bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Assembled Aggregates of Rod-Coil Block Copolymers and Their Solubilization and Encapsulation of Fullerenes
Authors: Jenekhe Samson A. , Chen X. Linda
Published: July 2002

Amphiphilic poly(phenylquinoline)-
block
-polystyrene rod-coil diblock copolymers were observed to self-organize into robust, micrometer-scale, spherical, vesicular, cylindrical, and lamellar aggregates from solution. These diverse aggregate morphologies were seen at each composition, but their size scale decreased with a decreasing fraction of the rigid-rod block. Compared to coil-coil block copolymer micelles, the present aggregates are larger by about two orders of magnitude and have aggregation numbers of over 10
8
. The spherical and cylindrical aggregates have large hollow cavities. Only spherical aggregates with aggregation numbers in excess of 10
9
were formed in the presence of fullerenes (C
60
, C
70
) in solution, resulting in the solubilization and encapsulation of over 10
10
fullerene molecules per aggregate.
Mutation in Transcription Factor
POU4F3
Associated with Inherited Progressive Hearing Loss in Humans
Authors: Vahava Oz , Morell Robert , Lynch Eric D. , Weiss Sigal , Kagan Marjory E. , Ahituv Nadav , Morrow Jan E. , Lee Ming K. , Skvorak Anne B. , Morton Cynthia C. , Blumenfeld Anat , Frydman Moshe , Friedman Thomas B. , King Mary-Claire , Avraham Karen B.
Published: July 2002

The molecular basis for autosomal dominant progressive nonsyndromic hearing loss in an Israeli Jewish family, Family H, has been determined. Linkage analysis placed this deafness locus,
DFNA15
, on chromosome 5q31. The human homolog of mouse
Pou4f3
, a member of the POU-domain family of transcription factors whose targeted inactivation causes profound deafness in mice, was physically mapped to the 25-centimorgan DFNA15-linked region. An 8–base pair deletion in the POU homeodomain of human
POU4F3
was identified in Family H. A truncated protein presumably impairs high-affinity binding of this transcription factor in a dominant negative fashion, leading to progressive hearing loss.
The Formation of Chondrules: Petrologic Tests of the Shock Wave Model
Authors: Connolly Harold C. , Love Stanley G.
Published: July 2002

Chondrules are millimeter-sized rounded igneous rocks within chondritic meteorites. Their textures and fractionated mineral chemistries suggest that they formed by repeated, localized, brief (minutes to hours) melting of cold aggregates of mineral dust in the protoplanetary nebula. Astrophysical models of chondrule formation have been unable to explain the petrologically diverse nature of chondrites. However, a nebular shock wave model for chondrule formation agrees with many of the observed petrologic and geochemical properties of chondrules and shows how particles within the nebula are sorted by size and how rims around chondrules are formed. It also explains the volatile-rich nature of chondrule rims and the chondrite matrix.
Time Scales and Heterogeneous Structure in Geodynamic Earth Models
Authors: Bunge Hans-Peter , Richards Mark A. , Lithgow-Bertelloni Carolina , Baumgardner John R. , Grand Stephen P. , Romanowicz Barbara A.
Published: July 2002

Computer models of mantle convection constrained by the history of Cenozoic and Mesozoic plate motions explain some deep-mantle structural heterogeneity imaged by seismic tomography, especially those related to subduction. They also reveal a 150-million-year time scale for generating thermal heterogeneity in the mantle, comparable to the record of plate motion reconstructions, so that the problem of unknown initial conditions can be overcome. The pattern of lowermost mantle structure at the core-mantle boundary is controlled by subduction history, although seismic tomography reveals intense large-scale hot (low-velocity) upwelling features not explicitly predicted by the models.
Strong Regularities in World Wide Web Surfing
Authors: Huberman Bernardo A. , Pirolli Peter L. T. , Pitkow James E. , Lukose Rajan M.
Published: July 2002

One of the most common modes of accessing information in the World Wide Web is surfing from one document to another along hyperlinks. Several large empirical studies have revealed common patterns of surfing behavior. A model that assumes that users make a sequence of decisions to proceed to another page, continuing as long as the value of the current page exceeds some threshold, yields the probability distribution for the number of pages that a user visits within a given Web site. This model was verified by comparing its predictions with detailed measurements of surfing patterns. The model also explains the observed Zipf-like distributions in page hits observed at Web sites.
Environmental Contributions to the Obesity Epidemic
Authors: Hill James O. , Peters John C.
Published: July 2002

The current epidemic of obesity is caused largely by an environment that promotes excessive food intake and discourages physical activity. Although humans have evolved excellent physiological mechanisms to defend against body weight loss, they have only weak physiological mechanisms to defend against body weight gain when food is abundant. Control of portion size, consumption of a diet low in fat and energy density, and regular physical activity are behaviors that protect against obesity, but it is becoming difficult to adopt and maintain these behaviors in the current environment. Because obesity is difficult to treat, public health efforts need to be directed toward prevention.
The Search for Human Obesity Genes
Authors: Comuzzie Anthony G. , Allison David B.
Published: July 2002

