bluuebunny/crossref_metadata_2025 huggingface dataset:
Competing influence of damage buildup and lattice vibrations on ion range profiles in Si
Authors: Posselt M. , Mäder M. , Grötzschel R. , Behar M.
Published: July 2003

Phosphorus depth profiles in Si obtained by 140 keV implantation in the [001] axial channel direction and in a direction 7° off axis are investigated at two different doses (5×1013 and 5×1015 cm−2) for implantation temperatures of 350 °C and room temperature (RT). At low dose and at channeling incidence, the penetration depth of implanted ions is higher at RT than at 350 °C. This behavior is caused by the dechanneling of lattice vibrations. At high dose, the temperature dependence of the shape of the implantation profile is opposite that at low dose, due to enhanced dechanneling by defect accumulation at RT. On the other hand, damage buildup does not occur at elevated temperature. The temperature dependence of the profiles obtained by tilted implantation is much less than for the channeled implants. The P profiles measured can be reproduced very well by atomistic simulations which take into account both lattice vibrations and defect accumulation during ion bombardment.
Irradiation-induced recovery of disorder in gallium nitride
Authors: Jiang W. , Weber W. J.
Published: July 2003

Gallium nitride has been irradiated to two fluences with energetic Au2+ ions at 300 K. Two different damage levels and depth profiles were produced that are characterized by near-surface damage accumulation and deeper-regime damage saturation. Thermal annealing at 873 K resulted in disorder recovery only in the near-surface region at low fluence. However, simultaneous irradiation with 5.4 MeV Si2+ ions during annealing at 873 K induced significant recovery over the entire damage profile at both low and high fluences. The irradiation-enhanced recovery is primarily attributed to defect-stimulated recovery and epitaxial recrystallization processes due to the creation of mobile Frenkel pairs.
Microscale electrospinning of polymer nanofiber interconnections
Authors: Kessick Royal , Tepper Gary
Published: July 2003

Polymer fiber interconnects were produced between microscale features on a substrate using only electrostatic forces. Electric-field-driven directed growth of nanoscale carboxymethylcellulose fibers was achieved between microscale droplets of a concentrated polymer solution. The fibers were studied using atomic force and scanning electron microscopy and were observed to emerge from the tip of conical protrusions formed at the surface of the droplets. The conical structures appear to be analogous to the characteristic Taylor cones formed in an electrospinning process and the process is interpreted as a microscale version of electrospinning requiring significantly lower driving potentials.
Thin film encapsulated flexible organic electroluminescent displays
Authors: Chwang Anna B. , Rothman Mark A. , Mao Sokhanno Y. , Hewitt Richard H. , Weaver Michael S. , Silvernail Jeff A. , Rajan Kamala , Hack Michael , Brown Julie J. , Chu Xi , Moro Lorenza , Krajewski Todd , Rutherford Nicole
Published: July 2003

We describe encapsulated passive matrix, video rate organic light-emitting diode (OLED) displays on flexible plastic substrates using a multilayer barrier encapsulation technology. The flexible OLED (FOLED™) displays are based on highly efficient electrophosphorescent OLED (PHOLED™) technology deposited on barrier coated plastic (Flexible Glass™ substrate) and are hermetically sealed with an optically transmissive multilayer barrier coating (Barix™ encapsulation). Preliminary lifetime to half initial luminance (L0∼100 cd/m2) of order 200 h is achieved on the passive matrix driven encapsulated 80 dpi displays; 2500 h lifetime is achieved on a dc tested encapsulated 5 mm2 FOLED test pixel. The encapsulated displays are flexed 1000 times around a 1 in. diameter cylinder and show minimal damage.
Molecular-beam epitaxy of the half-Heusler alloy NiMnSb on (In,Ga)As/InP (001)
Authors: Bach P. , Bader A. S. , Rüster C. , Gould C. , Becker C. R. , Schmidt G. , Molenkamp L. W. , Weigand W. , Kumpf C. , Umbach E. , Urban R. , Woltersdorf G. , Heinrich B.
Published: July 2003

We report the growth of the half-Heusler alloy NiMnSb on InP (001) by molecular-beam epitaxy using a lattice-matched (In,Ga)As buffer. High-resolution x-ray diffraction confirms a high crystalline quality. Spot-profile analysis low-energy electron diffraction measurements show well-defined surface reconstructions. The samples show the expected high Curie temperature and an uniaxial anisotropy.
Boron pile-up at the interface between plasma enhanced chemical vapor deposited TiSi2 film and BF2-doped Si
Authors: Lee Yoon-Jik , Sohn Hyun Chul , Chung Sung-Woong
Published: July 2003

We have investigated the redistribution of boron in BF2-doped Si substrate during plasma enhanced chemical vapor deposition (PECVD) of TiSi2 with secondary ion mass spectrometry. Boron concentration was observed to be increased at the TiSi2/Si interface after deposition of PECVD TiSi2. Contact resistance with PECVD TiSi2 was measured to be constant in the range of −30–125 °C, implying that the accumulated boron was electrically active and charge transport was field emission in nature.
Propagation of the electromagnetic field in fully coated near-field optical probes
Authors: Vaccaro L. , Aeschimann L. , Staufer U. , Herzig H. P. , Dändliker R.
Published: July 2003

