bluuebunny/crossref_metadata_2025 huggingface dataset:
The Structure of the Potassium Channel: Molecular Basis of K
+
Conduction and Selectivity
Authors: Doyle Declan A. , Cabral João Morais , Pfuetzner Richard A. , Kuo Anling , Gulbis Jacqueline M. , Cohen Steven L. , Chait Brian T. , MacKinnon Roderick
Published: July 2002

The potassium channel from
Streptomyces lividans
is an integral membrane protein with sequence similarity to all known K
+
channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 angstroms long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. Main chain carbonyl oxygen atoms from the K
+
channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K
+
ions but not smaller Na
+
ions. The selectivity filter contains two K
+
ions about 7.5 angstroms apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K
+
ions and the selectivity filter. The architecture of the pore establishes the physical principles underlying selective K
+
conduction.
Autoinducer of Virulence As a Target for Vaccine and Therapy AgainstStaphylococcus aureus
Authors: Balaban Naomi , Goldkorn Tzipora , Nhan Rachael T. , Dang Luong B. , Scott Steven , Ridgley Rose M. , Rasooly Avraham , Wright Susan C. , Larrick James W. , Rasooly Reuven , Carlson James R.
Published: July 2002

Staphylococcus aureuscauses pathologies ranging from minor skin infections to life-threatening diseases. Pathogenic effects are largely due to production of bacterial toxin, which is regulated by an RNA molecule, RNAIII. TheS. aureusprotein called RAP (RNAIII activating protein) activates RNAIII, and a peptide called RIP (RNAIII inhibiting peptide), produced by a nonpathogenic bacteria, inhibits RNAIII. Mice vaccinated with RAP or treated with purified or synthetic RIP were protected fromS. aureuspathology. Thus, these two molecules may provide useful approaches for the prevention and treatment of diseases caused byS. aureus.
A 100,000-Year Periodicity in the Accretion Rate of Interplanetary Dust
Authors: Kortenkamp Stephen J. , Dermott Stanley F.
Published: July 2002

Numerical modeling of the orbital evolution of interplanetary dust particles revealed that, over the past 1.2 million years, the rate of accretion of dust by Earth has varied by a factor of 2 to 3. These variations display a 100,000-year periodicity and are anticorrelated with Earth's changing orbital eccentricity. Extraterrestrial helium-3 concentrations in a deep-sea sediment core display a similar periodicity but are 50,000 years out of phase with the predicted variations. Also, because collisions between large bodies in the asteroid belt are inevitable, it is expected that large-amplitude stochastic variations on 107- to 108-year time scales would be superimposed on the 105-year periodic variations.
Entry of Alphaherpesviruses Mediated by Poliovirus Receptor-Related Protein 1 and Poliovirus Receptor
Authors: Geraghty Robert J. , Krummenacher Claude , Cohen Gary H. , Eisenberg Roselyn J. , Spear Patricia G.
Published: July 2002

A human member of the immunoglobulin superfamily was shown to mediate entry of several alphaherpesviruses, including herpes simplex viruses (HSV) 1 and 2, porcine pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1). This membrane glycoprotein is poliovirus receptor-related protein 1 (Prr1), designated here as HveC. Incubation of HSV-1 with a secreted form of HveC inhibited subsequent infection of a variety of cell lines, suggesting that HveC interacts directly with the virus. Poliovirus receptor (Pvr) itself mediated entry of PRV and BHV-1 but not of the HSV strains tested. HveC was expressed in human cells of epithelial and neuronal origin; it is the prime candidate for the coreceptor that allows both HSV-1 and HSV-2 to infect epithelial cells on mucosal surfaces and spread to cells of the nervous system.
Direct Stimulation of the Guanine Nucleotide Exchange Activity of p115 RhoGEF by Gα
13
Authors: Hart Matthew J. , Jiang Xuejun , Kozasa Tohru , Roscoe William , Singer William D. , Gilman Alfred G. , Sternweis Paul C. , Bollag Gideon
Published: July 2002

Signaling pathways that link extracellular factors to activation of the monomeric guanosine triphosphatase (GTPase) Rho control cytoskeletal rearrangements and cell growth. Heterotrimeric guanine nucleotide–binding proteins (G proteins) participate in several of these pathways, although their mechanisms are unclear. The GTPase activities of two G protein α subunits, Gα
12
and Gα
13
, are stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated Gα
13
bound tightly to p115 RhoGEF and stimulated its capacity to catalyze nucleotide exchange on Rho. In contrast, activated Gα
12
inhibited stimulation by Gα
13
. Thus, p115 RhoGEF can directly link heterotrimeric G protein α subunits to regulation of Rho.
Preparation of Photonic Crystals Made of Air Spheres in Titania
Authors: Wijnhoven Judith E. G. J. , Vos Willem L.
Published: July 2002

Three-dimensional crystals of air spheres in titania (TiO2) with radii between 120 and 1000 nanometers were made by filling the voids in artificial opals by precipitation from a liquid-phase chemical reaction and subsequently removing the original opal material by calcination. These macroporous materials are a new class of photonic band gap crystals for the optical spectrum. Scanning electron microscopy, Raman spectroscopy, and optical microscopy confirm the quality of the samples, and optical reflectivity demonstrates that the crystals are strongly photonic and near that needed to exhibit band gap behavior.
DARPP-32: Regulator of the Efficacy of Dopaminergic Neurotransmission
Authors: Fienberg A. A. , Hiroi N. , Mermelstein P. G. , Song W.-J. , Snyder G. L. , Nishi A. , Cheramy A. , O'Callaghan J. P. , Miller D. B. , Cole D. G. , Corbett R. , Haile C. N. , Cooper D. C. , Onn S. P. , Grace A. A. , Ouimet C. C. , White F. J. , Hyman S. E. , Surmeier D. J. , Girault J.-A. , Nestler E. J. , Greengard P.
Published: July 2002

