bluuebunny/crossref_metadata_2025 huggingface dataset:
Electromigration properties of copper-zirconium alloy interconnects
Authors: Igarashi Yasushi , Ito Toshio
Published: July 2002

Highly reliable interconnects for reducing electromigration failure were demonstrated using a Cu-Zr alloy. The Cu-Zr alloy separates into Cu and precipitates containing Cu-Zr compounds after annealing at 500 °C. The precipitates were observed at grain boundaries and interfaces between the Cu-Zr alloy and surrounding materials. Consequently, because the precipitates prevent the diffusion of Cu, the electromigration lifetimes of the Cu-Zr interconnects are 10 to 100 times longer than those of Cu interconnects. Moreover, the resistivity of the CuZr alloy after precipitation annealing is about 2 μΩ cm because the Zr concentration in the grain interior is below the detection limit of energy-dispersive x-ray spectrometry. Therefore, the Cu-Zr interconnects are suitable for future use in logic devices that will be operated at current densities higher than 1 MA/cm2 and at temperatures higher than 100 °C.
Si
3
N
4
on GaAs by direct electron cyclotron resonance plasma assisted nitridation of Si layer in Si/GaAs structure
Authors: Diatezua D. M. , Wang Z. , Park D. , Chen Z. , Rockett A. , Morkoc H.
Published: July 2002

Si 3 N 4 has been produced on GaAs with low interface trap densities by electron cyclotron resonance N2–He plasma assisted nitridation of a Si layer deposited on a GaAs (100) substrate. Nitridation at 150 and 400 °C was monitored by x-ray photoelectron spectroscopy (XPS) and produced stoichiometric Si3N4. The nitride layer thickness, as determined from XPS as a function of photoelectron takeoff angle, initially increased rapidly with nitridation time with a transition at a thickness of 12–18 Å to slower growth. Capacitance/voltage and conductance/angular frequency measurements were performed on metal-insulator-semiconductor capacitors fabricated from the nitrided samples. The results demonstrated interface trap densities with a minimum of 3.0×1011 eV−1 cm−2 when nitrided at 150 °C. At 400 °C the nitridation produced a poor quality interface, which resulted either from the higher temperature or from nitridation of all of the Si, leaving the Si3N4 in direct contact with the GaAs.
Factors contributing to sidewall roughness in a positive-tone, chemically amplified resist exposed by x-ray lithography
Authors: Reynolds Geoffrey W. , Taylor James W.
Published: July 2002

As device critical dimensions continue to decrease, sidewall roughness will become increasingly important. To address this issue, we have measured the sidewall roughness of a positive-tone, chemically amplified resist, Shipley APEX-E exposed by X-ray radiation. We have also examined factors that contribute to the overall sidewall roughness such as mask roughness, the development process, variations in acid diffusion, shot noise, and the effects of acid volatility. The overall sidewall roughness for fully developed nested lines, under normal processing conditions, is on the order of 4.3 nm root-mean-square (rms) and shows no dose dependence. Isolated lines, however, do demonstrate a dose-dependent sidewall roughness. Samples exposed with doses of 60–100 mJ/cm2 exhibit a monotonically decreasing trend in roughness from 6.5 to about 4.5 nm rms, respectively. The development process, in tandem with pattern-specific parameters, appears to cause this difference in the roughness between nested and isolated lines. The use of different masks and the development process are major contributors to the overall sidewall roughness. Differences in sidewall roughness due to the use of different masks are estimated to be about 1.5 nm rms. Roughness contributions from the development process are on the order of 2–3 nm rms and are shown to be time and concentration dependent. Other processing parameters, such as changing the post-exposure bake temperature and utilizing a top coat, have minor effects on the overall sidewall roughness.
Growth of carbon doping Ga0.47In0.53As using CBr4 by gas source molecular beam epitaxy for InP/InGaAs heterojunction bipolar transistor applications
Authors: Kuo H. C. , Ahmari D. , Moser B. G. , Mu J. , Hattendorf M. , Scott D. , Meyer R. , Feng M. , Stillman G. E.
Published: July 2002

In this article, we present the comparison of material quality and device performance of gas-source molecular beam epitaxy (GSMBE)- and metal-organic molecular beam epitaxy (MOMBE)-grown C-doped InGaAs and npn InGaAs/InP heterojunction bipolar transistors (HBTs). The results indicate that the crystal quality of GSMBE-grown samples is comparable to that of MOMBE-grown samples. The GSMBE-grown HBTs show excellent dc and high frequency performance. The dc current gain (β) was 37 at a collector current of 21 mA and the emitter-base and base-collector junction ideality factors were 1.14 and 1.04 indicating good junction properties. For high frequency performance, the fT and fmax are around 108 and 128 GHz for a 4000 Å InGaAs collector with an emitter area of 3×10 μm2. Finally, the thermal stability of C-doped InGaAs and its effects on InP/InGaAs HBT device reliability will be discussed.
Growth of ZnSe and ZnS films on Si(111) substrates with a nitrogen surface treatment
Authors: Méndez-Garcı́a V. H. , López-López M. , Hernández-Calderón I.
Published: July 2002

