bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and simulation studies of thermal flow of borophosphosilicate and phosphosilicate glasses
Authors: Thallikar Guru , Liao Hung , Cale Timothy S. , Myers Frank R.
Published: July 2002

We use EVOLVE−FLOW, a thin film thermal flow process simulator, to simulate the thermal flow of borophosphosilicate glass (BPSG) and phosphosilicate glass (PSG) thin films in trenches on patterned wafers, where two-dimensional surface evolution is appropriate. For a fixed anneal time, two parameters control the thin film flow processes: surface tension and viscosity. We demonstrate our simulator by reproducing flowed BPSG film profiles after a 15 min furnace annealing cycle. Digitized as-deposited BPSG film and substrate profiles from experimental scanning electron micrographs are used as initial profiles in the simulations. We then predict flowed phosphosilicate film profiles, and combine experiments and simulations to estimate the surface tension of PSG films in a rapid thermal annealing process. The viscosity of the PSG films is modeled as a function of temperature and phosphorus pentoxide concentration using an Arrhenius type equation. The estimated values of the viscosity and surface tension are used to simulate the PSG film profiles at different annealing times. The simulation results are in good agreement with experimental observations.
Effects of insulator surface roughness on Al-alloy film properties and electromigration performance in Al-alloy/Ti insulator layered interconnects
Authors: Onoda Hiroshi , Narita Tadashi , Touchi Kenshin , Hashimoto Keiichi
Published: July 2002

Effects of insulator surface roughness on the overlying aluminum alloy film properties and electromigration performance in Al alloy/Ti insulator layered interconnects have been investigated. Insulator surface roughness changes the roughness and crystallographic orientation of Al/Ti layered films formed on the insulator. In particular, the effect is prominent in the case of high-temperature sputtering of Al alloy films. A rough insulator surface deteriorates the roughness and crystallographic orientation of the Al alloy film formed on the insulator, while a smooth insulator surface improves those properties. The insulator surface roughness does not change the roughness and crystallographic orientation of the Al alloy film without a Ti underlayer. Ti roughness and crystallographic orientation are improved on a very smooth surface insulator resulting in improvement in the roughness and crystallographic orientation of the Al alloy film formed on the Ti layer. As a result, the electromigration performance in Al/Ti layered interconnects changes according to the underlayer insulator surface roughness.
Self-assembled monolayers exposed by metastable argon and metastable helium for neutral atom lithography and atomic beam imaging
Authors: Bard A. , Berggren K. K. , Wilbur J. L. , Gillaspy J. D. , Rolston S. L. , McClelland J. J. , Phillips W. D. , Prentiss M. , Whitesides G. M.
Published: July 2002

We used a beam of noble gas atoms in a metastable excited state to expose a thin (1.5 nm) self-assembled monolayer resist applied over a gold-coated silicon wafer. We determined exposure damage as a function of dose of metastable atoms by processing the samples in a wet-chemical etch to remove the gold from unprotected regions and then measuring the reflectivity with a laser and observing the microstructure with an atomic force microscope. We found that the minimum dose required to damage the resist substantially was 1.7(3)×1015 atoms/cm2 for metastable helium, and 25(7)×1015 atoms/cm2 for metastable argon.
Novel methodology for postexposure bake calibration and optimization based on electrical linewidth measurement and process metamodeling
Authors: Capodieci Luigi , Subramanian Ramkumar , Rangarajan Bharath , Heavlin William D. , Li Jiangwei , Bernard Doug A. , Boksha Victor V.
Published: July 2002

By combining electrical linewidth measurements and neural-network (NN) process metamodeling, lithography simulators can be calibrated in an efficient way. In this work we present a novel methodology for characterizing postexposure bake using a very large experimental data set, so that the calibrated model can be used as a truly predictive tool. The adoption of a special test reticle mask allowed us to collect more than 700 000 critical dimensions CDs from 24 silicon wafers for a matrix of postexposure bake (PEB) time, and temperature conditions. The lithographic patterns included isolated, semidense and dense lines for structures of 0.25, 0.20, 0.175, and 0.15 μm nominal size replicated across the exposure field and across the wafer. As a result of this particular metrology, each measured CD was associated with both topological (position on the wafer and position within the field) and process information (exposure dose, PEB time, and temperature). Database management techniques were implemented in order to extract and analyze such a massive data set. Process metamodeling (PMM) was used for the calibration of a PEB model describing the joint effect of photoacid diffusion and photoacid loss, coupled with a deprotection reaction. PMM creates a NN model of the PEB original model (a “model of a model”) so that the diffusion coefficient, the acid loss, and the deprotection rates can be estimated by inversion of the NN mapping. The comparisons between experimental and simulated data show excellent agreement that is maintained across the entire process space.
Nanofabrication in cellular engineering
Authors: Wilkinson C. D. W. , Curtis A. S. G. , Crossan J.
Published: July 2002

Biological cells are strongly influenced by the topography of the surface on which they live, both in cell culture and in an animal. They are guided along micron sized grooves and change their shape becoming more elongated. On the other hand, cells do not adhere to surfaces that are covered in small nanometrically sized pillars. These effects can be used for cellular engineering purposes to determine the behavior of cells and in particular to make prostheses for medical purposes. The differences in micro and nanofabrication techniques necessary to adapt normal semiconductor technology for these purposes are discussed. Patterning of plastics using mechanical methods (embossing and molding) is shown to have excellent resolution, can be used on biodegradable material and a large enough area of patterned material can be produced at a reasonable cost. An application of this technology to the repair of broken tendons is discussed in some detail. It is shown that a biodegradable membrane patterned by embossing with a fused silica master can be used to effect tendon repair. Not only does the tendon reheal, but the synovial channel that should surround the tendon and provide lubrication to the tendon, is reformed correctly.
Spatial frequency analysis of optical lithography resolution enhancement techniques
Authors: Brueck S. R. J. , Chen Xiaolan
Published: July 2002

