bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between the slope of the HD curve and the fundamental resist process contrast
Authors: Brunner Timothy A.
Published: July 2002

One of the fundamental tests for a resist process is to determine the characteristic curve of photoresist thickness versus exposure dose, sometimes called the HD plot. Standard analysis of characteristic curve data in an HD plot yields a slope which we term γHD. γHD is generally regarded as an experimental determination of the process contrast or process nonlinearity, and high values of it are considered desirable. It is possible to define a more fundamental measure of the process contrast, which we term γtrue. The present work describes the relationship between γtrue and γHD using a simplified theoretical treatment that includes the effects of resist absorption and substrate reflection. This relationship shows that increasing resist absorption tends to decrease γHD for positive resist processes. On the other hand, for negative resist processes, increasing resist absorption tends to increase |γHD|. Without accounting for the effects of absorption, |γHD| is a poor indicator of true process nonlinearity.
Effects of slurry formulations on chemical-mechanical polishing of low dielectric constant polysiloxanes: hydrido-organo siloxane and methyl silsesquioxane
Authors: Chen Wen-Chang , Yen Cheng-Tyng
Published: July 2002

In this study, the film properties and chemical-mechanical polishing (CMP) characteristics of the low dielectric constant polymers hydrido-organo siloxane and methyl silsesquioxane are presented. The molecular structure and film properties of both polymers were characterized by their Fourier transform infrared spectra, refractive indices, dielectric constants, and atomic force microscopy diagrams. The CMP characteristics were studied by using different kinds of slurries and surfactants. The investigated slurries included SiO2 based slurry (SS-25), ZrO2 based slurry (Al), and Al2O3 based slurry (8104/H2O). Three kinds of surfactants were used to increase the contact area between the abrasive and polymer surface and thus polishing results were affected, which included nonionic Triton X-100, anionic dodecylsulfate sodium salt, and cationic tetramethylammonium hydroxide. The experimental results suggest that the organic content, the hardness and charge status of the abrasive, the polarity and charge status of the surfactant significantly affect the polishing results. The present study demonstrates that the CMP characteristics of low dielectric constant polysiloxanes can be controlled both chemically and mechanically.
Depth profiling of ultrashallow B implants in silicon using a magnetic-sector secondary ion mass spectrometry instrument
Authors: Napolitani E. , Carnera A. , Storti R. , Privitera V. , Priolo F. , Mannino G. , Moffatt S.
Published: July 2002

A Cameca IMS-4f secondary ion mass spectrometry instrument has been applied to the study of the diffusion of ultralow energy B implants in crystalline silicon. Several analyses on sub-keV B implants have been performed by using low energy O2+ beams both before and after thermal annealing. The limits and the accuracy of the technique are discussed. It is shown that a 1.5 keV beam provides the depth resolution needed to accurately characterize, beyond the equilibrium depth (∼5 nm), a 500 eV B implant. This measurement protocol provides at the same time a significantly low detection limit (1×1015 at/cm3) and a very fast sputter rate (25 nm/min), necessary to characterize deep diffused profiles. Several artifacts are discussed, with emphasis to those affecting the tail region of the profiles.
Reduction of plasma induced damage in an inductively coupled plasma using pulsed source power
Authors: Samukawa Seiji , Noguchi Ko , Colonell Jennifer I. , Bogart Katherine H. A. , Malyshev Mikhail V. , Donnelly Vincent M.
Published: July 2002

Pulse-time-modulated plasmas have been proposed to overcome charging problems due to electron shading in ultralarge-scale integrated patterning. In this article, we report the effectiveness of pulse-power modulation of a commercial, inductively coupled plasma system in reducing topography-dependent charging, sensed by the reduction in the shift in threshold voltages of metal–oxide–semiconductor transistors. This plasma-induced damage during metal etching can be significantly reduced by turning the 13.56 MHz radio frequency (rf) power to the transformer-coupled coil antenna on and off, while maintaining a continuous rf bias power at 13.56 MHz. At an optimum condition of 50 μs on and 50 μs off, the severity of the device damage is reduced to nearly 1/5 that of continuous wave plasma. Thus, the use of pulse-time-modulated plasma is an effective and promising technique for suppressing topography-dependent charging during metal etching in a commercial reactor.
Is the tunneling electron really affected by electrostatic image forces?
Authors: Valeyev V. G. , Hagmann M. J.
Published: July 2002

The Keldysh–Green function technique in the representation of scattering states is used to study the dynamic conductance and the stationary current noise of a mesoscopic tunnel junction. It is shown that, despite the generally accepted viewpoint [M. Büttiker, Phys. Rev. B 45, 3807 (1992)], within the framework of the one-electron approximation the linear ac current response cannot be expressed in terms of the one-electron scattering matrix, but rather it is completely determined by the true electron wave functions in the region of the potential barrier. In addition to high-frequency device applications, the study of dynamic conductance has fundamental importance in providing information about the structure of the potential barrier. We analyze the linear ac current response of electron field emission and show that, if the tunneling electron is affected by the electrostatic image force, the low-frequency field emission stationary current noise spectral density has flicker-noise behavior ∼1/ω4/3 over a wide frequency range. Experimental evidence for this frequency dependence has been reported by a number of authors.
Heterostructures of pseudomorphic Ge1−yCy and Ge1−x−ySixCy alloys grown on Ge (001) substrates
Authors: Dashiell M. W. , Kolodzey J. , Boucaud P. , Yam Vy , Lourtioz J.-M.
Published: July 2002

