bluuebunny/crossref_metadata_2025 huggingface dataset:
Methodology for interference analysis using electromagnetic topology techniques
Authors: Kirawanich Phumin , Gunda Rahul , Kranthi Nakka S. , Kroenung Jeffery C. , Islam N. E.
Published: April 2004

For simulation codes based on the electromagnetic topology theory, a method to characterize electromagnetic interference and interactions between an external source and internal circuitry of a semi-shielded system is described. Simulation results based on this technique compare well with previously measured data. Analysis also shows that the high-frequency resonances on the cable voltage and current depend on the length of the cable and its termination impedances.
MgO
/p-
GaN
enhancement mode metal-oxide semiconductor field-effect transistors
Authors: Irokawa Y. , Nakano Y. , Ishiko M. , Kachi T. , Kim J. , Ren F. , Gila B. P. , Onstine A. H. , Abernathy C. R. , Pearton S. J. , Pan C.-C. , Chen G.-T. , Chyi J.-I.
Published: April 2004

We report the initial demonstration of an enhancement mode MgO/p-GaN metal-oxide-semiconductor field-effect transistor (MOSFET) utilizing Si+ ion-implanted regions under the source and drain to provide a source of minority carriers for inversion. The breakdown voltage for an 80-nm-thick MgO gate dielectric was ∼14 V, corresponding to a breakdown field strength of 1.75 MV cm−1 and the p-n junction formed between the p-epi and the source had a reverse breakdown voltage >15 V. Inversion of the channel was achieved for gate voltages above 6 V. The maximum transconductance was 5.4 μS mm−1 at a drain-source voltage of 5 V, comparable to the initial values reported for GaAs MOSFETs.
In situ magnetoresistance of Ni nanocontacts
Authors: Yang C.-S. , Zhang C. , Redepenning J. , Doudin B.
Published: April 2004

Magnetoresistance properties of Ni nanocontacts in the ballistic quantum regime are investigated in situ during closure and opening of electrochemically grown planar electrodes. The magnitude of conductance change when sweeping the magnetic field is of the order of the quantum conductance e2/h for conductance values spanning 1–100 quanta. The relative orientation of electric current and applied magnetic field changes the magnetoresistance sign, with symmetry properties reminiscent of bulk anisotropy magnetoresistance. Ex situ investigations of samples of higher conductance values, of the order of 1000 quanta, unambiguously show the analogy with bulk anisotropy magnetoresistance.
Formation of strain-induced Si-rich and Ge-rich nanowires at misfit dislocations in SiGe: A model supported by photoluminescence data
Authors: Martinelli Lucio , Marzegalli A. , Raiteri P. , Bollani M. , Montalenti F. , Miglio Leo , Chrastina D. , Isella G. , von Känel H.
Published: April 2004

Molecular dynamics simulations with the Tersoff potential of the strain distribution around 60° misfit dislocation in a heteroepitaxial SiGe film confirm that highly compressed and expanded, cylindrical nanometer-sized regions appear on opposite sides of the (111) glide plane. Such a configuration is suggested to generate opposite chemical potential gradients for Si and Ge diffusion and, as verified by a Monte Carlo simulation, in the formation of Si-rich and Ge-rich nanowires along the dislocation core. This model is supported by photoluminescence measurements as a function of annealing temperature and time.
Investigation of laser-induced cell lysis using time-resolved imaging
Authors: Rau Kaustubh R. , Guerra Arnold , Vogel Alfred , Venugopalan Vasan
Published: April 2004

Using time-resolved imaging, we investigated the lysis of confluent PtK2 cell cultures by pulsed laser microbeam irradiation. Images obtained at time delays of 0.5 ns to 50 μs demonstrate lysis to be mediated by laser-induced plasma formation resulting in pressure wave propagation and cavitation bubble formation. Image analysis enabled quantitative characterization of the pressure wave and cavitation bubble dynamics. The zone of cell damage exceeded the plasma size and serves to implicate cavitation bubble expansion as the primary agent of cell injury.
Domain wall displacement induced by subnanosecond pulsed current
Authors: Lim C. K. , Devolder T. , Chappert C. , Grollier J. , Cros V. , Vaurès A. , Fert A. , Faini G.
Published: April 2004

We show that a single current pulse as short as 0.4 ns can trigger domain wall (DW) displacement in spin-valve stripes of 0.3 μm width inserted into a coplanar waveguide. The experiments were carried out with varying current pulse amplitude, duration, polarity, and applied static magnetic field. In zero field, DW displacement occurs in the same direction as the conduction electron current. In finite applied field, the direction of DW displacement is that favored by the field orientation. In both cases, the DW displacement occurs only above a critical current density jc of the order of 106 A/cm2. The distance traveled by the DW along the stripe increases with the current pulse amplitude and applied field strength, but it does not depend on the pulse duration between 0.4 and 2 ns.
InAs/GaP/InGaP high-temperature power Schottky rectifier
Authors: Chen A. , Woodall J. M.
Published: April 2004

