bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-Cell Measurements of the Contributions of Cytosolic Na+ and K+ to Salt Tolerance
Authors: Carden David E. , Walker David J. , Flowers Timothy J. , Miller Anthony J.
Published: February 2003

Ion concentrations in the roots of two barley (Hordeum vulgare) varieties that differed in NaCl tolerance were compared after exposure to NaCl. Triple-barreled H+-, K+-, and Na+-selective microelectrodes were used to measure cytosolic activities of the three ions after 5 and 8 d of NaCl stress. In both varieties of barley, it was only possible to record successfully from root cortical cells because the epidermal cells appeared to be damaged. The data show that from the 1st d of full NaCl stress, there were differences in the way in which the two varieties responded. At 5 d, the tolerant variety maintained a 10-fold lower cytosolic Na+ than the more sensitive variety, although by 8 d the two varieties were not significantly different. At this time, the more tolerant variety was better at maintaining root cytosolic K+ in the high-NaCl background than was the more sensitive variety. In contrast to earlier work on K+-starved barley (Walker et al., 1996), there was no acidification of the cytosol associated with the decreased cytosolic K+ activity during NaCl stress. These single-cell measurements of cytosolic and vacuolar ion activities allow calculation of thermodynamic gradients that can be used to reveal (or predict) the type of active transporters at both the plasma membrane and tonoplast.
Zinc Efficiency Is Correlated with Enhanced Expression and Activity of Zinc-Requiring Enzymes in Wheat
Authors: Hacisalihoglu Gökhan , Hart Jonathan J. , Wang Yi-Hong , Cakmak Ismail , Kochian Leon V.
Published: February 2003

Zinc (Zn) is an essential micronutrient for plants. The ability of plants to maintain significant yields under low Zn is termed Zn efficiency (ZE) and its genetic and mechanistic basis is still not well understood. Previously, we showed that root Zn uptake did not play a role in ZE. In the current study, Zn-efficient and -inefficient wheat (Triticum aestivum) genotypes were grown for 13 d in chelate buffer nutrient solutions at low (0.1 pm), sufficient (150 pm), and high (1 μm) Zn2+ activities and analyzed for root-to-shoot translocation of Zn, subcellular leaf Zn distribution, and activity and expression of the Zn-requiring enzymes in leaves. No correlation between ZE and Zn translocation to the shoot was found. Furthermore, total and water-soluble concentrations of leaf Zn were not associated with ZE, and no differences in subcellular Zn compartmentation were found between Zn-efficient and -inefficient genotypes. However, the expression and activity of the Zn-requiring enzymes copper (Cu)/Zn superoxide dismutase (SOD) and carbonic anhydrase did correlate with differences in ZE. Northern analysis suggested that Cu/ZnSOD gene expression was up-regulated in the Zn-efficient genotype, Kirgiz, but not in inefficient BDME. Under Zn deficiency stress, the very Zn-efficient genotype Kirgiz and moderately Zn-efficient Dagdas exhibited an increased activity of Cu/ZnSOD and carbonic anhydrase when compared with Zn-inefficient BDME. These results suggest that Zn-efficient genotypes may be able to maintain the functioning of Zn-requiring enzymes under low Zn conditions; thus, biochemical Zn utilization may be an important component of ZE in wheat.
Ano hydrotropic responseRoot Mutant that Responds Positively to Gravitropism in Arabidopsis1,
Authors: Eapen Delfeena , Barroso Marı́a Luisa , Campos Marı́a Eugenia , Ponce Georgina , Corkidi Gabriel , Dubrovsky Joseph G. , Cassab Gladys I.
Published: February 2003

For most plants survival depends upon the capacity of root tips to sense and move towards water and other nutrients in the soil. Because land plants cannot escape environmental stress they use developmental solutions to remodel themselves in order to better adapt to the new conditions. The primary site for perception of underground signals is the root cap (RC). Plant roots have positive hydrotropic response and modify their growth direction in search of water. Using a screening system with a water potential gradient, we isolated ano hydrotropic response (nhr) semi-dominant mutant of Arabidopsis that continued to grow downwardly into the medium with the lowest water potential contrary to the positive hydrotropic and negative gravitropic response seen in wild type-roots. The lack of hydrotropic response of nhr1roots was confirmed in a system with a gradient in air moisture. The root gravitropic response of nhr1 seedlings was significantly faster in comparison with those of wild type. The frequency of the waving pattern in nhr1 roots was increased compared to those of wild type. nhr1 seedlings had abnormal root cap morphogenesis and reduced root growth sensitivity to abscisic acid (ABA) and the polar auxin transport inhibitor N-(1-naphtyl)phtalamic acid (NPA). These results showed that hydrotropism is amenable to genetic analysis and that an ABA signaling pathway participates in sensing water potential gradients through the root cap.
A Novel Small Heat Shock Protein Gene,vis1, Contributes to Pectin Depolymerization and Juice Viscosity in Tomato Fruit
Authors: Ramakrishna Wusirika , Deng Zhiping , Ding Chang-Kui , Handa Avtar K. , Ozminkowski Richard H.
Published: February 2003

