bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous and piezoelectric polarization effects in III–V nitride heterostructures
Authors: Yu E. T. , Dang X. Z. , Asbeck P. M. , Lau S. S. , Sullivan G. J.
Published: July 2002

The role of spontaneous and piezoelectric polarization in III–V nitride heterostructures is investigated. Polarization effects and crystal polarity are reviewed in the context of nitride heterostructure materials and device design, and a detailed analysis of their influence in nitride heterostructure field-effect transistors is presented. The combined effects of spontaneous and piezoelectric polarization are found to account well for carrier concentrations observed in AlGaN/GaN transistor structures with low to moderate Al concentrations, while the data for higher Al concentrations are consistent with defect formation in the AlGaN barrier. Theoretical analysis suggests that incorporation of In into the barrier and/or channel layers can substantially increase polarization charge at the heterojunction interface. The use of polarization effects to engineer Schottky barrier structures with large enhancements in barrier height is also discussed, and electrical characteristics of transistors with conventional and polarization-enhanced Schottky barrier gates are presented. The polarization-enhanced barrier is found to yield a marked reduction in gate leakage current, but to have little effect on transistor breakdown voltage.
Spectroscopic investigations of plasma damage of kapton
Authors: Lee Szetsen , Tien Yu-Chung , Hsu Chin-Fa
Published: July 2002

Kapton (polyimide) has been considered a potential candidate for particle reduction in plasma etching chambers. However, it is found that the lifetime of kapton’s ability to trap particles is limited. Beyond this limit, particle contamination becomes serious. In this study, two plasma etching recipes were used to test the particle/polymer trapping efficiency of kapton. Fourier transform infrared (FTIR) and ultraviolet (UV)-visible emission spectroscopies were used to study plasma–kapton interactions. It is found that the functional groups change on the kapton surface as observed by IR has a strong link to the change of features in plasma emission spectra. The increase of IR absorption of CFx (x=2 and 3) indicates the growth of fluorocarbon polymer on the kapton surface. The kapton surface was damaged, as is indicated by the change of C=O, –NH2, and C–H IR intensities and the variation of CN and SiF peaks in UV-visible emission spectra. Spectroscopic data show that kapton has a very good particle/polymer reduction efficiency when using a high-polymer recipe but it is not very efficient with an oxygen-rich recipe. Both IR absorption and UV-visible emission data are correlated to interpret the mechanisms of plasma damage of kapton.
The Role of Working Memory in Visual Selective Attention
Authors: de Fockert Jan W. , Rees Geraint , Frith Christopher D. , Lavie Nilli
Published: July 2002

The hypothesis that working memory is crucial for reducing distraction by maintaining the prioritization of relevant information was tested in neuroimaging and psychological experiments with humans. Participants performed a selective attention task that required them to ignore distractor faces while holding in working memory a sequence of digits that were in the same order (low memory load) or a different order (high memory load) on every trial. Higher memory load, associated with increased prefrontal activity, resulted in greater interference effects on behavioral performance from the distractor faces, plus increased face-related activity in the visual cortex. These findings confirm a major role for working memory in the control of visual selective attention.
In Situ Measurement of Grain Rotation During Deformation of Polycrystals
Authors: Margulies L. , Winther G. , Poulsen H. F.
Published: July 2002

Texture evolution governs many of the physical, chemical, and mechanical properties of polycrystalline materials, but texture models have only been tested on the macroscopic level, which makes it hard to distinguish between approaches that are conceptually very different. Here, we present a universal method for providing data on the underlying structural dynamics at the grain and subgrain level. The method is based on diffraction with focused hard x-rays. First results relate to the tensile deformation of pure aluminum. Experimental grain rotations are inconsistent with the classical Taylor and Sachs models.
Factors That Alter Rumen Microbial Ecology
Authors: Russell James B. , Rychlik Jennifer L.
Published: July 2002

Ruminant animals and ruminal microorganisms have a symbiotic relationship that facilitates fiber digestion, but domestic ruminants in developed countries are often fed an abundance of grain and little fiber. When ruminants are fed fiber-deficient rations, physiological mechanisms of homeostasis are disrupted, ruminal pH declines, microbial ecology is altered, and the animal becomes more susceptible to metabolic disorders and, in some cases, infectious disease. Some disorders can be counteracted by feed additives (for example, antibiotics and buffers), but these additives can alter the composition of the ruminal ecosystem even further.
Structural Basis of Transcription: An RNA Polymerase II Elongation Complex at 3.3 Å Resolution
Authors: Gnatt Averell L. , Cramer Patrick , Fu Jianhua , Bushnell David A. , Kornberg Roger D.
Published: July 2002

