bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Studies of Individual InAs Quantum Dots in GaAs: Few-Particle Effects
Authors: Landin L. , Miller M. S. , Pistol M.-E. , Pryor C. E. , Samuelson L.
Published: July 2002

Optical emission from individual strained indium arsenide (InAs) islands buried in gallium arsenide (GaAs) was studied. At low excitation power density, the spectra from these quantum dots consist of a single line. At higher excitation power density, additional emission lines appeared at both higher and lower energies, separated from the main line by about 1 millielectron volt. At even higher excitation power density, this set of lines was replaced by a broad emission peaking below the original line. The splittings were an order of magnitude smaller than the lowest single-electron or single-hole excited state energies, indicating that the fine structure results from few-particle interactions in the dot. Calculations of few-particle effects give splittings of the observed magnitude.
Stormy Weather in Galaxy Clusters
Authors: Burns Jack O.
Published: July 2002

Recent x-ray, optical, and radio observations coupled with particle and gas dynamics numerical simulations reveal an unexpectedly complex environment within clusters of galaxies, driven by ongoing accretion of matter from large-scale supercluster filaments. Mergers between clusters and continuous infall of dark matter and baryons from the cluster periphery produce long-lived “stormy weather” within the gaseous cluster atmosphere—shocks, turbulence, and winds of more than 1000 kilometers per second. This weather may be responsible for shaping a rich variety of extended radio sources, which in turn act as “barometers” and “anemometers” of cluster weather.
Structure and Function in the Nucleus
Authors: Lamond Angus I. , Earnshaw William C.
Published: July 2002

Current evidence suggests that the nucleus has a distinct substructure, albeit one that is dynamic rather than a rigid framework. Viral infection, oncogene expression, and inherited human disorders can each cause profound and specific changes in nuclear organization. This review summarizes recent progress in understanding nuclear organization, highlighting in particular the dynamic aspects of nuclear structure.
Platinum Catalysts for the High-Yield Oxidation of Methane to a Methanol Derivative
Authors: Periana Roy A. , Taube Douglas J. , Gamble Scott , Taube Henry , Satoh Takashi , Fujii Hiroshi
Published: July 2002

Platinum catalysts are reported for the direct, low-temperature, oxidative conversion of methane to a methanol derivative at greater than 70 percent one-pass yield based on methane. The catalysts are platinum complexes derived from the bidiazine ligand family that are stable, active, and selective for the oxidation of a carbon-hydrogen bond of methane to produce methyl esters. Mechanistic studies show that platinum(II) is the most active oxidation state of platinum for reaction with methane, and are consistent with reaction proceeding through carbon-hydrogen bond activation of methane to generate a platinum-methyl intermediate that is oxidized to generate the methyl ester product.
Multiple-Step Melting in Two-Dimensional Hexatic Liquid-Crystal Films
Authors: Chou Chia-Fu , Jin Anjun J. , Hui S. W. , Huang C. C. , Ho John T.
Published: July 2002

An unexpected three-stage melting transition has been observed in two-dimensional (2D) free-standing liquid-crystal films by in situ electron-diffraction and optical-reflectivity measurements. These data suggest the existence of two phases between the 2D solid and liquid: a hexatic phase and, at a higher temperature, an intermediate liquid phase with hexatic-like positional correlations (∼40 angstroms) but no long-range orientational order. Previous high-resolution heat-capacity measurements have revealed a divergent-like anomaly at the hexatic-liquid transition that sharply contradicts the predictions of 2D melting theories. The observation of an intermediate isotropic phase may alter our understanding of 2D melting and lead to reconciliation between current experiments and theories.
Inhibition of a
Mycobacterium tuberculosis
β-Ketoacyl ACP Synthase by Isoniazid
Authors: Mdluli Khisimuzi , Slayden Richard A. , Zhu YaQi , Ramaswamy Srinivas , Pan Xi , Mead David , Crane Deborah D. , Musser James M. , Barry Clifton E.
Published: July 2002

Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated
Mycobacterium tuberculosis
was shown to consist of a covalent complex of INH, AcpM, and a β-ketoacyl acyl carrier protein synthase, KasA. Amino acid–altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug.
Embryonic Folate Metabolism and Mouse Neural Tube Defects
Authors: Fleming Angeleen , Copp Andrew J.
Published: July 2002

Folic acid prevents 70 percent of human neural tube defects (NTDs) but its mode of action is unclear. The deoxyuridine suppression test detects disturbance of folate metabolism in homozygous
splotch
(
Pax3
) mouse embryos that are developing NTDs in vitro. Excessive incorporation of [
3
H]thymidine in
splotch
embryos indicates a metabolic deficiency in the supply of folate for the biosynthesis of pyrimidine. Exogenous folic acid and thymidine both correct the biosynthetic defect and prevent some NTDs in
splotch
homozygotes, whereas methionine has an exacerbating effect. These data support a direct normalization of neurulation by folic acid in humans and suggest a metabolic basis for folate action.
Fidelity of T Cell Activation Through Multistep T Cell Receptor ζ Phosphorylation
Authors: Kersh Ellen Neumeister , Shaw Andrey S. , Allen Paul M.
Published: July 2002