Understanding of the genetic influences on obesity has increased at a tremendous rate in recent years. By some estimates, 40 to 70 percent of the variation in obesity-related phenotypes in humans is heritable. Although several single-gene mutations have been shown to cause obesity in animal models, the situation in humans is considerably more complex. The most common forms of human obesity arise from the interactions of multiple genes, environmental factors, and behavior, and this complex etiology makes the search for obesity genes especially challenging. This article discusses the strategies currently being used to search for human obesity genes and recent promising results from these efforts.
Signals That Regulate Food Intake and Energy Homeostasis
Authors: Woods Stephen C. , Seeley Randy J. , Porte Daniel , Schwartz Michael W.
Published: July 2002

Feeding behavior is critical for survival. In addition to providing all of the body's macronutrients (carbohydrates, lipids, and proteins) and most micronutrients (minerals and vitamins), feeding behavior is a fundamental aspect of energy homeostasis, the process by which body fuel stored in the form of adipose tissue is held constant over long intervals. For this process to occur, the amount of energy consumed must match precisely the amount of energy expended. This review focuses on the molecular signals that modulate food intake while integrating the body's immediate and long-term energy needs.
A Defect-Tolerant Computer Architecture: Opportunities for Nanotechnology
Authors: Heath James R. , Kuekes Philip J. , Snider Gregory S. , Williams R. Stanley
Published: July 2002

Teramac is a massively parallel experimental computer built at Hewlett-Packard Laboratories to investigate a wide range of different computational architectures. This machine contains about 220,000 hardware defects, any one of which could prove fatal to a conventional computer, and yet it operated 100 times faster than a high-end single-processor workstation for some of its configurations. The defect-tolerant architecture of Teramac, which incorporates a high communication bandwith that enables it to easily route around defects, has significant implications for any future nanometer-scale computational paradigm. It may be feasible to chemically synthesize individual electronic components with less than a 100 percent yield, assemble them into systems with appreciable uncertainty in their connectivity, and still create a powerful and reliable data communications network. Future nanoscale computers may consist of extremely large-configuration memories that are programmed for specific tasks by a tutor that locates and tags the defects in the system.
The Quantum Event of Oceanic Crustal Accretion: Impacts of Diking at Mid-Ocean Ridges
Authors: Delaney J. R. , Kelley D. S. , Lilley M. D. , Butterfield D. A. , Baross J. A. , Wilcock W. S. D. , Embley R. W. , Summit M.
Published: July 2002

Seafloor diking-eruptive events represent the irreducible, quantum events of upper oceanic crustal accretion. They record events by which a large portion of the oceanic crust has formed through geological history. Since 1993, the U.S. Navy's real-time Sound Surveillance System has allowed location of ongoing acoustic signatures of dike emplacement and basalt eruptions at ridge crests in the northeast Pacific. These diking-eruptive events trigger a sequence of related, rapidly evolving physical, chemical, and biological processes. Magmatic volatiles released during these events may provide nutrients for communities of subseafloor microorganisms, some of which thrive in high-temperature anaerobic environments. Many of the organisms identified from these systems are Archaea. If microorganisms can thrive in the water-saturated pores and cracks within deep, volcanically active portions of our planet, other hydrothermally active planets may harbor similar life forms.
Inactivation of a Serotonin-Gated Ion Channel by a Polypeptide Toxin from Marine Snails
Authors: England Laura J. , Imperial Julita , Jacobsen Richard , Craig A. Grey , Gulyas Joseph , Akhtar Mateen , Rivier Jean , Julius David , Olivera Baldomero M.
Published: July 2002

The venom of predatory marine snails is a rich source of natural products that act on specific receptors and ion channels within the mammalian nervous system. A 41–amino acid peptide, σ-conotoxin GVIIIA, was purified on the basis of its ability to inactivate the 5-HT
3
receptor, an excitatory serotonin-gated ion channel. σ-Conotoxin contains a brominated tryptophan residue, which may be important for peptide activity because the endogenous ligand for the 5-HT
3
receptor is a hydroxylated derivative of tryptophan. σ-Conotoxin inactivates the 5-HT
3
receptor through competitive antagonism and is a highly selective inhibitor of this receptor. Serotonin receptors can now be included among the molecular targets of natural polypeptide neurotoxins.
An Integrated Model of the Transcription Complex in Elongation, Termination, and Editing
Authors: von Hippel Peter H.
Published: July 2002

Recent findings now allow the development of an integrated model of the thermodynamic, kinetic, and structural properties of the transcription complex in the elongation, termination, and editing phases of transcript formation. This model provides an operational framework for placing known facts and can be extended and modified to incorporate new advances. The most complete information about transcriptional mechanisms and their control continues to come from the
Escherichia coli
system, upon which most of the explicit descriptions provided here are based. The transcriptional machinery of higher organisms, despite its greater inherent complexity, appears to use many of the same general principles. Thus, the lessons of
E. coli
continue to be relevant.
Identification of LFA-1 as a Candidate Autoantigen in Treatment-Resistant Lyme Arthritis
Authors: Gross Dawn M. , Forsthuber Thomas , Tary-Lehmann Magdalena , Etling Carey , Ito Kouichi , Nagy Zoltan A. , Field Jodie A. , Steere Allen C. , Huber Brigitte T.
Published: July 2002