Fully metal-coated near-field optical probes, based on a cantilever design, have been studied theoretically and experimentally. Numerical simulations prove that these structures allow nonzero modal emission of the electromagnetic field through a 60-nm-thick metallic layer, that is opaque when deposited on flat substrates. The far-field intensity patterns recorded experimentally correspond to the ones calculated for the fundamental and first excited LP modes. Moreover, this study demonstrates that a high confinement of the electromagnetic energy can be reached in the near-field, when illuminated with radially polarized light. Finally, it was verified that the confinement of the field depends on the volume of the probe apex.
NiAi
1.74
Al
0.26
and NiSi1.83Ga0.17: Two materials with perfect lattice match to Si
Authors: Richter Klaus W. , Hiebl Kurt
Published: July 2003

We report on the preparation and characterization of two materials based on cubic NiSi2 (CaF2-type, cF12, Fm3̄m) that show no lattice mismatch to Si and are thus promising materials for perfect epitaxial films grown on silicon. The perfectly lattice-matched materials are special compositions within the extended solid solution phases NiSi2−xAlx and NiSi2−xGax with x=0.26 for Al and x=0.17 for Ga, respectively. The variations of bulk lattice parameters with the composition were studied by means of x-ray diffraction and the melting behavior of the solid solution phases was investigated by differential thermal analysis. Both phases are thermally stable up to temperatures around 1000 °C. Phase diagram investigations show that the respective phases are in thermodynamic equilibrium with pure silicon. The electrical conductivity of NiSi2−xAlx and NiSi2−xGax was studied on selected bulk samples between 4.2 and 300 K. Both materials show metallic behavior with specific room-temperature resistivities between 23 and 40 μΩ cm. The difference is mainly due to intrinsic defects in these compounds.
Holographic optical coherence imaging of tumor spheroids
Authors: Yu P. , Mustata M. , Turek J. J. , French P. M. W. , Melloch M. R. , Nolte D. D.
Published: July 2003

We present depth-resolved coherence-domain images of living tissue using a dynamic holographic semiconductor film. An AlGaAs photorefractive quantum-well device is used in an adaptive interferometer that records coherent backscattered (image-bearing) light from inside rat osteogenic sarcoma tumor spheroids up to 1 mm in diameter in vitro. The data consist of sequential holographic image frames at successive depths through the tumor represented as a visual video “fly-through.” The images from the tumor spheroids reveal heterogeneous structures presumably caused by necrosis and microcalcifications characteristic of human tumors in their early avascular growth.
Characteristics of plasma processed SiC nanocrystallites and nanorods
Authors: Qadri S. B. , Imam M. A. , Feng C. R. , Rath B. B. , Yousuf M. , Singh S. K.
Published: July 2003

Nanoparticles and nanorods of SiC were synthesized using arc-plasma processing of coarse particles. X-ray diffraction and Raman spectroscopic studies showed the presence of β-SiC and carbon nanotubes in the starting coarse particles and SiC nanorods in the ultrafine particles produced by plasma processing. Scanning electron microscopy and transmission electron microscopy confirmed the presence of carbon nanotubes in the starting material and nanorods of SiC in the plasma-processed samples.
Confinement of triplet energy on phosphorescent molecules for highly-efficient organic blue-light-emitting devices
Authors: Tokito Shizuo , Iijima Toshiki , Suzuri Yoshiyuki , Kita Hiroshi , Tsuzuki Toshimitsu , Sato Fumio
Published: July 2003

We have significantly improved the emission efficiency in an organic light-emitting device (OLED) based on iridium (III)bis[(4,6-di-fluoropheny)-pyridinato-N,C2′]picolinate (FIrpic). To improve the efficiency, 4,4′-bis(9-carbazolyl)-2,2′-dimethyl-biphenyl, which has a high triplet energy, was used as the carrier-transporting host for the emissive layer. The FIrpic-based OLED exhibited a maximum external quantum efficiency of 10.4%, corresponding to a current efficiency of 20.4 cd/A, and a maximum power efficiency of 10.5 lm/W. The efficiency was drastically improved compared to that of a previously reported FIrpic-based OLED. This result indicates that triplet energy is efficiently confined on FIrpic molecules, resulting in the high efficiency.
Structure of the nanocrystals in oxyfluoride glass ceramics
Authors: Beggiora M. , Reaney I. M. , Islam M. S.
Published: July 2003

The crystallization of fluoro-silicate glasses obtained using high-purity SiO2, AlO1.5, CdF2, PbF2, ZnF2, and ErF3 has been investigated. Upon heat treatment, PbF2 nanocrystals form which host most of the Er3+ ions. The major peaks obtained by x-ray diffraction suggest that the nanocrystals are fluorite structured, but the low volume fraction of nanocrystals and line broadening due to their small size mean that unambiguous identification of the crystal structure is impossible. Therefore, atomistic simulation techniques have been performed to investigate the mechanism of incorporation of Er3+ in the PbF2 nanocrystals and polycrystalline (1−x)PbF2–xErF3 ceramics have been fabricated to study the expected phase assemblage.
Growth of InP quantum dots on vicinal GaAs (100) substrates by metalorganic chemical vapor deposition
Authors: Zhang X. B. , Heller R. D. , Noh M. S. , Dupuis R. D. , Walter G. , Holonyak N.
Published: July 2003

