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Showing papers by "University of Tsukuba published in 2000"



Journal ArticleDOI
TL;DR: It is shown that Nrf2 controls the expression of a group of electrophile- and oxidative stress-inducible proteins and activities, which includes heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane transport (system xc −) activity.

1,367 citations


Journal ArticleDOI
TL;DR: It is proposed that HSCs gradually accumulate with age, accompanied by cells with less lymphoid differentiation potential, as a result of repeated self-renewal of HSCe, as well as among unseparated bone marrow cells.
Abstract: Little is known of age-associated functional changes in hematopoietic stem cells (HSCs). We studied aging HSCs at the clonal level by isolating CD34−/lowc-Kit+Sca-1+ lineage marker–negative (CD34−KSL) cells from the bone marrow of C57BL/6 mice. A population of CD34−KSL cells gradually expanded as age increased. Regardless of age, these cells formed in vitro colonies with stem cell factor and interleukin (IL)-3 but not with IL-3 alone. They did not form day 12 colony-forming unit (CFU)-S, indicating that they are primitive cells with myeloid differentiation potential. An in vivo limiting dilution assay revealed that numbers of multilineage repopulating cells increased twofold from 2 to 18 mo of age within a population of CD34−KSL cells as well as among unseparated bone marrow cells. In addition, we detected another compartment of repopulating cells, which differed from HSCs, among CD34−KSL cells of 18-mo-old mice. These repopulating cells showed less differentiation potential toward lymphoid cells but retained self-renewal potential, as suggested by secondary transplantation. We propose that HSCs gradually accumulate with age, accompanied by cells with less lymphoid differentiation potential, as a result of repeated self-renewal of HSCs.

675 citations


Journal ArticleDOI
TL;DR: The findings suggest that the large size of a (GT)n repeat in the HO-1 gene promoter may reduceHO-1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting in the development of CPE.
Abstract: Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5′-flanking region of human HO-1 gene shows length polymorphism and could modulate the level of gene transcription. To investigate the correlation between the length of the (GT)n repeat and susceptibility to the development of CPE, we screened the frequencies of alleles with varying numbers of (GT)n repeats in the HO-1 gene in 101 smokers with CPE and in 100 smokers without CPE. Polymorphisms of the (GT)n repeat were grouped into three classes: class S alleles (<25 repeats), class M alleles (25–29 repeats), and class L alleles (⩾30 repeats). The proportion of allele frequencies in class L, as well as the proportion of genotypic frequencies in the group with class L alleles (L/L, L/M, and L/S), was significantly higher in the smokers with CPE than in smokers without CPE. Moreover, we analyzed the promoter activities of the HO-1 gene carrying different (GT)n repeats (n=16, 20, 29, and 38), by transient-transfection assay in cultured cell lines. H2O2 exposure up-regulated the transcriptional activity of the HO-1 promoter/luciferase fusion genes with (GT)16 or (GT)20 but did not do so with (GT)29 or (GT)38. These findings suggest that the large size of a (GT)n repeat in the HO-1 gene promoter may reduce HO-1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting in the development of CPE.