Treatment-resistant Lyme arthritis is associated with immune reactivity to outer surface protein A (OspA) of
Borrelia burgdorferi
, the agent of Lyme disease, and the major histocompatibility complex class II allele
DRB1*0401
. The immunodominant epitope of OspA for T helper cells was identified. A homology search revealed a peptide from human leukocyte function–associated antigen-1 (hLFA-1) as a candidate autoantigen. Individuals with treatment-resistant Lyme arthritis, but not other forms of arthritis, generated responses to OspA, hLFA-1, and their highly related peptide epitopes. Identification of the initiating bacterial antigen and a cross-reactive autoantigen may provide a model for development of autoimmune disease.
Imperfect Oriented Attachment: Dislocation Generation in Defect-Free Nanocrystals
Authors: Penn R. Lee , Banfield Jillian F.
Published: July 2002

Dislocations are common defects in solids, yet all crystals begin as dislocation-free nuclei. The mechanisms by which dislocations form during early growth are poorly understood. When nanocrystalline materials grow by oriented attachment at crystallographically specific surfaces and there is a small misorientation at the interface, dislocations result. Spiral growth at two or more closely spaced screw dislocations provides a mechanism for generating complex polytypic and polymorphic structures. These results are of fundamental importance to understanding crystal growth.
Long-Range Electrostatic Trapping of Single-Protein Molecules at a Liquid-Solid Interface
Authors: Xu Xiao-Hong Nancy , Yeung Edward S.
Published: July 2002

The motion of single, dye-labeled protein molecules was monitored at various pH and ionic strengths within the 180-nanometer-thick evanescent-field layer at a fused-silica surface. Below the isoelectric point, molecules partitioning into the excitation region increased in number but maintained a random spatial distribution, implying that surface charge can influence the charged protein at distances beyond that of the electrical double-layer thickness. The residence times of the molecules in the interfacial layer also increased below the isoelectric point. However, immobilization on the solid surface for extended periods was not observed. Histograms of residence times exhibit nearly identical asymmetry as the corresponding elution peaks in capillary electrophoresis. These results are a direct verification of the statistical theory of chromatography at the single-molecule level, with the caveat that long-range trapping rather than adsorption is the dominant mechanism.
Ancient Mantle in a Modern Arc: Osmium Isotopes in Izu-Bonin-Mariana Forearc Peridotites
Authors: Parkinson Ian J. , Hawkesworth Chris J. , Cohen Anthony S.
Published: July 2002

Mantle peridotites drilled from the Izu-Bonin-Mariana forearc have unradiogenic
187
Os/
188
Os ratios (0.1193 to 0.1273), which give Proterozoic model ages of 820 to 1230 million years ago. If these peridotites are residues from magmatism during the initiation of subduction 40 to 48 million years ago, then the mantle that melted was much more depleted in incompatible elements than the source of mid-ocean ridge basalts (MORB). This result indicates that osmium isotopes record information about ancient melting events in the convecting upper mantle not recorded by incompatible lithophile isotope tracers. Subduction zones may be a graveyard for ancient depleted mantle material, and portions of the convecting upper mantle may be less radiogenic in osmium isotopes than previously recognized.
Tomographic Evidence for Localized Lithospheric Shear Along the Altyn Tagh Fault
Authors: Wittlinger Gérard , Tapponnier Paul , Poupinet Georges , Mei Jiang , Danian Shi , Herquel Georges , Masson Frédéric
Published: July 2002

Seismic tomography across the Altyn Tagh fault, at the north edge of the Tibetan Plateau, reveals a low
P
-wave velocity anomaly below the fault down to 140 kilometers. This anomaly probably reflects strike-slip shear in the lithosphere. Slip-partitioning may also induce a wedge of crust from the Tarim Basin to plunge into the mantle.
Direct Measurement of Femtomoles of Osmium and the
187
Os/
186
Os Ratio in Seawater
Authors: Levasseur Sylvain , Birck Jean-Louis , Allègre Claude J.
Published: July 2002

Two depth profiles of the osmium concentration and the
187
Os/
186
Os isotopic ratio in the Indian Ocean showed that the osmium concentration seems to be unaltered by chemical or biological processes occuring in seawater; accordingly, osmium is conservative. These data were obtained from an experimental method that eliminated the problems related to osmium preconcentration. This method led to a new evaluation of the concentration of osmium in seawater; the mean concentration of osmium and the
187
Os/
186
Os ratio are equal to 10.86 ± 0.07 picograms per kilogram and 8.80 ± 0.07, respectively. The results suggest the existence of an organocomplex that dominates the speciation of osmium in seawater.
An Integrated Nanoliter DNA Analysis Device
Authors: Burns Mark A. , Johnson Brian N. , Brahmasandra Sundaresh N. , Handique Kalyan , Webster James R. , Krishnan Madhavi , Sammarco Timothy S. , Man Piu M. , Jones Darren , Heldsinger Dylan , Mastrangelo Carlos H. , Burke David T.
Published: July 2002

A device was developed that uses microfabricated fluidic channels, heaters, temperature sensors, and fluorescence detectors to analyze nanoliter-size DNA samples. The device is capable of measuring aqueous reagent and DNA-containing solutions, mixing the solutions together, amplifying or digesting the DNA to form discrete products, and separating and detecting those products. No external lenses, heaters, or mechanical pumps are necessary for complete sample processing and analysis. Because all of the components are made using conventional photolithographic production techniques, they operate as a single closed system. The components have the potential for assembly into complex, low-power, integrated analysis systems at low unit cost. The availability of portable, reliable instruments may facilitate the use of DNA analysis in applications such as rapid medical diagnostics and point-of-use agricultural testing.
Unconditional Quantum Teleportation
Authors: Furusawa A. , Sørensen J. L. , Braunstein S. L. , Fuchs C. A. , Kimble H. J. , Polzik E. S.
Published: July 2002

