bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of gate patterning by using a hard mask on 0.25 μm technology and below
Authors: Lee H. C. , Creusen M. , Vanhaelemeersch S.
Published: July 2002

In this article, the feasibility of gate patterning for 0.25 μm technology and below by using a hard mask has been investigated in terms of polymerization, selectivity to the gate oxide, compatibility with deep ultraviolet lithography, and plasma damage. A 50 nm SiO2 hard mask is thick enough to protect the underlying polysilicon layer without profile distortion at the outermost lines. The use of a SiO2 hard mask also increases the gate oxide selectivity up to 45% as compared to a photoresist mask. The amount of carbon atoms in the etched gate oxide area is much lower for the SiO2 mask process than for the photoresist process. Carbon plays an important role in reducing the gate oxide selectivity and decreasing the oxide reliability. Due to local charging, oxide pitting along the polysilicon lines is much more pronounced when using a photoresist mask. Charging effects caused by electron shading were expected to be lower for the thin SiO2 mask due to the lower aspect ratio; however, from Qbd (charge to breakdown) measurements on overlapping capacitors, no significant difference between the SiO2 and the photoresist mask processes was observed. In the mean time, the 4.5 nm gate oxide was better than the 7 nm gate oxide in terms of oxide degradation by charging. In the regime of gate oxide thickness under 5 nm, physical damage by charging seems to be more of a concern than electrical damage. Consequently, a SiO2 hard mask process can provide clean, highly selective, and less damaged polysilicon gate patterning for 0.25 μm technology and below.
Optimal design using neural network and information analysis in plasma etching
Authors: Chen Junghui , Po-Tao Chu Paul , Shan Hill Wong David , Jang Shi-Shang
Published: July 2002

The goal of this article is to use operating data-based approaches for automating the manufacturing of submicron flash memory devices in semiconductor. This novel technique which combines the neural network and information inductive analysis has recently been proposed. It is used in this article to generate the recipe for plasma etching process design. Traditional plasma etching variables such as pressure, gas flows, temperature, rf power, etc., are used to build the neural network for predicting etching rate of polysilicon and field oxide, and the uniformity of field oxide. The information inductive analysis based on the information entropy and fuzzy clustering analysis is then utilized to look for the candidate points in each optimal region whose response surface is constructed based on the neural network model. With only a few runs, the best optimal condition getting close to the design requirements is found. Since the complexity of plasma modeling and design at the equipment level is presently ahead of theoretical method from a fundamental physical standpoint, the proposed method can effectively cope with nonlinear characteristics in the plasma etching process, giving good design directions and taking advantage of traditional statistical approaches. Using the proposed method within four runs and a total of 26 experimental points, the recipe that meets all specifications is found.
Alignment with exposed resist in photolithography
Authors: Burm J. , Tate A. , Kopf R. F. , Ryan R. W. , Hamm R. A. , Chirovsky L. M.
Published: July 2002

We have developed a method for producing alignment marks on a wafer using exposed photoresist. Alignment to the exposed pattern is possible without having to develop out the pattern, provided that there is enough contrast between the exposed and unexposed areas. The exposed pattern was easily found for alignment using the He–Ne laser alignment system in our stepper. Although the contrast between the exposed and unexposed resist was rather faint to the human eye, the contrast was greatly improved using a commercially available contrast enhancement layer, so this method can be used in contact lithography where multiple mask levels must be exposed prior to development. The ability to align to the exposed pattern prior to development is especially useful in stepper-based lithography. For example, wafers may be aligned using the stepper for multiple mask exposures or for multilevel resist schemes prior to pattern development. In addition, very thick resist can be exposed using multiple exposures and changing the depth of focus.
Growth, optical, and electron transport studies across isotype n-GaAs/n-Ge heterojunctions
Authors: Hudait Mantu Kumar , Krupanidhi S. B.
Published: July 2002

A diode structure consisting of a polar epilayer on a nonpolar substrate grown by metalorganic vapor phase epitaxy often faces problems of antiphase domain formation in the polar semiconductor and cross diffusion across the heterointerface. Ge outdiffusion into GaAs epilayers was studied by low temperature photoluminescence spectroscopy after etching the film from the surface. The absence of p-n junction formation inside the Ge substrate from interdiffusion of Ga and As has been studied by current-voltage characteristics using mesa diodes. These observations were confirmed by electrochemical capacitance voltage polaron profiler and secondary ion mass spectroscopy techniques. To understand the material quality and current conduction mechanism across the GaAs/Ge heterojunction, I-V characteristics of Si-doped n-GaAs/n-Ge isotype heterojunctions using Au Schottky diodes have been studied for different doping densities. A plethora of growth conditions appear in the literature concerning the attempt to grow antiphase domain (APD)-free GaAs on Ge. In the present case, even though the growth temperature regime is close to reported values, the main difference in minimizing APD formation may arise from the growth rates (∼3 μm/h) and the V/III ratio (∼88).
Multiwafer gas source molecular beam epitaxial system for production technology
Authors: Izumi Shigekazu , Kouji Yoshiharu , Hayafuji Norio
Published: July 2002