The crystal structure of RNA polymerase II in the act of transcription was determined at 3.3 Å resolution. Duplex DNA is seen entering the main cleft of the enzyme and unwinding before the active site. Nine base pairs of DNA-RNA hybrid extend from the active center at nearly right angles to the entering DNA, with the 3′ end of the RNA in the nucleotide addition site. The 3′ end is positioned above a pore, through which nucleotides may enter and through which RNA may be extruded during back-tracking. The 5′-most residue of the RNA is close to the point of entry to an exit groove. Changes in protein structure between the transcribing complex and free enzyme include closure of a clamp over the DNA and RNA and ordering of a series of “switches” at the base of the clamp to create a binding site complementary to the DNA-RNA hybrid. Protein–nucleic acid contacts help explain DNA and RNA strand separation, the specificity of RNA synthesis, “abortive cycling” during transcription initiation, and RNA and DNA translocation during transcription elongation.
Enforcement of Temporal Fidelity in Pyramidal Cells by Somatic Feed-Forward Inhibition
Authors: Pouille Frédéric , Scanziani Massimo
Published: July 2002

The temporal resolution of neuronal integration depends on the time window within which excitatory inputs summate to reach the threshold for spike generation. Here, we show that in rat hippocampal pyramidal cells this window is very narrow (less than 2 milliseconds). This narrowness results from the short delay with which disynaptic feed-forward inhibition follows monosynaptic excitation. Simultaneous somatic and dendritic recordings indicate that feed-forward inhibition is much stronger in the soma than in the dendrites, resulting in a broader integration window in the latter compartment. Thus, the subcellular partitioning of feed-forward inhibition enforces precise coincidence detection in the soma, while allowing dendrites to sum incoming activity over broader time windows.
Hydrodynamic Trail-Following in Harbor Seals (
Phoca vitulina
)
Authors: Dehnhardt Guido , Mauck Björn , Hanke Wolf , Bleckmann Horst
Published: July 2002

Marine mammals often forage in dark or turbid waters. Whereas dolphins use echolocation under such conditions, pinnipeds apparently lack this sensory ability. For seals hunting in the dark, one source of sensory information may consist of fish-generated water movements, which seals can detect with their highly sensitive whiskers. Water movements in the wake of fishes persist for several minutes. Here we show that blindfolded seals can use their whiskers to detect and accurately follow hydrodynamic trails generated by a miniature submarine. This shows that hydrodynamic information can be used for long-distance prey location.
Homeostatic Regulation of the Immune System by Receptor Tyrosine Kinases of the Tyro 3 Family
Authors: Lu Qingxian , Lemke Greg
Published: July 2002

Receptor tyrosine kinases and their ligands mediate cell-cell communication and interaction in many organ systems, but have not been known to act in this capacity in the mature immune system. We now provide genetic evidence that three closely related receptor tyrosine kinases, Tyro 3, Axl, and Mer, play an essential immunoregulatory role. Mutant mice that lack these receptors develop a severe lymphoproliferative disorder accompanied by broad-spectrum autoimmunity. These phenotypes are cell nonautonomous with respect to lymphocytes and result from the hyperactivation of antigen-presenting cells in which the three receptors are normally expressed.
The Glass Transition of Water, Based on Hyperquenching Experiments
Authors: Velikov V. , Borick S. , Angell C. A.
Published: July 2002

The glass transition temperature (
T
g
) in water is still uncertain, with conflicting values reported in the literature. As with other hyperquenched glasses, water exhibits a large relaxation exotherm on reheating at the normal rate of 10 kelvin (K) per minute. This release of heat indicates the transformation of a high enthalpy state to a lower one found in slow-cooled glasses. When the exotherm temperature is scaled by
T
g
, the good glass-formers show a common pattern. However, for hyperquenched water, when this analysis is performed using the commonly accepted
T
g
= 136 K, its behavior appears completely different, but this should not be the case because enthalpy relaxation is fundamental to the calorimetric glass transition. With
T
g
= 165 ± 5 K, normal behavior is restored in comparison with other hyperquenched glasses and with the binary solution behavior of network-former systems (H
2
O, ZnCl
2
, or BeF
2
plus a second component). This revised value has relevance to the understanding of water- biomolecule interactions.
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification
Authors: Gorre Mercedes E. , Mohammed Mansoor , Ellwood Katharine , Hsu Nicholas , Paquette Ron , Rao P. Nagesh , Sawyers Charles L.
Published: July 2002

Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl kinase domain known to form a critical hydrogen bond with the drug. This substitution of threonine with isoleucine was sufficient to confer STI-571 resistance in a reconstitution experiment. In three patients, resistance was associated with progressive
BCR-ABL
gene amplification. These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance.
Positive Regulation of T Cell Activation and Integrin Adhesion by the Adapter Fyb/Slap
Authors: Griffiths Emily K. , Krawczyk Connie , Kong Young-Yun , Raab Monika , Hyduk Sharon J. , Bouchard Denis , Chan Vera S. , Kozieradzki Ivona , Oliveira-dos-Santos Antonio J. , Wakeham Andrew , Ohashi Pamela S. , Cybulsky Myron I. , Rudd Christopher E. , Penninger Josef M.
Published: July 2002

The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb/Slap is also required in vivo for T cell–dependent immune responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion.
Logic Circuits with Carbon Nanotube Transistors
Authors: Bachtold Adrian , Hadley Peter , Nakanishi Takeshi , Dekker Cees
Published: July 2002