We have investigated the effects of substrate surface irradiation with nitrogen plasma prior to growth on the initial stages of the heteroepitaxy of ZnSe on Si(111). The reflection high-energy electron diffraction (RHEED) patterns during the pulsed molecular beam epitaxial growth of ZnSe on the N-plasma-treated Si surface showed very well-defined streaks with a twofold reconstruction indicating an atomically flat surface. In sharp contrast, during the initial stages of the ZnSe growth on untreated Si substrates, spotty RHEED patterns with a diffuse background were observed. A strong evidence of the two-dimensional ZnSe nucleation obtained on the N-plasma-treated Si surface was the clear presence of large-amplitude RHEED oscillations. Atomic force microscopy measurements confirmed that we have achieved a substantial improvement on the ZnSe heteroepitaxy on Si substrates. We show that this novel N-plasma substrate treatment is useful for the growth of other Zn-chalcogenides compounds on Si substrates.
Electron intersubband energy level spacing in self-organized In0.4Ga0.6As/GaAs quantum dot lasers from temperature-dependent modulation measurements
Authors: Klotzkin D. , Phillips J. , Jiang H. , Singh J. , Bhattacharya P.
Published: July 2002

We have determined the electron intersubband energy spacing in In0.4Ga0.6As/GaAs self-organized quantum dots from analysis of the temperature-dependent optical modulation response of single-mode lasers in which four dot layers from the gain region. The 3 dB modulation bandwidth increases from 7 GHz at 300 K to >20 GHz at 80 K. An intersubband energy spacing of 60 meV is measured. This value is in excellent agreement with the theoretically calculated value of 57.5 meV and verifies that intersubband relaxation in quantum dots occurs via electron-hole scattering.
Study of the SiO2-to-Si3N4 etch selectivity mechanism in the presence of polymers in fluorocarbon plasmas
Authors: Ku Victor , Parks Delbert
Published: July 2002

The polymerization effects in 27/2 MHz capacitively coupled fluorocarbon plasmas during high selectively subquarter-micron contact hole etching, with the film structure of silicon dioxide (SiO2)/silicon nitride (Si3N4)/silicide (TiSix), are investigated. A high etch selectivity chemistry is first used to remove SiO2, then Si3N4 is removed with another chemistry with high selectivity of Si3N4-to-TiSix. To obtain good etch selectivity of SiO2-to-Si3N4, fluorocarbon plasmas containing a high carbon to fluorine (C/F) ratio is usually employed. Polymerization readily occurs in chemistries having a high C/F ratio. These unsaturated polymers are reactive and stick easily to contact hole sidewalls and bottoms, creating thick polymer films. While the chemistry used to etch Si3N4 has shown acceptable selectivity as measured on a patterned singular film, fluorine from the polymer will severely degrade the etch selectivity of Si3N4-to-TiSix on fully processed wafers. Process developments started with a design of experiment on real production wafers in order to understand the roles of fluorocarbon polymer during the Si3N4 etching. Scanning electron microscope analysis of this polymer film and its effects are included as well as the electrical parametric testing data of contact resistances. Different polymer removing methods to restore the Si3N4-to-TiSix etch selectivity back were initiated and will be briefly discussed. While this investigation pertains to contact etch, this phenomenologically observed result could be applied to any highly selective etching of oxide versus nitride.
Deposition temperature effects of high density plasma chemical vapor deposition films for subquarter micron devices application
Authors: Tsan C. C. , Wang Y. L. , Wu Y. L. , Dun Jowei , Huan Y. S. , Feng M. S. , Chiu S. Y.
Published: July 2002

A detailed study for the high density plasma chemical vapor deposition (HDP-CVD) process was presented to prevent metal distortion issues and metal corrosion risk. The deposition temperature increased and then saturated as the film deposited, based on the correlation of wet-etch rate and deposition temperature. The stress of HDP-CVD film also trended up, but the deposition rate decreased. Lowering of the deposition temperature of HDP-CVD film was key to preventing the metal distortion. A two-step deposition recipe with 10 s Ar cooldown was developed to solve the metal distortion issue on subquarter micron devices.
Development of self-aligned contact technology for 0.18 μm static random access memory devices
Authors: Qiao Jianmin , Jin Bo , Phatak Prashant , Yu Jengyi , Geha Sam
Published: July 2002

A self-aligned contact (SAC) technology is developed for the application of electrical contacts between the local interconnect and the silicon diffusion regions for 0.18 μm static random access memory cells. The key components of this SAC technology include the deposition and gap fill of borophosphosilicate glass (BPSG) films, a selective oxide etch process, and metal-plug contact formation by Ti/TiN-liner silicidation and W filling. The BPSG film, deposited by plasma enhanced chemical vapor deposition, has exhibited an ability of filling 0.04 μm spaces with an aspect ratio (AR) of about 10:1 after reflow at 800 °C. Reduction of the reflow temperature without gap-fill deterioration by increasing the B incorporation in the BPSG film is not feasible due to an increase of BPSG defects. The oxide SAC etch performance is modulated by an oxide-to-nitride etch selectivity which has shown a strong dependence on the wafer temperature. The etch process window is improved by optimization of the process conditions including the wafer temperature uniformity. A novel SAC etch process was demonstrated for an ∼0.2 μm SAC opening. The electrical performance of a contact with an AR as high as 10:1 has met the design requirement, which has indicated sufficient liner silicidation and an excellent W plug process. Investigation of the contact resistance dependence on the contact AR has shown a reduction in contact resistance with increasing AR. All these findings are very instructive for our development projects.
Metal silicides synthesized by high current metal–ion implantation
Authors: Liu B. X. , Gao K. Y. , Zhu H. N.
Published: July 2002

