bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and implementation of a detector for on-axis electrons for enabling enhanced imaging of topographical structures
Authors: Munack Harry , Kögler Walter , Baumgarten Holger , Rübekohl Christian , Adamec Pavel , Degenhardt Ralf , Feuerbaum Hans-Peter , Winkler Dieter
Published: July 2002

A novel electron detection scheme for use in scanning electron microscopes is presented. The detector features enhanced imaging of topographical and especially high-aspect-ratio structures by selective detection of on-axis electrons. It consists of a magnetostatic beam separator which splits the on-axis backscattered and secondary electrons from the primary electron beam without causing first-order chromatic aberrations. The design concept has been proven by experimental evaluations which demonstrate the enhanced imaging capabilities of this new detector.
Minimizing damage during focused-ion-beam induced desorption of hydrogen
Authors: Fuhrmann H. , Candel A. , Döbeli M. , Mühle R.
Published: July 2002

The newly developed method of silicon surface structuring by local desorption of passivating hydrogen with a 30 keV Si+ focused ion beam has been investigated with respect to the damage induced by the irradiation. The substrate damage was analyzed by atomic force microscopy and thermal wave analysis. The measurements show that damage can be minimized if the substrate is heated to 200 °C during irradiation and dwell times below 20 μs are used for the exposure, even at a dose of 2×1015 cm−2, which exceeds the minimum dose required to define a feature by a factor of 10. The irradiated surfaces remain flat after KOH etching, the surface roughness being smaller than 0.3 nm for all samples.
Direct current and pulsed operation of contaminated liquid metal ion sources
Authors: Olson R. T. , Panitz J. A.
Published: July 2002

Gallium liquid metal ion sources (LMISs) have been exposed to common gas and liquid phase laboratory and vacuum system contaminants. Minor changes in the direct current and pulsed operation of the LMISs were observed after contaminant exposure. Time-of-flight mass analysis of the ion emission revealed that contaminant species are primarily field evaporated with the gallium substrate. Low vapor pressure contaminants have been observed to constitute a significant portion of the total emitted ion current.
Temperature-graded InAlAs buffers applied on InGaAs/InAlAs/InP high electron mobility transistor heterostructures
Authors: Arbiol J. , Peiró F. , Cornet A. , Michelakis K. , Georgakilas A.
Published: July 2002

In this work we studied the possibility of improving InGaAs/InAlAs-on-InP high electron mobility transistor (HEMT) devices by using temperature-graded InAlAs buffer layers with growing temperatures in the range of Tg=250–560 °C. Our specimens were grown by molecular beam epitaxy and we analyzed them using plane view and cross-sectional transmission electron microscopy, atomic force microscopy, scanning electron microscopy and Hall effect measurements. We found that growth at the optimum temperature (Tg=530 °C) of a thin InAlAs buffer sublayer between the InP substrate and the thick InAlAs buffer layer (grown at low or high Tg) can dramatically improve the crystalline quality of our HEMT devices. Therefore the growth temperature of the buffer could be used as engineering parameter to tailor the electronic properties of InAlAs layers without interfering with the layers’ crystalline quality, already assured by the first optimized nanometers.
Two Functional Channels from Primary Visual Cortex to Dorsal Visual Cortical Areas
Authors: Yabuta N. Harumi , Sawatari Atomu , Callaway Edward M.
Published: July 2002

Relationships between the M and P retino-geniculo-cortical visual pathways and “dorsal” visual areas were investigated by measuring the sources of local excitatory input to individual neurons in layer 4B of primary visual cortex. We found that contributions of the M and P pathways to layer 4B neurons are dependent on cell type. Spiny stellate neurons receive strong M input through layer 4Cα and no significant P input through layer 4Cβ. In contrast, pyramidal neurons in layer 4B receive strong input from both layers 4Cα and 4Cβ. These observations, along with evidence that direct input from layer 4B to area MT arises predominantly from spiny stellates, suggest that these different cell types constitute two functionally specialized subsystems.
Observations of Ozone Formation in Power Plant Plumes and Implications for Ozone Control Strategies
Authors: Ryerson T. B. , Trainer M. , Holloway J. S. , Parrish D. D. , Huey L. G. , Sueper D. T. , Frost G. J. , Donnelly S. G. , Schauffler S. , Atlas E. L. , Kuster W. C. , Goldan P. D. , Hübler G. , Meagher J. F. , Fehsenfeld F. C.
Published: July 2002

Data taken in aircraft transects of emissions plumes from rural U.S. coal-fired power plants were used to confirm and quantify the nonlinear dependence of tropospheric ozone formation on plume NO

x

(NO plus NO
2
) concentration, which is determined by plant NO

x

emission rate and atmospheric dispersion. The ambient availability of reactive volatile organic compounds, principally biogenic isoprene, was also found to modulate ozone production rate and yield in these rural plumes. Differences of a factor of 2 or greater in plume ozone formation rates and yields as a function of NO

x

and volatile organic compound concentrations were consistently observed. These large differences suggest that consideration of power plant NO

x

emission rates and geographic locations in current and future U.S. ozone control strategies could substantially enhance the efficacy of NO

x

reductions from these sources.
Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP
Authors: Lewis Jada , Dickson Dennis W. , Lin Wen-Lang , Chisholm Louise , Corral Anthony , Jones Graham , Yen Shu-Hui , Sahara Naruhiko , Skipper Lisa , Yager Debra , Eckman Chris , Hardy John , Hutton Mike , McGowan Eileen
Published: July 2002