Quantum teleportation of optical coherent states was demonstrated experimentally using squeezed-state entanglement. The quantum nature of the achieved teleportation was verified by the experimentally determined fidelity
F
exp
= 0.58 ± 0.02, which describes the match between input and output states. A fidelity greater than 0.5 is not possible for coherent states without the use of entanglement. This is the first realization of unconditional quantum teleportation where every state entering the device is actually teleported.
Predictability in the Midst of Chaos: A Scientific Basis for Climate Forecasting
Authors: Shukla J.
Published: July 2002

The Earth's atmosphere is generally considered to be an example of a chaotic system that is sensitively dependent on initial conditions. It is shown here that certain regions of the atmosphere are an exception. Wind patterns and rainfall in certain regions of the tropics are so strongly determined by the temperature of the underlying sea surface that they do not show sensitive dependence on the initial conditions of the atmosphere. Therefore, it should be possible to predict the large-scale tropical circulation and rainfall for as long as the ocean temperature can be predicted. If changes in tropical Pacific sea-surface temperature are quite large, even the extratropical circulation over some regions, especially over the Pacific–North American sector, is predictable.
Heterocyst Pattern Formation Controlled by a Diffusible Peptide
Authors: Yoon Ho-Sung , Golden James W.
Published: July 2002

Many filamentous cyanobacteria grow as multicellular organisms that show a developmental pattern of single nitrogen-fixing heterocysts separated by approximately 10 vegetative cells. Overexpression of a 54–base-pair gene,
patS
, blocked heterocyst differentiation in
Anabaena
sp. strain PCC 7120. A
patS
null mutant showed an increased frequency of heterocysts and an abnormal pattern. Expression of a
patS
-
gfp
reporter was localized in developing proheterocysts. The addition of a synthetic peptide corresponding to the last five amino acids of PatS inhibited heterocyst development. PatS appears to control heterocyst pattern formation through intercellular signaling mechanisms.
Requirement for p53 and p21 to Sustain G
2
Arrest After DNA Damage
Authors: Bunz F. , Dutriaux A. , Lengauer C. , Waldman T. , Zhou S. , Brown J. P. , Sedivy J. M. , Kinzler K. W. , Vogelstein B.
Published: July 2002

After DNA damage, many cells appear to enter a sustained arrest in the G
2
phase of the cell cycle. It is shown here that this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21. After disruption of either the p53 or the p21 gene, γ radiated cells progressed into mitosis and exhibited a G
2
DNA content only because of a failure of cytokinesis. Thus, p53 and p21 appear to be essential for maintaining the G
2
checkpoint in human cells.
Genome Sequence of the Nematode
C. elegans
: A Platform for Investigating Biology
Authors:   The C. elegans Sequencing Consortium*
Published: July 2002

The 97-megabase genomic sequence of the nematode
Caenorhabditis elegans
reveals over 19,000 genes. More than 40 percent of the predicted protein products find significant matches in other organisms. There is a variety of repeated sequences, both local and dispersed. The distinctive distribution of some repeats and highly conserved genes provides evidence for a regional organization of the chromosomes.
Neurobiology of the
Caenorhabditis elegans
Genome
Authors: Bargmann Cornelia I.
Published: July 2002

Neurotransmitter receptors, neurotransmitter synthesis and release pathways, and heterotrimeric GTP–binding protein (G protein)–coupled second messenger pathways are highly conserved between
Caenorhabditis elegans
and mammals, but gap junctions and chemosensory receptors have independent origins in vertebrates and nematodes. Most ion channels are similar to vertebrate channels but there are no predicted voltage-activated sodium channels. The
C. elegans
genome encodes at least 80 potassium channels, 90 neurotransmitter-gated ion channels, 50 peptide receptors, and up to 1000 orphan receptors that may be chemoreceptors. For many gene families,
C. elegans
has both conventional members and divergent outliers with weak homology to known genes; these outliers may provide insights into previously unknown functions of conserved protein families.
Chain Length Recognition: Core-Shell Supramolecular Assembly from Oppositely Charged Block Copolymers
Authors: Harada Atsushi , Kataoka Kazunori
Published: July 2002

Molecular recognition based on length was found to occur between oppositely charged pairs of flexible and randomly coiled block copolymers in an aqueous milieu. Matched pairs with the same block lengths of polyanions and polycations exclusively formed even in mixtures with different block lengths. These assemblies of the charged segments with matched chain lengths then formed larger core-shell–type supramolecular assemblies with an extremely narrow size distribution due to the strict phase separation between core- and shell-forming segments.
Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain
Authors: Ikonomidou Chrysanthy , Bosch Friederike , Miksa Michael , Bittigau Petra , Vöckler Jessica , Dikranian Krikor , Tenkova Tanya I. , Stefovska Vanya , Turski Lechoslaw , Olney John W.
Published: July 2002

Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. Blockade of
N
-methyl-
d
-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival. These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors.
Emergent Properties of Networks of Biological Signaling Pathways
Authors: Bhalla Upinder S. , Iyengar Ravi
Published: July 2002