Heterostructures of Ge1−yCy and Ge1−x−ySixCy on Ge (001) substrates with (0<y<0.001) and (0<x<0.05) were grown by low temperature molecular beam epitaxy (Tgrowth=275 °C). These carbon fractions exceed by nearly ten orders of magnitude the solid solubility of C in bulk germanium. High resolution x-ray diffraction reveals that the layers are pseudomorphic and have high crystalline quality and interface abruptness, evident from strong Pendellösung fringes and superlattice satellite peaks. The heterostructures are metastable due to the supersaturation of substitutional C in the lattice and the strained layers relax at high temperatures. From x-ray diffraction measurements, we conclude that the relaxation mechanism is due to the loss of C from substitutional sites, rather than by the formation of extended defects. We empirically determined the activation energies for the decrease of substitutional C in pseudomorphic Ge0.999C0.001 and Ge0.972Si0.027C0.0008 alloys to be 3.4 and 3.6 eV, respectively. Near band-edge photoluminescence is observed from pseudomorphic Ge1−yCy samples.
Controlled bond formation between chemical vapor deposition Si and ultrathin SiO2 layers
Authors: Yasuda T. , Nishizawa M. , Yamasaki S. , Tanaka K.
Published: July 2002

This article reports that chemically active sites on SiO2 surfaces can be either passivated or introduced intentionally by treating them in a proper chlorosilane gas, SiHnCl4−n (n=0,1,2). Our experiments of Si chemical vapor deposition on SiO2-covered Si have shown that Si deposition is suppressed on SiCl4- and SiHCl3-treated samples, while an SiH2Cl2 treatment drastically enhances Si nucleation. Thus, the chlorosilane treatment is a unique way for us to control the interface bonds between the SiO2 surface and the Si deposits on it. We also demonstrate resistless selective-area deposition using a SiHCl3-treated ultrathin SiO2 mask layer. Patterns are defined on the mask surface by direct electron-beam irradiation which induces Cl desorption thereby forming chemically reactive surface defects.
A Complex Pattern of Mantle Flow in the Lau Backarc
Authors: Smith Gideon P. , Wiens Douglas A. , Fischer Karen M. , Dorman Leroy M. , Webb Spahr C. , Hildebrand John A.
Published: July 2002

Shear-wave splitting analysis of local events recorded on land and on the ocean floor in the Tonga arc and Lau backarc indicate a complex pattern of azimuthal anisotropy that cannot be explained by mantle flow coupled to the downgoing plate. These observations suggest that the direction of mantle flow rotates from convergence-parallel in the Fiji plateau to north-south beneath the Lau basin and arc-parallel beneath the Tonga arc. These results correlate with helium isotopes that map mantle flow of the Samoan plume into the Lau basin through an opening tear in the Pacific plate.
Nitric Oxide and the Control of Firefly Flashing
Authors: Trimmer Barry A. , Aprille June R. , Dudzinski David M. , Lagace Christopher J. , Lewis Sara M. , Michel Thomas , Qazi Sanjive , Zayas Ricardo M.
Published: July 2002

Bioluminescent flashing is essential for firefly reproduction, yet the specific molecular mechanisms that control light production are not well understood. We report that light production by fireflies can be stimulated by nitric oxide (NO) gas in the presence of oxygen and that NO scavengers block bioluminescence induced by the neurotransmitter octopamine. NO synthase is robustly expressed in the firefly lantern in cells interposed between nerve endings and the light-producing photocytes. These results suggest that NO synthesis is a key determinant of flash control in fireflies.
Selective Transcription and Modulation of Resting T Cell Activity by Preintegrated HIV DNA
Authors: Wu Yuntao , Marsh Jon W.
Published: July 2002

The quiescent nature of most peripheral T cells poses an effective limitation to human immunodeficiency virus (HIV) replication and, in particular, to viral integration into the host chromatin. Two HIV proteins, Nef and Tat, increase T cell activity, but a requirement of integration for viral gene expression would preclude a role for these proteins in resting cells. Here, we report that HIV infection leads to selective transcription of the
nef
and
tat
genes before integration. This preintegration transcription in quiescent cells leads to increased T cell activation and viral replication.
The Formation of the First Star in the Universe
Authors: Abel Tom , Bryan Greg L. , Norman Michael L.
Published: July 2002

We describe results from a fully self-consistent three-dimensional hydrodynamical simulation of the formation of one of the first stars in the Universe. In current models of structure formation, dark matter initially dominates, and pregalactic objects form because of gravitational instability from small initial density perturbations. As they assemble via hierarchical merging, primordial gas cools through ro-vibrational lines of hydrogen molecules and sinks to the center of the dark matter potential well. The high-redshift analog of a molecular cloud is formed. As the dense, central parts of the cold gas cloud become self-gravitating, a dense core of ∼100
M
⊙
(where
M
⊙
is the mass of the Sun) undergoes rapid contraction. At particle number densities greater than 10
9
per cubic centimeter, a 1
M
⊙
protostellar core becomes fully molecular as a result of three-body H
2
formation. Contrary to analytical expectations, this process does not lead to renewed fragmentation and only one star is formed. The calculation is stopped when optical depth effects become important, leaving the final mass of the fully formed star somewhat uncertain. At this stage the protostar is accreting material very rapidly (∼10
−2
M
⊙
year
−1
). Radiative feedback from the star will not only halt its growth but also inhibit the formation of other stars in the same pregalactic object (at least until the first star ends its life, presumably as a supernova). We conclude that at most one massive (
M
≫ 1
M
⊙
) metal-free star forms per pregalactic halo, consistent with recent abundance measurements of metal-poor galactic halo stars.
Role of the Myosin Assembly Protein UNC-45 as a Molecular Chaperone for Myosin
Authors: Barral José M. , Hutagalung Alex H. , Brinker Achim , Hartl F. Ulrich , Epstein Henry F.
Published: July 2002

