bluuebunny/crossref_metadata_2025 huggingface dataset:
Size and arrangement of elementary fibrils in crystalline cellulose studied with scanning tunneling microscopy
Authors: Zhang Y. Z. , Chen X. L. , Liu J. , Gao P. J. , Shi D. X. , Pang S. J.
Published: July 2002

Scanning tunneling microscopy (STM) was used to investigate the ultrastructure of cellulose. The materials used in the experiments were cotton fiber, dewaxed cotton fiber, and microcrystalline cellulose. The results showed that the elementary fibrils in all these kinds of cellulose could be directly observed from the surface and cross-sectional view with high resolution. The elementary fibrils assembled together in parallel, and their lateral dimension showed a great variability in different kinds of cellulose, but was uniform in the same kind of cellulose. Elementary fibrils were the smallest structural units of cellulose, and they further aggregated into microfibrils, and the microfibrils constituted fibrils. In each gradation, the fibers piled up in parallel. STM was useful in studying the fine structure of cellulose.
Spatial variation of the etch rate for deep etching of silicon by reactive ion etching
Authors: Asp Mo/ller Andersen Bo , Hansen Ole , Kristensen Martin
Published: July 2002

The macroscopic uniformity of deep etching into silicon by reactive ion etching (RIE) with a SF6−O2 plasma was studied. The spatial variation of the etch rate across a 4 inch wafer in a single wafer system is a function of the process parameters and the configuration of the etch chamber. It was found that, for a constant load of silicon exposed to the plasma, the etch rate variation can be controlled through the applied rf power, the chamber pressure, and the gas mixture. It was also found that the etch rate uniformity varies with the load of silicon exposed to the plasma. The result is a balance between the flux of neutral radicals and the flux of energetic ions to the surface. This balance is due to the RIE etch mechanism, which involves synergism between the two fluxes.
Degradation measurements using fully processed test transistors in high density plasma reactors for failure analysis
Authors: Muniandy Ravisangar , Boylan Ron , Chin Roland , Bell Nick , Sankman Robert
Published: July 2002

The objective of this study was for it to serve as a guide for understanding high density plasma induced damage during wafer fabrication and etchback for device debug, electron-beam, and failure analysis. A study of electrical degradation of packaged and fully processed transistors that were functionally etched back was carried out. Two high density plasma technologies, electron cyclotron resonance (ECR) and inductively coupled plasma (ICP), from various vendors, were evaluated. Transconductance (gm), threshold voltage (Vt), subthreshold slope, and gate leakage (Ig) were measured before and after the functional etch. Degradation took place even without polysilicon being directly exposed to the plasma. It was found that there is a strong correlation between the threshold voltage shift, and gate current shift, and they exhibit a bimodal relationship. The gate edge intensive transistor was most susceptible to degradation. The design of the etchers seemed to be the key factor rather than the choice of technology (ECR or ICP) with regard to transistor degradation. Gate oxide breakdown due to the charging of metal lines, caused by nonuniform electrical charging of the surface, adequately explains the observed transistor parameter shifts.
Single-electron transistor as a charge sensor for semiconductor applications
Authors: Berman David , Zhitenev Nikolai B. , Ashoori Raymond C. , Smith Henry I. , Melloch Michael R.
Published: July 2002

We describe the use of aluminum single-electron transistors (SETs) to measure, with extremely high sensitivity, the fluctuation of charge in semiconductor quantum dots. Our method of fabricating SETs results in excellent reliability and reproducibility.
Field emission from ZrC and ZrC films on Mo field emitters
Authors: Mackie W. A. , Xie Tianbao , Matthews M. R. , Routh B. P. , Davis P. R.
Published: July 2002

We have been working for several years on field emission measurements from transition metal carbides. These studies have covered emission primarily from HfC and ZrC in the form of solid carbide emitters, thin film carbide overcoatings on single tip field emitters, and film coatings on field emitter arrays (FEAs). These carbide materials have work functions approximately 1 eV lower than Mo or Si, making them attractive candidates for low voltage microelectronic field emitter arrays. Uses for arrays or single emitters of these carbides include video displays, microwave applications, high current or small spot electron sources, and cold cathodes for operation in poor vacuums. Since Mo is one common FEA emitter material, we used it for an emitter substrate in this study. Our aim is to determine improvements in I(V) characteristics, emission stability, capability of emission at high currents and in poor vacuum or tube conditions, and the ability to withstand exposure to atmospheric pressure without degradation. Individually, fabricated Mo field emitters were dosed via plasma vapor deposition from a high-purity ZrCx source. The deposited film used for high currents were generally not heated but tested as deposited by field emission microscopy examination and determination of I(V) characteristics. The results of these experiments indicate that work function reductions of the order of 1 eV can be achieved along with the ability to emit at higher current levels. Stable high current emission has also been obtained in the 0.5 mA range with ZrC films on Mo. This represents a tenfold increase in the obtainable emission levels compared to emission from a clean Mo substrate. These data are also compared to field emission data from bulk ZrC emitters. Some observations of high current emission in μTorr vacuum levels are also presented. The mechanisms for these improvements are discussed along with the possible role of stoichiometry.
Electrophoresis of nanodiamond powder for cold cathode fabrication
Authors: Alimova A. N. , Chubun N. N. , Belobrov P. I. , Ya Detkov P. , Zhirnov V. V.
Published: July 2002