Dopaminergic neurons exert a major modulatory effect on the forebrain. Dopamine and adenosine 3′,5′-monophosphate–regulated phosphoprotein (32 kilodaltons) (DARPP-32), which is enriched in all neurons that receive a dopaminergic input, is converted in response to dopamine into a potent protein phosphatase inhibitor. Mice generated to contain a targeted disruption of the DARPP-32 gene showed profound deficits in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication. The results show that DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission.
Lunar Prospector: Overview
Authors: Binder Alan B.
Published: July 2002

Lunar Prospector is providing a global map of the composition of the moon and analyzing the moon's gravity and magnetic fields. It has been in a polar orbit around the moon since 16 January 1998. Neutron flux data show that there is abundant H, and hence probably abundant water ice, in the lunar polar regions. Gamma-ray and neutron data reveal the distribution of Fe, Ti, and other major and trace elements on the moon. The data delineate the global distributions of a key trace element–rich component of lunar materials called KREEP and of the major rock types. Magnetic mapping shows that the lunar magnetic fields are strong antipodal to Mare Imbrium and Mare Serenitatis and has discovered the smallest known magnetosphere, magnetosheath, and bow shock complex in the solar system. Gravity mapping has delineated seven new gravity anomalies and shown that the moon has a small Fe-rich core of about 300 km radius.
Design of Organic Molecules with Large Two-Photon Absorption Cross Sections
Authors: Albota Marius , Beljonne David , Brédas Jean-Luc , Ehrlich Jeffrey E. , Fu Jia-Ying , Heikal Ahmed A. , Hess Samuel E. , Kogej Thierry , Levin Michael D. , Marder Seth R. , McCord-Maughon Dianne , Perry Joseph W. , Röckel Harald , Rumi Mariacristina , Subramaniam Girija , Webb Watt W. , Wu Xiang-Li , Xu Chris
Published: July 2002

A strategy for the design of molecules with large two-photon absorption cross sections, δ, was developed, on the basis of the concept that symmetric charge transfer, from the ends of a conjugated system to the middle, or vice versa, upon excitation is correlated to enhanced values of δ. Synthesized bis(styryl)benzene derivatives with donor-π-donor, donor-acceptor-donor, and acceptor-donor-acceptor structural motifs exhibit exceptionally large values of δ, up to about 400 times that of
trans-
stilbene. Quantum chemical calculations performed on these molecules indicate that substantial symmetric charge redistribution occurs upon excitation and provide δ values in good agreement with experimental values. The combination of large δ and high fluorescence quantum yield or triplet yield exhibited by molecules developed here offers potential for unprecedented brightness in two-photon fluorescent imaging or enhanced photosensitivity in two-photon sensitization, respectively.
NF-κB Antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to Suppress Caspase-8 Activation
Authors: Wang Cun-Yu , Mayo Marty W. , Korneluk Robert G. , Goeddel David V. , Baldwin Albert S.
Published: July 2002

Tumor necrosis factor α (TNF-α) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-κB), which suppresses apoptosis by an unknown mechanism. The activation of NF-κB was found to block the activation of caspase-8. TRAF1 (TNFR-associated factor 1), TRAF2, and the inhibitor-of-apoptosis (IAP) proteins c-IAP1 and c-IAP2 were identified as gene targets of NF-κB transcriptional activity. In cells in which NF-κB was inactive, all of these proteins were required to fully suppress TNF-induced apoptosis, whereas c-IAP1 and c-IAP2 were sufficient to suppress etoposide-induced apoptosis. Thus, NF-κB activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-α–mediated apoptosis and that function more distally to suppress genotoxic agent–mediated apoptosis.
Evolution of Gamete Recognition Proteins
Authors: Vacquier Victor D.
Published: July 2002

REVIEW

Although fertilization has been studied for more than a century, the cell surface proteins mediating the process are only now becoming known. Gamete interaction in animals appears to be molecularly complex. Although it is difficult to generalize at present, diversity of structure may be a recurring theme in the evolution of fertilization proteins. Examples of rapid evolution of fertilization proteins by positive selection are known, and concerted evolution can influence the differentiation of gamete recognition proteins between closely related species.
Semiconductor Nanocrystals as Fluorescent Biological Labels
Authors: Bruchez Marcel , Moronne Mario , Gin Peter , Weiss Shimon , Alivisatos A. Paul
Published: July 2002

Semiconductor nanocrystals were prepared for use as fluorescent probes in biological staining and diagnostics. Compared with conventional fluorophores, the nanocrystals have a narrow, tunable, symmetric emission spectrum and are photochemically stable. The advantages of the broad, continuous excitation spectrum were demonstrated in a dual-emission, single-excitation labeling experiment on mouse fibroblasts. These nanocrystal probes are thus complementary and in some cases may be superior to existing fluorophores.
Triploblastic Animals More Than 1 Billion Years Ago: Trace Fossil Evidence from India
Authors: Seilacher Adolf , Bose Pradip K. , Pflüger Friedrich
Published: July 2002