A consistent frequency-space analysis of the effects of optical lithography resolution enhancement techniques including optical proximity correction, off-axis illumination, phase-shift masks, and imaging interferometric lithography is presented. The improvements for each of these techniques are directly related to the enhanced frequency-space coverage afforded. Optical proximity correction extends the frequency coverage out to ∼1.2–1.3×NA/λ where NA is the optical system numerical aperture and λ the exposure wavelength enabling κ1’s of ∼0.45 in the context of the usual Rayleigh resolution equation CD=κ1λ/NA. There are many possible configurations for off-axis illumination. For a quadrupole oriented at 45° to the (x, y) pattern axes, the maximum spatial frequency is extended to 2NA/λ or κ1∼0.43. Adding pupil plane filters to ensure a uniform modulation transfer function and orienting the quadrupole along the pattern axes allows extension to frequencies of 2NA/λ or κ1∼0.3. Phase shifts at the mask plane emphasize the high frequency image components by increasing the importance of the quadratic imaging terms and allow frequencies to 2NA/λ and κ1’s out to ∼0.35. Imaging interferometric lithography further extends the frequency coverage out to either (1+NA)/λ or 3NA/λ depending on the details with corresponding κ1 s of ∼0.23–0.2.
Core Level XPS Spectra of Silicon Carbide Using Zirconium and Magnesium Radiations
Authors: Chourasia A. R.
Published: July 2002

Core levels of silicon and carbon in the hexagonal form of silicon carbide have been studied by x-ray photoelectron spectroscopy. For this purpose, zirconium Lα (energy = 2042.4 eV) and magnesium Kα (energy = 1253.6 eV) radiations have been employed. The XPS data in the silicon 1s, 2s, 2p, and Auger KLL, and carbon 1s and Auger KLL regions are presented. The data set will serve as a source of valuable information for analyzing spectra associated with silicon and carbon in the insulating sample of silicon carbide.
High Macromolecular Synthesis with Low Metabolic Cost in Antarctic Sea Urchin Embryos
Authors: Marsh Adam G. , Maxson Robert E. , Manahan Donal T.
Published: July 2002

Assessing the energy costs of development in extreme environments is important for understanding how organisms can exist at the margins of the biosphere. Macromolecular turnover rates of RNA and protein were measured at –1.5°C during early development of an Antarctic sea urchin. Contrary to expectations of low synthesis with low metabolism at low temperatures, protein and RNA synthesis rates exhibited temperature compensation and were equivalent to rates in temperate sea urchin embryos. High protein metabolism with a low metabolic rate is energetically possible in this Antarctic sea urchin because the energy cost of protein turnover, 0.45 joules per milligram of protein, is 1/25th the values reported for other animals.
Remotely Sensed Biological Production in the Equatorial Pacific
Authors: Turk Daniela , McPhaden Michael J. , Busalacchi Antonio J. , Lewis Marlon R.
Published: July 2002

A combination of ship, buoy, and satellite observations in the tropical Pacific during the period from 1992 to 2000 provides a basin-scale perspective on the net effects of El Niño and La Niña on biogeochemical cycles. New biological production during the 1997–99 El Niño/La Niña period varied by more than a factor of 2. The resulting interannual changes in global carbon sequestration associated with the El Niño/La Niña cycle contributed to the largest known natural perturbation of the global carbon cycle over these time scales.
TRP-PLIK, a Bifunctional Protein with Kinase and Ion Channel Activities
Authors: Runnels Loren W. , Yue Lixia , Clapham David E.
Published: July 2002

We cloned and characterized a protein kinase and ion channel, TRP-PLIK. As part of the long transient receptor potential channel subfamily implicated in control of cell division, it is a protein that is both an ion channel and a protein kinase. TRP-PLIK phosphorylated itself, displayed a wide tissue distribution, and, when expressed in CHO-K1 cells, constituted a nonselective, calcium-permeant, 105-picosiemen, steeply outwardly rectifying conductance. The zinc finger containing α-kinase domain was functional. Inactivation of the kinase activity by site-directed mutagenesis and the channel's dependence on intracellular adenosine triphosphate (ATP) demonstrated that the channel's kinase activity is essential for channel function.
Observation of Fermi Pressure in a Gas of Trapped Atoms
Authors: Truscott Andrew G. , Strecker Kevin E. , McAlexander William I. , Partridge Guthrie B. , Hulet Randall G.
Published: July 2002

We report the attainment of simultaneous quantum degeneracy in a mixed gas of bosons (lithium-7) and fermions (lithium-6). The Fermi gas has been cooled to a temperature of 0.25 times the Fermi temperature by thermal collisions with the evaporatively cooled bosons. At this temperature, the spatial size of the gas is strongly affected by the Fermi pressure resulting from the Pauli exclusion principle and gives clear experimental evidence for quantum degeneracy.
Fully Conjugated Porphyrin Tapes with Electronic Absorption Bands That Reach into Infrared
Authors: Tsuda Akihiko , Osuka Atsuhiro
Published: July 2002