High throughput epitaxial wafer production is demonstrated by using a newly designed multiwafer gas source molecular beam epitaxy apparatus. The actual application data show excellent results of uniformity, cost performance, and material performance through practical mass production operation. Electron mobility as high as 124 000 cm2/V s is obtained at 77 K for a 7-μm-thick GaAs layer with a carrier concentration of 7.7×1013 cm−3. A typical surface defect density of 25 cm−2 is achieved for continuously grown 1.7-μm-thick metal–semiconductor field effect transistor (MESFET) structures. The uniformity of sheet resistance in n-GaAs and AlAs mole fractions in AlGaAs is less than 2.0% (1.5% and 0.27%, respectively) over a 27 cm diameter area. A quantitative throughput number for a typical growth of a MESFET structure is four 4 in. or seven 3 in. diameter wafers per 2.5 h in a continuous process flow.
Improvement of molecular beam epitaxy-grown low-temperature GaAs through p doping with Be and C
Authors: Specht P. , Lutz R. C. , Zhao R. , Weber E. R. , Liu W. K. , Bacher K. , Towner F. J. , Stewart T. R. , Luysberg M.
Published: July 2002

Nonstoichiometric GaAs thin layers can be produced in molecular beam epitaxy if they are grown at temperatures below 400 °C [low-temperature (LT)-GaAs]. Due to the incorporation of excess As in the form of native point defects, namely As antisite defects (AsGa), these layers exhibit ultrashort time response and, after annealing at 600 °C, excellent semi-insulating behavior. The ultrashort time response, however, is governed by the concentration of ionized antisites ([AsGa+]), which are just a few percent of the total concentration of antisites ([AsGa]). Additionally, thermal annealing leads to As precipitate formation and out-diffusion of point defects into adjacent layers. Recent studies have shown that p-type doping with Be increases the thermal stability of point defects and shortens the time response due to an increase in ionized antisites, while maintaining the high electrical resistivity in as-grown material. We report on the studies of p doping of LT-GaAs with Be and, alternatively, with C in order to enhance the thermal stability in semi-insulating thin layers with ultrashort carrier trapping times. The epilayers were characterized and their electronic properties investigated by time-resolved reflectivity transients and Hall measurements. The properties of as-grown and annealed thin layers will be discussed based on the results of defect concentrations. These results will be compared to those obtained in undoped LT-GaAs.
Evolution of microstructure and dislocation dynamics in InxGa1−xP graded buffers grown on GaP by metalorganic vapor phase epitaxy: Engineering device-quality substrate materials
Authors: Kim Andrew Y. , McCullough Wendy S. , Fitzgerald Eugene A.
Published: July 2002

This study explores the dislocation dynamics of strain relaxation in graded composition buffers of InxGa1−xP grown on GaP (InxGa1−xP/GaP) by metalorganic vapor phase epitaxy. Transmission electron microscopy, cathodoluminescence imaging, atomic force microscopy, and triple-axis x-ray diffraction are applied to the characterization of InxGa1−xP/GaP with final compositions ranging from x=0.09 to x=0.39 and growth temperatures ranging from 650 to 810 °C. The previously reported escalation of defect density with continued grading of InxGa1−xP/GaP beyond x∼0.3 is discovered to be due to the formation of dislocation pileups. A new defect microstructure with a branching morphology and featuring sharp local strain fields, hereafter referred to as branch defects, is observed to pin dislocations and cause the dislocation pileups. Branch defect morphology varies strongly with growth temperature, becoming significantly stronger with increasing growth temperature and causing severe material degradation above 700 °C. Further experiments show that branch defects evolve during growth and that the onset of branch defect formation is delayed by increasing growth temperature. Comparison with the literature suggests that the evolution of branch defects may control the microstructure of indium-bearing phosphides and arsenides over a very wide range of conditions. In the absence of branch defects at high growth temperatures and low indium compositions near x∼0.1, nearly ideal dislocation dynamics dominated by dislocation glide kinetics are recovered, providing the first experimental proof of a kinetic model for graded buffer relaxation. This new understanding of the evolution of microstructure and dislocation dynamics in InxGa1−xP/GaP suggests that growth temperature must be optimized as a function of composition for optimal material quality. A simple process optimization in InxGa1−xP/GaP graded to x=0.39 results in an overall threading dislocation density of 4.7×106 cm−2, which is the lowest reported value to date for x>0.3. Combining the new observations with earlier findings, we present three basic design rules for producing practical, device-quality graded buffers: branch defects must be avoided or suppressed, growth temperature must be maximized, and surface roughness must be minimized. Using these design rules, we also present optimization strategies for achieving device-quality substrate materials. Applying these design rules and optimization strategies, we hope to achieve threading dislocation densities of <106 cm−2 in InxGa1−xP/GaP over the full range of useful compositions.
Scanning probe lithography using a cantilever with integrated transistor for on-chip control of the exposing current
Authors: Wilder Kathryn , Quate Calvin F.
Published: July 2002

Scanning probe lithography uses electrons field emitted from a micromachined probe tip to expose organic polymer resists. The exposed pattern dimension is set by the electron dose delivered to the resist and can be controlled down to <30 nm. We have integrated a metal–oxide–semiconductor field-effect transistor (MOSFET) onto the cantilever chip to act as a current source to control the electron exposure dose from the tip. The silicon cantilever and tip form the drain of the MOSFET. In the saturation regime, the transistor acts as a voltage-controlled current source. A low voltage signal to the transistor gate sets the exposure dose. We describe the design and fabrication of this device and demonstrate that the integrated transistor can be used as the sole current-control electronics for uniform high-resolution lithography, eliminating the need for external circuitry.
Sharpening of field-ion specimens and positioning of features of interest by ion-beam milling
Authors: Larson D. J. , Russell K. F. , Cerezo A.
Published: July 2002