An InAs/GaP/InGaP rectifier has been fabricated using a semiconductor-semiconductor “Schottky” junction to utilize the thermal stability of the semiconductor-semiconductor interface. The InAs/GaP/InGaP system demonstrates rectifying characteristics with an ideality factor of 2.3 and a current–voltage extracted barrier height of 0.96 eV. It exhibits low reverse bias leakage current and achieves breakdown electric field of 0.6 MV/cm. The InAs/GaP/InGaP system maintains the rectifying characteristics up to 600 °C. Further improvement of the thermal stability is expected to be achieved by reducing the diffusion of Si dopant atoms across the InAs/GaP interface at high temperature.
Targeted mutations of the juxtamembrane tyrosines in the Kit receptor tyrosine kinase selectively affect multiple cell lineages
Authors: Kimura Yuki , Jones Nina , Klüppel Michael , Hirashima Masanori , Tachibana Kazunobu , Cohn Jason B. , Wrana Jeffrey L. , Pawson Tony , Bernstein Alan
Published: April 2004

Loss-of-function mutations in the murine dominantwhite spotting/c-kitlocus affect a diverse array of biological processes and cell lineages and cause a range of phenotypes, including severe anemia, defective pigmentation, sterility, mast cell deficits, a lack of interstitial cells of Cajal, spatial learning memory deficits, and defects in peripheral nerve regeneration. Here we show that tyrosine residues 567 and 569 in the juxtamembrane (Jx) domain of the murine Kit receptor tyrosine kinase are crucial for the function of Kit in melanogenesis and mast cell development, but are dispensable for the normal development of erythroid, interstitial cells of Cajal and germ cells. Furthermore, adult mice lacking both tyrosines exhibit splenomegaly, dysregulation of B-cell and megakaryocyte development, and enlarged stomachs. Analysis of signal transduction events induced by the mutant receptors after ligand stimulation indicates that Jx tyrosine mutations diminish receptor autophosphorylation and selectively attenuate activation of extracellular signal-regulated kinase/mitogen-activated protein kinases. Together, these observations demonstrate that the Jx domain of Kit plays a cell-type specific regulatory rolein vivoand illustrate how engineered mutations in Kit can be used to understand the complex biological and molecular events that result from activating a receptor tyrosine kinase.
The genetics of geometry
Authors: Coen Enrico , Rolland-Lagan Anne-Gaëlle , Matthews Mark , Bangham J. Andrew , Prusinkiewicz Przemyslaw
Published: April 2004

Although much progress has been made in understanding how gene expression patterns are established during development, much less is known about how these patterns are related to the growth of biological shapes. Here we describe conceptual and experimental approaches to bridging this gap, with particular reference to plant development where lack of cell movement simplifies matters. Growth and shape change in plants can be fully described with four types of regional parameter: growth rate, anisotropy, direction, and rotation. A key requirement is to understand how these parameters both influence and respond to the action of genes. This can be addressed by using mechanistic models that capture interactions among three components: regional identities, regionalizing morphogens, and polarizing morphogens. By incorporating these interactions within a growing framework, it is possible to generate shape changes and associated gene expression patterns according to particular hypotheses. The results can be compared with experimental observations of growth of normal and mutant forms, allowing further hypotheses and experiments to be formulated. We illustrate these principles with a study of snapdragon petal growth.
The effect of climatic forcing on population synchrony and genetic structuring of the Canadian lynx
Authors: Stenseth Nils Chr. , Ehrich Dorothee , Rueness Eli Knispel , Lingjærde Ole Chr. , Chan Kung-Sik , Boutin Stan , O'Donoghue Mark , Robinson David A. , Viljugrein Hildegunn , Jakobsen Kjetill S.
Published: April 2004

The abundance of Canadian lynx follows 10-year density fluctuations across the Canadian subcontinent. These cyclic fluctuations have earlier been shown to be geographically structured into three climatic regions: the Atlantic, Continental, and Pacific zones. Recent genetic evidence revealed an essentially similar spatial structuring. Introducing a new population model, the “climate forcing of ecological and evolutionary patterns” model, we link the observed ecological and evolutionary patterns. Specifically, we demonstrate that there is greater phase synchrony within climatic zones than between them and show that external climatic forcing may act as a synchronizer. We simulated genetic drift by using data on population dynamics generated by the climate forcing of ecological and evolutionary patterns model, and we demonstrate that the observed genetic structuring can be seen as an emerging property of the spatiotemporal ecological dynamics.
Chiral phosphoramide-catalyzed, enantioselective, directed cross-aldol reactions of aldehydes
Authors: Denmark Scott E. , Bui Tommy
Published: April 2004

Catalytic, enantioselective, directed cross-aldol reactions of aldehydes are described. The addition of isobutyraldehyde trichlorosilyl enolate 2 to various aldehydes in the presence of 10 mol % bisphosphoramide 4 provides aldol products in high yields with moderate to good enantioselectivities. The reaction works well with a wide range of aromatic, olefinic, and aliphatic aldehydes. Enantioselectivities are highly dependent on the electronic nature of the aldehyde substituent. Hammett studies reveal that enantioselectivity increases as aldehydes become either more electron rich or more electron poor.
Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects
Authors: Hirasawa Motoyuki , Ohshima Toshio , Takahashi Satoru , Longenecker Glenn , Honjo Yasuyuki , Veeranna  , Pant Harish C. , Mikoshiba Katsuhiko , Brady Roscoe O. , Kulkarni Ashok B.
Published: April 2004