We report the growth of InP self-assembled quantum dots (QDs) on In0.5Al0.5P and In0.5(Al0.6Ga0.4)0.5P matrices, lattice matched on 0°, 2°, 6°, and 25° off-axis (100) GaAs substrates by metalorganic chemical vapor deposition. The influence of the substrate misorientation on the morphology and cathodoluminescence (CL) properties of the InP QDs was investigated. We find that the density of QDs grown on both In0.5Al0.5P and In0.5(Al0.6Ga0.4)0.5P matrices increases with the misorientation angle up to 6° off (100). At the same time, the dispersion of the QD size is getting larger for the growth on an In0.5Al0.5P matrix, but not for the growth on an In0.5(Al0.6Ga0.4)0.5P matrix. The InP QDs grown on In0.5(Al0.6Ga0.4)0.5P on 25° off-axis substrates are two-dimensionally well ordered. Moreover, the ordering improves and the density of QDs increases with an increase in the deposition of InP. The room-temperature CL intensity of InP QDs grown on a 25° off In0.5(Al0.6Ga0.4)0.5P is much stronger than that for InP QDs grown on a 25°-off In0.5Al0.5P matrix.
(Re)Solving Space and Time: Fulfilment Issues in Online Grocery Retailing
Authors: Murphy Andrew J
Published: July 2003

There has been much hype and speculation in the media and in academe on the vitality and future of the ‘Internet economy’. In this paper the author uses case studies from Britain, Canada, New Zealand and the United States to assess the strengths and weaknesses of online grocery retailers, from national chain stores pursuing a ‘bricks and clicks' strategy to ‘pure-play’ startups. He argues that delivering groceries via the Internet to customer doorsteps requires ways of solving space and time that are markedly different from previous trends in food retail logistics. He holds that solving problems of space management creates problems in the management of time and vice versa. In particular, ‘e-tailers’ struggle with fulfilment costs and logistics, and have attempted to manage customers' time and locations to reduce these costs. Store-based operations may be best suited for short-term profitability (or loss minimisation), whereas warehouse-based fulfilment may hold future promise of greater efficiency and flexibility. The author suggests that online organic home delivery may be the most successful type of online food retailer, for its size, given greater customer commitment and problems with store-based supply of organic food.
A Nation Still Dividing: The British Census and Social Polarisation 1971–2001
Authors: Dorling Danny , Rees Phil
Published: July 2003

This paper presents an analysis of the degree to which the population of Britain has become more or less geographically polarised as compared with 1991 and earlier censuses. We use the Key Statistics for local authorities from the 2001 Census, released on 13 February 2003 by the census authorities. All of the variables from the 26 Key Statistics tables which can be compared over time with the 1991 Census are examined. The analysis is then extended for a subset of variables that were similarly measured in 1971 and 1981. We conclude that for key aspects of life in Britain, as recorded by the censuses, the nation has continued in the 1990s to divide socially geographically, often at a faster rate than was occurring in the 1980s or 1970s. Where there appears to have been a reduction in polarisation it tends to have been for those aspects of life which are now poorly measured by the census. The paper concludes with speculation about the possible reasons for the continued division of the country into areas now more easily than ever typified as being old and young, settled and migrant, black and white, or rich and poor. Finally the potential for the continued sociospatial polarisation of Britain is discussed. The paper begins with a fictional vignette.
A two-locus gene conversion model with selection and its application to the human
RHCE
and
RHD
genes
Authors: Innan Hideki
Published: July 2003

A two-locus gene conversion model with selection is developed. Under the
joint action of selection, mutation, gene conversion, recombination, and
random genetic drift, approximate formulas for the expectations of the moments
of allele frequencies and the expected amounts of variation within and between
two loci are obtained by a diffusion method assuming relatively strong
selection. It is shown that the pattern of allelic variation is mainly
determined by the balance between gene conversion and selection, because these
two mechanisms act in opposite directions. As an application of the
theoretical results, the human
RHCE
and
RHD
genes are
considered. The very high level of amino acid divergence between the two genes
is observed only in a short region around exon 7. It is known that exon 7
encodes amino acids that characterize the difference between the
RHCE
and
RHD
antigens. The observed pattern of DNA variation in this
region is consistent with the selection model developed in this article,
suggesting that strong selection might be working to maintain the
RHCE
/
RHD
antigen variation in the two-locus system. The
selection intensity is estimated on the basis of the theoretical result.
Identification of transcription coactivator OCA-B-dependent genes involved in antigen-dependent B cell differentiation by cDNA array analyses
Authors: Kim Unkyu , Siegel Rachael , Ren Xiaodi , Gunther Cary S. , Gaasterland Terry , Roeder Robert G.
Published: July 2003

The tissue-specific transcriptional coactivator OCA-B is required for antigen-dependent B cell differentiation events, including germinal center formation. However, the identity of OCA-B target genes involved in this process is unknown. This study has used large-scale cDNA arrays to monitor changes in gene expression patterns that accompany mature B cell differentiation. B cell receptor ligation alone induces many genes involved in B cell expansion, whereas B cell receptor and helper T cell costimulation induce genes associated with B cell effector function. OCA-B expression is induced by both B cell receptor ligation alone and helper T cell costimulation, suggesting that OCA-B is involved in B cell expansion as well as B cell function. Accordingly, several genes involved in cell proliferation and signaling, such asLck, Kcnn4, Cdc37, cyclin D3, B4galt1, andMs4a11, have been identified as OCA-B-dependent genes. Further studies on the roles played by these genes in B cells will contribute to an understanding of B cell differentiation.
Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine
Authors: Luo Yunping , Zhou He , Mizutani Masato , Mizutani Noriko , Reisfeld Ralph A. , Xiang Rong
Published: July 2003

Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuatedSalmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN-γ and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis.
Survey of naturally occurring CD4
+
T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses
Authors: Gnjatic Sacha , Atanackovic Djordje , Jäger Elke , Matsuo Mitsutoshi , Selvakumar Annamalai , Altorki Nasser K. , Maki Robert G. , Dupont Bo , Ritter Gerd , Chen Yao-Tseng , Knuth Alexander , Old Lloyd J.
Published: July 2003

NY-ESO-1 is one of the most immunogenic proteins described in human
cancers, based on its capacity to elicit simultaneous antibody and
CD8
+
T cell responses
in vivo
. Although HLA class II
restricted epitopes from NY-ESO-1 have been identified, no broad survey has
yet established the status of natural CD4
+
T cell responses in
cancer patients in relation to CD8
+
and antibody responses. We used
a recently developed general strategy for monitoring CD4
+
responses
that overcomes the need for prior knowledge of epitope or HLA restriction to
analyze a series of 31 cancer patients and healthy donors for the presence of
CD4
+
T cells to NY-ESO-1, and related this response to NY-ESO-1
expression in tumor cells and serum antibodies to NY-ESO-1. None of the 18
patients that tested seronegative for NY-ESO-1 had detectable CD4
+
T cell responses. On the contrary, 11 of 13 cancer patients with serum
antibodies to NY-ESO-1 had polyclonal CD4
+
T cell responses
directed against various known and previously undescribed NY-ESO-1 epitopes.
NY-ESO-1 peptide 80–109 was the most immunogenic, with 10 of 11 patients
responding to this peptide. We show here that 12-mer determinants from
NY-ESO-1 eliciting a CD4
+
T cell response were peptide 87–98
with promiscuous HLA class II presentation, peptide 108–119 restricted
by HLA-DP4, and peptides 121–132 and 145–156, both shorter
epitopes from previously described HLA-DR4 peptides, also presented by
HLA-DR7. This study represents the next step in compiling a comprehensive
picture of the adaptive immune response to NY-ESO-1, and provides a general
strategy for analyzing the CD4
+
T cell response to other tumor
antigens eliciting a humoral immune response.
Use of avian retroviral vectors to introduce transcriptional regulators into mammalian cells for analyses of tumor maintenance
Authors: Pao William , Klimstra David S. , Fisher Galen H. , Varmus Harold E.
Published: July 2003

A key issue in cancer biology is whether genetic lesions involved in tumor
initiation or progression are required for tumor maintenance. This question
can be addressed with mouse models that conditionally express oncogenic
transgenes, i.e., under the control of tetracycline (tet)-dependent
transcriptional regulators. We have developed a system for studying tumor
maintenance by using avian retroviral [i.e., replication-competent avian
leukosis virus long terminal repeat with splice acceptor (RCAS)] vectors to
deliver the reverse tet transcriptional transactivator (rtTA) gene to somatic
mammalian cells. rtTA can regulate any transgene in which the protein coding
sequence is preceded by a tet-operator (tet-o); RCAS viruses infect only cells
engineered to express ectopically the avian retroviral receptor, TVA. One
vector, RCAS-
rtTA-IRES-GFP
, also encodes GFP to identify infected
cells. Infection of cells from β-actin TVA transgenic mice with this
vector permits efficient regulation of tet-responsive transgenes. Sarcomas
arise when p53-deficient murine embryonic fibroblasts carrying β-actin
TVA and tet-o-

K-ras4b
G12D

transgenes are infected with
RCAS-
rtTA-IRES-GFP
and introduced into nude mice treated with the tet
analog, doxycycline (dox); when dox is withdrawn,

K-ras4b
G12D

levels fall, cells undergo apoptosis, and
tumors regress. Regression can be prevented by means of a genetic
complementation assay in which tumors are superinfected before dox withdrawal
with other RCAS viruses, such as those carrying an active allele of
K-ras
. Many TVA and tet-regulated transgenic mice have been
generated; thus, this method for somatic cell-specific and temporally
controlled gene expression may have broad applications for the study of
oncogenesis and tumor maintenance, as well as other cell functions and
development.
X-ray crystal structures of the WT and a hyper-accurate ribosome from
Escherichia coli
Authors: Vila-Sanjurjo Antón , Ridgeway William K. , Seymaner Veysel , Zhang Wen , Santoso Steve , Yu Kexin , Cate Jamie H. Doudna
Published: July 2003

