bluuebunny/crossref_metadata_2025 huggingface dataset:
Process control in semiconductor manufacturing
Authors: Butler S. W.
Published: July 2002

Semiconductor processing requirements are creating a need for better equipment capabilities with respect to process control. The goal of this paper is to propose the required capabilities and suggest what issues must be addressed in order for the equipment to have these capabilities. This paper will focus on the why and how of control, such as the components and various implementation forms of controllers, rather than specific algorithms. The major concepts of process control will be presented, such as multivariable control systems. The basic requirements for control to be possible will also be introduced. The role of metrology as pertaining to process control methods will be presented. The involvement of the process engineer with respect to control will be highlighted so that the proposed requirements for the flexibility and configurability of the equipment control system will be better understood. Examples of process control applications in semiconductor manufacturing will assist in explaining the concepts introduced in this paper.
AlGaAsSb/InGaSb quantum-well heterostructures for p-channel field-effect transistors
Authors: Klem J. F. , Lovejoy M. L.
Published: July 2002

We report the molecular-beam epitaxial growth and characterization of p-type modulation-doped AlGaAsSb/InGaSb quantum wells. Growth of AlGaAsSb with good compositional control was demonstrated with AlGaAs fractions up to 0.2. Characteristics of Schottky barrier contacts on AlGaSb and AlGaAsSb are compared. AlGaAs fractions of 0.1–0.15 in the doped barrier material of the modulation-doped structures lead to a significant reduction in measured low-field hole mobilities with respect to AlGaSb-barrier structures, with no measurable increase in the two-dimensional hole density. Incorporation of a thin AlGaSb spacer layer between the InGaSb quantum-well and AlGaAsSb doped layer greatly improves the measured mobilities.
Atomic scale reaction regulated in one-dimensional channels evidenced by scanning tunneling microscopy
Authors: Matsumoto Yuji , Tanaka Ken-ichi
Published: July 2002

By reacting (–Ag–O–) strings on Ag(110) with Cu atoms at room temperature, (–Cu–O–) strings were grown on the Ag(110) surface. The (–Cu–O–) chains grow along the [11̄0] direction and are ordered in a p2mg(2×2) structure on the Ag(110) surface. When a p2mg(2×2)(–Cu–O–)/Ag(110) surface was heated for several minutes at 570 K, the (–Cu–O–) strings were rearranged to a p(1×3) structure and the (–Cu–O–) strings underwent the preferential decomposition along the phase boundary of the p(1×3) domains. The decomposition of the (–Cu–O–) strings yielded uniform size (Cu)6 cluster dots (∼8 A) along the [11̄0] axis on the Ag(110) surface and its reverse reaction, the (Cu)6+O2→(–Cu–O–) string, took place also along the [11̄0] axis at room temperature.
Surface vibrational mode of ZnS nanoparticles
Authors: Xu Jianfeng , Mao Haitao , Sun Yue , Du Youwei
Published: July 2002

Raman scattering and infrared absorption from ZnS nanoparticles were measured. A broad peak was observed in Raman and infrared absorption spectra which can be attributed to the surface vibrational mode of ZnS nanoparticles.
Nanometer biodevice fabrication by electron beam lithography
Authors: Di Fabrizio Enzo , Grella Luca , Baciocchi Marco , Gentili Massimo , Ascoli Cesare , Cappella Brunero , Frediani Carlo , Morales Piero
Published: July 2002

A conventional electron beam lithography machine operated at 50 kV is used in this work to fabricate devices and structures for biophysical and molecular electronics applications featuring critical dimensions down to the nanometer region. Such nanostructures are used for deposition and manipulation of organic molecules; fabricated devices include fine pitch self-standing meshes for laser deposition of molecules, a bimetallic miniaturized glucose sensor and nanogaps for molecular trapping and probing. The developed process is described in detail and by means of Monte Carlo simulation, the various electron scattering processes are modelled. Critical issues, such as fabrication of nanogaps with dimension down to 5 nm, are also addressed.
Secondary electron imaging as a two-dimensional dopant profiling technique: Review and update
Authors: Venables D. , Jain H. , Collins D. C.
Published: July 2002

Secondary electron (SE) imaging of semiconductors reveals contrast between n- and p-type areas that can serve as the basis for a two-dimensional dopant profiling technique. In this article, recent experiments that address sensitivity, spatial resolution, calibration methodology, p/n junction effects, and sample preparation issues are reviewed and discussed for boron doped silicon. In addition, several examples of successful applications of SE imaging as a two-dimensional dopant profiling technique are presented.
Thermal decomposition of bulk and heteroepitaxial (100) InP surfaces: A combined in situ scanning electron microscopy and mass spectrometric study
Authors: Riesz Ferenc , Dobos L. , Karányi J.
Published: July 2002

The thermal decomposition of bulk and heteroepitaxial (100) InP surfaces is studied by in situ scanning electron microscopy combined with mass spectrometry. The onset of P evaporation coincides with the In droplet nucleation at about 480 °C and the major evaporation of phosphorous commences above 510 °C and corresponds to the serious deterioration of the surface. There is no significant difference between bulk and defected (heteroepitaxial InP/GaAs) samples. The relevance to InP technology is discussed.
Low temperature metal-organic chemical vapor deposition of tungsten nitride as diffusion barrier for copper metallization
Authors: Kelsey Jean E. , Goldberg Cindy , Nuesca Guillermo , Peterson Gregory , Kaloyeros Alain E. , Arkles Barry
Published: July 2002