The process of electrophoresis/dielectrophoresis of shock-synthesized nanodiamond powders on the large-area Si field emission arrays was studied. The process was found to be very sensitive to the modification of nanodiamond powder. The growth rate and film morphology of nanodiamond coatings on Si tips were investigated. Results in fabrication and testing of nanodiamond-based cold cathodes and sealed device prototypes are presented.
Use of ultrathin ZnSe dipole layers for band offset engineering at Ge and Si homo/heterojunctions
Authors: Wilks S. P. , Williams R. H. , Pan M. , Dunstan P. R. , Cowie B. C. C.
Published: July 2002

The ability to control semiconductor band discontinuities would allow solid devices to be specifically tailored so that efficiency and performance could be dramatically improved. This article reports the use of an ordered ZnSe monolayer to induce a valence band discontinuity at the Ge homojunction (0.38 eV), at the Ge–Si heterojunction (0.53 eV), and at the Si homojunction (∼0.2 eV). Soft x-ray photoemission was used to probe the interfaces as they were formed under ultrahigh vacuum conditions. The effect of overlayer band bending on the interpretation of band offset measurements is discussed. As the interfacial bonding and orientation of the dipole layer are key factors in determining the direction and magnitude of the band modification, x-ray standing wave measurements were performed on the Ge–ZnSe–Ge systems to identify the atomic structure of the junction. Se atoms were always found to bond to the Ge substrate in the a-top position, while the Zn atoms adopted the H3 sites, bonding to the overlayer. The results for these interfaces are interpreted in terms of the charge transfer; other factors such as strain and order are also addressed.
Three behavioral states observed in field emission from single-walled carbon nanotubes
Authors: Dean Kenneth A. , von Allmen Paul , Chalamala Babu R.
Published: July 2002

We observe three distinct behavioral states in field emission from single-walled carbon nanotubes between temperatures of 300 and 1800 K. At room temperature, nanotubes emit through adsorbate states correlated to the presence of water. These states are removed above 900 K. After adsorbate removal, the apparently clean nanotube state shows lower emission current and substantially reduced emission noise. Current-temperature measurements identify a deviation from metallic tunneling behavior. Nanotube field emission undergoes a second, field-stabilized transition at high temperatures which reduces the current by as much as five orders of magnitude relative to the room temperature current. This current decrease is 100% recoverable. In addition, the stable behavior of clean nanotube states breakdown at extremely high currents and temperatures. Rings form around the field emission images, similar to those observed in metals at extreme current densities. Under these extreme conditions, we also find evidence for the rearrangement of atoms on the nanotube caps.
Nanostructured diamond film on etched silicon and its field emission behavior
Authors: Xu N. S. , Chen Jian , Feng Y. T. , Deng S. Z.
Published: July 2002

Nanostructured diamond films were deposited on the etched silicon wafer by using dielectrophoresis method. The properties of the film were analyzed using scanning electron microscopy and micro-Raman spectrometry. Their field emission behavior was studied using an anode probe technique. A current density of 5 mA/cm2 was recorded at a field of 3.56 MV/m. This effect is attributed to the field enhancement at the rough silicon-diamond interface and the lower or even negative electron affinity of the diamond surface.
Fluorous Mixture Synthesis: A Fluorous-Tagging Strategy for the Synthesis and Separation of Mixtures of Organic Compounds
Authors: Luo Zhiyong , Zhang Qisheng , Oderaotoshi Yoji , Curran Dennis P.
Published: July 2002

The solution-phase synthesis of organic compounds as mixtures rather than in individual pure form offers efficiency advantages that are negated by the difficulty in separating and identifying the components of the final mixture. Here, a strategy for mixture synthesis that addresses these separation and identification problems is presented. A series of organic substrates was tagged with a series of fluorous tags of increasing fluorine content. The compounds were then mixed, and multistep reactions were conducted to make enantiomers or analogs of the natural product mappicine. The resulting tagged products were then demixed by fluorous chromatography (eluting in order of increasing fluorine content) to provide the individual pure components of the mixture, which were detagged to release the final products.
Solar Forcing of Drought Frequency in the Maya Lowlands
Authors: Hodell David A. , Brenner Mark , Curtis Jason H. , Guilderson Thomas
Published: July 2002

We analyzed lake-sediment cores from the Yucatan Peninsula, Mexico, to reconstruct the climate history of the region over the past 2600 years. Time series analysis of sediment proxies, which are sensitive to the changing ratio of evaporation to precipitation (oxygen isotopes and gypsum precipitation), reveal a recurrent pattern of drought with a dominant periodicity of 208 years. This cycle is similar to the documented 206-year period in records of cosmogenic nuclide production (carbon-14 and beryllium-10) that is thought to reflect variations in solar activity. We conclude that a significant component of century-scale variability in Yucatan droughts is explained by solar forcing. Furthermore, some of the maxima in the 208-year drought cycle correspond with discontinuities in Maya cultural evolution, suggesting that the Maya were affected by these bicentennial oscillations in precipitation.
In Silico Mapping of Complex Disease-Related Traits in Mice
Authors: Grupe Andrew , Germer Soren , Usuka Jonathan , Aud Dee , Belknap John K. , Klein Robert F. , Ahluwalia Mandeep K. , Higuchi Russell , Peltz Gary
Published: July 2002