Protein biosynthesis on the ribosome requires accurate reading of the
genetic code in mRNA. Two conformational rearrangements in the small ribosomal
subunit, a closing of the head and body around the incoming tRNA and an RNA
helical switch near the mRNA decoding site, have been proposed to select for
complementary base-pairing between mRNA codons and tRNA anticodons. We
determined x-ray crystal structures of the WT and a hyper-accurate variant of
the
Escherichia coli
ribosome at resolutions of 10 and 9 Å,
respectively, revealing that formation of the intact 70S ribosome from its two
subunits closes the conformation of the head of the small subunit independent
of mRNA decoding. Moreover, no change in the conformation of the switch helix
is observed in two steps of tRNA discrimination. These 70S ribosome structures
indicate that mRNA decoding is coupled primarily to movement of the small
subunit body, consistent with previous proposals, whereas closing of the head
and the helical switch may function in other steps of protein synthesis.
Toward a phylogenetic chronology of ancient Gaulish, Celtic, and Indo-European
Authors: Forster Peter , Toth Alfred
Published: July 2003

Indo-European is the largest and best-documented language family in the
world, yet the reconstruction of the Indo-European tree, first proposed in
1863, has remained controversial. Complications may include ascertainment bias
when choosing the linguistic data, and disregard for the wave model of 1872
when attempting to reconstruct the tree. Essentially analogous problems were
solved in evolutionary genetics by DNA sequencing and phylogenetic network
methods, respectively. We now adapt these tools to linguistics, and analyze
Indo-European language data, focusing on Celtic and in particular on the
ancient Celtic language of Gaul (modern France), by using bilingual
Gaulish–Latin inscriptions. Our phylogenetic network reveals an early
split of Celtic within Indo-European. Interestingly, the next branching event
separates Gaulish (Continental Celtic) from the British (Insular Celtic)
languages, with Insular Celtic subsequently splitting into Brythonic (Welsh,
Breton) and Goidelic (Irish and Scottish Gaelic). Taken together, the network
thus suggests that the Celtic language arrived in the British Isles as a
single wave (and then differentiated locally), rather than in the traditional
two-wave scenario (“P-Celtic” to Britain and
“Q-Celtic” to Ireland). The phylogenetic network furthermore
permits the estimation of time in analogy to genetics, and we obtain tentative
dates for Indo-European at 8100 BC ± 1,900 years, and for the arrival
of Celtic in Britain at 3200 BC ± 1,500 years. The phylogenetic method
is easily executed by hand and promises to be an informative approach for many
problems in historical linguistics.
Huntington disease expansion mutations in humans can occur before meiosis is completed
Authors: Yoon Song-Ro , Dubeau Louis , de Young Margot , Wexler Nancy S. , Arnheim Norman
Published: July 2003

Single-molecule DNA analysis of testicular germ cells isolated by laser
capture microdissection from two Huntington disease patients showed that
trinucleotide repeat expansion mutations were present before the end of the
first meiotic division, and some mutations were present even before meiosis
began. Most of the larger Huntington disease mutations were found in the
postmeiotic cell population, suggesting that expansions may continue to occur
during meiosis and/or after meiosis is complete. Defining the germ-line cell
compartments where the trinucleotide repeat expansions occur could help to
elucidate the underlying mechanisms of instability.
An unusual internal ribosomal entry site of inverted symmetry directs expression of a potato leafroll polerovirus replication-associated protein
Authors: Jaag Hannah Miriam , Kawchuk Lawrence , Rohde Wolfgang , Fischer Rainer , Emans Neil , Prüfer Dirk
Published: July 2003

Potato leafroll polerovirus (PLRV) genomic RNA acts as a polycistronic mRNA
for the production of proteins P0, P1, and P2 translated from the
5′-proximal half of the genome. Within the P1 coding region we
identified a 5-kDa replication-associated protein 1 (
Rap1
) essential
for viral multiplication. An internal ribosome entry site (IRES) with unusual
structure and location was identified that regulates
Rap1
translation. Core structural elements for internal ribosome entry include a
conserved AUG codon and a downstream GGAGAGAGAGG motif with inverted symmetry.
Reporter gene expression in potato protoplasts confirmed the internal ribosome
entry function. Unlike known IRES motifs, the PLRV IRES is located completely
within the coding region of
Rap1
at the center of the PLRV
genome.
Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase
Authors: Trebino Catherine E. , Stock Jeffrey L. , Gibbons Colleen P. , Naiman Brian M. , Wachtmann Timothy S. , Umland John P. , Pandher Karamjeet , Lapointe Jean-Martin , Saha Sipra , Roach Marsha L. , Carter Demetrius , Thomas Nathalie A. , Durtschi Becky A. , McNeish John D. , Hambor John E. , Jakobsson Per-Johan , Carty Thomas J. , Perez Jose R. , Audoly Laurent P.
Published: July 2003

Prostaglandin (PG)E
2
is a potent mediator of pain and
inflammation, and high levels of this lipid mediator are observed in numerous
disease states. The inhibition of PGE
2
production to control pain
and to treat diseases such as rheumatoid arthritis to date has depended on
nonsteroidal antiinflammatory agents such as aspirin. However, these agents
inhibit the synthesis of all prostanoids. To produce biologically active
PGE
2
, PGE synthases catalyze the isomerization of PGH
2
into PGE
2
. Recently, several PGE synthases have been identified and
cloned, but their role in inflammation is not clear. To study the
physiological role of the individual PGE synthases, we have generated by
targeted homologous recombination a mouse line deficient in microsomal PGE
synthase 1 (mPGES1) on the inbred DBA/1lacJ background. mPGES1-deficient
(mPGES1
-/-
) mice are viable and fertile and develop normally
compared with wild-type controls. However, mPGES1
-/-
mice displayed
a marked reduction in inflammatory responses compared with
mPGES1
+/+
mice in multiple assays. Here, we identify mPGES1 as the
PGE synthase that contributes to the pathogenesis of collagen-induced
arthritis, a disease model of human rheumatoid arthritis. We also show that
mPGES1 is responsible for the production of PGE
2
that mediates
acute pain during an inflammatory response. These findings suggest that mPGES1
provides a target for the treatment of inflammatory diseases and pain
associated with inflammatory states.
Informational constraints on optimal sex allocation in ants
Authors: Boomsma Jacobus J. , Nielsen Jannie , Sundström Liselotte , Oldham Neil J. , Tentschert Jutta , Petersen Hans Christian , Morgan E. David
Published: July 2003

