bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanocrystalline WC and WC/a-C composite coatings produced from intersected plasma fluxes at low deposition temperatures
Authors: Voevodin A. A. , O’Neill J. P. , Prasad S. V. , Zabinski J. S.
Published: July 2002

Low temperature vacuum deposition of tungsten carbide coatings, W1−yCy with compositions that varied from y=0 to 0.9, was investigated. Special attention was given to the production of nanocrystalline carbides with coatings of y>0.5. Previous attempts at producing WC with excess carbon at near room temperatures resulted in the formation of amorphous phases. In this study, crystalline WC was produced at 45 and 300 °C by the intersection of plasma fluxes from magnetron sputtering of tungsten and laser ablation of graphite. At both temperatures, formation of WC chemical bonding and nanocrystalline cubic β-WC1−x was observed using x-ray photoelectron spectroscopy and grazing angle x-ray diffraction when the carbon content was increased more than 30%. Increasing the substrate temperature to 300 °C did not affect the percentage of WC bonding, but it did promote considerable crystallization of cubic WC. As the carbon content was increased to more than 50%, a second phase consisting of amorphous carbon (a-C) was observed together with amorphitization of β-WC1−x. The a-C phase was identified as amorphous diamond-like carbon (DLC) by Raman spectroscopy. At 60–80 at. % C, a two phase structure was produced, which was composed of nanocrystalline β-WC1−x with 5–10 nm grains and amorphous DLC. The hardness of the WC/DLC composites was about 26 GPa based on nanoindentation tests. Correlation of the chemistry, microstructure, and mechanical properties of WC and WC/a-C coatings is discussed.
Unified disorder induced gap state model for insulator–semiconductor and metal–semiconductor interfaces
Authors: Hasegawa Hideki , Ohno Hideo
Published: July 2002

The energy location for the interface state density Nss minimum of the insulator–semiconductor (I–S) interface and the Fermi-level pinning position at the metal–semiconductor (M–S) interface are shown to coincide and to lie at the same position of 5.0 eV from the vacuum level for major tetrahedral semiconductors. Neither the unified defect model nor the metal induced gap state model can explain the novel striking correlation between the I–S and M–S interfaces. The correlation as well as the observed peculiar photoionization behavior of the I–S interface are explained by the novel unified disorder induced gap state (DIGS) model where DIGS pin or restrict the movement of the surface Fermi level. The above characteristic energy, EHO, is shown to be the Fermi energy of the DIGS spectrum which is given by the hybrid orbital energy of the sp3 bond of the host. The DIGS model explains remarkably well the behavior of the M–S interface formed on the bare or oxide covered semiconductor surface as well as the various features of Nss distribution of the I–S interface. The correlation between the DIGS-free heterojunction (S–S) interface and M–S/I–S interface is explained by the fact that EHO is a universal reference energy level of the host which is invariant under any off-diagonal interactions, as is evidenced by the alignment of transition metal deep levels, DX centers and EL2 with respect to EHO. Band offset at the S–S interface is proposed to be determined by the alignment of EHO which inevitably involves formation of interface dipole when two EHO levels lie at different positions from the vacuum level.
On the chemistry of passivated oxide–InP interfaces
Authors: Hollinger G. , Joseph J. , Robach Y. , Bergignat E. , Commère B. , Viktorovitch P. , Froment M.
Published: July 2002

Passivating native oxide films (≊150 Å) have been prepared by anodic oxidation of InP. X-ray photoelectron spectroscopy (XPS) chemical depth profiles reveal a double layer structure with indium-rich oxides at the surface and phosphorous-rich In(PO3)3 glass-like oxides at the interface. High quality metal–insulator–semiconductor (MIS) structures are obtained after removing the semiconducting indium-rich outer oxide layer. The passivating properties of the interfacial In(PO3)3 oxide are discussed on the basis of chemical bonding configurations in the native oxide. It is suggested that In(PO3)3 has better intrinsic passivating properties than InPO4.
GaN, AlN, and InN: A review
Authors: Strite S. , Morkoç H.
Published: July 2002

The status of research on both wurtzite and zinc-blende GaN, AlN, and InN and their alloys is reviewed including exciting recent results. Attention is paid to the crystal growth techniques, structural, optical, and electrical properties of GaN, AlN, InN, and their alloys. The various theoretical results for each material are summarized. We also describe the performance of several device structures which have been demonstrated in these materials. Near-term goals and critical areas in need of further research in the III–V nitride material system are identified.
The Human Transcriptome Map: Clustering of Highly Expressed Genes in Chromosomal Domains
Authors: Caron Huib , Schaik Barbera van , Mee Merlijn van der , Baas Frank , Riggins Gregory , Sluis Peter van , Hermus Marie-Christine , Asperen Ronald van , Boon Kathy , Voûte P. A. , Heisterkamp Siem , Kampen Antoine van , Versteeg Rogier
Published: July 2002