Many distinct signaling pathways allow the cell to receive, process, and respond to information. Often, components of different pathways interact, resulting in signaling networks. Biochemical signaling networks were constructed with experimentally obtained constants and analyzed by computational methods to understand their role in complex biological processes. These networks exhibit emergent properties such as integration of signals across multiple time scales, generation of distinct outputs depending on input strength and duration, and self-sustaining feedback loops. Feedback can result in bistable behavior with discrete steady-state activities, well-defined input thresholds for transition between states and prolonged signal output, and signal modulation in response to transient stimuli. These properties of signaling networks raise the possibility that information for “learned behavior” of biological systems may be stored within intracellular biochemical reactions that comprise signaling pathways.
13
C-Depleted Carbon Microparticles in >3700-Ma Sea-Floor Sedimentary Rocks from West Greenland
Authors: Rosing Minik T.
Published: July 2002

Turbiditic and pelagic sedimentary rocks from the Isua supracrustal belt in west Greenland [more than 3700 million years ago (Ma)] contain reduced carbon that is likely biogenic. The carbon is present as 2- to 5-micrometer graphite globules and has an isotopic composition of δ
13
C that is about –19 per mil (Pee Dee belemnite standard). These data and the mode of occurrence indicate that the reduced carbon represents biogenic detritus, which was perhaps derived from planktonic organisms.
Ancient Diets, Ecology, and Extinction of 5-Million-Year-Old Horses from Florida
Authors: MacFadden Bruce J. , Solounias Nikos , Cerling Thure E.
Published: July 2002

Six sympatric species of 5-million-year-old (late Hemphillian) horses from Florida existed during a time of major global change and extinction in terrestrial ecosystems. Traditionally, these horses were interpreted to have fed on abrasive grasses because of their high-crowned teeth. However, carbon isotopic and tooth microwear data indicate that these horses were not all C
4
grazers but also included mixed feeders and C
3
browsers. The late Hemphillian Florida sister species of the modern genus
Equus
was principally a browser, unlike the grazing diet of modern equids. Late Hemphillian horse extinctions in Florida involved two grazing and one browsing species.
Mycolactone: A Polyketide Toxin from
Mycobacterium ulcerans
Required for Virulence
Authors: George Kathleen M. , Chatterjee Delphi , Gunawardana Geewananda , Welty Diane , Hayman John , Lee Richard , Small P. L. C.
Published: July 2002

Mycobacterium ulcerans
is the causative agent of Buruli ulcer, a severe human skin disease that occurs primarily in Africa and Australia. Infection with
M. ulcerans
results in persistent severe necrosis without an acute inflammatory response. The presence of histopathological changes distant from the site of infection suggested that pathogenesis might be toxin mediated. A polyketide-derived macrolide designated mycolactone was isolated that causes cytopathicity and cell cycle arrest in cultured L929 murine fibroblasts. Intradermal inoculation of purified toxin into guinea pigs produced a lesion similar to that of Buruli ulcer in humans. This toxin may represent one of a family of virulence factors associated with pathology in mycobacterial diseases such as leprosy and tuberculosis.
Magma Flow Instability and Cyclic Activity at Soufriere Hills Volcano, Montserrat, British West Indies
Authors: Voight B. , Sparks R. S. J. , Miller A. D. , Stewart R. C. , Hoblitt R. P. , Clarke A. , Ewart J. , Aspinall W. P. , Baptie B. , Calder E. S. , Cole P. , Druitt T. H. , Hartford C. , Herd R. A. , Jackson P. , Lejeune A. M. , Lockhart A. B. , Loughlin S. C. , Luckett R. , Lynch L. , Norton G. E. , Robertson R. , Watson I. M. , Watts R. , Young S. R.
Published: July 2002

Dome growth at the Soufriere Hills volcano (1996 to 1998) was frequently accompanied by repetitive cycles of earthquakes, ground deformation, degassing, and explosive eruptions. The cycles reflected unsteady conduit flow of volatile-charged magma resulting from gas exsolution, rheological stiffening, and pressurization. The cycles, over hours to days, initiated when degassed stiff magma retarded flow in the upper conduit. Conduit pressure built with gas exsolution, causing shallow seismicity and edifice inflation. Magma and gas were then expelled and the edifice deflated. The repeat time-scale is controlled by magma ascent rates, degassing, and microlite crystallization kinetics. Cyclic behavior allows short-term forecasting of timing, and of eruption style related to explosivity potential.
Regulation of Chamber-Specific Gene Expression in the Developing Heart by
Irx4
Authors: Bao Zheng-Zheng , Bruneau Benoit G. , Seidman J. G. , Seidman Christine E. , Cepko Constance L.
Published: July 2002

The vertebrate heart consists of two types of chambers, the atria and the ventricles, which differ in their contractile and electrophysiological properties. Little is known of the molecular mechanisms by which these chambers are specified during embryogenesis. Here a chicken
iroquois
-related homeobox gene,
Irx4
, was identified that has a ventricle-restricted expression pattern at all stages of heart development. Irx4 protein was shown to regulate the chamber-specific expression of myosin isoforms by activating the expression of the ventricle myosin heavy chain–1 (
VMHC1
) and suppressing the expression of the atrial myosin heavy chain–1 (
AMHC1
) in the ventricles. Thus, Irx4 may play a critical role in establishing chamber-specific gene expression in the developing heart.
Single-Polymer Dynamics in Steady Shear Flow
Authors: Smith Douglas E. , Babcock Hazen P. , Chu Steven
Published: July 2002