The T cell receptor (TCR) αβ heterodimer interacts with its ligands with high specificity, but surprisingly low affinity. The role of the ζ component of the murine TCR in contributing to the fidelity of antigen recognition was examined. With sequence-specific phosphotyrosine antibodies, it was found that ζ undergoes a series of ordered phosphorylation events upon TCR engagement. Completion of phosphorylation steps is dependent on the nature of the TCR ligand. Thus, the phosphorylation steps establish thresholds for T cell activation. This study documents the sophisticated molecular events that follow the engagement of a low-affinity receptor.
Making Memories: Brain Activity that Predicts How Well Visual Experience Will Be Remembered
Authors: Brewer James B. , Zhao Zuo , Desmond John E. , Glover Gary H. , Gabrieli John D. E.
Published: July 2002

Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.
Forest Fires: An Example of Self-Organized Critical Behavior
Authors: Malamud Bruce D. , Morein Gleb , Turcotte Donald L.
Published: July 2002

Despite the many complexities concerning their initiation and propagation, forest fires exhibit power-law frequency-area statistics over many orders of magnitude. A simple forest fire model, which is an example of self-organized criticality, exhibits similar behavior. One practical implication of this result is that the frequency-area distribution of small and medium fires can be used to quantify the risk of large fires, as is routinely done for earthquakes.
Past Temperatures Directly from the Greenland Ice Sheet
Authors: Dahl-Jensen D. , Mosegaard K. , Gundestrup N. , Clow G. D. , Johnsen S. J. , Hansen A. W. , Balling N.
Published: July 2002

A Monte Carlo inverse method has been used on the temperature profiles measured down through the Greenland Ice Core Project (GRIP) borehole, at the summit of the Greenland Ice Sheet, and the Dye 3 borehole 865 kilometers farther south. The result is a 50,000-year-long temperature history at GRIP and a 7000-year history at Dye 3. The Last Glacial Maximum, the Climatic Optimum, the Medieval Warmth, the Little Ice Age, and a warm period at 1930 A.D. are resolved from the GRIP reconstruction with the amplitudes –23 kelvin, +2.5 kelvin, +1 kelvin, –1 kelvin, and +0.5 kelvin, respectively. The Dye 3 temperature is similar to the GRIP history but has an amplitude 1.5 times larger, indicating higher climatic variability there. The calculated terrestrial heat flow density from the GRIP inversion is 51.3 milliwatts per square meter.
New Goals for the U.S. Human Genome Project: 1998-2003
Authors: Collins Francis S. , Patrinos Ari , Jordan Elke , Chakravarti Aravinda , Gesteland Raymond , Walters LeRoy ,   the members of the DOE and NIH planning groups
Published: July 2002

The Human Genome Project has successfully completed all the major goals in its current 5-year plan, covering the period 1993–98. A new plan, for 1998–2003, is presented, in which human DNA sequencing will be the major emphasis. An ambitious schedule has been set to complete the full sequence by the end of 2003, 2 years ahead of previous projections. In the course of completing the sequence, a “working draft” of the human sequence will be produced by the end of 2001. The plan also includes goals for sequencing technology development; for studying human genome sequence variation; for developing technology for functional genomics; for completing the sequence of
Caenorhabditis elegans
and
Drosophila melanogaster
and starting the mouse genome; for studying the ethical, legal, and social implications of genome research; for bioinformatics and computational studies; and for training of genome scientists.
Phytochromes and Cryptochromes in the Entrainment of the
Arabidopsis
Circadian Clock
Authors: Somers David E. , Devlin Paul F. , Kay Steve A.
Published: July 2002

Circadian clocks are synchronized by environmental cues such as light. Photoreceptor-deficient
Arabidopsis thaliana
mutants were used to measure the effect of light fluence rate on circadian period in plants. Phytochrome B is the primary high-intensity red light photoreceptor for circadian control, and phytochrome A acts under low-intensity red light. Cryptochrome 1 and phytochrome A both act to transmit low-fluence blue light to the clock. Cryptochrome 1 mediates high-intensity blue light signals for period length control. The presence of cryptochromes in both plants and animals suggests that circadian input pathways have been conserved throughout evolution.
Xid
-Like Immunodeficiency in Mice with Disruption of the p85α Subunit of Phosphoinositide 3-Kinase
Authors: Suzuki Harumi , Terauchi Yasuo , Fujiwara Mari , Aizawa Shinichi , Yazaki Yoshio , Kadowaki Takashi , Koyasu Shigeo
Published: July 2002