High current metal–ion implantation by a metal vapor vacuum arc ion source was conducted to synthesize some metal silicides, which are important candidates as materials in microelectronics. It was found that C54-TiSi2, ZrSi2, NiSi2, CoSi2, β-FeSi2, NbSi2, and TaSi2 layers on Si wafers with good electric properties could be obtained directly after implantation at relatively low formation temperature and that the formation of α-FeSi2, NbSi2, TaSi2, tetragonal WSi2, and tetragonal MoSi2 required additional postannealing to improve their crystallinity as well as their electric properties. Interestingly, NiSi2 layers of superior crystallinity and thus electric property were obtained for the first time by Ni ion implantation with a selected current density of 35 μA/cm2, which heated the Si wafers to a specific temperature of 380 °C. Under such formation conditions, the lattice mismatch between the growing NiSi2 and the Si substrate was calculated to be zero. The resistivity of the NiSi2 layers obtained was much lower than that of the Ni disilicide synthesized by a solid-state reaction that required a formation temperature of over 750 °C. The formation mechanism of the metal silicides studied and their associated electrical properties are also discussed.
Plasma polymerized methylsilane. III. Process optimization for 193 nm lithography applications
Authors: Joubert O. , Fuard D. , Monget C. , Weidman T.
Published: July 2002

New photoresists and processes are required for sub 0.15 μm design rules, and currently an important effect is on-going for single layer resist optimization at 193 nm. Top surface imaging can be an interesting alternative approach. An all dry chemical vapor deposition (CVD) process based on plasma polymerized methylsilane (PPMS) or plasma polymerized dimethylsilane (PP2MS) provides a thin conformal and photosensitive layer at 193 nm. A thin amorphous film of Si–Si bonded material is deposited using plasma enhanced chemical vapor deposition (PECVD) with methylsilane or dimethylsilane as the gas precursor. Upon 193 nm exposure under air, photoinduced oxidation of the CVD resist occurs, generating a latent image. The image is then developed in a chlorine-based plasma (which removes the unexposed areas), providing a negative tone process. This mask can be used to pattern a thick organic underlayer to provide a general bilevel process. Lithographic results on both a 193 microstepper as well as a full field production stepper are presented: resolution down to 0.10 μm equal L/S was obtained. A preliminary comparison between PPMS and PP2MS materials is presented, including Fourier-transform infrared results, stability of the films in air and lithographic performance including line edge roughness.
Role of sidewall scattering in feature profile evolution during Cl2 and HBr plasma etching of silicon
Authors: Vyvoda M. A. , Li M. , Graves D. B. , Lee H. , Malyshev M. V. , Klemens F. P. , Lee J. T. C. , Donnelly V. M.
Published: July 2002

Coupling reactor-scale models of plasma etching equipment to device-scale models of feature profile evolution offers the potential for increased levels of virtual design of both capital equipment and process recipes. In this article, a combined reactor-and feature-scale model of crystalline silicon feature profile evolution is described, and simulation results of isolated trench and isolated line etching with Cl2 and HBr plasmas are compared to experimental data. By incorporating reactor-scale predictions of plasma properties along with assumptions concerning the details of energetic particle scattering from surfaces, we are able to predict both the etch rate and the shape of evolving features. Important in the comparison to experiment is the proper prediction of “microtrench”-free high aspect ratio trench etching in the case of HBr, contrasted with the occurrence of deep microtrenching when Cl2 plasmas were used. These results suggest that a thorough knowledge of the details of energetic ion scattering from all evolving surfaces is required before accurate feature profile evolution predictions can be made.
Characterization of InAs quantum dots in strained InxGa1−xAs quantum wells
Authors: Stintz A. , Liu G. T. , Gray A. L. , Spillers R. , Delgado S. M. , Malloy K. J.
Published: July 2002

The properties of InAs quantum dots placed in a strained InGaAs quantum well are investigated. The structures are grown by solid-source molecular beam epitaxy on GaAs substrates and are characterized using photoluminescence and atomic force microscopy. Emission wavelength and the optical quality of the quantum dots vary with growth temperature and also depend on the position of the dots in the well. A strong dependence of the dot properties on the capping conditions is established. A postgrowth anneal similar to a typical laser cladding growth results in a large photoluminescence (PL) blueshift and reduces the PL intensity by more than two orders of magnitude. It is shown that these dots-in-a-well structures have superior optical properties as compared to conventional InAs dots in a GaAs matrix, and their emission wavelength can be tuned past the technologically important wavelength of 1.3 μm.
Observation of direct (type-I) transitions in type-II InGaAs/AlAsSb heterostructures lattice matched to InP grown by molecular beam epitaxy
Authors: Mozume Teruo , Georgiev Nikolai , Yoshida Haruhiko , Neogi Arup , Nishimura Tetsuya
Published: July 2002

We report an optical study of InGaAs/AlAsSb heterostructures with a type-II band alignment that are lattice matched to InP substrates grown by molecular beam epitaxy. A strong direct transition involving a confined electron and a quasibound hole state (both in the InGaAs layer) is observed in photoluminescence spectra in a low excitation regime in addition to an interface-related indirect (type-II) transition between electrons confined in the InGaAs well and AlAsSb valence band. A direct transition between the confined electrons in the first excited subband and valence band of InGaAs is also observed in a 20 nm InGaAs heterostructure in the higher excitation power regime.
Internal stress of amorphous carbon nitride films
Authors: Aono Masami , Nitta Shoji , Katsuno Takashi , Iuchi Takeshi
Published: July 2002