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant β-amyloid precursor protein (APP), thus modulating the APP-Aβ (β-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed Aβ deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or Aβ influences the formation of neurofibrillary tangles. The interaction between Aβ and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.
Defective Lymphotoxin-β Receptor-Induced NF-κB Transcriptional Activity in NIK-Deficient Mice
Authors: Yin Li , Wu Lin , Wesche Holger , Arthur Cora D. , White J. Michael , Goeddel David V. , Schreiber Robert D.
Published: July 2002

The role of NF-κB–inducing kinase (NIK) in cytokine signaling remains controversial. To identify the physiologic functions of NIK, we disrupted the NIK locus by gene targeting. Although NIK
–/–
mice displayed abnormalities in both lymphoid tissue development and antibody responses, NIK
–/–
cells manifested normal NF-κB DNA binding activity when treated with a variety of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and lymphotoxin-β (LTβ). However, NIK was selectively required for gene transcription induced through ligation of LTβ receptor but not TNF receptors. These results reveal that NIK regulates the transcriptional activity of NF-κB in a receptor-restricted manner.
Experimental Verification of a Negative Index of Refraction
Authors: Shelby R. A. , Smith D. R. , Schultz S.
Published: July 2002

We present experimental scattering data at microwave frequencies on a structured metamaterial that exhibits a frequency band where the effective index of refraction (
n
) is negative. The material consists of a two-dimensional array of repeated unit cells of copper strips and split ring resonators on interlocking strips of standard circuit board material. By measuring the scattering angle of the transmitted beam through a prism fabricated from this material, we determine the effective
n
, appropriate to Snell's law. These experiments directly confirm the predictions of Maxwell's equations that
n
is given by the negative square root of
ɛ
·μ for the frequencies where both the permittivity (
ɛ
) and the permeability (μ) are negative. Configurations of geometrical optical designs are now possible that could not be realized by positive index materials.
Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
Authors: Wei Michael C. , Zong Wei-Xing , Cheng Emily H.-Y. , Lindsten Tullia , Panoutsakopoulou Vily , Ross Andrea J. , Roth Kevin A. , MacGregor Grant R. , Thompson Craig B. , Korsmeyer Stanley J.
Published: July 2002

Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a “BH3-domain–only” BCL-2 family member, triggers the homooligomerization of “multidomain” conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both
Bax
and
Bak
, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a “multidomain” proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli.
The Recent Increase in Atlantic Hurricane Activity: Causes and Implications
Authors: Goldenberg Stanley B. , Landsea Christopher W. , Mestas-Nuñez Alberto M. , Gray William M.
Published: July 2002

The years 1995 to 2000 experienced the highest level of North Atlantic hurricane activity in the reliable record. Compared with the generally low activity of the previous 24 years (1971 to 1994), the past 6 years have seen a doubling of overall activity for the whole basin, a 2.5-fold increase in major hurricanes (≥50 meters per second), and a fivefold increase in hurricanes affecting the Caribbean. The greater activity results from simultaneous increases in North Atlantic sea-surface temperatures and decreases in vertical wind shear. Because these changes exhibit a multidecadal time scale, the present high level of hurricane activity is likely to persist for an additional ∼10 to 40 years. The shift in climate calls for a reevaluation of preparedness and mitigation strategies.
Diversity and Productivity in a Long-Term Grassland Experiment
Authors: Tilman David , Reich Peter B. , Knops Johannes , Wedin David , Mielke Troy , Lehman Clarence
Published: July 2002

Plant diversity and niche complementarity had progressively stronger effects on ecosystem functioning during a 7-year experiment, with 16-species plots attaining 2.7 times greater biomass than monocultures. Diversity effects were neither transients nor explained solely by a few productive or unviable species. Rather, many higher-diversity plots outperformed the best monoculture. These results help resolve debate over biodiversity and ecosystem functioning, show effects at higher than expected diversity levels, and demonstrate, for these ecosystems, that even the best-chosen monocultures cannot achieve greater productivity or carbon stores than higher-diversity sites.
Trans
-Suppression of Misfolding in an Amyloid Disease
Authors: Hammarström Per , Schneider Frank , Kelly Jeffery W.
Published: July 2002