A metal-organic chemical vapor deposition process has been developed for the growth of amorphous tungsten nitride thin films for barrier layer applications in ultralarge scale integration copper interconnect schemes. The process employs tungsten hexacarbonyl, [W(CO)6] and ammonia (NH3) as, respectively, the tungsten and nitrogen sources. Tungsten nitride films were produced within a wide process window, including a substrate temperature of 200–350 °C, W(CO)6 flow rate of 1–20 sccm, reactor pressure of 0.2–0.5 Torr, and NH3 flow rates of 100–500 sccm. The films were analyzed by x-ray photoelectron spectroscopy, cross-section scanning electron microscopy, x-ray diffraction, transmission electron microscopy, four-point resistivity probe, and Rutherford backscattering spectrometry. These studies indicated that the films consisted predominantly of a W2N phase. Films were grown with carbon and oxygen concentrations ⩽5 at. %, even at the lowest processing temperature investigated, where precursor dissociation would be expected to be the least efficient given the reduced thermal budget available to the decomposition reaction. Films deposited below 275 °C were amorphous, while those deposited between 275 and 350 °C were polycrystalline. Resistivities as low as 123 μΩ cm were achieved for 50-nm-thick films, with corresponding step coverage better than 90% in nominal 0.25 μm trench structures with aspect ratio of 4:1.
Recent advances in secondary ion mass spectrometry to characterize ultralow energy ion implants
Authors: Chia Victor K. F. , Mount Gary R. , Edgell Michael J. , Magee Charles W.
Published: July 2002

The need to measure depth profiles of ultralow energy (ULE) ion implants in silicon, required for ⩽180 nm IC device technology, has placed unprecedented requirements of high depth resolution and depth accuracy for the technique of secondary ion mass spectrometry (SIMS). The classic SIMS approaches to depth profiling ion implants employed in ⩾250 nm device technologies are not valid for characterizing ULE implants. One reason is that the SIMS artifacts, typically observed at ⩽30 nm, now occur in the depth range of the ULE implant. Two approaches have been proposed to overcome this. They are (i) oblique incidence bombardment, at less than 60° to the surface normal, with oxygen flooding, and (ii) normal incidence bombardment without oxygen flooding. The principle of both these approaches is the same, and requires the analytical surface to be modified to promote consistent secondary ion yields. Studies show the need to reduce the bombarding angle to <60° when using oxygen flooding. Depth profiling with this analytical condition is 3× faster than by normal incidence bombardment. When using normal incidence bombardment, a greater shift towards the surface is observed due to a differential sputtering rate in the very near-surface region. With either approach, the depth resolution is the same after this initial sputtering rate increase. Oblique incidence bombardment appears to be the best approach to characterize both “as-implanted” and annealed ULE ion implants under ONE instrumental condition.
F-doped and H2-impregnated synthetic SiO2 glasses for 157 nm optics
Authors: Mizuguchi Masafumi , Skuja Linards , Hosono Hideo , Ogawa Tohru
Published: July 2002

Optical transmission change and point defect formation by irradiation with F2 excimer laser light (∼10 mJ/cm2/pulse×3.6×105 pulses, λ=157 nm) were examined for four types of synthetic SiO2 glasses: wet (OH content: 1.7×1019 cm−3), dry (OH content: <1×1016 cm−3), F-doped (F content: 2.2×1020–4.2×1020 cm−3, OH content: <1×1016 cm−3), and H2-impregnated (OH content; 1.9×1018 cm−3, H2 content; 1×1018 cm−3) SiO2 glasses. Intense optical absorption bands peaking at 4.8 and 5.8 eV, which are attributed to nonbridging oxygen hole center and E′ center, respectively, and a shoulder at ∼7 eV were induced in the wet and dry specimens after the irradiation. On the other hand, the intensities of absorption bands induced in the F-doped and H2-impregnated specimens were smaller by an order of magnitude than those in other specimens. The internal (reflection-corrected) transmittance at the wavelength of 157 nm for 5 mm thick samples after the irradiation was 87% for the F-doped, 82% for the H2-impregnated, 14% for the wet, and 2.4% for the dry silica glasses. The present results show that F doping or H2 impregnation is an effective way to improve resistance of SiO2 glasses to F2 laser damage.
Ion-etch produced damage on InAs(100) studied through collective-mode electronic Raman scattering
Authors: Tanzer T. A. , Bohn P. W. , Roshchin I. V. , Green L. H.
Published: July 2002

Raman scattering and x-ray photoelectron spectroscopy are used to study the damage induced by low energy Ar+ milling on InAs(100) surfaces. Evidence for etch-induced lattice damage is obtained even under the mildest conditions employed. Etching at 75 V creates an In-rich surface and reduces the intensity of scattering from the unscreened longitudinal optic (LO) phonon in the near-surface region. Etching at higher voltages creates damage states that increase the carrier concentration at depths at least as large as the Raman probe depth (∼100 Å). Postetch annealing at 500 °C in ultrahigh vacuum restores the LO phonon mode to its original intensity, the carrier concentration to original levels, and a stoichiometric (In:As=1:1) surface composition. Etch-induced lattice damage in the near-surface region, which is subsequently removed by annealing at optimal temperatures, is the only mechanism consistent with all the inelastic light scattering and composition results.
Tailoring etch directionality in a deep reactive ion etching tool
Authors: Ayón A. A. , Nagle S. , Fréchette L. , Epstein A. , Schmidt M. A.
Published: July 2002