We have studied the characteristics of amorphous carbon nitride (a-CNx) films as low dielectric constant materials for ultralarge scale integration. In this article the initial internal stress of a-CNx films is studied and discussed. The stress in a single-layer film on a substrate is determined using the measured radius of curvature and Stoney’s equation. a-CNx films are prepared by a reactive radio frequency magnetron sputtering on the ultrathin quartz glass substrates. It is observed that the internal stress in a-CNx depends mainly on the substrate temperature increasing from about 10 to 50 MPa of compressive nature. These values are about one tenth of that for hydrogenated amorphous silicon (a-Si:H) prepared by a plasma-enhanced chemical vapor deposition.
Role of the ABC Transporter Mdl1 in Peptide Export from Mitochondria
Authors: Young Lesley , Leonhard Klaus , Tatsuta Takashi , Trowsdale John , Langer Thomas
Published: July 2002

ATP-binding cassette (ABC) adenosine triphosphatases actively transport a wide variety of compounds across biological membranes. Here, the ABC protein Mdl1 was identified as an intracellular peptide transporter localized in the inner membrane of yeast mitochondria. Mdl1 was required for mitochondrial export of peptides with molecular masses of ∼2100 to 600 daltons generated by proteolysis of inner-membrane proteins by the m-AAA protease in the mitochondrial matrix. Proteolysis by the i-AAA protease in the intermembrane space led to the release of similar-sized peptides independent of Mdl1. Thus, two pathways of peptide efflux from mitochondria exist that may allow communication between mitochondria and their cellular environment.
Centrosome-Dependent Exit of Cytokinesis in Animal Cells
Authors: Piel Matthieu , Nordberg Joshua , Euteneuer Ursula , Bornens Michel
Published: July 2002

As an organelle coupling nuclear and cytoplasmic divisions, the centrosome is essential to mitotic fidelity, and its inheritance could be critical to understanding cell transformation. Investigating the behavior of the centrosome in living mitotic cells, we documented a transient and remarkable postanaphase repositioning of this organelle, which apparently controls the release of central microtubules from the midbody and the completion of cell division. We also observed that the absence of the centrosome leads to defects in cytokinesis. Together with recent results in yeasts, our data point to a conserved centrosome-dependent pathway that integrates spatial controls into the decision of completing cell division, which requires the repositioning of the centrosome organelle.
Explosive Rhetoric
Authors: Benford Gregory
Published: July 2002

The Nuclear Muse
Literature, Physics, and the First Atomic Bombs. John Canaday. University of Wisconsin Press, Madison, 2000. 328 pp. $60. ISBN 0-299-16850-6. Paper, $22.95. ISBN 0-299-16854-9.

In a volume intended to straddle the boundary between science and the humanities, Canaday applies the techniques of literary criticism to examine the roles rhetoric in forming and expressing the ideas of nuclear physicists before, during, and after World War II.
Viral Immunology from Math
Authors: Bangham Charles R. M. , Asquith Becca
Published: July 2002

Virus Dynamics
Mathematical Principles of Immunology and Virology. Martin A. Nowak and Robert M. May. Oxford University Press, Oxford, 2000. 249 pp. $70, £40. ISBN 0-19-850418-7. Paper, $34.95, £19.50. ISBN 0-19-850417-9.

Nowak and May use mathematical models to explore the interactions between viruses and immune cells and the spread of infectious diseases within patients.
Developments from a Beneficial Bark
Authors: McGuire William P.
Published: July 2002

The Story of Taxol
Nature and Politics in the Pursuit of an Anti-cancer Drug. Jordan Goodman and Vivien Walsh. Cambridge University Press, New York, 2001. 296 pp. $27.95, £18.95. ISBN 0-521-56123-X

The authors examine the development of taxol from a natural plant product to the leading anti-cancer drug. They focus on the conflicts and controversies that arose from the interactions among cancer researchers, government agencies, the pharmaceutical industry, and even environmental activists.
Strange and Unconventional Isotope Effects in Ozone Formation
Authors: Gao Yi Qin , Marcus R. A.
Published: July 2002

The puzzling mass-independent isotopic enrichment in ozone formation contrasts markedly with the more recently observed large unconventional mass-dependent ratios of the individual ozone formation rate constants in certain systems. An RRKM (Rice, Ramsperger, Kassel, Marcus)-based theory is used to treat both effects. Restrictions of symmetry on how energy is shared among the rotational/vibrational states of the ozone isotopomer, together with an analysis of the competition between the transition states of its two exit channels, permit the calculation of isotope effects consistent with a wide array of experimental results.
Communication Breakdown?
Authors: Carroll Sean B.
Published: July 2002

The Century of the Gene
. Evelyn Fox Keller. Harvard University Press, Cambridge, MA, 2000. 190 pp. $22.95, £15.95. ISBN 0-674-00372-1.

Sketching some highlights from the history of genetics and considering what the future may bring, Keller calls for biologists to shed their reductionistic, gene-centered approaches to challenging questions of evolution and development.
Soluble and Colloidal Iron in the Oligotrophic North Atlantic and North Pacific
Authors: Wu Jingfeng , Boyle Edward , Sunda William , Wen Liang-Saw
Published: July 2002

In the oligotrophic North Atlantic and North Pacific, ultrafiltration studies show that concentrations of soluble iron and soluble iron-binding organic ligands are much lower than previously presumed “dissolved” concentrations, which were operationally defined as that passing through a 0.4-micrometer pore filter. Our studies indicate that substantial portions of the previously presumed “dissolved” iron (and probably also iron-binding ligands) are present in colloidal size range. The soluble iron and iron-binding organic ligands are depleted at the surface and enriched at depth, similar to distributions of major nutrients. By contrast, colloidal iron shows a maximum at the surface and a minimum in the upper nutricline. Our results suggest that “dissolved” iron may be less bioavailable to phytoplankton than previously thought and that iron removal through colloid aggregation and settling should be considered in models of the oceanic iron cycle.
Proposed Square Spiral Microfabrication Architecture for Large Three-Dimensional Photonic Band Gap Crystals
Authors: Toader Ovidiu , John Sajeev
Published: July 2002