Scandium(III)-catalyzed oxidation of
meso-meso–
linked zinc(II)-porphyrin arrays (up to dodecamers) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) led to efficient formation of triply
meso-meso
–, β-β–, and β-β–linked zinc(II)-oligoiporphyrins with 62 to 91% yields. These fused tape-shaped porphyrin arrays display extremely red-shifted absorption bands that reflect extensively π-conjugated electronic systems and a low excitation gap. The lowest electronic absorption bands become increasingly intensified and red-shifted upon the increase in the number of porphyrins and eventually reach a peak electronic excitation for the dodecamer at ∼3500 wavenumber. The one-electron oxidation potentials also decreased progressively upon the increase in the number of porphyrins. These properties in long and rigid molecular shapes suggest their potential use as molecular wires.
Promotion of NEDD8-CUL1 Conjugate Cleavage by COP9 Signalosome
Authors: Lyapina Svetlana , Cope Gregory , Shevchenko Anna , Serino Giovanna , Tsuge Tomohiko , Zhou Chunshui , Wolf Dieter A. , Wei Ning , Shevchenko Andrej , Deshaies Raymond J.
Published: July 2002

SCF ubiquitin ligases control various processes by marking regulatory proteins for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are regulated, we sought proteins that interact with the human SCF component CUL1. The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8 from
Schizosaccharomyces pombe
CUL1 in vivo and in vitro. Multiple NEDD8-modified proteins uniquely accumulated in CSN-deficient
S. pombe
cells. We propose that the broad spectrum of activities previously attributed to CSN subunits—including repression of photomorphogenesis, activation of JUN, and activation of p27 nuclear export—underscores the importance of dynamic cycles of NEDD8 attachment and removal in biological regulation.
Role of T-bet in Commitment of T
H
1 Cells Before IL-12-Dependent Selection
Authors: Mullen Alan C. , High Frances A. , Hutchins Anne S. , Lee Hubert W. , Villarino Alejandro V. , Livingston David M. , Kung Andrew L. , Cereb Nezih , Yao Tso-Pang , Yang Soo Y. , Reiner Steven L.
Published: July 2002

How cytokines control differentiation of helper T (T
H
) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies T
H
1 effector fate by targeting chromatin remodeling to individual interferon-γ (IFN-γ) alleles and by inducing IL-12 receptor β2 expression. Subsequently, it appears that IL-12/STAT4 serves two essential functions in the development of T
H
1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-γ synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce T
H
fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.
A GDP/GTP Exchange Factor Involved in Linking a Spatial Landmark to Cell Polarity
Authors: Kang Pil Jung , Sanson Anthony , Lee Bongyong , Park Hay-Oak
Published: July 2002

In both animal and yeast cells, signaling pathways involving small guanosine triphosphatases (GTPases) regulate polarized organization of the actin cytoskeleton. In the budding yeast
Saccharomyces cerevisiae
, the Ras-like GTPase Bud1/Rsr1 and its guanosine 5′-diphosphate (GDP)/guanosine 5′-triphosphate (GTP) exchange factor Bud5 are involved in the selection of a specific site for growth, thus determining cell polarity. We found that Bud5 is localized at the cell division site and the presumptive bud site. Its localization is dependent on potential cellular landmarks, such as Bud3 and Axl2/Bud10 in haploid cells and Bud8 and Bud9 in diploid cells. Bud5 also physically interacts with Axl2/Bud10, a transmembrane glycoprotein, suggesting that a receptor-like transmembrane protein recruits a GDP/GTP exchange factor to connect an intrinsic spatial signal to oriented cell growth.
Coupled Transcription and Translation Within Nuclei of Mammalian Cells
Authors: Iborra Francisco J. , Jackson Dean A. , Cook Peter R.
Published: July 2002

It is widely assumed that the vital processes of transcription and translation are spatially separated in eukaryotes and that no translation occurs in nuclei. We localized translation sites by incubating permeabilized mammalian cells with [
3
H]lysine or lysyl–transfer RNA tagged with biotin or BODIPY; although most nascent polypeptides were cytoplasmic, some were found in discrete nuclear sites known as transcription “factories.” Some of this nuclear translation also depends on concurrent transcription by RNA polymerase II. This coupling is simply explained if nuclear ribosomes translate nascent transcripts as those transcripts emerge from still-engaged RNA polymerases, much as they do in bacteria.
Epigenetic Instability in ES Cells and Cloned Mice
Authors: Humpherys David , Eggan Kevin , Akutsu Hidenori , Hochedlinger Konrad , Rideout William M. , Biniszkiewicz Detlev , Yanagimachi Ryuzo , Jaenisch Rudolf
Published: July 2002

Cloning by nuclear transfer (NT) is an inefficient process in which most clones die before birth and survivors often display growth abnormalities. In an effort to correlate gene expression with survival and fetal overgrowth, we have examined imprinted gene expression in both mice cloned by nuclear transfer and in the embryonic stem (ES) cell donor populations from which they were derived. The epigenetic state of the ES cell genome was found to be extremely unstable. Similarly, variation in imprinted gene expression was observed in most cloned mice, even in those derived from ES cells of the same subclone. Many of the animals survived to adulthood despite widespread gene dysregulation, indicating that mammalian development may be rather tolerant to epigenetic aberrations of the genome. These data imply that even apparently normal cloned animals may have subtle abnormalities in gene expression.
Queen Control of Sex Ratio in Fire Ants
Authors: Passera L. , Aron S. , Vargo E. L. , Keller L.
Published: July 2002