We have characterized a novel small heat shock protein gene,viscosity 1 (vis1) from tomato (Lycopersicon esculentum) and provide evidence that it plays a role in pectin depolymerization and juice viscosity in ripening fruits. Expression of vis1 is negatively associated with juice viscosity in diverse tomato genotypes. vis1exhibits DNA polymorphism among tomato genotypes, and the alleles vis1-hta (high-transcript accumulator; accession no. AY128101) andvis1-lta (low transcript accumulator; accession no. AY128102) are associated with thinner and thicker juice, respectively. Segregation of tomato lines heterogeneous forvis1 alleles indicates that vis1influences pectin depolymerization and juice viscosity in ripening fruits. vis1 is regulated by fruit ripening and high temperature and exhibits a typical heat shock protein chaperone function when expressed in bacterial cells. We propose that VIS1 contributes to physiochemical properties of juice, including pectin depolymerization, by reducing thermal denaturation of depolymerizing enzymes during daytime elevated temperatures.
Gene Expression in Autumn Leaves
Authors: Bhalerao Rupali , Keskitalo Johanna , Sterky Fredrik , Erlandsson Rikard , Björkbacka Harry , Birve Simon Jonsson , Karlsson Jan , Gardeström Per , Gustafsson Petter , Lundeberg Joakim , Jansson Stefan
Published: February 2003

Two cDNA libraries were prepared, one from leaves of a field-grown aspen (Populus tremula) tree, harvested just before any visible sign of leaf senescence in the autumn, and one from young but fully expanded leaves of greenhouse-grown aspen (Populus tremula × tremuloides). Expressed sequence tags (ESTs; 5,128 and 4,841, respectively) were obtained from the two libraries. A semiautomatic method of annotation and functional classification of the ESTs, according to a modified Munich Institute of Protein Sequences classification scheme, was developed, utilizing information from three different databases. The patterns of gene expression in the two libraries were strikingly different. In the autumn leaf library, ESTs encoding metallothionein, early light-inducible proteins, and cysteine proteases were most abundant. Clones encoding other proteases and proteins involved in respiration and breakdown of lipids and pigments, as well as stress-related genes, were also well represented. We identified homologs to many known senescence-associated genes, as well as seven different genes encoding cysteine proteases, two encoding aspartic proteases, five encoding metallothioneins, and 35 additional genes that were up-regulated in autumn leaves. We also indirectly estimated the rate of plastid protein synthesis in the autumn leaves to be less that 10% of that in young leaves.
A Low-Starch Barley Mutant, Risø 16, Lacking the Cytosolic Small Subunit of ADP-Glucose Pyrophosphorylase, Reveals the Importance of the Cytosolic Isoform and the Identity of the Plastidial Small Subunit
Authors: Johnson Philip E. , Patron Nicola J. , Bottrill Andrew R. , Dinges Jason R. , Fahy Brendan F. , Parker Mary L. , Waite Darren N. , Denyer Kay
Published: February 2003

To provide information on the roles of the different forms of ADP-glucose pyrophosphorylase (AGPase) in barley (Hordeum vulgare) endosperm and the nature of the genes encoding their subunits, a mutant of barley, Risø 16, lacking cytosolic AGPase activity in the endosperm was identified. The mutation specifically abolishes the small subunit of the cytosolic AGPase and is attributable to a large deletion within the coding region of a previously characterized small subunit gene that we have called Hv.AGP.S.1. The plastidial AGPase activity in the mutant is unaffected. This shows that the cytosolic and plastidial small subunits of AGPase are encoded by separate genes. We purified the plastidial AGPase protein and, using amino acid sequence information, we identified the novel small subunit gene that encodes this protein. Studies of the Risø 16 mutant revealed the following. First, the reduced starch content of the mutant showed that a cytosolic AGPase is required to achieve the normal rate of starch synthesis. Second, the mutant makes both A- and B-type starch granules, showing that the cytosolic AGPase is not necessary for the synthesis of these two granule types. Third, analysis of the phylogenetic relationships between the various small subunit proteins both within and between species, suggest that the cytosolic AGPase single small subunit gene probably evolved from a leaf single small subunit gene.
Metabolic Engineering of Valine- and Isoleucine-Derived Glucosinolates in Arabidopsis Expressing CYP79D2 from Cassava
Authors: Mikkelsen Michael Dalgaard , Halkier Barbara Ann
Published: February 2003

