bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the grain structure on the Fermi level in polycrystalline silicon: A quantum size effect?
Authors: Lifshitz N. , Luryi S. , Sheng T. T.
Published: July 2002

It has been observed by several authors that metal-oxide-semiconductor devices with polycrystalline Si (poly-Si) gates behave differently depending on the doping species in poly-Si: the work-function difference between the silicon substrate and the gate (φPS) is higher when the gates are doped with arsenic than when they are doped with phosphorus. As a function of the doping devel, this difference becomes first noticeable at ∼1019 cm−3, and then it increases for heavier doped materials, reaching 120 meV near the dopant solubility limit. We believe that the different behavior of φPS can be explained by different grain textures at the poly-Si/SiO2 interface. Our transmission electron microscopy of the films indicates that while P-doped material consists of large (≊3000 Å) grains, As-doped poly-Si preserves its as-deposited columnar structure, even after a high-temperature anneal. Moreover, at the interface with the gate oxide an as-deposited microstructure with very small (≊100 Å) ‘‘embrionic’’ grains is preserved. On the basis of these observations, we suggest a model for the different behavior of φPS. The model is based on a quantum size effect which becomes important for such small grain dimensions at the interface in As-doped poly-Si. This effect drastically reduces the number of states available in the conduction band at low energies and thus forces a more complete filling of the impurity band. The resulting shift of the Fermi level provides a qualitative explanation for the observed puzzling difference between the work functions of As- and P-doped poly-Si.
Electro-optical logic operations with two-electrode distributed feedback injection lasers
Authors: Liou K.-Y. , Burrus C. A. , Koren U. , Koch T. L.
Published: July 2002

A complete set of and, or, nand, nor, and invert logic gates is demonstrated using a distributed feedback (DFB) injection laser with two-electrode current control. The logic operation is based on the high-speed two-wavelength switching using the two-mode degeneracy property of DFB lasers that we have demonstrated recently. A 400-ps switching time, limited by the speed of the electrical signal, was observed. The device is compatible with future photonic integrated circuit and wide-band optical fiber transmission technologies.
Optical studies of GaAs quantum well based field-effect transistor
Authors: Delalande C. , Orgonasi J. , Brum J. A. , Bastard G. , Voos M. , Weimann G. , Schlapp W.
Published: July 2002

The optical response of a GaAs-Ga(Al)As one-side-modulation-doped quantum well is studied by photoluminescence and excitation spectroscopy at T=2 K. The electronic concentration is controlled in a field-effect-transistor-like structure. 1011 cm−2 electrons are sufficient to wipe out the strong excitonic resonances which dominate the photoluminescence excitation spectrum when the well is depleted of its carriers. While the lowest lying excitation peak coincides with the maximum of the photoluminescence line when the GaAs channel is empty, the two peaks move in opposite directions with increasing carrier concentration due to the inflating Fermi surface and to band-gap renormalization effects.
Model calculation on the Meyer–Neldel rule for the field-effect conductance of hydrogenated amorphous silicon
Authors: Yoon Byung-Gook , Lee Choochon
Published: July 2002

A model calculation was carried out to study the Meyer–Neldel rule of the field-effect conductance of hydrogenated amorphous silicon (a-Si:H). It was found that the shift of Fermi level and the potential profile in the sample with temperature can explain the Meyer–Neldel rule if a model density of states of a-Si:H is properly chosen. So it is of doubt to think that the conductivity prefactor varies in a single sample of band-bending case, as assumed by some authors.
Mode-locked infrared sensor
Authors: Coon D. D. , Perera A. G. U.
Published: July 2002

Injection mode infrared detector concepts are expanded to incorporate the nonlinear dynamics concept of mode locking. The first successful demonstration of this approach is reported. The detectors employ extrinsic silicon and have large output signals which require no electronic amplification. Mode locking greatly reduces fluctuations in detector output without a corresponding reduction in detector responsivity. The results could lead to the development of a new class of sensors which exploit recent work on the distinction between deterministic fluctuations in nonlinear systems and intrinsic noise.
Single lobe operation of a 40-element laser array in an external ring laser cavity
Authors: Goldberg Lew , Weller J. F.
Published: July 2002

Single lobe operation of a 40-element GaAlAs gain guided coupled stripe array emitting 500 mW cw is obtained in an external ring laser cavity. The cavity arrangement is equivalent to self-injection locking of the array by its own output, which is first spatially filtered by a single mode fiber. Diffraction-limited lobe width of 0.13° and single mode operation are demonstrated with a 90 mW single mode fiber output.
Phase and spatial coherence measurements on diode arrays: Comparison to supermode theory
Authors: Dente Gregory C. , Wilson Kimberley A. , Salvi Theodore C. , Depatie David
Published: July 2002

We describe a simple method for measuring the output phase and spatial coherence of semiconductor lasers and laser arrays.
AlGaAs multiple-wavelength light-emitting bar grown by laser-assisted metalorganic chemical vapor deposition
Authors: Epler J. E. , Chung H. F. , Treat D. W. , Paoli T. L.
Published: July 2002

