redistribution of Be atoms, and so Gaussian-type profiles remain, even after high-temperature annealing (∼950 °C).
Excimer laser-assisted metalorganic vapor phase epitaxy of CdTe on GaAs
Authors: Zinck J. J. , Brewer P. D. , Jensen J. E. , Olson G. L. , Tutt L. W.
Published: July 2002

We have successfully grown CdTe (111) on GaAs (100) at 165 °C using a 248 nm excimer laser to photodissociate dimethylcadmium and diethyltellurium in the gas phase. Good crystalline quality of the layers is confirmed by x-ray diffractometry. Growth rates up to 2 μm/h have been recorded in real time using time-resolved reflectivity. Auger analysis reveals that the films are stoichiometric throughout the thickness of the layer, and that carbon and oxygen contaminants are below the level of detectability. We have used laser-induced fluorescence spectroscopy to examine the photodissociation mechanism of diethyltellurium and have observed a linear dependence of Te atom production on excimer laser power.
Short-wavelength (∼625 nm) room-temperature continuous laser operation of In0.5(AlxGa1−x)0.5P quantum well heterostructures
Authors: Nam D. W. , Deppe D. G. , Holonyak N. , Fletcher R. M. , Kuo C. P. , Osentowski T. D. , Craford M. G.
Published: July 2002

Data are presented demonstrating very-short-wavelength (625 nm) room-temperature (300 K) continuous (cw) photopumped laser operation of In1−y(AlxGa1−x)yP-In1−y (AlxGa1−x)yP quantum well heterostructures grown lattice matched (y≊0.5) on a GaAs substrate via metalorganic chemical vapor deposition. In addition, 300 K pulsed laser operation (Jth∼104 A/cm2, 625 nm) of diodes fabricated from the same crystal is described.
Pseudomorphic ZnSe/n-GaAs doped-channel field-effect transistors by interrupted molecular beam epitaxy
Authors: Studtmann G. D. , Gunshor R. L. , Kolodziejski L. A. , Melloch M. R. , Cooper J. A. , Pierret R. F. , Munich D. P. , Choi C. , Otsuka N.
Published: July 2002

The fabrication and current-voltage characteristics of the first depletion-mode field-effect transistors based on a pseudomorphic ZnSe/n-GaAs heterointerface are described. The devices are doped-channel field-effect transistors produced by means of interrupted growth with the use of two separate molecular beam epitaxy systems. Very strong (visible to the naked eye) reflection high-energy electron diffraction intensity oscillations persist for 120 periods when ZnSe is nucleated on the GaAs epilayer. The current-voltage characteristics of the transistors are close to ideal; channel modulation indicates that the Fermi level is not pinned at the ZnSe/GaAs interface.
Laser-assisted metalorganic molecular beam epitaxy of GaAs
Authors: Donnelly V. M. , Tu C. W. , Beggy J. C. , McCrary V. R. , Lamont M. G. , Harris T. D. , Baiocchi F. A. , Farrow R. C.
Published: July 2002

We report preliminary studies of the growth of homoepitaxial GaAs by laser-assisted metalorganic molecular beam epitaxy, using triethylgallium (TEGa) and As4 sources and a 193 nm ArF excimer laser. Laser irradiation results in a high, selective-area growth rate at temperatures below 450 °C, where pyrolytic growth is very slow. The process is extremely efficient, with roughly unit probability for impinging TEGa molecules sticking and being dissociated by laser radiation to form GaAs. From the strong dependence on laser fluence, the growth enhancement process appears to be pyrolytic in nature (because of transient heating by the pulsed laser) and not photolytic. The cross section for photolysis must be at least ten times lower than the gas-phase value (9×10−18 cm2). The surface morphology of films grown at 400 °C is rough at threshold fluences (∼0.10 J/cm2), but becomes smooth at higher fluences (∼0.13 J/cm2). These regions with relatively smooth surfaces exhibit enhanced photoluminescence yields compared to areas receiving less intense laser radiation.
Laser-modified molecular beam epitaxial growth of (Al)GaAs on GaAs and (Ca,Sr)F2/GaAs substrates
Authors: Tu C. W. , Donnelly V. M. , Beggy J. C. , Baiocchi F. A. , McCrary V. R. , Harris T. D. , Lamont M. G.
Published: July 2002

We report results on the effect of a 193 nm ArF excimer laser on molecular beam epitaxial growth of (Al)GaAs on GaAs substrates and GaAs on lattice-matched (Ca,Sr)F2/GaAs heterostructures. For growth on GaAs substrates, regions exposed to the laser show photoluminescence and excellent channeling as determined by Rutherford backscattering spectroscopy, whereas regions outside the laser show no photoluminescence. For growth on (Ca,Sr)F2 surfaces, laser irradiation inhibits the growth of GaAs for fluences above a critical value of 0.12 J/cm2 pulse because of laser-induced desorption of absorbed Ga atoms, which are relatively weakly bound to (Ca,Sr)F2, compared to GaAs surfaces.
Effect of annealing on the optical properties of HgTe-CdTe superlattices
Authors: Leopold D. J. , Broerman J. G. , Peterman D. J. , Wroge M. L.
Published: July 2002