The chromosomal position of human genes is rapidly being established. We integrated these mapping data with genome-wide messenger RNA expression profiles as provided by SAGE (serial analysis of gene expression). Over 2.45 million SAGE transcript tags, including 160,000 tags of neuroblastomas, are presently known for 12 tissue types. We developed algorithms to assign these tags to UniGene clusters and their chromosomal position. The resulting Human Transcriptome Map generates gene expression profiles for any chromosomal region in 12 normal and pathologic tissue types. The map reveals a clustering of highly expressed genes to specific chromosomal regions. It provides a tool to search for genes that are overexpressed or silenced in cancer.
Redox State of Mars' Upper Mantle and Crust from Eu Anomalies in Shergottite Pyroxenes
Authors: Wadhwa M.
Published: July 2002

The oxidation state of basaltic martian meteorites is determined from the partitioning of europium (Eu) in their pyroxenes. The estimated redox conditions for these samples correlate with their initial neodymium and strontium isotopic compositions. This is interpreted to imply varying degrees of interaction between the basaltic parent melts, derived from a source in the martian mantle, and a crustal component. Thus, the mantle source of these martian basalts may have a redox state close to that of the iron-wüstite buffer, whereas the martian crust may be more oxidized (with a redox state higher than or equal to that of the quartz-fayalite-magnetite buffer). A difference in redox state of more than 3 log units between mantle and crustal reservoirs on Mars could result from oxidation of the crust by a process such as aqueous alteration, together with a subsequent lack of recycling of this oxidized crust through the reduced upper mantle.
Sudden Productivity Collapse Associated with the Triassic-Jurassic Boundary Mass Extinction
Authors: Ward P. D. , Haggart J. W. , Carter E. S. , Wilbur D. , Tipper H. W. , Evans T.
Published: July 2002

The end-Triassic mass extinction is one of the five most catastrophic in Phanerozoic Earth history. Here we report carbon isotope evidence of a pronounced productivity collapse at the boundary, coincident with a sudden extinction among marine plankton, from stratigraphic sections on the Queen Charlotte Islands, British Columbia, Canada. This signal is similar to (though smaller than) the carbon isotope excursions associated with the Permian-Triassic and Cretaceous-Tertiary events.
Toward Automated Synthesis of Oligosaccharides and Glycoproteins
Authors: Sears Pamela , Wong Chi-Huey
Published: July 2002

The discovery of previously unknown functions associated with carbohydrates and the study of their structure-function relations are of current interest in carbohydrate chemistry and biology. Progress in this area is, however, hampered by the lack of convenient and effective tools for the synthesis and analysis of oligosaccharides and glycoconjugates. Development of automated synthesis of such materials is necessary to facilitate research in this field. This review describes recent advances in carbohydrate synthesis, with particular focus on developments that have potential application to the automated synthesis of oligosaccharides, glycopeptides, and glycoproteins.
G Protein Regulation of Ion Channels and Abscisic Acid Signaling in
Arabidopsis
Guard Cells
Authors: Wang Xi-Qing , Ullah Hemayet , Jones Alan M. , Assmann Sarah M.
Published: July 2002

The phytohormone abscisic acid (ABA) promotes plant water conservation by decreasing the apertures of stomatal pores in the epidermis through which water loss occurs. We found that
Arabidopsis thaliana
plants harboring transferred DNA insertional mutations in the sole prototypical heterotrimeric GTP-binding (G) protein α subunit gene,
GPA1
, lack both ABA inhibition of guard cell inward K
+
channels and pH-independent ABA activation of anion channels. Stomatal opening in
gpa1
plants is insensitive to inhibition by ABA, and the rate of water loss from
gpa1
mutants is greater than that from wild-type plants. Manipulation of G protein status in guard cells may provide a mechanism for controlling plant water balance.
Ultraviolet Emission from a Diamond pn Junction
Authors: Koizumi Satoshi , Watanabe Kenji , Hasegawa Masataka , Kanda Hisao
Published: July 2002

We report the realization of an ultraviolet light–emitting diode with the use of a diamond pn junction. The pn junction was formed from a boron-doped p-type diamond layer and phosphorus-doped n-type diamond layer grown epitaxially on the {111} surface of single crystalline diamond. The pn junction exhibited good diode characteristics, and at forward bias of about 20 volts strong ultraviolet light emission at 235 nanometers was observed and was attributed to free exciton recombination.
Femtomolar Sensitivity of Metalloregulatory Proteins Controlling Zinc Homeostasis
Authors: Outten Caryn E. , O'Halloran and Thomas V.
Published: July 2002

Intracellular zinc is thought to be available in a cytosolic pool of free or loosely bound Zn(II) ions in the micromolar to picomolar range. To test this, we determined the mechanism of zinc sensors that control metal uptake or export in
Escherichia coli
and calibrated their response against the thermodynamically defined free zinc concentration. Whereas the cellular zinc quota is millimolar, free Zn(II) concentrations that trigger transcription of zinc uptake or efflux machinery are femtomolar, or six orders of magnitude less than one atom per cell. This is not consistent with a cytosolic pool of free Zn(II) and suggests an extraordinary intracellular zinc-binding capacity. Thus, cells exert tight control over cytosolic metal concentrations, even for relatively low-toxicity metals such as zinc.
Room-Temperature Ultraviolet Nanowire Nanolasers
Authors: Huang Michael H. , Mao Samuel , Feick Henning , Yan Haoquan , Wu Yiying , Kind Hannes , Weber Eicke , Russo Richard , Yang Peidong
Published: July 2002