Some intriguing bedding plane features that were observed in the Mesoproterozoic Chorhat Sandstone are biological and can be interpreted as the burrows of wormlike undermat miners (that is, infaunal animals that excavated tunnels underneath microbial mats). These burrows suggest that triploblastic animals existed more than a billion years ago. They also suggest that the diversification of animal designs proceeded very slowly before the appearance of organisms with hard skeletons, which was probably the key event in the Cambrian evolutionary explosion, and before the ecological changes that accompanied that event.
Measuring the Spin Polarization of a Metal with a Superconducting Point Contact
Authors: Soulen R. J. , Byers J. M. , Osofsky M. S. , Nadgorny B. , Ambrose T. , Cheng S. F. , Broussard P. R. , Tanaka C. T. , Nowak J. , Moodera J. S. , Barry A. , Coey J. M. D.
Published: July 2002

A superconducting point contact is used to determine the spin polarization at the Fermi energy of several metals. Because the process of supercurrent conversion at a superconductor-metal interface (Andreev reflection) is limited by the minority spin population near the Fermi surface, the differential conductance of the point contact can reveal the spin polarization of the metal. This technique has been applied to a variety of metals where the spin polarization ranges from 35 to 90 percent: Ni
0.8
Fe
0.2
, Ni, Co, Fe, NiMnSb, La
0.7
Sr
0.3
MnO
3
, and CrO
2
.
Arabidopsis thaliana
: A Model Plant for Genome Analysis
Authors: Meinke David W. , Cherry J. Michael , Dean Caroline , Rounsley Steven D. , Koornneef Maarten
Published: July 2002

Arabidopsis thaliana
is a small plant in the mustard family that has become the model system of choice for research in plant biology. Significant advances in understanding plant growth and development have been made by focusing on the molecular genetics of this simple angiosperm. The 120-megabase genome of
Arabidopsis
is organized into five chromosomes and contains an estimated 20,000 genes. More than 30 megabases of annotated genomic sequence has already been deposited in GenBank by a consortium of laboratories in Europe, Japan, and the United States. The entire genome is scheduled to be sequenced by the end of the year 2000. Reaching this milestone should enhance the value of
Arabidopsis
as a model for plant biology and the analysis of complex organisms in general.
In Search of the First Flower: A Jurassic Angiosperm,
Archaefructus
, from Northeast China
Authors: Sun Ge , Dilcher David L. , Zheng Shaoling , Zhou Zhekun
Published: July 2002

Angiosperm fruiting axes were discovered from the Upper Jurassic of China. Angiosperms are defined by carpels enclosing ovules, a character demonstrated in this fossil. This feature is lacking in other fossils reported to be earliest angiosperms. The fruits are small follicles formed from conduplicate carpels helically arranged. Adaxial elongate stigmatic crests are conspicuous on each carpel. The basal one-third of the axes bore deciduous organs of uncertain affinities. No scars of subtending floral organs are present to define the individual fertile parts as floral units, but the leaf-like structures subtending each axis define them as flowers. These fruiting axes have primitive characters and characters not considered primitive.
Molecular Basis of T Cell Inactivation by CTLA-4
Authors: Lee Kyung-Mi , Chuang Ellen , Griffin Matthew , Khattri Roli , Hong David K. , Zhang Weiguo , Straus David , Samelson Lawrence E. , Thompson Craig B. , Bluestone Jeffrey A.
Published: July 2002

CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex ζ chain in primary T cells. The association of TCRζ with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56
lck
-induced tyrosine phosphorylation. Coexpression of the CTLA-4–associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRζ bound to CTLA-4 and abolished the p56
lck
-inducible TCRζ–CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRζ and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.
Phytoplankton Community Structure and the Drawdown of Nutrients and CO
2
in the Southern Ocean
Authors: Arrigo Kevin R. , Robinson Dale H. , Worthen Denise L. , Dunbar Robert B. , DiTullio Giacomo R. , VanWoert Michael , Lizotte Michael P.
Published: July 2002

Data from recent oceanographic cruises show that phytoplankton community structure in the Ross Sea is related to mixed layer depth. Diatoms dominate in highly stratified waters, whereas
Phaeocystis antarctica
assemblages dominate where waters are more deeply mixed. The drawdown of both carbon dioxide (CO
2
) and nitrate per mole of phosphate and the rate of new production by diatoms are much lower than that measured for
P. antarctica
. Consequently, the capacity of the biological community to draw down atmospheric CO
2
and transport it to the deep ocean could diminish dramatically if predicted increases in upper ocean stratification due to climate warming should occur.
Self-Oriented Regular Arrays of Carbon Nanotubes and Their Field Emission Properties
Authors: Fan Shoushan , Chapline Michael G. , Franklin Nathan R. , Tombler Thomas W. , Cassell Alan M. , Dai Hongjie
Published: July 2002