Silicon deep reactive ion etching is a process that produces projected two-dimensional shapes due to the inability to control the direction of the energetic ions arriving at the surface of a wafer. The resulting etched profiles present sidewalls which are nominally 90° to the wafer surface. However, we have developed and demonstrated a new technique that allows us to control the angle that trenches make with respect to the wafer surface. This scheme exploits the charging of buried dielectric layers to achieve ion steering and thus control the direction of the etch. The measured angle variation was controlled between −32° and +32° with respect to a line orthogonal to the wafer surface. We report and describe this new technique to control etch angle.
Process diagnostics and thickness metrology using in situ mass spectrometry for the chemical vapor deposition of W from H2/WF6
Authors: Gougousi Theodosia , Xu Yiheng , Kidder John N. , Rubloff Gary W. , Tilford Charles R.
Published: July 2002

Quadrupole mass spectrometry has been used to monitor reactant and product partial pressures in a selective W chemical vapor deposition process. A 4/1H2/WF6 molar reactant ratio was used to produce W films on Si wafers, at 67 Pa (0.5 Torr) total pressure, and for wafer temperatures around 400 °C. A relatively fast response time (∼4 s) sensor system sampled gas directly from a commercial Ulvac ERA-1000 reactor in order to minimize the effect of wall reactions. The signal from the volatile HF product, integrated over the deposition cycle, and corrected for contributions from reactions in the ion-source region of the quadrupole and for sensor drifts, was found to vary linearly with the weight of the W film deposited, to within an uncertainty of ∼7%. This provides the basis for real-time, noninvasive thickness metrology to drive process control. Depletion of both H2 and WF6 reactants was observed. The time integral of the H2 reactant depletion was also linearly related to the film weight, though the data exhibited a somewhat larger scatter due to the low conversion efficiency of the process. In addition, volatile SiF4 and SiHF3 products of the initial rapid W nucleation reaction on the Si surface were clearly observed, indicating that initial surface conditions may be monitored in real time under selective growth conditions.
Continuous Fatty Acid Oxidation and Reduced Fat Storage in Mice Lacking Acetyl-CoA Carboxylase 2
Authors: Abu-Elheiga Lutfi , Matzuk Martin M. , Abo-Hashema Khaled A. H. , Wakil Salih J.
Published: July 2002

Malonyl–coenzyme A (malonyl-CoA), generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key metabolite in the regulation of energy homeostasis. Here, we show thatAcc2−/−mutant mice have a normal life span, a higher fatty acid oxidation rate, and lower amounts of fat. In comparison to the wild type, Acc2-deficient mice had 10- and 30-fold lower levels of malonyl-CoA in heart and muscle, respectively. The fatty acid oxidation rate in the soleus muscle of theAcc2−/−mice was 30% higher than that of wild-type mice and was not affected by addition of insulin; however, addition of insulin to the wild-type muscle reduced fatty acid oxidation by 45%. The mutant mice accumulated 50% less fat in their adipose tissue than did wild-type mice. These results raise the possibility that pharmacological manipulation of ACC2 may lead to loss of body fat in the context of normal caloric intake.
Antibody Catalysis of the Oxidation of Water
Authors: Wentworth Paul , Jones Lyn H. , Wentworth Anita D. , Zhu Xueyong , Larsen Nicholas A. , Wilson Ian A. , Xu Xin , Goddard William A. , Janda Kim D. , Eschenmoser Albert , Lerner Richard A.
Published: July 2002

Recently we reported that antibodies can generate hydrogen peroxide (H
2
O
2
) from singlet molecular oxygen (
1
O
2
*). We now show that this process is catalytic, and we identify the electron source for a quasi-unlimited generation of H
2
O
2
. Antibodies produce up to 500 mole equivalents of H
2
O
2
from
1
O
2
*, without a reduction in rate, and we have excluded metals or Cl
–
as the electron source. On the basis of isotope incorporation experiments and kinetic data, we propose that antibodies use H
2
O as an electron source, facilitating its addition to
1
O
2
* to form H
2
O
3
as the first intermediate in a reaction cascade that eventually leads to H
2
O
2
. X-ray crystallographic studies with xenon point to putative conserved oxygen binding sites within the antibody fold where this chemistry could be initiated. Our findings suggest a protective function of immunoglobulins against
1
O
2
* and raise the question of whether the need to detoxify
1
O
2
* has played a decisive role in the evolution of the immunoglobulin fold.
Caenorhabditis elegansp53: Role in Apoptosis, Meiosis, and Stress Resistance
Authors: Derry W. Brent , Putzke Aaron P. , Rothman Joel H.
Published: July 2002

We have identified a homolog of the mammalian p53 tumor suppressor protein in the nematodeCaenorhabditis elegansthat is expressed ubiquitously in embryos. The gene encoding this protein,cep-1, promotes DNA damage–induced apoptosis and is required for normal meiotic chromosome segregation in the germ line. Moreover, although somatic apoptosis is unaffected,cep-1mutants show hypersensitivity to hypoxia-induced lethality and decreased longevity in response to starvation-induced stress. Overexpression of CEP-1 promotes widespread caspase-independent cell death, demonstrating the critical importance of regulating p53 function at appropriate levels. These findings show thatC. elegansp53 mediates multiple stress responses in the soma, and mediates apoptosis and meiotic chromosome segregation in the germ line.
Probing Protein Electrostatics with a Synthetic Fluorescent Amino Acid
Authors: Cohen Bruce E. , McAnaney Tim B. , Park Eun Sun , Jan Yuh Nung , Boxer Steven G. , Jan Lily Yeh
Published: July 2002