Workers of the ant
Formica truncorum
specialize in rearing females
or males depending on the number of fathers of a colony. These split sex
ratios increase inclusive fitness, but it has remained unknown how workers
assess the number of patrilines in their colonies and to what extent their
reproductive decisions are constrained by lack of information. By analysis of
the quantitative variation in cuticular hydrocarbon profiles of workers of
multiply mated queens, we show that the heritable component of recognition
cues is low and that the extent of sex ratio biasing toward males is
correlated with patriline differences in hydrocarbon profiles. Workers are
thus able to capitalize on colony-level relatedness asymmetry, but their
inclusive fitness is constrained by uninformative recognition cues. These
results are consistent with the hypothesis that the occasional expression of
nepotistic phenotypes favoring full-sisters over half-sisters maintains
selection against informative recognition cues. We evaluate how inclusive
fitness theory may be used to predict the number and kind of recognition cues
in insect societies of a specific relatedness structure.
Complex landscape of protein structural dynamics unveiled by nanosecond Laue crystallography
Authors: Bourgeois Dominique , Vallone Beatrice , Schotte Friedrich , Arcovito Alessandro , Miele Adriana E. , Sciara Giuliano , Wulff Michael , Anfinrud Philip , Brunori Maurizio
Published: July 2003

Although conformational changes are essential for the function of proteins,
little is known about their structural dynamics at atomic level resolution.
Myoglobin (Mb) is the paradigm to investigate conformational dynamics because
it is a simple globular heme protein displaying a photosensitivity of the
iron–ligand bond. Upon laser photodissociation of carboxymyoglobin Mb a
nonequilibrium population of protein structures is generated that relaxes over
a broad time range extending from picoseconds to milliseconds. This process is
associated with migration of the ligand to cavities in the matrix and with a
reduction in the geminate rebinding rate by several orders of magnitude. Here
we report nanosecond time-resolved Laue diffraction data to 1.55-Å
resolution on a Mb mutant, which depicts the sequence of structural events
associated with this extended relaxation. Motions of the distal E-helix,
including the mutated residue Gln-64(E7), and of the CD-turn are found to lag
significantly (100–300 ns) behind local rearrangements around the heme
such as heme tilting, iron motion out of the heme plane, and swinging of the
mutated residue Tyr-29(B10), all of which occur promptly (≤3 ns). Over the
same delayed time range, CO is observed to migrate from a cavity distal to the
heme known to bind xenon (called Xe4) to another such cavity proximal to the
heme (Xe1). We propose that the extended relaxation of the globin moiety
reflects reequilibration among conformational substates known to play an
essential role in controlling protein function.
High-frequency gene transfer from the chloroplast genome to the nucleus
Authors: Stegemann Sandra , Hartmann Stefanie , Ruf Stephanie , Bock Ralph
Published: July 2003

Eukaryotic cells arose through endosymbiotic uptake of free-living bacteria
followed by massive gene transfer from the genome of the endosymbiont to the
host nuclear genome. Because this gene transfer took place over a time scale
of hundreds of millions of years, direct observation and analysis of primary
transfer events has remained difficult. Hence, very little is known about the
evolutionary frequency of gene transfer events, the size of transferred genome
fragments, the molecular mechanisms of the transfer process, or the
environmental conditions favoring its occurrence. We describe here a genetic
system based on transgenic chloroplasts carrying a nuclear selectable marker
gene that allows the efficient selection of plants with a nuclear genome that
carries pieces transferred from the chloroplast genome. We can select such
gene transfer events from a surprisingly small population of plant cells,
indicating that the escape of genetic material from the chloroplast to the
nuclear genome occurs much more frequently than generally believed and thus
may contribute significantly to intraspecific and intraorganismic genetic
variation.
A dual mechanism controlling the localization and function of exocytic v-SNAREs
Authors: Martinez-Arca Sonia , Rudge Rachel , Vacca Marcella , Raposo Graça , Camonis Jacques , Proux-Gillardeaux Véronique , Daviet Laurent , Formstecher Etienne , Hamburger Alexandre , Filippini Francesco , D'Esposito Maurizio , Galli Thierry
Published: July 2003