The organization of myosin into motile cellular structures requires precise temporal and spatial regulation. Proteins containing a UCS (UNC-45/CRO1/She4p) domain are necessary for the incorporation of myosin into the contractile ring during cytokinesis and into thick filaments during muscle development. We report that the carboxyl-terminal regions of UNC-45 bound and exerted chaperone activity on the myosin head. The amino-terminal tetratricopeptide repeat domain of UNC-45 bound the molecular chaperone Hsp90. Thus, UNC-45 functions both as a molecular chaperone and as an Hsp90 co-chaperone for myosin, which can explain previous findings of altered assembly and decreased accumulation of myosin in UNC-45 mutants of
Caenorhabditis elegans
.
Repeated and Sudden Reversals of the Dipole Field Generated by a Spherical Dynamo Action
Authors: Li Jinghong , Sato Tetsuya , Kageyama Akira
Published: July 2002

Using long-duration, three-dimensional magnetohydrodynamic simulation, we found that the magnetic dipole field generated by a dynamo action in a rotating spherical shell repeatedly reverses its polarity at irregular intervals (that is, punctuated reversal). Although the total convection energy and magnetic energy alternate between a high-energy state and a low-energy state, the dipole polarity can reverse only at high-energy states where the north-south symmetry of the convection pattern is broken and the columnar vortex structure becomes vulnerable. Another attractive finding is that the quadrupole mode grows, exceeding the dipole mode before the reversal; this may help to explain how Earth's magnetic field reverses.
Much About Motion in the Mantle
Authors: Ricard Yanick
Published: July 2002

Mantle Convection in the Earth and Planets
. Gerald Schubert, Donald L. Turcotte, and Peter Olson. Cambridge University Press, Cambridge, 2001. 956 pp. $200, £140. ISBN 0-521-35367-X. Paper, $74.95, £49.95. ISBN 0-521-79836-1.

The authors offer researchers and graduate students a comprehensive synthesis of our current understanding of mantle convection within Earth, the other terrestrial planets, the Moon, and Jupiter's Galilean satellites.
The Elements of an Education
Authors: Kadanoff Leo P.
Published: July 2002

Uncle Tungsten
Memories of a Chemical Boyhood. Oliver Sacks. Knopf, New York, 2001. 350 pp. $25. ISBN 0-375-40448-1. Picador (Macmillan), London. £17.00. ISBN 0-330-39027-9.

This memoir by the noted neurologist and author focuses on his early fascination with metals, gasses, the periodic table, and chemistry experiments.
A Convincing Call for Conservation
Authors: Myers Norman
Published: July 2002

The Future of Life
. Edward O. Wilson. Knopf, New York, 2002. 254 pp. $22, C$33. ISBN 0-679-45078-5.

Wilson offers an up-to-date summary of the state of threats to biodiversity and argues for a plan to rescue Earth's biological heritage.
Locating the Summit of the Oil Peak
Authors: Charpentier Ronald R.
Published: July 2002

Hubbert's Peak
The Impending World Oil Shortage. Kenneth S. Deffeyes. Princeton University Press, Princeton, NJ, 2001. 220 pp. $24.95, £17.95. ISBN 0-691-09086-6.

Estimating that world oil production will peak before 2008 and then be unable to keep up with demand, Deffeyes argues that it is now time to develop alternative energy sources and conservation measures.
Bridging the Genotype-Phenotype Gap
Authors: Omholt Stig W.
Published: July 2002

Foundations of Systems Biology
. Hiroaki Kitano, Ed. MIT Press, Cambridge, MA, 2001. 313 pp., illus. $45, £30.95. ISBN 0-262-11266-3.

This collection of papers is intended to survey the current state of research in the nascent field of systems biology and to outline a vision for future work toward a systems-level understanding of structures such as gene and metabolic networks.
Heroic Battles of the Protein Wars
Authors: Eisenberg David
Published: July 2002

Nature's Robots
A History of Proteins. Charles Tanford and Jacqueline Reynolds. Oxford University Press, Oxford, 2001. 312 pp. $27.50, £18.99. ISBN 0-19-850466-7.

Tanford and Reynolds provide a spirited narrative of the development of our understanding of proteins and their diverse and important roles in biological systems.
Habeas Corpus
Authors: Vogel Steven
Published: July 2002

The Oxford Companion to the Body
. Colin Blakemore and Sheila Jennett, Eds. Oxford University Press, Oxford, 2001. 778 pp. $55, £40. ISBN 0-19-852403-X.

Some 350 authors present 1200-plus articles that consider aspects of the human body from diverse perspectives-not only anatomical, physiological, and medical approaches but cultural, historical, and artistic ones as well.
At the Dawn of Tyranny
Authors: Carter Elizabeth
Published: July 2002

Uruk Mesopotamia & Its Neighbors
Cross-Cultural Interactions in the Era of State Formation. Mitchell S. Rothman, Ed. School of American Research Press, Santa Fe, NM, 2001. 578 pp. $60. ISBN 1-930618-02-6. Paper, $24.95. ISBN 1-930618-03-4. James Currey, Oxford, 2002. £45. ISBN 0-85255-461-3. Paper, £16.95. ISBN 0-85255-460-5.