We demonstrate logic circuits with field-effect transistors based on single carbon nanotubes. Our device layout features local gates that provide excellent capacitive coupling between the gate and nanotube, enabling strong electrostatic doping of the nanotube from
p
-doping to
n
-doping and the study of the nonconventional long-range screening of charge along the one-dimensional nanotubes. The transistors show favorable device characteristics such as high gain (>10), a large on-off ratio (>10
5
), and room-temperature operation. Importantly, the local-gate layout allows for integration of multiple devices on a single chip. Indeed, we demonstrate one-, two-, and three-transistor circuits that exhibit a range of digital logic operations, such as an inverter, a logic NOR, a static random-access memory cell, and an ac ring oscillator.
Logic Gates and Computation from Assembled Nanowire Building Blocks
Authors: Huang Yu , Duan Xiangfeng , Cui Yi , Lauhon Lincoln J. , Kim Kyoung-Ha , Lieber Charles M.
Published: July 2002

Miniaturization in electronics through improvements in established “top-down” fabrication techniques is approaching the point where fundamental issues are expected to limit the dramatic increases in computing seen over the past several decades. Here we report a “bottom-up” approach in which functional device elements and element arrays have been assembled from solution through the use of electronically well-defined semiconductor nanowire building blocks. We show that crossed nanowire p-n junctions and junction arrays can be assembled in over 95% yield with controllable electrical characteristics, and in addition, that these junctions can be used to create integrated nanoscale field-effect transistor arrays with nanowires as both the conducting channel and gate electrode. Nanowire junction arrays have been configured as key OR, AND, and NOR logic-gate structures with substantial gain and have been used to implement basic computation.
Low-Frequency Signals in Long Tree-Ring Chronologies for Reconstructing Past Temperature Variability
Authors: Esper Jan , Cook Edward R. , Schweingruber Fritz H.
Published: July 2002

Preserving multicentennial climate variability in long tree-ring records is critically important for reconstructing the full range of temperature variability over the past 1000 years. This allows the putative “Medieval Warm Period” (MWP) to be described and to be compared with 20th-century warming in modeling and attribution studies. We demonstrate that carefully selected tree-ring chronologies from 14 sites in the Northern Hemisphere (NH) extratropics can preserve such coherent large-scale, multicentennial temperature trends if proper methods of analysis are used. In addition, we show that the average of these chronologies supports the large-scale occurrence of the MWP over the NH extratropics.
Crystal Structure of Arp2/3 Complex
Authors: Robinson Robert C. , Turbedsky Kirsi , Kaiser Donald A. , Marchand Jean-Baptiste , Higgs Henry N. , Choe Senyon , Pollard Thomas D.
Published: July 2002

We determined a crystal structure of bovine Arp2/3 complex, an assembly of seven proteins that initiates actin polymerization in eukaryotic cells, at 2.0 angstrom resolution. Actin-related protein 2 (Arp2) and Arp3 are folded like actin, with distinctive surface features. Subunits ARPC2 p34 and ARPC4 p20 in the core of the complex associate through long carboxyl-terminal α helices and have similarly folded amino-terminal α/β domains. ARPC1 p40 is a seven-blade β propeller with an insertion that may associate with the side of an actin filament. ARPC3 p21 and ARPC5 p16 are globular α-helical subunits. We predict that WASp/Scar proteins activate Arp2/3 complex by bringing Arp2 into proximity with Arp3 for nucleation of a branch on the side of a preexisting actin filament.
Combinatorial Synthesis of Genetic Networks
Authors: Guet Călin C. , Elowitz Michael B. , Hsing Weihong , Leibler Stanislas
Published: July 2002

A central problem in biology is determining how genes interact as parts of functional networks. Creation and analysis of synthetic networks, composed of well-characterized genetic elements, provide a framework for theoretical modeling. Here, with the use of a combinatorial method, a library of networks with varying connectivity was generated in
Escherichia coli
. These networks were composed of genes encoding the transcriptional regulators LacI, TetR, and lambda CI, as well as the corresponding promoters. They displayed phenotypic behaviors resembling binary logical circuits, with two chemical “inputs” and a fluorescent protein “output.” Within this simple system, diverse computational functions arose through changes in network connectivity. Combinatorial synthesis provides an alternative approach for studying biological networks, as well as an efficient method for producing diverse phenotypes in vivo.
Metabolic Enzymes of Mycobacteria Linked to Antioxidant Defense by a Thioredoxin-Like Protein
Authors: Bryk R. , Lima C. D. , Erdjument-Bromage H. , Tempst P. , Nathan C.
Published: July 2002

Mycobacterium tuberculosis
(Mtb) mounts a stubborn defense against oxidative and nitrosative components of the immune response. Dihydrolipoamide dehydrogenase (Lpd) and dihydrolipoamide succinyltransferase (SucB) are components of α-ketoacid dehydrogenase complexes that are central to intermediary metabolism. We find that Lpd and SucB support Mtb's antioxidant defense. The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD. The 2.0 angstrom AhpD crystal structure reveals a thioredoxin-like active site that is responsive to lipoamide. We propose that Lpd, SucB (the only lipoyl protein detected in Mtb), AhpD, and AhpC together constitute a nicotinamide adenine dinucleotide (reduced)–dependent peroxidase and peroxynitrite reductase. AhpD thus represents a class of thioredoxin-like molecules that enables an antioxidant defense.
Repairing the Injured Spinal Cord
Authors: Schwab Martin E.
Published: July 2002