570 citations


Journal ArticleDOI
TL;DR: The compact physical size of the chicken genome, combined with the large size of its genetic map and the observed degree of conserved synteny, makes the chicken a valuable model organism in the genomics as well as the postgenomics era.
Abstract: A consensus linkage map has been developed in the chicken that combines all of the genotyping data from the three available chicken mapping populations. Genotyping data were contributed by the laboratories that have been using the East Lansing and Compton reference populations and from the Animal Breeding and Genetics Group of the Wageningen University using the Wageningen/Euribrid population. The resulting linkage map of the chicken genome contains 1889 loci. A framework map is presented that contains 480 loci ordered on 50 linkage groups. Framework loci are defined as loci whose order relative to one another is supported by odds greater then 3. The possible positions of the remaining 1409 loci are indicated relative to these framework loci. The total map spans 3800 cM, which is considerably larger than previous estimates for the chicken genome. Furthermore, although the physical size of the chicken genome is threefold smaller then that of mammals, its genetic map is comparable in size to that of most mammals. The map contains 350 markers within expressed sequences, 235 of which represent identified genes or sequences that have significant sequence identity to known genes. This improves the contribution of the chicken linkage map to comparative gene mapping considerably and clearly shows the conservation of large syntenic regions between the human and chicken genomes. The compact physical size of the chicken genome, combined with the large size of its genetic map and the observed degree of conserved synteny, makes the chicken a valuable model organism in the genomics as well as the postgenomics era. The linkage maps, the two-point lod scores, and additional information about the loci are available at web sites in Wageningen (http://www.zod.wau.nl/vf/research/chicken/frame_chicken.html) and East Lansing (http://poultry.mph.msu.edu/).

456 citations


Journal Article
TL;DR: Results indicate that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma and clear cell carcinoma of the ovary.
Abstract: Loss of heterozygosity (LOH) at locus 10q23.3 and mutation of the PTEN tumor suppressor gene occur frequently in both endometrial carcinoma and ovarian endometrioid carcinoma. To investigate the potential role of the PTEN gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas, and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations within the entire coding region of the PTEN gene. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%), and 13 of 23 solitary endometrial cysts (56.5%). In 5 endometrioid carcinomas synchronous with endometriosis, 3 cases displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 1 displayed no LOH events in either lesion. In 7 clear cell carcinomas synchronous with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 3 displayed no LOH events in either lesion. In no cases were there LOH events in the endometriosis only. Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%), and 7 of 34 solitary endometrial cysts (20.6%). These results indicate that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma and clear cell carcinoma of the ovary.

444 citations


Journal ArticleDOI
TL;DR: Results indicate that interference of transcription by the binding of TAFII130 with expanded polyQ stretches is involved in the pathogenetic mechanisms underlying neurodegeneration.
Abstract: At least eight inherited neurodegenerative diseases are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches are implicated, the molecular mechanisms of neurodegeneration remain unclear. We found that expanded polyQ stretches preferentially bind to TAFII130, a coactivator involved in cAMP-responsive element binding protein (CREB)-dependent transcriptional activation, and strongly suppress CREB-dependent transcriptional activation. The suppression of CREB-dependent transcription and the cell death induced by polyQ stretches were restored by the co-expression of TAFII130. Our results indicate that interference of transcription by the binding of TAFII130 with expanded polyQ stretches is involved in the pathogenetic mechanisms underlying neurodegeneration.

411 citations


Journal ArticleDOI
01 Apr 2000-Blood
TL;DR: It is concluded that hematopoietic stem cells expand in the fetal liver maintaining their level of repopulating potential.

367 citations


Journal ArticleDOI
TL;DR: The mutant mtDNA was transmitted maternally, and its accumulation induced mitochondrial dysfunction in various tissues and most of these mice died because of renal failure, suggesting the involvement of mtDNA mutations in the pathogeneses of new diseases.
Abstract: Mice carrying mitochondrial DNA (mtDNA) with pathogenic mutations would provide a system in which to study how mutant mtDNAs are transmitted and distributed in tissues, resulting in expression of mitochondrial diseases. However, no effective procedures are available for the generation of these mice. Isolation of mouse cells without mtDNA (rho0) enabled us to trap mutant mtDNA that had accumulated in somatic tissues into rho0 cells repopulated with mtDNA (cybrids). We isolated respiration-deficient cybrids with mtDNA carrying a deletion and introduced this mtDNA into fertilized eggs. The mutant mtDNA was transmitted maternally, and its accumulation induced mitochondrial dysfunction in various tissues. Moreover, most of these mice died because of renal failure, suggesting the involvement of mtDNA mutations in the pathogeneses of new diseases.