Room-temperature ultraviolet lasing in semiconductor nanowire arrays has been demonstrated. The self-organized, <0001> oriented zinc oxide nanowires grown on sapphire substrates were synthesized with a simple vapor transport and condensation process. These wide band-gap semiconductor nanowires form natural laser cavities with diameters varying from 20 to 150 nanometers and lengths up to 10 micrometers. Under optical excitation, surface-emitting lasing action was observed at 385 nanometers, with an emission linewidth less than 0.3 nanometer. The chemical flexibility and the one-dimensionality of the nanowires make them ideal miniaturized laser light sources. These short-wavelength nanolasers could have myriad applications, including optical computing, information storage, and microanalysis.
Molecular Evidence for the Early Colonization of Land by Fungi and Plants
Authors: Heckman Daniel S. , Geiser David M. , Eidell Brooke R. , Stauffer Rebecca L. , Kardos Natalie L. , Hedges S. Blair
Published: July 2002

The colonization of land by eukaryotes probably was facilitated by a partnership (symbiosis) between a photosynthesizing organism (phototroph) and a fungus. However, the time when colonization occurred remains speculative. The first fossil land plants and fungi appeared 480 to 460 million years ago (Ma), whereas molecular clock estimates suggest an earlier colonization of land, about 600 Ma. Our protein sequence analyses indicate that green algae and major lineages of fungi were present 1000 Ma and that land plants appeared by 700 Ma, possibly affecting Earth's atmosphere, climate, and evolution of animals in the Precambrian.
BAFF-R, a Newly Identified TNF Receptor That Specifically Interacts with BAFF
Authors: Thompson Jeffrey S. , Bixler Sarah A. , Qian Fang , Vora Kalpit , Scott Martin L. , Cachero Teresa G. , Hession Catherine , Schneider Pascal , Sizing Irene D. , Mullen Colleen , Strauch Kathy , Zafari Mohammad , Benjamin Christopher D. , Tschopp Jurg , Browning Jeffrey L. , Ambrose Christine
Published: July 2002

B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.
Water-Induced Fabric Transitions in Olivine
Authors: Jung Haemyeong , Karato Shun-ichiro
Published: July 2002

The interpretation of seismic anisotropy in Earth's upper mantle has traditionally been based on the fabrics (lattice-preferred orientation) of relatively water-poor olivine. Here we show that when a large amount of water is added to olivine, the relation between flow geometry and seismic anisotropy undergoes marked changes. Some of the puzzling observations of seismic anisotropy in the upper mantle, including the anomalous anisotropy in the central Pacific and the complicated anisotropy in subduction zones, can be attributed to the enrichment of water in these regions.
Requirement of Borate Cross-Linking of Cell Wall Rhamnogalacturonan II for
Arabidopsis
Growth
Authors: O'Neill Malcolm A. , Eberhard Stefan , Albersheim Peter , Darvill Alan G.
Published: July 2002

Turgor-driven plant cell growth depends on wall structure. Two allelic
l
-fucose–deficient
Arabidopsis thaliana
mutants (
mur1-1
and
1-2
) are dwarfed and their rosette leaves do not grow normally.
mur1
leaf cell walls contain normal amounts of the cell wall pectic polysaccharide rhamnogalacturonan II (RG-II), but only half exists as a borate cross-linked dimer. The altered structure of
mur1
RG-II reduces the rate of formation and stability of this cross-link. Exogenous aqueous borate rescues the defect. The reduced cross-linking of RG-II in dwarf
mur1
plants indicates that plant growth depends on wall pectic polysaccharide organization.
Snf1--a Histone Kinase That Works in Concert with the Histone Acetyltransferase Gcn5 to Regulate Transcription
Authors: Lo Wan-Sheng , Duggan Laura , Tolga N. C. , Emre  , Belotserkovskya Rimma , Lane William S. , Shiekhattar Ramin , Berger Shelley L.
Published: July 2002

Modification of histones is an important element in the regulation of gene expression. Previous work suggested a link between acetylation and phosphorylation, but questioned its mechanistic basis. We have purified a histone H3 serine-10 kinase complex from
Saccharomyces cerevisiae
and have identified its catalytic subunit as Snf1. The Snf1/AMPK family of kinases function in conserved signal transduction pathways. Our results show that Snf1 and the acetyltransferase Gcn5 function in an obligate sequence to enhance
INO1
transcription by modifying histone H3 serine-10 and lysine-14. Thus, phosphorylation and acetylation are targeted to the same histone by promoter-specific regulation by a kinase/acetyltransferase pair, supporting models of gene regulation wherein transcription is controlled by coordinated patterns of histone modification.
Kinetic Stabilization of the α-Synuclein Protofibril by a Dopamine-α-Synuclein Adduct
Authors: Conway Kelly A. , Rochet Jean-Christophe , Bieganski Robert M. , Lansbury Peter T.
Published: July 2002