The contributors consider the implications of recent data on economic, political, and social aspects of the period during which the first states emerged in Mesopotamia, long considered the model case for the evolution of complex societies.
Role of GTP Hydrolysis in Fission of Caveolae Directly from Plasma Membranes
Authors: Schnitzer Jan E. , Oh Phil , McIntosh Deirdre P.
Published: July 2002

Caveolae are specialized invaginated cell surface microdomains of undefined function. A cell-free system that reconstituted fission of caveolae from lung endothelial plasma membranes was developed. Addition of cytosol and the hydrolysis of guanosine triphosphate (GTP) induced caveolar fission. The budded caveolae were isolated as vesicles rich in caveolin and the sialoglycolipid G
M1
but not glycosyl-phosphatidylinositol (GPI)-anchored proteins. These vesicles contained the molecular machinery for endocytosis and transcytosis. In permeabilized endothelial cells, GTP stimulated, whereas GTPγS prevented, caveolar budding and endocytosis of the cholera toxin B chain to endosomes. Thus, caveolae may bud to form discrete carrier vesicles that participate in membrane trafficking.
Chinese Researchers Debate Rash of Plagiarism Cases
Authors: Xiguang Li , Lei Xiong
Published: July 2002

Beijing--Three recent cases of plagiarism by Chinese scientists have triggered a vigorous national discussion of the problem and how institutions should respond. Although Chinese officials took swift action in these cases, there is no consensus on the best way to reduce or eliminate such unethical behavior.
The Imaging of Individual Atoms
Authors: Jefferson David A.
Published: July 2002

Atomic structural analysis methods, such as x-ray diffraction, are useful but very indirect ways of imaging. More desirable are direct methods, which show straightforwardly the positions of atoms and molecules. In his Perspective, Jefferson describes the evolution of direct atomic scale imaging and, in particular, results presented in the same issue by Nellist and Pennycook (
p. 413
) on imaging of catalytic surfaces.
Dust Measurements During Galileo's Approach to Jupiter and Io Encounter
Authors: Grün E. , Hamilton D. P. , Riemann R. , Dermott S. , Fechtig H. , Gustafson B. A. , Hanner M. S. , Heck A. , Horanyi M. , Kissel J. , Krüger H. , Lindblad B. A. , Linkert D. , Linkert G. , Mann I. , McDonnell J A. M. , Morfill G. E. , Polanskey C. , Schwehm G. , Srama R. , Zook H. A.
Published: July 2002

About a hundred dust impacts per day were detected during the first week in December 1995 by Galileo during its approach to Jupiter. These impacts were caused by submicrometer-sized particles that were just above the detection limit. After the closest approach to Io on 7 December, impacts of these small particles ceased. This effect is expected for dust grains emitted from Io that exit the field of view of the instrument after the flyby. The impact rate of bigger micrometer-sized dust grains continued to increase toward Jupiter. These dust particles are in orbit about Jupiter or are interplanetary grains that are gravitationally concentrated near Jupiter.
Attractant Signaling by an Aspartate Chemoreceptor Dimer with a Single Cytoplasmic Domain
Authors: Gardina Paul J. , Manson Michael D.
Published: July 2002

Signal transduction across cell membranes often involves interactions among identical receptor subunits, but the contribution of individual subunits is not well understood. The chemoreceptors of enteric bacteria mediate attractant responses by interrupting a phosphotransfer circuit initiated at receptor complexes with the protein kinase CheA. The aspartate receptor (Tar) is a homodimer, and oligomerized cytoplasmic domains stimulate CheA activity much more than monomers do in vitro. Intragenic complementation was used to show in
Escherichia coli
that heterodimers containing one full-length and one truncated Tar subunit mediated responses to aspartate in the presence of full-length Tar homodimers that could not bind aspartate. Thus, a Tar dimer containing only one cytoplasmic domain can initiate an attractant (inhibitory) signal, although it may not be able to stimulate kinase activity of CheA.
How Not to Pick a Physicist?
Authors: Glanz James
Published: July 2002

Standardized tests are under fire again—this time from physicists who say their field's graduate-school exam, the physics Graduate Record Examination, overlooks real physics talent and worsens the field's gender disparity. A small but increasingly vocal minority is arguing that the test's rigid, multiple-choice format should be modified or the test should be dropped entirely as a criterion for entry into graduate school.
Designing a Census in Which All Americans Count
Authors: Roush Wade
Published: July 2002

The U.S. Census Bureau and Congress tussle over new plan for the decennial census that would include statistical sampling and analysis of groups, such as African Americans, which, historically, have been undercounted.
Chronology for Fluctuations in Late Pleistocene Sierra Nevada Glaciers and Lakes
Authors: Phillips Fred M. , Zreda Marek G. , Benson Larry V. , Plummer Mitchell A. , Elmore David , Sharma Pankaj
Published: July 2002

Mountain glaciers, because of their small size, are usually close to equilibrium with the local climate and thus should provide a test of whether temperature oscillations in Greenland late in the last glacial period are part of global-scale climate variability or are restricted to the North Atlantic region. Correlation of cosmogenic chlorine-36 dates on Sierra Nevada moraines with a continuous radiocarbon-dated sediment record from nearby Owens Lake shows that Sierra Nevada glacial advances were associated with Heinrich events 5, 3, 2, and 1.
Requirement of Rigid-Body Motion of Transmembrane Helices for Light Activation of Rhodopsin
Authors: Farrens David L. , Altenbach Christian , Yang Ke , Hubbell Wayne L. , Khorana H. Gobind
Published: July 2002