The haplodiploid sex-determination system of ants gives rise to conflict between queens and workers over colony sex ratios, and the female-biased allocation ratios seen in many species suggest that workers often prevail in this conflict. We exchanged queens between male- and female-specialist colonies of the fire ant
Solenopsis invicta
. These exchanges quickly reversed the sex-ratio biases of adopting colonies. The sex ratio of queen-laid eggs differed strongly between male- and female-specialist colonies. These findings suggest that queens can force workers to raise male sexuals by limiting the number of female brood and help to explain why sex investment ratios lie between the queen and worker equilibria in this and many other ant species.
Coupling of the TCR to Integrin Activation by SLAP-130/Fyb
Authors: Peterson Erik J. , Woods Melody L. , Dmowski Sally A. , Derimanov Geo , Jordan Martha S. , Wu Jennifer N. , Myung Peggy S. , Liu Qing-Hua , Pribila Jonathan T. , Freedman Bruce D. , Shimizu Yoji , Koretzky Gary A.
Published: July 2002

SLAP-130/Fyb (SLP-76–associated phosphoprotein or Fyn-binding protein; also known as Fyb/Slap) is a hematopoietic-specific adapter, which associates with and modulates function of SH2-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76). T cells from mice lacking SLAP-130/Fyb show markedly impaired proliferation following CD3 engagement. In addition, the T cell receptor (TCR) in SLAP-130/Fyb mutant cells fails to enhance integrin-dependent adhesion. Although TCR-induced actin polymerization is normal, TCR-stimulated clustering of the integrin LFA-1 is defective in SLAP-130/Fyb–deficient cells. These data indicate that SLAP-130/Fyb is important for coupling TCR-mediated actin cytoskeletal rearrangement with activation of integrin function, and for T cells to respond fully to activating signals.
Hedgehog Signaling: A Tale of Two Lipids
Authors: Ingham Philip W.
Published: July 2002

Hedgehog proteins constitute one of the major classes of intercellular signals that control inductive interactions during animal development. These proteins undergo unusual lipid modifications and signal through an unconventional transmembrane protein receptor that is characterized by a sequence motif implicated in sterol sensing. Recent studies suggest that the lipid adducts regulate the range and potency of the signals, whereas the sterol-sensing domain is essential for receptor activity.
MAPKK-Independent Activation of p38α Mediated by TAB1-Dependent Autophosphorylation of p38α
Authors: Ge Baoxue , Gram Hermann , Di Padova Franco , Huang Betty , New Liguo , Ulevitch Richard J. , Luo Ying , Han Jiahuai
Published: July 2002

Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38α MAPK that does not involve the prototypic kinase cascade. Rather it depends on interaction of p38α with TAB1 [transforming growth factor-β–activated protein kinase 1 (TAK1)–binding protein 1] leading to autophosphorylation and activation of p38α. We detected formation of a TRAF6-TAB1-p38α complex and showed stimulus-specific TAB1-dependent and TAB1-independent p38α activation. These findings suggest that alternative activation pathways contribute to the biological responses of p38α to various stimuli.
Influence of SHIP on the NK Repertoire and Allogeneic Bone Marrow Transplantation
Authors: Wang Jia-Wang , Howson Julie M. , Ghansah Tomar , Desponts Caroline , Ninos John M. , May Sarah L. , Nguyen Kim H. T. , Toyama-Sorimachi Noriko , Kerr William G.
Published: July 2002

Natural killer cell (NK) receptors for major histocompatibility complex (MHC) class I influence engraftment and graft-versus-tumor effects after allogeneic bone marrow transplantation. We find that SH2-containing inositol phosphatase (SHIP) influences the repertoire of NK receptors. In adult SHIP
−/−
mice, the NK compartment is dominated by cells that express two inhibitory receptors capable of binding either self or allogeneic MHC ligands. This promiscuous repertoire has significant functional consequences, because SHIP
−/−
mice fail to reject fully mismatched allogeneic marrow grafts and show enhanced survival after such transplants. Thus, SHIP plays an important role in two processes that limit the success of allogeneic marrow transplantation: graft rejection and graft-versus-host disease.
Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail
Authors: Jacobs Steven A. , Khorasanizadeh Sepideh
Published: July 2002

The chromodomain of the HP1 family of proteins recognizes histone tails with specifically methylated lysines. Here, we present structural, energetic, and mutational analyses of the complex between the
Drosophila
HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing. The histone tail inserts as a β strand, completing the β-sandwich architecture of the chromodomain. The methylammonium group is caged by three aromatic side chains, whereas adjacent residues form discerning contacts with one face of the chromodomain. Comparison of dimethyl- and trimethyllysine-containing complexes suggests a role for cation-π and van der Waals interactions, with trimethylation slightly improving the binding affinity.
Female Germ Cell Aneuploidy and Embryo Death in Mice Lacking the Meiosis-Specific Protein SCP3
Authors: Yuan Li , Liu Jian-Guo , Hoja Mary-Rose , Wilbertz Johannes , Nordqvist Katarina , Höög Christer
Published: July 2002