The substantia nigra in Parkinson's disease (PD) is depleted of dopaminergic neurons and contains fibrillar Lewy bodies comprising primarily α-synuclein. We screened a library to identify drug-like molecules to probe the relation between neurodegeneration and α-synuclein fibrilization. All but one of 15 fibril inhibitors were catecholamines related to dopamine. The inhibitory activity of dopamine depended on its oxidative ligation to α-synuclein and was selective for the protofibril-to-fibril conversion, causing accumulation of the α-synuclein protofibril. Adduct formation provides an explanation for the dopaminergic selectivity of α-synuclein–associated neurotoxicity in PD and has implications for current and future PD therapeutic and diagnostic strategies.
Mediterranean Sea Surface Radiocarbon Reservoir Age Changes Since the Last Glacial Maximum
Authors: Siani Giuseppe , Paterne Martine , Michel Elisabeth , Sulpizio Roberto , Sbrana Alessandro , Arnold Maurice , Haddad Geoffrey
Published: July 2002

Sea surface reservoir ages must be known to establish a common chronological framework for marine, continental, and cryospheric paleoproxies, and are crucial for understanding ocean-continent climatic relationships and the paleoventilation of the ocean. Radiocarbon dates of planktonic foraminifera and tephra contemporaneously deposited over Mediterranean marine and terrestrial regions reveal that the reservoir ages were similar to the modern one (∼400 years) during most of the past 18,000 carbon-14 years. However, reservoir ages increased by a factor of 2 at the beginning of the last deglaciation. This is attributed to changes of the North Atlantic thermohaline circulation during the massive ice discharge event Heinrich 1.
Natural Restoration of the Species-Area Relation for a Lizard After a Hurricane
Authors: Schoener Thomas W. , Spiller David A. , Losos Jonathan B.
Published: July 2002

We document the decimation and recovery of the commonest lizard species,
Anolis sagrei
, on 66 islands in the Bahamas that were directly hit by Hurricane Floyd in September 1999. Before the hurricane, an island's area was a better predictor of the occurrence of
A. sagrei
than was its altitude. Immediately after, altitude was a better predictor: Apparently all lizards on islands lower than about 3 meters maximum elevation perished in the storm surge. After about 1 year, area again became the better predictor. By 19 months after the hurricane,
A. sagrei
populations occurred on 88% of the islands they formerly occupied. Recovery occurred via overwater colonization and propagation from eggs that survived inundation, mechanisms that were enhanced by larger island area. Thus, natural processes first destroyed and then quickly restored a highly regular species-area distribution.
A Portrait of Alzheimer Secretases--New Features and Familiar Faces
Authors: Esler William P. , Wolfe Michael S.
Published: July 2002

The amyloid β-peptide (Aβ) is a principal component of the cerebral plaques found in the brains of patients with Alzeheimer's disease (AD). This insoluble 40– to 42–amino acid peptide is formed by the cleavage of the Aβ precursor protein (APP). The three proteases that cleave APP, α-, β-, and γ-secretases, have been implicated in the etiology of AD. β-Secretase is a membrane-anchored protein with clear homology to soluble aspartyl proteases, and α-secretase displays characteristics of certain membrane-tethered metalloproteases. γ-Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalytic component of this protease. Identification of the α-, β-, and γ-secretases provides potential targets for designing new drugs to treat AD.
A Combined Experimental and Computational Strategy to Define Protein Interaction Networks for Peptide Recognition Modules
Authors: Tong Amy Hin Yan , Drees Becky , Nardelli Giuliano , Bader Gary D. , Brannetti Barbara , Castagnoli Luisa , Evangelista Marie , Ferracuti Silvia , Nelson Bryce , Paoluzi Serena , Quondam Michele , Zucconi Adriana , Hogue Christopher W. V. , Fields Stanley , Boone Charles , Cesareni Gianni
Published: July 2002

Peptide recognition modules mediate many protein-protein interactions critical for the assembly of macromolecular complexes. Complete genome sequences have revealed thousands of these domains, requiring improved methods for identifying their physiologically relevant binding partners. We have developed a strategy combining computational prediction of interactions from phage-display ligand consensus sequences with large-scale two-hybrid physical interaction tests. Application to yeast SH3 domains generated a phage-display network containing 394 interactions among 206 proteins and a two-hybrid network containing 233 interactions among 145 proteins. Graph theoretic analysis identified 59 highly likely interactions common to both networks. Las17 (Bee1), a member of the Wiskott-Aldrich Syndrome protein (WASP) family of actin-assembly proteins, showed multiple SH3 interactions, many of which were confirmed in vivo by coimmunoprecipitation.
Spider Silk Fibers Spun from Soluble Recombinant Silk Produced in Mammalian Cells
Authors: Lazaris Anthoula , Arcidiacono Steven , Huang Yue , Zhou Jiang-Feng , Duguay François , Chretien Nathalie , Welsh Elizabeth A. , Soares Jason W. , Karatzas Costas N.
Published: July 2002