Mice with a targeted gene disruption of p85α, a regulatory subunit of phosphoinositide 3-kinase, had impaired B cell development at the pro–B cell stage, reduced numbers of mature B cells and peritoneal CD5
+
Ly-1 B cells, reduced B cell proliferative responses, and no T cell–independent antibody production. These phenotypes are nearly identical to those of Btk
−/−
or
xid
(X-linked immunodeficiency) mice. These results provide evidence that p85α is functionally linked to the Btk pathway in antigen receptor–mediated signal transduction and is pivotal in B cell development and functions.
Cytokinin Activation of
Arabidopsis
Cell Division Through a D-Type Cyclin
Authors: Riou-Khamlichi Catherine , Huntley Rachael , Jacqmard Annie , Murray James A.H.
Published: July 2002

Cytokinins are plant hormones that regulate plant cell division. The D-type cyclin CycD3 was found to be elevated in a mutant of
Arabidopsis
with a high level of cytokinin and to be rapidly induced by cytokinin application in both cell cultures and whole plants. Constitutive expression of CycD3 in transgenic plants allowed induction and maintenance of cell division in the absence of exogenous cytokinin. Results suggest that cytokinin activates
Arabidopsis
cell division through induction of CycD3 at the G
1
-S cell cycle phase transition.
Superradiance in a Torus Magnetosphere Around a Black Hole
Authors: van Putten Maurice H. P. M.
Published: July 2002

The coalescence of a neutron star and a black hole in a binary system is believed to form a torus around a Kerr black hole. A similarly shaped magnetosphere then results from the remnant magnetic field of the neutron star. In the strong-field case, it contains a cavity for plasma waves located between the barrier of the gravitational potential and the surrounding torus. This cavity may be unstable to superradiance of electromagnetic waves. Superradiant amplification of such waves, initially excited by turbulence in the torus, should inflate into a bubble in a time as short as ∼0.75 (1 percent/|ε|
2
)(
M
/7
M
⊙
) seconds ∼0.15 to 1.5 seconds, assuming an efficiency |ε|
2
= 0.5 to 5 percent and a mass
M
= 7
M
⊙
. These bubbles may burst and repeat, of possible relevance to intermittency in cosmological γ-ray bursts. The model predicts γ-ray bursts to be anticorrelated with their gravitational wave emissions.
Australopithecus garhi
: A New Species of Early Hominid from Ethiopia
Authors: Asfaw Berhane , White Tim , Lovejoy Owen , Latimer Bruce , Simpson Scott , Suwa Gen
Published: July 2002

The lack of an adequate hominid fossil record in eastern Africa between 2 and 3 million years ago (Ma) has hampered investigations of early hominid phylogeny. Discovery of 2.5 Ma hominid cranial and dental remains from the Hata beds of Ethiopia's Middle Awash allows recognition of a new species of
Australopithecus
. This species is descended from
Australopithecus afarensis
and is a candidate ancestor for early
Homo
. Contemporary postcranial remains feature a derived humanlike humeral/femoral ratio and an apelike upper arm–to–lower arm ratio.
Separate Signals for Target Selection and Movement Specification in the Superior Colliculus
Authors: Horwitz Gregory D. , Newsome William T.
Published: July 2002

At any given instant, multiple potential targets for saccades are present in the visual world, implying that a “selection process” within the brain determines the target of the next eye movement. Some superior colliculus (SC) neurons begin discharging seconds before saccade initiation, suggesting involvement in target selection or, alternatively, in postselectional saccade preparation. SC neurons were recorded in monkeys who selected saccade targets on the basis of motion direction in a visual display. Some neurons carried a direction-selective visual signal, consistent with a role in target selection in this task, whereas other SC neurons appeared to be more involved in postselection specification of saccade parameters.
Interaction of RAFT1 with Gephyrin Required for Rapamycin-Sensitive Signaling
Authors: Sabatini David M. , Barrow Roxanne K. , Blackshaw Seth , Burnett Patrick E. , Lai Michael M. , Field Michael E. , Bahr Ben A. , Kirsch Joachim , Betz Heinrich , Snyder Solomon H.
Published: July 2002

RAFT1 (rapamycin and FKBP12 target 1; also called FRAP or mTOR) is a member of the ATM (ataxia telangiectasia mutated)–related family of proteins and functions as the in vivo mediator of the effects of the immunosuppressant rapamycin and as an important regulator of messenger RNA translation. In mammalian cells RAFT1 interacted with gephyrin, a widely expressed protein necessary for the clustering of glycine receptors at the cell membrane of neurons. RAFT1 mutants that could not associate with gephyrin failed to signal to downstream molecules, including the p70 ribosomal S6 kinase and the eIF-4E binding protein, 4E-BP1. The interaction with gephyrin ascribes a function to the large amino-terminal region of an ATM-related protein and reveals a role in signal transduction for the clustering protein gephyrin.
Bone Marrow as a Potential Source of Hepatic Oval Cells
Authors: Petersen B. E. , Bowen W. C. , Patrene K. D. , Mars W. M. , Sullivan A. K. , Murase N. , Boggs S. S. , Greenberger J. S. , Goff J. P.
Published: July 2002