362 citations


Journal ArticleDOI
TL;DR: In this paper, the authors demonstrated involvement of the ventral tegmental area (VTA) dopaminergic system in orexin-induced hyperlocomotion and stereotypy in rats.

360 citations


Journal ArticleDOI
TL;DR: A mouse Fc receptor, designated Fcα/μR, and its human homolog, that bind both IgM and IgA with intermediate or high affinity are described that are involved in the primary stages of the immune response to microbes.
Abstract: IgM is the first antibody to be produced in a humoral immune response and plays an important role in the primary stages of immunity Here we describe a mouse Fc receptor, designated Fc alpha/microR, and its human homolog, that bind both IgM and IgA with intermediate or high affinity Fc alpha/microR is constitutively expressed on the majority of B lymphocytes and macrophages Cross-linking Fc alpha/microR expressed on a pro-B cell line Ba/F3 transfectant with soluble IgM or IgM-coated microparticles induced internalization of the receptor Fc alpha/microR also mediated primary B lymphocyte endocytosis of IgM-coated Staphylococcus aureus Thus, Fc alpha/microR is involved in the primary stages of the immune response to microbes

Journal ArticleDOI
TL;DR: In this article, a series of Bi-layered compounds with orthorhombic distortion and relaxor-type ferroelectric properties were investigated, and the properties of these compounds were investigated at the macroscopic scale.
Abstract: Crystal structures and ferroelectric properties of a series of Bi-layered compounds, ${\mathrm{CaBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9},$ ${\mathrm{SrBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9},$ and ${\mathrm{BaBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9},$ were investigated. The structures of ${\mathrm{CaBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9}$ and ${\mathrm{SrBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9}$ are orthorhombic, while that of ${\mathrm{BaBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9}$ is pseudotetragonal on the macroscopic scale but consists of microdomains with orthorhombic distortion. The ferroelectric Curie temperature of ${\mathrm{CaBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9}$ was over 600 \ifmmode^\circ\else\textdegree\fi{}C, and that of ${\mathrm{SrBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9}$ was over 300 \ifmmode^\circ\else\textdegree\fi{}C. ${\mathrm{BaBi}}_{2}{\mathrm{Ta}}_{2}{\mathrm{O}}_{9},$ in contrast, showed relaxor-type ferroelectric behavior; that is, in the plot of temperature dependence of dielectric constant, a broad peak appeared around 60 \ifmmode^\circ\else\textdegree\fi{}C. As the size of the A-site cation decreases from ${\mathrm{Ba}}^{2+}$ to ${\mathrm{Ca}}^{2+},$ the lattice mismatch between ${\mathrm{TaO}}_{2}$ and $A\mathrm{O}$ planes in the perovskite-type unit of $A{\mathrm{Ta}}_{2}{\mathrm{O}}_{7}$ increases and the structural distortion becomes more pronounced. This distortion leads to the higher Curie temperature and the larger spontaneous ferroelectric polarization.

Journal ArticleDOI
TL;DR: Significantly, residual induction of GST by antioxidants is apparent in the Nrf2 mutant mouse, indicating the existence of an alternative mechanism of gene activation.
Abstract: An overview is provided of the cancer chemoprevention actions of phenolic antioxidants and 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline (ethoxyquin). These agents principally appear to exert their beneficial effects through induction of phase II drug-metabolizing enzymes such as glutathione S-transferase (GST). The requirement for oxidative metabolism of the synthetic antioxidants to carbonyl-containing compounds, including quinones, in order that they can induce gene expression is discussed. Previous work has shown that the basic leucine zipper transcription factor Nrf2 is involved in induction of GST by the phenolic antioxidant butylated hydroxyanisole (BHA). Evidence is provided from a mouse possessing a targeted disruption of the Nrf2 gene that, in murine liver, the transcription factor regulates basal expression of several class Alpha and class Mu GST subunits, but not class Pi GST. In the Nrf2 knock-out mouse, hepatic induction of class Alpha and class Mu GST by BHA and the synthetic antioxidant ethoxyquin is similarly impaired, suggesting that these agents affect gene activation by a related mechanism. Significantly, residual induction of GST by antioxidants is apparent in the Nrf2 mutant mouse, indicating the existence of an alternative mechanism of gene activation.