The synthesis of massive arrays of monodispersed carbon nanotubes that are self-oriented on patterned porous silicon and plain silicon substrates is reported. The approach involves chemical vapor deposition, catalytic particle size control by substrate design, nanotube positioning by patterning, and nanotube self-assembly for orientation. The mechanisms of nanotube growth and self-orientation are elucidated. The well-ordered nanotubes can be used as electron field emission arrays. Scaling up of the synthesis process should be entirely compatible with the existing semiconductor processes, and should allow the development of nanotube devices integrated into silicon technology.
Reciprocal Inhibitory Connections and Network Synchrony in the Mammalian Thalamus
Authors: Huntsman Molly M. , Porcello Darrell M. , Homanics Gregg E. , DeLorey Timothy M. , Huguenard John R.
Published: July 2002

Neuronal rhythmic activities within thalamocortical circuits range from partially synchronous oscillations during normal sleep to hypersynchrony associated with absence epilepsy. It has been proposed that recurrent inhibition within the thalamic reticular nucleus serves to reduce synchrony and thus prevents seizures. Inhibition and synchrony in slices from mice devoid of the γ-aminobutyric acid type-A (GABA
A
) receptor β
3
subunit were examined, because in rodent thalamus, β
3
is largely restricted to reticular nucleus. In β
3
knockout mice, GABA
A
-mediated inhibition was nearly abolished in reticular nucleus, but was unaffected in relay cells. In addition, oscillatory synchrony was dramatically intensified. Thus, recurrent inhibitory connections within reticular nucleus act as “desynchronizers.”
Population Biology, Evolution, and Infectious Disease: Convergence and Synthesis
Authors: Levin Bruce R. , Lipsitch Marc , Bonhoeffer Sebastian
Published: July 2002

Traditionally, the interest of population and evolutionary biologists in infectious diseases has been almost exclusively in their role as agents of natural selection in higher organisms. Recently, this interest has expanded to include the genetic structure and evolution of microparasite populations, the mechanisms of pathogenesis and the immune response, and the population biology, ecology, and evolutionary consequences of medical and public health interventions. This article describes recent work in these areas, emphasizing the ways in which quantitative, population-biological approaches have been contributing to the understanding of infectious disease and the design and evaluation of interventions for their treatment and prevention.
Genesis and Evolution of the 1997-98 El Niño
Authors: McPhaden Michael J.
Published: July 2002

The 1997–98 El Niño was, by some measures, the strongest on record, with major climatic impacts felt around the world. A newly completed tropical Pacific atmosphere-ocean observing system documented this El Niño from its rapid onset to its sudden demise in greater detail than was ever before possible. The unprecedented measurements challenge existing theories about El Niño–related climate swings and suggest why climate forecast models underpredicted the strength of the El Niño before its onset.
A Computational Screen for Methylation Guide snoRNAs in Yeast
Authors: Lowe Todd M. , Eddy Sean R.
Published: July 2002

Small nucleolar RNAs (snoRNAs) are required for ribose 2′-O-methylation of eukaryotic ribosomal RNA. Many of the genes for this snoRNA family have remained unidentified in
Saccharomyces cerevisiae
, despite the availability of a complete genome sequence. Probabilistic modeling methods akin to those used in speech recognition and computational linguistics were used to computationally screen the yeast genome and identify 22 methylation guide snoRNAs, snR50 to snR71. Gene disruptions and other experimental characterization confirmed their methylation guide function. In total, 51 of the 55 ribose methylated sites in yeast ribosomal RNA were assigned to 41 different guide snoRNAs.
Unconditional Security of Quantum Key Distribution over Arbitrarily Long Distances
Authors: Lo Hoi-Kwong , Chau H. F.
Published: July 2002

Quantum key distribution is widely thought to offer unconditional security in communication between two users. Unfortunately, a widely accepted proof of its security in the presence of source, device, and channel noises has been missing. This long-standing problem is solved here by showing that, given fault-tolerant quantum computers, quantum key distribution over an arbitrarily long distance of a realistic noisy channel can be made unconditionally secure. The proof is reduced from a noisy quantum scheme to a noiseless quantum scheme and then from a noiseless quantum scheme to a noiseless classical scheme, which can then be tackled by classical probability theory.
Crystal Structure of a Conserved Ribosomal Protein-RNA Complex
Authors: Conn Graeme L. , Draper David E. , Lattman Eaton E. , Gittis Apostolos G.
Published: July 2002

The structure of a highly conserved complex between a 58-nucleotide domain of large subunit ribosomal RNA and the RNA-binding domain of ribosomal protein L11 has been solved at 2.8 angstrom resolution. It reveals a precisely folded RNA structure that is stabilized by extensive tertiary contacts and contains an unusually large core of stacked bases. A bulge loop base from one hairpin of the RNA is intercalated into the distorted major groove of another helix; the protein locks this tertiary interaction into place by binding to the intercalated base from the minor groove side. This direct interaction with a key ribosomal RNA tertiary interaction suggests that part of the role of L11 is to stabilize an unusual RNA fold within the ribosome.
PKS1, a Substrate Phosphorylated by Phytochrome That Modulates Light Signaling in
Arabidopsis
Authors: Fankhauser Christian , Yeh Kuo-Chen , Clark J. , Lagarias  , Zhang Hong , Elich Tedd D. , Chory Joanne
Published: July 2002

Plants constantly monitor their light environment in order to grow and develop optimally, in part through use of the phytochromes, which sense red/far-red light. A phytochrome binding protein, PKS1 (phytochrome kinase substrate 1), was identified that is a substrate for light-regulated phytochrome kinase activity in vitro. In vivo experiments suggest that PKS1 is phosphorylated in a phytochrome-dependent manner and negatively regulates phytochrome signaling. The data suggest that phytochromes signal by serine-threonine phosphorylation.
Wing Rotation and the Aerodynamic Basis of Insect Flight
Authors: Dickinson Michael H. , Lehmann Fritz-Olaf , Sane Sanjay P.
Published: July 2002