The first optical device fabricated from epitaxial material grown by laser-assisted crystal growth is reported. The device is an AlGaAs multiple-wavelength light-emitting bar in which the Al composition of the active layer, and thus the emission wavelength, varies as a function of position along the bar. The Al composition is photochemically patterned during growth with an in situ Ar+ laser beam. The energy band gap increases from a minimum of 1.475 eV to a maximum of 1.52 eV over a 4 mm section of the bar. The spatial dependence of the energy band gap is roughly Gaussian and corresponds to the laser intensity profile. The electroluminescent data are presented along with a brief discussion of the laser-assisted crystal growth process.
Importance of interface hydraulic condition on the generation of second bulk compressional wave in porous media
Authors: Rasolofosaon Patrick N. J.
Published: July 2002

The fundamental prediction of Biot’s thoery [J. Acoust. Soc. Am. 28, 168 (1956)] for propagation of acoustic waves in saturated porous media is the existence of a second compressional wave (SCW). This wave has been observed experimentally by Plona [Appl. Phys. Lett. 36, 259 (1980)]. In this work, we modify Plona’s experiments on saturated porous plates by sealing off interface permeability using a thin coat of paint on both sides of the plates. Our work focuses on the influence of this coating on the observed acoustic waves. No SCW generation is observed on coated plates which was predicted by Geertsma and Smit [Geophysics 41, 169 (1961)] using Biot’s theory. Furthermore, due to total energy conservation, the generation of the SCW substantially modifies the energy of the other ordinary waves. A comparison between experimental and synthetic signals using Biot’s theory shows good agreement. These results show the importance of free fluid transfer at the interface between the porous medium and the fluid for the generation of the SCW.
Equivalence between interface traps in SiO2/Si generated by radiation damage and hot-electron injection
Authors: Nishioka Yasushiro , da Silva Eronides F. , Ma T. P.
Published: July 2002

We have made a comparison between the interface traps generated in the metal/SiO2/Si structure by x-ray ionizing radiation and Fowler–Nordheim hot-electron injection, and found very strong similarities between the two. More specifically, the qualitative features of the energy distribution of the interface traps, their post-damage time-dependence behavior, and their dependence on the gate bias while being damaged are all very much alike, supporting the notion that the same types of interfacial defects are generated by the two different processes.
Model for facet and sidewall defect formation during selective epitaxial growth of (001) silicon
Authors: Drowley C. I. , Reid G. A. , Hull R.
Published: July 2002

An atomistic growth model is used to explain sidewall facet and defect formation during selective epitaxial growth of (001) silicon. Films grown through oxide windows with {110} sidewall orientations exhibit facets (typically {311} planes) adjacent to the sidewall. This region also has a high density of twins. Films grown in windows oriented to have {100} sidewalls have no sidewall facets and a very low defect density. The facet morphology and twin formation at {110} sidewalls are both explained by the influence of the oxide on nucleation of {111} planes. Similar considerations indicate that films grown along {100} sidewalls are less susceptible to facet and defect formation, as observed. Experimental data on film morphology and defect structure are used to support the model.
Effect of group V/III flux ratio on the reliability of GaAs/Al0.3Ga0.7As laser diodes prepared by molecular beam epitaxy
Authors: Hayakawa T. , Takahashi K. , Suyama T. , Kondo M. , Yamamoto S. , Hijikata T.
Published: July 2002

The effect of group V/III flux ratio γ on the reliability of GaAs/Al0.3Ga0.7As double-heterostructure lasers grown by molecular beam epitaxy at 720 °C has been studied. The threshold current does not change with γ. By contrast, the degradation rate strongly depends on γ and it takes a minimum at γ∼3 where the photoluminescence intensity of the Al0.3Ga0.7As cladding layer is maximum. In the case of γ∼3, the degradation rate is lower than that of lasers grown by liquid phase epitaxy.
Schottky barriers of epitaxial NiSi2 on Si(111)
Authors: Ospelt M. , Henz J. , Flepp L. , von Känel H.
Published: July 2002

We have investigated the Schottky-barrier heights of high-quality epitaxial type-A- and type-B-oriented NiSi2 on n-doped Si(111). Current-voltage and photoresponse techniques have been used. The barrier height of type-A NiSi2 is found to be low (0.64 eV), whereas type-B NiSi2 yields a high barrier of 0.76 eV. Ideality factors very close to unity (1.00–1.02) have been observed both for type-A NiSi2 as well as for type B.
Optical pulse generation with a frequency shifted feedback laser
Authors: Kowalski F. V. , Shattil S. J. , Hale P. D.
Published: July 2002

A pulsed ring dye laser is constructed in which the light is shifted in frequency before being fed back into the gain medium. The active medium is R6G dye pumped by a continuous wave argon-ion laser. An acousto-optic modulator is used to shift the frequency of the light inside the ‘‘cavity.’’ With this device, we have generated optical pulses with a 9.6 ps FWHM of the autocorrelation trace and measured periods as short as 0.9 ns.
Theoretical approach to the electronic states and core exciton of superlattice ZnSe/GaAs
Authors: Shen Dingli , Zhang Kaiming , Fu Rouli
Published: July 2002

The energy-band structures of superlattice ZnSe/GaAs(001) are calculated using the semiempirical tight binding method. The fundamental gap and effective mass are studied with the variation of layer thickenss. The appearance of core excitons related to impurities B, Al, and Ga is found to be possible in (ZnSe)5/(GaAs)5, qualitatively consistent with a Ga-bound exciton peak observed in a corresponding heterojunction experiment. It is proposed that interface states would exist at the conduction-band edge of this material.
Early expression of antiinsulin autoantibodies of humans and the NOD mouse: Evidence for early determination of subsequent diabetes
Authors: Yu Liping , Robles David T. , Abiru Norio , Kaur Paramjit , Rewers Marian , Kelemen Katalin , Eisenbarth George S.
Published: July 2002