Electrostatics affect virtually all aspects of protein structure and activity and are particularly important in proteins whose primary function is to stabilize charge. Here we introduce a fluorescent amino acid, Aladan, which can probe the electrostatic character of a protein at multiple sites. Aladan is exceptionally sensitive to the polarity of its surroundings and can be incorporated site-selectively at buried and exposed sites, in both soluble and membrane proteins. Steady-state and time-resolved fluorescence measurements of Aladan residues at different buried and exposed sites in the B1 domain of protein G suggest that its interior is polar and heterogeneous.
Systems Biology: A Brief Overview
Authors: Kitano Hiroaki
Published: July 2002

To understand biology at the system level, we must examine the structure and dynamics of cellular and organismal function, rather than the characteristics of isolated parts of a cell or organism. Properties of systems, such as robustness, emerge as central issues, and understanding these properties may have an impact on the future of medicine. However, many breakthroughs in experimental devices, advanced software, and analytical methods are required before the achievements of systems biology can live up to their much-touted potential.
Design and Control of Wave Propagation Patterns in Excitable Media
Authors: Sakurai Tatsunari , Mihaliuk Eugene , Chirila Florin , Showalter Kenneth
Published: July 2002

Intricate patterns of wave propagation are exhibited in a chemical reaction-diffusion system with spatiotemporal feedback. Wave behavior is controlled by feedback-regulated excitability gradients that guide propagation in specified directions. Waves interacting with boundaries and with other waves are observed when interaction terms are incorporated into the control algorithm. Spatiotemporal feedback offers wide flexibility for designing and controlling wave behavior in excitable media.
The Fas Signaling Pathway: More Than a Paradigm
Authors: Wajant Harald
Published: July 2002

Apoptosis and related forms of cell death have central importance in development, homeostasis, tumor surveillance, and the function of the immune system. Apoptosis is initiated by two principal pathways. The intrinsic pathway emerges from mitochondria, whereas the extrinsic pathway is activated by the ligation of death receptors. This Viewpoint introduces the basic mechanisms of the extrinsic pathway, using the example of the prototypical death receptor Fas and its role in apoptosis, but it also points out the increasingly understood importance of this receptor as a non-apoptotic signal transducer.
Pass the Butter …
Authors: Martin Gail
Published: July 2002

The Hedgehog family of signaling molecules is essential for a variety of developmental processes. In this issue, Porter
et al
. (
p. 255
) identify the lipid adduct to
Sonic hedgehog
—necessary for its function in vertebrate head development—as cholesterol. In his Perspective, Martin discusses how this new function for cholesterol may be the first example of a modification used by many signaling molecules.
Self-Sterility in
Arabidopsis
Due to Defective Pollen Tube Guidance
Authors: Wilhelmi Laura K. , Preuss Daphne
Published: July 2002

In flowering plants, a series of cell-cell interactions govern the delivery of sperm to the ovules through precise guidance of pollen tubes. Two
Arabidopsis
genes,
POP2
and
POP3
, were found that mediate pollen tube guidance and are critical for self-fertility in diploid reproductive cells. The
pop2
and
pop3
mutations exhibited genetic redundancy: Self-sterility occurred only when male and female tissues were defective in both genes. This phenotype resembles that found in many self-incompatible species.
Social Dilemmas and Internet Congestion
Authors: Huberman Bernardo A. , Lukose Rajan M.
Published: July 2002

Because the Internet is a public good and its numerous users are not charged in proportion to their use, it appears rational for individuals to consume bandwidth greedily while thinking that their actions have little effect on the overall performance of the Internet. Because every individual can reason this way, the whole Internet's performance can degrade considerably, which makes everyone worse off. An analysis of the congestions created by such dilemmas predicts that they are intermittent in nature with definite statistical properties leading to short-lived spikes in congestion. Internet latencies were measured over a wide range of conditions and locations and were found to confirm these predictions, thus providing a possible microscopic mechanism for the observed intermittent congestions of the Internet.
Regioselective Stepwise Growth of Dendrimer Units in the Internal Voids of a Main Dendrimer
Authors: Galliot Christophe , Larré Christophe , Caminade Anne-Marie , Majoral Jean-Pierre
Published: July 2002

Dendrimers constitute a class of polymers with unique properties and applications resulting from the presence of internal voids and of a large number of functionalities on the surface. The development of a macromolecular chemistry within the cavities of dendrimers is illustrated here. Two examples of construction of six dendrimer units within the cascade structure of a main dendrimer are reported. The preparation of these multidendritic systems involves the regioselective modification of the framework of the central dendrimer to create internal reactive centers, followed by the stepwise synthesis of the six dendritic macromolecules.
Requirement for the CD95 Receptor-Ligand Pathway in c-Myc-Induced Apoptosis
Authors: Hueber Anne-Odile , Zörnig Martin , Lyon Debbie , Suda Takashi , Nagata Shigekazu , Evan Gerard I.
Published: July 2002

Induction of apoptosis by oncogenes like c-
myc
may be important in restraining the emergence of neoplasia. However, the mechanism by which c-
myc
induces apoptosis is unknown. CD95 (also termed Fas or APO-1) is a cell surface transmembrane receptor of the tumor necrosis factor receptor family that activates an intrinsic apoptotic suicide program in cells upon binding either its ligand CD95L or antibody. c-
myc
–induced apoptosis was shown to require interaction on the cell surface between CD95 and its ligand. c-Myc acts downstream of the CD95 receptor by sensitizing cells to the CD95 death signal. Moreover, IGF-I signaling and Bcl-2 suppress c-
myc
–induced apoptosis by also acting downstream of CD95. These findings link two apoptotic pathways previously thought to be independent and establish the dependency of Myc on CD95 signaling for its killing activity.
Suppression of Volcanism During Rapid Extension in the Basin and Range Province, United States
Authors: Gans P. B. , Bohrson W. A.
Published: July 2002