Cyclin-dependent kinase 5 (Cdk5) is essential for the proper development of the CNS, as is evident from the perinatal lethality of conventional Cdk5 knockout (Cdk5-/-) mice. Cdk5 is also implicated in numerous complex functions of the adult CNS such as synaptic transmission, synaptic plasticity, and neuronal signaling. To elucidate the molecular roles of Cdk5 in the adult CNS, we have abrogated neuronal expression of Cdk5 in perinatal mice by using a cre-loxP system. The Cdk5-loxP flanked mice were crossed with the cre-transgenic mice in which the cre expression is driven by the murine neurofilament-heavy chain promoter, resulting in generation of viable Cdk5 conditional knockout mice with the restricted deletion of the Cdk5 gene in specific neurons beginning around embryonic day 16.5. Twenty-five percent of the Cdk5 conditional knockout mice carrying the heterozygous cre allele had neuronal migration defects confined to brain areas where neuronal migration continues through the perinatal period. These results indicate that abrogation of Cdk5 expression in mature neurons results in a viable mouse model that offers further opportunities to investigate the molecular roles of Cdk5 in the adult CNS.
Coauthorship networks and patterns of scientific collaboration
Authors: Newman M. E. J.
Published: April 2004

By using data from three bibliographic databases in biology, physics, and mathematics, respectively, networks are constructed in which the nodes are scientists, and two scientists are connected if they have coauthored a paper. We use these networks to answer a broad variety of questions about collaboration patterns, such as the numbers of papers authors write, how many people they write them with, what the typical distance between scientists is through the network, and how patterns of collaboration vary between subjects and over time. We also summarize a number of recent results by other authors on coauthorship patterns.
The simultaneous evolution of author and paper networks
Authors: Börner Katy , Maru Jeegar T. , Goldstone Robert L.
Published: April 2004

There has been a long history of research into the structure and evolution of mankind's scientific endeavor. However, recent progress in applying the tools of science to understand science itself has been unprecedented because only recently has there been access to high-volume and high-quality data sets of scientific output (e.g., publications, patents, grants) and computers and algorithms capable of handling this enormous stream of data. This article reviews major work on models that aim to capture and recreate the structure and dynamics of scientific evolution. We then introduce a general process model that simultaneously grows coauthor and paper citation networks. The statistical and dynamic properties of the networks generated by this model are validated against a 20-year data set of articles published in PNAS. Systematic deviations from a power law distribution of citations to papers are well fit by a model that incorporates a partitioning of authors and papers into topics, a bias for authors to cite recent papers, and a tendency for authors to cite papers cited by papers that they have read. In this TARL model (for topics, aging, and recursive linking), the number of topics is linearly related to the clustering coefficient of the simulated paper citation network.
User-controlled mapping of significant literatures
Authors: White Howard D. , Lin Xia , Buzydlowski Jan W. , Chen Chaomei
Published: April 2004

We apply a version of our web-based literature-mapping system to PNAS for 1971-2002, as indexed by the National Library of Medicine and the Institute for Scientific Information. Given a single input term from a user, a medical subject heading, a cocited author, or a cocited journal,pnaslinkrapidly displays views in which that term and the other 24 terms that most frequently co-occur with it in a bibliographic database are interrelated in ways suggesting fruitful combinations for document retrieval. The interrelationships are produced by two algorithms, pathfinder networks and Kohonen-style self-organizing maps.pnaslinkdisplays are themselves interactive interfaces that can retrieve documents from digital libraries (e.g., PNAS Online). This style of visualizing knowledge domains is called “localized” because it does not attempt to map the indexing of literatures in full but concentrates on the top terms in an “associative thesaurus” reflecting user interests. It also permits swift remappings, as the user recognizes terms worth pursuing.pnaslinkis illustrated with maps drawn from the literature of population genetics. Some comparative and evaluative comments are added, one from a domain expert indicating that the face validity of the system may be tempered by insufficient specificity in the indexing terms being mapped.
The world of geography: Visualizing a knowledge domain with cartographic means
Authors: Skupin André
Published: April 2004

From an informed critique of existing methods to the development of original tools, cartographic engagement can provide a unique perspective on knowledge domain visualization. Along with a discussion of some principles underlying a cartographically informed visualization methodology, results of experiments involving several thousand conference abstracts will be sketched and their plausibility reflected on.
A method for finding communities of related genes
Authors: Wilkinson Dennis M. , Huberman Bernardo A.
Published: April 2004

We present a method for creating a network of gene co-occurrences from the literature and partitioning it into communities of related genes. The way in which our method identifies communities makes it likely that the component genes of each community will be related by their function. The method processes a large database of article abstracts, synthesizing information from many sources to shed light on groups of genes that have been shown to interact. It is a tool to be used by researchers in the biomedical sciences to swiftly search for known interactions and to provide insight into unexplored connections. The partitioning procedure is designed to be particularly applicable to large networks in which individual nodes may play a role in more than one community. In this paper, we explain the details of the method, in particular the partitioning process. We also apply the method to produce communities of genes related to colon cancer and show that the results are useful.
Finding scientific topics
Authors: Griffiths Thomas L. , Steyvers Mark
Published: April 2004

A first step in identifying the content of a document is determining which topics that document addresses. We describe a generative model for documents, introduced by Blei, Ng, and Jordan [Blei, D. M., Ng, A. Y. & Jordan, M. I. (2003)J. Machine Learn. Res.3, 993-1022], in which each document is generated by choosing a distribution over topics and then choosing each word in the document from a topic selected according to this distribution. We then present a Markov chain Monte Carlo algorithm for inference in this model. We use this algorithm to analyze abstracts from PNAS by using Bayesian model selection to establish the number of topics. We show that the extracted topics capture meaningful structure in the data, consistent with the class designations provided by the authors of the articles, and outline further applications of this analysis, including identifying “hot topics” by examining temporal dynamics and tagging abstracts to illustrate semantic content.
An unsupervised method for the extraction of propositional information from text
Authors: Dennis Simon
Published: April 2004