Atom-probe field-ion microscopy is a powerful technique used to study microstructural features such as precipitates and grain boundaries. However, the amount of material which can be analyzed in a field-ion specimen is usually limited by the blunting effects of field evaporation. This limitation can be overcome by the use of ion-beam milling to resharpen field-ion specimens blunted by evaporation. In addition, ion-beam milling allows the positioning of features of interest in the apex region of electropolished field-ion specimens. Ion milling has been found to proceed in two stages. Stage I is a radius-reduction stage during which there is only limited removal of material directly from the apex region, but the radius of curvature at the apex is reduced. Stage II milling occurs after some sharpening of field-ion specimens has taken place and results in a more rapid translation of the specimen apex position with respect to features in the sample. The rate of material removal along the specimen axis direction depends on the specimen shank angle.
Front end of line considerations for progression beyond the 100 nm node ultrashallow junction requirements
Authors: Rinn Cleavelin C. , Covington Billy C. , Larson Lawrence A.
Published: July 2002

For complementary metal–oxide–semiconductor (CMOS) technology to meet the demanding scaling requirements for ultrashallow junctions and the low contact resistivity necessary for device fabrication below the 100 nm technology node, significant technological barriers will need to be overcome. Numerous solutions have been proposed and a considerable amount of research and development is currently in progress to determine which, if any, of the proposed processes can provide a definitive cost-effective solution that simultaneously meets all CMOS source and drain requirements. In this article, we present a brief overview of some of the techniques that have been proposed for ultrashallow junction and low contact resistance formation and that are currently at the forefront for front end of line (FEOL) consideration. The current status of each potential technological solution is reviewed and we will highlight the advantages and disadvantages associated with each. The FEOL process areas that we will restrict our discussion to include conventional and alternative doping and annealing techniques. Our goal is to indicate the current status of the research and development of these novel techniques for the formation of ultrashallow junctions and low resistivity contacts and to indicate the barriers that must be overcome in each process to make it a viable, cost effective technique.
Evaluation of exposure dose repeatability in synchrotron radiation lithography
Authors: Itoga Kenji , Sumitani Hiroaki , Watanabe Hiroshi , Kumada Teruhiko , Kodera Itsuo , Satoh Shinichi , Ogushi Nobuaki , Oishi Satoshi , Edo Ryou , Yamamoto Takeshi , Watanabe Yutaka
Published: July 2002

The stabilization of exposure dose repeatability is one of the key factors in reducing the critical dimension variation in synchrotron radiation lithography. We have evaluated and improved the exposure dose repeatability of the full field exposure system, which employs a cylindrically convex mirror. The beam size spreads with the stored current in the storage ring, which causes the major exposure dose errors. The maximum exposure dose error is evaluated to be ±4.0% according to the ray trace simulation, and it is expected to reduce the error to ±0.6% using exposure time compensation. We have evaluated the improvement of the exposure dose repeatability experimentally by using the stabilized resist process. Critical dimension variations of less than ±2 nm between six wafers exposed over several days were obtained. This result indicates that the practical exposure dose error is almost consistent with the calculated value, having a variation of less than ±1.0%.
Defect observation on a 12-in. silicon wafer using large sample atomic force microscopy
Authors: Nishimura T. , Wakiyama S. , Yasutake M. , Sugano Y. , Fujino N.
Published: July 2002

As semiconductor devices have become more highly integrated and miniaturized, defects originating within single-crystal silicon occur more frequently. Defect observation of silicon wafer surfaces using atomic force microscopy (AFM) is an analysis technique that reduces defect density on silicon surfaces and, thereby, increases yield (Ref. ). We have developed an AFM that can directly observe the entire surface of next-trend, 12-in. wafers. We observed the defects of 12-in. Czochralski (CZ) wafers and compared the results with those of 8-in. wafers. We also observed the defects of 12-in. epitaxial Si wafers as a reference. The defects of the 12- and 8-in. CZ wafers are similar, and the 12-in. wafers display two types of defects in the silicon crystals: (1) Crystal originated particle, which is a shape surrounded by a {111} facet, and (2) dislocation loops. These defects are caused when crystals are lifted, and reflect the lifting conditions (Ref. ). Although, there were fewer defects on the epitaxial Si wafers than on the CZ wafers, defects like hillock were found on the epitaxial Si wafers.
Prebreakdown and breakdown investigation of needle-plane vacuum gaps in the micron/submicron regime
Authors: Muzykov P. G. , Ma Xianyun , Sudarshan T. S.
Published: July 2002

This article reports investigations of insulation failure of needle-plane gaps of micrometric dimensions. Using a piezoelectric translational stage it is possible to set the gap spacing in the range between 0.1 and 40 μm with a resolution less than 0.04 μm. The prebreakdown and breakdown characteristics of the needle-plane gap were investigated as a function of the gap spacing, emitter radius, ambient pressure, and conditioning effects. The experimental results showed that the breakdown voltage of a microtip-plane gap is relatively high. For a 2 μm radius tip set at a 1 μm gap distance from a planar electrode, the breakdown voltage was about 500 V. It was found that an increase of pressure from 10−6 to 10−2 Torr did not influence the value of the threshold voltage for breakdown. dc glow discharge conditioning in air at a pressure of ∼1 Torr increased the value of threshold voltage for breakdown in vacuum by about 20%–30%. The obtained prebreakdown characteristics of microtip type gaps is very important for the development of vacuum microelectronic devices; specifically, these data provide valuable insights to the practical limits to which microtip-gate gaps can be stressed in practical field emitter arrays in field emission displays.
Capturing a Photoexcited Molecular Structure Through Time-Domain X-ray Absorption Fine Structure
Authors: Chen Lin X. , Jäger Wighard J. H. , Jennings Guy , Gosztola David J. , Munkholm Anneli , Hessler Jan P.
Published: July 2002