HgTe-CdTe superlattices of high crystalline quality, and with negligible interdiffusion, have been successfully grown at low substrate temperatures (150–170 °C) by molecular beam epitaxy. Optical spectra exhibiting multiple steplike absorption edge features have been measured on as-grown and thermally annealed samples. The data provide valuable information on the superlattice subband structure when coupled with a suitable model. These results then can be used to obtain semiquantitative measures of layer interdiffusion along with such quantities as valence-band offset and strain. To observe subband structure in the optical data, it is necessary to fabricate samples having homogeneous HgTe and CdTe layer thicknesses in the superlattice growth direction. Homogeneity of layers was achieved by carefully controlling elemental source fluxes and shutter times during the epitaxial growth process. Substantial changes in the subband-related absorption structure could be induced by annealing the superlattice samples at temperatures just slightly above the growth temperature. An observed shift of the fundamental absorption edge to higher energy, as well as an apparent broadening of the subband absorption structure upon annealing, can be explained by interdiffusion of HgTe and CdTe layers.
Photocurrent enhancement in a GaAs metal-semiconductor-metal photodetector due to ultrasmall Au islands
Authors: Koscielniak W. C. , Kolbas R. M. , Littlejohn M. A. , Licznerski B. W.
Published: July 2002

A new GaAs metal-semiconductor-metal photodetector has been demonstrated which uses ultrasmall gold islands deposited on a lightly doped epitaxial layer. The fabricated devices showed an appreciable photocurrent enhancement with respect to conventional metal-semiconductor-metal devices at a bias of less than 4 V and soft breakdown characteristics above 4 V. Details of the fabrication procedure are presented, and some possible mechanisms to explain this enhancement are suggested.
Characterization of InP/GaAs epilayers grown on Si substrates by low-pressure organometallic vapor phase epitaxy
Authors: Lee M. K. , Wuu D. S. , Tung H. H. , Yu K. Y. , Huang K. C.
Published: July 2002

Heteroepitaxial growth of InP on Si with an intermediate GaAs buffer layer by low-pressure organometallic vapor phase epitaxy is reported. Excellent crystallinity of InP epilayers with specular surfaces can be reproducibly obtained. The carrier concentration profile shows that the carrier distribution in the InP layer is very uniform, while an apparent reduction in concentration occurs at the InP/GaAs interface. The 77 K photoluminescence (PL) of the InP layer exhibits a strong near-band-edge emission. No evident shift in PL peak energy for the InP/GaAs/Si sample compared with that for the InP homoepitaxial sample was first observed in this study. These results are superior to those reported previously for the InP/Si heteroepitaxy.
Determination of the fixed oxide charge and interface trap densities for buried oxide layers formed by oxygen implantation
Authors: Brady F. T. , Li S. S. , Burk D. E. , Krull W. A.
Published: July 2002

Capacitance-voltage measurements were used to analyze buried oxide layers formed by the implantation of oxygen into silicon substrates. The analysis is based on the extension of conventional metal/oxide/semiconductor capacitor theory to the two buried oxide interfaces of the epilayer/oxide/substrate structure. The processing parameters include oxygen doses of 1.8 or 2.0×1018 cm−2, implant temperature of 500 °C, and anneal temperature of 1250 °C for 2 or 16 h. The results are fixed oxide charge densities of 2–3×1011 and 1–2×1010 cm−2 for the epi/oxide and substrate/oxide interfaces, respectively; interface trap densities are 0.5 to 2×1011 cm−2 eV−1 for the epi/oxide interface, and not measurable for the substrate/oxide interface. The epilayer/oxide interface was found to be more sensitive to processing variations than the substrate/oxide interface.
Energy transport in aluminum targets irradiated by a 263-nm laser
Authors: Yamauchi A. , Tanaka K. A. , Kodama R. , Kado M. , Yamanaka T. , Mochizuki T. , Nakai S. , Yamanaka C.
Published: July 2002

Emission from the rear side of 263-nm laser irradiated thin foil targets shows the temporal profile of rear surface heating by several processes with different energy transport mechanisms. Formation and decay of shock waves are observed by varying target thickness. Propagation of a thermal conduction wave is clearly separated from the shock propagation.
Unstable resonator with phase-unifying coupler for high-power lasers
Authors: Yasui Koji , Tanaka Masaaki , Yagi Shigenori
Published: July 2002

A novel unstable resonator with a phase-unifying output coupler has been developed. The output coupler structured with a partial-reflection region in its center surrounded by an antireflection region unifies the phases of laser beams passing through these regions. Thus, a near-Gaussian far-field pattern beam has been obtained with a divergence full-angle of 1.08 mrad on the application to a high-power cw CO2 laser.
Optical and electronic properties of an amorphous silicon-germanium alloy with a 1.28 eV optical gap
Authors: Kolodzey J. , Schwarz R. , Aljishi S. , Chu V. , Shen D.-S. , Fauchet P. M. , Wagner S.
Published: July 2002

We report the deposition and comprehensive evaluation of a hydrogenated, fluorinated amorphous silicon-germanium alloy with an optical gap of 1.28 eV. This low-gap alloy of the a-Si, Ge system possesses a small midgap defect density (6.5×1016 cm−3), and useful electron (σph/σd=23) and hole (LD=0.13 μm) transport properties. The alloy was grown by radio-frequency plasma-enhanced decomposition of SiF4, GeF4, and H2 in a reactor built to ultrahigh-vacuum specifications.
Nonlinear optical absorption in an n-InGaAsP/p-InP heterodoping superlattice
Authors: Kobayashi H. , Yamauchi Y. , Ando H.
Published: July 2002