Glucosinolates are amino acid-derived natural products that, upon hydrolysis, typically release isothiocyanates with a wide range of biological activities. Glucosinolates play a role in plant defense as attractants and deterrents against herbivores and pathogens. A key step in glucosinolate biosynthesis is the conversion of amino acids to the corresponding aldoximes, which is catalyzed by cytochromes P450 belonging to the CYP79 family. Expression of CYP79D2 from cassava (Manihot esculenta Crantz.) in Arabidopsis resulted in the production of valine (Val)- and isoleucine-derived glucosinolates not normally found in this ecotype. The transgenic lines showed no morphological phenotype, and the level of endogenous glucosinolates was not affected. The novel glucosinolates were shown to constitute up to 35% of the total glucosinolate content in mature rosette leaves and up to 48% in old leaves. Furthermore, at increased concentrations of these glucosinolates, the proportion of Val-derived glucosinolates decreased. As the isothiocyanates produced from the Val- and isoleucine-derived glucosinolates are volatile, metabolically engineered plants producing these glucosinolates have acquired novel properties with great potential for improvement of resistance to herbivorous insects and for biofumigation.
Combining Quantitative Trait Loci Analysis and an Ecophysiological Model to Analyze the Genetic Variability of the Responses of Maize Leaf Growth to Temperature and Water Deficit
Authors: Reymond Matthieu , Muller Bertrand , Leonardi Agnès , Charcosset Alain , Tardieu François
Published: February 2003

Ecophysiological models predict quantitative traits of one genotype in any environment, whereas quantitative trait locus (QTL) models predict the contribution of alleles to quantitative traits under a limited number of environments. We have combined both approaches by dissecting into effects of QTLs the parameters of a model of maize (Zea mays) leaf elongation rate (LER; H. Ben Haj Salah, F. Tardieu [1997] Plant Physiol 114: 893–900). Response curves of LER to meristem temperature, water vapor pressure difference, and soil water status were established in 100 recombinant inbred lines (RILs) of maize in six experiments carried out in the field or in the greenhouse. All responses were linear and common to different experiments, consistent with the model. A QTL analysis was carried out on the slopes of these responses by composite interval mapping confirmed by bootstrap analysis. Most QTLs were specific of one response only. QTLs of abscisic acid concentration in the xylem sap colocalized with QTLs of response to soil water deficit and conferred a low response. Each parameter of the ecophysiological model was computed as the sum of QTL effects, allowing calculation of parameters for 11 new RILs and two parental lines. LERs were simulated and compared with measurements in a growth chamber experiment. The combined model accounted for 74% of the variability of LER, suggesting that it has a general value for any RIL under any environment.
Sudden Exposure to Solar UV-B Radiation Reduces Net CO2 Uptake and Photosystem I Efficiency in Shade-Acclimated Tropical Tree Seedlings
Authors: Krause G. Heinrich , Grube Esther , Virgo Aurelio , Winter Klaus
Published: February 2003

Tree seedlings developing in the understory of the tropical forest have to endure short periods of high-light stress when tree-fall gaps are formed, and direct solar radiation, including substantial UV light, reaches the leaves. In experiments simulating the opening of a tree-fall gap, the response of photosynthesis in leaves of shade-acclimated seedlings (Anacardium excelsum,Virola surinamensis, and Calophyllum longifolium) to exposure to direct sunlight (for 20–50 min) was investigated in Panama (9°N). To assess the effects of solar UV-B radiation (280–320 nm), the sunlight was filtered through plastic films that selectively absorbed UV-B or transmitted the complete spectrum. The results document a strong inhibition of CO2assimilation by sun exposure. Light-limited and light-saturated rates of photosynthetic CO2 uptake by the leaves were affected, which apparently occurred independently of a simultaneous inhibition of potential photosystem (PS) II efficiency. The ambient UV-B light substantially contributed to these effects. The photochemical capacity of PSI, measured as absorbance change at 810 nm in saturating far-red light, was not significantly affected by sun exposure of the seedlings. However, a decrease in the efficiency of P700 photooxidation by far-red light was observed, which was strongly promoted by solar UV-B radiation. The decrease in PSI efficiency may result from enhanced charge recombination in the reaction center, which might represent an incipient inactivation of PSI, but contributes to thermal dissipation of excessive light energy and thereby to photoprotection.
Comparative Transcriptional Profiling of Placenta and Endosperm in Developing Maize Kernels in Response to Water Deficit
Authors: Yu Long-Xi , Setter Tim L.
Published: February 2003