Continental extension and volcanism are generally thought to be complementary. Stratigraphic and structural data from some highly extended parts of the Basin and Range province reveal instead that rapid extension appears to have suppressed volcanism. This relation may reflect enhanced crystallization of midcrustal magmas during extension resulting from exsolution of magmatic volatiles, increased interaction of magmas with meteoric water, and dispersal of magma into smaller bodies. Some rift environments may thus be characterized by voluminous synextensional plutonism with little or no concomitant volcanism.
Shape Transition of Germanium Nanocrystals on a Silicon (001) Surface from Pyramids to Domes
Authors: Medeiros-Ribeiro Gilberto , Bratkovski Alexander M. , Kamins Theodore I. , Ohlberg Douglas A. A. , Williams R. Stanley
Published: July 2002

Chemical vapor deposition of germanium onto the silicon (001) surface at atmospheric pressure and 600 degrees Celsius has previously been shown to produce distinct families of smaller (up to 6 nanometers high) and larger (all approximately 15 nanometers high) nanocrystals. Under ultrahigh-vacuum conditions, physical vapor deposition at approximately the same substrate temperature and growth rate produced a similar bimodal size distribution. In situ scanning tunneling microscopy revealed that the smaller square-based pyramids transform abruptly during growth to significantly larger multifaceted domes, and that few structures with intermediate size and shape remain. Both nanocrystal shapes have size-dependent energy minima that result from the interplay between strain relaxation at the facets and stress concentration at the edges. A thermodynamic model similar to a phase transition accounts for this abrupt morphology change.
Incorporation of Photoluminescent Polarizers into Liquid Crystal Displays
Authors: Weder Christoph , Sarwa Christian , Montali Andrea , Bastiaansen Cees , Smith Paul
Published: July 2002

Liquid crystal displays, the dominant flat panel display technology, are limited in brightness and energy efficiency because of the use of absorbing polarizers and color filters. Liquid crystal–based photoluminescent display devices have been fabricated that use thin, polarized photoluminescent layers that have highly anisotropic absorption or emission. These layers both polarize light and generate bright color. This approach can simplify device design and substantially increase device brightness, contrast, efficiency, and (in specific configurations) viewing angle.
Searching the World Wide Web
Authors: Lawrence Steve , Giles C. Lee
Published: July 2002

The coverage and recency of the major World Wide Web search engines was analyzed, yielding some surprising results. The coverage of any one engine is significantly limited: No single engine indexes more than about one-third of the “indexable Web,” the coverage of the six engines investigated varies by an order of magnitude, and combining the results of the six engines yields about 3.5 times as many documents on average as compared with the results from only one engine. Analysis of the overlap between pairs of engines gives an estimated lower bound on the size of the indexable Web of 320 million pages.
Brain Activity During Speaking: From Syntax to Phonology in 40 Milliseconds
Authors: Turennout Miranda van , Hagoort Peter , Brown Colin M.
Published: July 2002

In normal conversation, speakers translate thoughts into words at high speed. To enable this speed, the retrieval of distinct types of linguistic knowledge has to be orchestrated with millisecond precision. The nature of this orchestration is still largely unknown. This report presents dynamic measures of the real-time activation of two basic types of linguistic knowledge, syntax and phonology. Electrophysiological data demonstrate that during noun-phrase production speakers retrieve the syntactic gender of a noun before its abstract phonological properties. This two-step process operates at high speed: the data show that phonological information is already available 40 milliseconds after syntactic properties have been retrieved.
A Tunable Kondo Effect in Quantum Dots
Authors: Cronenwett Sara M. , Oosterkamp Tjerk H. , Kouwenhoven Leo P.
Published: July 2002

A tunable Kondo effect has been realized in small quantum dots. A dot can be switched from a Kondo system to a non-Kondo system as the number of electrons on the dot is changed from odd to even. The Kondo temperature can be tuned by means of a gate voltage as a single-particle energy state nears the Fermi energy. Measurements of the temperature and magnetic field dependence of a Coulomb-blockaded dot show good agreement with predictions of both equilibrium and nonequilibrium Kondo effects.
Circular Polarization in Star- Formation Regions: Implications for Biomolecular Homochirality
Authors: Bailey Jeremy , Chrysostomou Antonio , Hough J. H. , Gledhill T. M. , McCall Alan , Clark Stuart , Ménard François , Tamura Motohide
Published: July 2002

Strong infrared circular polarization resulting from dust scattering in reflection nebulae in the Orion OMC-1 star-formation region has been observed. Circular polarization at shorter wavelengths might have been important in inducing chiral asymmetry in interstellar organic molecules that could be subsequently delivered to the early Earth by comets, interplanetary dust particles, or meteors. This could account for the excess ofl–amino acids found in the Murchison meteorite and could explain the origin of the homochirality of biological molecules.
Neptune's Partial Rings: Action of Galatea on Self-Gravitating Arc Particles
Authors: Salo Heikki , Hänninen Jyrki
Published: July 2002

Numerical simulations of Neptune's arcs show that self-gravity between macroscopic arc particles can prevent interparticle impacts and thereby stabilize their resonant confinement by Galatea, a satellite of Neptune. Stable subkilometer arc particles provide a source for replenishing the observed dust and explain the clumpy substructure seen in arcs. A few confining kilometer-sized particles between the major arc components can account for the observed arc widths spanning several resonance sites. The modeled distribution of dust is consistent with observations and helps to explain how embedded satellites may affect the structure and evolution of planetary ring systems.
Prevention of Population Cycles by Parasite Removal
Authors: Hudson Peter J. , Dobson Andy P. , Newborn Dave
Published: July 2002