Absorptive optical nonlinearity in an n-InGaAsP/p-InP heterodoping superlattice grown by vapor phase epitaxy is investigated. Although change in the absorption coefficient per an excited carrier obtained for the doping superlattice is comparable to that of bulk material, larger nonlinear absorption is induced by unit-intensity light illumination. This enhancement is attributable to prolonged carrier recombination lifetime due to the separation of electrons and holes in space. The nonlinear absorption caused by accumulated photocarriers can be explained by the combination of two effects: blocking of direct band-to-band transition in real space (band filling effect), and change in probability of indirect transition in real space (Franz–Keldysh effect) due to a modified internal electric field.
Mode control in broad-area diode lasers by thermally induced lateral index tailoring
Authors: Hohimer J. P. , Hadley G. R. , Owyoung A.
Published: July 2002

Broad-area diode lasers that emit in the fundamental mode under short-pulse excitation are observed to evolve into higher order lateral modes with increasing pulse width. Our data provide convincing evidence that the lateral refractive index profile arising from junction heating plays a dominant role in determining the lateral emission modes in these devices for long-pulse and cw operation. Furthermore, we show that an external focused laser heat source can be used to modify the lateral index profile in a broad-area laser and thus control the lasing mode. In particular, we demonstrate that ≲50 mW of absorbed heating power is sufficient to counteract the effects of internal junction heating and restore fundamental mode operation at cw injection currents as high as 1.5 Ithreshold. Our results suggest that fundamental mode operation of broad-area devices at high-power levels might be realized by incorporating a tailored lateral index profile to compensate for internal junction heating.
High-quality GaInAsP/InP heterostructures grown by low-pressure metalorganic chemical vapor deposition on silicon substrates
Authors: Razeghi M. , Omnes F. , Defour M. , Maurel Ph.
Published: July 2002

High-quality bulk InP and double heterostructure InP/GaInAsP/InP have been grown on silicon substrates by a low-pressure metalorganic chemical vapor deposition growth technique. X-ray diffraction patterns, as well as structural characterizations, indicate that the layers have very good crystalline quality. An intense photoluminescence signal from the quaternary alloy GaxIn1−xAsyP1−y has been recorded at room temperature, at the expected value of 1.3 μm.
Characterization of oval defects in molecular beam epitaxy Ga0.7Al0.3As layers by spatially resolved cathodoluminescence
Authors: Papadopoulo A. C. , Alexandre F. , Bresse J. F.
Published: July 2002

Oval defects in silicon-doped Ga0.7Al0.3As molecular beam epitaxy grown layers are studied by filtered cathodoluminescence at low temperatures (10 K) in a scanning electron microscope. The spectra obtained inside and outside the defects exhibit very different main emission lines which can be explained by an important variation of the Al/Ga ratio at the center of the defects; this hypothesis is confirmed by localized Auger electron spectroscopy.
Characteristics of p-n junctions fabricated on Hg1−xCdxTe epilayers grown by molecular beam epitaxy
Authors: Faurie J. P. , Sivananthan S. , Lange M. , Dewames R. E. , Vandewyck A. M. B. , Williams G. M. , Yamini Dan , Yao E.
Published: July 2002

p-n junctions have been fabricated, using the ion implantation technique, on a Hg1−xCdxTe epilayer grown by molecular beam epitaxy (MBE) on a CdTe(111)B substrate. These junctions have been made on as-grown p-type layers, 12 μm thick. The layer (x=0.34) exhibits at 77 K a hole mobility of 800 cm2 V−1 s−1 and a carrier concentration of 3.6×1015 cm−3. The diode dark currents in the diffusion regime and the spectral response attest to the excellent uniformity in composition of the layer. We have also established that in the diffusion regime the data can be explained by the ideal diode equation with electrical parameters measured on the as-grown MBE layers. We consider this an important step in the understanding of the relationship between material parameters and device performance.
Evidence of Schottky emission in scanning tunneling microscopes operated in ambient air
Authors: Jahanmir J. , West P. E. , Rhodin T. N.
Published: July 2002

We demonstrate that the electron transfer mechanism in scanning tunneling microscopes operated in air follows the Schottky equation. Schottky emission dominates electron transfer mechanism in microscopes operated in air because of low effective potential barrier heights. This is supported by currents and gap distances that are larger than when tunneling is the predominant electron transfer mechanism.
Changes in fracture surface composition and morphology with time in vacuum in YBa2Cu3O7−x
Authors: Kroeger D. M. , Brynestad J. , Padgett R. A.
Published: July 2002

Changes in fracture surface composition and morphology with time after fracture in a high vacuum environment are observed in the high transition temperature oxide superconductor YBa2 Cu3 O7−x . Morphological changes involving several grains and extending over distances of tens of microns are seen. Changes in fracture surface morphology are, at least in some cases, preceded by changes in surface composition as determined from Auger electron spectroscopy, and can occur at room temperature in the absence of electron beam excitation.
Superconductivity and magnetic properties of high T
c Bi-Sr-Ca-Cu-O superconductors
Authors: Kumakura H. , Takahashi K. , Dietderich D. R. , Togano K. , Maeda H.
Published: July 2002