Recent developments in question-answering systems have demonstrated that approaches based on propositional analysis of source text, in conjunction with formal inference systems, can produce substantive improvements in performance over surface-form approaches. [Voorhees, E. M. (2002) inEleventh Text Retrieval Conference, eds. Voorhees, E. M. & Buckland, L. P.,http://trec.nist.gov/pubs/trec11/t11_proceedings.html]. However, such systems are hampered by the need to create broad-coverage knowledge bases by hand, making them difficult to adapt to new domains and potentially fragile if critical information is omitted. To demonstrate how this problem might be addressed, the Syntagmatic Paradigmatic model, a memory-based account of sentence processing, is used to autonomously extract propositional knowledge from unannotated text. The Syntagmatic Paradigmatic model assumes that people store a large number of sentence instances. When trying to interpret a new sentence, similar sentences are retrieved from memory and aligned with the new sentence by using String Edit Theory. The set of alignments can be considered an extensional interpretation of the sentence. Extracting propositional information in this way not only permits the model to answer questions for which the relevant facts are explicitly stated in the text but also allows the model to take advantage of “inference by coincidence,” where implicit inference occurs as an emergent property of the mechanism. To illustrate the potential of this approach, the model is tested for its ability to determine the winners of tennis matches as reported on the Association of Tennis Professionals web site.
O
-nitroso aldol synthesis: Catalytic enantioselective route to α-aminooxy carbonyl compounds via enamine intermediate
Authors: Momiyama Norie , Torii Hiromi , Saito Susumu , Yamamoto Hisashi
Published: April 2004

The approach using pyrrolidine enamine as substrate has been studied for this synthesis, and an important catalyst structural feature has been developed. After survey of pyrrolidine-based Brønsted acid catalyst, tetrazole catalyst (3f) was found to be optimal in synthesis of aminooxy carbonyl compounds in high yields, with complete enantioselectivity not only for aldehydes but also for ketones.
Isolation of glutamate transport-coupled charge flux and estimation of glutamate uptake at the climbing fiber–Purkinje cell synapse
Authors: Brasnjo Gabor , Otis Thomas S.
Published: April 2004

Excitatory amino acid transporters (EAATs) located on neurons and glia are responsible for limiting extracellular glutamate concentrations, but specific contributions made by neuronal and glial EAATs have not been determined. At climbing fiber to Purkinje cell (PC) synapses in cerebellum, a fraction of released glutamate is rapidly bound and inactivated by neuronal EAATs located on postsynaptic PCs. Because transport involves a stoichiometric movement of ions and is electrogenic, postsynaptic currents mediated by EAATs should permit precise calculation of the amount of postsynaptic glutamate uptake. However, this is possible only if a stoichiometric EAAT current can be isolated from all other contaminating signals. We used synaptic stimulation and photolysis of caged glutamate to characterize the current in PCs that is resistant to high concentrations of glutamate receptor antagonists. Some of this response is inhibited by the high-affinity EAAT antagonist TBOA (dl-threo-β-benzyloxyaspartic acid), whereas the remaining current shows properties inconsistent with glutamate transport. By subtracting this residual non-EAAT current from the response recorded in glutamate receptor antagonists, we have obtained an estimate of postsynaptic uptake near physiological temperature. Analysis of such synaptic EAAT currents suggests that, on average, postsynaptic EAATs take up ≈1,300,000 glutamate molecules in response to a single climbing fiber action potential.
Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition–cyclization strategy: Synthesis of (–)-flustramine B
Authors: Austin Joel F. , Kim Sung-Gon , Sinz Christopher J. , Xiao Wen-Jing , MacMillan David W. C.
Published: April 2004

Pyrroloindoline and bispyrroloindoline are a subclass of alkaloid structural motifs that commonly exhibit biological activity. An enantioselective organocatalytic approach to the synthesis of pyrroloindoline architecture is described. The addition–cyclization of tryptamines with α,β-unsaturated aldehydes in the presence of imidazolidinone catalysts 1 and 8 provides pyrroloindoline adducts in high yield and excellent enantioselectivities. This transformation is successful for a wide range of tryptamine and α,β-unsaturated aldehyde substrates. This amine-catalyzed sequence has been extended to the enantioselective construction of furanoindoline frameworks. Application of this pyrroloindoline-forming reaction to natural product synthesis has been accomplished in the context of the enantioselective synthesis of (–)-flustramine B.
Mapping subsets of scholarly information
Authors: Ginsparg Paul , Houle Paul , Joachims Thorsten , Sul Jae-Hoon
Published: April 2004

We illustrate the use of machine learning techniques to analyze, structure, maintain, and evolve a large online corpus of academic literature. An emerging field of research can be identified as part of an existing corpus, permitting the implementation of a more coherent community structure for its practitioners.
Asymmetric autocatalysis and its implications for the origin of homochirality
Authors: Blackmond Donna G.
Published: April 2004

An autocatalytic reaction in which the reaction product serves as a catalyst to produce more of itself and to suppress production of its enantiomer serves as a mechanistic model for the evolution of homochirality. The Soai reaction provided experimental confirmation of this concept, nearly 50 years after it was first proposed. This Perspective offers a rationalization of the Soai autocatalytic reaction; accounting for enantiomeric excess and rate observations, that is both simple as well as gratifying in its implications for the chemical origin of life.
MethanogenicArchaeaand human periodontal disease
Authors: Lepp Paul W. , Brinig Mary M. , Ouverney Cleber C. , Palm Katherine , Armitage Gary C. , Relman David A.
Published: April 2004