The transthyretin (TTR) amyloid diseases, representative of numerous misfolding disorders, are of considerable interest because there are mutations that cause or suppress disease. The Val
30
→ Met
30
(V30M) TTR mutation is the most prevalent cause of familial amyloid polyneuropathy in heterozygotes, whereas a Thr
119
→ Met
119
(T119M) mutation on the second TTR allele protects V30M carriers from disease. Here, we show that the incorporation of one or more T119M TTR subunits into a predominantly V30M tetramer strongly stabilized the mixed tetramer against dissociation. Dissociation is required for amyloid formation, so these findings provide a molecular explanation for intragenic
trans
-suppression of amyloidosis. The data also suggest a potential therapeutic strategy, provide insight into tissue-specific deposition and amyloid composition, and support the validity of the amyloid hypothesis in human disease.
The Organic Content of the Tagish Lake Meteorite
Authors: Pizzarello Sandra , Huang Yongsong , Becker Luann , Poreda Robert J. , Nieman Ronald A. , Cooper George , Williams Michael
Published: July 2002

The Tagish Lake meteorite fell last year on a frozen lake in Canada and may provide the most pristine material of its kind. Analyses have now shown this carbonaceous chondrite to contain a suite of soluble organic compounds (∼100 parts per million) that includes mono- and dicarboxylic acids, dicarboximides, pyridine carboxylic acids, a sulfonic acid, and both aliphatic and aromatic hydrocarbons. The insoluble carbon exhibits exclusive aromatic character, deuterium enrichment, and fullerenes containing “planetary” helium and argon. The findings provide insight into an outcome of early solar chemical evolution that differs from any seen so far in meteorites.
Aerosols, Climate, and the Hydrological Cycle
Authors: Ramanathan V. , Crutzen P. J. , Kiehl J. T. , Rosenfeld D.
Published: July 2002

Human activities are releasing tiny particles (aerosols) into the atmosphere. These human-made aerosols enhance scattering and absorption of solar radiation. They also produce brighter clouds that are less efficient at releasing precipitation. These in turn lead to large reductions in the amount of solar irradiance reaching Earth's surface, a corresponding increase in solar heating of the atmosphere, changes in the atmospheric temperature structure, suppression of rainfall, and less efficient removal of pollutants. These aerosol effects can lead to a weaker hydrological cycle, which connects directly to availability and quality of fresh water, a major environmental issue of the 21st century.
Specificity and Stability in Topology of Protein Networks
Authors: Maslov Sergei , Sneppen Kim
Published: July 2002

Molecular networks guide the biochemistry of a living cell on multiple levels: Its metabolic and signaling pathways are shaped by the network of interacting proteins, whose production, in turn, is controlled by the genetic regulatory network. To address topological properties of these two networks, we quantified correlations between connectivities of interacting nodes and compared them to a null model of a network, in which all links were randomly rewired. We found that for both interaction and regulatory networks, links between highly connected proteins are systematically suppressed, whereas those between a highly connected and low-connected pairs of proteins are favored. This effect decreases the likelihood of cross talk between different functional modules of the cell and increases the overall robustness of a network by localizing effects of deleterious perturbations.
Role of Erv29p in Collecting Soluble Secretory Proteins into ER-Derived Transport Vesicles
Authors: Belden William J. , Barlowe Charles
Published: July 2002

Proteins are transported from the endoplasmic reticulum (ER) in vesicles formed by coat protein complex II (COPII). Soluble secretory proteins are thought to leave the ER in these vesicles by “bulk flow” or through recognition by hypothetical shuttling receptors. We found that Erv29p, a conserved transmembrane protein, was directly required for packaging glycosylated pro-α-factor (gpαf) into COPII vesicles in
Saccharomyces cerevisiae
. Further, an Erv29p-gpαf complex was isolated from ER-derived transport vesicles. In vivo, export of gpαf from the ER was saturable and depended on the expression level of Erv29p. These results indicate that membrane receptors can link soluble cargo proteins to the COPII coat.
Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor β
Authors: Zhu Yan , Bian Zhao , Lu Ping , Karas Richard H. , Bao Lin , Cox Daniel , Hodgin Jeffrey , Shaul Philip W. , Thorén Peter , Smithies Oliver , Gustafsson Jan-Åke , Mendelsohn Michael E.
Published: July 2002

Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor β (ERβ)–deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERβ-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERβ-deficient mice. Vascular smooth muscle cells isolated from ERβ-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERβ-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERβ in the regulation of vascular function and blood pressure.
Requirement of
Math1
for Secretory Cell Lineage Commitment in the Mouse Intestine
Authors: Yang Qi , Bermingham Nessan A. , Finegold Milton J. , Zoghbi Huda Y.
Published: July 2002

The mouse small intestinal epithelium consists of four principal cell types deriving from one multipotent stem cell: enterocytes, goblet, enteroendocrine, and Paneth cells. Previous studies showed that
Math1
, a basic helix-loop-helix (bHLH) transcription factor, is expressed in the gut. We find that loss of
Math1
leads to depletion of goblet, enteroendocrine, and Paneth cells without affecting enterocytes. Colocalization of
Math1
with Ki-67 in some proliferating cells suggests that secretory cells (goblet, enteroendocrine, and Paneth cells) arise from a common progenitor that expresses
Math1
, whereas absorptive cells (enterocytes) arise from a progenitor that is
Math1
-independent. The continuous rapid renewal of these cells makes the intestinal epithelium a model system for the study of stem cell regeneration and lineage commitment.
A Thermally Re-mendable Cross-Linked Polymeric Material
Authors: Chen Xiangxu , Dam Matheus A. , Ono Kanji , Mal Ajit , Shen Hongbin , Nutt Steven R. , Sheran Kevin , Wudl Fred
Published: July 2002