Aneuploidy (trisomy or monosomy) is the leading genetic cause of pregnancy loss in humans and results from errors in meiotic chromosome segregation. Here, we show that the absence of synaptonemal complex protein 3 (SCP3) promotes aneuploidy in murine oocytes by inducing defective meiotic chromosome segregation. The abnormal oocyte karyotype is inherited by embryos, which die in utero at an early stage of development. In addition, embryo death in
SCP3
-deficient females increases with advancing maternal age. We found that SCP3 is required for chiasmata formation and for the structural integrity of meiotic chromosomes, suggesting that altered chromosomal structure triggers nondisjunction.
SCP3
is thus linked to inherited aneuploidy in female germ cells and provides a model system for studying age-dependent degeneration in oocytes.
Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK
Authors: Wu Hai , Kanatous Shane B. , Thurmond Frederick A. , Gallardo Teresa , Isotani Eiji , Bassel-Duby Rhonda , Williams R. Sanders
Published: July 2002

Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium/calmodulin–dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis, up-regulation of mitochondrial enzymes involved in fatty acid metabolism and electron transport, and reduced susceptibility to fatigue during repetitive contractions. CaMK induced expression of peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), a master regulator of mitochondrial biogenesis in vivo, and activated the PGC-1 gene promoter in cultured myocytes. Thus, a calcium-regulated signaling pathway controls mitochondrial biogenesis in mammalian cells.
An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
Authors: Beg Amer A. , Baltimore David
Published: July 2002

Studies on mice deficient in nuclear factor kappa B (NF-κB) subunits have shown that this transcription factor is important for lymphocyte responses to antigens and cytokine-inducible gene expression. In particular, the RelA (p65) subunit is required for induction of tumor necrosis factor-α (TNF-α)-dependent genes. Treatment of RelA-deficient (RelA
−/−
) mouse fibroblasts and macrophages with TNF-α resulted in a significant reduction in viability, whereas RelA
+/+
cells were unaffected. Cytotoxicity to both cell types was mediated by TNF receptor 1. Reintroduction of RelA into RelA
−/−
fibroblasts resulted in enhanced survival, demonstrating that the presence of RelA is required for protection from TNF-α. These results have implications for the treatment of inflammatory and proliferative diseases.
Maturation of a Central Glutamatergic Synapse
Authors: Wu G.-Y. , Malinow R. , Cline H. T.
Published: July 2002

Whole-cell recordings from optic tectal neurons in
Xenopus
tadpoles were used to study the maturation of a glutamatergic synapse. The first glutamatergic transmission is mediated only by
N
-methyl-D-aspartate (NMDA) receptors and is silent at resting potentials. More mature synapses acquire transmission by α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. This maturational program is mimicked by postsynaptic expression of constitutively active calcium-calmodulin-dependent protein kinase II (CaMKII). Newly formed synapses may be silent unless sufficient depolarization is provided by coincident activity that could activate postsynaptic CaMKII, resulting in the appearance of AMPA responses.
Neuroprotection by Aspirin and Sodium Salicylate Through Blockade of NF-κB Activation
Authors: Grilli Mariagrazia , Pizzi Marina , Memo Maurizio , Spano PierFranco
Published: July 2002

Aspirin (acetylsalicylic acid) is a commonly prescribed drug with a wide pharmacological spectrum. At concentrations compatible with amounts in plasma during chronic anti-inflammatory therapy, acetylsalicylic acid and its metabolite sodium salicylate were found to be protective against neurotoxicity elicited by the excitatory amino acid glutamate in rat primary neuronal cultures and hippocampal slices. The site of action of the drugs appeared to be downstream of glutamate receptors and to involve specific inhibition of glutamate-mediated induction of nuclear factor kappa B. These results may contribute to the emerging theme of anti-inflammatory drugs and neurodegeneration.
Immune Hyperactivation of HIV-1-Infected T Cells Mediated by Tat and the CD28 Pathway
Authors: Ott Melanie , Emiliani Stephane , Van Lint Carine , Herbein Georges , Lovett Jennie , Chirmule Narendra , McCloskey Thomas , Pahwa Savita , Verdin Eric
Published: July 2002

Human immunodeficiency virus-type 1 (HIV-1) infection is characterized by a chronic state of immune hyperactivation in patients. Infection of human peripheral blood lymphocytes with HIV-1 in vitro resulted in increased interleukin-2 (IL-2) secretion in response to T cell activation via the CD3 and CD28 receptors. Expression of the HIV-1 transactivator Tat recapitulated this phenotype and was associated with increased IL-2 secretion in response to costimulation with CD3 plus CD28. IL-2 superinduction by Tat occurred at the transcriptional level, was mediated by the CD28-responsive element in the IL-2 promoter, and was exclusively dependent on the 29 amino acids encoded by the second exon of Tat.
A Plastid of Probable Green Algal Origin in Apicomplexan Parasites
Authors: Köhler Sabine , Delwiche Charles F. , Denny Paul W. , Tilney Lewis G. , Webster Paul , Wilson R. J. M. , Palmer Jeffrey D. , Roos David S.
Published: July 2002

Protozoan parasites of the phylum Apicomplexa contain three genetic elements: the nuclear and mitochondrial genomes characteristic of virtually all eukaryotic cells and a 35-kilobase circular extrachromosomal DNA. In situ hybridization techniques were used to localize the 35-kilobase DNA of
Toxoplasma gondii
to a discrete organelle surrounded by four membranes. Phylogenetic analysis of the
tufA
gene encoded by the 35-kilobase genomes of coccidians
T. gondii
and
Eimeria tenella
and the malaria parasite
Plasmodium falciparum
grouped this organellar genome with cyanobacteria and plastids, showing consistent clustering with green algal plastids. Taken together, these observations indicate that the Apicomplexa acquired a plastid by secondary endosymbiosis, probably from a green alga.
Phylogenetic Methods Come of Age: Testing Hypotheses in an Evolutionary Context
Authors: Huelsenbeck John P. , Rannala Bruce
Published: July 2002