Archaeahave been isolated from the human colon, vagina, and oral cavity, but have not been established as causes of human disease. In this study, we reveal a relationship between the severity of periodontal disease and the relative abundance of archaeal small subunit ribosomal RNA genes (SSU rDNA) in the subgingival crevice by using quantitative PCR. Furthermore, the relative abundance of archaeal small subunit rDNA decreased at treated sites in association with clinical improvement.Archaeawere harbored by 36% of periodontitis patients and were restricted to subgingival sites with periodontal disease. The presence of archaeal cells at these sites was confirmed by fluorescentin situhybridization. The archaeal community at diseased sites was dominated by aMethanobrevibacter oralis-like phylotype and a distinctMethanobrevibactersubpopulation related to archaea that inhabit the gut of numerous animals. We hypothesize that methanogens participate in syntrophic relationships in the subgingival crevice that promote colonization by secondary fermenters during periodontitis. Because they are potential alternative syntrophic partners, our finding of largerTreponemapopulations sites without archaea provides further support for this hypothesis.
Effects of acute and chronic administration of β-adrenoceptor ligands on airway function in a murine model of asthma
Authors: Callaerts-Vegh Zsuzsanna , Evans Kenda L. J. , Dudekula Noornabi , Cuba Donald , Knoll Brian J. , Callaerts Patrick F. K. , Giles Heather , Shardonofsky Felix R. , Bond Richard A.
Published: April 2004

The clinical effects of treatment withn β-adrenoceptor (β-AR) agonists and antagonists in heart failure vary with duration of therapy, as do the effects of β-AR agonists in asthma. Therefore, we hypothesized that chronic effects of “β-blockers” in asthma may differ from those observed acutely. We tested this hypothesis in an antigen (ovalbumin)-driven murine model of asthma. Airway resistance responses (
R
aw
) to the muscarinic agonist methacholine were measured by using the forced oscillation technique. In comparison with nontreated asthmatic mice, we observed that: (
i
) The β-AR antagonists nadolol or carvedilol, given as a single i.v. injection (acute treatment) 15 min before methacholine, increased methacholine-elicited peak
R
aw
values by 33.7% and 67.7% (
P
< 0.05), respectively; when either drug was administered for 28 days (chronic treatment), the peak
R
aw
values were decreased by 43% (
P
< 0.05) and 22.9% (
P
< 0.05), respectively. (
ii
) Chronic treatment with nadolol or carvedilol significantly increased β-AR densities in lung membranes by 719% and 828%, respectively. (
iii
) Alprenolol, a β-blocker with partial agonist properties at β-ARs, behaved as a β-AR agonist, and acutely reduced peak
R
aw
value by 75.7% (
P
< 0.05); chronically, it did not alter
R
aw
.(
iv
) Salbutamol, a β-AR partial agonist, acutely decreased peak
R
aw
by 41.1%; chronically, it did not alter
R
aw
. (
v
) None of the β-blockers produced significant changes in eosinophil number recovered in bronchoalveolar lavage. These results suggest that β-AR agonists and β-blockers with inverse agonist properties may exert reciprocating effects on cellular signaling dependent on duration of administration.
Enhanced translation of a chloroplast-expressed
Rbc
S gene restores small subunit levels and photosynthesis in nuclear
Rbc
S antisense plants
Authors: Dhingra Amit , Portis Archie R. , Daniell Henry
Published: April 2004

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a key enzyme that converts atmospheric carbon to food and supports life on this planet. Its low catalytic activity and specificity for oxygen leads to photorespiration, severely limiting photosynthesis and crop productivity. Consequently, Rubisco is a primary target for genetic engineering. Separate localization of the genes in the nuclear and chloroplast genomes and a complex assembly process resulting in a very low catalytic activity of hybrid Rubisco enzymes have rendered several earlier attempts of Rubisco engineering unsuccessful. Here we demonstrate that the
Rbc
S gene, when integrated at a transcriptionally active spacer region of the chloroplast genome, in a nuclear
Rbc
S antisense line and expressed under the regulation of heterologous (gene 10) or native (
psb
A) UTRs, results in the assembly of a functional holoenzyme and normal plant growth under ambient CO
2
conditions, fully shortcircuiting nuclear control of gene regulation. There was ≈150-fold more
Rbc
S transcript in chloroplast transgenic lines when compared with the nuclear
Rbc
S antisense line, whereas the wild type has 7-fold more transcript. The small subunit protein levels in the gene 10/
Rbc
S and
psb
A/
Rbc
S plants were 60% and 106%, respectively, of the wild type. Photosynthesis of gene 10/
Rbc
S plants was approximately double that of the antisense plants, whereas that of
psb
A/
Rbc
S plants was restored almost completely to the wild-type rates. These results have opened an avenue for using chloroplast engineering for the evaluation of foreign Rubisco genes
in planta
that eventually can result in achieving efficient photosynthesis and increased crop productivity.
Nanohydrodynamics simulations: An atomistic view of the Rayleigh–Taylor instability
Authors: Kadau Kai , Germann Timothy C. , Hadjiconstantinou Nicolas G. , Lomdahl Peter S. , Dimonte Guy , Holian Brad Lee , Alder Berni J.
Published: April 2004