The regular cyclic fluctuations in vertebrate numbers have intrigued scientists for more than 70 years, and yet the cause of such cycles has not been clearly demonstrated. Red grouse populations in Britain exhibit cyclic fluctuations in abundance, with periodic crashes. The hypothesis that these fluctuations are caused by the impact of a nematode parasite on host fecundity was tested by experimentally reducing parasite burdens in grouse. Treatment of the grouse population prevented population crashes, demonstrating that parasites were the cause of the cyclic fluctuations.
The Looming Threat of Bioterrorism
Authors: Henderson Donald A.
Published: July 2002

Biological weapons have recently attracted the attention and the resources of the nation. Discerning the nature of the threat of bioweapons as well as appropriate responses to them requires greater attention to the biological characteristics of these instruments of war and terror. The dominant paradigm of a weapon as a nuclear device that explodes or a chemical cloud that is set adrift leaves us ill-equipped conceptually and practically to assess and thus to prevent the potentially devastating effects of bioterrorism. Strengthening the public health and infectious disease infrastructure is an effective step toward averting the suffering that could be wrought by a terrorist's use of a biological agent.
Function of WW Domains as Phosphoserine- or Phosphothreonine-Binding Modules
Authors: Lu Pei-Jung , Zhou Xiao Zhen , Shen Minhui , Lu Kun Ping
Published: July 2002

Protein-interacting modules help determine the specificity of signal transduction events, and protein phosphorylation can modulate the assembly of such modules into specific signaling complexes. Although phosphotyrosine-binding modules have been well-characterized, phosphoserine- or phosphothreonine-binding modules have not been described. WW domains are small protein modules found in various proteins that participate in cell signaling or regulation. WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with properties similar to those of SRC homology 2 domains. Phosphoserine- or phosphothreonine-binding activity was required for Pin1 to interact with its substrates in vitro and to perform its essential function in vivo.
Complexity in Chemistry
Authors: Whitesides George M. , Ismagilov Rustem F.
Published: July 2002

“Complexity” is a subject that is beginning to be important in chemistry. Historically, chemistry has emphasized the approximation of complex nonlinear processes by simpler linear ones. Complexity is becoming a profitable approach to a wide range of problems, especially the understanding of life.
An Infrared Spectral Match Between GEMS and Interstellar Grains
Authors: Bradley John P. , Keller Lindsay P. , Snow Theodore P. , Hanner Martha S. , Flynn George J. , Gezo Joseph C. , Clemett Simon J. , Brownlee Donald E. , Bowey Janet E.
Published: July 2002

Infrared spectral properties of silicate grains in interplanetary dust particles (IDPs) were compared with those of astronomical silicates. The ∼10-micrometer silicon-oxygen stretch bands of IDPs containing enstatite (MgSiO3), forsterite (Mg2SiO4), and glass with embedded metal and sulfides (GEMS) exhibit fine structure and bandwidths similar to those of solar system comets and some pre–main sequence Herbig Ae/Be stars. Some GEMS exhibit a broad, featureless silicon-oxygen stretch band similar to those observed in interstellar molecular clouds and young stellar objects. These GEMS provide a spectral match to astronomical “amorphous” silicates, one of the fundamental building blocks from which the solar system is presumed to have formed.
Mouse Models of Tumor Development in Neurofibromatosis Type 1
Authors: Cichowski Karen , Shih T. Shane , Schmitt Earlene , Santiago Sabrina , Reilly Karlyne , McLaughlin Margaret E. , Bronson Roderick T. , Jacks Tyler
Published: July 2002

Neurofibromatosis type 1 (NF1) is a prevalent familial cancer syndrome resulting from germ line mutations in theNF1tumor suppressor gene. Hallmark features of the disease are the development of benign peripheral nerve sheath tumors (neurofibromas), which can progress to malignancy. Unlike humans, mice that are heterozygous for a mutation inNf1do not develop neurofibromas. However, as described here, chimeric mice composed in part ofNf1−/−cells do, which demonstrates that loss of the wild-typeNf1allele is rate-limiting in tumor formation. In addition, mice that carry linked germ line mutations inNf1andp53develop malignant peripheral nerve sheath tumors (MPNSTs), which supports a cooperative and causal role for p53 mutations in MPNST development. These two mouse models provide the means to address fundamental aspects of disease development and to test therapeutic strategies.
Mouse Tumor Model for Neurofibromatosis Type 1
Authors: Vogel Kristine S. , Klesse Laura J. , Velasco-Miguel Susana , Meyers Kimberly , Rushing Elizabeth J. , Parada Luis F.
Published: July 2002

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by increased incidence of benign and malignant tumors of neural crest origin. Mutations that activate the protooncogeneras, such as loss ofNf1, cooperate with inactivating mutations at thep53tumor suppressor gene during malignant transformation. One hundred percent of mice harboring nullNf1andp53alleles in cis synergize to develop soft tissue sarcomas between 3 and 7 months of age. These sarcomas exhibit loss of heterozygosity at both gene loci and express phenotypic traits characteristic of neural crest derivatives and human NF1 malignancies.
Quantum Impurity in a Nearly Critical Two-Dimensional Antiferromagnet
Authors: Sachdev Subir , Buragohain Chiranjeeb , Vojta Matthias
Published: July 2002