We present a blueprint for a three-dimensional photonic band gap (PBG) material that is amenable to large-scale microfabrication on the optical scale using glancing angle deposition methods. The proposed chiral crystal consists of square spiral posts on a tetragonal lattice. In the case of silicon posts in air (direct structure), the full PBG can be as large as 15% of the gap center frequency, whereas for air posts in a silicon background (inverted structure) the maximum PBG is 24% of the center frequency. This PBG occurs between the fourth and fifth bands of the photon dispersion relation and is very robust to variations (disorder) in the geometrical parameters of the crystal.
An Oceanic Cold Reversal During the Last Deglaciation
Authors: Stenni Barbara , Masson-Delmotte Valerie , Johnsen Sigfus , Jouzel Jean , Longinelli Antonio , Monnin Eric , Röthlisberger Regine , Selmo Enrico
Published: July 2002

A detailed deuterium excess profile measured along the Dome C EPICA (European Project for Ice Coring in Antarctica) core reveals the timing and strength of the sea surface temperature changes at the source regions for Dome C precipitation. We infer that an Oceanic Cold Reversal took place in the southern Indian Ocean, 800 years after the Antarctic Cold Reversal. The temperature gradient between the oceanic moisture source and Antarctica is similar to the Dome C sodium profile during the deglaciation, illustrating the strong link between this gradient and the strength of the atmospheric circulation.
Southward Migration of the Intertropical Convergence Zone Through the Holocene
Authors: Haug Gerald H. , Hughen Konrad A. , Sigman Daniel M. , Peterson Larry C. , Röhl Ursula
Published: July 2002

Titanium and iron concentration data from the anoxic Cariaco Basin, off the Venezuelan coast, can be used to infer variations in the hydrological cycle over northern South America during the past 14,000 years with subdecadal resolution. Following a dry Younger Dryas, a period of increased precipitation and riverine discharge occurred during the Holocene “thermal maximum.” Since ∼5400 years ago, a trend toward drier conditions is evident from the data, with high-amplitude fluctuations and precipitation minima during the time interval 3800 to 2800 years ago and during the “Little Ice Age.” These regional changes in precipitation are best explained by shifts in the mean latitude of the Atlantic Intertropical Convergence Zone (ITCZ), potentially driven by Pacific-based climate variability. The Cariaco Basin record exhibits strong correlations with climate records from distant regions, including the high-latitude Northern Hemisphere, providing evidence for global teleconnections among regional climates.
Metabolic Regulation of Brain Aβ by Neprilysin
Authors: Iwata Nobuhisa , Tsubuki Satoshi , Takaki Yoshie , Shirotani Keiro , Lu Bao , Gerard Norma P. , Gerard Craig , Hama Emi , Lee Hahn-Jun , Saido Takaomi C.
Published: July 2002

Amyloid β peptide (Aβ), the pathogenic agent of Alzheimer's disease (AD), is a physiological metabolite in the brain. We examined the role of neprilysin, a candidate Aβ-degrading peptidase, in the metabolism using neprilysin gene-disrupted mice. Neprilysin deficiency resulted in defects both in the degradation of exogenously administered Aβ and in the metabolic suppression of the endogenous Aβ levels in a gene dose-dependent manner. The regional levels of Aβ in the neprilysin-deficient mouse brain were in the distinct order of hippocampus, cortex, thalamus/striatum, and cerebellum, where hippocampus has the highest level and cerebellum the lowest, correlating with the vulnerability to Aβ deposition in brains of humans with AD. Our observations suggest that even partial down-regulation of neprilysin activity, which could be caused by aging, can contribute to AD development by promoting Aβ accumulation.
Discovery of Hidden Blazars
Authors: Ma Feng , Wills Beverley J.
Published: July 2002

Every radio-loud quasar may have blazar activities, according to a unified scheme where the differences in both optical and radio observations of radio-loud quasars are the result of different viewing angles. We have predicted that blazars may be detected using emission line ratio variations caused by variable illumination of gas clouds in the broad emission line region. In a spectroscopic search of 62 quasars at a redshift of about 2, we have discovered large (>20%) variations of the emission line ratios, CIV/CIII] or CIV/Lyα, when compared with data taken more than 10 years ago. This result is consistent with our prediction and supports the unification scheme for radio-loud quasars.
The Human Nuclear Xenobiotic Receptor PXR: Structural Determinants of Directed Promiscuity
Authors: Watkins Ryan E. , Wisely G. Bruce , Moore Linda B. , Collins Jon L. , Lambert Millard H. , Williams Shawn P. , Willson Timothy M. , Kliewer Steven A. , Redinbo Matthew R.
Published: July 2002

The human nuclear pregnane X receptor (hPXR) activates cytochrome P450-3A expression in response to a wide variety of xenobiotics and plays a critical role in mediating dangerous drug-drug interactions. We present the crystal structures of the ligand-binding domain of hPXR both alone and in complex with the cholesterol-lowering drug SR12813 at resolutions of 2.5 and 2.75 angstroms, respectively. The hydrophobic ligand-binding cavity of hPXR contains a small number of polar residues, permitting SR12813 to bind in three distinct orientations. The position and nature of these polar residues were found to be critical for establishing the precise pharmacologic activation profile of PXR. Our findings provide important insights into how hPXR detects xenobiotics and may prove useful in predicting and avoiding drug-drug interactions.
RNA Silencing in Plants--Defense and Counterdefense
Authors: Vance Vicki , Vaucheret Hervé
Published: July 2002