With the development of an insulin autoantibody (IAA) assay performed in 96-well filtration plates, we have evaluated prospectively the development of IAA in NOD mice (from 4 weeks of age) and children (from 7 to 10 months of age) at genetic risk for the development of type 1 diabetes. NOD mice had heterogeneous expression of IAA despite being inbred. IAA reached a peak between 8 and 16 weeks and then declined. IAA expression by NOD mice at 8 weeks of age was strongly associated with early development of diabetes, which occurred at 16–18 weeks of age (NOD mice IAA+at 8 weeks: 83% (5/6) diabetic by 18 weeks versus 11% (1/9) of IAA negative at 8 weeks;P< .01). In man, IAA was frequently present as early as 9 months of age, the first sampling time. Of five children found to have persistent IAA before 1 year of age, four have progressed to diabetes (all before 3.5 years of age) and the fifth is currently less than age 2. Of the 929 children not expressing persistent IAA before age 1, only one has progressed to diabetes to date (age onset 3), and this child expressed IAA at his second visit (age 1.1). In new onset patients, the highest levels of IAA correlated with an earlier age of diabetes onset. Our data suggest that the program for developing diabetes of NOD mice and humans is relatively “fixed” early in life and, for NOD mice, a high risk of early development of diabetes is often determined by 8 weeks of age. With such early determination of high risk of progression to diabetes, immunologic therapies in humans may need to be tested in children before the development of IAA for maximal efficacy.
Genetic analysis of speciation by means of introgression into
Drosophila melanogaster
Authors: Sawamura Kyoichi , Davis Andrew W. , Wu Chung-I
Published: July 2002

In the last decade, the genetic basis of reproductive isolation has
been shown to be surprisingly polygenic, and yet even the most
efficient system currently in use could lend itself to molecular
analysis only in highly selected cases. By extending the recent
discovery of fertility rescue between
Drosophila
melanogaster
and
Drosophila simulans
, we show
that this hybridization can permit systematic and precise delineation
of the genetic and molecular basis of speciation. In a region of 5% of
the
D. simulans
genome introgressed into
D.
melanogaster
, we discover at least six genes of hybrid male
sterility and none for female sterility by deficiency mapping. A single
case of hybrid inviability has been tracked down to a 3-Kb element that
was inserted into the
Cyclin E
locus during species
hybridization. The extent of interspecific genetic divergence
underlying hybrid male sterility, especially in contrast with the low
degree of inviability and female sterility, is far greater than
expected from previous studies.
Antibodies to human fetal erythroid cells from a nonimmune phage antibody library
Authors: Huie Michael A. , Cheung Mei-Chi , Muench Marcus O. , Becerril Baltazar , Kan Yuet W. , Marks James D.
Published: July 2002

The ability to isolate fetal nucleated red blood cells (NRBCs) from
the maternal circulation makes possible prenatal genetic analysis
without the need for diagnostic procedures that are invasive for the
fetus. Such isolation requires antibodies specific to fetal NRBCs. To
generate a panel of antibodies to antigens present on fetal NRBCs, a
new type of nonimmune phage antibody library was generated in which
multiple copies of antibody fragments are displayed on each phage.
Antibody fragments specific for fetal NRBCs were isolated by extensive
predepletion of the phage library on adult RBCs and white blood cells
(WBCs) followed by positive selection and amplification on fetal liver
erythroid cells. After two rounds of selection, 44% of the antibodies
analyzed bound fetal NRBCs, with two-thirds of these showing no binding
of WBCs. DNA fingerprint analysis revealed the presence of at least 16
unique antibodies. Antibody specificity was confirmed by flow
cytometry, immunohistochemistry, and immunofluorescence of total fetal
liver and adult RBCs and WBCs. Antibody profiling suggested the
generation of antibodies to previously unknown fetal RBC antigens. We
conclude that multivalent display of antibodies on phage leads to
efficient selection of panels of specific antibodies to cell surface
antigens. The antibodies generated to fetal RBC antigens may have
clinical utility for isolating fetal NRBCs from maternal circulation
for noninvasive prenatal genetic diagnosis. Some of the antibodies may
also have possible therapeutic utility for erythroleukemia.
Reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of
l
-dopa using rAAV-mediated gene transfer
Authors: Kirik Deniz , Georgievska Biljana , Burger Corinna , Winkler Christian , Muzyczka Nicholas , Mandel Ronald J. , Björklund Anders
Published: July 2002