Conformational changes are thought to underlie the activation of heterotrimeric GTP-binding protein (G protein)—coupled receptors. Such changes in rhodopsin were explored by construction of double cysteine mutants, each containing one cysteine at the cytoplasmic end of helix C and one cysteine at various positions in the cytoplasmic end of helix F. Magnetic dipolar interactions between spin labels attached to these residues revealed their proximity, and changes in their interaction upon rhodopsin light activation suggested a rigid body movement of helices relative to one another. Disulfide cross-linking of the helices prevented activation of transducin, which suggests the importance of this movement for activation of rhodopsin.
U1-Mediated Exon Definition Interactions Between AT-AC and GT-AG Introns
Authors: Wu Qiang , Krainer Adrian R.
Published: July 2002

A minor class of metazoan introns has well-conserved splice sites with 5′-AU-AC-3′ boundaries, compared to the 5′-GU-AG-3′ boundaries and degenerate splice sites of conventional introns. Splicing of the AT-AC intron 2 of a sodium channel (SCN4A) precursor messenger RNA in vitro did not require inhibition of conventional splicing and required adenosine triphosphate, magnesium, and U12 small nuclear RNA (snRNA). When exon 3 was followed by the 5′ splice site from the downstream conventional intron, splicing of intron 2 was greatly stimulated. This effect was U1 snRNA-dependent, unlike the basal AT-AC splicing reaction. Therefore, U1-mediated exon definition interactions can coordinate the activities of major and minor spliceosomes.
A New Way to Ask the Experts—Rating Radioactive Waste Risks
Authors: Kerr Richard A.
Published: July 2002

How do you assess the risks of rare but catastrophic events, like a volcanic eruption at the proposed Yucca Mountain nuclear waste repository? That question has plagued science policy-makers for years, and now many geoscientists are using a new way to mathematically combine the risk and uncertainty estimates from a panel of experts. In the case of Yucca Mountain, this “expert elicitation” method has just yielded some surprising results.
Rare Habitats Vie for Protection
Authors: Schmidt Karen
Published: July 2002

A new approach to protecting biodiversity targets beleaguered habitat types, even if they don't house extraordinary numbers of species. This approach gives more weight to areas outside the tropics and organisms other than plants.
Quantum Hysteresis in Molecular Magnets
Authors: Chudnovsky Eugene M.
Published: July 2002

Magnetic materials normally exhibit a smooth response to external fields, but recent experiments reported in
Physical Review Letters
yield stepwise response curves. In his Perspective, Chudnovsky discusses the results, which may be evidence for quantum behavior on a macroscopic scale.
Tracing Backbone Evolution Through a Tunicate's Lost Tail
Authors: Pennisi Elizabeth
Published: July 2002

Tunicates spend their adult lives as sedentary invertebrates, but their larvae enjoy life with a tail and other vertebratelike characters. Now, as reported on page
1205
, clever experiments with two species of tunicates show that most of the larvae's vertebratelike traits may be turned on by a single gene, Manx. In a milestone for developmental biology, the experiments apparently re-create an evolutionary change that occurred in the history of one tunicate species.
Biosphere 2 and Biodiversity--The Lessons So Far
Authors: Cohen Joel E. , Tilman David
Published: July 2002

A committee of ecologists recently visited the enclosed ecosystem of Biosphere 2 in order to advise the new scientific managers of the structure on how it may be used in ecological research. Cohen, a member of the committee, describes the lessons that have emerged to date from the confinement of eight individuals in Biosphere 2 for 2 years about the interrelatedness of plants and animals in ecological systems.
Oceanic Carbon Dioxide Uptake in a Model of Century-Scale Global Warming
Authors: Sarmiento Jorge L. , Le Quéré Corinne
Published: July 2002

In a model of ocean-atmosphere interaction that excluded biological processes, the oceanic uptake of atmospheric carbon dioxide (CO
2
) was substantially reduced in scenarios involving global warming relative to control scenarios. The primary reason for the reduced uptake was the weakening or collapse of the ocean thermohaline circulation. Such a large reduction in this ocean uptake would have a major impact on the future growth rate of atmospheric CO
2
. Model simulations that include a simple representation of biological processes show a potentially large offsetting effect resulting from the downward flux of biogenic carbon. However, the magnitude of the offset is difficult to quantify with present knowledge.
Expanding the Eukaryote's Cast of Chaperones
Authors: Pennisi Elizabeth
Published: July 2002

In order for proteins to function normally, they must fold into the correct three-dimensional shapes, a task they accomplish with the aid of special proteins called “chaperones.” Three papers in this issue (
pp.1713
,
1715
, and
1718
) are now making it clear that, at least in higher organisms, protein folding is far more complex than researchers had suspected. It seems to involve a whole retinue of chaperone proteins, including certain members of the immunophilin family—among the first evidence of what the normal function might be for these proteins, which are best known as the targets of immunosuppressive drugs.
Atomic Mouse Probes the Lifetime of a Quantum Cat
Authors: Taubes Gary
Published: July 2002

How do you detect a Schrödinger's cat—an object that straddles two quantum states at once, like a cat that is both dead and alive? You let a mouse run past its nose and see what happens to the mouse. Physicists have now done the experiment with a microwave field (the cat) in an indeterminate quantum state and an atom (the mouse) prepared so that it can react to the dead-and-alive state of the cat.
Condensed Matter Physics: Magnetoresistance in Layered Manganite Compounds
Authors: Goldman Allen M.
Published: July 2002

Magnetoresistance is an effect in which the electrical resistance of a material changes in a magnetic field. This phenomenon is of great importance in magnetic data recording, where a magnetoresistive sensor detects the patterns of bits on magnetic storage media. In his Perspective, Goldman discusses results reported in the same issue by Kimura
et al
. (
p. 1698
) that reveal how current is carried in an important group of materials, the layered manganites.
Development: A Fin-de-Siècle Achievement: Charting New Waters in Vertebrate Biology
Authors: Grunwald David Jonah
Published: July 2002