Magnetization measurements were performed at 77 K on Bi-Sr-Ca-Cu-O compounds having zero resistance temperatures at 103 and 82 K. The lower critical field Hc1 of the 103 K material was found to be 60% less than the Hc1 of YBa2Cu3O7. This suggests that the material has a higher Hc2 . The new compound also has less magnetization hysteresis than the YBa2Cu3O7 compound.
Effects of substrate misorientation on the structural properties of CdTe(111) grown by molecular beam epitaxy on GaAs(100)
Authors: Reno J. L. , Gourley P. L. , Monfroy G. , Faurie J. P.
Published: July 2002

CdTe (111) layers were grown by molecular beam epitaxy on oriented and misoriented GaAs (100) substrates. The layers were characterized by x-ray diffraction and photoluminescence microscopy. The results indicate that the CdTe layers grown on GaAs (100) misoriented 2° towards the [110] direction had peaks with full width at half-maximum up to four times narrower than either of the other orientations tested. Only threading dislocations were visible on this orientation by photoluminescence microscopy. These results indicate that the structural quality of CdTe grown on GaAs can be significantly improved by the use of an appropriately misoriented substrate.
Effect of laser pulse duration on short wavelength emission from femtosecond and picosecond laser-produced Ta plasmas
Authors: Wood O. R. , Silfvast W. T. , Tom H. W. K. , Knox W. H. , Fork R. L. , Brito-Cruz C. H. , Downer M. C. , Maloney P. J.
Published: July 2002

The efficiency, duration, and spectral content of the emission from laser-produced Ta plasmas in the 10–71 nm spectral region have been measured for laser pulse durations ranging from 100 fs to 70 ps. Efficiencies from 0.3% for 100 fs pulses to 2.65% for 70 ps pulses, x-ray pulse durations from less than 10 ps for 100 fs excitation pulses to 105 ps for 70 ps excitation pulses, and spectral content peaking in the 17–35 nm region were measured for 1 mJ pulses at intensities from 1011 to 5×1014 W/cm2.
Observation of free excitons in room-temperature photoluminescence of GaAs/AlGaAs single quantum wells
Authors: Fujiwara K. , Tsukada N. , Nakayama T.
Published: July 2002

Observation of free excitons is reported in room-temperature photoluminescence of nominally undoped GaAs/AlGaAs single quantum wells grown by molecular beam epitaxy. A comparative study with parallel-conduction photocurrent spectroscopy shows that a sharp luminescence peak with a linewidth of 14 meV observed for the 6.1-nm-wide well coincides within 2 meV with the n=1 heavy-hole free-exciton resonance line at excess carrier densities less than 1017 cm−3. Excitonic decay channels dominate the luminescence spectrum even at room temperature as a result of quantum confinement effects, although photogenerated carriers are also provided for photocurrents by exciton dissociations.
Photoluminescence and magnetoreflectivity study of Zn1−xFexSe epilayers
Authors: Liu X. , Petrou A. , Jonker B. T. , Prinz G. A. , Krebs J. J. , Warnock J.
Published: July 2002

Single-crystal films of (001)Zn1−xFexSe (x=0.017, 0.027, 0.043) grown by molecular beam epitaxy on (001)GaAs have been studied using reflectivity and photoluminescence spectroscopies. Data have been obtained over the temperature range 4–77 K in magnetic fields up to 8 T in the spectral region near the band gap of 2.8 eV. The luminescence spectra show the two lowest interband excitonic transitions. From these spectra, the Zeeman splitting of the bands and the corresponding Fe2+-band electron exchange integrals were determined. The temperature dependence of the band splitting was determined through reflectivity measurements. These studies confirm the fact that Zn1−xFexSe exhibits Van Vleck paramagnetism and yield the spin-orbit splitting of the lowest Fe2+ crystal field states.
Influence of short coherence length on the superconducting proximity effect of silicon-coupled junctions
Authors: Hatano M. , Nishino T. , Murai F. , Kawabe U.
Published: July 2002

Superconducting critical currents of NbN-Si-NbN and Nb-Si-Nb junctions with a coplanar structure are measured as a function of temperature and of the spacing between superconducting electrodes. The current decreases exponentially with increasing temperature above 4.2 K and with increasing spacing. It is found that the coherence length in the semiconductor is determined only by the physical properties of the semiconductor, even though the superconducting electrode with a short coherence length such as NbN is used. Moreover, the measured coherence length in Si agrees with the value derived from the model of Seto and Van Duzer [J. Low Temp. Phys. LT-13, 323 (1972)].
A recombinant vaccine expressed in the milk of transgenic mice protects
Aotus
monkeys from a lethal challenge with
Plasmodium falciparum
Authors: Stowers Anthony W. , Chen Li-how , Zhang Yanling , Kennedy Michael C. , Zou Lanling , Lambert Lynn , Rice Timothy J. , Kaslow David C. , Saul Allan , Long Carole A. , Meade Harry , Miller Louis H.
Published: July 2002