Certain cell, molecular, and bioengineering strategies for repairing the injured spinal cord are showing encouraging results (either alone or in combination) in animal models, with limited recovery of mobility being reported in some cases.
Neurofibromas in NF1: Schwann Cell Origin and Role of Tumor Environment
Authors: Zhu Yuan , Ghosh Pritam , Charnay Patrick , Burns Dennis K. , Parada Luis F.
Published: July 2002

Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose functional loss results in the development of benign neurofibromas that can progress to malignancy. Neurofibromas are complex tumors composed of axonal processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through use of a conditional (
cre
/
lox
) allele, we show that loss of NF1 in the Schwann cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic as well as heterozygosity in non-neoplastic cells. The requirement for a permissive haploinsufficient environment to allow tumorigenesis may have therapeutic implications for NF1 and other familial cancers.
Demographic Characteristics and Population Dynamical Patterns of Solitary Birds
Authors: Sæther Bernt-Erik , Engen Steinar , Matthysen Erik
Published: July 2002

In birds and many other animals, there are large interspecific differences in the magnitude of annual variation in population size. Using time-series data on populations of solitary bird species, we found that fluctuations in population size of solitary birds were affected by the deterministic characteristics of the population dynamics as well as the stochastic factors. In species with highly variable populations, annual variation in recruitment was positively related to the return rate of adults between successive breeding seasons. In stable populations, more recruits were found in years with low return rates of breeding adults. This identifies a gradient, associated with the position of the species along a “slow-fast” continuum of life history variation, from highly variable populations with a recruitment-driven demography to stable, strongly density-regulated populations with a survival-restricted demography. These results suggest that patterns in avian population fluctuations can be predicted from a knowledge of life-history characteristics and/or temporal variation in certain demographic traits.
Intra- and Interspecific Variation in Primate Gene Expression Patterns
Authors: Enard Wolfgang , Khaitovich Philipp , Klose Joachim , Zöllner Sebastian , Heissig Florian , Giavalisco Patrick , Nieselt-Struwe Kay , Muchmore Elaine , Varki Ajit , Ravid Rivka , Doxiadis Gaby M. , Bontrop Ronald E. , Pääbo Svante
Published: July 2002

Although humans and their closest evolutionary relatives, the chimpanzees, are 98.7% identical in their genomic DNA sequences, they differ in many morphological, behavioral, and cognitive aspects. The underlying genetic basis of many of these differences may be altered gene expression. We have compared the transcriptome in blood leukocytes, liver, and brain of humans, chimpanzees, orangutans, and macaques using microarrays, as well as protein expression patterns of humans and chimpanzees using two-dimensional gel electrophoresis. We also studied three mouse species that are approximately as related to each other as are humans, chimpanzees, and orangutans. We identified species-specific gene expression patterns indicating that changes in protein and gene expression have been particularly pronounced in the human brain.
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Authors: Brummelkamp Thijn R. , Bernards René , Agami Reuven
Published: July 2002

Mammalian genetic approaches to study gene function have been hampered by the lack of tools to generate stable loss-of-function phenotypes efficiently. We report here a new vector system, named pSUPER, which directs the synthesis of small interfering RNAs (siRNAs) in mammalian cells. We show that siRNA expression mediated by this vector causes efficient and specific down-regulation of gene expression, resulting in functional inactivation of the targeted genes. Stable expression of siRNAs using this vector mediates persistent suppression of gene expression, allowing the analysis of loss-of-function phenotypes that develop over longer periods of time. Therefore, the pSUPER vector constitutes a new and powerful system to analyze gene function in a variety of mammalian cell types.
Resolution of Lung Inflammation by CD44
Authors: Teder Priit , Vandivier R. William , Jiang Dianhua , Liang Jiurong , Cohn Lauren , Puré Ellen , Henson Peter M. , Noble Paul W.
Published: July 2002

Successful repair after tissue injury and inflammation requires resolution of the inflammatory response and removal of extracellular matrix breakdown products. We have examined whether the cell-surface adhesion molecule and hyaluronan receptor CD44 plays a role in resolving lung inflammation. CD44-deficient mice succumb to unremitting inflammation following noninfectious lung injury, characterized by impaired clearance of apoptotic neutrophils, persistent accumulation of hyaluronan fragments at the site of tissue injury, and impaired activation of transforming growth factor–β
1
. This phenotype was partially reversed by reconstitution with CD44
+
cells, thus demonstrating a critical role for this receptor in resolving lung inflammation.
A 160,000-Year Record of Dune Development and Atmospheric Circulation in Southern Arabia
Authors: Preusser Frank , Radies Dirk , Matter Albert
Published: July 2002