Experimental murine genetic models of complex human disease show great potential for understanding human disease pathogenesis. To reduce the time required for analysis of such models from many months down to milliseconds, a computational method for predicting chromosomal regions regulating phenotypic traits and a murine database of single nucleotide polymorphisms were developed. After entry of phenotypic information obtained from inbred mouse strains, the phenotypic and genotypic information is analyzed in silico to predict the chromosomal regions regulating the phenotypic trait.
Using Selective Withdrawal to Coat Microparticles
Authors: Cohen Itai , Li Hui , Hougland James L. , Mrksich Milan , Nagel Sidney R.
Published: July 2002

We report a method that uses the process of selective withdrawal of one fluid through a second immiscible fluid to coat small particles with polymer films. Fluid is withdrawn through a tube with its orifice slightly above a water-oil interface. Upon increasing the flow rate, there is a transition from a state where only oil is withdrawn to a state where the water, containing the particles to be coated and appropriate prepolymer reagents, is entrained in a thin spout along with the oil. The entrained particles eventually cause the spout interface to break, producing a thin coat of controllable thickness around each particle, which can be subsequently polymerized using chemical reagents, light, or heat. This method allows flexibility in the chemical composition and thickness of the conformal coatings.
Spermiogenesis Deficiency in Mice Lacking the
Trf2
Gene
Authors: Zhang Di , Penttila Tarja-Leena , Morris Patricia L. , Teichmann Martin , Roeder Robert G.
Published: July 2002

The discovery of TATA-binding protein–related factors (TRFs) has suggested alternative mechanisms for gene-specific transcriptional regulation and raised interest in their biological functions. In contrast to recent observations of an embryonic lethal phenotype for TRF2 inactivation in
Caenorhabditis elegans
and
Xenopus laevis
, we found that
Trf2
-deficient mice are viable. However,
Trf2
–/–
mice are sterile because of a severe defect in spermiogenesis. Postmeiotic round spermatids advance at most to step 7 of differentiation but fail to progress to the elongated form, and gene-specific transcription deficiencies were identified. We speculate that mammals may have evolved more specialized TRF2 functions in the testis that involve transcriptional regulation of genes essential for spermiogenesis.
Auditory Spatial Receptive Fields Created by Multiplication
Authors: Peña José Luis , Konishi Masakazu
Published: July 2002

Examples of multiplication by neurons or neural circuits are scarce, although many computational models use this basic operation. The owl's auditory system computes interaural time (ITD) and level (ILD) differences to create a two-dimensional map of auditory space. Space-specific neurons are selective for combinations of ITD and ILD, which define, respectively, the horizontal and vertical dimensions of their receptive fields. A multiplication of separate postsynaptic potentials tuned to ITD and ILD, rather than an addition, can account for the subthreshold responses of these neurons to ITD-ILD pairs. Other nonlinear processes improve the spatial tuning of the spike output and reduce the fit to the multiplicative model.
Paleolithic Technology and Human Evolution
Authors: Ambrose Stanley H.
Published: July 2002

Human biological and cultural evolution are closely linked to technological innovations. Direct evidence for tool manufacture and use is absent before 2.5 million years ago (Ma), so reconstructions of australopithecine technology are based mainly on the behavior and anatomy of chimpanzees. Stone tool technology, robust australopithecines, and the genus
Homo
appeared almost simultaneously 2.5 Ma. Once this adaptive threshold was crossed, technological evolution was accompanied by increased brain size, population size, and geographical range. Aspects of behavior, economy, mental capacities, neurological functions, the origin of grammatical language, and social and symbolic systems have been inferred from the archaeological record of Paleolithic technology.
Far-Reaching Effects of the Hawaiian Islands on the Pacific Ocean-Atmosphere System
Authors: Xie Shang-Ping , Liu W. Timothy , Liu Qinyu , Nonaka Masami
Published: July 2002

Using satellite data, we detected a wind wake trailing westward behind the Hawaiian Islands for 3000 kilometers, a length many times greater than observed anywhere else on Earth. This wind wake drives an eastward ocean current that draws warm water from the Asian coast 8000 kilometers away, leaving marked changes in surface and subsurface ocean temperature. Standing in the path of the steady trade winds, Hawaii triggers an air-sea interaction that provides the feedback to sustain the influence of these small islands over a long stretch of the Pacific Ocean.
Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly
Authors: Nakayama Jun-ichi , Rice Judd C. , Strahl Brian D. , Allis C. David , Grewal Shiv I. S.
Published: July 2002

The assembly of higher order chromatin structures has been linked to the covalent modifications of histone tails. We provide in vivo evidence that lysine 9 of histone H3 (H3 Lys
9
) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast. Both the conserved chromo- and SET domains of Clr4 are required for H3 Lys
9
methylation in vivo. Localization of Swi6, a homolog of
Drosophila
HP1, to heterochomatic regions is dependent on H3 Lys
9
methylation. Moreover, an H3-specific deacetylase Clr3 and a β-propeller domain protein Rik1 are required for H3 Lys
9
methylation by Clr4 and Swi6 localization. These data define a conserved pathway wherein sequential histone modifications establish a “histone code” essential for the epigenetic inheritance of heterochromatin assembly.
Polarization Mode Control of Two-Dimensional Photonic Crystal Laser by Unit Cell Structure Design
Authors: Noda Susumu , Yokoyama Mitsuru , Imada Masahiro , Chutinan Alongkarn , Mochizuki Masamitsu
Published: July 2002