Nanohydrodynamics simulations, hydrodynamics on the nanometer and nanosecond scale by molecular dynamics simulations for up to 100 million particles, are performed on the latest generation of supercomputers. Such simulations exhibit Rayleigh–Taylor instability, the mixing of a heavy fluid on top of a light in the presence of a gravitational field, initiated by thermal fluctuations at the interface, leading to the chaotic regime in the long-time evolution of the mixing process. The early-time behavior is in general agreement with linear analysis of continuum theory (Navier–Stokes), and the late-time behavior agrees quantitatively with experimental observations. Nanohydrodynamics provides insights into the turbulent mixing process that are inaccessible to either continuum calculations or to experiment.
Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth
Authors: Noren Nicole K. , Lu Mark , Freeman Andrew L. , Koolpe Mitchell , Pasquale Elena B.
Published: April 2004

Receptor tyrosine kinases of the Eph family are up-regulated in different types of cancer. EphB4 and its ligand ephrin-B2 have been linked to breast cancer, but little is known about how this receptor–ligand complex may contribute to oncogenesis. The Eph receptors transmit forward signals via their kinase domain and reverse signals via their transmembrane ephrin-B ligands. Therefore, we used EphB4 that were lacking the kinase domain and tagged with EGFP (EphB4ΔC-EGFP) to differentiate between EphB4 and ephrin-B2 signaling. Interestingly, we found that expression of EphB4ΔC-EGFP in breast cancer cells increases tumor growth in a mouse xenograft model. Given the undetectable EphB4 activation in the tumor cells, dominant negative effects of EphB4ΔC-EGFP are unlikely to explain the increased tumor growth. Examination of the tumors revealed that ephrin-B2 is primarily expressed in the vasculature and that the EphB4ΔC-EGFP tumors have a higher blood content than control tumors, concomitant with increased size of blood vessels. In support of an effect on the vasculature, the extracellular domain of EphB4 attracts endothelial cells
in vitro
and stimulates endothelial cell invasion, survival, and proliferation, all crucial factors for angiogenesis. These results support a model in which EphB4 promotes tumor growth by stimulating angiogenesis through ephrin-B2.
Evidence of tectorial membrane radial motion in a propagating mode of a complex cochlear model
Authors: Cai Hongxue , Shoelson Brett , Chadwick Richard S.
Published: April 2004

Knowledge of vibratory patterns in the cochlea is crucial to understanding the stimulation of mechanosensory cells. Experiments to determine the motion of the cochlear partition and surrounding fluid are extremely challenging. As a result, the motion data are incomplete and often contradictory. The bending mechanism of hair bundles, thought to be related to the shear motion and endolymphatic flow between the tectorial membrane (TM) and reticular lamina (RL), is controversial. We, therefore, extend the frequency range of our previous hybrid analytical–finite-element approach to model the basal as well as apical regions of the guinea pig cochlea. We solve the fluid-solid interaction eigenvalue problem for the axial wavenumber, fluid pressure, and vibratory relative motions of the cochlear partition as a function of frequency. A simple monophasic vibratory mode of the basilar membrane is found at both ends of the cochlea. However, this simple movement is associated with a complex frequency-dependent relative deformation between the TM and the RL. We provide evidence of a radial component of TM motion that is out of phase with the RL and that facilitates the bending of outer hair cell stereocilia at appropriate frequencies at both the cochlear base and apex.
Unique domain anchoring of Src to synaptic NMDA receptors via the mitochondrial protein NADH dehydrogenase subunit 2
Authors: Gingrich Jeffrey R. , Pelkey Kenneth A. , Fam Sami R. , Huang Yueqiao , Petralia Ronald S. , Wenthold Robert J. , Salter Michael W.
Published: April 2004

Src is the prototypic protein tyrosine kinase and is critical for controlling diverse cellular functions. Regions in Src define structural and functional domains conserved in many cell signaling proteins. Src also contains a region of low sequence conservation termed the unique domain, the function of which has until now remained enigmatic. Here, we show that the unique domain of Src is a protein–protein interaction region and we identify NADH dehydrogenase subunit 2 (ND2) as a Src unique domain-interacting protein. ND2 is a subunit of complex I in mitochondria, but we find that ND2 interacts with Src outside this organelle at excitatory synapses in the brain. ND2 acts as an adapter protein anchoring Src to the
N
-methyl-
d
-aspartate (NMDA) receptor complex, and is crucial for Src regulation of synaptic NMDA receptor activity. By showing an extramitochondrial action for a protein encoded in the mitochondrial genome, we identify a previously unsuspected means by which mitochondria regulate cellular function, suggesting a new paradigm that may be of general relevance for control of Src signaling.
Long-term impacts of logging on forest diversity in Madagascar
Authors: Brown Kerry A. , Gurevitch Jessica
Published: April 2004

Ecological perturbations can either be necessary for maintaining tropical forest diversity or responsible for its decline, depending on the scale, nature, and frequency of the disturbance. Anthropogenic disturbances such as logging and subsistence agriculture may promote the establishment of nonnative, invasive plant species, potentially affecting forest structure and diversity even long after the perturbation has ceased. We investigated the impacts of logging 50 and 150 years ago on tropical forest vegetation in Madagascar, a “hotspot” of biodiversity. Logging was the overriding factor influencing establishment of nonnative plants. Sites once logged never recovered native species diversity because of the dominance and persistence of invasive species.
Immunopathological Basis of Virus‐induced Myocarditis
Authors: Maier Reinhard , Krebs Philippe , Ludewig Burkhard
Published: April 2004