Aeolian deposits in the Wahiba Sands, Sultanate of Oman, reveal patterns of atmospheric circulation over the past 160,000 years. Luminescence dating indicates a correlation of dune activity with periods of low global sea level and decreased monsoon intensity. Evidence from dune orientation and sedimentary structures shows exclusively northbound transport of sand during times of high- latitude glaciation. These results are in contrast to the current paleocirculation model that assumes an increase of northwesterly winds because of a southward shift of the Intertropical Convergence Zone. Our results indicate that the circulation pattern during glacial times was comparable to that of the present.
Scanned Probe Imaging of Single-Electron Charge States in Nanotube Quantum Dots
Authors: Woodside Michael T. , McEuen Paul L.
Published: July 2002

An atomic force microscope was used to study single-electron motion in nanotube quantum dots. By applying a voltage to the microscope tip, the number of electrons occupying the quantum dot could be changed, causing Coulomb oscillations in the nanotube conductance. Spatial maps of these oscillations were used to locate individual dots and to study the electrostatic coupling between the dot and the tip. The electrostatic forces associated with single electrons hopping on and off the quantum dot were also measured. These forces changed the amplitude, frequency, and quality factor of the cantilever oscillation, demonstrating how single-electron motion can interact with a mechanical oscillator.
Schizophrenia: Diverse Approaches to a Complex Disease
Authors: Sawa Akira , Snyder Solomon H.
Published: July 2002

Schizophrenia is a debilitating mental illness that affects 1% of the population. Despite intensive study, its molecular etiology remains enigmatic. Like many common diseases, schizophrenia is multifactorial in origin, with both genetic and environmental contributions likely playing an important role in the manifestation of symptoms. Recent advances based on pharmacological studies, brain imaging analyses, and genetic research are now converging on tantalizing leads that point to a central role for several neurotransmitters, including dopamine, glutamate, and serotonin, that may interface with neurodevelopmental defects reflecting disease-related genetic aberrations. Here, we provide a brief overview of the parallel approaches being used to identify the molecular causes of schizophrenia and discuss possible directions for future research.
G Protein Pathways
Authors: Neves Susana R. , Ram Prahlad T. , Iyengar Ravi
Published: July 2002

The heterotrimeric guanine nucleotide–binding proteins (G proteins) are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. The extracellular signals are received by members of a large superfamily of receptors with seven membrane-spanning regions that activate the G proteins, which route the signals to several distinct intracellular signaling pathways. These pathways interact with one another to form a network that regulates metabolic enzymes, ion channels, transporters, and other components of the cellular machinery controlling a broad range of cellular processes, including transcription, motility, contractility, and secretion. These cellular processes in turn regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis.
Cholesterol Modification of Hedgehog Signaling Proteins in Animal Development
Authors: Porter Jeffery A. , Young Keith E. , Beachy Philip A.
Published: July 2002

Hedgehog (Hh) proteins comprise a family of secreted signaling molecules essential for patterning a variety of structures in animal embryogenesis. During biosynthesis, Hh undergoes an autocleavage reaction, mediated by its carboxyl-terminal domain, that produces a lipid-modified amino-terminal fragment responsible for all known Hh signaling activity. Here it is reported that cholesterol is the lipophilic moiety covalently attached to the amino-terminal signaling domain during autoprocessing and that the carboxyl-terminal domain acts as an intramolecular cholesterol transferase. This use of cholesterol to modify embryonic signaling proteins may account for some of the effects of perturbed cholesterol biosynthesis on animal development.
Nanocapillarity and Chemistry in Carbon Nanotubes
Authors: Ugarte D. , Châtelain A. , de Heer W. A.
Published: July 2002

Open carbon nanotubes were filled with molten silver nitrate by capillary forces. Only those tubes with inner diameters of 4 nanometers or more were filled, suggesting a capillarity size dependence as a result of the lowering of the nanotube-salt interface energy with increasing curvature of the nanotube walls. Nanotube cavities should also be less chemically reactive than graphite and may serve as nanosize test tubes. This property has been illustrated by monitoring the decomposition of silver nitrate within nanotubes in situ in an electron microscope, which produced chains of silver nanobeads separated by high-pressure gas pockets.
Late Complications of Immune Deviation Therapy in a Nonhuman Primate
Authors: Genain Claude P. , Abel Kristina , Belmar Nicole , Villinger François , Rosenberg Daniel P. , Linington Christopher , Raine Cedric S. , Hauser Stephen L.
Published: July 2002

The administration of antigens in soluble form can induce antigen-specific immune tolerance and suppress experimental autoimmune diseases. In a marmoset model of multiple sclerosis induced by myelin oligodendrocyte glycoprotein (MOG), marmosets tolerized to MOG were protected against acute disease, but after tolerization treatment a lethal demyelinating disorder emerged. In these animals, MOG-specific T cell proliferative responses were transiently suppressed, cytokine production was shifted from a T helper type 1 (T
H
1) to a T
H
2 pattern, and titers of autoantibodies to MOG were enhanced. Thus, immune deviation can increase concentrations of pathogenic autoantibodies and in some circumstances exacerbate autoimmune disease.
Requirement for the Transcription Factor LSIRF/IRF4 for Mature B and T Lymphocyte Function
Authors: Mittrücker Hans-Willi , Matsuyama Toshifumi , Grossman Alex , Kündig Thomas M. , Potter Julia , Shahinian Arda , Wakeham Andrew , Patterson Bruce , Ohashi Pamela S. , Mak Tak W.
Published: July 2002