We have developed a transparent organic polymeric material that can repeatedly mend or “re-mend” itself under mild conditions. The material is a tough solid at room temperature and below with mechanical properties equaling those of commercial epoxy resins. At temperatures above 120°C, approximately 30% (as determined by solid-state nuclear magnetic resonance spectroscopy) of “intermonomer” linkages disconnect but then reconnect upon cooling, This process is fully reversible and can be used to restore a fractured part of the polymer multiple times, and it does not require additional ingredients such as a catalyst, additional monomer, or special surface treatment of the fractured interface.
Atomic-Level Observation of Disclination Dipoles in Mechanically Milled, Nanocrystalline Fe
Authors: Murayama M. , Howe J. M. , Hidaka H. , Takaki S.
Published: July 2002

Plastic deformation of materials occurs by the motion of defects known as dislocations and disclinations. High-resolution transmission electron microscopy was used to directly reveal the individual dislocations that constitute partial disclination dipoles in nanocrystalline, body-centered cubic iron that had undergone severe plastic deformation by mechanical milling. The mechanisms by which the formation and migration of such partial disclination dipoles during deformation allow crystalline solids to fragment and rotate at the nanometer level are described. Such rearrangements are important basic phenomena that occur during material deformation, and hence, they may be critical in the formation of nanocrystalline metals by mechanical milling and other deformation processes.
Brain to Plasma Amyloid-β Efflux: a Measure of Brain Amyloid Burden in a Mouse Model of Alzheimer's Disease
Authors: DeMattos Ronald B. , Bales Kelly R. , Cummins David J. , Paul Steven M. , Holtzman David M.
Published: July 2002

The deposition of amyloid-β (Aβ) peptides into amyloid plaques precedes the cognitive dysfunction of Alzheimer's disease (AD) by years. Biomarkers indicative of brain amyloid burden could be useful for identifying individuals at high risk for developing AD. As in AD in humans, baseline plasma Aβ levels in a transgenic mouse model of AD did not correlate with brain amyloid burden. However, after peripheral administration of a monoclonal antibody to Aβ (m266), we observed a rapid increase in plasma Aβ and the magnitude of this increase was highly correlated with amyloid burden in the hippocampus and cortex. This method may be useful for quantifying brain amyloid burden in patients at risk for or those who have been diagnosed with AD.
Partitioning of Lipid-Modified Monomeric GFPs into Membrane Microdomains of Live Cells
Authors: Zacharias David A. , Violin Jonathan D. , Newton Alexandra C. , Tsien Roger Y.
Published: July 2002

Many proteins associated with the plasma membrane are known to partition into submicroscopic sphingolipid- and cholesterol-rich domains called lipid rafts, but the determinants dictating this segregation of proteins in the membrane are poorly understood. We suppressed the tendency of
Aequorea
fluorescent proteins to dimerize and targeted these variants to the plasma membrane using several different types of lipid anchors. Fluorescence resonance energy transfer measurements in living cells revealed that acyl but not prenyl modifications promote clustering in lipid rafts. Thus the nature of the lipid anchor on a protein is sufficient to determine submicroscopic localization within the plasma membrane.
Genomewide Analysis of mRNA Processing in Yeast Using Splicing-Specific Microarrays
Authors: Clark Tyson A. , Sugnet Charles W. , Ares Manuel
Published: July 2002

Introns interrupt almost every eukaryotic protein-coding gene, yet how the splicing apparatus interprets the genome during messenger RNA (mRNA) synthesis is poorly understood. We designed microarrays to distinguish spliced from unspliced RNA for each intron-containing yeast gene and measured genomewide effects on splicing caused by loss of 18 different mRNA processing factors. After accommodating changes in transcription and decay by using gene-specific indexes, functional relationships between mRNA processing factors can be identified through their common effects on spliced and unspliced RNA. Groups of genes with different dependencies on mRNA processing factors are also apparent. Quantitative polymerase chain reactions confirm the array-based finding that Prp17p and Prp18p are not dispensable for removal of introns with short branchpoint-to-3′ splice site distances.
Maneuvering in the Complex Path from Genotype to Phenotype
Authors: Strohman Richard
Published: July 2002

Human disease phenotypes are controlled not only by genes but by lawful self-organizing networks that display system-wide dynamics. These networks range from metabolic pathways to signaling pathways that regulate hormone action. When perturbed, networks alter their output of matter and energy which, depending on the environmental context, can produce either a pathological or a normal phenotype. Study of the dynamics of these networks by approaches such as metabolic control analysis may provide new insights into the pathogenesis and treatment of complex diseases.
Role of Delayed Nuclear Envelope Breakdown and Mitosis in
Wolbachia
-Induced Cytoplasmic Incompatibility
Authors: Tram Uyen , Sullivan William
Published: July 2002