The early post-pollination phase of maize (Zea mays) development is particularly sensitive to water deficit stress. Using cDNA microarray, we studied transcriptional profiles of endosperm and placenta/pedicel tissues in developing maize kernels under water stress. At 9 d after pollination (DAP), placenta/pedicel and endosperm differed considerably in their transcriptional responses. In placenta/pedicel, 79 genes were significantly affected by stress and of these 89% were up-regulated, whereas in endosperm, 56 genes were significantly affected and 82% of these were down-regulated. Only nine of the stress-regulated genes were in common between these tissues. Hierarchical cluster analysis indicated that different sets of genes were regulated in the two tissues. After rewatering at 9 DAP, profiles at 12 DAP suggested that two regulons exist, one for genes responding specifically to concurrent imposition of stress, and another for genes remaining affected after transient stress. In placenta, genes encoding recognized stress tolerance proteins, including heat shock proteins, chaperonins, and major intrinsic proteins, were the largest class of genes regulated, all of which were up-regulated. In contrast, in endosperm, genes in the cell division and growth category represented a large class of down-regulated genes. Several cell wall-degrading enzymes were expressed at lower levels than in controls, suggesting that stress delayed normal advance to programmed cell death in the central endosperm. We suggest that the responsiveness of placenta to whole-plant stress factors (water potential, abscisic acid, and sugar flux) and of endosperm to indirect factors may play key roles in determining the threshold for kernel abortion.
Powdery Mildew-Induced Mla mRNAs Are Alternatively Spliced and Contain Multiple Upstream Open Reading Frames
Authors: Halterman Dennis A. , Wei Fusheng , Wise Roger P.
Published: February 2003

In barley (Hordeum vulgare), theMla13 powdery mildew resistance gene confersRar1-dependent, AvrMla13-specific resistance to Blumeria graminis f. sp.hordei (Bgh). We have identified cDNA and genomic copies of Mla13 and used this coiled-coil nucleotide-binding site leucine-rich repeat protein-encoding gene as a model for the regulation of host resistance to obligate biotrophic fungi in cereals. We demonstrate quantitatively that a rapid increase in the accumulation of Mla transcripts and transcripts of the Mla-signaling genes, Rar1 andSgt1, is triggered between 16 and 20 h post inoculation, the same time frame that haustoria of avirulentBgh make contact with the host cell plasma membrane. An abundance of Mla13 cDNAs revealed five classes of transcript leader regions containing two alternatively spliced introns and up to three upstream open reading frames (uORFs). Alternative splicing of introns in the transcript leader region results in a different number of uORFs and variability in the size of uORF2. These results indicate that regulation of Mlatranscript accumulation is not constitutive and that induction is coordinately controlled by recognition-specific factors. The sudden increase in specific transcript levels could account for the rapid defense response phenotype conferred by Mla6 andMla13.
Fructan 1-Exohydrolases. β-(2,1)-Trimmers during Graminan Biosynthesis in Stems of Wheat? Purification, Characterization, Mass Mapping, and Cloning of Two Fructan 1-Exohydrolase Isoforms,
Authors: Van den Ende Wim , Clerens Stefan , Vergauwen Rudy , Van Riet Liesbet , Van Laere André , Yoshida Midori , Kawakami Akira
Published: February 2003

Graminan-type fructans are temporarily stored in wheat (Triticum aestivum) stems. Two phases can be distinguished: a phase of fructan biosynthesis (green stems) followed by a breakdown phase (stems turning yellow). So far, no plant fructan exohydrolase enzymes have been cloned from a monocotyledonous species. Here, we report on the cloning, purification, and characterization of two fructan 1-exohydrolase cDNAs (1-FEH w1 andw2) from winter wheat stems. Similar to dicot plant 1-FEHs, they are derived from a special group within the cell wall-type invertases characterized by their low isoelectric points. The corresponding isoenzymes were purified to electrophoretic homogeneity, and their mass spectra were determined by quadrupole-time-of-flight mass spectrometry. Characterization of the purified enzymes revealed that inulin-type fructans [β-(2,1)] are much better substrates than levan-type fructans [β-(2,6)]. Although both enzymes are highly identical (98% identity), they showed different substrate specificity toward branched wheat stem fructans. Although 1-FEH activities were found to be considerably higher during the fructan breakdown phase, it was possible to purify substantial amounts of 1-FEH w2 from young, fructan biosynthesizing wheat stems, suggesting that this isoenzyme might play a role as a β-(2,1)-trimmer throughout the period of active graminan biosynthesis. In this way, the species and developmental stage-specific complex fructan patterns found in monocots might be determined by the relative proportions and specificities of both fructan biosynthetic and breakdown enzymes.
Identification of Mutants of Arabidopsis Defective in Acclimation of Photosynthesis to the Light Environment
Authors: Walters Robin G. , Shephard Freya , Rogers Jennifer J.M. , Rolfe Stephen A. , Horton Peter
Published: February 2003

In common with many other higher plant species, Arabidopsis undergoes photosynthetic acclimation, altering the composition of the photosynthetic apparatus in response to fluctuations in its growth environment. The changes in photosynthetic function that result from acclimation can be detected in a noninvasive manner by monitoring chlorophyll (Chl) fluorescence. This technique has been used to develop a screen that enables the rapid identification of plants defective atACCLIMATION OF PHOTOSYNTHESIS TO THE ENVIRONMENT(APE) loci. The application of this screen to a population of T-DNA-transformed Arabidopsis has successfully led to the identification of a number of mutant lines with altered Chl fluorescence characteristics. Analysis of photosynthesis and pigment composition in leaves from three such mutants showed that they had altered acclimation responses to the growth light environment, each having a distinct acclimation-defective phenotype, demonstrating that screening for mutants using Chl fluorescence is a viable strategy for the investigation of acclimation. Sequencing of the genomic DNA flanking the T-DNA elements showed that in the ape1mutant, a gene was disrupted that encodes a protein of unknown function but that appears to be specific to photosynthetic organisms, whereas the ape2 mutant carries an insertion in the region of the TPT gene encoding the chloroplast inner envelope triose phosphate/phosphate translocator.
WVD2 and WDL1 Modulate Helical Organ Growth and Anisotropic Cell Expansion in Arabidopsis
Authors: Yuen Christen Y.L. , Pearlman Rebecca S. , Silo-suh Laura , Hilson Pierre , Carroll Kathleen L. , Masson Patrick H.
Published: February 2003