Spider silks are protein-based “biopolymer” filaments or threads secreted by specialized epithelial cells as concentrated soluble precursors of highly repetitive primary sequences. Spider dragline silk is a flexible, lightweight fiber of extraordinary strength and toughness comparable to that of synthetic high-performance fibers. We sought to “biomimic” the process of spider silk production by expressing in mammalian cells the dragline silk genes (
ADF-3
/
MaSpII
and
MaSpI
) of two spider species. We produced soluble recombinant (rc)–dragline silk proteins with molecular masses of 60 to 140 kilodaltons. We demonstrated the wet spinning of silk monofilaments spun from a concentrated aqueous solution of soluble rc–spider silk protein (ADF-3; 60 kilodaltons) under modest shear and coagulation conditions. The spun fibers were water insoluble with a fine diameter (10 to 40 micrometers) and exhibited toughness and modulus values comparable to those of native dragline silks but with lower tenacity. Dope solutions with rc–silk protein concentrations >20% and postspinning draw were necessary to achieve improved mechanical properties of the spun fibers. Fiber properties correlated with finer fiber diameter and increased birefringence.
The Giant Crocodyliform
Sarcosuchus
from the Cretaceous of Africa
Authors: Sereno Paul C. , Larsson Hans C. E. , Sidor Christian A. , Gado Boubé
Published: July 2002

New fossils of the giant African crocodyliform
Sarcosuchus imperator
clarify its skeletal anatomy, growth patterns, size, longevity, and phylogenetic position. The skull has an expansive narial bulla and elongate jaws studded with stout, smooth crowns that do not interlock. The jaw form suggests a generalized diet of large vertebrates, including fish and dinosaurs.
S. imperator
is estimated to have grown to a maximum body length of at least 11 to 12 meters and body weight of about 8 metric tons over a life-span of 50 to 60 years. Unlike its closest relatives, which lived as specialized piscivores in marginal marine habitats,
S. imperator
thrived in fluvial environments.
Rapid Killing of
Streptococcus pneumoniae
with a Bacteriophage Cell Wall Hydrolase
Authors: Loeffler Jutta M. , Nelson Daniel , Fischetti Vincent A.
Published: July 2002

Nasopharyngeal carriage is the major reservoir for
Streptococcus pneumoniae
in the community. Although eliminating this reservoir would greatly reduce disease occurrence, no suitable intervention has been available for this purpose. We show here that seconds after contact, a purified pneumococcal bacteriophage lytic enzyme (Pal) is able to kill 15 common serotypes of pneumococci, including highly penicillin-resistant strains. In vivo, previously colonized mice revealed undetectable pneumococcal titers 5 hours after a single enzyme treatment. Pal enzyme had little or no effect on microorganisms normally found in the human oropharynx, and Pal-resistant pneumococci could not be detected after extensive exposure to the enzyme.
Third-Generation Biomedical Materials
Authors: Hench Larry L. , Polak Julia M.
Published: July 2002

Whereas second-generation biomaterials were designed to be either resorbable or bioactive, the next generation of biomaterials is combining these two properties, with the aim of developing materials that, once implanted, will help the body heal itself.
Capturing Chromosome Conformation
Authors: Dekker Job , Rippe Karsten , Dekker Martijn , Kleckner Nancy
Published: July 2002

We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast
Saccharomyces cerevisiae
, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the G
1
stage of the cell cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring.
Dependence of EPSP Efficacy on Synapse Location in Neocortical Pyramidal Neurons
Authors: Williams Stephen R. , Stuart Greg J.
Published: July 2002

Neurons receive thousands of synaptic inputs throughout elaborate dendritic trees. Here we determine the somatic impact of excitatory postsynaptic potentials (EPSPs) generated at known dendritic sites in neocortical pyramidal neurons. As inputs became more distal, somatic EPSP amplitude decreased, whereas use-dependent depression increased. Despite marked attenuation (>40-fold), when coactivated within a narrow time window (∼10 milliseconds), distal EPSPs could directly influence action potential output following dendritic spike generation. These findings reveal that distal EPSPs are ineffective sources of background somatic excitation, but through coincidence detection have a powerful transient signaling role.
A S
N
2 Reaction That Avoids Its Deep Potential Energy Minimum
Authors: Sun Lipeng , Song Kihyung , Hase William L.
Published: July 2002

Chemical dynamics trajectory simulations were used to study the atomic-level mechanisms of the OH
−
+ CH
3
F → CH
3
OH + F
−
S
N
2 nucleophilic substitution reaction. The reaction dynamics, from the [OH⋯CH
3
⋯F]
−
central barrier to the reaction products, are simulated by ab initio direct dynamics. The reaction's potential energy surface has a deep minimum in the product exit channel arising from the CH
3
OH⋯F
−
hydrogen-bonded complex. Statistical theories of unimolecular reaction rates assume that the reactive system becomes trapped in this minimum and forms an intermediate, with random redistribution of its vibrational energy, but the majority of the trajectories (90%) avoided this potential energy minimum and instead dissociated directly to products. This finding is discussed in terms of intramolecular vibrational energy redistribution (IVR) and the relation between IVR and molecular structure. The finding of this study may be applicable to other reactive systems where there is a hierarchy of time scales for intramolecular motions and thus inefficient IVR.
Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein
Authors: Hartl F. Ulrich , Hayer-Hartl Manajit
Published: July 2002

Efficient folding of many newly synthesized proteins depends on assistance from molecular chaperones, which serve to prevent protein misfolding and aggregation in the crowded environment of the cell. Nascent chain–binding chaperones, including trigger factor, Hsp70, and prefoldin, stabilize elongating chains on ribosomes in a nonaggregated state. Folding in the cytosol is achieved either on controlled chain release from these factors or after transfer of newly synthesized proteins to downstream chaperones, such as the chaperonins. These are large, cylindrical complexes that provide a central compartment for a single protein chain to fold unimpaired by aggregation. Understanding how the thousands of different proteins synthesized in a cell use this chaperone machinery has profound implications for biotechnology and medicine.
Structural Insights into Group II Intron Catalysis and Branch-Site Selection
Authors: Zhang Lan , Doudna Jennifer A.
Published: July 2002