The enhanced aerodynamic performance of insects results from an interaction of three distinct yet interactive mechanisms: delayed stall, rotational circulation, and wake capture. Delayed stall functions during the translational portions of the stroke, when the wings sweep through the air with a large angle of attack. In contrast, rotational circulation and wake capture generate aerodynamic forces during stroke reversals, when the wings rapidly rotate and change direction. In addition to contributing to the lift required to keep an insect aloft, these two rotational mechanisms provide a potent means by which the animal can modulate the direction and magnitude of flight forces during steering maneuvers. A comprehensive theory incorporating both translational and rotational mechanisms may explain the diverse patterns of wing motion displayed by different species of insects.
Vessel Cooption, Regression, and Growth in Tumors Mediated by Angiopoietins and VEGF
Authors: Holash J. , Maisonpierre P. C. , Compton D. , Boland P. , Alexander C. R. , Zagzag D. , Yancopoulos G. D. , Wiegand S. J.
Published: July 2002

In contrast with the prevailing view that most tumors and metastases begin as avascular masses, evidence is presented here that a subset of tumors instead initially grows by coopting existing host vessels. This coopted host vasculature does not immediately undergo angiogenesis to support the tumor but instead regresses, leading to a secondarily avascular tumor and massive tumor cell loss. Ultimately, however, the remaining tumor is rescued by robust angiogenesis at the tumor margin. The expression patterns of the angiogenic antagonist angiopoietin-2 and of pro-angiogenic vascular endothelial growth factor (VEGF) suggest that these proteins may be critical regulators of this balance between vascular regression and growth.
Environmental Engineering: Energy Value of Replacing Waste Disposal with Resource Recovery
Authors: Iranpour R. , Stenstrom M. , Tchobanoglous G. , Miller D. , Wright J. , Vossoughi M.
Published: July 2002

Although in the past, environmental engineering has been primarily concerned with waste disposal, the focus of the field is now shifting toward viewing wastes as potential resources. Because reclamation usually consumes less energy than producing new materials, increasing reclamation not only reduces pollution but saves energy. Technological innovations contributing to this shift are summarized here, and are variously classified as emerging technologies or research topics, as either new departures or incremental improvements, and as opportunistic innovations, or examples of a unifying strategy. Both liquid and solid waste examples are given, such as a recent discovery of effects in disinfecting microfiltered reclaimed wastewater with ultraviolet light. In addition to its value in reducing pollution and conserving energy, this reorientation of environmental engineering could contribute to a more general shift toward greater cooperation among organizations dealing with the environment.
Fas Ligand: A Sensor for DNA Damage Critical in Skin Cancer Etiology
Authors: Hill Laurie L. , Ouhtit Allal , Loughlin Susan M. , Kripke Margaret L. , Ananthaswamy Honnavara N. , Owen-Schaub Laurie B.
Published: July 2002

DNA-damaged cells can either repair the DNA or be eliminated through a homeostatic control mechanism termed “cellular proofreading.” Elimination of DNA-damaged cells after ultraviolet radiation (UVR) through sunburn cell (apoptotic keratinocyte) formation is thought to be pivotal for the removal of precancerous skin cells. Sunburn cell formation was found to be dependent on Fas ligand (FasL), a pro-apoptotic protein induced by DNA damage. Chronic exposure to UVR caused 14 of 20 (70 percent) FasL-deficient mice and 1 of 20 (5 percent) wild-type mice to accumulate p53 mutations in the epidermis. Thus, FasL-mediated apoptosis is important for skin homeostasis, suggesting that the dysregulation of Fas-FasL interactions may be central to the development of skin cancer.
Hafnium Isotope Stratigraphy of Ferromanganese Crusts
Authors: Lee Der-Chuen , Halliday Alex N. , Hein James R. , Burton Kevin W. , Christensen John N. , Günther Detlef
Published: July 2002

A Cenozoic record of hafnium isotopic compositions of central Pacific deep water has been obtained from two ferromanganese crusts. The crusts are separated by more than 3000 kilometers but display similar secular variations. Significant fluctuations in hafnium isotopic composition occurred in the Eocene and Oligocene, possibly related to direct advection from the Indian and Atlantic oceans. Hafnium isotopic compositions have remained approximately uniform for the past 20 million years, probably reflecting increased isolation of the central Pacific. The mechanisms responsible for the increase in
87
Sr/
86
Sr in seawater through the Cenozoic apparently had no effect on central Pacific deep-water hafnium.
Rapid Infection of Oral Mucosal-Associated Lymphoid Tissue with Simian Immunodeficiency Virus
Authors: Stahl-Hennig Christiane , Steinman Ralph M. , Tenner-Racz Klara , Pope Melissa , Stolte Nicole , Mätz-Rensing Kerstin , Grobschupff Gudrun , Raschdorff Birgit , Hunsmann Gerhard , Racz Paul
Published: July 2002