Two strains of transgenic mice have been generated that
secrete into their milk a malaria vaccine candidate, the 42-kDa
C-terminal portion of
Plasmodium falciparum
merozoite
surface protein 1 (MSP1
42
). One strain secretes an
MSP1
42
with an amino acid sequence homologous to that of
the FVO parasite line, the other an MSP1
42
where two
putative N-linked glycosylation sites in the FVO sequence have been
removed. Both forms of MSP1
42
were purified from whole milk
to greater than 91% homogeneity at high yields. Both proteins are
recognized by a panel of monoclonal antibodies and have identical N
termini, but are clearly distinguishable by some biochemical
properties. These two antigens were each emulsified with Freund's
adjuvant and used to vaccinate
Aotus nancymai
monkeys,
before challenge with the homologous
P. falciparum
FVO
parasite line. Vaccination with a positive control molecule, a
glycosylated form of MSP1
42
produced in the baculovirus
expression system, successfully protected five of six monkeys. By
contrast, vaccination with the glycosylated version of milk-derived
MSP1
42
conferred no protection compared with an adjuvant
control. Vaccination with the nonglycosylated, milk-derived
MSP1
42
successfully protected the monkeys, with 4/5
animals able to control an otherwise lethal infection with
P.
falciparum
compared with 1/7 control animals. Analysis of the
different vaccines used suggested that the differing nature of the
glycosylation patterns may have played a critical role in determining
efficacy. This study demonstrates the potential for producing
efficacious malarial vaccines in transgenic animals.
pRB induces Sp1 activity by relieving inhibition mediated by MDM2
Authors: Johnson-Pais Teresa , Degnin Catherine , Thayer Mathew J.
Published: July 2002

pRB activates transcription by a poorly understood mechanism that
involves relieving negative regulation of the promoter specificity
factor Sp1. We show here that MDM2 inhibits Sp1-mediated transcription,
that MDM2 binds directly to Sp1
in vitro
as well as
in vivo
, and that MDM2 inhibits the DNA-binding activity
of Sp1. Forced expression of pRB relieves MDM2-mediated repression, and
interaction of pRB with the MDM2-Sp1 complex releases Sp1 and restores
DNA binding. These results suggest a model in which the opposing
activities of MDM2 and pRB regulate Sp1 DNA-binding and transcriptional
activity.
Systematic identification of mutations that constitutively activate the angiotensin II type 1A receptor by screening a randomly mutated cDNA library with an original pharmacological bioassay
Authors: Parnot Charles , Bardin Sabine , Miserey-Lenkei Stéphanie , Guedin Denis , Corvol Pierre , Clauser Eric
Published: July 2002

The constitutive activation of G-protein-coupled receptors is a major new approach to investigating their physiopathology and pharmacology. A large number of spontaneous and site-directed mutations resulting in constitutive activity have been identified, but systematic mapping of the amino acids involved for a given receptor would be extremely useful for complete elucidation of the molecular mechanisms underlying its activation. We carried out such mapping for the angiotensin II type 1A (AT
1A
) receptor by screening a randomly mutated cDNA library after expressing the mutated clones in eukaryotic cells. To test the AT
1A
mutants generated, we developed an original, specific, and highly sensitive assay based on the properties of CGP42112A. This classical AT
2
agonist is a weak partial agonist of the wild-type AT
1A
receptor and becomes a full agonist for constitutively active AT
1A
mutants, as shown experimentally and in allostery-based theoretical models. Activation of the mutated receptors by CGP42112A was monitored by using the bioluminescent protein æquorin, a very sensitive and specific sensor of intracellular calcium mobilization. The screening of 4,800 clones, providing an exhaustive coverage of all of the mutations generated, led to the identification of 16 mutations in sequences encoding the transmembrane domains that were responsible for high sensitivity to CGP42112A. The constitutive activity was confirmed by agonist-independent production of inositol phosphates, which showed that at least half of the clones had significantly increased basal activity. These data demonstrate that this new type of approach is very efficient for the systematic identification of constitutively active mutants of G-protein-coupled receptors.
Disruption of a long-range cis-acting regulator for
Shh
causes preaxial polydactyly
Authors: Lettice Laura A. , Horikoshi Taizo , Heaney Simon J. H. , van Baren Marijke J. , van der Linde Herma C. , Breedveld Guido J. , Joosse Marijke , Akarsu Nurten , Oostra Ben A. , Endo Naoto , Shibata Minoru , Suzuki Mikio , Takahashi Eiichi , Shinka Toshikatsu , Nakahori Yutaka , Ayusawa Dai , Nakabayashi Kazuhiko , Scherer Stephen W. , Heutink Peter , Hill Robert E. , Noji Sumihare
Published: July 2002

Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of
Shh
is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (
Ssq
). The genetic lesions in both lie within the same respective intron of the
LMBR1
/
Lmbr1
gene, which resides ≈1 Mb away from
Shh
. Genetic analysis of
Ssq
reveals that the
Lmbr1
gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of
Shh
. This regulator is most likely the target for generating PPD mutations in human.
High-frequency intrachromosomal gene conversion induced by triplex-forming oligonucleotides microinjected into mouse cells
Authors: Luo Zhongjun , Macris Margaret A. , Faruqi A. Fawad , Glazer Peter M.
Published: July 2002