We demonstrate polarization mode selection in a two-dimensional (2D) photonic crystal laser by controlling the geometry of the unit cell structure. As the band diagram of the square-lattice photonic crystal is influenced by the unit cell structure, calculations reveal that changing the structure from a circular to an elliptical geometry should result in a strong modification of the electromagnetic field distributions at the band edges. Such a structural modification is expected to provide a mechanism for controlling the polarization modes of the emitted light. A square-lattice photonic crystal with the elliptical unit cell structure has been fabricated and integrated with a gain media. The observed coherent 2D lasing action with a single wavelength and controlled polarization is in good agreement with the predicted behavior.
Sorting of Striatal and Cortical Interneurons Regulated by Semaphorin-Neuropilin Interactions
Authors: Marı́n Oscar , Yaron Avraham , Bagri Anil , Tessier-Lavigne Marc , Rubenstein John L. R.
Published: July 2002

Most striatal and cortical interneurons arise from the basal telencephalon, later segregating to their respective targets. Here, we show that migrating cortical interneurons avoid entering the striatum because of a chemorepulsive signal composed at least in part of semaphorin 3A and semaphorin 3F. Migrating interneurons expressing neuropilins, receptors for semaphorins, are directed to the cortex; those lacking them go to the striatum. Loss of neuropilin function increases the number of interneurons that migrate into the striatum. These observations reveal a mechanism by which neuropilins mediate sorting of distinct neuronal populations into different brain structures, and provide evidence that, in addition to guiding axons, these receptors also control neuronal migration in the central nervous system.
Empowering Aristotle
Authors: Geertz Clifford
Published: July 2002

Making Social Science Matter
Why Social Inquiry Fails and How It Can Succeed Again. Bent Flyvbjerg. Cambridge University Press, Cambridge, 2001. 214 pp. $54.95, £37.50. ISBN 0-521-77268-0. Paper, $19.95, £13.95. ISBN 0-521-77568-X.

Deploying theoretical arguments, methodological guidelines, and examples drawn from his practical experiences in planning and development, Flyvbjerg argues that the social sciences will best be advanced by abandoning the aspiration to resemble natural science.
Undergraduate Research, Graduate Mentoring, and the University's Mission
Authors: González Cristina
Published: July 2002

Undergraduate research and graduate mentoring have received a great deal of attention in recent times. What do these activities have in common? They both speak to the primary mission of the research university, which is not merely carrying out research but training students to do research. The knowledge-based global economy, with its wealth of information and opportunities, has increased undergraduate students' need for research skills as well as graduate students' desire for personal guidance. As the research university matures, the boundaries between graduate and undergraduate education are blurring. Indeed, if we focus on the learning process, we find not two but five levels of learning at the research university: lower division, upper division, master's, doctoral, and postdoctoral. All five levels form a continuum, a series of gradual steps. The mission of the university is to introduce students to research, to inspire in them a passion for discovery at each of these levels.
A Circadian Output in
Drosophila
Mediated by
Neurofibromatosis-1
and Ras/MAPK
Authors: Williams Julie A. , Su Henry S. , Bernards Andre , Field Jeffrey , Sehgal Amita
Published: July 2002

Output from the circadian clock controls rhythmic behavior through poorly understood mechanisms. In
Drosophila
, null mutations of the
neurofibromatosis-1
(
Nf1
) gene produce abnormalities of circadian rhythms in locomotor activity. Mutant flies show normal oscillations of the clock genes
period
(
per
) and
timeless
(
tim
) and of their corresponding proteins, but altered oscillations and levels of a clock-controlled reporter. Mitogen-activated protein kinase (MAPK) activity is increased in
Nf1
mutants, and the circadian phenotype is rescued by loss-of-function mutations in the Ras/MAPK pathway. Thus,
Nf1
signals through Ras/MAPK in
Drosophila
. Immunohistochemical staining revealed a circadian oscillation of phospho-MAPK in the vicinity of nerve terminals containing pigment-dispersing factor (PDF), a secreted output from clock cells, suggesting a coupling of PDF to Ras/MAPK signaling.
Regulation of Cutaneous Malignancy by γδ T Cells
Authors: Girardi Michael , Oppenheim David E. , Steele Carrie R. , Lewis Julia M. , Glusac Earl , Filler Renata , Hobby Paul , Sutton Brian , Tigelaar Robert E. , Hayday Adrian C.
Published: July 2002

The localization of γδ T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking γδ cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, major histocompatibility complex–related molecules structurally resembling human MICA. Each of these is a ligand for NKG2d, a receptor expressed by cytolytic T cells and natural killer (NK) cells. In vitro, skin-associated NKG2d
+
γδ cells killed skin carcinoma cells by a mechanism that was sensitive to blocking NKG2d engagement. Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy.
Segregation of Nitrogen Fixation and Oxygenic Photosynthesis in the Marine Cyanobacterium
Trichodesmium
Authors: Berman-Frank Ilana , Lundgren Pernilla , Chen Yi-Bu , Küpper Hendrik , Kolber Zbigniew , Bergman Birgitta , Falkowski Paul
Published: July 2002