Grunwald comments on the 36 papers in the December issue of
Development
from the laboratories of Nüsslein-Vollhard and Driever, which report the results of a massive genetic screen of development in the zebrafish.
The Origin of the Great Bend of the Nile from SIR-C/X-SAR Imagery
Authors: Stern Robert J. , Abdelsalam Mohamed Gamal
Published: July 2002

The course of the Nile in northern Sudan follows a contorted path through Precambrian bedrock. Radar imagery shows that basement structures control the river's course in this region. Northward-flowing segments follow Precambrian fabrics, whereas east-west segments follow faults of much younger age. These faults may reflect recent uplift of the Nubian Swell and deflection of the river to the southwest to form the great bend of the Nile.
Capturing the Dynamic Behavior of Adsorbed Polymers
Authors: Balazs Anna C.
Published: July 2002

Inert surfaces can be made reactive, and active surfaces inert, by means of a thin coating of polymer. Such surface films are used in paints, plastic fabrication, corrosion resistive coatings, and medical applications. In her Perspective, Balazs discusses new results reported by Fytas
et al.
in the same issue (
p. 2041
) in which the collective motions of polymer chains anchored at a surface have been studied by a powerful optical technique: dynamic light scattering. The data provided by this technique can illuminate the link between microscopic polymer behavior and macroscopic properties of polymer coatings.
Enhancement of Class II-Restricted T cell Responses by Costimulatory NK Receptors for Class I MHC Proteins
Authors: Mandelboim Ofer , Davis Daniel M. , Reyburn Hugh T. , Valés-Gómez Mar , Sheu Eric G. , Pazmany Laszlo , Strominger Jack L.
Published: July 2002

An important feature of the human immune system is the ability of T cells to respond to small quantities of antigen. Class II major histocompatibility complex (MHC)-restricted T cells that expressed a costimulatory natural killer (NK) cell receptor for class I MHC proteins were cloned. In the presence of low doses of superantigen, the proliferative response of these T cell clones was three- to ninefold greater when the T cells were costimulated by way of the NK receptor. Thus, the action of costimulatory NK receptors on T cells may play a significant role in initiating and sustaining immune responses.
Structural and Functional Conservation of the
Caenorhabditis elegans
Timing Gene
clk-1
Authors: Ewbank Jonathan J. , Barnes Thomas M. , Lakowski Bernard , Lussier Marc , Bussey Howard , Hekimi Siegfried
Published: July 2002

Mutations in the
Caenorhabditis elegans
gene
clk-1
affect biological timing and extend longevity. The gene
clk-1
was identified, and the cloned gene complemented the
clk-1
phenotypes and restored normal longevity. The CLK-1 protein was found to be conserved among eukaryotes, including humans, and structurally similar to the yeast metabolic regulator Cat5p (also called Coq7p). These proteins contain a tandem duplication of a core 82-residue domain.
clk-1
complemented the phenotype of
cat5/coq7
null mutants, demonstrating that
clk-1
and
CAT5/COQ7
share biochemical function and that
clk-1
acts at the level of cellular physiology.
Action Potentials Reconsidered
Authors: Zador Anthony
Published: July 2002

Spikes.
Exploring the Neural Code. FRED RIEKE, DAVID WARLAND, ROB DE RUYTER VAN STEVENINCK, and WILLIAM BIALEK. MIT Press, Cambridge, MA, 1996. xviii, 395 pp., illus. $45 or £38.50. ISBN 0-262-18174-6. Computational Neuroscience. A Bradford Book.
Magnetic Field Alignment of Ordered Silicate-Surfactant Composites and Mesoporous Silica
Authors: Tolbert Sarah H. , Firouzi Ali , Stucky Galen D. , Chmelka Bradley F.
Published: July 2002

Macroscopic orientational ordering of the pores of condensed hexagonal mesostructured silica (MCM-41) was achieved through alignment of an unpolymerized, hexagonal, lyotropic silicate-surfactant liquid crystal in a high magnetic field. This alignment was preserved after polymerization of the silicate species by acid treatment. Subsequent calcination to remove the surfactant yielded a mesoporous silica solid that retained both macroscopic pore alignment and mesoscale periodicity. Potential applications of such liquid crystal processing strategies range from the formation of anisotropic silica-based bulk ceramics to the production of oriented mesoporous thin films for chemical sensors, separations, catalysis, or host-guest applications.
Characterization of an Avian Influenza A (H5N1) Virus Isolated from a Child with a Fatal Respiratory Illness
Authors: Subbarao Kanta , Klimov Alexander , Katz Jacqueline , Regnery Helen , Lim Wilina , Hall Henrietta , Perdue Michael , Swayne David , Bender Catherine , Huang Jing , Hemphill Mark , Rowe Thomas , Shaw Michael , Xu Xiyan , Fukuda Keiji , Cox Nancy
Published: July 2002

An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.
Signaling from Rho to the Actin Cytoskeleton Through Protein Kinases ROCK and LIM-kinase
Authors: Maekawa Midori , Ishizaki Toshimasa , Boku Shuken , Watanabe Naoki , Fujita Akiko , Iwamatsu Akihiro , Obinata Takashi , Ohashi Kazumasa , Mizuno Kensaku , Narumiya Shuh
Published: July 2002

The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. The small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM-kinase. Cofilin was phosphorylated in N1E-115 neuroblastoma cells during lysophosphatidic acid–induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK. ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM-kinase, which in turn was activated to phosphorylate cofilin. Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632–sensitive manner. These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton.
Failure to Regulate TNF-Induced NF-κB and Cell Death Responses in A20-Deficient Mice
Authors: Lee Eric G. , Boone David L. , Chai Sophia , Libby Shon L. , Chien Marcia , Lodolce James P. , Ma Averil
Published: July 2002