RNA silencing is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. In plants, it serves as an antiviral defense, and many plant viruses encode suppressors of silencing. The emerging view is that RNA silencing is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and that it may become a powerful tool to manipulate gene expression experimentally.
Paradise Regained
Authors: Knapp Sandra
Published: July 2002

The Eden Project
. Bodelva, St. Austell, Cornwall PL24 2 SG, UK.
www.edenproject.org.uk/

An abandoned china-clay pit in Cornwall has been filled with a new science center that highlights plant communities from around the world. Linked geodesic domes shelter selections from humid tropical and dry temperate biomes.
A Private-Sector Perspective
Authors: Goldman Michael A.
Published: July 2002

Transducing the Genome
Information, Anarchy, and Revolution in the Biomedical Sciences. Gary Zweiger. McGraw-Hill, New York, 2001. 287 pp. $24.95. ISBN 0-07-136980-5.

This exploration of the emergence and significance of genomics offers non-specialist readers an insider's view of the changes information technology and the entrepreneurial approach have brought to biomedicine.
A Role for the RNase III Enzyme DCR-1 in RNA Interference and Germ Line Development in
Caenorhabditis elegans
Authors: Knight Scott W. , Bass Brenda L.
Published: July 2002

An early event in RNA interference (RNAi) is the cleavage of the initiating double-stranded RNA (dsRNA) to short pieces, 21 to 23 nucleotides in length. Here we describe a null mutation in
dicer-1
(
dcr-1
), a gene proposed to encode the enzyme that generates these short RNAs. We find that
dcr-1
(−/−) animals have defects in RNAi under some, but not all, conditions. Mutant animals have germ line defects that lead to sterility, suggesting that cleavage of dsRNA to short pieces is a requisite event in normal development.
A Genomic-Systems Biology Map for Cardiovascular Function
Authors: Stoll Monika , Cowley Allen W. , Tonellato Peter J. , Greene Andrew S. , Kaldunski Mary L. , Roman Richard J. , Dumas Pierre , Schork Nicholas J. , Wang Zhitao , Jacob Howard J.
Published: July 2002

With the draft sequence of the human genome available, there is a need to better define gene function in the context of systems biology. We studied 239 cardiovascular and renal phenotypes in 113 male rats derived from an F
2
intercross and mapped 81 of these traits onto the genome. Aggregates of traits were identified on chromosomes 1, 2, 7, and 18. Systems biology was assessed by examining patterns of correlations (“physiological profiles”) that can be used for gene hunting, mechanism-based physiological studies, and, with comparative genomics, translating these data to the human genome.
Bmf: A Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis
Authors: Puthalakath Hamsa , Villunger Andreas , O'Reilly Lorraine A. , Beaumont Jennifer G. , Coultas Leigh , Cheney Richard E. , Huang David C. S. , Strasser Andreas
Published: July 2002

Bcl-2 family members bearing only the BH3 domain are essential inducers of apoptosis. We identified a BH3-only protein, Bmf, and show that its BH3 domain is required both for binding to prosurvival Bcl-2 proteins and for triggering apoptosis. In healthy cells, Bmf is sequestered to myosin V motors by association with dynein light chain 2. Certain damage signals, such as loss of cell attachment (anoikis), unleash Bmf, allowing it to translocate and bind prosurvival Bcl-2 proteins. Thus, at least two mammalian BH3-only proteins, Bmf and Bim, function to sense intracellular damage by their localization to distinct cytoskeletal structures.
The Role of Sleep in Learning and Memory
Authors: Maquet Pierre
Published: July 2002

Sleep has been implicated in the plastic cerebral changes that underlie learning and memory. Indications that sleep participates in the consolidation of fresh memory traces come from a wide range of experimental observations. At the network level, reactivations during sleep of neuronal assemblies recently challenged by new environmental circumstances have been reported in different experimental designs. These neuronal assemblies are proposed to be involved in the processing of memory traces during sleep. However, despite this rapidly growing body of experimental data, evidence for the influence of sleep discharge patterns on memory traces remains fragmentary. The underlying role of sleep in learning and memory has yet to be precisely characterized.
Clear View of a Promising Future
Authors: Rutter Michael
Published: July 2002

Brave New Brain
Conquering Mental Illness in the Era of the Genome. Nancy C. Andreasen. Oxford University Press, New York, 2001. 380 pp. $29.95. ISBN 0-19-514509-7.

Writing for a broad audience, Andreasen explores how our understanding of mental illness can be advanced through research on mapping the brain and mapping the human genome.
Lack of Acrosome Formation in Hrb-Deficient Mice
Authors: Kang-Decker Ningling , Mantchev George T. , Juneja Subhash C. , McNiven Mark A. , van Deursen Jan M. A.
Published: July 2002

The sperm acrosome is essential for sperm-egg fusion and is often defective in men with nonobstructive infertility. Here we report that male mice with a null mutation in Hrb are infertile and display round-headed spermatozoa that lack an acrosome. In wild-type spermatids, Hrb is associated with the cytosolic surface of proacrosomic transport vesicles that fuse to create a single large acrosomic vesicle at step 3 of spermiogenesis. Although proacrosomic vesicles form in spermatids that lack Hrb, the vesicles are unable to fuse, blocking acrosome development at step 2. We conclude that Hrb is required for docking and/or fusion of proacrosomic vesicles during acrosome biogenesis.
The Tagish Lake Meteorite: A Possible Sample from a D-Type Asteroid
Authors: Hiroi Takahiro , Zolensky Michael E. , Pieters Carle M.
Published: July 2002