Intrastriatal delivery of the tyrosine hydroxylase gene by viral vectors is being explored as a tool for local delivery of
l
-dopa in animals with lesions of the nigrostriatal pathway. The functional effects reported using this approach have been disappointing, probably because the striatal
l
-dopa levels attained have been too low. In the present study, we have defined a critical threshold level of
l
-dopa, 1.5 pmol/mg of tissue, that has to be reached to induce any significant functional effects. Using new generation high-titer recombinant adeno-associated virus vectors, we show that levels of striatal
l
-dopa production exceeding this threshold can be obtained provided that tyrosine hydroxylase is coexpressed with the cofactor synthetic enzyme, GTP-cyclohydrolase-1. After striatal transduction with this combination of vectors, substantial functional improvement in both drug-induced and spontaneous behavior was observed in rats with either complete or partial 6hydroxydopamine lesions of the nigrostriatal pathway. However, complete reversal of motor deficits occurred only in animals in which part of the striatal dopamine innervation was left intact. Spared nigrostriatal fibers thus may convert
l
-dopa to dopamine and store and release dopamine in a more physiologically relevant manner in the denervated striatum to mediate better striatal output-dependent motor function. We conclude that intrastriatal
l
-dopa delivery may be a viable strategy for treatment and control of adverse side effects associated with oral
l
-dopa therapy such as on-off fluctuations and drug-induced dyskinesias in patients with Parkinson's disease.
Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands
Authors: Tocchini-Valentini G. , Rochel N. , Wurtz J. M. , Mitschler A. , Moras D.
Published: July 2002

The crystal structures of the ligand-binding domain (LBD) of the
vitamin D receptor complexed to 1α,25(OH)
2
D
3
and the 20-epi analogs, MC1288 and KH1060, show that the protein
conformation is identical, conferring a general character to the
observation first made for retinoic acid receptor (RAR) that, for a
given LBD, the agonist conformation is unique, the ligands adapting to
the binding pocket. In all complexes, the A- to D-ring moieties of the
ligands adopt the same conformation and form identical contacts with
the protein. Differences are observed only for the 17β-aliphatic
chains that adapt their conformation to anchor the 25-hydroxyl group to
His-305 and His-397. The inverted geometry of the C20 methyl group
induces different paths of the aliphatic chains. The ligands exhibit a
low-energy conformation for MC1288 and a more strained conformation for
the two others. KH1060 compensates this energy cost by additional
contacts. Based on the present data, the explanation of the
superagonist effect is to be found in higher stability and longer
half-life of the active complex, thereby excluding different
conformations of the ligand binding domain.
Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy
Authors: Valentin Antonio , Rosati Margherita , Patenaude Daniel J. , Hatzakis Angelos , Kostrikis Leondios G. , Lazanas Marios , Wyvill Kathleen M. , Yarchoan Robert , Pavlakis George N.
Published: July 2002

We have identified a subset of CD56
+
CD3
−
human natural killer (NK) cells that express CD4 and the HIV coreceptors CCR5 and CXCR4. These cells can be productively infected
in vitro
by both CCR5- and CXCR4-using molecular clones of HIV-1 in a CD4-dependent manner. Analysis of HIV-infected persons showed that viral DNA is present in purified NK cells, and virus could be rescued from these cells after
in vitro
cultivation. Longitudinal analysis of the HIV-1 DNA levels in NK cells from patients after 1–2 years of highly active antiretroviral therapy indicated that NK cells remain persistently infected and account for a substantial amount of the viral DNA in peripheral blood mononuclear cells. These results demonstrate that a subset of non-T cells with NK markers are persistently infected and suggest that HIV infection of NK cells is important for virus persistence. The properties of the virus reservoir in these cells should be considered in attempts to further optimize antiretroviral therapies.
Quantum optical implementation of Grover's algorithm
Authors: Scully Marlan O. , Zubairy M. S.
Published: July 2002

We present a scheme for a quantum optical implementation of
Grover's algorithm based on resonant atomic interactions with
classical fields and dispersive couplings with quantized cavity fields.
The proposed scheme depends on preparation of entangled states and is
within current state-of-the-art technology.
Absence of stable intermediates on the folding pathway of barnase
Authors: Takei Jiro , Chu Rui-Ai , Bai Yawen
Published: July 2002

Barnase is one of the few protein models that has been studied
extensively for protein folding. Previous studies led to the conclusion
that barnase folds through a very stable submillisecond intermediate
(≈3 kcal/mol). The structure of this intermediate was characterized
intensively by using a protein engineering approach. This intermediate
has now been reexamined with three direct and independent methods.
(
i
) Hydrogen exchange experiments show very small
protection factors (≈2) for the putative intermediate, indicating a
stability of ≈0.0 kcal/mol. (
ii
)
Denaturant-dependent unfolding of the putative intermediate is
noncooperative and indicates a stability less than 0.0 kcal/mol.
(
iii
) The logarithm of the unfolding rate constant of
native barnase vs. denaturant concentrations is not linear. Together
with the measured rate (“
I
” to
N
),
this nonlinear behavior accounts for almost all of the protein
stability, leaving only about 0.3 kcal/mol that could be attributed
to the rapidly formed intermediate. Other observations previously
interpreted to support the presence of an intermediate are now known to
have alternative explanations. These results cast doubts on the
previous conclusions on the nature of the early folding state in
barnase and therefore should have important implications in
understanding the early folding events of barnase and other proteins in
general.
A conserved genetic module that encodes the major virion components in both the coliphage T4 and the marine cyanophage S-PM2
Authors: Hambly Emma , Tétart Francoise , Desplats Carine , Wilson William H. , Krisch Henry M. , Mann Nicholas H.
Published: July 2002