A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor κB (NF-κB) activity and tumor necrosis factor (TNF)–mediated programmed cell death (PCD). TNF dramatically increases A20 messenger RNA expression in all tissues. Mice deficient for A20 develop severe inflammation and cachexia, are hypersensitive to both lipopolysaccharide and TNF, and die prematurely. A20-deficient cells fail to terminate TNF-induced NF-κB responses. These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-κB responses in vivo.
Acquisition of Chloramphenicol Resistance by the Linearization and Integration of the Entire Staphylococcal Plasmid pC194 into the Chromosome of
Streptococcus pneumoniae
Authors: Widdowson Carol A. , Adrian Peter V. , Klugman Keith P.
Published: July 2002

Chloramphenicol resistance in
Streptococcus pneumoniae
was associated with
cat
, which has 100% identity with
cat
pC194
from
Staphylococcus aureus
. Inverse PCR with primers specific for pC194 confirmed that in some isolates the entire staphylococcal plasmid was present in the
S. pneumoniae
chromosome, with linearization having occurred between
cat
pC194
and the origin of replication.
Identification of
Cryptosporidium parvum
Dihydrofolate Reductase Inhibitors by Complementation in
Saccharomyces cerevisiae
Authors: Brophy Victoria Hertle , Vasquez John , Nelson Richard G. , Forney John R. , Rosowsky Andre , Sibley Carol Hopkins
Published: July 2002

There is a pressing need for drugs effective against the opportunistic protozoan pathogen
Cryptosporidium parvum
. Folate metabolic enzymes and enzymes of the thymidylate cycle, particularly dihydrofolate reductase (DHFR), have been widely exploited as chemotherapeutic targets. Although many DHFR inhibitors have been synthesized, only a few have been tested against
C. parvum
. To expedite and facilitate the discovery of effective anti-
Cryptosporidium
antifolates, we have developed a rapid and facile method to screen potential inhibitors of
C. parvum
DHFR using the model eukaryote,
Saccharomyces cerevisiae
. We expressed the DHFR genes of
C. parvum
,
Plasmodium falciparum
,
Toxoplasma gondii
,
Pneumocystis carinii
, and humans in the same DHFR-deficient yeast strain and observed that each heterologous enzyme complemented the yeast DHFR deficiency. In this work we describe our use of the complementation system to screen known DHFR inhibitors and our discovery of several compounds that inhibited the growth of yeast reliant on the
C. parvum
enzyme. These same compounds were also potent or selective inhibitors of the purified recombinant
C. parvum
DHFR enzyme. Six novel lipophilic DHFR inhibitors potently inhibited the growth of yeast expressing
C. parvum
DHFR. However, the inhibition was nonselective, as these compounds also strongly inhibited the growth of yeast dependent on the human enzyme. Conversely, the antibacterial DHFR inhibitor trimethoprim and two close structural analogs were highly selective, but weak, inhibitors of yeast complemented by the
C. parvum
enzyme. Future chemical refinement of the potent and selective lead compounds identified in this study may allow the design of an efficacious antifolate drug for the treatment of cryptosporidiosis.
Evernimicin (SCH27899) Inhibits both Translation and 50S Ribosomal Subunit Formation in
Staphylococcus aureus
Cells
Authors: Champney W. Scott , Tober Craig L.
Published: July 2002

The effects of the everninomicin antibiotic evernimicin (SCH27899) on growing
Staphylococcus aureus
cells were investigated. Cellular growth rates and viable cell numbers decreased with increasing antibiotic concentrations. The rate of protein synthesis, measured as
35
S-amino acid incorporation, declined in parallel with the growth rate. Significantly, the formation of the 50S ribosomal subunit was inhibited in a dose-dependent fashion as well. 30S ribosomal subunit synthesis was not affected over the same concentration range. Evernimicin did not stimulate the breakdown of mature ribosomal subunits. Pulse-chase labeling experiments revealed a reduced rate of 50S subunit formation in drug-treated cells. Two erythromycin-resistant strains of
S. aureus
that carried the
ermC
gene were as sensitive as wild-type cells to antibiotic inhibition. In addition, two methicillin-resistant
S. aureus
organisms, one sensitive to erythromycin and one resistant to the macrolide, showed similar sensitivities to evernimicin. These results suggest a use for this novel antimicrobial agent against antibiotic-resistant bacterial infections.
Phenotypic Expression of Oxacillin Resistance in
Staphylococcus epidermidis
: Roles of
mecA
Transcriptional Regulation and Resistant-Subpopulation Selection
Authors: Dickinson Tanja M. , Archer Gordon L.
Published: July 2002