To test the ability of triple helix-forming oligonucleotides (TFOs) to promote recombination within chromosomal sites in mammalian cells, a mouse LTK
−
cell line was established carrying two mutant copies of the herpes simplex virus thymidine kinase (TK) gene as direct repeats in a single chromosomal locus. Recombination between these repeats can produce a functional TK gene and occurs at a spontaneous frequency of 4 × 10
−6
under standard culture conditions. When cells were microinjected with TFOs designed to bind to a 30-bp polypurine site situated between the two TK genes, recombination was observed at frequencies in the range of 1%, 2,500-fold above the background. Recombination was induced efficiently by injection of both psoralen-conjugated TFOs (followed by long-wave UVA light; 1.2%) and unconjugated TFOs alone (1.0%). Control oligomers of scrambled sequence but identical base composition were ineffective, and no TFO-induced recombination was seen in a control LTK
−
cell line carrying an otherwise identical dual TK gene construct lacking the 30-bp polypurine target site. TFOs transfected with cationic lipids also induced recombinants in a highly sequence-specific manner but were less effective, with induced recombination frequencies of 6- to 7-fold over background. Examination of the TFO-induced recombinants by genomic Southern blotting revealed gene conversion events in which both TK genes were retained, but either the upstream (57%) or the downstream gene (43%) was corrected to wild type. These results suggest that, with efficient intracellular delivery, TFOs may be effective tools to promote site-specific recombination and targeted modification of chromosomal loci.
Self-similar intermediate asymptotics for nonlinear degenerate parabolic free-boundary problems that occur in image processing
Authors: Barenblatt G. I.
Published: July 2002

In the boundary layers around the edges of images, basic nonlinear parabolic equations for image intensity used in image processing assume a special degenerate asymptotic form. An asymptotic self-similar solution to this degenerate equation is obtained in an explicit form. The solution reveals a substantially nonlinear effect—the formation of sharp steps at the edges of the images, leading to edge enhancement. Positions of the steps and the time shift parameter cannot be determined by direct construction of a self-similar solution; they depend on the initial condition of the pre-self-similar solution. The free-boundary problem is formulated describing the image intensity evolution in the boundary layer.
Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum.
Authors: Silva A M , Lee A Y , Gulnik S V , Maier P , Collins J , Bhat T N , Collins P J , Cachau R E , Luker K E , Gluzman I Y , Francis S E , Oksman A , Goldberg D E , Erickson J W
Published: July 2002

Plasmodium falciparum is the major causative agent of malaria, a disease of worldwide importance. Resistance to current drugs such as chloroquine and mefloquine is spreading at an alarming rate, and our antimalarial armamentarium is almost depleted. The malarial parasite encodes two homologous aspartic proteases, plasmepsins I and II, which are essential components of its hemoglobin-degradation pathway and are novel targets for antimalarial drug development. We have determined the crystal structure of recombinant plasmepsin II complexed with pepstatin A. This represents the first reported crystal structure of a protein from P. falciparum. The crystals contain molecules in two different conformations, revealing a remarkable degree of interdomain flexibility of the enzyme. The structure was used to design a series of selective low molecular weight compounds that inhibit both plasmepsin II and the growth of P. falciparum in culture.
Population dynamics of flaviviruses revealed by molecular phylogenies.
Authors: Zanotto P M , Gould E A , Gao G F , Harvey P H , Holmes E C
Published: July 2002

The phylogeny of 123 complete envelope gene sequences was reconstructed in order to understand the evolution of tick- and mosquito-borne flaviviruses. An analysis of phylogenetic tree structure reveals a continual and asymmetric branching process in the tick-borne flaviviruses, compared with an explosive radiation in the last 200 years in viruses transmitted by mosquitoes. The distinction between these two viral groups probably reflects differences in modes of dispersal, propagation, and changes in the size of host populations. The most serious implication of this work is that growing human populations are being exposed to an expanding range of increasingly diverse viral strains.
Intrinsic compressibility and volume compression in solvated proteins by molecular dynamics simulation at high pressure.
Authors: Paci E , Marchi M
Published: July 2002

Constant pressure and temperature molecular dynamics techniques have been employed to investigate the changes in structure and volumes of two globular proteins, superoxide dismutase and lysozyme, under pressure. Compression (the relative changes in the proteins' volumes), computed with the Voronoi technique, is closely related with the so-called protein intrinsic compressibility, estimated by sound velocity measurements. In particular, compression computed with Voronoi volumes predicts, in agreement with experimental estimates, a negative bound water contribution to the apparent protein compression. While the use of van der Waals and molecular volumes underestimates the intrinsic compressibilities of proteins, Voronoi volumes produce results closer to experimental estimates. Remarkably, for two globular proteins of very different secondary structures, we compute identical (within statistical error) protein intrinsic compressions, as predicted by recent experimental studies. Changes in the protein interatomic distances under compression are also investigated. It is found that, on average, short distances compress less than longer ones. This nonuniform contraction underlines the peculiar nature of the structural changes due to pressure in contrast with temperature effects, which instead produce spatially uniform changes in proteins. The structural effects observed in the simulations at high pressure can explain protein compressibility measurements carried out by fluorimetric and hole burning techniques. Finally, the calculation of the proteins static structure factor shows significant shifts in the peaks at short wavenumber as pressure changes. These effects might provide an alternative way to obtain information concerning compressibilities of selected protein regions.
Regulation of N-methyl-D-aspartate-induced toxicity in the neostriatum: a role for metabotropic glutamate receptors?
Authors: Colwell C S , Altemus K L , Cepeda C , Levine M S
Published: July 2002