In the modern ocean, a significant amount of nitrogen fixation is attributed to filamentous, nonheterocystous cyanobacteria of the genus
Trichodesmium.
In these organisms, nitrogen fixation is confined to the photoperiod and occurs simultaneously with oxygenic photosynthesis. Nitrogenase, the enzyme responsible for biological N
2
fixation, is irreversibly inhibited by oxygen in vitro. How nitrogenase is protected from damage by photosynthetically produced O
2
was once an enigma. Using fast repetition rate fluorometry and fluorescence kinetic microscopy, we show that there is both temporal and spatial segregation of N
2
fixation and photosynthesis within the photoperiod. Linear photosynthetic electron transport protects nitrogenase by reducing photosynthetically evolved O
2
in photosystem I (PSI). We postulate that in the early evolutionary phase of oxygenic photosynthesis, nitrogenase served as an electron acceptor for anaerobic heterotrophic metabolism and that PSI was favored by selection because it provided a micro-anaerobic environment for N
2
fixation in cyanobacteria.
Deposition of Conformal Copper and Nickel Films from Supercritical Carbon Dioxide
Authors: Blackburn Jason M. , Long David P. , Cabañas Albertina , Watkins James J.
Published: July 2002

Device-quality copper and nickel films were deposited onto planar and etched silicon substrates by the reduction of soluble organometallic compounds with hydrogen in a supercritical carbon dioxide solution. Exceptional step coverage on complex surfaces and complete filling of high-aspect-ratio features of less than 100 nanometers width were achieved. Nickel was deposited at 60°C by the reduction of bis(cyclopentadienyl)nickel and copper was deposited from either copper(I) or copper(II) compounds onto the native oxide of silicon or metal nitrides with seed layers at temperatures up to 200°C and directly on each surface at temperatures above 250°C. The latter approach provides a single-step means for achieving high-aspect-ratio feature fill necessary for copper interconnect structures in future generations of integrated circuits.
Neocortex Patterning by the Secreted Signaling Molecule FGF8
Authors: Fukuchi-Shimogori Tomomi , Grove Elizabeth A.
Published: July 2002

A classic model proposes that the mammalian neocortex is divided into areas early in neurogenesis, but the molecular mechanisms that generate the area map have been elusive. Here we provide evidence that FGF8 regulates development of the map from a source in the anterior telencephalon. Using electroporation-mediated gene transfer in mouse embryos, we show that augmenting the endogenous anterior FGF8 signal shifts area boundaries posteriorly, reducing the signal shifts them anteriorly, and introducing a posterior source of FGF8 elicits partial area duplications, revealed by ectopic somatosensory barrel fields. These findings support a role for FGF signaling in specifying positional identity in the neocortex.
Skinny Hedgehog, an Acyltransferase Required for Palmitoylation and Activity of the Hedgehog Signal
Authors: Chamoun Zeina , Mann Randall K. , Nellen Denise , von Kessler Doris P. , Bellotto Manolo , Beachy Philip A. , Basler Konrad
Published: July 2002

One of the most dominant influences in the patterning of multicellular embryos is exerted by the Hedgehog (Hh) family of secreted signaling proteins. Here, we identify a segment polarity gene in
Drosophila melanogaster
,
skinny hedgehog
(
ski
), and show that its product is required in Hh-expressing cells for production of appropriate signaling activity in embryos and in the imaginal precursors of adult tissues. The
ski
gene encodes an apparent acyltransferase, and we provide genetic and biochemical evidence that Hh proteins from
ski
mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification. Our results suggest that
ski
encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of Hh, and further demonstrate that this lipid modification is required for the embryonic and larval patterning activities of the Hh signal.
Crystal Structure of the Extracellular Segment of Integrin αVβ3
Authors: Xiong Jian-Ping , Stehle Thilo , Diefenbach Beate , Zhang Rongguang , Dunker Reinhardt , Scott David L. , Joachimiak Andrzej , Goodman Simon L. , Arnaout M. Amin
Published: July 2002

Integrins are αβ heterodimeric receptors that mediate divalent cation-dependent cell-cell and cell-matrix adhesion through tightly regulated interactions with ligands. We have solved the crystal structure of the extracellular portion of integrin αVβ3 at 3.1 Å resolution. Its 12 domains assemble into an ovoid “head” and two “tails.” In the crystal, αVβ3 is severely bent at a defined region in its tails, reflecting an unusual flexibility that may be linked to integrin regulation. The main inter-subunit interface lies within the head, between a seven-bladed β-propeller from αV and an A domain from β3, and bears a striking resemblance to the Gα/Gβ interface in G proteins. A metal ion–dependent adhesion site (MIDAS) in the βA domain is positioned to participate in a ligand-binding interface formed of loops from the propeller and βA domains. MIDAS lies adjacent to a calcium-binding site with a potential regulatory function.
Visualization of DNA Replication on Individual Epstein-Barr Virus Episomes
Authors: Norio Paolo , Schildkraut Carl L.
Published: July 2002

The duplication of the mammalian genome is an organized event, but there is limited information about the precision of the duplication program at specific genetic loci. We developed an approach that allows DNA replication events to be visualized in individual DNA molecules. Studying the latent replication of Epstein-Barr virus episomes, we show that different initiation sites are used to commence DNA replication from a specific portion of the viral genome (zone), whereas termination does not seem to be genomically defined. We conclude that initiation zones and pausing sites are major organizers of the duplication program, but initiation, fork progression, and termination of replication can vary in each molecule.
γ-Secretase Cleavage and Nuclear Localization of ErbB-4 Receptor Tyrosine Kinase
Authors: Ni Chang-Yuan , Murphy M. Paul , Golde Todd E. , Carpenter Graham
Published: July 2002