The early events during infection with an immunodeficiency virus were followed by application of pathogenic simian immunodeficiency virus atraumatically to the tonsils of macaques. Analyses by virologic assays and in situ hybridization revealed that the infection started locally in the tonsils, a mucosal-associated lymphoid organ, and quickly spread to other lymphoid tissues. At day 3, there were few infected cells, but then the number increased rapidly, reaching a high plateau between days 4 and 7. The infection was not detected in the dendritic cell–rich squamous epithelium to which the virus was applied; instead, it was primarily in CD4
+
tonsillar T cells, close to the specialized antigen-transporting epithelium of the tonsillar crypts. Transport of the virus and immune-activating stimuli across this epithelium would allow mucosal lymphoid tissue to function in the atraumatic transmission of immunodeficiency viruses.
In Vivo Protein Transduction: Delivery of a Biologically Active Protein into the Mouse
Authors: Schwarze Steven R. , Ho Alan , Vocero-Akbani Adamina , Dowdy Steven F.
Published: July 2002

Delivery of therapeutic proteins into tissues and across the blood-brain barrier is severely limited by the size and biochemical properties of the proteins. Here it is shown that intraperitoneal injection of the 120-kilodalton β-galactosidase protein, fused to the protein transduction domain from the human immunodeficiency virus TAT protein, results in delivery of the biologically active fusion protein to all tissues in mice, including the brain. These results open new possibilities for direct delivery of proteins into patients in the context of protein therapy, as well as for epigenetic experimentation with model organisms.
Lower Mantle Lateral Heterogeneity Beneath the Caribbean Sea
Authors: Tibuleac Ileana Madalina , Herrin Eugene
Published: July 2002

Seismic wave reflections from Earth's core recorded at seismic arrays in North America from events in the Caribbean Islands, Venezuela, and the Mid-Atlantic Ridge have observed slownesses more than 64 percent greater than predicted by the IASPEI91 standard Earth model.Pwaves turning in the lowermost mantle beneath the same region also have anomalous slowness. The slowness anomalies are not accompanied by significant travel time residuals and appear to be caused by lateral inhomogeneities in the velocity structure of the lower mantle.
Male Attractiveness and Differential Testosterone Investment in Zebra Finch Eggs
Authors: Gil Diego , Graves Jeff , Hazon Neil , Wells Alan
Published: July 2002

Good-genes hypotheses of sexual selection predict that offspring fathered by preferred males should have increased viability resulting from superior genetic quality. Several studies of birds have reported findings consistent with this prediction, but maternal effects are an important confounding variable. Those studies that have attempted to control for maternal effects have only considered differential maternal investment after egg laying. However, female birds differentially deposit testosterone in the eggs, and this influences the development of the chick. This study shows that female birds deposit higher amounts of testosterone and 5α-dihydrotestosterone in their eggs when mated to more attractive males.
Emergence of Scaling in Random Networks
Authors: Barabási Albert-László , Albert Réka
Published: July 2002

Systems as diverse as genetic networks or the World Wide Web are best described as networks with complex topology. A common property of many large networks is that the vertex connectivities follow a scale-free power-law distribution. This feature was found to be a consequence of two generic mechanisms: (i) networks expand continuously by the addition of new vertices, and (ii) new vertices attach preferentially to sites that are already well connected. A model based on these two ingredients reproduces the observed stationary scale-free distributions, which indicates that the development of large networks is governed by robust self-organizing phenomena that go beyond the particulars of the individual systems.
Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring
Authors: Golub T. R. , Slonim D. K. , Tamayo P. , Huard C. , Gaasenbeek M. , Mesirov J. P. , Coller H. , Loh M. L. , Downing J. R. , Caligiuri M. A. , Bloomfield C. D. , Lander E. S.
Published: July 2002

Although cancer classification has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery) or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case. A class discovery procedure automatically discovered the distinction between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) without previous knowledge of these classes. An automatically derived class predictor was able to determine the class of new leukemia cases. The results demonstrate the feasibility of cancer classification based solely on gene expression monitoring and suggest a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
CFTR Chloride Channel Regulation by an Interdomain Interaction
Authors: Naren Anjaparavanda P. , Cormet-Boyaka Estelle , Fu Jian , Villain Matteo , Blalock J. Edwin , Quick Michael W. , Kirk Kevin L.
Published: July 2002

The cystic fibrosis gene encodes a chloride channel, CFTR (cystic fibrosis transmembrane conductance regulator), that regulates salt and water transport across epithelial tissues. Phosphorylation of the cytoplasmic regulatory (R) domain by protein kinase A activates CFTR by an unknown mechanism. The amino-terminal cytoplasmic tail of CFTR was found to control protein kinase A–dependent channel gating through a physical interaction with the R domain. This regulatory activity mapped to a cluster of acidic residues in the NH
2
-terminal tail; mutating these residues proportionately inhibited R domain binding and CFTR channel function. CFTR activity appears to be governed by an interdomain interaction involving the amino-terminal tail, which is a potential target for physiologic and pharmacologic modulators of this ion channel.
In Situ Observation of the Formation of 10 Å Phase from Talc + H
2
O at Mantle Pressures and Temperatures
Authors: Chinnery Nicholas J. , Pawley Alison R. , Clark Simon M.
Published: July 2002