Wild-type Arabidopsis roots develop a wavy pattern of growth on tilted agar surfaces. For many Arabidopsis ecotypes, roots also grow askew on such surfaces, typically slanting to the right of the gravity vector. We identified a mutant, wvd2-1, that displays suppressed root waving and leftward root slanting under these conditions. These phenotypes arise from transcriptional activation of the novel WAVE-DAMPENED2(WVD2) gene by the cauliflower mosaic virus 35S promoter in mutant plants. Seedlings overexpressing WVD2 exhibit constitutive right-handed helical growth in both roots and etiolated hypocotyls, whereas the petioles of WVD2-overexpressing rosette leaves exhibit left-handed twisting. Moreover, the anisotropic expansion of cells is impaired, resulting in the formation of shorter and stockier organs. In roots, the phenotype is accompanied by a change in the arrangement of cortical microtubules within peripheral cap cells and cells at the basal end of the elongation zone. WVD2transcripts are detectable by reverse transcriptase-polymerase chain reaction in multiple organs of wild-type plants. Its predicted gene product contains a conserved region named “KLEEK,” which is found only in plant proteins. The Arabidopsis genome possesses seven other genes predicted to encode KLEEK-containing products. Overexpression of one of these genes, WVD2-LIKE 1, which encodes a protein with regions of similarity to WVD2 extending beyond the KLEEK domain, results in phenotypes that are highly similar towvd2-1. Silencing of WVD2 and its paralogs results in enhanced root skewing in the wild-type direction. Our observations suggest that at least two members of this gene family may modulate both rotational polarity and anisotropic cell expansion during organ growth.
Principal role changes and influence on principal recruitment and selection
Authors: Whitaker Kathryn S.
Published: February 2003

This article presents an overview of the changing role of principals and head teachers from an international perspective. The role changes of local site management, increased accountability, the tension between management and leadership, altered relationships with community, and dilemmas related to school choice are described. The article makes a connection between principal role changes and difficulties in recruitment and retention of principals internationally. Data are presented on principal shortages in several countries. The article concludes with several recommendations to address principal recruitment and retention issues.
Symbol of Perfect Proportions
Authors: Maor Eli
Published: February 2003

The Golden Ratio
The Story of Phi, the World's Most Astonishing Number. Mario Livio. Broadway Books, New York, 2002. 304 pp. $24.95. C$37.95. ISBN 0-7679-0815-5.

Discussing the appearances (actual or imagined) of phi in an astonishing variety of places, Livio explores the relation between mathematics and the physical world.
Crystallographic and Spectroscopic Characterization of a Nonheme Fe(IV)=O Complex
Authors: Rohde Jan-Uwe , In Jun-Hee , Lim Mi Hee , Brennessel William W. , Bukowski Michael R. , Stubna Audria , Münck Eckard , Nam Wonwoo , Que Lawrence
Published: February 2003

Following the heme paradigm, it is often proposed that dioxygen activation by nonheme monoiron enzymes involves an iron(IV)=oxo intermediate that is responsible for the substrate oxidation step. Such a transient species has now been obtained from a synthetic complex with a nonheme macrocyclic ligand and characterized spectroscopically. Its high-resolution crystal structure reveals an iron-oxygen bond length of 1.646(3) angstroms, demonstrating that a terminal iron(IV)=oxo unit can exist in a nonporphyrin ligand environment and lending credence to proposed mechanisms of nonheme iron catalysis.
NON-COMMUTATIVE SPACE–TIME OF DOUBLY SPECIAL RELATIVITY THEORIES
Authors: KOWALSKI-GLIKMAN J. , NOWAK S.
Published: February 2003

Doubly Special Relativity (DSR) theory is a recently proposed theory with two observer-independent scales (of velocity and mass), which is to describe a kinematic structure underlining the theory of Quantum Gravity. We observe that there are infinitely many DSR constructions of the energy–momentum sector, each of whose can be promoted to the κ-Poincaré quantum (Hopf) algebra. Then we use the co-product of this algebra and the Heisenberg double construction of κ-deformed phase space in order to derive the non-commutative space–time structure and the description of the whole of DSR phase space. Next we show that contrary to the ambiguous structure of the energy momentum sector, the space–time of the DSR theory is unique and related to the theory with non-commutative space–time proposed long ago by Snyder. This theory provides non-commutative version of Minkowski space–time enjoying ordinary Lorentz symmetry. It turns out that when one builds a natural phase space on this space–time, its intrinsic length parameter ℓ becomes observer-independent.
Asynchronous States and the Emergence of Synchrony in Large Networks of Interacting Excitatory and Inhibitory Neurons
Authors: Hansel D. , Mato G.
Published: February 2003