Journal ArticleDOI
TL;DR: Evidence is provided that one hematopoietic stem cells regenerates at least one HSC in culture, and these regenerated repopulating cells could be further transplanted into secondary recipients.
Abstract: Little is known about how hematopoietic stem cells (HSCs) self-renew. We studied the regeneration of HSCs in culture. Effects of various cytokines on cell division of CD34(-/low) c-Kit(+)Sca-1(+) lineage marker-negative (CD34(-)KSL) bone marrow cells of the mouse were first evaluated in serum-free single cell culture. We then performed a competitive repopulation assay on divided cells to ask if such cell division involved self-renewal of HSCs. In the presence of stem cell factor (SCF), thrombopoietin (TPO) induced a first cell division of CD34(-)KSL cells more efficiently than did interleukin (IL)-3 or IL-6. Multilineage repopulating cells were detected in a significant proportion of cells derived from single cells in culture with TPO and SCF, although this culture condition led to a substantial decrease in HSC number. These regenerated repopulating cells could be further transplanted into secondary recipients. When paired daughter cells were separately studied, one of a pair gave rise to repopulating cells with self-renewal potential, suggesting asymmetric self-renewal division. This study provides evidence that one HSC regenerates at least one HSC in culture.

Journal ArticleDOI
TL;DR: It is suggested that DNPI functions in heterogeneous neuron populations as a neuron-specific Na(+)-dependent inorganic phosphate cotransport system predominantly expressed in the diencephalon of the rat.

Journal ArticleDOI
TL;DR: It is demonstrated that hepatic progenitor cells are enriched by FACS and suggested approaches to supplanting organ allografting and improving artificial‐organ hepatic support are suggested.

Journal ArticleDOI
TL;DR: In this article, the Cu(I)-catalyzed boration of an α,β-enone using a diboron is described, where the combination of a Cu(1) salt and tributylphosphine is an effective catalyst system.

Journal ArticleDOI
TL;DR: The use of aptamer‐derived oligomers to analyze the Tat of HIV and the possible applications of such constructs in the field of biosensors are reported.
Abstract: Background We reported an aptamer, RNATat that binds to the Tat protein of HIV with two orders of magnitude greater (133-fold) affinity over the TAR RNA of HIV-1 and specifically inhibits the Tat-dependent trans-activation of transcription, both in vitro and in vivo (demonstrated in the accompanying article, Yamamoto et al., this issue pp. 371–388). We now report the use of aptamer-derived oligomers to analyze the Tat of HIV and the possible applications of such constructs in the field of biosensors. Results To make new molecular beacon, we constructed two RNA oligomers that derived from RNATat. To one of the split RNA oligomers that forms a hairpin structure, the fluorophore and quencher were attached at the 5′- and 3′-ends, respectively. Specifically in the presence of Tat or its peptides, but not in the presence of other RNA binding proteins, the two oligomers undergo a conformational change to form a duplex that leads to relieving of fluorophore from the quencher, and thus a significant enhancement of the fluorescence of fluorescein was observed. Conclusion A novel strategy for exploiting aptamers in the analysis of Tat (analyte) has been described. A similar strategy could be used to study other analytes such as proteins and small molecules. In addition, the molecular beacon aptamer requires half the length of target sequence (eight nucleotides) in comparison with molecular beacons. Thus, it is conceivable that we could insert an analyte-binding site into molecular beacons to convert them to signalling beacons.