Glutamate release activates multiple receptors that interact with each other and thus determine the response of the cell. Exploring these interactions is critical to developing an understanding of the functional consequences of synaptic transmission. Activation of metabotropic glutamate receptors (mGluRs) inhibits N-methyl-D-aspartate (NMDA)-evoked responses measured electrophysiologically in neostriatal slices. The present study examines the functional consequences of this regulation using infrared differential interference contrast videomicroscopy to measure and characterize glutamate receptor-induced cell swelling in a neostriatal brain slice preparation. This swelling is, in many cases, a prelude to necrotic cell death and the dye trypan blue was used to confirm that swelling can result in the death of neostriatal cells. Activation of mGluRs by the agonist 1-aminocyclopentane-1,3-dicarboxylic acid (tACPD) inhibited NMDA but not amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-induced swelling. This regulation was cell-type specific as tACPD did not alter NMDA-induced swelling in pyramidal cells of the hippocampus. Importantly, these findings could be extended to in vivo preparations. Pretreatment with tACPD limited the size of lesions and associated behavioral deficits induced by intrastriatal administration of the NMDA receptor agonist quinolinic acid.
Extending the chemistry that supports genetic information transfer in vivo: phosphorothioate DNA, phosphorothioate RNA, 2'-O-methyl RNA, and methylphosphonate DNA.
Authors: Thaler D S , Liu S , Tombline G
Published: July 2002

DNA and RNA are the polynucleotides known to carry genetic information in life. Chemical variants of DNA and RNA backbones have been used in structure-function and biosynthesis studies in vitro, and in antisense pharmacology, where their properties of nuclease resistance and enhanced cellular uptake are important. This study addressed the question of whether the base(s) attached to artificial backbones encodes genetic information that can be transferred in vivo. Oligonucleotides containing chemical variants of DNA or RNA were used as primers for site-specific mutagenesis of bacteriophage f1. Progeny phage were scored both genetically and physically for the inheritance of information originally encoded by bases attached to the nonstandard backbones. Four artificial backbone chemistries were tested: phosphorothioate DNA, phosphorothioate RNA, 2'-O-methyl RNA and methylphosphonate DNA. All four were found capable of faithful information transfer from their attached bases when one or three artificial positions were flanked by normal DNA. Among oligonucleotides composed entirely of nonstandard backbones, only phosphorothioate DNA supported genetic information transfer in vivo.
Induction of host signal transduction pathways by
Helicobacter pylori
Authors: Segal Ellyn D. , Lange C. , Covacci A. , Tompkins L. S. , Falkow S.
Published: July 2002

Adherence of
Helicobacter pylori
to cultured gastric epithelial cells is associated with several cellular events, including the tyrosine phosphorylation of a 145-kDa host protein; the reorganization of the host cell actin and associated cellular proteins, like vasodilator-stimulated phosphoprotein, adjacent to the attached bacterial cell; and the subsequent release of the cytokine, interleukin 8 (IL-8).
H. pylori
isolated from patients with ulcer disease and gastric cancer contain a DNA insertion, the cag pathogenicity island (PAI), that is not present in bacteria isolated from individuals with asymptomatic infection. Mutations in a number of PAI genes abolish tyrosine phosphorylation and IL-8 synthesis but not the cytoskeletal rearrangements. Kinase inhibition studies suggest there are two distinct pathways operative in stimulating IL-8 release from host cells and one of these
H. pylori
pathways is independent of the tyrosine phosphorylation step.
Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis
Authors: Prakken Berent J. , van der Zee Ruurd , Anderton Stephen M. , van Kooten Peter J. S. , Kuis Wietse , van Eden Willem
Published: July 2002

Adjuvant arthritis (AA) can be induced in Lewis rats by immunization with mycobacterial antigens. Passive transfer of a T cell clone recognizing the 180–188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) was found to induce AA. In the present study, we investigated whether tolerance was obtained for this AA-associated T cell epitope after intranasal or s.c. administration of a peptide containing this epitope. Two 15-mer peptides containing the mycobacterial hsp60 sequences 176–190 and 211–225 were used; 176–190 contained the T cell epitope 180–188, which was recognized by the arthritogenic T cell clone A2b and was the immunodominant hsp60 T cell epitope after induction of AA, and 211–225 contained a T cell epitope that was recognized both after induction of arthritis with wholeMycobacterium tuberculosisand after immunization with mycobacterial hsp60. In rats treated intranasally or subcutaneously with 176–190 and immunized with mycobacterial hsp60, proliferative responses to 176–190 were reduced. Proliferative responses to 211–225 and to whole mycobacterial hsp60 were not affected. AA was inhibited intranasally in the 176–190-treated rats but not in the 211–225-treated rats. Moreover, intranasal 176–190 led to similar arthritis-protective effects in a nonmicrobially induced experimental arthritis (avridine-induced arthritis). Therefore, tolerance for a disease-triggering, microbial cartilage-mimicking epitope may cause resistance to arthritis irrespective of the actual trigger leading to development of the disease.
Enhancement of cellulose production by expression of sucrose synthase in
Acetobacter xylinum
Authors: Nakai Tomonori , Tonouchi Naoto , Konishi Teruko , Kojima Yukiko , Tsuchida Takayasu , Yoshinaga Fumihiro , Sakai Fukumi , Hayashi Takahisa
Published: July 2002