Sequence analysis of a 10-kb region of the genome of the marine
cyanomyovirus S-PM2 reveals a homology to coliphage T4 that extends as
a contiguous block from gene (g)18 to g23. The order of the S-PM2 genes
in this region is similar to that of T4, but there are insertions and
deletions of small ORFs of unknown function. In T4, g18 codes for the
tail sheath, g19, the tail tube, g20, the head portal protein, g21, the
prohead core protein, g22, a scaffolding protein, and g23, the major
capsid protein. Thus, the entire module that determines the structural
components of the phage head and contractile tail is conserved between
T4 and this cyanophage. The significant differences in the morphology
of these phages must reflect the considerable divergence of the amino
acid sequence of their homologous virion proteins, which uniformly
exceeds 50%. We suggest that their enormous diversity in the sea could
be a result of genetic shuffling between disparate phages mediated by
such commonly shared modules. These conserved sequences could
facilitate genetic exchange by providing partially homologous
substrates for recombination between otherwise divergent phage genomes.
Such a mechanism would thus expand the pool of phage genes accessible
by recombination to all those phages that share common modules.
Global configuration of single titin molecules observed through chain-associated rhodamine dimers
Authors: Grama László , Somogyi Béla , Kellermayer Miklós S. Z.
Published: July 2002

The global configuration of individual, surface-adsorbed molecules
of the giant muscle protein titin, labeled with rhodamine conjugates,
was followed with confocal microscopy. Fluorescence-emission
intensity was reduced because of self-quenching caused by the close
spacing between rhodamine dye molecules that formed dimers. In the
presence of chemical denaturants, fluorescence intensity increased,
reversibly, up to 5-fold in a fast reaction; the kinetics were followed
at the single-molecule level. We show that dimers formed in a
concentrated rhodamine solution dissociate when exposed to chemical
denaturants. Furthermore, titin denaturation, followed by means
of tryptophan fluorescence, is dominated by a slow reaction.
Therefore, the rapid fluorescence change of the single molecules
reflects the direct action of the denaturants on rhodamine dimers
rather than the unfolding/refolding of the protein. Upon acidic
denaturation, which we have shown not to dissociate rhodamine dimers,
fluorescence intensity change was minimal, suggesting that dimers
persist because the unfolded molecule has contracted into a small
volume. The highly contractile nature of the acid-unfolded protein
molecule derives from a significant increase in chain flexibility. We
discuss the potential implications this finding could have for the
passive mechanical behavior of striated muscle.
Gene expression profiles of light-induced apoptosis in arrestin/rhodopsin kinase-deficient mouse retinas
Authors: Choi Sangdun , Hao Wenshan , Chen Ching-Kang , Simon Melvin I.
Published: July 2002

To examine the molecular processes that lead to light-induced retinal degeneration, mutant mice deficient in arrestin and rhodopsin kinase were raised in the dark and then subjected to relatively low doses of white light. The kinetics of the subsequent induction of apoptosis, change in mRNA transcript level, and photoreceptor cell death were monitored. Analysis of transcript profiles identified clusters of genes that responded differently to illumination, including a cluster of photoreceptor-specific genes that showed marked decreases in levels long before morphological damage could be readily ascertained. The behaviors of other gene clusters demonstrate the coordinate induction of stress gene responses early in the course of irradiation. There was little, if any, change in transcript levels corresponding to genes associated with the initiation of apoptosis or antiapoptotic effects. Transcript analysis provides insight into the patterns of gene expression that are associated with the different stages of retinal degeneration in this model system.
Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4
+
and CD8
+
T cell turnover in HIV-infected patients
Authors: Lempicki Richard A. , Kovacs Joseph A. , Baseler Michael W. , Adelsberger Joseph W. , Dewar Robin L. , Natarajan Ven , Bosche Marjorie C. , Metcalf Julia A. , Stevens Randy A. , Lambert Laurie A. , Alvord W. Gregory , Polis Michael A. , Davey Richard T. , Dimitrov Dimiter S. , Lane H. Clifford
Published: July 2002

To evaluate the effects of HIV infection on T cell turnover, we
examined levels of DNA synthesis in lymph node and peripheral blood
mononuclear cell subsets by using
ex vivo
labeling with
BrdUrd. Compared with healthy controls (
n
= 67),
HIV-infected patients (
n
= 57) had significant
increases in the number and fraction of dividing CD4
+
and
CD8
+
T cells. Higher percentages of dividing
CD4
+
and CD8
+
T cells were noted in patients
with the higher viral burdens. No direct correlation was noted between
rates of T cell turnover and CD4
+
T cell counts. Marked
reductions in CD4
+
and CD8
+
T cell
proliferation were seen in 11/11 patients 1–12 weeks after
initiation of highly active antiretroviral therapy (HAART). These
reductions persisted for the length of the study (16–72 weeks).
Decreases in naïve T cell proliferation correlated with
increases in the levels of T cell receptor rearrangement excision
circles. Division of CD4
+
and CD8
+
T cells
increased dramatically in association with rapid increases in HIV-1
viral loads in 9/9 patients 5 weeks after termination of HAART and
declined to pre-HAART-termination levels 8 weeks after reinitiation of
therapy. These data are consistent with the hypothesis that HIV-1
infection induces a viral burden-related, global activation of the
immune system, leading to increases in lymphocyte proliferation.
Gene gun-mediated skin transfection with interleukin 12 gene results in regression of established primary and metastatic murine tumors.
Authors: Rakhmilevich A L , Turner J , Ford M J , McCabe D , Sun W H , Sondel P M , Grota K , Yang N S
Published: July 2002