Bone marrow stem cells develop into hematopoietic and mesenchymal lineages but have not been known to participate in production of hepatocytes, biliary cells, or oval cells during liver regeneration. Cross-sex or cross-strain bone marrow and whole liver transplantation were used to trace the origin of the repopulating liver cells. Transplanted rats were treated with 2-acetylaminofluorene, to block hepatocyte proliferation, and then hepatic injury, to induce oval cell proliferation. Markers for Y chromosome, dipeptidyl peptidase IV enzyme, and L21-6 antigen were used to identify liver cells of bone marrow origin. From these cells, a proportion of the regenerated hepatic cells were shown to be donor-derived. Thus, a stem cell associated with the bone marrow has epithelial cell lineage capability.
Modeling Astrophysical Phenomena in the Laboratory with Intense Lasers
Authors: Remington Bruce A. , Arnett David , Paul R. , Drake  , Takabe Hideaki
Published: July 2002

Astrophysical research has traditionally been divided into observations and theoretical modeling or a combination of both. A component sometimes missing has been the ability to quantitatively test the observations and models in an experimental setting where the initial and final states are well characterized. Intense lasers are now being used to recreate aspects of astrophysical phenomena in the laboratory, allowing the creation of experimental test beds where observations and models can be quantitatively compared with laboratory data. Experiments are under development at intense laser facilities to test and refine our understanding of phenomena such as supernovae, supernova remnants, gamma-ray bursts, and giant planets.
Comparative Genomics of BCG Vaccines by Whole-Genome DNA Microarray
Authors: Behr M. A. , Wilson M. A. , Gill W. P. , Salamon H. , Schoolnik G. K. , Rane S. , Small P. M.
Published: July 2002

Bacille Calmette-Guérin (BCG) vaccines are live attenuated strains of
Mycobacterium bovis
administered to prevent tuberculosis. To better understand the differences between
M. tuberculosis
,
M. bovis
, and the various BCG daughter strains, their genomic compositions were studied by performing comparative hybridization experiments on a DNA microarray. Regions deleted from BCG vaccines relative to the virulent
M. tuberculosis
H37Rv reference strain were confirmed by sequencing across the missing segment of the H37Rv genome. Eleven regions (encompassing 91 open reading frames) of H37Rv were found that were absent from one or more virulent strains of
M. bovis
. Five additional regions representing 38 open reading frames were present in
M. bovis
but absent from some or all BCG strains; this is evidence for the ongoing evolution of BCG strains since their original derivation. A precise understanding of the genetic differences between closely related Mycobacteria suggests rational approaches to the design of improved diagnostics and vaccines.
Gold Solubility in Supercritical Hydrothermal Brines Measured in Synthetic Fluid Inclusions
Authors: Loucks Robert R. , Mavrogenes John A.
Published: July 2002

Dissolved gold contents in chloride brines that were experimentally saturated with gold, magnetite, iron sulfides, orthoclase, and muscovite at 550° to 725°C and 100 to 400 megapascals are reported here. Microsamples of the fluid were isolated at the experimental temperature and pressure as fluid inclusions in quartz. Individual fluid inclusions were opened by laser ablation and analyzed by inductively coupled plasma mass spectrometry. The results show that gold solubility as sulfide species in supercritical brines is far higher than previously supposed. Dissolved gases such as molecular hydrogen sulfide that are ineffective metal-complexing agents at low pressures evidently become highly effective at high pressures.
Stability, Precision, and Near-24-Hour Period of the Human Circadian Pacemaker
Authors: Czeisler Charles A. , Duffy Jeanne F. , Shanahan Theresa L. , Brown Emery N. , Mitchell Jude F. , Rimmer David W. , Ronda Joseph M. , Silva Edward J. , Allan James S. , Emens Jonathan S. , Dijk Derk-Jan , Kronauer Richard E.
Published: July 2002

Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.
Electrostatic Repulsion of Positively Charged Vesicles and Negatively Charged Objects
Authors: Aranda-Espinoza Helim , Chen Yi , Dan Nily , Lubensky T. C. , Nelson Philip , Ramos Laurence , Weitz D. A.
Published: July 2002

A positively charged, mixed bilayer vesicle in the presence of negatively charged surfaces (for example, colloidal particles) can spontaneously partition into an adhesion zone of definite area and another zone that repels additional negative objects. Although the membrane itself has nonnegative charge in the repulsive zone, negative counterions on the interior of the vesicle spontaneously aggregate there and present a net negative charge to the exterior. Beyond the fundamental result that oppositely charged objects can repel, this mechanism helps to explain recent experiments on surfactant vesicles.
An Allele of
COL9A2
Associated with Intervertebral Disc Disease
Authors: Annunen Susanna , Paassilta Petteri , Lohiniva Jaana , Perälä Merja , Pihlajamaa Tero , Karppinen Jaro , Tervonen Osmo , Kröger Heikki , Lähde Seppo , Vanharanta Heikki , Ryhänen Lasse , Göring Harald H. H. , Ott Jürg , Prockop Darwin J. , Ala-Kokko Leena
Published: July 2002