The conformational dynamics of individual, flexible polymers in steady shear flow were directly observed by the use of video fluorescence microscopy. The probability distribution for the molecular extension was determined as a function of shear rate, γ˙, for two different polymer relaxation times, τ. In contrast to the behavior in pure elongational flow, the average polymer extension in shear flow does not display a sharp coil-stretch transition. Large, aperiodic temporal fluctuations were observed, consistent with end-over-end tumbling of the molecule. The rate of these fluctuations (relative to the relaxation rate) increased as the Weissenberg number,γ˙τ, was increased.
Abnormal Spindle Protein, Asp, and the Integrity of Mitotic Centrosomal Microtubule Organizing Centers
Authors: do Carmo Avides Maria , Glover David M.
Published: July 2002

The product of the
abnormal spindle
(
asp
) gene was found to be an asymmetrically localized component of the centrosome during mitosis, required to focus the poles of the mitotic spindle in vivo. Removing Asp protein function from
Drosophila melanogaster
embryo extracts, either by mutation or immunodepletion, resulted in loss of their ability to restore microtubule-organizing center activity to salt-stripped centrosome preparations. This was corrected by addition of purified Asp protein. Thus, Asp appears to hold together the microtubule-nucleating γ-tubulin ring complexes that organize the mitotic centrosome.
Role of Pitx1 Upstream of Tbx4 in Specification of Hindlimb Identity
Authors: Logan Malcolm , Tabin Clifford J.
Published: July 2002

In spite of recent breakthroughs in understanding limb patterning, the genetic factors determining the differences between the forelimb and the hindlimb have not been understood. The genes
Pitx1
and
Tbx4
encode transcription factors that are expressed throughout the developing hindlimb but not forelimb buds. Misexpression of
Pitx1
in the chick wing bud induced distal expression of
Tbx4
, as well as
HoxC10
and
HoxC11
, which are normally restricted to hindlimb expression domains. Wing buds in which
Pitx1
was misexpressed developed into limbs with some morphological characteristics of hindlimbs: the flexure was altered to that normally observed in legs, the digits were more toe-like in their relative size and shape, and the muscle pattern was transformed to that of a leg.
Notch Signaling: Cell Fate Control and Signal Integration in Development
Authors: Artavanis-Tsakonas Spyros , Rand Matthew D. , Lake Robert J.
Published: July 2002

Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development. Signals exchanged between neighboring cells through the Notch receptor can amplify and consolidate molecular differences, which eventually dictate cell fates. Thus, Notch signals control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis.
A Mid-European Decadal Isotope-Climate Record from 15,500 to 5000 Years B.P.
Authors: Grafenstein Ulrich von , Erlenkeuser Helmut , Brauer Achim , Jouzel Jean , Johnsen Sigfus J.
Published: July 2002

Oxygen-isotope ratios of precipitation (δ
18
O
P
) inferred from deep-lake ostracods from the Ammersee (southern Germany) provide a climate record with decadal resolution. The record in detail shows many of the rapid climate shifts seen in central Greenland ice cores between 15,000 and 5000 years before the present (B.P.). Negative excursions in the estimated δ
18
O
P
from both of these records likely reflect short weakenings of the thermohaline circulation caused by episodic discharges of continental freshwater into the North Atlantic. Deviating millennial-scale trends, however, indicate that climate gradients between Europe and Greenland changed systematically, reflecting a gradual rearrangement of North Atlantic circulation during deglaciation.
Microfabrication Inside Capillaries Using Multiphase Laminar Flow Patterning
Authors: Kenis Paul J. A. , Ismagilov Rustem F. , Whitesides George M.
Published: July 2002

The reaction of species in solutions flowing laminarly (without turbulent mixing) inside capillaries was used as the basis for a broadly applicable method of microfabrication. In this method, patterning occurs as a result of transport of reactive species to interfaces within the capillary by laminar flow. A wide range of chemistries can be used to generate structures with feature sizes of less than 5 micrometers and with spatial localization to within 5 micrometers. The method is applicable to the patterning of metals, organic polymers, inorganic crystals, and ceramics on the inner walls of preformed capillaries, using both additive and subtractive processes.
Mechanisms of Climate Warming at the End of the Paleocene
Authors: Bains Santo , Corfield Richard M. , Norris Richard D.
Published: July 2002

An abrupt episode of global warming marked the end of the Paleocene epoch. Oxygen and carbon isotope records from two widely separated sites support the notion that degassing of biogenic methane hydrate may have been an important factor in altering Earth's climate. The data show evidence for multiple injections of methane, separated by intervals in which the carbon cycle was in stasis. Correlations between the two sites suggest that even these small-scale events were global in nature.
Cell Activation and Apoptosis by Bacterial Lipoproteins Through Toll-like Receptor-2
Authors: Aliprantis Antonios O. , Yang Ruey-Bing , Mark Melanie R. , Suggett Shelly , Devaux Brigitte , Radolf Justin D. , Klimpel Gary R. , Godowski Paul , Zychlinsky Arturo
Published: July 2002

Apoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens. All bacterial pathogens produce lipoproteins (BLPs), which trigger the innate immune response. BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor–2 (hTLR2). BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2. In addition, BLPs stimulated nuclear factor–κB, a transcriptional activator of multiple host defense genes, and activated the respiratory burst through hTLR2. Thus, hTLR2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.
AP-2 Recruitment to Synaptotagmin Stimulated by Tyrosine-Based Endocytic Motifs
Authors: Haucke Volker , Camilli Pietro De
Published: July 2002