ErbB-4 is a transmembrane receptor tyrosine kinase that regulates cell proliferation and differentiation. After binding of its ligand heregulin (HRG) or activation of protein kinase C (PKC) by 12-
O
-tetradecanoylphorbol-13-acetate (TPA), the ErbB-4 ectodomain is cleaved by a metalloprotease. We now report a subsequent cleavage by γ-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus. γ-Secretase cleavage was prevented by chemical inhibitors or a dominant negative presenilin. Inhibition of γ-secretase also prevented growth inhibition by HRG. γ-Secretase cleavage of ErbB-4 may represent another mechanism for receptor tyrosine kinase–mediated signaling.
A Prokaryotic Voltage-Gated Sodium Channel
Authors: Ren Dejian , Navarro Betsy , Xu Haoxing , Yue Lixia , Shi Qing , Clapham David E.
Published: July 2002

The pore-forming subunits of canonical voltage-gated sodium and calcium channels are encoded by four repeated domains of six-transmembrane (6TM) segments. We expressed and characterized a bacterial ion channel (NaChBac) from
Bacillus halodurans
that is encoded by one 6TM segment. The sequence, especially in the pore region, is similar to that of voltage-gated calcium channels. The expressed channel was activated by voltage and was blocked by calcium channel blockers. However, the channel was selective for sodium. The identification of NaChBac as a functionally expressed bacterial voltage-sensitive ion-selective channel provides insight into both voltage-dependent activation and divalent cation selectivity.
Formation of Stable Chlorinated Hydrocarbons in Weathering Plant Material
Authors: Myneni Satish C. B.
Published: July 2002

Though several chlorinated organic compounds produced by humans are carcinogenic and toxic, some are also produced by the biotic and abiotic processes in the environment. In situ x-ray spectroscopy data indicate that natural organic matter in soils, sediments, and natural waters contain stable, less volatile organic compounds with chlorinated phenolic and aliphatic groups as the principal Cl forms. These compounds are formed at rapid rates from the transformation of inorganic Cl during humification of plant material and, thus, play a critical role in the cycling of Cl and of several major and trace elements in the environment and may influence human health.
Placebo and Opioid Analgesia-- Imaging a Shared Neuronal Network
Authors: Petrovic Predrag , Kalso Eija , Petersson Karl Magnus , Ingvar Martin
Published: July 2002

It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomography, we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC. We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia, but not during the pain-only condition. These findings indicate a related neural mechanism in placebo and opioid analgesia.
A Class of Potent Antimalarials and Their Specific Accumulation in Infected Erythrocytes
Authors: Wengelnik Kai , Vidal Valérie , Ancelin Marie L. , Cathiard Anne-Marie , Morgat Jean Louis , Kocken Clemens H. , Calas Michèle , Herrera Socrates , Thomas Alan W. , Vial Henri J.
Published: July 2002

During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth of the human malaria parasites
Plasmodium falciparum
and
P. vivax
and was 1000-fold less toxic to mammalian cell lines. A radioactive derivative specifically accumulated in infected erythrocytes to levels several hundredfold higher than in the surrounding medium, and very low dose G25 therapy completely cured monkeys infected with
P. falciparum
and
P. cynomolgi
.
The Cause of Carbon Isotope Minimum Events on Glacial Terminations
Authors: Spero Howard J. , Lea David W.
Published: July 2002

The occurrence of carbon isotope minima at the beginning of glacial terminations is a common feature of planktic foraminifera carbon isotopic records from the Indo-Pacific, sub-Antarctic, and South Atlantic. We use the δ
13
C record of a thermocline-dwelling foraminifera,
Neogloboquadrina dutertrei
, and surface temperature estimates from the eastern equatorial Pacific to demonstrate that the onset of δ
13
C minimum events and the initiation of Southern Ocean warming occurred simultaneously. Timing agreement between the marine record and the δ
13
C minimum in an Antarctic atmospheric record suggests that the deglacial events were a response to the breakdown of surface water stratification, renewed Circumpolar Deep Water upwelling, and advection of low δ
13
C waters to the convergence zone at the sub-Antarctic front. On the basis of age agreement between the absolute δ
13
C minimum in surface records and the shift from low to high δ
13
C in the deep South Atlantic, we suggest that the δ
13
C rise that marks the end of the carbon isotope minima was due to the resumption of North Atlantic Deep Water influence in the Southern Ocean.
A New UAG-Encoded Residue in the Structure of a Methanogen Methyltransferase
Authors: Hao Bing , Gong Weimin , Ferguson Tsuneo K. , James Carey M. , Krzycki Joseph A. , Chan Michael K.
Published: July 2002

Genes encoding methanogenic methylamine methyltransferases all contain an in-frame amber (UAG) codon that is read through during translation. We have identified the UAG-encoded residue in a 1.55 angstrom resolution structure of the
Methanosarcina barkeri
monomethylamine methyltransferase (MtmB). This structure reveals a homohexamer comprised of individual subunits with a TIM barrel fold. The electron density for the UAG-encoded residue is distinct from any of the 21 natural amino acids. Instead it appears consistent with a lysine in amide-linkage to (4
R
,5
R
)-4-substituted-pyrroline-5-carboxylate. We suggest that this amino acid be named
l
-pyrrolysine.
Stephen Jay Gould à la recherche du temps perdu
Authors: Futuyma Douglas J.
Published: July 2002

The Structure of Evolutionary Theory
.
By Stephen Jay Gould
. Belknap (Harvard University Press), Cambridge, MA, 2002. 1457 pp. $39.95, £27.50, €45.90. ISBN 0-674-00613-5.