We investigate theoretically the conditions for the emergence of synchronous activity in large networks, consisting of two populations of extensively connected neurons, one excitatory and one inhibitory. The neurons are modeled with quadratic integrate-and-fire dynamics, which provide a very good approximation for the subthreshold behavior of a large class of neurons. In addition to their synaptic recurrent inputs, the neurons receive a tonic external input that varies from neuron to neuron. Because of its relative simplicity, this model can be studied analytically. We investigate the stability of the asynchronous state (AS) of the network with given average firing rates of the two populations. First, we show that the AS can remain stable even if the synaptic couplings are strong. Then we investigate the conditions under which this state can be destabilized. We show that this can happen in four generic ways. The first is a saddle-node bifurcation, which leads to another state with different average firing rates. This bifurcation, which occurs for strong enough recurrent excitation, does not correspond to the emergence of synchrony. In contrast, in the three other instability mechanisms, Hopf bifurcations, which correspond to the emergence of oscillatory synchronous activity, occur. We show that these mechanisms can be differentiated by the firing patterns they generate and their dependence on the mutual interactions of the inhibitory neurons and cross talk between the two populations. We also show that besides these codimension 1 bifurcations, the system can display several codimension 2 bifurcations: Takens-Bogdanov, Gavrielov-Guckenheimer, and double Hopf bifurcations.
A Constrained EM Algorithm for Principal Component Analysis
Authors: Ahn Jong-Hoon , Oh Jong-Hoon
Published: February 2003

We propose a constrained EM algorithm for principal component analysis (PCA) using a coupled probability model derived from single-standard factor analysis models with isotropic noise structure. The single probabilistic PCA, especially for the case where there is no noise, can find only a vector set that is a linear superposition of principal components and requires postprocessing, such as diagonalization of symmetric matrices. By contrast, the proposed algorithm finds the actual principal components, which are sorted in descending order of eigenvalue size and require no additional calculation or postprocessing. The method is easily applied to kernel PCA. It is also shown that the new EM algorithm is derived from a generalized least-squares formulation.
Synchronous Firing and Higher-Order Interactions in Neuron Pool
Authors: Amari Shun-ichi , Nakahara Hiroyuki , Wu Si , Sakai Yutaka
Published: February 2003

The stochastic mechanism of synchronous firing in a population of neurons is studied from the point of view of information geometry. Higher-order interactions of neurons, which cannot be reduced to pairwise correlations, are proved to exist in synchronous firing. In a neuron pool where each neuron fires stochastically, the probability distribution q(r) of the activity r, which is the fraction of firing neurons in the pool, is studied. When q(r) has a widespread distribution, in particular, when q(r) has two peaks, the neurons fire synchronously at one time and are quiescent at other times. The mechanism of generating such a probability distribution is interesting because the activity r is concentrated on its mean value when each neuron fires independently, because of the law of large numbers. Even when pairwise interactions, or third-order interactions, exist, the concentration is not resolved. This shows that higher-order interactions are necessary to generate widespread activity distributions. We analyze a simple model in which neurons receive common overlapping inputs and prove that such a model can have a widespread distribution of activity, generating higher-order stochastic interactions.
Interspike Interval Correlations, Memory, Adaptation, and Refractoriness in a Leaky Integrate-and-Fire Model with Threshold Fatigue
Authors: Chacron Maurice J. , Pakdaman Khashayar , Longtin André
Published: February 2003

Neuronal adaptation as well as interdischarge interval correlations have been shown to be functionally important properties of physiological neurons. We explore the dynamics of a modified leaky integrate-and-fire (LIF) neuron, referred to as the LIF with threshold fatigue, and show that it reproduces these properties. In this model, the postdischarge threshold reset depends on the preceding sequence of discharge times. We show that in response to various classes of stimuli, namely, constant currents, step currents, white gaussian noise, and sinusoidal currents, the model exhibits new behavior compared with the standard LIF neuron. More precisely, (1) step currents lead to adaptation, that is, a progressive decrease of the discharge rate following the stimulus onset, while in the standard LIF, no such patterns are possible; (2) a saturation in the firing rate occurs in certain regimes, a behavior not seen in the LIF neuron; (3) interspike intervals of the noise-driven modified LIF under constant current are correlated in a way reminiscent of experimental observations, while those of the standard LIF are independent of one another; (4) the magnitude of the correlation coefficients decreases as a function of noise intensity; and (5) the dynamics of the sinusoidally forced modified LIF are described by iterates of an annulus map, an extension to the circle map dynamics displayed by the LIF model. Under certain conditions, this map can give rise to sensitivity to initial conditions and thus chaotic behavior.
Reliability of Spike Timing Is a General Property of Spiking Model Neurons
Authors: Brette Romain , Guigon Emmanuel
Published: February 2003