SNARE [soluble NSF (
N
-ethylmaleimide-sensitive factor) attachment
protein receptor] proteins are essential for membrane fusion but their
regulation is not yet fully understood. We have previously shown that the
amino-terminal Longin domain of the v-SNARE TI-VAMP (tetanus
neurotoxin-insensitive vesicle-associated membrane protein)/VAMP7 plays an
inhibitory role in neurite outgrowth. The goal of this study was to
investigate the regulation of TI-VAMP as a model of v-SNARE regulation. We
show here that the Longin domain (LD) plays a dual role. First, it negatively
regulates the ability of TI-VAMP and of a Longin/Synaptobrevin chimera to
participate in SNARE complexes. Second, it interacts with the adaptor complex
AP-3 and this interaction targets TI-VAMP to late endosomes. Accordingly, in
mocha
cells lacking AP-3δ, TI-VAMP is retained in an early
endosomal compartment. Furthermore, TI-VAMPc, an isoform of TI-VAMP lacking
part of the LD, does not interact with AP-3, and therefore is not targeted to
late endosomes; however, this shorter LD still inhibits SNARE-complex
formation. These findings support a mechanism controlling both localization
and function of TI-VAMP through the LD and clathrin adaptors. Moreover, they
point to the amino-terminal domains of SNARE proteins as multifunctional
modules responsible for the fine tuning of SNARE function.
GATA-1-dependent transcriptional repression of
GATA-2
via disruption of positive autoregulation and domain-wide chromatin remodeling
Authors: Grass Jeffrey A. , Boyer Meghan E. , Pal Saumen , Wu Jing , Weiss Mitchell J. , Bresnick Emery H.
Published: July 2003

Interplay among GATA transcription factors is an important determinant of
cell fate during hematopoiesis. Although GATA-2 regulates hematopoietic stem
cell function, mechanisms controlling
GATA-2
expression are
undefined. Of particular interest is the repression of
GATA-2
,
because sustained
GATA-2
expression in hematopoietic stem and
progenitor cells alters hematopoiesis.
GATA-2
transcription is
derepressed in erythroid precursors lacking GATA-1, but the underlying
mechanisms are unknown. Using chromatin immunoprecipitation analysis, we show
that GATA-1 binds a highly restricted upstream region of the ≈70-kb
GATA-2
domain, despite >80 GATA sites throughout the domain.
GATA-2 also binds this region in the absence of GATA-1. Genetic
complementation studies in GATA-1-null cells showed that GATA-1 rapidly
displaces GATA-2, which is coupled to transcriptional repression. GATA-1 also
displaces CREB-binding protein (CBP), despite the fact that GATA-1 binds CBP
in other contexts. Repression correlates with reduced histone acetylation
domain-wide, but not altered methylation of histone H3 at lysine 4. The GATA
factor-binding region exhibited cell-type-specific enhancer activity in
transient transfection assays. We propose that GATA-1 instigates
GATA-2
repression by means of disruption of positive autoregulation,
followed by establishment of a domain-wide repressive chromatin structure.
Such a mechanism is predicted to be critical for the control of
hematopoiesis.
A large pool of releasable vesicles in a cortical glutamatergic synapse
Authors: Hallermann Stefan , Pawlu Christian , Jonas Peter , Heckmann Manfred
Published: July 2003

To probe exocytosis at a cortical glutamatergic synapse, we made
capacitance measurements in whole-cell recorded hippocampal mossy fiber
terminals. Evaluation of different methods by using a morphology-based
equivalent electrical model revealed that quantitative capacitance
measurements are possible in this presynaptic structure. Voltage pulses
leading to presynaptic Ca
2+
inflow evoked large capacitance signals
that showed saturation with increasing pulse duration. The mean peak
capacitance increase was 100 fF, corresponding to a pool of ≈1,400
releasable vesicles. Thus hippocampal mossy fiber synapses have a vesicular
“maxipool.” Large pool size and rapid vesicle recycling may
underlie the uniquely large extent of activity-dependent plasticity in this
synapse.
Peptide synthesis with a template-like RNA guide and aminoacyl phosphate adaptors
Authors: Tamura Koji , Schimmel Paul
Published: July 2003

The genetic code is thought to have developed from an early system of
RNA-dependent peptide synthesis. To investigate one kind of template-like
peptide synthesis that might emerge from an RNA world, we constructed highly
reactive aminoacyl phosphate oligonucleotides as adaptors that bound to RNA
guide sequences. The reactive aminoacyl groups mimic a chemistry found in
modern protein biosynthesis. Guide sequence interactions with adaptors were
borrowed in part from universal contacts seen between tRNAs and rRNA. With
these constructions, di- and tripeptides formed in a single guide
sequence-dependent reaction. The order of amino acids was not random but
directional in a way consistent with substrate reactivities. No ribosomes or
ribozymes were required. Thus, aminoacyl phosphate adaptors and RNA guides
could, in principle, have been intermediates in the transition from the RNA
world to modern template-dependent protein synthesis.
Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia
Authors: Miyakawa Tsuyoshi , Leiter Lorene M. , Gerber David J. , Gainetdinov Raul R. , Sotnikova Tatyana D. , Zeng Hongkui , Caron Marc G. , Tonegawa Susumu
Published: July 2003