Development of an x-ray–transparent capsule that is suitable for water-saturated experiments has allowed the high-pressure and high-temperature synthesis of 10 angstrom phase from talc + H
2
O to be observed in situ in a multianvil apparatus with synchrotron radiation. The reaction talc + H
2
O = 10 angstrom phase was observed within 20 minutes at 6 gigapascals and 500°C. The higher pressure vapor-absent reaction talc = 10 angstrom phase + enstatite + coesite was also observed. The 10 angstrom phase is therefore a good candidate for transporting water into Earth's mantle at subduction zones. The in situ technique may allow the hydration of other high-pressure mantle phases to be observed under dynamic conditions.
Sexual Transmission and Propagation of SIV and HIV in Resting and Activated CD4
+
T Cells
Authors: Zhang Z.-Q. , Schuler T. , Zupancic M. , Wietgrefe S. , Staskus K. A. , Reimann K. A. , Reinhart T. A. , Rogan M. , Cavert W. , Miller C. J. , Veazey R. S. , Notermans D. , Little S. , Danner S. A. , Richman D. D. , Havlir D. , Wong J. , Jordan H. L. , Schacker T. W. , Racz P. , Tenner-Racz K. , Letvin N. L. , Wolinsky S. , Haase A. T.
Published: July 2002

In sexual transmission of simian immunodeficiency virus, and early and later stages of human immunodeficiency virus–type 1 (HIV-1) infection, both viruses were found to replicate predominantly in CD4
+
T cells at the portal of entry and in lymphoid tissues. Infection was propagated not only in activated and proliferating T cells but also, surprisingly, in resting T cells. The infected proliferating cells correspond to the short-lived population that produces the bulk of HIV-1. Most of the HIV-1–infected resting T cells persisted after antiretroviral therapy. Latently and chronically infected cells that may be derived from this population pose challenges to eradicating infection and developing an effective vaccine.
Large On-Off Ratios and Negative Differential Resistance in a Molecular Electronic Device
Authors: Chen J. , Reed M. A. , Rawlett A. M. , Tour J. M.
Published: July 2002

A molecule containing a nitroamine redox center (2′-amino-4-ethynylphenyl-4′-ethynylphenyl-5′-nitro-1-benzenethiol) was used in the active self-assembled monolayer in an electronic device. Current-voltage measurements of the device exhibited negative differential resistance and an on-off peak-to-valley ratio in excess of 1000:1.
Setting the Standards: Quality Control in the Secretory Pathway
Authors: Ellgaard Lars , Molinari Maurizio , Helenius Ari
Published: July 2002

A variety of quality control mechanisms operate in the endoplasmic reticulum and in downstream compartments of the secretory pathway to ensure the fidelity and regulation of protein expression during cell life and differentiation. As a rule, only proteins that pass a stringent selection process are transported to their target organelles and compartments. If proper maturation fails, the aberrant products are degraded. Quality control improves folding efficiency by retaining proteins in the special folding environment of the endoplasmic reticulum, and it prevents harmful effects that could be caused by the deployment of incompletely folded or assembled proteins.
Stimulation of Bone Formation in Vitro and in Rodents by Statins
Authors: Mundy G. , Garrett R. , Harris S. , Chan J. , Chen D. , Rossini G. , Boyce B. , Zhao M. , Gutierrez G.
Published: July 2002

Osteoporosis and other diseases of bone loss are a major public health problem. Here it is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents. This effect was associated with increased expression of the bone morphogenetic protein–2 (
BMP-2
) gene in bone cells. Lovastatin and simvastatin increased bone formation when injected subcutaneously over the calvaria of mice and increased cancellous bone volume when orally administered to rats. Thus, in appropriate doses, statins may have therapeutic applications for the treatment of osteoporosis.
Activation Tagging of the Floral Inducer
FT
Authors: Kardailsky Igor , Shukla Vipula K. , Ahn Ji Hoon , Dagenais Nicole , Christensen Sioux K. , Nguyen Jasmine T. , Chory Joanne , Harrison Maria J. , Weigel Detlef
Published: July 2002

FLOWERING LOCUS T
(
FT
), which acts in parallel with the meristem-identity gene
LEAFY
(
LFY
) to induce flowering of
Arabidopsis
, was isolated by activation tagging. Like
LFY
,
FT
acts partially downstream of
CONSTANS
(
CO
), which promotes flowering in response to long days. Unlike many other floral regulators, the deduced sequence of the FT protein does not suggest that it directly controls transcription or transcript processing. Instead, it is similar to the sequence of TERMINAL FLOWER 1 (TFL1), an inhibitor of flowering that also shares sequence similarity with membrane-associated mammalian proteins.
Constraints on Slow Earthquake Dynamics from a Swarm in Central Italy
Authors: Crescentini Luca , Amoruso Antonella , Scarpa Roberto
Published: July 2002

Several clustered slow earthquakes have been recorded by a geodetic interferometer in central Italy. The strain rise times of the events range from tens to thousands of seconds, and the seismic moment scales with the square root of the rise time. This scaling law contrasts with the conservative assumption of constant rupture velocity in fault modeling but is consistent with the occurrence of a slow rupture propagation analogous to heat diffusion in a slab.
Binding of Transcription Termination Protein Nun to Nascent RNA and Template DNA
Authors: Watnick Randolph S. , Gottesman Max E.
Published: July 2002