The determination of the structure of transient molecules, such as photoexcited states, in disordered media (such as in solution) usually requires methods with high temporal resolution. The transient molecular structure of a reaction intermediate produced by photoexcitation of NiTPP-L
2
(NiTPP, nickeltetraphenylporphyrin; L, piperidine) in solution was determined by x-ray absorption fine structure (XAFS) data obtained on a 14-nanosecond time scale from a third-generation synchrotron source. The XAFS measurements confirm that photoexcitation leads to the rapid removal of both axial ligands to produce a transient square-planar intermediate, NiTPP, with a lifetime of 28 nanoseconds. The transient structure of the photodissociated intermediate is nearly identical to that of the ground state NiTPP, suggesting that the intermediate adopts the same structure as the ground state in a noncoordinating solvent before it recombines with two ligands to form the more stable octahedrally coordinated NiTPP-L
2
.
Geometric Manipulation of Trapped Ions for Quantum Computation
Authors: Duan L.-M. , Cirac J. I. , Zoller P.
Published: July 2002

We propose an experimentally feasible scheme to achieve quantum computation based solely on geometric manipulations of a quantum system. The desired geometric operations are obtained by driving the quantum system to undergo appropriate adiabatic cyclic evolutions. Our implementation of the all-geometric quantum computation is based on laser manipulation of a set of trapped ions. An all-geometric approach, apart from its fundamental interest, offers a possible method for robust quantum computation.
Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets
Authors: Lumelsky Nadya , Blondel Olivier , Laeng Pascal , Velasco Ivan , Ravin Rea , McKay Ron
Published: July 2002

Although the source of embryonic stem (ES) cells presents ethical concerns, their use may lead to many clinical benefits if differentiated cell types can be derived from them and used to assemble functional organs. In pancreas, insulin is produced and secreted by specialized structures, islets of Langerhans. Diabetes, which affects 16 million people in the United States, results from abnormal function of pancreatic islets. We have generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells. The cells self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons. Glucose triggers insulin release from these cell clusters by mechanisms similar to those employed in vivo. When injected into diabetic mice, the insulin-producing cells undergo rapid vascularization and maintain a clustered, islet-like organization.
A Mite Species That Consists Entirely of Haploid Females
Authors: Weeks Andrew R. , Marec Frantisek , Breeuwer Johannes A. J.
Published: July 2002

The dominance of the diploid state in higher organisms, with haploidy generally confined to the gametic phase, has led to the perception that diploidy is favored by selection. This view is highlighted by the fact that no known female organism within the Metazoa exists exclusively (or even for a prolonged period) in a haploid state. We used fluorescence microscopy and variation at nine microsatellite loci to show that the false spider mite,
Brevipalpus phoenicis
, consists of haploid female parthenogens. We show that this reproductive anomaly is caused by infection by an undescribed endosymbiotic bacterium, which results in feminization of haploid genetic males.
Persistence of Native-Like Topology in a Denatured Protein in 8 M Urea
Authors: Shortle David , Ackerman Michael S.
Published: July 2002

Experimental methods have demonstrated that when a protein unfolds, not all of its structure is lost. Here we report measurement of residual dipolar couplings in denatured forms of the small protein staphylococcal nuclease oriented in strained polyacrylamide gels. A highly significant correlation among the dipolar couplings for individual residues suggests that a native-like spatial positioning and orientation of chain segments (topology) persists to concentrations of at least 8 molar urea. These data demonstrate that long-range ordering can occur well before a folding protein attains a compact conformation, a conclusion not anticipated by any of the standard models of protein folding.
Stability and Structure of MgSiO
3
Perovskite to 2300-Kilometer Depth in Earth's Mantle
Authors: Shim Sang-Heon , Duffy Thomas S. , Shen Guoyin
Published: July 2002

Unexplained features have been observed seismically near the middle (∼1700-kilometer depth) and bottom of the Earth's lower mantle, and these could have important implications for the dynamics and evolution of the planet. (Mg,Fe)SiO
3
perovskite is expected to be the dominant mineral in the deep mantle, but experimental results are discrepant regarding its stability and structure. Here we report in situ x-ray diffraction observations of (Mg,Fe)SiO
3
perovskite at conditions (50 to 106 gigapascals, 1600 to 2400 kelvin) close to a mantle geotherm from three different starting materials, (Mg
0.9
Fe
0.1
)SiO enstatite, MgSiO
3
glass, and an MgO+SiO
2
mixture. Our results confirm the stability of (Mg,Fe)SiO
3
perovskite to at least 2300-kilometer depth in the mantle. However, diffraction patterns above 83 gigapascals and 1700 kelvin (1900-kilometer depth) cannot presently rule out a possible transformation from
Pbnm
perovskite to one of three other possible perovskite structures with space group
P
2
1
/
m
,
Pmmn
, or
P
4
2
/
nmc
.
Vascular Abnormalities and Deregulation of
VEGF
in
Lkb1
-Deficient Mice
Authors: Ylikorkala Antti , Rossi Derrick J. , Korsisaari Nina , Luukko Keijo , Alitalo Kari , Henkemeyer Mark , Mäkelä Tomi P.
Published: July 2002