The responses of neurons to time-varying injected currents are reproducible on a trial-by-trial basis in vitro, but when a constant current is injected, small variances in interspike intervals across trials add up, eventually leading to a high variance in spike timing. It is unclear whether this difference is due to the nature of the input currents or the intrinsic properties of the neurons. Neuron responses can fail to be reproducible in two ways: dynamical noise can accumulate over time and lead to a desynchronization over trials, or several stable responses can exist, depending on the initial condition. Here we show, through simulations and theoretical considerations, that for a general class of spiking neuron models, which includes, in particular, the leaky integrate-and-fire model as well as nonlinear spiking models, aperiodic currents, contrary to periodic currents, induce reproducible responses, which are stable under noise, change in initial conditions and deterministic perturbations of the input. We provide a theoretical explanation for aperiodic currents that cross the threshold.
Spatiochromatic Receptive Field Properties Derived from Information-Theoretic Analyses of Cone Mosaic Responses to Natural Scenes
Authors: Doi Eizaburo , Inui Toshio , Lee Te-Won , Wachtler Thomas , Sejnowski Terrence J.
Published: February 2003

Neurons in the early stages of processing in the primate visual system efficiently encode natural scenes. In previous studies of the chromatic properties of natural images, the inputs were sampled on a regular array, with complete color information at every location. However, in the retina cone photoreceptors with different spectral sensitivities are arranged in a mosaic. We used an unsupervised neural network model to analyze the statistical structure of retinal cone mosaic responses to calibrated color natural images. The second-order statistical dependencies derived from the covariance matrix of the sensory signals were removed in the first stage of processing. These decorrelating filters were similar to type I receptive fields in parvo- or konio-cellular LGN in both spatial and chromatic characteristics. In the subsequent stage, the decorrelated signals were linearly transformed to make the output as statistically independent as possible, using independent component analysis. The independent component filters showed luminance selectivity with simple-cell-like receptive fields, or had strong color selectivity with large, often double-opponent, receptive fields, both of which were found in the primary visual cortex (V1). These results show that the “form” and “color” channels of the early visual system can be derived from the statistics of sensory signals.
Efficient Greedy Learning of Gaussian Mixture Models
Authors: Verbeek J. J. , Vlassis N. , Kröse B.
Published: February 2003

This article concerns the greedy learning of gaussian mixtures. In the greedy approach, mixture components are inserted into the mixture one aftertheother.We propose a heuristic for searching for the optimal component to insert. In a randomized manner, a set of candidate new components is generated. For each of these candidates, we find the locally optimal new component and insert it into the existing mixture. The resulting algorithm resolves the sensitivity to initialization of state-of-the-art methods, like expectation maximization, and has running time linear in the number of data points and quadratic in the (final) number of mixture components. Due to its greedy nature, the algorithm can be particularly useful when the optimal number of mixture components is unknown. Experimental results comparing the proposed algorithm to other methods on density estimation and texture segmentation are provided.
Dietary exposures to persistent organic pollutants
Authors: Jensen E , Egan SK , Canady RA , Bolger PM
Published: February 2003

As one of the main components of risk assessment, exposure assessment plays a key role in evaluating risk. Many different scenarios can be developed to estimate the risk from exposure to chemicals such as persistent organic pollutants (POPs). The US Food and Drug Administration (FDA)’s Center for Food Safety and Applied Nutrition (CFSAN) is primarily interested in POPs as humans may be exposed to these compounds through food. Examples of POPs found in food include dioxins, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers, and some pesticide chemicals. This overview discusses various sources of data that CFSAN has used to estimate dietary exposure to POPs, and provides an example of a recent calculation of an estimate for dietary exposure for consumers in the USA to dioxins in the food supply.
Potential technology for studying dosimetry and response to airborne chemical and biological pollutants
Authors: Timchalk Charles , Trease Harold E , Trease Lynn L , Minard Kevin R , Corley Richard A
Published: February 2003

Advances in computational, and imaging techniques have enabled the rapid development of three-dimensional (3-D) models of biological systems in unprecedented detail. Using these advances, 3-D models of the lungs and nasal passages of the rat and human are being developed to ultimately improve predictions of airborne pollutant dosimetry. Techniques for imaging the respiratory tract by magnetic resonance imaging (MRI) were developed to improve the speed and accuracy of geometric data collection for mesh reconstruction. The MRI resolution is comparable to that obtained by manual measurements but at much greater speed and accuracy. Newly developed software (NWGrid) was utilized to translate imaging data from MR into 3-D mesh structures. Together, these approaches significantly reduced the time to develop a 3-D model. This more robust airway structure will ultimately facilitate modeling gas or vapor exchange between the respiratory tract and vasculature as well as enable linkages of dosimetry with cell response models. The 3-D, finite volume, viscoelastic mesh structures form the geometric basis for computational fluid dynamics modeling of inhalation, exhalation and the delivery of individual particles (or concentrations of gas or vapors) to discrete regions of the respiratory tract. The ability of these 3-D models to resolve dosimetry at such a high level of detail will require new techniques to measure regional airflows and particulate deposition for model validation.
A typical path model of tracheobronchial clearance of inhaled particles in rats
Authors: Kimmel Edgar C , Reboulet James E , Carpenter Robert L
Published: February 2003