Particle-mediated (gene gun) in vivo delivery of the murine interleukin 12 (IL-12) gene in an expression plasmid was evaluated for antitumor activity. Transfer of IL-12 cDNA into epidermal cells overlying an implanted intradermal tumor resulted in detectable levels (266.0 +/- 27.8 pg) of the transgenic protein at the skin tissue treatment site. Despite these low levels of transgenic IL-12, complete regression of established tumors (0.4-0.8 cm in diameter) was achieved in mice bearing Renca, MethA, SA-1, or L5178Y syngeneic tumors. Only one to four treatments with IL-12 cDNA-coated particles, starting on day 7 after tumor cell implantation, were required to achieve complete tumor regression. This antitumor effect was CD8+ T cell-dependent and led to the generation of tumor-specific immunological memory. By using a metastatic P815 tumor model, we further showed that a delivery of IL-12 cDNA into the skin overlying an advanced intradermal tumor, followed by tumor excision and three additional IL-12 gene transfections, could significantly inhibit systemic metastases, resulting in extended survival of test mice. These results suggest that gene gun-mediated in vivo delivery of IL-12 cDNA should be further developed for potential clinical testing as an approach for human cancer gene therapy.
Severed corticospinal axons recover electrophysiologic control of muscle activity after x-ray therapy in lesioned adult spinal cord.
Authors: Kalderon N , Fuks Z
Published: July 2002

Mechanical injury to the adult mammalian spinal cord results in permanent loss of structural integrity at the lesion site and of the brain-controlled function distal to the lesion. Some of these consequences were permanently averted by altering the cellular constituents at the lesion site with x-irradiation delivered within a critical time window after injury. We have reported in a separate article that x-irradiation of sectioned adult rat spinal cord resulted in restitution of structural continuity and regrowth of severed corticospinal axons across and deep into the distal stump. Here, we report that after x-ray therapy of the lesion site severed corticospinal axons of transected adult rat spinal cord recover electrophysiologic control of activity of hindlimb muscles innervated by motoneurons distal to the lesion. The degree of recovery of control of muscle activity was directly related to the degree of restitution of structural integrity. This restitution of electrophysiologic function implies that the regenerating corticospinal axons reestablish connectivity with neurons within the target field in the distal stump. Our data suggest that recovery of structural continuity is a sufficient condition for the axotomized corticospinal neurons to regain some of their disrupted function in cord regions distal to the lesion site.
Patterning of functional antibodies and other proteins by photolithography of silane monolayers.
Authors: Mooney J F , Hunt A J , McIntosh J R , Liberko C A , Walba D M , Rogers C T
Published: July 2002

We have demonstrated the assembly of two-dimensional patterns of functional antibodies on a surface. In particular, we have selectively adsorbed micrometer-scale regions of biotinylated immunoglobulin that exhibit specific antigen binding after adsorption. The advantage of this technique is its potential adaptability to adsorbing arbitrary proteins in tightly packed monolayers while retaining functionality. The procedure begins with the formation of a self-assembled monolayer of n-octadecyltrimethoxysilane (OTMS) on a silicon dioxide surface. This monolayer can then be selectively removed by UV photolithography. Under appropriate solution conditions, the OTMS regions will adsorb a monolayer of bovine serum albumin (BSA), while the silicon dioxide regions where the OTMS has been removed by UV light will adsorb less than 2% of a monolayer, thus creating high contrast patterned adsorption of BSA. The attachment of the molecule biotin to the BSA allows the pattern to be replicated in a layer of streptavidin, which bonds to the biotinylated BSA and in turn will bond an additional layer of an arbitrary biotinylated protein. In our test case, functionality of the biotinylated goat antibodies raised against mouse immunoglobulin was demonstrated by the specific binding of fluorescently labeled mouse IgG.
Dominant negative inhibition by fragments of a monomeric enzyme
Authors: Michaels John-Edward A. , Schimmel Paul , Shiba Kiyotaka , Miller W. Todd
Published: July 2002

Dominant negative inhibition is most commonly seen when a mutant
subunit of a multisubunit protein is coexpressed with the wild-type
protein so that assembly of a functional oligomer is impaired. By
analogy, it should be possible to interfere with the functional
assembly of a monomeric enzyme by interfering with the folding pathway.
Experiments
in vitro
by others suggested that fragments
of a monomeric enzyme might be exploited for this purpose. We report
here dominant negative inhibition of bacterial cell growth by
expression of fragments of a tRNA synthetase. Inhibition is
fragment-specific, as not all fragments cause inhibition. An inhibitory
fragment characterized in more detail forms a specific complex with the
intact enzyme
in vivo
, leading to enzyme inactivation.
This fragment also associated stoichiometrically with the full-length
enzyme
in vitro
after denaturation and refolding, and
the resulting complex was catalytically inactive. Inhibition therefore
appears to arise from an interruption in the folding pathway of the
wild-type enzyme, thus suggesting a new strategy to design dominant
negative inhibitors of monomeric enzymes.
On the origin of the order Artiodactyla.
Authors: Rose K D
Published: July 2002