Group II self-splicing introns catalyze autoexcision from precursor RNA transcripts by a mechanism strikingly similar to that of the spliceosome, an RNA-protein assembly responsible for splicing together the protein-coding parts of most eukaryotic pre-mRNAs. Splicing in both cases initiates via nucleophilic attack at the 5′ splice site by the 2′ OH of a conserved intron adenosine residue, creating a branched (lariat) intermediate. Here, we describe the crystal structure at 3.0 Å resolution of a 70-nucleotide RNA containing the catalytically essential domains 5 and 6 of the yeast ai5γ group II self-splicing intron, revealing an unexpected two-nucleotide bulged structure around the branch-point adenosine in domain 6.
A Complex with Chromatin Modifiers That Occupies E2F- and Myc-Responsive Genes in G
0
Cells
Authors: Ogawa Hidesato , Ishiguro Kei-ichiro , Gaubatz Stefan , Livingston David M. , Nakatani Yoshihiro
Published: July 2002

E2F-6 contributes to gene silencing in a manner independent of retinoblastoma protein family members. To better elucidate the molecular mechanism of repression by E2F-6, we have purified the factor from cultured cells. E2F-6 is found in a multimeric protein complex that contains Mga and Max, and thus the complex can bind not only to the E2F-binding site but also to Myc- and Brachyury-binding sites. Moreover, the complex contains chromatin modifiers such as a novel histone methyltransferase that modifies lysine 9 of histone H3, HP1γ, and Polycomb group (PcG) proteins. The E2F-6 complex preferentially occupies target promoters in G
0
cells rather than in G
1
cells. These data suggest that these chromatin modifiers contribute to silencing of E2F- and Myc-responsive genes in quiescent cells.
Modeling the Heart--from Genes to Cells to the Whole Organ
Authors: Noble Denis
Published: July 2002

Successful physiological analysis requires an understanding of the functional interactions between the key components of cells, organs, and systems, as well as how these interactions change in disease states. This information resides neither in the genome nor even in the individual proteins that genes code for. It lies at the level of protein interactions within the context of subcellular, cellular, tissue, organ, and system structures. There is therefore no alternative to copying nature and computing these interactions to determine the logic of healthy and diseased states. The rapid growth in biological databases; models of cells, tissues, and organs; and the development of powerful computing hardware and algorithms have made it possible to explore functionality in a quantitative manner all the way from the level of genes to the physiological function of whole organs and regulatory systems. This review illustrates this development in the case of the heart. Systems physiology of the 21st century is set to become highly quantitative and, therefore, one of the most computer-intensive disciplines.
Is Face Processing Species-Specific During the First Year of Life?
Authors: Pascalis Olivier , de Haan Michelle , Nelson Charles A.
Published: July 2002

Between 6 and 10 months of age, the infant's ability to discriminate among native speech sounds improves, whereas the same ability to discriminate among foreign speech sounds decreases. Our study aimed to determine whether this perceptual narrowing is unique to language or might also apply to face processing. We tested discrimination of human and monkey faces by 6-month-olds, 9-month-olds, and adults, using the visual paired-comparison procedure. Only the youngest group showed discrimination between individuals of both species; older infants and adults only showed evidence of discrimination of their own species. These results suggest that the “perceptual narrowing” phenomenon may represent a more general change in neural networks involved in early cognition.
Nonvolcanic Deep Tremor Associated with Subduction in Southwest Japan
Authors: Obara Kazushige
Published: July 2002

Deep long-period tremors were recognized and located in a nonvolcanic region in southwest Japan. Epicenters of the tremors were distributed along the strike of the subducting Philippine Sea plate over a length of 600 kilometers. The depth of the tremors averaged about 30 kilometers, near the Mohorovic discontinuity. Each tremor lasted for at most a few weeks. The location of the tremors within the subduction zone indicates that the tremors may have been caused by fluid generated by dehydration processes from the slab.
Vitamin D Receptor As an Intestinal Bile Acid Sensor
Authors: Makishima Makoto , Lu Timothy T. , Xie Wen , Whitfield G. Kerr , Domoto Hideharu , Evans Ronald M. , Haussler Mark R. , Mangelsdorf David J.
Published: July 2002

The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1α,25-dihydroxyvitamin D
3
[1,25(OH)
2
D
3
]. We show that VDR also functions as a receptor for the secondary bile acid lithocholic acid (LCA), which is hepatotoxic and a potential enteric carcinogen. VDR is an order of magnitude more sensitive to LCA and its metabolites than are other nuclear receptors. Activation of VDR by LCA or vitamin D induced expression in vivo of CYP3A, a cytochrome P450 enzyme that detoxifies LCA in the liver and intestine. These studies offer a mechanism that may explain the proposed protective effects of vitamin D and its receptor against colon cancer.
Self-Assembly at All Scales
Authors: Whitesides George M. , Grzybowski Bartosz
Published: July 2002

Self-assembly is the autonomous organization of components into patterns or structures without human intervention. Self-assembling processes are common throughout nature and technology. They involve components from the molecular (crystals) to the planetary (weather systems) scale and many different kinds of interactions. The concept of self-assembly is used increasingly in many disciplines, with a different flavor and emphasis in each.
The New Genomics: Global Views of Biology
Authors: Lander Eric S.
Published: July 2002

What will happen after a complete sequence of the human genome is available? Eric Lander argues that it will be the beginning of a new phase of research. He presents 10 goals for the future that are related to a global view of biology.