The spin dynamics of an arbitrary localized impurity in an insulating two-dimensional antiferromagnet, across the host transition from a paramagnet with a spin gap to a Néel state, is described. The impurity spin susceptibility has a Curie-like divergence at the quantum-critical coupling, but with a universal effective spin that is neither an integer nor a half-odd integer. In the Néel state, the transverse impurity susceptibility is a universal number divided by the host spin stiffness (which determines the energy cost to slow twists in the orientation of the Néel order). These and numerous other results for the thermodynamics, Knight shift, and magnon damping have important applications in experiments on layered transition metal oxides.
Heavy Nitrogen in Carbonatites of the Kola Peninsula: A Possible Signature of the Deep Mantle
Authors: Dauphas Nicolas , Marty Bernard
Published: July 2002

Nitrogen and argon isotopes were measured in carbonatites and associated rocks from the Kola Peninsula in Russia. The Kola mantle source, which is thought to be located in the deep mantle, is enriched in heavy nitrogen (+3 per mil relative to air) as compared to Earth's surface (atmosphere and crust, +2 per mil) and the shallow mantle (–4 per mil). Recycling of oceanic crust (+6 per mil) or metal-silicate partitioning may account for the nitrogen isotopic composition of the deep mantle.
Timing the Ancestor of the HIV-1 Pandemic Strains
Authors: Korber B. , Muldoon M. , Theiler J. , Gao F. , Gupta R. , Lapedes A. , Hahn B. H. , Wolinsky S. , Bhattacharya T.
Published: July 2002

HIV-1 sequences were analyzed to estimate the timing of the ancestral sequence of the main group of HIV-1, the strains responsible for the AIDS pandemic. Using parallel supercomputers and assuming a constant rate of evolution, we applied maximum-likelihood phylogenetic methods to unprecedented amounts of data for this calculation. We validated our approach by correctly estimating the timing of two historically documented points. Using a comprehensive full-length envelope sequence alignment, we estimated the date of the last common ancestor of the main group of HIV-1 to be 1931 (1915–41). Analysis of a gag gene alignment, subregions of envelope including additional sequences, and a method that relaxed the assumption of a strict molecular clock also supported these results.
Northridge Earthquake Damage Caused by Geologic Focusing of Seismic Waves
Authors: Davis Paul M. , Rubinstein Justin L. , Liu Kelly H. , Gao Stephen S. , Knopoff Leon
Published: July 2002

Despite being located 21 kilometers from the epicenter of the 1994 Northridge earthquake (magnitude 6.7), the city of Santa Monica experienced anomalously concentrated damage with Mercalli intensity IX, an intensity as large as that experienced in the vicinity of the epicenter. Seismic records from aftershocks suggest that the damage resulted from the focusing of seismic waves by several underground acoustic lenses at depths of about 3 kilometers, formed by the faults that bound the northwestern edge of the Los Angeles basin. The amplification was greatest for high-frequency waves and was less powerful at lower frequencies, which is consistent with focusing theory and finite-difference simulations.
Randomized Comparison of Linezolid (PNU-100766) versus Oxacillin-Dicloxacillin for Treatment of Complicated Skin and Soft Tissue Infections
Authors: Stevens Dennis L. , Smith Leon G. , Bruss Jon B. , McConnell-Martin Maureen A. , Duvall Sue E. , Todd Wesley Mark , Hafkin Barry
Published: July 2002

This randomized, double-blind, multicenter trial compared the efficacy and safety of linezolid, an oxazolidinone, with those of oxacillin-dicloxacillin in patients with complicated skin and soft tissue infections. A total of 826 hospitalized adult patients were randomized to receive linezolid (600 mg intravenously [i.v.]) every 12 h or oxacillin (2 g i.v.) every 6 h; following sufficient clinical improvement, patients were switched to the respective oral agents (linezolid [600 mg orally] every 12 h or dicloxacillin [500 mg orally] every 6 hours). Primary efficacy variables were clinical cure rates in both the intent-to-treat (ITT) population and clinically evaluable (CE) patients and microbiological success rate in microbiologically evaluable (ME) patients. Safety and tolerability were evaluated in the ITT population. Demographics and baseline characteristics were similar across treatment groups in the 819 ITT patients. In the ITT population, the clinical cure rates were 69.8 and 64.9% in the linezolid and oxacillin-dicloxacillin groups, respectively (P= 0.141; 95% confidence interval −1.58 to 11.25). In 298 CE linezolid-treated patients, the clinical cure rate was 88.6%, compared with a cure rate of 85.8% in 302 CE patients who received oxacillin-dicloxacillin. In 143 ME linezolid-treated patients, the microbiological success rate was 88.1%, compared with a success rate of 86.1% in 151 ME patients who received oxacillin-dicloxacillin. Both agents were well tolerated; most adverse events were of mild-to-moderate intensity. No serious drug-related adverse events were reported in the linezolid group. These data support the use of linezolid for the treatment of adults with complicated skin and soft tissue infections.
Characterization of the Tn
916
-like Transposon Tn
3872
in a Strain of
Abiotrophia defectiva
(
Streptococcus defectivus
) Causing Sequential Episodes of Endocarditis in a Child
Authors: Poyart Claire , Quesne Gilles , Acar Philippe , Berche Patrick , Trieu-Cuot Patrick
Published: July 2002

Clinical blood isolates from three sequential episodes of endocarditis occurring over a 6-month period in a child with a malformative cardiopathy were investigated. All isolates identified as
Abiotrophia defectiva
were resistant to erythromycin-clindamycin and to tetracycline-minocycline, due to the presence of sequences homologous to the erythromycin resistance gene
ermB
and to the tetracycline resistance gene
tet
(M), respectively. These resistance genes were located on a chromosomally borne composite Tn
916
-related transposon. These results demonstrate the involvement of conjugative transposons in the dissemination of antibiotic resistance in the genus
Abiotrophia
.
Dihydropteroate Synthase of
Mycobacterium leprae
and Dapsone Resistance
Authors: Williams Diana L. , Spring Laynette , Harris Eugene , Roche Paul , Gillis Thomas P.
Published: July 2002