The
LKB1
tumor suppressor gene, mutated in Peutz-Jeghers syndrome, encodes a serine/threonine kinase of unknown function. Here we show that mice with a targeted disruption of
Lkb1
die at midgestation, with the embryos showing neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development was also severely affected; the mutant placentas exhibited defective labyrinth layer development and the fetal vessels failed to invade the placenta. These phenotypes were associated with tissue-specific deregulation of vascular endothelial growth factor (
VEGF
) expression, including a marked increase in the amount of
VEGF
messenger RNA. Moreover, VEGF production in cultured

Lkb1
−/−

fibroblasts was elevated in both normoxic and hypoxic conditions. These findings place
Lkb1
in the VEGF signaling pathway and suggest that the vascular defects accompanying Lkb1 loss are mediated at least in part by VEGF.
Climatic Impact of Tropical Lowland Deforestation on Nearby Montane Cloud Forests
Authors: Lawton R. O. , Nair U. S. , Pielke R. A. , Welch R. M.
Published: July 2002

Tropical montane cloud forests (TMCFs) depend on predictable, frequent, and prolonged immersion in cloud. Clearing upwind lowland forest alters surface energy budgets in ways that influence dry season cloud fields and thus the TMCF environment. Landsat and Geostationary Operational Environmental Satellite imagery show that deforested areas of Costa Rica's Caribbean lowlands remain relatively cloud-free when forested regions have well-developed dry season cumulus cloud fields. Further, regional atmospheric simulations show that cloud base heights are higher over pasture than over tropical forest areas under reasonable dry season conditions. These results suggest that land use in tropical lowlands has serious impacts on ecosystems in adjacent mountains.
RNA: Guiding Gene Silencing
Authors: Matzke Marjori , Matzke Antonius J. M. , Kooter Jan M.
Published: July 2002

In diverse organisms, small RNAs derived from cleavage of double-stranded RNA can trigger epigenetic gene silencing in the cytoplasm and at the genome level. Small RNAs can guide posttranscriptional degradation of complementary messenger RNAs and, in plants, transcriptional gene silencing by methylation of homologous DNA sequences. RNA silencing is a potent means to counteract foreign sequences and could play an important role in plant and animal development.
Metabolic Activity of Subsurface Life in Deep-Sea Sediments
Authors: D'Hondt Steven , Rutherford Scott , Spivack Arthur J.
Published: July 2002

Global maps of sulfate and methane in marine sediments reveal two provinces of subsurface metabolic activity: a sulfate-rich open-ocean province, and an ocean-margin province where sulfate is limited to shallow sediments. Methane is produced in both regions but is abundant only in sulfate-depleted sediments. Metabolic activity is greatest in narrow zones of sulfate-reducing methane oxidation along ocean margins. The metabolic rates of subseafloor life are orders of magnitude lower than those of life on Earth's surface. Most microorganisms in subseafloor sediments are either inactive or adapted for extraordinarily low metabolic activity.
Negative Regulation of Neural Stem/Progenitor Cell Proliferation by the
Pten
Tumor Suppressor Gene in Vivo
Authors: Groszer Matthias , Erickson Rebecca , Scripture-Adams Deirdre D. , Lesche Ralf , Trumpp Andreas , Zack Jerome A. , Kornblum Harley I. , Liu Xin , Wu Hong
Published: July 2002

The mechanisms controlling neural stem cell proliferation are poorly understood. Here we demonstrate that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells in vivo and in vitro. Mice lacking PTEN exhibited enlarged, histoarchitecturally abnormal brains, which resulted from increased cell proliferation, decreased cell death, and enlarged cell size. Neurosphere cultures revealed a greater proliferation capacity for tripotent
Pten
–/–
central nervous system stem/progenitor cells, which can be attributed, at least in part, to a shortened cell cycle. However, cell fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferation.
A Phosphatase Associated with Metastasis of Colorectal Cancer
Authors: Saha Saurabh , Bardelli Alberto , Buckhaults Phillip , Velculescu Victor E. , Rago Carlo , Croix Brad St. , Romans Katharine E. , Choti Michael A. , Lengauer Christoph , Kinzler Kenneth W. , Vogelstein Bert
Published: July 2002

To gain insights into the molecular basis for metastasis, we compared the global gene expression profile of metastatic colorectal cancer with that of primary cancers, benign colorectal tumors, and normal colorectal epithelium. Among the genes identified, the
PRL-3
protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In 3 of 12 metastases examined, multiple copies of the
PRL-3
gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the
PRL-3
gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions.
Warming of the Southern Ocean Since the 1950s
Authors: Gille Sarah T.
Published: July 2002