Higher plants efficiently conserve energy ATP in cellulose biosynthesis by expression of sucrose synthase, in which the high free energy between glucose and fructose in sucrose can be conserved and used for the synthesis of UDP-glucose. A mixture of sucrose synthase and bacterial cellulose synthase proceeded to form UDP-glucose from sucrose plus UDP and to synthesize 1,4-β-glucan from the sugar nucleotide. The mutant sucrose synthase, which mimics phosphorylated sucrose synthase, enhanced the reaction efficiency (
V
max
/
K
m
) on 1,4-β-glucan synthesis, in which the incorporation of glucose from sucrose was increased at low concentrations of UDP. Because UDP formed after glucosyl transfer can be directly recycled with sucrose synthase, UDP-glucose formed appears to show high turnover with cellulose synthase in the coupled reaction. The expression of sucrose synthase in
Acetobacter xylinum
not only changed sucrose metabolism but also enhanced cellulose production, in which UDP-glucose was efficiently formed from sucrose. Although the level of UDP-glucose in the transformant with mutant sucrose synthase cDNA was only 1.6-fold higher than that in plasmid-free cells, the level of UDP was markedly decreased in the transformant. The results show that sucrose synthase serves to channel carbon directly from sucrose to cellulose and recycles UDP, which prevents UDP build-up in cellulose biosynthesis.
Generalized flows, intrinsic stochasticity, and turbulent transport
Authors: Vanden Eijnden Weinan E , Vanden Eijnden Eric
Published: July 2002

The study of passive scalar transport in a turbulent velocity field leads naturally to the notion of generalized flows, which are families of probability distributions on the space of solutions to the associated ordinary differential equations which no longer satisfy the uniqueness theorem for ordinary differential equations. Two most natural regularizations of this problem, namely the regularization via adding small molecular diffusion and the regularization via smoothing out the velocity field, are considered. White-in-time random velocity fields are used as an example to examine the variety of phenomena that take place when the velocity field is not spatially regular. Three different regimes, characterized by their degrees of compressibility, are isolated in the parameter space. In the regime of intermediate compressibility, the two different regularizations give rise to two different scaling behaviors for the structure functions of the passive scalar. Physically, this means that the scaling depends on Prandtl number. In the other two regimes, the two different regularizations give rise to the same generalized flows even though the sense of convergence can be very different. The “one force, one solution” principle is established for the scalar field in the weakly compressible regime, and for the difference of the scalar in the strongly compressible regime, which is the regime of inverse cascade. Existence and uniqueness of an invariant measure are also proved in these regimes when the transport equation is suitably forced. Finally incomplete self similarity in the sense of Barenblatt and Chorin is established.
The use of oral topically acting glucocorticosteroids in the treatment of inflammatory bowel disease
Authors: Rutgeerts P.
Published: July 2002

Glucocorticosteroids are the mainstay of treatment of active Crohn′s disease and ulcerative colitis. These drugs however carry important cosmetic short‐term side effects and when used long‐term they induce severe irreversible complications. Topically acting glucocorticosteroids, especially budesonide, have been designed to achieve local effect at the site of inflammation without systemic effects of the drug. The first results of clinical trials are promising and budesonide has been shown to have an improved safety with almost comparable efficacy in comparison with prednisolone. The optimal enema dose seems to be 2 mg/100 ml at night whereas 9 mg o.m. is the optimal dose to treat ileal or right ileocolonic Crohn′s disease. Topically acting GCS, like standard GCS are not effective for maintenance of remission of Crohn′s disease or recurrence prevention after resection of the involved Crohn′s segment.
Immunotherapy of Crohn′s disease
Authors: van Montfrans C. , Camoglio L. , van Deventer S. J. H.
Published: July 2002

Although the initiating events of Crohn′s disease are unknown, models of experimental colitis have provided new insights in the immunologically mediated pathways of mucosal inflammation. In Crohn′s disease activated mucosal T lymphocytes produce proinflammatory cytokines within the mucosal compartment. With this understanding, there has been a shift in past years from the use of unspecific anti‐inflammatory agents (corticosteroids, aminosalicylates) to the use of immunomodulatory drugs (azathioprine, methotrexate). Moreover, novel strategies have been designed for specific targets in Crohn′s disease, in particular T lymphocytes and cytokines. In an open label study treatment of steroid‐refractory Crohn′s disease with anti‐ CD4+ antibodies was well tolerated and showed clinical benefit. However, a sustained depletion of the CD4+ cells precluded further clinical trials. In controlled clinical studies, anti‐tumour necrosis factor (TNF‐α) antibodies induced com plete remissions and few side effects were observed. One study suggested efficacy in active Crohn′s disease of recombinant interleukin‐10. Long term treatment studies will have to answer questions about the indications for use, benefit and toxicity. Altogether, these results hold promise for future management of Crohn′s disease, where disease‐modifying interventions and strategies that effectively maintain disease remission will play a key role.