A mathematical description of particle clearance from the ciliated conducting airways (tracheobronchial region) of the lungs in rats was developed, assuming that particles on the mucus blanket behave as a fluid and adhere to principles of fluid flow described by the continuity equation. Effective particle transport velocities for given generations of airways were estimated from reported tracheal mucus velocities. Using typical rat airway geometry and estimated particle transport velocities, solutions of sets of rate equations for transport from each generation of airways were summed to estimate total particle clearance from the tracheobronchial region of the lung as a function of time. Aerosol particle size distribution (MMAD ranging from 0.1 to 4.2 μm, and sg from 1 to 2.7) and concentration data from several investigators were used to predict short-term, tracheobronchial clearance (retention) in rats up to 24 h following exposure. Comparisons between predicted and observed retention showed an average difference between model predictions, and observed fractional retention of initial lung or body burden was 4.9%, with a tendency toward underprediction of clearance of particles >3.0 μm.
An ‘injury-time integral’ model for extrapolating from acute to chronic effects of phosgene
Authors: Hatch GE , Kodavanti U , Crissman K , Slade R , Costa D
Published: February 2003

The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the `concentration×time’ ( C×T) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (male Fischer 344) were exposed (six hours/day) to air or 0.1, 0.2, 0.5 and 1.0 ppm of phosgene one time or on a repeated regimen for up to 12 weeks as follows: 0.1 ppm (five days/week), 0.2 ppm (five days/week), 0.5 ppm (two days/week), or 1.0 ppm (one day/week) (note that the C×T for the three highest exposures was the same). Animals were sacrificed at 4, 8, and 12 weeks during the exposure and after four weeks recovery. Bronchoalveolar lavage (BAL) was performed 18 hours after the last exposure for each time period and the BAL supernatant assayed for protein. Elevated BAL fluid protein was defined as `acute injury’, diminished response after repeated exposure was defined as `adaptation’, and increased lung hydroxyproline or trichrome staining for collagen was defined as `chronic injury’. Results indicated that exposures that cause maximal chronic injury involve high exposure concentrations and longer times between exposures, not high C×T products. A conceptual model is presented that explains the lack of C×T correlation by the fact that adaptation reduces an `injury-time integral’ as phosgene exposure is lengthened from acute to subchronic. At high exposure concentrations, the adaptive response appears to be overwhelmed, causing a continued injury-time integral, which appears to be related to appearance of chronic injury. The adaptive response is predicted to disappear if the time between exposures is lengthened, leading to a continued high injury-time integral and chronic injury. It has generally been assumed that long, continuous exposures of rodents is a conservative approach for detecting possible chronic effects. The present study suggests that such an approach my not be conservative, but might actually mask effects that could occur under intermittent exposure conditions.
Phase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma
Authors: Quinn Jennifer A. , Reardon David A. , Friedman Allan H. , Rich Jeremy N. , Sampson John H. , Provenzale James M. , McLendon Roger E. , Gururangan Sridharan , Bigner Darell D. , Herndon James E. , Avgeropoulos Nicholas , Finlay Jonathan , Tourt-Uhlig Sandra , Affronti Mary Lou , Evans Brandon , Stafford-Fox Valerie , Zaknoen Sara , Friedman Henry S.
Published: February 2003

Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma.

Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m2/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity.

Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to ∞ months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced ≥ grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death.

Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.
Vaccination With Irradiated Autologous Tumor Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor Augments Antitumor Immunity in Some Patients With Metastatic Non–Small-Cell Lung Carcinoma
Authors: Salgia Ravi , Lynch Thomas , Skarin Arthur , Lucca Joan , Lynch Cathleen , Jung Ken , Hodi F. Stephen , Jaklitsch Michael , Mentzer Steve , Swanson Scott , Lukanich Jean , Bueno Raphael , Wain John , Mathisen Douglas , Wright Cameron , Fidias Panos , Donahue Dean , Clift Shirley , Hardy Steve , Neuberg Donna , Mulligan Richard , Webb Iain , Sugarbaker David , Mihm Martin , Dranoff Glenn
Published: February 2003

Purpose: We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non–small-cell lung cancer (NSCLC), we conducted a phase I clinical trial.

Patients and Methods: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 × 106, 4 × 106, or 1 × 107cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals.

Results: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/106cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed.

Conclusion: Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.