Heart diseases are an important cause of morbidity and mortality in industrialized countries. Dilated
cardiomyopathy (DCM), one of the most common heart diseases, may be the consequence of infectionassociated
myocardits. Coxsackievirus B3 (CVB3) can be frequently detected in the inflamed heart
muscle. CVB3‐induced acute myocarditis is most likely the consequence of direct virus‐induced
myocyte damage, whereas chronic CVB3 infection‐associated heart disease is dominated by its
immunopathological sequelae. Bona fide autoimmunity, for example, directed against cardiac myosin,
may favor chronic destructive immune damage in the heart muscle and thereby promote the
development of DCM. The immunopathogenesis of myocarditis and subsequent DCM induced either
by pathogens or autoantigens can be investigated in well‐established animal models. In this article, we
review recent studies on the role of viruses, with particular emphasis on CVB3, and different
immunological effector mechanisms in initiation and progression of myocarditis.
Testing for Antiphospholipid Antibody (aPL) Specificities in Retrospective “Normal” Cerebral Spinal Fluid (CSF)
Authors: Sokol D. K. , Wagenknecht D. R. , McIntyre J. A.
Published: April 2004

Antiphospholipid antibodies (aPL) have been found in the blood of patients with systemic and
neurological disease. The rare reports of aPL in cerebral spinal fluid (CSF) have been limited mostly to
IgG and IgM anticardiolipin (aCL). Our published finding of IgA aPE in the CSF of a young stroke
victim prompted us to establish “normal” CSF aPL values for a panel of aPL, which included aCL,
antiphosphatidylserine (aPS), antiphosphatidylethanolamine (aPE) and antiphosphatidylcholine (aPC).
CSF samples were tested by ELISA for IgG, IgM and IgA aPL. In addition, the CSF samples were
tested for activity in the presence and absence of phospholipid (PL) binding plasma‐proteins. A total of
24 data points were obtained for each CSF sample.We tested 59 CSF samples obtained from 59 patients
who were undergoing evaluation for systemic or neurologic diseases. All CSF samples had normal
protein, glucose and cell counts. Ten of the 59 CSF samples (17%) had elevated aPL optical density
(OD) values an order of magnitude higher than the other 49 CSF samples for one or more aPL
specificity and/or isotype. One CSF sample had both PL‐binding protein dependent and independent
IgG aPE activity. Another CSF sample showed both IgG aPE and aPC reactivity. The remaining eight
CSF samples showed single aPL findings; IgG aPE (5), IgG aPC (1), IgG aCL (1) and IgM aPC (1).
Seven of 10 patients with elevated CSF values were females. As expected, most “normal” aPL OD
values were substantially lower in CSF than those we have reported in blood samples from volunteer
blood donors.
Genetic Analysis of Cytokine Promoters in Nonhuman Primates: Implications for Th1/Th2 Profile Characteristics and SIV Disease Pathogenesis
Authors: Bostik Pavel , Watkins Melanie , Villinger Francois , Ansari Aftab A.
Published: April 2004

The shift from a predominant synthesis of prototype
Th1 cytokines to Th2 or Th0 type of cytokines by antigen
activated PBMC′s from HIV infected humans and SIV infected
disease susceptible rhesus macaques (RM) has been shown to
be associated with disease progression. Paradoxically, antigen
activated PBMC′s from sooty mangabeys (SM), which are naturally
infected with SIV and are disease resistant despite high viral loads,
maintain a predominant Th2 cytokine profile. It has been reasoned
that the resistance to perturbations of cytokine synthesis by slow
and/or nonprogressor HIV infected patients and SIV infected disease
susceptible RM is secondary to inherited polymorphisms within
the promoter regions for cytokines. Similar promoter polymorphisms
could also contribute to the cytokine profile of PBMC′s from SM. To
address this issue promoter regions for the major Th1/Th2 cytokines
from RM and SM were cloned and sequenced. Sequence analysis
of promoter fragments of IL‐4, IL‐10, IL‐12 p40, IFN‐gamma and
TNF‐alpha from the two monkey species showed varying degree of
homology ranging from high degree of homology detected for
IFN‐gamma promoter (>99%) to relatively high degree of polymorphism
detected for TNF‐alpha promoter (94% homology). In addition, several
variable regions within the promoters of IL‐12 p40, IL‐10 and
TNF‐alpha in the two species contain polymorphisms in sequences
that constitute binding sites of known transcription factors (TF). Such
differences are likely to differentially bind TF and thus either
qualitatively and/or quantitatively affect the regulation of cytokine
synthesis in these two species and potentially
contribute to disease progression and/or resistance.
Circulating Immune Complexes among Diabetic Children
Authors: Nicoloff George , Blazhev Alexander , Petrova Chaika , Christova Petkana
Published: April 2004