Intervertebral disc disease is one of the most common musculoskeletal disorders. A number of environmental and anthropometric risk factors may contribute to it, and recent reports have suggested the importance of genetic factors as well. The
COL9A2
gene, which codes for one of the polypeptide chains of collagen IX that is expressed in the intervertebral disc, was screened for sequence variations in individuals with intervertebral disc disease. The analysis identified a putative disease-causing sequence variation that converted a codon for glutamine to one for tryptophan in six out of the 157 individuals but in none of 174 controls. The tryptophan allele cosegregated with the disease phenotype in the four families studied, giving a lod score (logarithm of odds ratio) for linkage of 4.5, and subsequent linkage disequilibrium analysis conditional on linkage gave an additional lod score of 7.1.
Light-Dependent Sequestration of TIMELESS by CRYPTOCHROME
Authors: Ceriani M. Fernanda , Darlington Thomas K. , Staknis David , Más Paloma , Petti Allegra A. , Weitz Charles J. , Kay Steve A.
Published: July 2002

Most organisms have circadian clocks consisting of negative feedback loops of gene regulation that facilitate adaptation to cycles of light and darkness. In this study, CRYPTOCHROME (CRY), a protein involved in circadian photoperception in
Drosophila
, is shown to block the function of PERIOD/TIMELESS (PER/TIM) heterodimeric complexes in a light-dependent fashion. TIM degradation does not occur under these conditions; thus, TIM degradation is uncoupled from abrogation of its function by light. CRY and TIM are part of the same complex and directly interact in yeast in a light-dependent fashion. PER/TIM and CRY influence the subcellular distribution of these protein complexes, which reside primarily in the nucleus after the perception of a light signal. Thus, CRY acts as a circadian photoreceptor by directly interacting with core components of the circadian clock.
Detecting Protein Function and Protein-Protein Interactions from Genome Sequences
Authors: Marcotte Edward M. , Pellegrini Matteo , Ng Ho-Leung , Rice Danny W. , Yeates Todd O. , Eisenberg David
Published: July 2002

A computational method is proposed for inferring protein interactions from genome sequences on the basis of the observation that some pairs of interacting proteins have homologs in another organism fused into a single protein chain. Searching sequences from many genomes revealed 6809 such putative protein-protein interactions in
Escherichia coli
and 45,502 in yeast. Many members of these pairs were confirmed as functionally related; computational filtering further enriches for interactions. Some proteins have links to several other proteins; these coupled links appear to represent functional interactions such as complexes or pathways. Experimentally confirmed interacting pairs are documented in a Database of Interacting Proteins.
Decreased Rates of Alluvial Sediment Storage in the Coon Creek Basin, Wisconsin, 1975-93
Authors: Trimble Stanley W.
Published: July 2002

The total measured rate of alluvial sediment accretion in the agricultural Coon Creek Basin for the period 1975–93 was only about 6 percent of the rate that occurred in the 1930s, but the distributed changes within the basin were highly variable and systematic. Sediment yield (efflux), however, remained relatively constant despite large stream and valley changes within the basin. These observations demonstrate (i) that sediment sources, sinks, and fluxes vary widely over time and space and (ii) that, although improved soil conservation measures have decreased soil erosion, the downstream effects are complex.
Functional Interaction of BRCA1-Associated BARD1 with Polyadenylation Factor CstF-50
Authors: Kleiman Frida E. , Manley James L.
Published: July 2002

Polyadenylation of messenger RNA precursors requires a complex protein machinery that is closely integrated with the even more complex transcriptional apparatus. Here a polyadenylation factor, CstF-50 (cleavage stimulation factor), is shown to interact in vitro and in intact cells with a nuclear protein of previously unknown function, BRCA1-associated RING domain protein (BARD1). The BARD1-CstF-50 interaction inhibits polyadenylation in vitro. BARD1, like CstF-50, also interacts with RNA polymerase II. These results indicate that BARD1-mediated inhibition of polyadenylation may prevent inappropriate RNA processing during transcription, perhaps at sites of DNA repair, and they reveal an unanticipated integration of diverse nuclear events.
The Mammalian Gene Collection
Authors: Strausberg Robert L. , Feingold Elise A. , Klausner Richard D. , Collins Francis S.
Published: July 2002

The Mammalian Gene Collection (MGC) project is a new effort by the NIH to generate full-length complementary DNA (cDNA) resources. This project will provide publicly accessible resources to the full research community. The MGC project entails the production of libraries, sequencing, and database and repository development, as well as the support of library construction, sequencing, and analytic technologies dedicated to the goal of obtaining a full set of human and other mammalian full-length (open reading frame) sequences and clones of expressed genes.
Epigenetics: Regulation Through Repression
Authors: Wolffe Alan P. , Matzke Marjori A.
Published: July 2002

Epigenetics is the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic phenomena have major economic and medical relevance, and several, such as imprinting and paramutation, violate Mendelian principles. Recent discoveries link the recognition of nucleic acid sequence homology to the targeting of DNA methylation, chromosome remodeling, and RNA turnover. Although epigenetic mechanisms help to protect cells from parasitic elements, this defense can complicate the genetic manipulation of plants and animals. Essential for normal development, epigenetic controls become misdirected in cancer cells and other human disease syndromes.
Role of Metal-Oxide Interface in Determining the Spin Polarization of Magnetic Tunnel Junctions
Authors: De Teresa Jose Maria , Barthélémy Agnès , Fert Albert , Contour Jean Pierre , Montaigne François , Seneor Pierre
Published: July 2002