In this magnum opus, Gould offers a history of the core concepts of Darwinism, considers recent critiques of these ideas, and provides a detailed account of his own synthesis of evolutionary theories.
Crystal Engineering: from Structure to Function
Authors: Hollingsworth Mark D.
Published: July 2002

Modern crystal engineering has emerged as a rich discipline whose success requires an iterative process of synthesis, crystallography, crystal structure analysis, and computational methods. By focusing on the molecular recognition events during nucleation and growth, chemists have uncovered new ways of controlling the internal structure and symmetry of crystals and of producing materials with useful chemical and physical properties.
Signaling Pathways for PC12 Cell Differentiation: Making the Right Connections
Authors: Vaudry D. , Stork P. J. S. , Lazarovici P. , Eiden L. E.
Published: July 2002

A key issue in signal transduction is how signaling pathways common to many systems—so-called canonical signaling cassettes—integrate signals from molecules having a wide spectrum of activities, such as hormones and neurotrophins, to deliver distinct biological outcomes. The neuroendocrine cell line PC12, derived from rat pheochromocytoma, provides an example of how one canonical signaling cassette—the Raf → mitogen-activated protein kinase kinase (MEK) → extracellular signal-regulated kinase (ERK) pathway—can promote distinct outcomes, which in this case include neuritogenesis, gene induction, and proliferation. Two growth hormones, epidermal growth factor (EGF) and nerve growth factor (NGF), use the same pathway to cause PC12 proliferation and differentiation, respectively. In addition, pituitary adenylate cyclase–activating polypeptide (PACAP), a neurotransmitter that also causes differentiation, uses the same canonical cassette as NGF but in a different way. The Connections Map for PC12 Cell Differentiation brings into focus the complex array of specific cellular responses that rely on canonical signal transduction systems.
Promotion of Mitochondrial Membrane Complex Assembly by a Proteolytically Inactive Yeast Lon
Authors: Rep Martijn , van Dijl Jan Maarten , Suda Kitaru , Schatz Gottfried , Grivell Leslie A. , Suzuki Carolyn K.
Published: July 2002

Afg3p and Rca1p are adenosine triphosphate (ATP)-dependent metalloproteases in yeast mitochondria. Cells lacking both proteins exhibit defects in respiration-dependent growth, degradation of mitochondrially synthesized proteins, and assembly of inner-membrane complexes. Defects in growth and protein assembly, but not in degradation, were suppressed by overproduction of yeast mitochondrial Lon, an ATP-dependent serine protease. Suppression by Lon was enhanced by inactivation of the proteolytic site and was prevented by mutation of the ATP-binding site. It is suggested that the mitochondrial proteases Lon, Afg3p, and Rca1p can also serve a chaperone-like function in the assembly of mitochondrial protein complexes.
Intracrystalline Transformation of Olivine to Wadsleyite and Ringwoodite Under Subduction Zone Conditions
Authors: Kerschhofer Ljuba , Sharp Thomas G. , Rubie David C.
Published: July 2002

Experiments on Mg
1.8
Fe
0.2
SiO
4
olivine at 18 to 20 gigapascals and 1000° to 1400°C show that transformation to the high-pressure polymorphs wadsleyite and ringwoodite involves two competing nucleation mechanisms when the grain size of the olivine is large: (i) incoherent nucleation on olivine grain boundaries and (ii) coherent intracrystalline nucleation of ringwoodite lamellae on shear-induced stacking faults in olivine on the (100) planes, followed by the nucleation of wadsleyite on the ringwoodite. The large amount of intracrystalline transformation, which occurs under low differential stress under the pressure and temperature conditions of the mantle transition zone, suggests that shear-induced intracrystalline transformation of olivine to wadsleyite and ringwoodite is important in subducting slabs.
The World Wide Web as an Instructional Tool
Authors: Barrie John M. , Presti David E.
Published: July 2002

The Internet—and its graphically attractive application, the World Wide Web (WWW)—is potentially a powerful educational tool. Barrie and Presti discuss three ways in which the WWW can be profitably used in education: as a giant encyclopedia, as a virtual classroom, and as a supplement to conventional courses.
Signaling by the
Escherichia coli
Aspartate Chemoreceptor Tar with a Single Cytoplasmic Domain per Dimer
Authors: Tatsuno Ichiro , Homma Michio , Oosawa Kenji , Kawagishi Ikuro
Published: July 2002

Many transmembrane receptors are oligomeric proteins. Binding of a ligand may alter the oligomeric state of the receptor, induce structural changes within the oligomer, or both. The bacterial aspartate chemoreceptor Tar forms a homodimer in the presence or absence of ligands. Tar mediates attractant and repellent responses by modulating the activity of the cytoplasmic kinase CheA. In vivo intersubunit suppression was used to show that certain combinations of full-length and truncated mutant Tar proteins complemented each other to restore attractant responses to aspartate. These results suggest that heterodimers with only one intact cytoplasmic domain are functional. The signaling mechanism may require interactions between dimers or conformational changes within a single cytoplasmic domain.
Treaty Draft Raises Scientific Hackles
Authors: Lawler Andrew
Published: July 2002