The MICs for many oxacillin-resistant (OR)
Staphylococcus epidermidis
(ORSE) strains are below the
Staphylococcus aureus
methicillin or oxacillin resistance breakpoint. The difficulty detecting the OR phenotype in
S. epidermidis
may be due to extreme heterotypy in resistance expression and/or transcriptional repression of
mecA
, the OR gene, by MecI. To determine the role of these factors in the phenotypic expression of ORSE, 17 geographically diverse
mecI
+
ORSE isolates representing 14 distinct pulsed-field gel electrophoresis pulse types (>3 band differences) were investigated. Thirteen of the 14 types contained
mecI
and
mecA
promoter-operator sequences known to be associated with maximal
mecA
repression, and in all isolates,
mecA
transcription was repressed. All 17 were heterotypic in their resistance expression. Oxacillin MICs ranged from 1 to 128 μg/ml and increased for 16 of 17 isolates after β-lactam induction. Allelic replacement inactivation of
mecI
in three isolates similarly resulted in a four- to sevenfold increase in MIC. In the two of these three isolates producing β-lactamase,
mecA
transcription was regulated by both
mecI
and β-lactamase regulatory sequences. Heterotypic expression of resistance in these three isolates was unaffected by either β-lactam induction or
mecI
inactivation. However, prolonged incubation in concentrations of oxacillin just sufficient to produce a lag in growth (0.5 to 1.0 μg/ml) converted the population resistance expression from heterotypic to homotypic. Homotypic conversion could also be demonstrated in microtiter wells during MIC determinations in one isolate for which the MIC was high. We conclude that the phenotypic expression of
S. epidermidis
OR in broth can be affected both by
mecA
transcriptional regulation and by subpopulation resistance expression.
Interactions of Ofloxacin and Erythromycin with the Multidrug Resistance Protein (MRP) in MRP-Overexpressing Human Leukemia Cells
Authors: Terashi Kenji , Oka Mikio , Soda Hiroshi , Fukuda Minoru , Kawabata Shigeru , Nakatomi Katsumi , Shiozawa Ken , Nakamura Takashi , Tsukamoto Kazuhiro , Noguchi Yuji , Suenaga Mitsuhiro , Tei Chuwa , Kohno Shigeru
Published: July 2002

To investigate interactions between the multidrug resistance protein (MRP) and antimicrobial agents, we examined the effects of 12 agents on vincristine sensitivity and efflux of the calcein acetoxy-methyl ester (calcein-AM) of a MRP substrate in MRP-overexpressing cells. Only ofloxacin and erythromycin enhanced sensitivity with increased intracellular vincristine accumulation and inhibited the calcein-AM efflux. Our findings suggest that the two agents are possible MRP substrates and may competitively inhibit MRP function as a drug efflux pump.
Single-Oral-Dose Azithromycin Prophylaxis against Experimental Streptococcal or Staphylococcal Aortic Valve Endocarditis
Authors: Tsitsika Artemis , Pefanis Angelos , Perdikaris George S. , Donta Ismini , Karayiannakos Panayiotis , Giamarellou Helen
Published: July 2002

Azithromycin and ampicillin protected 94 and 72% of animals challenged with
Streptococcus oralis
, respectively (
P
= 0.177), while azithromycin and vancomycin protected 59 and 94% of the methicillin-resistant
Staphylococcus aureus
(MRSA)-challenged animals, respectively (
P
= 0.018). Azithromycin is effective in preventing experimental streptococcal endocarditis, but against MRSA it is less effective than vancomycin.
In Vitro Activities of MK-826 (L-749,345) against 363 Strains of Anaerobic Bacteria
Authors: Wexler Hannah M. , Molitoris Denise , Finegold Sydney M.
Published: July 2002

The activity of MK-826 was compared to the activities of cefoxitin, ceftriaxone, imipenem, and meropenem against 363 gram-negative and gram-positive anaerobes by using NCCLS procedures. At least 98% of the strains were susceptible to the carbapenems. All strains of
Clostridium perfringens
,
Fusobacterium nucleatum
,
Peptostreptococcus
, and
Sutterella wadsworthensis
were susceptible to all agents tested.
Antimalarial Activities of Peptide Antibiotics Isolated from Fungi
Authors: Nagaraj G. , Uma M. V. , Shivayogi M. S. , Balaram Hemalatha
Published: July 2002

Malaria caused by
Plasmodium falciparum
is a major public health problem in the developing countries of the world. Clinical treatment of malaria has become complicated due to the occurrence of infections caused by drug resistant parasites. Secondary metabolites from fungi are an attractive source of chemotherapeutic agents. This work reports the isolation and in vitro antiplasmodial activities of peptide antibiotics of fungal origin. The three peptide antibiotics used in this study were efrapeptins, zervamicins, and antiamoebin. The high-performance liquid chromatography-purified peptides were characterized by nuclear magnetic resonance and mass spectral analysis. All three fungal peptides kill
P. falciparum
in culture with 50% inhibitory concentrations in the micromolar range. A possible mode of action of these peptide antibiotics on
P. falciparum
is presented.
Determination of Dosing Guidelines for Stavudine (2′,3′-Didehydro-3′-Deoxythymidine) in Children with Human Immunodeficiency Virus Infection
Authors: Kaul Sanjeev , Kline Mark W. , Church Joseph A. , Dunkle Lisa M.
Published: July 2002

The results of the development of dosing guidelines for stavudine in human immunodeficiency virus (HIV)-infected children are summarized. Included in the integrated analyses were 21 and 33 HIV-infected pediatric and adult patients, respectively, from three phase I-II studies. Data for 21 children and 18 adults who received intravenous doses of 0.125 to 2 and 0.5 to 1 mg/kg of body weight, respectively, were used for the determination of dosing guidelines; exposure data for 16 children and 15 adults who received oral doses of 1 to 2 and 0.5 to 1 mg/kg/day, respectively, were used to validate the dosing recommendations for children. Significant relationships were observed between total body clearance (in milliliters per minute) in children and adults combined and demographic parameters of age, body weight, and body surface area (
R
2
= 0.77 to 0.80;
P
= 0.0001). Models of approximated pediatric dose based on clearance values and direct adult exposure yielded a stavudine dosage of 2 mg/kg/day for children of ≤30 kg of body weight and 1 mg/kg/day (adult dose) for children of >30 kg of body weight.