Lymphocyte-specific interferon regulatory factor (LSIRF) (now called IRF4) is a transcription factor expressed only in lymphocytes. Mice deficient in IRF4 showed normal distribution of B and T lymphocyes at 4 to 5 weeks of age but developed progressive generalized lymphadenopathy. IRF4-deficient mice exhibited a profound reduction in serum immunoglobulin concentrations and did not mount detectable antibody responses. T lymphocyte function was also impaired in vivo; these mice could not generate cytotoxic or antitumor responses. Thus, IRF4 is essential for the function and homeostasis of both mature B and mature T lymphocytes.
A Unified Theory Based on
SO
(5) Symmetry of Superconductivity and Antiferromagnetism
Authors: Zhang Shou-Cheng
Published: July 2002

The complex phase diagram of high-critical temperature (
T
c
) superconductors can be deduced from an
SO
(5) symmetry principle that unifies antiferromagnetism and
d
-wave superconductivity. The approximate
SO
(5) symmetry has been derived from the microscopic Hamiltonian, and it becomes exact under renormalization group flow toward a bicritical point. This symmetry enables the construction of a
SO
(5) quantum nonlinear σ model that describes the phase diagram and the effective low-energy dynamics of the system. This model naturally explains the basic phenomenology of the high-
T
c
superconductors from the insulating to the underdoped and the optimally doped region.
Combinatorial Control Required for the Specificity of Yeast MAPK Signaling
Authors: Madhani Hiten D. , Fink Gerald R.
Published: July 2002

In yeast, an overlapping set of mitogen-activated protein kinase (MAPK) signaling components controls mating, haploid invasion, and pseudohyphal development. Paradoxically, a single downstream transcription factor, Ste12, is necessary for the execution of these distinct programs. Developmental specificity was found to require a transcription factor of the TEA/ATTS family, Tec1, which cooperates with Ste12 during filamentous and invasive growth. Purified derivatives of Ste12 and Tec1 bind cooperatively to enhancer elements called filamentation and invasion response elements (FREs), which program transcription that is specifically responsive to the MAPK signaling components required for filamentous growth. An FRE in the
TEC1
promoter functions in a positive feedback loop required for pseudohyphal development.
Mitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts
Authors: Irani Kaikobad , Xia Yong , Zweier Jay L. , Sollott Steven J. , Der Channing J. , Fearon Eric R. , Sundaresan Maitrayee , Finkel Toren , Goldschmidt-Clermont Pascal J.
Published: July 2002

NIH 3T3 fibroblasts stably transformed with a constitutively active isoform of p21
Ras
, H-Ras
V12
(v-H-Ras or EJ-Ras), produced large amounts of the reactive oxygen species superoxide (·O
2
−
). ·O
2
−
production was suppressed by the expression of dominant negative isoforms of Ras or Rac1, as well as by treatment with a farnesyltransferase inhibitor or with diphenylene iodonium, a flavoprotein inhibitor. The mitogenic activity of cells expressing H-Ras
V12
was inhibited by treatment with the chemical antioxidant
N
-acetyl-L-cysteine. Mitogen-activated protein kinase (MAPK) activity was decreased and c-Jun N-terminal kinase (JNK) was not activated in H-Ras
V12
-transformed cells. Thus, H-Ras
V12
-induced transformation can lead to the production of ·O
2
−
through one or more pathways involving a flavoprotein and Rac1. The implication of a reactive oxygen species, probably ·O
2
−
, as a mediator of Ras-induced cell cycle progression independent of MAPK and JNK suggests a possible mechanism for the effects of antioxidants against Ras-induced cellular transformation.
Kinetics of Response in Lymphoid Tissues to Antiretroviral Therapy of HIV-1 Infection
Authors: Cavert Winston , Notermans Daan W. , Staskus Katherine , Wietgrefe Stephen W. , Zupancic Mary , Gebhard Kristin , Henry Keith , Zhang Zhi-Qiang , Mills Roger , McDade Hugh , Goudsmit Jaap , Danner Sven A. , Haase Ashley T.
Published: July 2002

In lymphoid tissue, where human immunodeficiency virus–type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by ≥3.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared >99.9 percent of virus from the secondary lymphoid tissue reservoir.
Photodissociation of I
2
−
(Ar)

n

Clusters Studied with Anion Femtosecond Photoelectron Spectroscopy
Authors: Greenblatt B. Jefferys , Zanni Martin T. , Neumark Daniel M.
Published: July 2002