Clathrin-mediated endocytosis is initiated by the recruitment of the clathrin adaptor protein AP-2 to the plasma membrane where the membrane protein synaptotagmin is thought to act as a docking site. AP-2 also interacts with endocytic motifs present in other cargo proteins. Peptides with a tyrosine-based endocytic motif stimulated binding of AP-2 to synaptotagmin and enhanced AP-2 recruitment to the plasma membrane of neuronal and non-neuronal cells. This suggests a mechanism by which nucleation of clathrin-coated pits is stimulated by the loading of cargo proteins.
Asteroidal Water Within Fluid Inclusion-Bearing Halite in an H5 Chondrite, Monahans (1998)
Authors: Zolensky Michael E. , Bodnar Robert J. , Gibson Everett K. , Nyquist Laurence E. , Reese Young , Shih Chi-Yu , Wiesmann Henry
Published: July 2002

Crystals of halite and sylvite within the Monahans (1998) H5 chondrite contain aqueous fluid inclusions. The fluids are dominantly sodium chloride–potassium chloride brines, but they also contain divalent cations such as iron, magnesium, or calcium. Two possible origins for the brines are indigenous fluids flowing within the asteroid and exogenous fluids delivered into the asteroid surface from a salt-containing icy object.
Fossil Plants and Global Warming at the Triassic-Jurassic Boundary
Authors: McElwain J. C. , Beerling D. J. , Woodward F. I.
Published: July 2002

The Triassic-Jurassic boundary marks a major faunal mass extinction, but records of accompanying environmental changes are limited. Paleobotanical evidence indicates a fourfold increase in atmospheric carbon dioxide concentration and suggests an associated 3° to 4°C “greenhouse” warming across the boundary. These environmental conditions are calculated to have raised leaf temperatures above a highly conserved lethal limit, perhaps contributing to the >95 percent species-level turnover of Triassic-Jurassic megaflora.
Postdoctoral Patterns, Career Advancement, and Problems
Authors: Nerad Maresi , Cerny Joseph
Published: July 2002

Postdoctoral appointments can have different functions and meanings, depending on the field and whether the postdoc is a man or a woman. The
Ph.D.'s—Ten Years Later
study confirmed that in biochemistry, the postdoc, not the Ph.D., has become the general proving ground for excellence both in academia and industry. Because they spent a longer time in these “mandatory” postdocs, biochemists had the largest proportion of untenured faculty 10 to 13 years after the Ph.D. In mathematics, where substantially fewer postdoctoral positions are available, Ph.D.'s taking postdocs are more likely to obtain faculty positions, but this is true only for men. University administrators should be accountable for monitoring the total time spent in these positions and should provide administrative assistance for skills training, career growth, and the job search. In addition, creative solutions concerning the dual-career couple phenomenon are necessary.
Constitutive Activation of Toll-Mediated Antifungal Defense in Serpin-Deficient
Drosophila
Authors: Levashina Elena A. , Langley Emma , Green Clare , Gubb David , Ashburner Michael , Hoffmann Jules A. , Reichhart Jean-Marc
Published: July 2002

The antifungal defense of
Drosophila
is controlled by the
spaetzle/Toll/cactus
gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by the
spaetzle
and
Toll
gene products. Spaetzle was cleaved by proteolytic enzymes to its active ligand form shortly after immune challenge, and cleaved Spaetzle was constitutively present in
Spn43Ac
-deficient flies. Hence,
Spn43Ac
negatively regulates the Toll signaling pathway, and Toll does not function as a pattern recognition receptor in the
Drosophila
host defense.
X-ray Crystallographic Structure of the Norwalk Virus Capsid
Authors: Prasad B. V. V. , Hardy Michele E. , Dokland Terje , Bella Jordi , Rossmann Michael G. , Estes Mary K.
Published: July 2002

Norwalk virus, a noncultivatable human calicivirus, is the major cause of epidemic gastroenteritis in humans. The first x-ray structure of a calicivirus capsid, which consists of 180 copies of a single protein, has been determined by phase extension from a low-resolution electron microscopy structure. The capsid protein has a protruding (P) domain connected by a flexible hinge to a shell (S) domain that has a classical eight-stranded β-sandwich motif. The structure of the P domain is unlike that of any other viral protein with a subdomain exhibiting a fold similar to that of the second domain in the eukaryotic translation elongation factor–Tu. This subdomain, located at the exterior of the capsid, has the largest sequence variation among Norwalk-like human caliciviruses and is likely to contain the determinants of strain specificity and cell binding.
Evolutionarily Conserved Pathways of Energetic Connectivity in Protein Families
Authors: Lockless Steve W. , Ranganathan Rama
Published: July 2002

For mapping energetic interactions in proteins, a technique was developed that uses evolutionary data for a protein family to measure statistical interactions between amino acid positions. For the PDZ domain family, this analysis predicted a set of energetically coupled positions for a binding site residue that includes unexpected long-range interactions. Mutational studies confirm these predictions, demonstrating that the statistical energy function is a good indicator of thermodynamic coupling in proteins. Sets of interacting residues form connected pathways through the protein fold that may be the basis for efficient energy conduction within proteins.
A Direct Estimate of the Human αβ T Cell Receptor Diversity
Authors: Arstila T. Petteri , Casrouge Armanda , Baron Véronique , Even Jos , Kanellopoulos Jean , Kourilsky Philippe
Published: July 2002