The role of the metal-oxide interface in determining the spin polarization of electrons tunneling from or into ferromagnetic transition metals in magnetic tunnel junctions is reported. The spin polarization of cobalt in tunnel junctions with an alumina barrier is positive, but it is negative when the barrier is strontium titanate or cerium lanthanite. The results are ascribed to bonding effects at the transition metal–barrier interface. The influence of the electronic structure of metal-oxide interfaces on the spin polarization raises interesting fundamental problems and opens new ways to optimize the magnetoresistance of tunnel junctions.
Contact-Dependent Inhibition of Cortical Neurite Growth Mediated by Notch Signaling
Authors: Šestan Nenad , Artavanis-Tsakonas Spyros , Rakic Pasko
Published: July 2002

The exuberant growth of neurites during development becomes markedly reduced as cortical neurons mature. In vitro studies of neurons from mouse cerebral cortex revealed that contact-mediated Notch signaling regulates the capacity of neurons to extend and elaborate neurites. Up-regulation of Notch activity was concomitant with an increase in the number of interneuronal contacts and cessation of neurite growth. In neurons with low Notch activity, which readily extend neurites, up-regulation of Notch activity either inhibited extension or caused retraction of neurites. Conversely, in more mature neurons that had ceased their growth after establishing numerous connections and displayed high Notch activity, inhibition of Notch signaling promoted neurite extension. Thus, the formation of neuronal contacts results in activation of Notch receptors, leading to restriction of neuronal growth and a subsequent arrest in maturity.
Epigenetic Inheritance of Active Chromatin After Removal of the Main Transactivator
Authors: Cavalli Giacomo , Paro Renato
Published: July 2002

The
Drosophila
Polycomb and trithorax group proteins act through chromosomal elements such as
Fab-7
to maintain repressed or active gene expression, respectively. A
Fab-7
element is switched from a silenced to a mitotically heritable active state by an embryonic pulse of transcription. Here, histone H4 hyperacetylation was found to be associated with
Fab-7
after activation, suggesting that H4 hyperacetylation may be a heritable epigenetic tag of the activated element. Activated
Fab-7
enables transcription of a gene even after withdrawal of the primary transcription factor. This feature may allow epigenetic maintenance of active states of developmental genes after decay of their early embryonic regulators.
Heterozygous Germ Line
hCHK2
Mutations in Li-Fraumeni Syndrome
Authors: Bell Daphne W. , Varley Jennifer M. , Szydlo Tara E. , Kang Deborah H. , Wahrer Doke C. R. , Shannon Kristen E. , Lubratovich Marcie , Verselis Sigitas J. , Isselbacher Kurt J. , Fraumeni Joseph F. , Birch Jillian M. , Li Frederick P. , Garber Judy E. , Haber Daniel A.
Published: July 2002

The
hCHK2
gene encodes the human homolog of the yeast Cds1 and Rad53 G
2
checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in
hCHK2
occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the
TP53
gene. These observations suggest that
hCHK2
is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G
2
checkpoint in yeast.
AIDS as a Zoonosis: Scientific and Public Health Implications
Authors: Hahn Beatrice H. , Shaw George M. , De Kevin M. , Cock  , Sharp Paul M.
Published: July 2002

Evidence of simian immunodeficiency virus (SIV) infection has been reported for 26 different species of African nonhuman primates. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, are the cause of acquired immunodeficiency syndrome (AIDS) in humans. Together, they have been transmitted to humans on at least seven occasions. The implications of human infection by a diverse set of SIVs and of exposure to a plethora of additional human immunodeficiency virus–related viruses are discussed.
Crystal Structure of the Ribonucleoprotein Core of the Signal Recognition Particle
Authors: Batey Robert T. , Rambo Robert P. , Lucast Louise , Rha Brian , Doudna Jennifer A.
Published: July 2002

The signal recognition particle (SRP), a protein-RNA complex conserved in all three kingdoms of life, recognizes and transports specific proteins to cellular membranes for insertion or secretion. We describe here the 1.8 angstrom crystal structure of the universal core of the SRP, revealing protein recognition of a distorted RNA minor groove. Nucleotide analog interference mapping demonstrates the biological importance of observed interactions, and genetic results show that this core is functional in vivo. The structure explains why the conserved residues in the protein and RNA are required for SRP assembly and defines a signal sequence recognition surface composed of both protein and RNA.
Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery
Authors: Rudolph Karl Lenhard , Chang Sandy , Millard Melissa , Schreiber-Agus Nicole , DePinho Ronald A.
Published: July 2002

Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR
−/−
mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of “telomerase therapy” for such diseases.
Green, Catalytic Oxidation of Alcohols in Water
Authors: Brink Gerd-Jan ten , Arends Isabel W. C. E. , Sheldon Roger A.
Published: July 2002