Anion femtosecond photoelectron spectroscopy was used to follow the dynamics of the I
2
−
(Ar)
6
and I
2
−
(Ar)
20
clusters subsequent to photodissociation of the I
2
−
chromophore. The experiments showed that photodissociation of the I
2
−
moiety in I
2
−
(Ar)
6
is complete by approximately 200 femtoseconds, just as in bare I
2
−
, but also that attractive interactions between the departing anion fragment and the solvent atoms persisted for 1200 femtoseconds. Photodissociation of I
2
−
(Ar)
20
results in caging of the I
2
−
followed by recombination and vibrational relaxation on the excited
Ã
2
Π

g
,3/2

and the ground
X̃
2
Σ

u

+
states; these processes are complete in 35 and 200 picoseconds, respectively.
Requirement of Guanosine Triphosphate-Bound Ran for Signal-Mediated Nuclear Protein Export
Authors: Richards Stephanie A. , Carey Kimberly L. , Macara Ian G.
Published: July 2002

A leucine-rich nuclear export signal (NES) allows rapid export of proteins from cell nuclei. Microinjection studies revealed a role for the guanosine triphosphatase (GTPase) Ran in NES-mediated export. Nuclear injection of a Ran mutant (Thr
24
→ Asn) blocked protein export but not import, whereas depletion of the Ran nucleotide exchange factor RCC1 blocked protein import but not export. However, injection of Ran GTPase-activating protein (RanGAP) into RCC1-depleted cell nuclei inhibited export. Coinjection with Ran mutants insensitive to RanGAP prevented this inhibition. Therefore, NES-mediated protein export appears to require a Ran-GTP complex but does not require Ran-dependent GTP hydrolysis.
Discrete Intensity Jumps and Intramolecular Electronic Energy Transfer in the Spectroscopy of Single Conjugated Polymer Molecules
Authors: Bout David A. Vanden , Yip Wai-Tak , Hu Dehong , Fu Dian-Kui , Swager Timothy M. , Barbara Paul F.
Published: July 2002

Single
-
molecule fluorescence spectroscopy of a multichromophoric conjugated polymer (molecular weight ∼20,000) revealed surprising single-step photobleaching kinetics and acute jumps in fluorescence intensity. These jumps were shown not to result from spectral diffusion and were attributed to fluctuations in the quantum yield of emission for the molecules. The data indicate efficient intramolecular electronic energy transfer along the polymer chain to a localized fluorescence-quenching polymer defect. The defects are created by reversible photochemistry of the polymer. These findings have implications for the use of conjugated polymers in light-emitting diode displays and sensors.
Synaptic Efficacy Enhanced by Glial Cells in Vitro
Authors: Pfrieger Frank W. , Barres Barbara A.
Published: July 2002

In the developing nervous system, glial cells guide axons to their target areas, but it is unknown whether they help neurons to establish functional synaptic connections. The role of glial cells in synapse formation and function was studied in cultures of purified neurons from the rat central nervous system. In glia-free cultures, retinal ganglion cells formed synapses with normal ultrastructure but displayed little spontaneous synaptic activity and high failure rates in evoked synaptic transmission. In cocultures with neuroglia, the frequency and amplitude of spontaneous postsynaptic currents were potentiated by 70-fold and 5-fold, respectively, and fewer transmission failures occurred. Glial cells increased the action potential–independent quantal release by 12-fold without affecting neuronal survival. Thus, developing neurons in culture form inefficient synapses that require glial signals to become fully functional.
Crystal Structure of Pentalenene Synthase: Mechanistic Insights on Terpenoid Cyclization Reactions in Biology
Authors: Lesburg Charles A. , Zhai Guangzhi , Cane David E. , Christianson David W.
Published: July 2002

The crystal structure of pentalenene synthase at 2.6 angstrom resolution reveals critical active site features responsible for the cyclization of farnesyl diphosphate into the tricyclic hydrocarbon pentalenene. Metal-triggered substrate ionization initiates catalysis, and the α-barrel active site serves as a template to channel and stabilize the conformations of reactive carbocation intermediates through a complex cyclization cascade. The core active site structure of the enzyme may be preserved among the greater family of terpenoid synthases, possibly implying divergence from a common ancestral synthase to satisfy biological requirements for increasingly diverse natural products.
Life and Death of Neurons in the Aging Brain
Authors: Morrison John H. , Hof Patrick R.
Published: July 2002

Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.
Mesoporous Platinum Films from Lyotropic Liquid Crystalline Phases
Authors: Attard George S. , Bartlett Philip N. , Coleman Nicholas R. B. , Elliott Joanne M. , Owen John R. , Wang Jin Hai
Published: July 2002

The lyotropic liquid crystalline phases of surfactants exhibit a rich polymorphism of structures that have long-range periodicities and whose characteristic repeat distances range from 2 to 15 nanometers. The electrochemical reduction of platinum salts confined to the aqueous environments of these phases leads to the deposition of platinum films that have a well-defined long-ranged porous nanostructure and high specific surface areas. These results suggest that the use of liquid crystalline plating solutions could be a versatile way to create mesoporous electrodes for batteries, fuel cells, electrochemical capacitors, and sensors.
Space Geodetic Observations of Nazca-South America Convergence Across the Central Andes
Authors: Norabuena Edmundo , Leffler-Griffin Lisa , Mao Ailin , Dixon Timothy , Stein Seth , Sacks I. Selwyn , Ocola Leonidas , Ellis Michael
Published: July 2002