Journal ArticleDOI
TL;DR: In this paper, a real-space representation of the electron wave functions and calculating the dynamics in real-time was presented, which increases the efficiency for calculating the interaction and decreases storage requirements and allows the entire frequency dependent dielectric function to be calculated at once.
Abstract: We present an algorithm to calculate the linear response of periodic systems in the time-dependent density functional theory, using a real-space representation of the electron wave functions and calculating the dynamics in real time. The real-space formulation increases the efficiency for calculating the interaction, and the real-time treatment decreases storage requirements and allows the entire frequency-dependent dielectric function to be calculated at once. We give as examples the dielectric functions of a simple metal, lithium, and an elemental insulator, diamond.

Journal ArticleDOI
TL;DR: In this article, the current processing and resultant properties of standard Nitinol wire for guide-wire applications are reviewed and a review of the fatigue properties of thermomechanically-treated Ni wire is presented.
Abstract: Summary The purpose of this paper is to review the current processing and resultant properties of standard Nitinol wire for guide-wire applications. Optimised Ti-50.8at%Ni wire was manufactured according to industry standards by precise control of the composition, cold work and continuous strain-age annealing. Mechanical properties of this wire are reported from 100°C to 200°C to demonstrate the effects of test temperature. Within the ‘superelastic window’ the plateau stresses are linearly related to test temperature. Additional ageing treatments can be used as a tool to fine-tune transformation temperatures and mechanical properties. A review of the fatigue properties of thermomechanically-treated Nitinol wire shows that they are affected by test temperature, stress and strain.

Journal ArticleDOI
TL;DR: In this article, the authors used radio format changes to test hypotheses on innovations as catalysts for non-mimetic change in organizations and found that the social and competitive relations of the innovator to a given organization are modifiers of the catalytic effect.
Abstract: This paper uses data on radio format changes to test hypotheses on innovations as catalysts for nonmimetic change in organizations. Innovations are difficult to interpret using existing schemata, causing organizations to search for information on the opportunities and threats implicit in observed innovations. Such search may lead to mimetic adoption of the innovation or, more likely, to more varied nonmimetic change. Results show an effect of innovations on the rate of nonmimetic change in radio markets, with innovations in large or nearby markets having greater effect and innovations by large organizations having less effect. The social and competitive relations of the innovator to a given organization are thus modifiers of the catalytic effect. These findings have implications for theories of innovation, competition, and organizational isomorphism.

Proceedings Article
01 May 2000
TL;DR: LREC2000: the 2nd International Conference on Language Resources and Evaluation, May 31 - June 2, 2000, Athens, Greece.
Abstract: LREC2000: the 2nd International Conference on Language Resources and Evaluation, May 31 - June 2, 2000, Athens, Greece.

Journal ArticleDOI
TL;DR: It is suggested that the NPY system could be the one of downstream pathways by which orexin-A induces feeding behavior, because BIBO3304 did not completely abolish orexIn-A-induced feeding behavior.

Journal ArticleDOI
TL;DR: In this paper, the Bowen ratio energy balance method was used to analyze microwave measurements from 1992 to 1994 in Naiman (lat. 42°58′N, long. 120°43′E, 345m asl), Inner Mongolia, China to elucidate desertification mechanisms.

Journal ArticleDOI
TL;DR: Findings implicate a positive loop production of SREBP-1c through the SRE complex, possibly leading to the overshoot in induction of S REBP- 1c and its downstream genes seen in the livers of refed mice.

Journal ArticleDOI
TL;DR: The magnetic rigidity of the cosmic-ray proton and helium spectra was reliably determined by highly precise measurement of the circular track in a uniform solenoidal magnetic field of 1 Tesla as discussed by the authors.
Abstract: We report cosmic-ray proton and helium spectra in energy ranges of 1 to 120 GeV and 1 to 54 GeV/nucleon, respectively, measured by a balloon flight of the BESS spectrometer in 1998. The magnetic-rigidity of the cosmic-rays was reliably determined by highly precise measurement of the circular track in a uniform solenoidal magnetic field of 1 Tesla. Those spectra were determined within overall uncertainties of +-5 % for protons and +- 10 % for helium nuclei including statistical and systematic errors.