Autonomous Lagrangian Circulation Explorer floats recorded temperatures in depths between 700 and 1100 meters in the Southern Ocean throughout the 1990s. These temperature records are systematically warmer than earlier hydrographic temperature measurements from the region, suggesting that mid-depth Southern Ocean temperatures have risen 0.17°C between the 1950s and the 1980s. This warming is faster than that of the global ocean and is concentrated within the Antarctic Circumpolar Current, where temperature rates of change are comparable to Southern Ocean atmospheric temperature increases.
The Genome of the Natural Genetic Engineer
Agrobacterium tumefaciens
C58
Authors: Wood Derek W. , Setubal Joao C. , Kaul Rajinder , Monks Dave E. , Kitajima Joao P. , Okura Vagner K. , Zhou Yang , Chen Lishan , Wood Gwendolyn E. , Almeida Nalvo F. , Woo Lisa , Chen Yuching , Paulsen Ian T. , Eisen Jonathan A. , Karp Peter D. , Bovee Donald , Chapman Peter , Clendenning James , Deatherage Glenda , Gillet Will , Grant Charles , Kutyavin Tatyana , Levy Ruth , Li Meng-Jin , McClelland Erin , Palmieri Anthony , Raymond Christopher , Rouse Gregory , Saenphimmachak Channakhone , Wu Zaining , Romero Pedro , Gordon David , Zhang Shiping , Yoo Heayun , Tao Yumin , Biddle Phyllis , Jung Mark , Krespan William , Perry Michael , Gordon-Kamm Bill , Liao Li , Kim Sun , Hendrick Carol , Zhao Zuo-Yu , Dolan Maureen , Chumley Forrest , Tingey Scott V. , Tomb Jean-Francois , Gordon Milton P. , Olson Maynard V. , Nester Eugene W.
Published: July 2002

The 5.67-megabase genome of the plant pathogen
Agrobacterium tumefaciens
C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of
A. tumefaciens
and the plant symbiont
Sinorhizobium meliloti
suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the
A. tumefaciens
sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles.
Estimation of Epidemic Size and Incubation Time Based on Age Characteristics of vCJD in the United Kingdom
Authors: Valleron Alain-Jacques , Boelle Pierre-Yves , Will Robert , Cesbron Jean-Yves
Published: July 2002

The size of the variant Creutzfeldt-Jakob Disease (vCJD) epidemic in the United Kingdom is a major public health concern and a subject of speculation. The cases are young (mean age = 28). Assuming that the risk of developing the disease in susceptible exposed subjects decreases exponentially with age after age 15, that all infections occurred between 1980 and 1989, and that the distribution of the incubation period is lognormal, we estimate that the mean duration of the incubation period is 16.7 years [95% confidence interval (CI): 12.4 to 23.2] and that the total number of cases will be 205 (upper limit of the 95% CI: 403).
A Bacterial Guanine Nucleotide Exchange Factor Activates ARF on
Legionella
Phagosomes
Authors: Nagai Hiroki , Kagan Jonathan C. , Zhu Xinjun , Kahn Richard A. , Roy Craig R.
Published: July 2002

The intracellular pathogen
Legionella pneumophila
subverts vesicle traffic in eukaryotic host cells to create a vacuole that supports replication. The
dot/icm
genes encode a protein secretion apparatus that
L. pneumophila
require for biogenesis of this vacuole. Here we show that
L. pneumophila
produce a protein called RalF that functions as an exchange factor for the ADP ribosylation factor (ARF) family of guanosine triphosphatases (GTPases). The RalF protein is required for the localization of ARF on phagosomes containing
L. pneumophila
. Translocation of RalF protein through the phagosomal membrane is a
dot/icm
-dependent process. Thus, RalF is a substrate of the Dot/Icm secretion apparatus.
Layer-by-Layer Growth of Binary Colloidal Crystals
Authors: Velikov Krassimir P. , Christova Christina G. , Dullens Roel P. A. , van Blaaderen Alfons
Published: July 2002

We report the growth of binary colloidal crystals with control over the crystal orientation through a simple layer-by-layer process. Well-ordered single binary colloidal crystals with a stoichiometry of large (L) and small (S) particles of LS
2
and LS were generated. In addition, we observed the formation of an LS
3
superstructure. The structures formed as a result of the templating effect of the first layer and the forces exerted by the surface tension of the drying liquid. By using spheres of different composition, one component can be selectively removed, as is demonstrated in the growth of a hexagonal non–close-packed colloidal crystal.
Lateral Hopping of Molecules Induced by Excitation of Internal Vibration Mode
Authors: Komeda T. , Kim Y. , Kawai Maki , Persson B. N. J. , Ueba H.
Published: July 2002

We demonstrate electron-stimulated migration for carbon monoxide (CO) molecules adsorbed on the Pd(110) surface, which is initiated by the excitation of a high-frequency (HF) vibrational mode (C–O stretching mode) with inelastic tunneling electrons from the tip of scanning tunneling microscopy. The hopping phenomenon, however, cannot be detected for CO/Cu(110), even though the hopping barrier is lower than in the CO/Pd(110) case. A theoretical model, which is based on the anharmonic coupling between low-frequency modes (the hindered-translational mode related to the lateral hopping) and the HF mode combined with electron-hole pair excitation, can explain why the hopping of CO is observed on Pd(110) but not on Cu(110).
Helioseismic Measurement of Solar Torsional Oscillations
Authors: Vorontsov S. V. , Christensen-Dalsgaard J. , Schou J. , Strakhov V. N. , Thompson M. J.
Published: July 2002