The bacterium
Wolbachia
manipulates reproduction in millions of insects worldwide; the most common effect is cytoplasmic incompatibility (CI). We found that CI resulted from delayed nuclear envelope breakdown of the male pronucleus in
Nasonia vitripennis
. This caused asynchrony between the male and female pronuclei and, ultimately, loss of paternal chromosomes at the first mitosis. When
Wolbachia
were present in the egg, synchrony was restored, which explains suppression of CI in these crosses. These results suggest that
Wolbachia
target cell cycle regulatory proteins. A striking consequence of CI is that it alters the normal pattern of reciprocal centrosome inheritance in
Nasonia.
Balancing Life-Style and Genomics Research for Disease Prevention
Authors: Willett Walter C.
Published: July 2002

Genetic and environmental factors, including diet and life-style, both contribute to cardiovascular disease, cancers, and other major causes of mortality, but various lines of evidence indicate that environmental factors are most important. Overly enthusiastic expectations regarding the benefits of genetic research for disease prevention have the potential to distort research priorities and spending for health. However, integration of new genetic information into epidemiologic studies can help clarify causal relations between both life-style and genetic factors and risks of disease. Thus, a balanced approach should provide the best data to make informed choices about the most effective means to prevent disease.
The Danger Model: A Renewed Sense of Self
Authors: Matzinger Polly
Published: July 2002

For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign.
Life and the Evolution of Earth's Atmosphere
Authors: Kasting James F. , Siefert Janet L.
Published: July 2002

Harvesting light to produce energy and oxygen (photosynthesis) is the signature of all land plants. This ability was co-opted from a precocious and ancient form of life known as cyanobacteria. Today these bacteria, as well as microscopic algae, supply oxygen to the atmosphere and churn out fixed nitrogen in Earth's vast oceans. Microorganisms may also have played a major role in atmosphere evolution before the rise of oxygen. Under the more dim light of a young sun cooler than today's, certain groups of anaerobic bacteria may have been pumping out large amounts of methane, thereby keeping the early climate warm and inviting. The evolution of Earth's atmosphere is linked tightly to the evolution of its biota.
Rapid Changes in Flowering Time in British Plants
Authors: Fitter A. H. , Fitter R. S. R.
Published: July 2002

The average first flowering date of 385 British plant species has advanced by 4.5 days during the past decade compared with the previous four decades: 16% of species flowered significantly earlier in the 1990s than previously, with an average advancement of 15 days in a decade. Ten species (3%) flowered significantly later in the 1990s than previously. These data reveal the strongest biological signal yet of climatic change. Flowering is especially sensitive to the temperature in the previous month, and spring-flowering species are most responsive. However, large interspecific differences in this response will affect both the structure of plant communities and gene flow between species as climate warms. Annuals are more likely to flower early than congeneric perennials, and insect-pollinated species more than wind-pollinated ones.
Control of Spatiotemporal Coherence of a Thalamic Oscillation by Corticothalamic Feedback
Authors: Contreras Diego , Destexhe Alain , Sejnowski Terrence J. , Steriade Mircea
Published: July 2002

The mammalian thalamus is the gateway to the cortex for most sensory modalities. Nearly all thalamic nuclei also receive massive feedback projections from the cortical region to which they project. In this study, the spatiotemporal properties of synchronized thalamic spindle oscillations (7 to 14 hertz) were investigated in barbiturate-anesthetized cats, before and after removal of the cortex. After complete ipsilateral decortication, the long-range synchronization of thalamic spindles in the intact cortex hemisphere changed into disorganized patterns with low spatiotemporal coherence. Local thalamic synchrony was still present, as demonstrated by dual intracellular recordings from nearby neurons. In the cortex, synchrony was insensitive to the disruption of horizontal intracortical connections. These results indicate that the global coherence of thalamic oscillations is determined by corticothalamic projections.
Modulation of Insulin Activities by Leptin
Authors: Cohen Batya , Novick Daniela , Rubinstein Menachem
Published: July 2002

Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB-R. Variants of OB-R are found in other tissues, but their function is unknown. Here, an OB-R variant was found in human hepatic cells. Exposure of these cells to leptin, at concentrations comparable with those present in obese individuals, caused attenuation of several insulin-induced activities, including tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1, and down-regulation of gluconeogenesis. In contrast, leptin increased the activity of IRS-1-associated phosphatidylinositol 3-kinase. These in vitro studies raise the possibility that leptin modulates insulin activities in obese individuals.
Control of Memory Formation Through Regulated Expression of a CaMKII Transgene
Authors: Mayford Mark , Bach Mary Elizabeth , Huang Yan-You , Wang Lei , Hawkins Robert D. , Kandel Eric R.
Published: July 2002