Alcohol oxidations are typically performed with stoichiometric reagents that generate heavy-metal waste and are usually run in chlorinated solvents. A water-soluble palladium(II) bathophenanthroline complex is a stable recyclable catalyst for the selective aerobic oxidation of a wide range of alcohols to aldehydes, ketones, and carboxylic acids in a biphasic water-alcohol system. The use of water as a solvent and air as the oxidant makes the reaction interesting from both an economic and environmental point of view.
Gene Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 Disease
Authors: Cavazzana-Calvo Marina , Hacein-Bey Salima , Basile Geneviève de Saint , Gross Fabian , Yvon Eric , Nusbaum Patrick , Selz Françoise , Hue Christophe , Certain Stéphanie , Casanova Jean-Laurent , Bousso Philippe , Deist Françoise Le , Fischer Alain
Published: July 2002

Severe combined immunodeficiency–X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the γc cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective γc Moloney retrovirus–derived vector and ex vivo infection of CD34
+
cells. After a 10-month follow-up period, γc transgene–expressing T and NK cells were detected in two patients. T, B, and NK cell counts and function, including antigen-specific responses, were comparable to those of age-matched controls. Thus, gene therapy was able to provide full correction of disease phenotype and, hence, clinical benefit.
Structure of the Light-Driven Chloride Pump Halorhodopsin at 1.8 Å Resolution
Authors: Kolbe Michael , Besir Hüseyin , Essen Lars-Oliver , Oesterhelt Dieter
Published: July 2002

Halorhodopsin, an archaeal rhodopsin ubiquitous in Haloarchaea, uses light energy to pump chloride through biological membranes. Halorhodopsin crystals were grown in a cubic lipidic phase, which allowed the x-ray structure determination of this anion pump at 1.8 angstrom resolution. Halorhodopsin assembles to trimers around a central patch consisting of palmitic acid. Next to the protonated Schiff base between Lys
242
and the isomerizable retinal chromophore, a single chloride ion occupies the transport site. Energetic calculations on chloride binding reveal a combination of ion-ion and ion-dipole interactions for stabilizing the anion 18 angstroms below the membrane surface. Ion dragging across the protonated Schiff base explains why chloride and proton translocation modes are mechanistically equivalent in archaeal rhodopsins.
Is El Niño Changing?
Authors: Fedorov Alexey V. , Philander S. George
Published: July 2002

Recent advances in observational and theoretical studies of El Niño have shed light on controversies concerning the possible effect of global warming on this phenomenon over the past few decades and in the future. El Niño is now understood to be one phase of a natural mode of oscillation—La Niña is the complementary phase—that results from unstable interactions between the tropical Pacific Ocean and the atmosphere. Random disturbances maintain this neutrally stable mode, whose properties depend on the background (time-averaged) climate state. Apparent changes in the properties of El Niño could reflect the importance of random disturbances, but they could also be a consequence of decadal variations of the background state. The possibility that global warming is affecting those variations cannot be excluded.
Ultrafast Electron Localization Dynamics Following Photo-Induced Charge Transfer
Authors: Yeh Alvin T. , Shank Charles V. , McCusker James K.
Published: July 2002

Molecular dynamics occurring in the earliest stages following photo-induced charge transfer were investigated. Femtosecond time-resolved absorption anisotropy measurements on [Ru(bpy)
3
]
2+
, where bpy is 2,2′-bipyridine, reveal a time dependence in nitrile solutions attributed to initial delocalization of the excited state over all three ligands followed by charge localization onto a single ligand. The localization process is proposed to be coupled to nondiffusive solvation dynamics. In contrast, measurements sampling population dynamics show spectral evolution associated with wave packet motion on the excited state surface that is independent of solvent. The results therefore reveal two important contributions to the evolution of charge transfer states in condensed phase, one that is strongly coupled to the surrounding environment and another that follows a potential internal to the molecule.
Proximity of Chromosomal Loci That Participate in Radiation-Induced Rearrangements in Human Cells
Authors: Nikiforova Marina N. , Stringer James R. , Blough Ruthann , Medvedovic Mario , Fagin James A. , Nikiforov Yuri E.
Published: July 2002

Rearrangements involving the
RET
gene are common in radiation-associated papillary thyroid cancer (PTC). The
RET
/PTC1 type of rearrangement is an inversion of chromosome 10 mediated by illegitimate recombination between the
RET
and the
H4
genes, which are 30 megabases apart. Here we ask whether despite the great linear distance between them,
RET
and
H4
recombination might be promoted by their proximity in the nucleus. We used two-color fluorescence in situ hybridization and three-dimensional microscopy to map the positions of the
RET
and
H4
loci within interphase nuclei. At least one pair of
RET
and
H4
was juxtaposed in 35% of normal human thyroid cells and in 21% of peripheral blood lymphocytes, but only in 6% of normal mammary epithelial cells. Spatial contiguity of
RET
and
H4
may provide a structural basis for generation of
RET
/PTC1 rearrangement by allowing a single radiation track to produce a double-strand break in each gene at the same site in the nucleus.
Structure of the Protease Domain of Memapsin 2 (β-Secretase) Complexed with Inhibitor
Authors: Hong Lin , Koelsch Gerald , Lin Xinli , Wu Shili , Terzyan Simon , Ghosh Arun K. , Zhang Xuenjun C. , Tang Jordan
Published: July 2002