The use of molecular phylogenies to examine evolutionary questions has become commonplace with the automation of DNA sequencing and the availability of efficient computer programs to perform phylogenetic analyses. The application of computer simulation and likelihood ratio tests to evolutionary hypotheses represents a recent methodological development in this field. Likelihood ratio tests have enabled biologists to address many questions in evolutionary biology that have been difficult to resolve in the past, such as whether host-parasite systems are cospeciating and whether models of DNA substitution adequately explain observed sequences.
The Roles of γ1 Heavy Chain Membrane Expression and Cytoplasmic Tail in IgG1 Responses
Authors: Kaisho Tsuneyasu , Schwenk Frieder , Rajewsky Klaus
Published: July 2002

In antibody responses, B cells switch from the expression of immunoglobulin (Ig) μ and δ heavy (H) chains to that of other Ig classes (α, γ, or ɛ), each with a distinct effector function. Membrane-bound forms of α, γ, and ɛ, but not μ and δ, have highly conserved cytoplasmic tails. Mutant mice unable to express membrane γ1 H chains or producing tailless γ1 H chains failed to generate efficient IgG1 responses and IgG1 memory. H chain membrane expression after class switching is thus required for these functions, and class switching equips the B cell antigen receptor with a regulatory cytoplasmic tail that naı̈ve B cells lack.
Regulation of Protein Phosphatase 2A by Direct Interaction with Casein Kinase 2α
Authors: Hériché Jean-Karim , Lebrin Franck , Rabilloud Thierry , Leroy Didier , Chambaz Edmond M. , Goldberg Yves
Published: July 2002

Timely deactivation of kinase cascades is crucial to the normal control of cell signaling and is partly accomplished by protein phosphatase 2A (PP2A). The catalytic (α) subunit of the serine-threonine kinase casein kinase 2 (CK2) bound to PP2A in vitro and in mitogen-starved cells; binding required the integrity of a sequence motif common to CK2α and SV40 small t antigen. Overexpression of CK2α resulted in deactivation of mitogen-activated protein kinase kinase (MEK) and suppression of cell growth. Moreover, CK2α inhibited the transforming activity of oncogenic Ras, but not that of constitutively activated MEK. Thus, CK2α may regulate the deactivation of the mitogen-activated protein kinase pathway.
In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography
Authors: Tearney Guillermo J. , Brezinski Mark E. , Bouma Brett E. , Boppart Stephen A. , Pitris Costas , Southern James F. , Fujimoto James G.
Published: July 2002

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as “optical biopsy,” was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.
Detection of Soft X-rays and a Sensitive Search for Noble Gases in Comet Hale-Bopp (C/1995 O1)
Authors: Krasnopolsky Vladimir A. , Mumma Michael J. , Abbott Mark , Flynn Brian C. , Meech Karen J. , Yeomans Donald K. , Feldman Paul D. , Cosmovici Cristiano B.
Published: July 2002

An image of comet Hale-Bopp (C/1995 O1) in soft x-rays reveals a central emission offset from the nucleus, as well as an extended emission feature that does not correlate with the dust jets seen at optical wavelengths. Neon was found to be depleted in the cometary ice by more than a factor of 25 relative to solar abundance, which suggests that ices in Hale-Bopp formed at (or later experienced) temperatures higher than 25 kelvin. A helium line emission at a wavelength of 584 angstroms was detected and may be attributable to charge transfer of solar wind α particles in the cometary coma. Ionized oxygen and another helium line contribute to an emission observed at 538 angstroms.
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis
Authors: Sleat David E. , Donnelly Robert J. , Lackland Henry , Liu Chang-Gong , Sohar Istvan , Pullarkat Raju K. , Lobel Peter
Published: July 2002

Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease whose defective gene has remained elusive. A molecular basis for LINCL was determined with an approach applicable to other lysosomal storage diseases. When the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, a single protein was identified that is absent in LINCL. Sequence comparisons suggest that this protein is a pepstatin-insensitive lysosomal peptidase, and a corresponding enzymatic activity was deficient in LINCL autopsy specimens. Mutations in the gene encoding this protein were identified in LINCL patients but not in normal controls.
DNA Solution of the Maximal Clique Problem
Authors: Ouyang Qi , Kaplan Peter D. , Liu Shumao , Libchaber Albert
Published: July 2002

The maximal clique problem has been solved by means of molecular biology techniques. A pool of DNA molecules corresponding to the total ensemble of six-vertex cliques was built, followed by a series of selection processes. The algorithm is highly parallel and has satisfactory fidelity. This work represents further evidence for the ability of DNA computing to solve NP-complete search problems.
Interneuron Migration from Basal Forebrain to Neocortex: Dependence on
Dlx
Genes
Authors: Anderson S. A. , Eisenstat D. D. , Shi L. , Rubenstein J. L. R.
Published: July 2002