One of the major limitations in the use of genetically modified mice for studying cognitive functions is the lack of regional and temporal control of gene function. To overcome these limitations, a forebrain-specific promoter was combined with the tetracycline transactivator system to achieve both regional and temporal control of transgene expression. Expression of an activated calcium-independent form of calcium-calmodulin-dependent kinase II (CaMKII) resulted in a loss of hippocampal long-term potentiation in response to 10-hertz stimulation and a deficit in spatial memory, a form of explicit memory. Suppression of transgene expression reversed both the physiological and the memory deficit. When the transgene was expressed at high levels in the lateral amygdala and the striatum but not other forebrain structures, there was a deficit in fear conditioning, an implicit memory task, that also was reversible. Thus, the CaMKII signaling pathway is critical for both explicit and implicit memory storage, in a manner that is independent of its potential role in development.
Identification of a Gene That Causes Primary Open Angle Glaucoma
Authors: Stone Edwin M. , Fingert John H. , Alward Wallace L. M. , Nguyen Thai D. , Polansky Jon R. , Sunden Sara L. F. , Nishimura Darryl , Clark Abbot F. , Nystuen Arne , Nichols Brian E. , Mackey David A. , Ritch Robert , Kalenak Jeffrey W. , Craven E. Randy , Sheffield Val C.
Published: July 2002

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (
GLC1A
) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (
TIGR
) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.
Exploiting the HIV-Chemokine Nexus
Authors: Cohen Jon
Published: July 2002

Researchers now have an understanding of the intricate mechanism by which the AIDS virus enters cells. They are racing to turn this understanding into new therapies and are hoping it will provide clues to new vaccines and animal models to study the disease.
Tooling Around—Dates Show Early Siberian Settlement
Authors: Holden Constance
Published: July 2002

A Report on page
1281
presents new thermoluminescence dates on primitive stone tools from Siberia. The results suggest that early humans lived there as early as 260,000 years ago—long before anthropologists thought they were capable of surviving such a bitter climate.
Role of Transforming Growth Factor-β in Long-Term Synaptic Facilitation in
Aplysia
Authors: Zhang Fan , Endo Shogo , Cleary Leonard J. , Eskin Arnold , Byrne John H.
Published: July 2002

The role of transforming growth factor-β (TGF-β) in long-term synaptic facilitation was examined in isolated
Aplysia
ganglia. Treatment with TGF-β1 induced long-term facilitation (24 and 48 hours), but not short-term (5 to 15 minutes) or intermediate-term (2 to 4 hours) facilitation. The long-term effects of TGF-β1 were not additive with those of serotonin. Moreover, serotonin-induced facilitation was blocked by an inhibitor of TGF-β. Thus, activation of TGF-β may be part of the cascade of events underlying long-term sensitization, consistent with the hypothesis that signaling molecules that participate in development also have roles in adult neuronal plasticity.
Dinitrogen Bridged Gold Clusters
Authors: Shan Hui , Yang Yi , James Alan J. , Sharp Paul R.
Published: July 2002

A family of dinitrogen complexes, [(LAu)
6
(N
2
)]
2+
(L = a phosphine), with the dinitrogen unit bridging two clusters of three gold atoms have been prepared from hydrazine and [(LAu)
3
(O)]
+
. Structural characterization of the PPh
2
i
Pr (Ph, phenyl;
i
Pr, isopropyl) derivative shows a nitrogen-nitrogen single-bond distance indicative of hydrazido (N
2
4−
) character for the dinitrogen unit. The complexes can be reduced and protonated to give low [13% when L = PPh
2
Me (Me, methyl)] to quantitative [100% when L = P(
p
-MeOC
6
H
5
)
3
] yields of ammonia, establishing that bonding of dinitrogen to six metal atoms can lead to facile cleavage of the nitrogen-nitrogen bond.
Stabilization of β-Catenin by Genetic Defects in Melanoma Cell Lines
Authors: Rubinfeld Bonnee , Robbins Paul , El-Gamil Mona , Albert Iris , Porfiri Emilio , Polakis Paul
Published: July 2002

Signal transduction by β-catenin involves its posttranslational stabilization and downstream coupling to the Lef and Tcf transcription factors. Abnormally high amounts of β-catenin were detected in 7 of 26 human melanoma cell lines. Unusual messenger RNA splicing and missense mutations in the β-catenin gene (
CTNNB1
) that result in stabilization of the protein were identified in six of the lines, and the adenomatous polyposis coli tumor suppressor protein (APC) was altered or missing in two others. In the APC-deficient cells, ectopic expression of wild-type APC eliminated the excess β-catenin. Cells with stabilized β-catenin contained a constitutive β-catenin-Lef-1 complex. Thus, genetic defects that result in up-regulation of β-catenin may play a role in melanoma progression.
Photometric Behavior of Comet Hale-Bopp (C/1995 O1) Before Perihelion
Authors: Schleicher David G. , Lederer Susan M. , Millis Robert L. , Farnham Tony L.
Published: July 2002

Narrowband photometric observations of comet Hale-Bopp (C/1995 O1) between 25 July 1995 and 15 February 1997 indicated gas and dust production rates of 20 and 100 times greater, respectively, than observed at the same heliocentric distances for comet P/Halley in 1985. Hale-Bopp produced dust at a rate greater than has been observed for any other comet at any distance since at least 1977. On the basis of the observed production rate of the hydroxyl molecule, the calculated minimum effective diameter of Hale-Bopp's nucleus is 17 kilometers, but the actual diameter of the nucleus is likely to be at least two to three times larger. The chemical composition of Hale-Bopp is consistent with that of other long-period comets originating from the Oort Cloud.
Potent Inhibition of HIV-1 Infectivity in Macrophages and Lymphocytes by a Novel CCR5 Antagonist
Authors: Simmons Graham , Clapham Paul R. , Picard Laurent , Offord Robin E. , Rosenkilde Mette M. , Schwartz Thue W. , Buser Raphaële , Wells Timothy N. C. , Proudfoot Amanda E. I.
Published: July 2002