A new type of carbonaceous chondrite, the Tagish Lake meteorite, exhibits a reflectance spectrum similar to spectra observed from the D-type asteroids, which are relatively abundant in the outer solar system beyond the main asteroid belt and have been inferred to be more primitive than any known meteorite. Until the Tagish Lake fall, these asteroids had no analog in the meteorite collections. The Tagish Lake meteorite is a carbon-rich (4 to 5 weight %), aqueously altered carbonaceous chondrite and contains high concentrations of presolar grains and carbonate minerals, which is consistent with the expectation that the D-type asteroids were originally made of primitive materials and did not experience any extensive heating.
Dielectrophoretic Assembly of Electrically Functional Microwires from Nanoparticle Suspensions
Authors: Hermanson Kevin D. , Lumsdon Simon O. , Williams Jacob P. , Kaler Eric W. , Velev Orlin D.
Published: July 2002

A new class of microwires can be assembled by dielectrophoresis from suspensions of metallic nanoparticles. The wires are formed in the gaps between planar electrodes and can grow faster than 50 micrometers per second to lengths exceeding 5 millimeters. They have good ohmic conductance and automatically form electrical connections to conductive islands or particles. The thickness and the fractal dimension of the wires can be controlled, and composite wires with a metallic core surrounded by a latex shell can be assembled. The simple assembly process and their high surface-to-volume ratio make these structures promising for wet electronic and bioelectronic circuits.
Modulation of Blood Fluke Development in the Liver by Hepatic CD4
+
Lymphocytes
Authors: Davies Stephen J. , Grogan Jane L. , Blank Rebecca B. , Lim K. C. , Locksley Richard M. , McKerrow James H.
Published: July 2002

We have identified an alternate developmental pathway in the life cycle of the trematode pathogen
Schistosoma mansoni
. This pathway is used in immunodeficient hosts in which the parasite fails to receive appropriate signals from the host immune system. Helminth development is altered at an early stage during infection, resulting in the appearance of attenuated forms that prolong survival of host and parasite. Hepatic CD4
+
T lymphocyte populations are an integral component of the immune signal recognized by the parasite.
Tumstatin, an Endothelial Cell-Specific Inhibitor of Protein Synthesis
Authors: Maeshima Yohei , Sudhakar Akulapalli , Lively Julie C. , Ueki Kohjiro , Kharbanda Surender , Kahn C. Ronald , Sonenberg Nahum , Hynes Richard O. , Kalluri Raghu
Published: July 2002

Tumstatin is a 28-kilodalton fragment of type IV collagen that displays both anti-angiogenic and proapoptotic activity. Here we show that tumstatin functions as an endothelial cell–specific inhibitor of protein synthesis. Through a requisite interaction with αVβ3 integrin, tumstatin inhibits activation of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3-kinase), protein kinase B (PKB/Akt), and mammalian target of rapamycin (mTOR), and it prevents the dissociation of eukaryotic initiation factor 4E protein (eIF4E) from 4E-binding protein 1. These results establish a role for integrins in mediating cell-specific inhibition of cap-dependent protein synthesis and suggest a potential mechanism for tumstatin's selective effects on endothelial cells.
Proving Watson-Crickery, Napkin by Napkin
Authors: Comfort Nathaniel
Published: July 2002

Meselson, Stahl, and the Replication of DNA
A History of "The Most Beautiful Experiment in Biology". Frederic Lawrence Holmes. Yale University Press, New Haven, CT, 2001. 515 pp. $40, £30. ISBN 0-300-08540-0.

Holmes provides a comprehensive account of the route to Meselson and Stahl's classical demonstration of the semi-conservative replication of DNA, and he discusses the reception, influence, and subsequent reputation of the experiment.
Everyday Impacts of a Most Influential Theory
Authors: Goldsmith Timothy H.
Published: July 2002

Evolution
. WGBH Educational Foundation, Boston, and Clear Blue Sky Productions, Seattle, WA. On PBS, evenings, 24 to 27 September 2001.

Evolution
The Triumph of an Idea . by Carl Zimmer. HarperCollins, New York, 2001. 384 pp. $40, C$59.95. ISBN 0-06-019906-7.

This seven-part television series and the companion book are parts of a multifaceted project that aims to explain evolution ("one of the most...misunderstood principles of life") to the general public. Both combine findings from modern genetics, molecular biology, and paleontology with examples from the grocery store, medicine cabinet, and everyday life.
Dnmt3L and the Establishment of Maternal Genomic Imprints
Authors: Bourc'his Déborah , Xu Guo-Liang , Lin Chyuan-Sheng , Bollman Brooke , Bestor Timothy H.
Published: July 2002