Insulin dependent diabetes mellitus (IDDM) is an autoimmune
disease associated with the presence of different types of autoantibodies. The
presence of these antibodies and the corresponding antigens in the circulation
leads to the formation of circulating immune complexes (CIC). CIC are known to
persist in the blood for long periods of time. Such CIC following deposition in
the small blood vessels have the potential to lead to microangiopathy with
debilitating clinical consequences. The aim of our pilot study was to investigate
whether a correlation exists between CIC and the development of microvascular
complications in diabetic children. Isolation of a new glycoprotein complement
inhibition factor (CIF) from the parasitic plant Cuscuta europea seed, which appears
to bind specifically to complement component C3 has provided an unique tool
for the measurement of immune complexes by means of ELISA‐type techniques
(CIF‐ELISA). We studied the levels of CIC (IgG, IgM and IgA) in 58 diabetic
children (mean age 12.28±4.04 years, diabetes duration 5.3±3.7 years), 29 of
them had vascular complications (group 1) and the other 29 were without
vascular complications (group 2). As controls, we studied sera samples from
21 healthy children (mean age 13.54±4.03 years). Sera from the diabetic
patients showed statistically significant higher levels of CIC IgG ( p=0.03) than
sera from the control group. In sera from group 1 values of CIC IgG showed
statistically significant higher levels than controls (0.720±0.31 vs. 0.46±0.045;
p=0.011) Sera from 59% of the patients were positive for CIC IgG, 36% for CIC
IgM and 9% for CIC IgA. Among 26 patients with microalbuminuria, sera from
17/26 (65%) were positive for CIC IgG, 8/26 (31%) for CIC IgM and 2/26 (8%) for
CIC IgA. CIC IgG correlated with HbA1c (r=0.51; p=0.005) and microalbuminuria
(r=0.42, p=0.033). CIC IgA correlated with
age (r=0.44, p=0.03). CIC IgM
correlated with the duration of diabetes (r=0.63, p=0.02). These findings suggest
that elevated levels of CIC IgG are associated with the development of early diabetic nephropathy.
Neurological Dysfunction Associated with Antiphospholipid Syndrome: Histopathological Brain Findings of Thrombotic Changes in a Mouse Model
Authors: Ziporen Lea , Polak-Charcon Sylvia , Korczyn D. Amos , Goldberg Iris , Afek Arnon , Kopolovic Juri , Chapman Joab , Shoenfeld Yehuda
Published: April 2004

The aim of this work was to study the pathological
processes underlying neurological dysfunctions displayed by
BALB/C mice induced with experimental antiphospholipid syndrome
(APS), as we have previously reported. Experimental APS was induced in
female BALB/C mice by immunization with a pathogenic monoclonal anticardiolipin
(aCL) antibody, H‐3 (n=10), or an irrelevant immunoglobulin in controls (n=10).
Mice immunized with H‐3 developed clinical and neurological manifestations of
APS, including: embryo resorption, thrombocytopenia neurological defects and
behavioral disturbances. In mouse sera, the titer of various autoantibodies were
elevated, including: anti‐phospholipids (aPLs), anti‐2 glycoprotein‐I (β2GPI),
anti‐endothelial cell antibodies (AECA) and low titer of anti‐dsDNA antibodies. Five
months after APS induction, mice were sacrificed and brain tissue specimens were
processed for hematoxylin and eosin (H&E), immunofluorescence staining and
transmission electron microscopy (TEM). H&E staining of cortical tissue derived
from all APS mice revealed mild inflammation, localized mainly in the meninges.
Prominent IgG deposits in the large vessel walls and perivascular IgG leakage
were observed by immunofluorescence. No large thrombi were observed in large
vessels. However, EM evaluation of cerebral tissue revealed pathological
changes in the microvessels. Thrombotic occlusion of capillaries in combination
with mild inflammation was the main finding and may underlie
the neurological defects displayed by mice with APS.
Relationship between Pollen Counts and Weather Variables in East‐Mediterranean Coast of Turkey
Authors: Altintaş Derya Ufuk , Karakoç Gülbin Bingöl , Yilmaz Mustafa , Pinar Münevver , Kendirli Seval Güneçer , Çakan Halil
Published: April 2004

Background: Aeroallergen sampling provides information
regarding the onset, duration and severity of the pollen season that clinicians
use to guide allergen selection for skin testing and treatment.

Objectives: This atmospheric survey reports (1) airborne pollen
contributions in Adana in one‐year period (2) pollen onset, duration and
peak level (3) the relationship between airborne pollen and selected
meteorological variables and; (4)
effects on symptoms in pollen allergic children.

Methods: Pollen sampling was performed with a volumetric Burkard
Spore Trap. Meteorological data were measured daily from April 2001 to
April 2002. Asthma symptom scores were investigated in 186 pollen allergic
children that were on follow up in pediatric
allergy outpatient clinics during same period.

Results: Average measurements included 82.5% tree pollen,
7.7% grass pollen and 9.8% herb pollen 54 taxa were identified
during one year. The most prominent tree pollens were Cupressaceae,
Eucalyptus and Pinus. The most common herb was Chenopodiaceae
pollen family. When airborne pollen levels were examined in relation to
single meteorological conditions; daily variations in total pollen counts
were not significantly correlated with any variable studied (humidity,
rainfall, temperature and wind) (p>0.05). On the
other hand, statistically significant relationship between pollen concentration and symptom scores
were found (p>0.05). Positive correlations were seen
between both Gramineae and Herb pollen, and humidity and rainfall from March to
July. However, positive correlations were detected between tree pollen
counts and temperature and humidity in May and June.

Conclusion: This survey is the first volumetric airborne
pollen analysis conducted in the survey area in Adana. This study
suggested that the effects of weather on pollen count and symptom
scores in this population could not be clearly identified with the evaluation
of one‐year data. However, pollen counts had effect on allergic symptoms
in pollen allergic children. Examination of the complex interaction of multiple
whether parameters would perhaps more fully elucidate the relationship
between meteorology and aerobiology and provide the clinician with
information necessary to forecast pollen prevalence. An awareness of
the ever chancing, local aeroallergen patterns requires regular monitoring. Such
awareness serves as a useful guide in the effective
testing and treatment of atopic patients.