The chemokine receptors CXCR4 and CCR5 have recently been shown to act as coreceptors, in concert with CD4, for human immunodeficiency virus–type 1 (HIV-1) infection. RANTES and other chemokines that interact with CCR5 and block infection of peripheral blood mononuclear cell cultures inhibit infection of primary macrophages inefficiently at best. If used to treat HIV-1–infected individuals, these chemokines could fail to influence HIV replication in nonlymphocyte compartments while promoting unwanted inflammatory side effects. A derivative of RANTES that was created by chemical modification of the amino terminus, aminooxypentane (AOP)–RANTES, did not induce chemotaxis and was a subnanomolar antagonist of CCR5 function in monocytes. It potently inhibited infection of diverse cell types (including macrophages and lymphocytes) by nonsyncytium-inducing, macrophage-tropic HIV-1 strains. Thus, activation of cells by chemokines is not a prerequisite for the inhibition of viral uptake and replication. Chemokine receptor antagonists like AOP-RANTES that achieve full receptor occupancy at nanomolar concentrations are strong candidates for the therapy of HIV-1–infected individuals.
Basal Cell Carcinomas in Mice Overexpressing Sonic Hedgehog
Authors: Oro Anthony E. , Higgins Kay M. , Hu Zhilan , Bonifas Jeannette M. , Epstein Ervin H. , Scott Matthew P.
Published: July 2002

Mutations in the tumor suppressor gene
PATCHED
(
PTC
) are found in human patients with the basal cell nevus syndrome, a disease causing developmental defects and tumors, including basal cell carcinomas. Gene regulatory relationships defined in the fruit fly
Drosophila
suggest that overproduction of Sonic hedgehog (SHH), the ligand for PTC, will mimic loss of
ptc
function. It is shown here that transgenic mice overexpressing SHH in the skin develop many features of basal cell nevus syndrome, demonstrating that SHH is sufficient to induce basal cell carcinomas in mice. These data suggest that
SHH
may have a role in human tumorigenesis.
Tropospheric Chemistry and Transport
Authors: Kley Dieter
Published: July 2002

Oxidation rates of trace gases in the troposphere depend on species-specific rate coefficients and are predominantly governed by the concentration of the hydroxyl radical (OH), the most important oxidizing molecule in the troposphere. The concentration of OH is in local photochemical steady state; it is, however, dependent on the concentration of trace gases such as ozone, water vapor, volatile organic compounds, and oxides of nitrogen. Diffusive and advective transport processes influence and change the concentrations of these trace gases. Oxidative and transport time scales are often of similar magnitude, which leads to coupling between tropospheric chemistry and transport.
TRUST: A Deterministic Algorithm for Global Optimization
Authors: Barhen Jacob , Protopopescu Vladimir , Reister David
Published: July 2002

An approach to solving continuous global optimization problems was developed. It builds on two innovative concepts, subenergy tunneling and non-Lipschitzian terminal repellers, to ensure escape from local minima in a fast, reliable, and computationally efficient manner. The generally applicable methodology is embodied in the TRUST (terminal repeller unconstrained subenergy tunneling) algorithm, which is deterministic, scalable, and easy to implement. Benchmark results show that TRUST is faster and more accurate than previously reported global optimization techniques. An application of TRUST to a large-scale exploratory seismology problem of substantial computational complexity (that is, residual statics corrections) is also reported.
Localization of
Xenopus
Vg1 mRNA by Vera Protein and the Endoplasmic Reticulum
Authors: Deshler James O. , Highett Martin I. , Schnapp Bruce J.
Published: July 2002

In many organisms, pattern formation in the embryo develops from the polarized distributions of messenger RNAs (mRNAs) in the egg. In
Xenopus
, the mRNA encoding Vg1, a growth factor involved in mesoderm induction, is localized to the vegetal cortex of oocytes. A protein named Vera was shown to be involved in Vg1 mRNA localization. Vera cofractionates with endoplasmic reticulum (ER) membranes, and endogenous Vg1 mRNA is associated with a subcompartment of the ER. Vera may promote mRNA localization in
Xenopus
oocytes by mediating an interaction between the Vg1 3′ untranslated region and the ER subcompartment.
The Early Faint Sun Paradox: Organic Shielding of Ultraviolet-Labile Greenhouse Gases
Authors: Sagan Carl , Chyba Christopher
Published: July 2002