Space geodetic data recorded rates and directions of motion across the convergent boundary zone between the oceanic Nazca and continental South American plates in Peru and Bolivia. Roughly half of the overall convergence, about 30 to 40 millimeters per year, accumulated on the locked plate interface and can be released in future earthquakes. About 10 to 15 millimeters per year of crustal shortening occurred inland at the sub-Andean foreland fold and thrust belt, indicating that the Andes are continuing to build. Little (5 to 10 millimeters per year) along-trench motion of coastal forearc slivers was observed, despite the oblique convergence.
A Potassium Channel Mutation in Neonatal Human Epilepsy
Authors: Biervert Christian , Schroeder Björn C. , Kubisch Christian , Berkovic Samuel F. , Propping Peter , Jentsch Thomas J. , Steinlein Ortrud K.
Published: July 2002

Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene (
KCNQ2
) located on 20q13.3 was isolated and found to be expressed in brain. Expression of
KCNQ2
in frog (
Xenopus laevis
) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five–base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.
A Structural Scaffolding of Intermediate Filaments in Health and Disease
Authors: Fuchs Elaine , Cleveland Don W.
Published: July 2002

The cytoplasm of animal cells is structured by a scaffolding composed of actin microfilaments, microtubules, and intermediate filaments. Intermediate filaments, so named because their 10-nanometer diameter is intermediate between that of microfilaments (6 nanometers) and microtubules (23 nanometers), assemble into an anastomosed network within the cytoplasm. In combination with a recently identified class of cross-linking proteins that mediate interactions between intermediate filaments and the other cytoskeletal networks, evidence is reviewed here that intermediate filaments provide a flexible intracellular scaffolding whose function is to structure cytoplasm and to resist stresses externally applied to the cell. Mutations that weaken this structural framework increase the risk of cell rupture and cause a variety of human disorders.
Interaction of a Golgi-Associated Kinesin-Like Protein with Rab6
Authors: Echard Arnaud , Jollivet Florence , Martinez Olivier , Lacapère Jean-Jacques , Rousselet Annie , Janoueix-Lerosey Isabelle , Goud Bruno
Published: July 2002

Rab guanosine triphosphatases regulate vesicular transport and membrane traffic within eukaryotic cells. Here, a kinesin-like protein that interacts with guanosine triphosphate (GTP)–bound forms of Rab6 was identified. This protein, termed Rabkinesin-6, was localized to the Golgi apparatus and shown to play a role in the dynamics of this organelle. The carboxyl-terminal domain of Rabkinesin-6, which contains the Rab6-interacting domain, inhibited the effects of Rab6-GTP on intracellular transport. Thus, a molecular motor is a potential effector of a Rab protein, and coordinated action between members of these two families of proteins could control membrane dynamics and directional vesicular traffic.
Regulation of Neurotransmitter Release Kinetics by NSF
Authors: Schweizer Felix E. , Dresbach Thomas , DeBello William M. , O'Connor Vincent , Augustine George J. , Betz Heinrich
Published: July 2002

NSF (
N
-ethylmaleimide–sensitive factor) is an adenosine triphosphatase (ATPase) that contributes to a protein complex essential for membrane fusion. The synaptic function of this protein was investigated by injecting, into the giant presynaptic terminal of squid, peptides that inhibit the ATPase activity of NSF stimulated by the soluble NSF attachment protein (SNAP). These peptides reduced the amount and slowed the kinetics of neurotransmitter release as a result of actions that required vesicle turnover and occurred at a step subsequent to vesicle docking. These results define NSF as an essential participant in synaptic vesicle exocytosis that regulates the kinetics of neurotransmitter release and, thereby, the integrative properties of synapses.
Sensorimotor Adaptation in Speech Production
Authors: Houde John F. , Jordan Michael I.
Published: July 2002

Human subjects are known to adapt their motor behavior to a shift of the visual field brought about by wearing prism glasses over their eyes. The analog of this phenomenon was studied in the speech domain. By use of a device that can feed back transformed speech signals in real time, subjects were exposed to phonetically sensible, online perturbations of their own speech patterns. It was found that speakers learn to adjust their production of a vowel to compensate for feedback alterations that change the vowel's perceived phonetic identity; moreover, the effect generalizes across phonetic contexts and to different vowels.
Species Distributions, Land Values, and Efficient Conservation
Authors: Ando Amy , Camm Jeffrey , Polasky Stephen , Solow Andrew
Published: July 2002

Efforts at species conservation in the United States have tended to be opportunistic and uncoordinated. Recently, however, ecologists and economists have begun to develop more systematic approaches. Here, the problem of efficiently allocating scarce conservation resources in the selection of sites for biological reserves is addressed. With the use of county-level data on land prices and the incidence of endangered species, it is shown that accounting for heterogeneity in land prices results in a substantial increase in efficiency in terms of either the cost of achieving a fixed coverage of species or the coverage attained from a fixed budget.