Bands of slower and faster rotation, the so-called torsional oscillations, are observed at the Sun's surface to migrate in latitude over the 11-year solar cycle. Here, we report on the temporal variations of the Sun's internal rotation from solar p-mode frequencies obtained over nearly 6 years by the Michelson Doppler Imager (MDI) instrument on board the Solar and Heliospheric Observatory (SOHO) satellite. The entire solar convective envelope appears to be involved in the torsional oscillations, with phase propagating poleward and equatorward from midlatitudes at all depths throughout the convective envelope.
The Effect of Algal Symbionts on the Accuracy of Sr/Ca Paleotemperatures from Coral
Authors: Cohen Anne L. , Owens Kathryn E. , Layne Graham D. , Shimizu Nobumichi
Published: July 2002

The strontium-to-calcium ratio (Sr/Ca) of reef coral skeleton is commonly used as a paleothermometer to estimate sea surface temperatures (SSTs) at crucial times in Earth's climate history. However, these estimates are disputed, because uptake of Sr into coral skeleton is thought to be affected by algal symbionts (zooxanthellae) living in the host tissue. Here, we show that significant distortion of the Sr/Ca temperature record in coral skeleton occurs in the presence of algal symbionts. Seasonally resolved Sr/Ca in coral without symbionts reflects local SSTs with a temperature sensitivity equivalent to that of laboratory aragonite precipitated at equilibrium and the nighttime skeletal deposits of symbiotic reef corals. However, up to 65% of the Sr/Ca variability in symbiotic skeleton is related to symbiont activity and does not reflect water temperature.
Seismic Evidence for Olivine Phase Changes at the 410- and 660-Kilometer Discontinuities
Authors: Lebedev Sergei , Chevrot Sébastien , van der Hilst Rob D.
Published: July 2002

The view that the seismic discontinuities bounding the mantle transition zone at 410- and 660-kilometer depths are caused by isochemical phase transformations of the olivine structure is debated. Combining converted-wave measurements in East Asia and Australia with seismic velocities from regional tomography studies, we observe a correlation of the thickness of, and wavespeed variations within, the transition zone that is consistent with olivine structural transformations. Moreover, the seismologically inferred Clapeyron slopes are in agreement with the mineralogical Clapeyron slopes of the (Mg,Fe)
2
SiO
4
spinel and postspinel transformations.
Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level
Authors: Moore Corey B. , John Mina , James Ian R. , Christiansen Frank T. , Witt Campbell S. , Mallal Simon A.
Published: July 2002

Antigen-specific T cell immunity is HLA-restricted. Human immunodeficiency virus–type 1 (HIV-1) mutations that allow escape from host immune responses may therefore be HLA allele–specific. We analyzed HIV-1 reverse transcriptase sequences from a large HLA-diverse population of HIV-1–infected individuals. Polymorphisms in HIV-1 were most evident at sites of least functional or structural constraint and frequently were associated with particular host HLA class I alleles. Absence of polymorphism was also HLA allele–specific. At a population level, the degree of HLA-associated selection in viral sequence was predictive of viral load. These results support a fundamental role for HLA-restricted immune responses in driving and shaping HIV-1 evolution in vivo.
A High-Resolution Paleoclimate Record Spanning the Past 25,000 Years in Southern East Africa
Authors: Johnson Thomas C. , Brown Erik T. , McManus James , Barry Sylvia , Barker Philip , Gasse Françoise
Published: July 2002

High-resolution profiles of the mass accumulation rate of biogenic silica and other geochemical proxies in two piston cores from northern Lake Malawi provide a climate signal for this part of tropical Africa spanning the past 25,000 years. The biogenic silica mass accumulation rate was low during the relatively dry late Pleistocene, when the river flux of silica to the lake was suppressed. Millennial-scale fluctuations, due to upwelling intensity, in the late Pleistocene climate of the Lake Malawi basin appear to have been closely linked to the Northern Hemisphere climate until 11 thousand years ago. Relatively cold conditions in the Northern Hemisphere coincided with more frequent north winds over the Malawi basin, perhaps resulting from a more southward migration of the Intertropical Convergence Zone.
The Interaction of Alba, a Conserved Archaeal Chromatin Protein, with Sir2 and Its Regulation by Acetylation
Authors: Bell Stephen D. , Botting Catherine H. , Wardleworth Benjamin N. , Jackson Stephen P. , White Malcolm F.
Published: July 2002

The conserved Sir2 family of proteins has protein deacetylase activity that is dependent on NAD (the oxidized form of nicotinamide adenine dinucleotide). Although histones are one likely target for the enzymatic activity of eukaryotic Sir2 proteins, little is known about the substrates and roles of prokaryotic Sir2 homologs. We reveal that an archaeal Sir2 homolog interacts specifically with the major archaeal chromatin protein, Alba, and that Alba exists in acetylated and nonacetylated forms. Furthermore, we show that Sir2 can deacetylate Alba and mediate transcriptional repression in a reconstituted in vitro transcription system. These data provide a paradigm for how Sir2 family proteins influence transcription and suggest that modulation of chromatin structure by acetylation arose before the divergence of the archaeal and eukaryotic lineages.
Probing High-Barrier Pathways of Surface Reactions by Scanning Tunneling Microscopy
Authors: Dürr M. , Biedermann A. , Hu Z. , Höfer U. , Heinz T. F.
Published: July 2002