Although previous analyses indicate that neocortical neurons originate from the cortical proliferative zone, evidence suggests that a subpopulation of neocortical interneurons originates within the subcortical telencephalon. For example, γ-aminobutyric acid (GABA)–expressing cells migrate in vitro from the subcortical telencephalon into the neocortex. The number of GABA-expressing cells in neocortical slices is reduced by separating the neocortex from the subcortical telencephalon. Finally, mice lacking the homeodomain proteins DLX-1 and DLX-2 show no detectable cell migration from the subcortical telencephalon to the neocortex and also have few GABA-expressing cells in the neocortex.
Common and Distinct Roles of DFos and DJun During
Drosophila
Development
Authors: Riesgo-Escovar Juan R. , Hafen Ernst
Published: July 2002

The
Drosophila
homolog of c-Jun regulates epithelial cell shape changes during the process of dorsal closure in mid-embryogenesis. Here, mutations in the
DFos
gene are described. In dorsal closure, DFos cooperates with DJun by regulating the expression of
dpp
; Dpp acts as a relay signal that triggers cell shape changes and
DFos
expression in neighboring cells. In addition to the joint requirement of DFos and DJun during dorsal closure, DFos functions independently of DJun during early stages of embryogenesis. These findings demonstrate common and distinct roles of DFos and DJun during embryogenesis and suggest a conserved link between AP-1 (activating protein-1) and TGF-β (transforming growth factor–β) signaling during epithelial cell shape changes.
A Euryarchaeal Lysyl-tRNA Synthetase: Resemblance to Class I Synthetases
Authors: Ibba Michael , Morgan Susan , Curnow Alan W. , Pridmore David R. , Vothknecht Ute C. , Gardner Warren , Lin Winston , Woese Carl R. , Söll Dieter
Published: July 2002

The sequencing of euryarchaeal genomes has suggested that the essential protein lysyl–transfer RNA (tRNA) synthetase (LysRS) is absent from such organisms. However, a single 62-kilodalton protein with canonical LysRS activity was purified from
Methanococcus maripaludis
, and the gene that encodes this protein was cloned. The predicted amino acid sequence of
M. maripaludis
LysRS is similar to open reading frames of unassigned function in both
Methanobacterium thermoautotrophicum
and
Methanococcus jannaschii
but is unrelated to canonical LysRS proteins reported in eubacteria, eukaryotes, and the crenarchaeote
Sulfolobus solfataricus
. The presence of amino acid motifs characteristic of the Rossmann dinucleotide-binding domain identifies
M. maripaludis
LysRS as a class I aminoacyl–tRNA synthetase, in contrast to the known examples of this enzyme, which are class II synthetases. These data question the concept that the classification of aminoacyl–tRNA synthetases does not vary throughout living systems.
Geomagnetic Modulation of the
36
Cl Flux in the GRIP Ice Core, Greenland
Authors: Baumgartner S. , Beer J. , Masarik J. , Wagner G. , Meynadier L. , Synal H.-A.
Published: July 2002

Geomagnetic field strength is expected to affect the production rate of cosmogenic isotopes such as beryllium-10, carbon-14, or chlorine-36. Chlorine-36 data from the Greenland Ice Core Project (GRIP) ice core agree well with a production rate calculation based on a paleomagnetic reconstruction for the past 100,000 years over both long- and short-term variations. A chlorine-36 peak at 38,000 years ago previously found in the beryllium-10 record from the Vostok ice core can be explained by a period of low geomagnetic field intensity.
Recognition of Stress-Induced MHC Molecules by Intestinal Epithelial γδ T Cells
Authors: Groh Veronika , Steinle Alexander , Bauer Stefan , Spies Thomas
Published: July 2002

T cells with variable region V
δ
1 γδ T cell receptors (TCRs) are distributed throughout the human intestinal epithelium and may function as sentinels that respond to self antigens. The expression of a major histocompatibility complex (MHC) class I–related molecule, MICA, matches this localization. MICA and the closely related MICB were recognized by intestinal epithelial T cells expressing diverse V
δ
1 γδ TCRs. These interactions involved the α1α2 domains of MICA and MICB but were independent of antigen processing. With intestinal epithelial cell lines, the expression and recognition of MICA and MICB could be stress-induced. Thus, these molecules may broadly regulate protective responses by the V
δ
1 γδ T cells in the epithelium of the intestinal tract.
Large-Scale Identification, Mapping, and Genotyping of Single-Nucleotide Polymorphisms in the Human Genome
Authors: Wang David G. , Fan Jian-Bing , Siao Chia-Jen , Berno Anthony , Young Peter , Sapolsky Ron , Ghandour Ghassan , Perkins Nancy , Winchester Ellen , Spencer Jessica , Kruglyak Leonid , Stein Lincoln , Hsie Linda , Topaloglou Thodoros , Hubbell Earl , Robinson Elizabeth , Mittmann Michael , Morris Macdonald S. , Shen Naiping , Kilburn Dan , Rioux John , Nusbaum Chad , Rozen Steve , Hudson Thomas J. , Lipshutz Robert , Chee Mark , Lander Eric S.
Published: July 2002

Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A genetic map was constructed showing the location of 2227 of these SNPs. Prototype genotyping chips were developed that allow simultaneous genotyping of 500 SNPs. The results provide a characterization of human diversity at the nucleotide level and demonstrate the feasibility of large-scale identification of human SNPs.
Promotion of Met-tRNA
i
Met
Binding to Ribosomes by yIF2, a Bacterial IF2 Homolog in Yeast
Authors: Choi Sang Ki , Lee Joon H. , Zoll Wendy L. , Merrick William C. , Dever Thomas E.
Published: July 2002