The author is at the Whitehead Institute for Biomedical Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Molecular Evidence for Deep Precambrian Divergences Among Metazoan Phyla
Authors: Wray Gregory A. , Levinton Jeffrey S. , Shapiro Leo H.
Published: July 2002

A literal reading of the fossil record suggests that the animal phyla diverged in an “explosion” near the beginning of the Cambrian period. Calibrated rates of molecular sequence divergence were used to test this hypothesis. Seven independent data sets suggest that invertebrates diverged from chordates about a billion years ago, about twice as long ago as the Cambrian. Protostomes apparently diverged from chordates well before echinoderms, which suggests a prolonged radiation of animal phyla. These conclusions apply specifically to divergence times among phyla; the morphological features that characterize modern animal body plans, such as skeletons and coeloms, may have evolved later.
Synchronized Terrestrial Atmospheric Deglacial Records Around the North Atlantic
Authors: Björck Svante , Kromer Bernd , Johnsen Sigfus , Bennike Ole , Hammarlund Dan , Lemdahl Geoffrey , Possnert Göran , Rasmussen Tine Lander , Wohlfarth Barbara , Hammer Claus Uffe , Spurk Marco
Published: July 2002

On the basis of synchronization of three carbon-14 (
14
C)-dated lacustrine sequences from Sweden with tree ring and ice core records, the absolute age of the Younger Dryas-Preboreal climatic shift was determined to be 11,450 to 11,390 ± 80 years before the present. A 150-year-long cooling in the early Preboreal, associated with rising Δ
14
C values, is evident in all records and indicates an ocean ventilation change. This cooling is similar to earlier deglacial coolings, and box-model calculations suggest that they all may have been the result of increased freshwater forcing that inhibited the strength of the North Atlantic heat conveyor, although the Younger Dryas may have begun as an anomalous meltwater event.
Cell Cycle Checkpoints: Preventing an Identity Crisis
Authors: Elledge Stephen J.
Published: July 2002

Cell cycle checkpoints are regulatory pathways that control the order and timing of cell cycle transitions and ensure that critical events such as DNA replication and chromosome segregation are completed with high fidelity. In addition, checkpoints respond to damage by arresting the cell cycle to provide time for repair and by inducing transcription of genes that facilitate repair. Checkpoint loss results in genomic instability and has been implicated in the evolution of normal cells into cancer cells. Recent advances have revealed signal transduction pathways that transmit checkpoint signals in response to DNA damage, replication blocks, and spindle damage. Checkpoint pathways have components shared among all eukaryotes, underscoring the conservation of cell cycle regulatory machinery.
Inflorescence Commitment and Architecture in
Arabidopsis
Authors: Bradley Desmond , Ratcliffe Oliver , Vincent Coral , Carpenter Rosemary , Coen Enrico
Published: July 2002

Flowering plants exhibit one of two types of inflorescence architecture: indeterminate, in which the inflorescence grows indefinitely, or determinate, in which a terminal flower is produced. The indeterminate condition is thought to have evolved from the determinate many times, independently. In two mutants in distantly related species,
terminal flower 1
in
Arabidopsis
and
centroradialis
in
Antirrhinum
, inflorescences that are normally indeterminate are converted to a determinate architecture. The
Antirrhinum
gene
CENTRORADIALIS
(
CEN
) and the
Arabidopsis
gene
TERMINAL FLOWER 1
(
TFL1
) were shown to be homologous, which suggests that a common mechanism underlies indeterminacy in these plants. However, unlike
CEN
,
TFL1
is also expressed during the vegetative phase, where it delays the commitment to inflorescence development and thus affects the timing of the formation of the inflorescence meristem as well as its identity.
An Information-Intensive Approach to the Molecular Pharmacology of Cancer
Authors: Weinstein John N. , Myers Timothy G. , O'Connor Patrick M. , Friend Stephen H. , Fornace Albert J. , Kohn Kurt W. , Fojo Tito , Bates Susan E. , Rubinstein Lawrence V. , Anderson N. Leigh , Buolamwini John K. , van Osdol William W. , Monks Anne P. , Scudiero Dominic A. , Sausville Edward A. , Zaharevitz Daniel W. , Bunow Barry , Viswanadhan Vellarkad N. , Johnson George S. , Wittes Robert E. , Paull Kenneth D.
Published: July 2002

Since 1990, the National Cancer Institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI
50
) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI
50
values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.
Interaction of CED-4 with CED-3 and CED-9: A Molecular Framework for Cell Death
Authors: Chinnaiyan Arul M. , O'Rourke Karen , Lane Brian R. , Dixit Vishva M.
Published: July 2002