Memapsin 2 (β-secretase) is a membrane-associated aspartic protease involved in the production of β-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S
4
to S
2
′ are well defined. A kink of the inhibitor chain at P
2
′ and the change of chain direction of P
3
′ and P
4
′ may be mimicked to provide inhibitor selectivity.
Dimer Preparation That Mimics the Transition State for the Adsorption of H
2
on the Si(100)-2 × 1 Surface
Authors: Buehler Emily J. , Boland John J.
Published: July 2002

A chemically induced dimer configuration was prepared on the silicon (Si) (100) surface and was characterized by scanning tunneling microscopy (STM) and spectroscopy (STS). These prepared dimers, which are essentially untilted and differ both electronically and structurally from the dynamically tilting dimers normally found on this surface, are more reactive than normal dimers. For molecular hydrogen (H
2
) adsorption, the enhancement is about 10
9
at room temperature. There is no appreciable barrier for the H
2
reaction at prepared sites, indicating the prepared configuration closely approximates the actual dimer structure in the transition state. This previously unknown ability to prepare specific surface configurations has important implications for understanding and controlling reaction dynamics on semiconductor surfaces.
Hurricane Disturbance and Tropical Tree Species Diversity
Authors: Vandermeer John , Cerda Iñigo Granzow de la , Boucher Douglas , Perfecto Ivette , Ruiz Javier
Published: July 2002

The debate over the maintenance of high diversity of tree species in tropical forests centers on the role of tree-fall gaps as a primary source of disturbance. Using a 10-year data series accumulated since Hurricane Joan struck the Caribbean coast of Nicaragua in 1988, we examined the pattern of species accumulation over time and with increased sampling of individuals. Our analysis shows that the pattern after a hurricane differs from the pattern after a simple tree-fall disturbance, and we conclude that pioneers are limited in large disturbances and thus do not suppress other species the way they do in smaller disturbances.
A Kingdom-Level Phylogeny of Eukaryotes Based on Combined Protein Data
Authors: Baldauf Sandra L. , Roger A. J. , Wenk-Siefert I. , Doolittle W. F.
Published: July 2002

Current understanding of the higher order systematics of eukaryotes relies largely on analyses of the small ribosomal subunit RNA (SSU rRNA). Independent testing of these results is still limited. We have combined the sequences of four of the most broadly taxonomically sampled proteins available to create a roughly parallel data set to that of SSU rRNA. The resulting phylogenetic tree shows a number of striking differences from SSU rRNA phylogeny, including strong support for most major groups and several major supergroups.
From Marrow to Brain: Expression of Neuronal Phenotypes in Adult Mice
Authors: Brazelton Timothy R. , Rossi Fabio M. V. , Keshet Gilmor I. , Blau Helen M.
Published: July 2002

After intravascular delivery of genetically marked adult mouse bone marrow into lethally irradiated normal adult hosts, donor-derived cells expressing neuronal proteins (neuronal phenotypes) developed in the central nervous system. Flow cytometry revealed a population of donor-derived cells in the brain with characteristics distinct from bone marrow. Confocal microscopy of individual cells showed that hundreds of marrow-derived cells in brain sections expressed gene products typical of neurons (NeuN, 200-kilodalton neurofilament, and class III β-tubulin) and were able to activate the transcription factor cAMP response element–binding protein (CREB). The generation of neuronal phenotypes in the adult brain 1 to 6 months after an adult bone marrow transplant demonstrates a remarkable plasticity of adult tissues with potential clinical applications.
Creating Long-Lived Superhydrophobic Polymer Surfaces Through Mechanically Assembled Monolayers
Authors: Genzer Jan , Efimenko Kirill
Published: July 2002

We show that elastomeric surfaces can be tailored using “mechanically assembled monolayers” (MAMs), structures that are fabricated by combining self-assembly of surface grafting molecules with mechanical manipulation of the grafting points in the underlying elastic surface. The versatility of this surface modification method is demonstrated by fabricating MAMs with semifluorinated (SF) molecules. These SF-MAMs have superior nonwetting and barrier properties in that they are “superhydrophobic” and nonpermeable. We also establish that these material characteristics do not deteriorate even after prolonged exposure to water, which usually causes surface reconstruction in conventionally prepared SF self-assembled monolayers.
Complex Disease and the New Clinical Sciences
Authors: Rees Jonathan
Published: July 2002

Medical research today is dominated by a genocentric point of view. At the same time, clinical discovery and patient-oriented research have become less common. Here, I suggest that these developments are interdependent, each representing the flip side of an inaccurate view of how clinical advance occurs.