Delivery of the initiator methionine transfer RNA (Met-tRNA
i
Met
) to the ribosome is a key step in the initiation of protein synthesis. Previous results have indicated that this step is catalyzed by the structurally dissimilar translation factors in prokaryotes and eukaryotes—initiation factor 2 (IF2) and eukaryotic initiation factor 2 (eIF2), respectively. A bacterial IF2 homolog has been identified in both eukaryotes and archaea. By using a combination of molecular genetic and biochemical studies, the
Saccharomyces cerevisiae
IF2 homolog is shown to function in general translation initiation by promoting Met-tRNA
i
Met
binding to ribosomes. Thus, the mechanism of protein synthesis in eukaryotes and prokaryotes is more similar than was previously realized.
Optimizing Gaze Control in Three Dimensions
Authors: Tweed Douglas , Haslwanter Thomas , Fetter Michael
Published: July 2002

Horizontal and vertical movements of the human eye bring new objects to the center of the visual field, but torsional movements rotate the visual world about its center. Ocular torsion stays near zero during head-fixed gaze shifts, and eye movements to visual targets are thought to be driven by purely horizontal and vertical commands. Here, analysis of eye-head gaze shifts revealed that gaze commands were three-dimensional, with a separate neural control system for torsion. Active torsion optimized gaze control as no two-dimensional system could have, stabilizing the retinal image as quickly as possible when it would otherwise have spun around the fixation point.
Fertilization Defects in Sperm from Mice Lacking Fertilin β
Authors: Cho Chunghee , O'Dell Bunch Donna , Faure Jean-Emmanuel , Goulding Eugenia H. , Eddy Edward M. , Primakoff Paul , Myles Diana G.
Published: July 2002

Fertilin, a member of the ADAM family, is found on the plasma membrane of mammalian sperm. Sperm from mice lacking fertilin β were shown to be deficient in sperm-egg membrane adhesion, sperm-egg fusion, migration from the uterus into the oviduct, and binding to the egg zona pellucida. Egg activation was unaffected. The results are consistent with a direct role of fertilin in sperm-egg plasma membrane interaction. Fertilin could also have a direct role in sperm-zona binding or oviduct migration; alternatively, the effects on these functions could result from the absence of fertilin activity during spermatogenesis.
The Evolutionary Dynamics of Sex Determination
Authors: Marı́n Ignacio , Baker Bruce S.
Published: July 2002

REVIEW

There is substantial cytogenetic data indicating that the process of sex determination can evolve relatively rapidly. However, recent molecular studies on the evolution of the regulatory genes that control sex determination in the insect
Drosophila melanogaster
, the nematode
Caenorhabditis elegans
, and mammals suggest that, although certain sex determination regulatory genes have evolved relatively rapidly, other sex determination regulatory genes are quite conserved. Thus, studies of the evolution of sex determination, a process that appears to have elements that undergo substantial evolutionary change and others that may be conserved, could provide substantial insights into the kinds of forces that both drive and constrain the evolution of developmental hierarchies.
A Structural Basis for Recognition of A·T and T·A Base Pairs in the Minor Groove of B-DNA
Authors: Kielkopf Clara L. , White Sarah , Szewczyk Jason W. , Turner James M. , Baird Eldon E. , Dervan Peter B. , Rees Douglas C.
Published: July 2002

Polyamide dimers containing three types of aromatic rings—pyrrole, imidazole, and hydroxypyrrole—afford a small-molecule recognition code that discriminates among all four Watson-Crick base pairs in the minor groove. The crystal structure of a specific polyamide dimer-DNA complex establishes the structural basis for distinguishing T·A from A·T base pairs. Specificity for the T·A base pair is achieved by means of distinct hydrogen bonds between pairs of substituted pyrroles on the ligand and the O2 of thymine and N3 of adenine. In addition, shape-selective recognition of an asymmetric cleft between the thymine-O2 and the adenine-C2 was observed. Although hitherto similarities among the base pairs in the minor groove have been emphasized, the structure illustrates differences that allow specific minor groove recognition.
Bifurcation of Lipid and Protein Kinase Signals of PI3Kγ to the Protein Kinases PKB and MAPK
Authors: Bondeva Tzvetanka , Pirola Luciano , Bulgarelli-Leva Ginette , Rubio Ignacio , Wetzker Reinhard , Wymann Matthias P.
Published: July 2002

Phosphoinositide 3-kinases (PI3Ks) activate protein kinase PKB (also termed Akt), and PI3Kγ activated by heterotrimeric guanosine triphosphate–binding protein can stimulate mitogen-activated protein kinase (MAPK). Exchange of a putative lipid substrate-binding site generated PI3Kγ proteins with altered or aborted lipid but retained protein kinase activity. Transiently expressed, PI3Kγ hybrids exhibited wortmannin-sensitive activation of MAPK, whereas a catalytically inactive PI3Kγ did not. Membrane-targeted PI3Kγ constitutively produced phosphatidylinositol 3,4,5-trisphosphate and activated PKB but not MAPK. Moreover, stimulation of MAPK in response to lysophosphatidic acid was blocked by catalytically inactive PI3Kγ but not by hybrid PI3Kγs. Thus, two major signals emerge from PI3Kγ: phosphoinositides that target PKB and protein phosphorylation that activates MAPK.