Calcineurin (CN), a calcium- and calmodulin-dependent protein phosphatase,
plays a significant role in the central nervous system. Previously, we
reported that forebrain-specific CN knockout mice (CN mutant mice) have
impaired working memory. To further analyze the behavioral effects of CN
deficiency, we subjected CN mutant mice to a comprehensive behavioral test
battery. Mutant mice showed increased locomotor activity, decreased social
interaction, and impairments in prepulse inhibition and latent inhibition. In
addition, CN mutant mice displayed an increased response to the locomotor
stimulating effects of MK-801. Collectively, the abnormalities of CN mutant
mice are strikingly similar to those described for schizophrenia. We propose
that alterations affecting CN signaling could comprise a contributing factor
in schizophrenia pathogenesis.
Erasure of CpG methylation in
Arabidopsis
alters patterns of histone H3 methylation in heterochromatin
Authors: Tariq Muhammad , Saze Hidetoshi , Probst Aline V. , Lichota Jacek , Habu Yoshiki , Paszkowski Jerzy
Published: July 2003

In mammals and plants, formation of heterochromatin is associated with
hypermethylation of DNA at CpG sites and histone H3 methylation at lysine 9.
Previous studies have revealed that maintenance of DNA methylation in
Neurospora
and
Arabidopsis
requires histone H3 methylation.
A feedback loop from DNA methylation to histone methylation, however, is less
understood. Its recent examination in
Arabidopsis
with a partial loss
of function in DNA methyltransferase 1 (responsible for maintenance of CpG
methylation) yielded conflicting results. Here we report that complete removal
of CpG methylation in an
Arabidopsis
mutant null for DNA maintenance
methyltransferase results in a clear loss of histone H3 methylation at lysine
9 in heterochromatin and also at heterochromatic loci that remain
transcriptionally silent. Surprisingly, these dramatic alterations are not
reflected in heterochromatin relaxation.
Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations
Authors: Muzet Nicolas , Guillot Benoît , Jelsch Christian , Howard Eduardo , Lecomte Claude
Published: July 2003

The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-NDFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the programmoproby using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from theambersoftware dictionary are compared. The electrostatic complementarity between the cofactor NADP+and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.
Shape bistability of a membrane neck: A toggle switch to control vesicle content release
Authors: Frolov Vadim A. , Lizunov Vladimir A. , Dunina-Barkovskaya Antonina Ya. , Samsonov Andrey V. , Zimmerberg Joshua
Published: July 2003

Shape dynamics and permeability of a membrane neck connecting a vesicle and
plasma membrane are considered. The neck is modeled by a lipid membrane tubule
extended between two parallel axisymmetric rings. Within a range of lengths,
defined by system geometry and mechanical properties of the membrane, the
tubule has two stable shapes: catenoidal microtubule and cylindrical
nanotubule. The permeabilities of these two shapes, measured as ionic
conductivity of the tubule interior, differ by up to four orders of magnitude.
Near the critical length the transitions between the shapes occur within less
than a millisecond. Theoretical estimates show that the shape switching is
controlled by a single parameter, the tubule length. Thus the tubule
connection can operate as a conductivity microswitch, toggling the release of
vesicle content in such cellular processes as “kiss-and-run”
exocytosis. In support of this notion, bistable behavior of membrane
connections between vesicles and the cell plasma membrane in macrophages is
demonstrated.
A look at neural integration in the human auditory system through the stapedius muscle reflex
Authors: Zwislocki Jozef J.
Published: July 2003

Ipsilateral and contralateral stapedius muscle contractions were studied as functions of the sound pressure level (SPL) and duration of 2-kHz tone bursts. The study complemented a preceding study in which temporal summation of stapedius muscle contractions produced by pairs of short tone bursts was determined and analyzed. The muscle contractions were determined indirectly by measuring changes in the acoustic impedance they produced at the tympanic membrane. The data for the stapedius muscle contraction as a function of tone-burst duration were derived from another study and analyzed in part with the help of the SPL functions obtained in the present study. According to the experimental results, the stapedius muscle contraction produced by contralateral stimulation follows a compressive power function paralleling both the cochlear output and loudness functions. The ipsilateral contraction follows an expansive power function. Mathematical analysis showed that the muscle tension due to contralateral stimulation increases with tone duration approximately according to the characteristic of a linear integrator having an exponentially decaying memory with a time constant that increases with SPL from ≈200 to 370 msec. The simple relationship appears to be possible because of mutual cancellation of neural-processing characteristics preceding and following the temporal integration.
Tau filaments from human brain and from
in vitro
assembly of recombinant protein show cross-β structure
Authors: Berriman John , Serpell Louise C. , Oberg Keith A. , Fink Anthony L. , Goedert Michel , Crowther R. Anthony
Published: July 2003

Abnormal filaments consisting of hyperphosphorylated microtubule-associated
protein tau form in the brains of patients with Alzheimer's disease, Down's
syndrome, and various dementing tauopathies. In Alzheimer's disease and Down's
syndrome, the filaments have two characteristic morphologies referred to as
paired helical and straight filaments, whereas in tauopathies, there is a
wider range of morphologies. There has been controversy in the literature
concerning the internal molecular fine structure of these filaments, with
arguments for and against the cross-β structure demonstrated in many
other amyloid fibers. The difficulty is to produce from brain pure
preparations of filaments for analysis. One approach to avoid the need for a
pure preparation is to use selected area electron diffraction from small
groups of filaments of defined morphology. Alternatively, it is possible to
assemble filaments
in vitro
from expressed tau protein to produce a
homogeneous specimen suitable for analysis by electron diffraction, x-ray
diffraction, and Fourier transform infrared spectroscopy. Using both these
approaches, we show here that native filaments from brain and filaments
assembled
in vitro
from expressed tau protein have a clear
cross-β structure.