Complementary sets of genes are epigenetically silenced in male and female gametes in a process termed genomic imprinting. The
Dnmt3L
gene is expressed during gametogenesis at stages where genomic imprints are established. Targeted disruption of
Dnmt3L
caused azoospermia in homozygous males, and heterozygous progeny of homozygous females died before midgestation. Bisulfite genomic sequencing of DNA from oocytes and embryos showed that removal of Dnmt3L prevented methylation of sequences that are normally maternally methylated. The defect was specific to imprinted regions, and global genome methylation levels were not affected. Lack of maternal methylation imprints in heterozygous embryos derived from homozygous mutant oocytes caused biallelic expression of genes that are normally expressed only from the allele of paternal origin. The key catalytic motifs characteristic of DNA cytosine methyltransferases have been lost from Dnmt3L, and the protein is more likely to act as a regulator of imprint establishment than as a DNA methyltransferase.
A Transcriptional Switch Mediated by Cofactor Methylation
Authors: Xu Wei , Chen Hongwu , Du Keyong , Asahara Hiroshi , Tini Marc , Emerson Beverly M. , Montminy Marc , Evans Ronald M.
Published: July 2002

We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.
Reverse Transcriptase-Mediated Tropism Switching in
Bordetella
Bacteriophage
Authors: Liu Minghsun , Deora Rajendar , Doulatov Sergei R. , Gingery Mari , Eiserling Frederick A. , Preston Andrew , Maskell Duncan J. , Simons Robert W. , Cotter Peggy A. , Parkhill Julian , Miller Jeff F.
Published: July 2002

Host-pathogen interactions are often driven by mechanisms that promote genetic variability. We have identified a group of temperate bacteriophages that generate diversity in a gene, designated
mtd
(major tropism determinant), which specifies tropism for receptor molecules on host
Bordetella
species. Tropism switching is the result of a template-dependent, reverse transcriptase–mediated process that introduces nucleotide substitutions at defined locations within
mtd
. This cassette-based mechanism is capable of providing a vast repertoire of potential ligand-receptor interactions.
The Initial Mass Function of Stars: Evidence for Uniformity in Variable Systems
Authors: Kroupa Pavel
Published: July 2002

The distribution of stellar masses that form in one star formation event in a given volume of space is called the initial mass function (IMF). The IMF has been estimated from low-mass brown dwarfs to very massive stars. Combining IMF estimates for different populations in which the stars can be observed individually unveils an extraordinary uniformity of the IMF. This general insight appears to hold for populations including present-day star formation in small molecular clouds, rich and dense massive star-clusters forming in giant clouds, through to ancient and metal-poor exotic stellar populations that may be dominated by dark matter. This apparent universality of the IMF is a challenge for star formation theory, because elementary considerations suggest that the IMF ought to systematically vary with star-forming conditions.
Imaging Sites of Receptor Dephosphorylation by PTP1B on the Surface of the Endoplasmic Reticulum
Authors: Haj Fawaz G. , Verveer Peter J. , Squire Anthony , Neel Benjamin G. , Bastiaens Philippe I. H.
Published: July 2002

When bound by extracellular ligands, receptor tyrosine kinases (RTKs) on the cell surface transmit critical signals to the cell interior. Although signal termination is less well understood, protein tyrosine phosphatase–1B (PTP1B) is implicated in the dephosphorylation and inactivation of several RTKs. However, PTP1B resides on the cytoplasmic surface of the endoplasmic reticulum (ER), so how and when it accesses RTKs has been unclear. Using fluorescence resonance energy transfer (FRET) methods, we monitored interactions between the epidermal- and platelet-derived growth factor receptors and PTP1B. PTP1B-catalyzed dephosphorylation required endocytosis of the receptors and occurred at specific sites on the surface of the ER. Most of the RTKs activated at the cell surface showed interaction with PTP1B after internalization, establishing that RTK activation and inactivation are spatially and temporally partitioned within cells.
Cultural Traces of a Vital Fluid
Authors: Schmidt Kerstin
Published: July 2002

Blood
Perspectives on Art, Power, Politics and Pathology. mak.frankfurt and Schirn Kunsthalle, Frankfurt am Main, Germany. 11 November 2001 to 27 January 2002.
www.bloodexhibition.de

Blood
Art, Power, Politics and Pathology. James M. Bradburne, Ed. Prestel, Munich, 2001. 272 pp. Paper, $65. ISBN 3-7913-2600-7.

This interdisciplinary exhibit explores cultural, emotional, social, and scientific aspects of our changing understanding of what blood is and what it does.
Postsynaptic Induction of BDNF-Mediated Long-Term Potentiation
Authors: Kovalchuk Yury , Hanse Eric , Kafitz Karl W. , Konnerth Arthur
Published: July 2002

Brain-derived neurotrophic factor (BDNF) and other neurotrophins are critically involved in long-term potentiation (LTP). Previous reports point to a presynaptic site of neurotrophin action. By imaging dentate granule cells in mouse hippocampal slices, we identified BDNF-evoked Ca
2+
transients in dendrites and spines, but not at presynaptic sites. Pairing a weak burst of synaptic stimulation with a brief dendritic BDNF application caused an immediate and robust induction of LTP. LTP induction required activation of postsynaptic Ca
2+
channels and
N
-methyl-
d
-aspartate receptors and was prevented by the blockage of postsynaptic Ca
2+
transients. Thus, our results suggest that BDNF-mediated LTP is induced postsynaptically. Our finding that dendritic spines are the exclusive synaptic sites for rapid BDNF-evoked Ca
2+
signaling supports this conclusion.
A Brief For Power and Against Weapons
Authors: von Hippel Frank N.
Published: July 2002

Megawatts and Megatons
A Turning Point in the Nuclear Age?. Richard L. Garwin and Georges Charpak. New York, Knopf, 2001. 431 pp. $30, C$45. ISBN 0-375-40394-9.

Blending explanations of the physics of nuclear energy and nuclear weapons with policy analyses, the authors argue for accepting the benefits of nuclear power and acting to reduce the dangers of nuclear weaponry.