A move to strengthen the rights of companies to restrict access to databases they compile has touched a raw nerve among science officials in Washington. This month the presidents of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine warned that a proposal to be discussed at upcoming international trade talks in Geneva could make it harder and more expensive for scientists to gain access to data.
Animal Origins
Authors: Vermeij Geerat J.
Published: July 2002

The fossil record suggests that animals evolved 565 million years ago (Ma) during the Vendian period of the latest Neoproterozoic era. By the beginning of the Cambrian period of the Paleozoic era, an explosive proliferation had established all of the major groups of animals. In their report, Wray
et al
. (
p. 568
) use genetic evidence to move the origins of animals back to between 1000 to 1200 Ma. In his Perspective, Vermeij discusses the implications of this big shift in the evolutionary time line.
Atomic Landscapes Beckon Researchers
Authors: Service Robert F.
Published: July 2002

At two recent meetings, physicists and chemists explored new strategies for observing conformation changes in individual molecules and etching ever smaller features on computer chips.
Climatic and Hydrologic Oscillations in the Owens Lake Basin and Adjacent Sierra Nevada, California
Authors: Benson Larry V. , Burdett James W. , Kashgarian Michaele , Lund Steve P. , Phillips Fred M. , Rye Robert O.
Published: July 2002

Oxygen isotope and total inorganic carbon values of cored sediments from the Owens Lake basin, California, indicate that Owens Lake overflowed most of the time between 52,500 and 12,500 carbon-14 (
14
C) years before present (B.P.). Owens Lake desiccated during or after Heinrich event H1 and was hydrologically closed during Heinrich event H2. The magnetic susceptibility and organic carbon content of cored sediments indicate that about 19 Sierra Nevada glaciations occurred between 52,500 and 23,500
14
C years B.P. Most of the glacial advances were accompanied by decreases in the amount of discharge reaching Owens Lake. Comparison of the timing of glaciation with the lithic record of North Atlantic core V23-81 indicates that the number of mountain glacial cycles and the number of North Atlantic lithic events were about equal between 39,000 and 23,500
14
C years B.P.
Change of a Catalytic Reaction Carried Out by a DNA Replication Protein
Authors: Noirot-Gros Marie-Françoise , Ehrlich Stanislav D.
Published: July 2002

The RepA protein of plasmid pC194 initiates and terminates rolling circle replication. At initiation, it forms a 5′-phosphotyrosyl DNA link, whereas at termination, a glutamate residue directs hydrolytic cleavage of the newly synthesized origin, and the resulting 3′-hydroxyl group undergoes transesterification with the phosphotyrosine link. The protein is thus released from DNA, and the termination is uncoupled from reinitiation of replication. Replacement of the glutamate with tyrosine in RepA altered this mechanism, so that termination occurred by two successive transesterifications and became coupled to reinitiation. This result suggests that various enzymes involved in DNA cleavage and rejoining may have similar mechanistic and evolutionary roots.
A Role for Phosphoinositide 3-Kinase in Bacterial Invasion
Authors: Ireton Keith , Payrastre Bernard , Chap Hugues , Ogawa Wataru , Sakaue Hiroshi , Kasuga Masato , Cossart Pascale
Published: July 2002

Listeria monocytogenes
is a bacterial pathogen that invades cultured nonphagocytic cells. Inhibitors and a dominant negative mutation were used to demonstrate that efficient entry requires the phosphoinositide (PI) 3-kinase p85α-p110. Infection with
L. monocytogenes
caused rapid increases in cellular amounts of PI(3,4)P
2
and PI(3,4,5)P
3
, indicating that invading bacteria stimulated PI 3-kinase activity. This stimulation required the bacterial protein InlB, host cell tyrosine phosphorylation, and association of p85α with one or more tyrosine-phosphorylated proteins. This role for PI 3-kinase in bacterial entry may have parallels in some endocytic events.
TNF- and Cancer Therapy-Induced Apoptosis: Potentiation by Inhibition of NF-κB
Authors: Wang Cun-Yu , Mayo Marty W. , Baldwin Albert S.
Published: July 2002

Many cells are resistant to stimuli that can induce apoptosis, but the mechanisms involved are not fully understood. The activation of the transcription factor nuclear factor-kappa B (NF-κB) by tumor necrosis factor (TNF), ionizing radiation, or daunorubicin (a cancer chemotherapeutic compound), was found to protect from cell killing. Inhibition of NF-κB nuclear translocation enhanced apoptotic killing by these reagents but not by apoptotic stimuli that do not activate NF-κB. These results provide a mechanism of cellular resistance to killing by some apoptotic reagents, offer insight into a new role for NF-κB, and have potential for improvement of the efficacy of cancer therapies.
Nonstationary Phase of the Plio-Pleistocene Asian Monsoon
Authors: Clemens Steven C. , Murray David W. , Prell Warren L.
Published: July 2002

Paleoclimate records indicate that the strength of the Asian summer monsoon is sensitive to orbital forcing at the obliquity and precession periods (41,000 and 23,000 years, respectively) and the extent of Northern Hemisphere glaciation. Over the past 2.6 million years, the timing (phase) of strong monsoons has changed by ∼83 degrees in the precession and ∼124 degrees in the obliquity bands relative to the phase of maximum global ice volume (inferred from the marine oxygen isotope record). These results suggest that one or both of these systems is nonstationary relative to orbital forcing.