Generation and maintenance of an effective repertoire of T cell antigen receptors are essential to the immune system, yet the number of distinct T cell receptors (TCRs) expressed by the estimated 10
12
T cells in the human body is not known. In this study, TCR gene amplification and sequencing showed that there are about 10
6
different β chains in the blood, each pairing, on the average, with at least 25 different α chains. In the memory subset, the diversity decreased to 1 × 10
5
to 2 × 10
5
different β chains, each pairing with only a single α chain. Thus, the naı̈ve repertoire is highly diverse, whereas the memory compartment, here one-third of the T cell population, contributes less than 1 percent of the total diversity.
Persistence of Memory CD8 T Cells in MHC Class I-Deficient Mice
Authors: Murali-Krishna Kaja , Lau Lisa L. , Sambhara Suryaprakash , Lemonnier Francois , Altman John , Ahmed Rafi
Published: July 2002

An understanding of how T cell memory is maintained is crucial for the rational design of vaccines. Memory T cells were shown to persist indefinitely in major histocompatibility complex (MHC) class I–deficient mice and retained the ability to make rapid cytokine responses upon reencounter with antigen. In addition, memory CD8 T cells, unlike naı̈ve cells, divided without MHC–T cell receptor interactions. This “homeostatic” proliferation is likely to be important in maintaining memory T cell numbers in the periphery. Thus, after naı̈ve CD8 T cells differentiate into memory cells, they evolve an MHC class I–independent “life-style” and do not require further stimulation with specific or cross-reactive antigen for their maintenance.
A Breakdown of
Brassica
Self-Incompatibility in ARC1 Antisense Transgenic Plants
Authors: Stone Sophia L. , Arnoldo MaryAnne , Goring Daphne R.
Published: July 2002

Self-incompatibility, the rejection of self pollen, is the most widespread mechanism by which flowering plants prevent inbreeding. In
Brassica
, the S receptor kinase (SRK) has been implicated in the self-incompatibility response, but the molecular mechanisms involving SRK are unknown. One putative downstream effector for SRK is ARC1, a protein that binds to the SRK kinase domain. Here it is shown that suppression of ARC1 messenger RNA levels in the self-incompatible
Brassica napus
W1 line is correlated with a partial breakdown of self-incompatibility, resulting in seed production. This provides strong evidence that ARC1 is a positive effector of the
Brassica
self-incompatibility response.
Building Neural Representations of Habits
Authors: Jog Mandar S. , Kubota Yasuo , Connolly Christopher I. , Hillegaart Viveka , Graybiel Ann M.
Published: July 2002

Memories for habits and skills (“implicit or procedural memory”) and memories for facts (“explicit or episodic memory”) are built up in different brain systems and are vulnerable to different neurodegenerative disorders in humans. So that the striatum-based mechanisms underlying habit formation could be studied, chronic recordings from ensembles of striatal neurons were made with multiple tetrodes as rats learned a T-maze procedural task. Large and widely distributed changes in the neuronal activity patterns occurred in the sensorimotor striatum during behavioral acquisition, culminating in task-related activity emphasizing the beginning and end of the automatized procedure. The new ensemble patterns remained stable during weeks of subsequent performance of the same task. These results suggest that the encoding of action in the sensorimotor striatum undergoes dynamic reorganization as habit learning proceeds.
Complex Shear Wave Velocity Structure Imaged Beneath Africa and Iceland
Authors: Ritsema Jeroen , Heijst Hendrik Jan van , Woodhouse John H.
Published: July 2002

A model of three-dimensional shear wave velocity variations in the mantle reveals a tilted low velocity anomaly extending from the core-mantle boundary (CMB) region beneath the southeastern Atlantic Ocean into the upper mantle beneath eastern Africa. This anomaly suggests that Cenozoic flood basalt volcanism in the Afar region and active rifting beneath the East African Rift is linked to an extensive thermal anomaly at the CMB more than 45 degrees away. In contrast, a low velocity anomaly beneath Iceland is confined to the upper mantle.
Perforin Gene Defects in Familial Hemophagocytic Lymphohistiocytosis
Authors: Stepp Susan E. , Dufourcq-Lagelouse Rémi , Deist Françoise Le , Bhawan Sadhna , Certain Stéphanie , Mathew Porunelloor A. , Henter Jan-Inge , Bennett Michael , Fischer Alain , Basile Geneviève de Saint , Kumar Vinay
Published: July 2002

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, rapidly fatal, autosomal recessive immune disorder characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines. Linkage analyses indicate that FHL is genetically heterogeneous and linked to 9q21.3-22, 10q21-22, or another as yet undefined locus. Sequencing of the coding regions of the perforin gene of eight unrelated 10q21-22–linked FHL patients revealed homozygous nonsense mutations in four patients and missense mutations in the other four patients. Cultured lymphocytes from patients had defective cytotoxic activity, and immunostaining revealed little or no perforin in the granules. Thus, defects in perforin are responsible for 10q21-22–linked FHL. Perforin-based effector systems are, therefore, involved not only in the lysis of abnormal cells but also in the down-regulation of cellular immune activation.