The ability of scanning tunneling microscopy to probe the pathways of thermally activated high-barrier surface processes is frequently limited by competing low-barrier processes that can confuse measurement of the true initial and final configuration. We introduce an approach to circumvent this difficulty by driving the surface process with nanosecond laser heating. The method is applied to determine the pathway of recombinative desorption in the H/Si(001) system. The observed configuration of dangling bonds after laser heating reveals that the desorbed hydrogen molecules are not formed on single dimers, but rather from neighboring silicon dimers via an interdimer reaction pathway.
Comparative Genome Sequencing for Discovery of Novel Polymorphisms in
Bacillus anthracis
Authors: Read Timothy D. , Salzberg Steven L. , Pop Mihai , Shumway Martin , Umayam Lowell , Jiang Lingxia , Holtzapple Erik , Busch Joseph D. , Smith Kimothy L. , Schupp James M. , Solomon Daniel , Keim Paul , Fraser Claire M.
Published: July 2002

Comparison of the whole-genome sequence of
Bacillus anthracis
isolated from a victim of a recent bioterrorist anthrax attack with a reference reveals 60 new markers that include single nucleotide polymorphisms (SNPs), inserted or deleted sequences, and tandem repeats. Genome comparison detected four high-quality SNPs between the two sequenced
B. anthracis
chromosomes and seven differences among different preparations of the reference genome. These markers have been tested on a collection of anthrax isolates and were found to divide these samples into distinct families. These results demonstrate that genome-based analysis of microbial pathogens will provide a powerful new tool for investigation of infectious disease outbreaks.
An Expanding Universe of Noncoding RNAs
Authors: Storz Gisela
Published: July 2002

Noncoding RNAs (ncRNAs) have been found to have roles in a great variety of processes, including transcriptional regulation, chromosome replication, RNA processing and modification, messenger RNA stability and translation, and even protein degradation and translocation. Recent studies indicate that ncRNAs are far more abundant and important than initially imagined. These findings raise several fundamental questions: How many ncRNAs are encoded by a genome? Given the absence of a diagnostic open reading frame, how can these genes be identified? How can all the functions of ncRNAs be elucidated?
Discovery of X-ray and Extreme Ultraviolet Emission from Comet C/Hyakutake 1996 B2
Authors: Lisse C. M. , Dennerl K. , Englhauser J. , Harden M. , Marshall F. E. , Mumma M. J. , Petre R. , Pye J. P. , Ricketts M. J. , Schmitt J. , Trümper J. , West R. G.
Published: July 2002

During its close approach to Earth, comet C/Hyakutake 1996 B2 was observed at extreme ultraviolet and x-ray wavelengths with the Röntgen X-ray Satellite and Rossi X-ray Timing Explorer. The emission morphology was symmetric with respect to a vector from the comet's nucleus toward the sun, but not symmetric around the direction of motion of the comet with respect to interplanetary dust. A slowly varying emission and a large impulsive event that varied on time scales of 1 to 2 hours were observed. An interaction between the comet and the solar wind/solar magnetic field seems to be the most likely mechanism for the observed emission.
Crystal Structure of DNA Recombination Protein RuvA and a Model for Its Binding to the Holliday Junction
Authors: Rafferty John B. , Sedelnikova Svetlana E. , Hargreaves David , Artymiuk Peter J. , Baker Patrick J. , Sharples Gary J. , Mahdi Akeel A. , Lloyd Robert G. , Rice David W.
Published: July 2002

The
Escherichia coli
DNA binding protein RuvA acts in concert with the helicase RuvB to drive branch migration of Holliday intermediates during recombination and DNA repair. The atomic structure of RuvA was determined at a resolution of 1.9 angstroms. Four monomers of RuvA are related by fourfold symmetry in a manner reminiscent of a four-petaled flower. The four DNA duplex arms of a Holliday junction can be modeled in a square planar configuration and docked into grooves on the concave surface of the protein around a central pin that may facilitate strand separation during the migration reaction. The model presented reveals how a RuvAB-junction complex may also accommodate the resolvase RuvC.
Conditional Circadian Dysfunction of the
Arabidopsis early-flowering 3
Mutant
Authors: Hicks Karen A. , Millar Andrew J. , Carré Isabelle A. , Somers David E. , Straume Martin , Meeks-Wagner D. Ry , Kay Steve A.
Published: July 2002

Photoperiodic responses, such as the daylength-dependent control of reproductive development, are associated with a circadian biological clock. The photoperiod-insensitive
early-flowering 3
(
elf3
) mutant of
Arabidopsis thaliana
lacks rhythmicity in two distinct circadian-regulated processes. This defect was apparent only when plants were assayed under constant light conditions.
elf3
mutants retain rhythmicity in constant dark and anticipate light/dark transitions under most light/dark regimes. The conditional arrhythmic phenotype suggests that the circadian pacemaker is intact in darkness in
elf3
mutant plants, but the transduction of light signals to the circadian clock is impaired.
Patterning the Vertebrate Neuraxis
Authors: Lumsden Andrew , Krumlauf Robb
Published: July 2002

Neuraxial patterning is a continuous process that extends over a protracted period of development. During gastrulation a crude anteroposterior pattern, detectable by molecular markers, is conferred on the neuroectoderm by signals from the endomesoderm that are largely inseparable from those of neural induction itself. This coarse-grained pattern is subsequently reinforced and refined by diverse, locally acting mechanisms. Segmentation and long-range signaling from organizing centers are prominent among the emerging principles governing regional pattern.