Two
Mycobacterium leprae
genes,
folP1
and
folP2
, encoding putative dihydropteroate synthases (DHPS), were studied for enzymatic activity and for the presence of mutations associated with dapsone resistance. Each gene was cloned and expressed in a
folP
knockout mutant of
Escherichia coli
(C600Δ
folP
::Km
r
). Expression of
M. leprae folP1
in C600Δ
folP
::Km
r
conferred growth on a folate-deficient medium, and bacterial lysates exhibited DHPS activity. This recombinant displayed a 256-fold-greater sensitivity to dapsone (measured by the MIC) than wild-type
E. coli
C600, and 50-fold less dapsone was required to block (expressed as the 50% inhibitory concentration [IC
50
]) the DHPS activity of this recombinant. When the
folP1
genes of several dapsone-resistant
M. leprae
clinical isolates were sequenced, two missense mutations were identified. One mutation occurred at codon 53, substituting an isoleucine for a threonine residue (T53I) in the DHPS-1, and a second mutation occurred in codon 55, substituting an arginine for a proline residue (P55R). Transformation of the C600Δ
folP
::Km
r
knockout with plasmids carrying either the T53I or the P55R mutant allele did not substantially alter the DHPS activity compared to levels produced by recombinants containing wild-type
M. leprae folP1
. However, both mutations increased dapsone resistance, with P55R having the greatest affect on dapsone resistance by increasing the MIC 64-fold and the IC
50
68-fold. These results prove that the
folP1
of
M. leprae
encodes a functional DHPS and that mutations within this gene are associated with the development of dapsone resistance in clinical isolates of
M. leprae
. Transformants created with
M. leprae folP2
did not confer growth on the C600Δ
folP
::Km
r
knockout strain, and DNA sequences of
folP2
from dapsone-susceptible and -resistant
M. leprae
strains were identical, indicating that this gene does not encode a functional DHPS and is not involved in dapsone resistance in
M. leprae
.
Disposition of Intravenous Pyrimethamine in Healthy Volunteers
Authors: Almond D. S. , Szwandt I. S. F. , Edwards G. , Lee M. G. , Winstanley P. A.
Published: July 2002

A proportion of patients with AIDS and toxoplasmic encephalitis (TE) sustain low plasma pyrimethamine concentrations during oral treatment, possibly because of incomplete and variable bioavailability. We wanted to develop a safe, practicable intravenous (i.v.) formulation of pyrimethamine and characterize its disposition in healthy volunteers. A neutral, aqueous, sterile solution of pyrimethamine was produced and presented in sealed glass ampoules. Pyrimethamine (1 mg/kg) was given to eight healthy male volunteers by i.v. infusion over 2 h, and blood was sampled over a 2 week period. Pyrimethamine levels in plasma were measured by high-performance liquid chromatography. The drug was well tolerated by all volunteers, and there were no changes in vital signs, electrocardiogram, hematology, or biochemical parameters. The maximum pyrimethamine concentration of 2,089 ± 565 ng ml−1(mean ± standard deviation) was achieved shortly after the end of the infusion; thereafter, concentrations declined in a log-linear manner, with a half-life of 140 ± 31 h.
Efficacies of Sordarin Derivatives GM193663, GM211676, and GM237354 in a Murine Model of Systemic Coccidioidomycosis
Authors: Clemons Karl V. , Stevens David A.
Published: July 2002

Sordarin derivatives (Glaxo Wellcome) are a new class of compounds that selectively inhibit fungal protein synthesis and have a broad spectrum of activity. Systemic coccidioidomycosis was established in female CD-1 mice infected with
Coccidioides immitis
, and therapy was begun on day 4 with either GM193663, GM211676, GM237354, fluconazole, or no treatment; compounds were given twice daily orally for 19 days at 20 or 100 mg/kg/day. The serum pharmacokinetics of the compounds were studied in uninfected mice. The MICs of GM193663, GM211676, and GM237354 for
C. immitis
were 1.56, 0.39, and 0.39 μg/ml, respectively, and the minimum fungicidal concentrations were 6.25, 3.13, and 0.39 μg/ml, respectively. Peak serum levels (sampled at 1 to 2 h) after a single 50-mg/kg dose were 9.8 μg/ml for GM193663, 13 μg/ml for GM211676, and 6.0 μg/ml for GM237354. No accumulation occurred after 19 days of dosing, and peak levels were lower at 3.2 μg/ml for GM193663, 4.0 μg/ml for GM211676, and <2.5 μg/ml for GM237354. We estimate that the
t
1/2
for each compound in serum is <2 h. In vivo, all compounds showed dose-responsive efficacy, significantly prolonging survival over the control groups (100% lethal dose); 80 to 100% of the mice given the 100-mg/kg doses of fluconazole or a GM drug survived. All 100-mg/kg/day regimens were equivalent. At 20 mg/kg/day, GM211676 was equivalent to 100 mg of fluconazole/kg/day, indicating that GM211676 was ∼5-fold more efficacious. No mice surviving the 49 days of the experiment were free of infection. All drugs dose responsively reduced the fungal burden in the spleen, liver, and lungs, and GM237354 at 100 mg/kg/day was superior to all of the other regimens in the reduction of burden in all organs.
C. immitis
was susceptible both in vitro and in vivo to the GM compounds, which were found to be equivalent or superior to fluconazole. These results are encouraging, indicating that further testing in other models of fungal disease is warranted.