The first known members of the order Artiodactyla appeared suddenly throughout the Holarctic region at the beginning of the Eocene. They are characterized by distinctive cursorial skeletal specializations. Owing to their abrupt appearance and the lack of transitional forms, the origin of the order is problematic. Descent from a "condylarth," specifically the arctocyonid Chriacus, has been suggested based on dental resemblances, but until now postcranial anatomy seemed to preclude close relationship between Arctocyonidae and Artiodactyla. A middle Paleocene specimen of a small arctocyonid (?Chriacus) reported here is much more similar to the oldest artiodactyl, Diacodexis, in the derived condition of the hindlimb, reviving the possibility that Artiodactyla evolved from an arctocyonid.
Interface between culturally based preferences and genetic preferences: female mate choice in Poecilia reticulata.
Authors: Dugatkin L A
Published: July 2002

The relative contribution of genetic and socio-cultural factors in the shaping of behavior is of fundamental importance to biologists and social scientists, yet it has proven to be extremely difficult to study in a controlled, experimental fashion. Here I describe experiments that examined the strength of genetic and cultural (imitative) factors in determining female mate choice in the guppy, Poecilia reticulata. Female guppies from the Paria River in Trinidad have a genetic, heritable preference for the amount of orange body color possessed by males. Female guppies will, however, also copy (imitate) the mate choice of other females in that when two males are matched for orange color, an "observer" female will copy the mate choice of another ("model") female. Three treatments were undertaken in which males differed by an average of 12%, 24%, or 40% of the total orange body color. In all cases, observer females viewed a model female prefer the less colorful male. When males differed by 12% or 24%, observer females preferred the less colorful male and thus copied the mate choice of others, despite a strong heritable preference for orange body color in males. When males differed by 40% orange body color, however, observer females preferred the more colorful male and did not copy the mate choice of the other female. In this system, then, imitation can "override" genetic preferences when the difference between orange body color in males is small or moderate, but genetic factors block out imitation effects when the difference in orange body color in males is large. This experiment provides the first attempt to experimentally examine the relative strength of cultural and genetic preferences for a particular trait and suggests that these two factors moderate one another in shaping social behavior.
Slip complexity in dynamic models of earthquake faults.
Authors: Langer J S , Carlson J M , Myers C R , Shaw B E
Published: July 2002

We summarize recent evidence that models of earthquake faults with dynamically unstable friction laws but no externally imposed heterogeneities can exhibit slip complexity. Two models are described here. The first is a one-dimensional model with velocity-weakening stick-slip friction; the second is a two-dimensional elastodynamic model with slip-weakening friction. Both exhibit small-event complexity and chaotic sequences of large characteristic events. The large events in both models are composed of Heaton pulses. We argue that the key ingredients of these models are reasonably accurate representations of the properties of real faults.
Stability and dynamics in a hyperthermophilic protein with melting temperature close to 200°C
Authors: Hiller Reuben , Zhou Zhi H. , Adams Michael W. W. , Englander S. Walter
Published: July 2002

The rubredoxin protein from the hyperthermophilic archaebacteriumPyrococcus furiosuswas examined by a hydrogen exchange method. Even though the protein does not exhibit reversible thermal unfolding, one can determine its stability parameters—free energy, enthalpy, entropy, and melting temperature—and also the distribution of stability throughout the protein, by using hydrogen exchange to measure the reversible cycling of the protein between native and unfolded states that occurs even under native conditions.
Approximation algorithms
Authors: Schulz Andreas S. , Shmoys David B. , Williamson David P.
Published: July 2002

Increasing global competition, rapidly changing markets, and
greater consumer awareness have altered the way in which corporations
do business. To become more efficient, many industries have sought to
model some operational aspects by gigantic optimization problems. It is
not atypical to encounter models that capture 10
6
separate
“yes” or “no” decisions to be made. Although one could, in
principle, try all 2

10
6

possible solutions to find the
optimal one, such a method would be impractically slow. Unfortunately,
for most of these models, no algorithms are known that find optimal
solutions with reasonable computation times. Typically, industry must
rely on solutions of unguaranteed quality that are constructed in an
ad hoc
manner. Fortunately, for some of these models
there are good approximation algorithms: algorithms that produce
solutions quickly that are provably close to optimal. Over the past 6
years, there has been a sequence of major breakthroughs in our
understanding of the design of approximation algorithms and of limits
to obtaining such performance guarantees; this area has been one of the
most flourishing areas of discrete mathematics and theoretical computer
science.
Gas-phase NO
+
affinities
Authors: Cacace F. , de Petris G. , Pepi F.
Published: July 2002