Atmospheric mixing ratios of ∼10
−5 ± 1
for ammonia on the early Earth would have been sufficient, through the resulting greenhouse warming, to counteract the temperature effects of the faint early sun. One argument against such model atmospheres has been the short time scale for ammonia photodissociation by solar ultraviolet light. Here it is shown that ultraviolet absorption by steady-state amounts of high-altitude organic solids produced from methane photolysis may have shielded ammonia sufficiently that ammonia resupply rates were able to maintain surface temperatures above freezing.
Lamina-Specific Connectivity in the Brain: Regulation by N-Cadherin, Neurotrophins, and Glycoconjugates
Authors: Inoue Akihiro , Sanes Joshua R.
Published: July 2002

In the vertebrate brain, neurons grouped in parallel laminae receive distinct sets of synaptic inputs. In the avian optic tectum, arbors and synapses of most retinal axons are confined to 3 of 15 laminae. The adhesion molecule N-cadherin and cell surface glycoconjugates recognized by a plant lectin are selectively associated with these “retinorecipient” laminae. The lectin and a monoclonal antibody to N-cadherin perturbed laminar selectivity in distinct fashions. In contrast, neurotrophins increased the complexity of retinal arbors without affecting their laminar distribution. Thus, cell surface molecules and soluble trophic factors may collaborate to shape lamina-specific arbors in the brain, with the former predominantly affecting their position and the latter their size.
Elementary Calcium-Release Units Induced by Inositol Trisphosphate
Authors: Horne John H. , Meyer Tobias
Published: July 2002

The extent to which inositol 1,4,5-trisphosphate (InsP
3
)–induced calcium signals are localized is a critical parameter for understanding the mechanism of effector activation. The spatial characteristics of InsP
3
-mediated calcium signals were determined by targeting a dextran-based calcium indicator to intracellular membranes through the in situ addition of a geranylgeranyl lipid group. Elementary calcium-release events observed with this indicator typically lasted less than 33 milliseconds, had diameters less than 2 micrometers, and were uncoupled from each other by the calcium buffer EGTA. Cellwide calcium transients are likely to result from synchronized triggering of such local release events, suggesting that calcium-dependent effector proteins could be selectively activated by localization near sites of local calcium release.
Specific Oxidative Cleavage of Carotenoids by VP14 of Maize
Authors: Schwartz Steven H. , Tan Bao Cai , Gage Douglas A. , Zeevaart Jan A. D. , McCarty Donald R.
Published: July 2002

The plant growth regulator abscisic acid (ABA) is formed by the oxidative cleavage of an epoxy-carotenoid. The synthesis of other apocarotenoids, such as vitamin A in animals, may occur by a similar mechanism. In ABA biosynthesis, oxidative cleavage is the first committed reaction and is believed to be the key regulatory step. A new ABA-deficient mutant of maize has been identified and the corresponding gene,
Vp14
, has been cloned. The recombinant VP14 protein catalyzes the cleavage of 9-
cis
-epoxy-carotenoids to form C
25
apo-aldehydes and xanthoxin, a precursor of ABA in higher plants.
Identification of a Chemokine Receptor Encoded by Human Cytomegalovirus as a Cofactor for HIV-1 Entry
Authors: Pleskoff Olivier , Tréboute Carole , Brelot Anne , Heveker Nikolaus , Seman Michel , Alizon Marc
Published: July 2002

The human cytomegalovirus encodes a β-chemokine receptor (US28) that is distantly related to the human chemokine receptors CCR5 and CXCR4, which also serve as cofactors for the entry into cells of human immunodeficiency virus–type 1 (HIV-1). Like CCR5, US28 allowed infection of CD4-positive human cell lines by primary isolates of HIV-1 and HIV-2, as well as fusion of these cell lines with cells expressing the viral envelope proteins. In addition, US28 mediated infection by cell line–adapted HIV-1 for which CXCR4 was an entry cofactor.
Selective Functionalization of Alkanes by Transition-Metal Boryl Complexes
Authors: Waltz Karen M. , Hartwig John F.
Published: July 2002

Simple transition-metal complexes of the formula Cp*M(CO)nBR2[Cp* = C5(CH3)5] containing an electrophilic, covalently bound main-group ligand react with alkanes and release products resulting from selective functionalization of an alkane at the terminal position. These reactions produce alkylboronate esters, which are common reagents in organic synthesis. Thus, the boryl complexes are rare chemical reagents that react selectivity at the terminal position of an alkane to provide simple functionalized products. Mechanistic analysis shows that ligand dissociation is induced photochemically and that thermal reaction of the resulting intermediate occurs with alkanes.
Neighborhoods and Violent Crime: A Multilevel Study of Collective Efficacy
Authors: Sampson Robert J. , Raudenbush Stephen W. , Earls Felton
Published: July 2002

It is hypothesized that collective efficacy, defined as social cohesion among neighbors combined with their willingness to intervene on behalf of the common good, is linked to reduced violence. This hypothesis was tested on a 1995 survey of 8782 residents of 343 neighborhoods in Chicago, Illinois. Multilevel analyses showed that a measure of collective efficacy yields a high between-neighborhood reliability and is negatively associated with variations in violence, when individual-level characteristics, measurement error, and prior violence are controlled. Associations of concentrated disadvantage and residential instability with violence are largely mediated by collective efficacy.