Previous genetic studies of the nematode
Caenorhabditis elegans
identified three important components of the cell death machinery. CED-3 and CED-4 function to kill cells, whereas CED-9 protects cells from death. Here CED-9 and its mammalian homolog Bcl-x
L
(a member of the Bcl-2 family of cell death regulators) were both found to interact with and inhibit the function of CED-4. In addition, analysis revealed that CED-4 can simultaneously interact with CED-3 and its mammalian counterparts interleukin-1β-converting enzyme (ICE) and FLICE. Thus, CED-4 plays a central role in the cell death pathway, biochemically linking CED-9 and the Bcl-2 family to CED-3 and the ICE family of pro-apoptotic cysteine proteases.
Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked
Authors: Yang Jie , Liu Xuesong , Bhalla Kapil , Kim Caryn Naekyung , Ibrado Ana Maria , Cai Jiyang , Peng Tsung-I , Jones Dean P. , Wang Xiaodong
Published: July 2002

Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria. Overexpression of Bcl-2 prevents cells from undergoing apoptosis in response to a variety of stimuli. Cytosolic cytochrome c is necessary for the initiation of the apoptotic program, suggesting a possible connection between Bcl-2 and cytochrome c, which is normally located in the mitochondrial intermembrane space. Cells undergoing apoptosis were found to have an elevation of cytochrome c in the cytosol and a corresponding decrease in the mitochondria. Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria.
Local Hormone Networks and Intestinal T Cell Homeostasis
Authors: Wang Jin , Whetsell Michael , Klein John R.
Published: July 2002

Neuroendocrine hormones of the hypothalamus-pituitary-thyroid axis can exert positive or negative immunoregulatory effects on intestinal lymphocytes. Small intestine epithelial cells were found to express receptors for thyrotropin-releasing hormone (TRH) and to be a primary source of intestine-derived thyroid-stimulating hormone (TSH). The gene for the TSH receptor (TSH-R) was expressed in intestinal T cells but not in epithelial cells, which suggested a hormone-mediated link between lymphoid and nonhematopoietic components of the intestine. Because mice with congenitally mutant TSH-R (
hyt
/
hyt
mice) have a selectively impaired intestinal T cell repertoire, TSH may be a key immunoregulatory mediator in the intestine.
Exploitation of Mammalian Host Cell Functions by Bacterial Pathogens
Authors: Finlay B. Brett , Cossart Pascale
Published: July 2002

Interest in bacterial pathogenesis has recently increased because of antibiotic resistance, the emergence of new pathogens and the resurgence of old ones, and the lack of effective therapeutics. The molecular and cellular mechanisms of microbial pathogenesis are currently being defined, with precise knowledge of both the common strategies used by multiple pathogenic bacteria and the unique tactics evolved by individual species to help establish infection. What is emerging is a new appreciation of how bacterial pathogens interact with host cells. Many host cell functions, including signal transduction pathways, cytoskeletal rearrangements, and vacuolar trafficking, are exploited, and these are the focus of this review. A bonus of this work is that bacterial virulence factors are providing new tools to study various aspects of mammalian cell functions, in addition to mechanisms of bacterial disease. Together these developments may lead to new therapeutic strategies.
Geometric Control of Cell Life and Death
Authors: Chen Christopher S. , Mrksich Milan , Huang Sui , Whitesides George M. , Ingber Donald E.
Published: July 2002

Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension. Cell spreading also was varied while maintaining the total cell-matrix contact area constant by changing the spacing between multiple focal adhesion-sized islands. Cell shape was found to govern whether individual cells grow or die, regardless of the type of matrix protein or antibody to integrin used to mediate adhesion. Local geometric control of cell growth and viability may therefore represent a fundamental mechanism for developmental regulation within the tissue microenvironment.
Membrane and Morphological Changes in Apoptotic Cells Regulated by Caspase-Mediated Activation of PAK2
Authors: Rudel Thomas , Bokoch Gary M.
Published: July 2002

Apoptosis of Jurkat T cells induced the caspase-mediated proteolytic cleavage of p21-activated kinase 2 (PAK2). Cleavage occurred between the amino-terminal regulatory domain and the carboxyl-terminal catalytic domain, which generated a constitutively active PAK2 fragment. Stable Jurkat cell lines that expressed a dominant-negative PAK mutant were resistant to the Fas-induced formation of apoptotic bodies, but had an enhanced externalization of phosphatidylserine at the cell surface. Thus, proteolytic activation of PAK2 represents a guanosine triphosphatase–independent mechanism of PAK regulation that allows PAK2 to regulate morphological changes that are seen in apoptotic cells.
The Late Neogene
87
Sr/
86
Sr Record of Lowland Himalayan Rivers
Authors: Quade Jay , Roe Lois , DeCelles Peter G. , Ojha Tank P.
Published: July 2002

Fossil shells and paleosol carbonate from ancestral Himalayan river deposits provide a
87
Sr/
86
Sr record of lowland Himalayan river water during the late Neogene. Reconstructed
87
Sr/
86
Sr river values increased sharply in the late Miocene, probably marking the beginning of exhumation of high-
87
Sr/
86
Sr metalimestones, more in the central than in the western Himalayas. These results imply that the marine
87
Sr/
86
Sr record may not be a proxy for silicate weathering or consumption of atmospheric CO
2
resulting from that weathering.