Journal ArticleDOI
TL;DR: The results demonstrate that isoliquiritigenin and butein inhibit cell proliferation and induce apoptosis in B16 melanoma cells and it seems that the pathway by which the chalcones induce apoptose may be independent of p53 and dependent on proteins of the Bcl-2 family.
Abstract: We investigated the growth inhibitory activity of several flavonoids, including apigenin, luteolin, kaempherol, quercetin, butein, isoliquiritigenin, naringenin, genistein, and daizein against B16 mouse melanoma 4A5 cells. Isoliquiritigenin and butein, belonging to the chalcone group, markedly suppressed the growth of B16 melanoma cells and induced cell death. The other flavonoids tested showed little growth inhibitory activity and scarcely caused cell death. In cells treated with isoliquiritigenin or butein, condensation of nuclei and fragmentation of nuclear DNA, which are typical phenomena of apoptosis, were observed by Hoechst 33258 staining and by agarose gel electrophoresis of DNA. Flowcytometric analysis showed that isoliquiritigenin and butein increased the proportion of hypodiploid cells in the population of B16 melanoma cells. These results demonstrate that isoliquiritigenin and butein inhibit cell proliferation and induce apoptosis in B16 melanoma cells. Extracellular glucose decreased the proportion of hypodiploid cells that appeared as a result of isoliquiritigenin treatment. p53 was not detected in cells treated with either of these chalcones, however, protein of the Bcl-2 family were detected. The level of expression of Bax in cells treated with either of these chalcones was markedly elevated and the level of Bcl-XL decreased slightly. Isoliquiritigenin did not affect Bcl-2 expression, but butein down-regulated Bcl-2 expression. From these results, it seems that the pathway by which the chalcones induce apoptosis may be independent of p53 and dependent on proteins of the Bcl-2 family. It was supposed that isoliquiritigenin induces apoptosis in B16 cells by a mechanism involving inhibition of glucose transmembrane transport and promotion of Bax expression. On the other hand, it was suggested that butein induces apoptosis via down-regulation of Bcl-2 expression and promotion of Bax expression. This mechanism differs from the isoliquiritigenin induction pathway.

Journal ArticleDOI
TL;DR: The magnetic rigidity of the cosmic ray was reliably determined by highly precise measurement of the circular track in a uniform solenoidal magnetic field of 1 T in 1998 as discussed by the authors, and the cosmic-ray proton and helium spectra were determined within overall uncertainties of ±5% for protons and ±10% for helium nuclei including statistical and systematic errors.
Abstract: We report cosmic-ray proton and helium spectra in energy ranges of 1-120 GeV nucleon-1 and 1-54 GeV nucleon-1, respectively, measured by a flight of the Balloon-borne Experiment with Superconducting Spectrometer (BESS) in 1998. The magnetic rigidity of the cosmic ray was reliably determined by highly precise measurement of the circular track in a uniform solenoidal magnetic field of 1 T. Those spectra were determined within overall uncertainties of ±5% for protons and ±10% for helium nuclei including statistical and systematic errors.

Journal ArticleDOI
TL;DR: Quasiparticle dispersion in Bi2Sr2CaCu2O8 is investigated with improved angular resolution as a function of temperature and doping, and unlike the linear dispersion predicted by the band calculation, the data show a sharp break in dispersion at 50+/-15 meV binding energy where the velocity changes by a factor of 2 or more.
Abstract: Quasiparticle dispersion in Bi2Sr2CaCu2O8 is investigated with improved angular resolution as a function of temperature and doping. Unlike the linear dispersion predicted by the band calculation, the data show a sharp break in dispersion at 50+/-15 meV binding energy where the velocity changes by a factor of 2 or more. This change provides an energy scale in the quasiparticle self-energy. This break in dispersion is evident at and away from the d-wave node line, but the magnitude of the dispersion change decreases with temperature and with increasing doping.