The amino-terminal arginine-rich motif of coliphage HK022 Nun binds phage λ nascent transcript, whereas the carboxyl-terminal domain interacts with RNA polymerase (RNAP) and blocks transcription elongation. RNA binding is inhibited by zinc (Zn
2+
) and stimulated by
Escherichia coli
NusA. To study these interactions, the Nun carboxyl terminus was extended by a cysteine residue conjugated to a photochemical cross-linker. The carboxyl terminus contacted NusA and made Zn
2+
-dependent intramolecular contacts. When Nun was added to a paused transcription elongation complex, it cross-linked to the DNA template. Nun may arrest transcription by anchoring RNAP to DNA.
Cognitive Modularity and Genetic Disorders
Authors: Paterson S. J. , Brown J. H. , Gsödl M. K. , Johnson M. H. , Karmiloff-Smith A.
Published: July 2002

This study challenges the use of adult neuropsychological models for explaining developmental disorders of genetic origin. When uneven cognitive profiles are found in childhood or adulthood, it is assumed that such phenotypic outcomes characterize infant starting states, and it has been claimed that modules subserving these abilities start out either intact or impaired. Findings from two experiments with infants with Williams syndrome (a phenotype selected to bolster innate modularity claims) indicate a within-syndrome double dissociation: For numerosity judgments, they do well in infancy but poorly in adulthood, whereas for language, they perform poorly in infancy but well in adulthood. The theoretical and clinical implications of these results could lead to a shift in focus for studies of genetic disorders.
Three-Dimensional Direct Imaging of Structural Relaxation Near the Colloidal Glass Transition
Authors: Weeks Eric R. , Crocker J. C. , Levitt Andrew C. , Schofield Andrew , Weitz D. A.
Published: July 2002

Confocal microscopy was used to directly observe three-dimensional dynamics of particles in colloidal supercooled fluids and colloidal glasses. The fastest particles moved cooperatively; connected clusters of these mobile particles could be identified; and the cluster size distribution, structure, and dynamics were investigated. The characteristic cluster size grew markedly in the supercooled fluid as the glass transition was approached, in agreement with computer simulations; at the glass transition, however, there was a sudden drop in their size. The clusters of fast-moving particles were largest near the α-relaxation time scale for supercooled colloidal fluids, but were also present, albeit with a markedly different nature, at shorter β-relaxation time scales, in both supercooled fluid and glass colloidal phases.
A Simple Model for Complex Dynamical Transitions in Epidemics
Authors: Earn David J. D. , Rohani Pejman , Bolker Benjamin M. , Grenfell Bryan T.
Published: July 2002

Dramatic changes in patterns of epidemics have been observed throughout this century. For childhood infectious diseases such as measles, the major transitions are between regular cycles and irregular, possibly chaotic epidemics, and from regionally synchronized oscillations to complex, spatially incoherent epidemics. A simple model can explain both kinds of transitions as the consequences of changes in birth and vaccination rates. Measles is a natural ecological system that exhibits different dynamical transitions at different times and places, yet all of these transitions can be predicted as bifurcations of a single nonlinear model.
Adaptive Recognition by Nucleic Acid Aptamers
Authors: Hermann Thomas , Patel Dinshaw J.
Published: July 2002

Nucleic acid molecules play crucial roles in diverse biological processes including the storage, transport, processing, and expression of the genetic information. Nucleic acid aptamers are selected in vitro from libraries containing random sequences of up to a few hundred nucleotides. Selection is based on the ability to bind ligand molecules with high affinity and specificity. Three-dimensional structures have been determined at high resolution for a number of aptamers in complex with their cognate ligands. Structures of aptamer complexes reveal the key molecular interactions conferring specificity to the aptamer-ligand association, including the precise stacking of flat moieties, specific hydrogen bonding, and molecular shape complementarity. These basic principles of discriminatory molecular interactions in aptamer complexes parallel recognition events central to many cellular processes involving nucleic acids.
Quantization of Multiparticle Auger Rates in Semiconductor Quantum Dots
Authors: Klimov V. I. , Mikhailovsky A. A. , McBranch D. W. , Leatherdale C. A. , Bawendi M. G.
Published: July 2002

We have resolved single-exponential relaxation dynamics of the 2-, 3-, and 4-electron-hole pair states in nearly monodisperse cadmium selenide quantum dots with radii ranging from 1 to 4 nanometers. Comparison of the discrete relaxation constants measured for different multiple-pair states indicates that the carrier decay rate is cubic in carrier concentration, which is characteristic of an Auger process. We observe that in the quantum-confined regime, the Auger constant is strongly size-dependent and decreases with decreasing the quantum dot size as the radius cubed.
Localization of the G Protein βγ Complex in Living Cells During Chemotaxis
Authors: Jin Tian , Zhang Ning , Long Yu , Parent Carole A. , Devreotes Peter N.
Published: July 2002

Gradients of chemoattractants elicit signaling events at the leading edge of a cell even though chemoattractant receptors are uniformly distributed on the cell surface. In highly polarized
Dictyostelium discoideum
amoebas, membrane-associated βγ subunits of heterotrimeric guanine nucleotide–binding proteins (G proteins) were localized in a shallow anterior-posterior gradient. A uniformly applied chemoattractant generated binding sites for pleckstrin homology (PH) domains on the inner surface of the membrane in a pattern similar to that of the Gβγ subunits. Loss of cell polarity resulted in uniform distribution of both the Gβγ subunits and the sensitivity of PH domain recruitment. These observations indicate that Gβγ subunits are not sufficiently localized to restrict signaling events to the leading edge but that their distribution may determine the relative chemotactic sensitivity of polarized cells.