A scale of relative gas-phase NO
+
binding energies
(BEs) has been constructed by evaluation of NO
+
-transfer
equilibria L
1
NO
+
+ L
2
⇌
L
2
NO
+
+ L
1
by Fourier-transform ion
cyclotron resonance mass spectrometry and by application of the kinetic
method, based on the metastable fragmentation of
L
1
(NO
+
)L
2
nitryl-ion bound dimers.
The relative scale, anchored to the NO
+
affinity of water,
for 52 ligands, including alkyl halides, alkyl nitrates, alcohols,
nitroalkanes, nitriles, aldehydes, ketones, and aromatic and
heterocyclic compounds, led to an absolute NO
+
affinity
scale. The results are compared with those of an earlier study, and the
apparent discrepancies are traced to a different choice of the absolute
BE value used as the reference standard. The NO
+
BEs fit a
satisfactorily linear correlation when plotted versus the corresponding
proton affinities (PAs). The NO
+
BEs, while much lower than
the PAs, are nevertheless higher than the corresponding BEs of the
strictly related NO
2
+
cation, a result consistent with
the experimental and theoretical results currently available on the
structure and the stability of NO
+
and NO
2
+
complexes. The NO
+
BE vs. PA correlation allows one to
estimate within 1–2 kcal·mol
−1
the NO
+
BE of the molecules included in the comprehensive PA compilations
currently available. For example, the correlation gives the following
NO
+
affinities of the DNA bases, in
kcal·mol
−1
(1 kcal = 4.18 kJ): adenine, 40.3;
cytosine, 40.4; guanine, 40.1; and thymine, 34.9. The experimental
NO
+
BE of thymine, the only one accessible to direct
measurement, amounts to 35.6 ± 2 kcal·mol
−1
,
which underlines the predictive value of the correlation. This study
reports the second successful extension of the kinetic method to the
evaluation of the
absolute
BEs of polyatomic cations,
following our recent application to the strictly related
NO
2
+
ion.
Representational difference analysis of a committed myeloid progenitor cell line reveals evidence for bilineage potential
Authors: Lawson Nathan D. , Berliner Nancy
Published: July 2002

In this study we have sought to characterize a committed myeloid progenitor cell line in an attempt to isolate general factors that may promote differentiation. We used cDNA representational difference analysis (RDA), which allows analysis of differential gene expression, to compare EML and EPRO cells. We have isolated nine differentially expressed cDNA fragments as confirmed by slot blot, Northern, and PCR analysis. Three of nine sequences appear to be novel whereas the identity of the remaining fragments suggested that the EPRO cell line is multipotent. Among the isolated sequences were eosinophilic, monocytic, and neutrophilic specific genes. Therefore, we tested the ability of EPRO cells to differentiate along multiple myeloid lineages and found that EPRO cells exhibited morphologic maturation into either monocyte/macrophages or neutrophils, but not eosinophils. Furthermore, when EPRO cells were exposed to ATRA, neutrophil specific genes were induced, whereas monocytic markers were induced by phorbol ester treatment. This study highlights the use of cDNA RDA in conjunction with the EML/EPRO cell line to isolate markers associated with macrophage and neutrophil differentiation and establishes the usefulness of this system in the search for factors involved in myeloid commitment.
Smooth muscle myosin mutants containing a single tryptophan reveal molecular interactions at the actin-binding interface
Authors: Yengo C. M. , Fagnant P. M. , Chrin L. , Rovner A. S. , Berger C. L.
Published: July 2002

Elucidation of the molecular details of the cyclic actomyosin interaction requires the ability to examine structural changes at specific sites in the actin-binding interface of myosin. To study these changes dynamically, we have expressed two mutants of a truncated fragment of chicken gizzard smooth muscle myosin, which includes the motor domain and essential light chain (MDE). These mutants were engineered to contain a single tryptophan at (Trp-546) or near (Trp-625) the putative actin-binding interface. Both 546- and 625-MDE exhibited actin-activated ATPase and actin-binding activities similar to wild-type MDE. Fluorescence emission spectra and acrylamide quenching of 546- and 625-MDE suggest that Trp-546 is nearly fully exposed to solvent and Trp-625 is less than 50% exposed in the presence and absence of ATP, in good agreement with the available crystal structure data. The spectrum of 625-MDE bound to actin was quite similar to the unbound spectrum indicating that, although Trp-625 is located near the 50/20-kDa loop and the 50-kDa cleft of myosin, its conformation does not change upon actin binding. However, a 10-nm blue shift in the peak emission wavelength of 546-MDE observed in the presence of actin indicates that Trp-546, located in the A-site of the lower 50-kDa subdomain of myosin, exists in a more buried environment and may directly interact with actin in the rigor acto-S1 complex. This change in the spectrum of Trp-546 constitutes direct evidence for a specific molecular interaction between residues in the A-site of myosin and actin.
The polyoma virus T antigen interferes with interferon-inducible gene expression
Authors: Weihua Xiao , Ramanujam Sujatha , Lindner Daniel J. , Kudaravalli Rama D. , Freund Robert , Kalvakolanu Dhananjaya V.
Published: July 2002

Murine polyoma virus (MPyV) is a small DNA virus that induces tumors in multiple tissues of infected host. In this investigation, we show that cell lines derived from wild type virus-induced breast tumors are resistant to the growth inhibitory action of interferon β (IFN-β). Furthermore, replication of heterologous viruses such as vesicular stomatitis virus and encephalomyocarditis virus was not inhibited by IFN-β in these cells. This effect was due to inhibition of IFN-stimulated gene expression by viral T antigen. Activation of IFN-stimulated gene factor 3 was inhibited in cells derived from a tumor induced by wild-type MPyV but not those from a mutant that lacks the pRB binding site of the large T antigen. Similarly IFN-γ-inducible gene expression was also inhibited in cells transformed by wild-type virus. The levels of components of IFN-stimulated gene factor 3 and signal transducing Janus tyrosine kinases were comparable between the cells transformed by the wild-type and mutant viruses. The viral large T antigen bound to Janus tyrosine kinase 1 and inactivated signaling through IFN receptors. Thus, these studies identify a mechanism of viral resistance to IFN action.