Showing papers by "Academia Sinica published in 1999"
TL;DR: Using the MIM model, a stepwise selection procedure with likelihood ratio test statistic as a criterion is proposed to identify QTL and the best strategy of marker-assisted selection for trait improvement for a specific purpose and requirement can be explored.
Abstract: A new statistical method for mapping quantitative trait loci (QTL), called multiple interval mapping (MIM), is presented. It uses multiple marker intervals simultaneously to fit multiple putative QTL directly in the model for mapping QTL. The MIM model is based on Cockerham's model for interpreting genetic parameters and the method of maximum likelihood for estimating genetic parameters. With the MIM approach, the precision and power of QTL mapping could be improved. Also, epistasis between QTL, genotypic values of individuals, and heritabilities of quantitative traits can be readily estimated and analyzed. Using the MIM model, a stepwise selection procedure with likelihood ratio test statistic as a criterion is proposed to identify QTL. This MIM method was applied to a mapping data set of radiata pine on three traits: brown cone number, tree diameter, and branch quality scores. Based on the MIM result, seven, six, and five QTL were detected for the three traits, respectively. The detected QTL individually contributed from approximately 1 to 27% of the total genetic variation. Significant epistasis between four pairs of QTL in two traits was detected, and the four pairs of QTL contributed approximately 10.38 and 14.14% of the total genetic variation. The asymptotic variances of QTL positions and effects were also provided to construct the confidence intervals. The estimated heritabilities were 0.5606, 0.5226, and 0. 3630 for the three traits, respectively. With the estimated QTL effects and positions, the best strategy of marker-assisted selection for trait improvement for a specific purpose and requirement can be explored. The MIM FORTRAN program is available on the worldwide web (http://www.stat.sinica.edu.tw/chkao/).
941 citations
TL;DR: In this article, the authors derive a new approach that allows one to obtain many classes of nonseparable, spatio-temporal stationary covariance functions and fit several such classes to spatiotemporal data on wind speed over a region in the tropical western Pacific ocean.
Abstract: Suppose that a random process Z(s;t), indexed in space and time, has spatio-temporal stationary covariance C(h;u), where h ∈ ℝd (d ≥ 1) is a spatial lag and u ∈ ℝ is a temporal lag. Separable spatio-temporal covariances have the property that they can be written as a product of a purely spatial covariance and a purely temporal covariance. Their ease of definition is counterbalanced by the rather limited class of random processes to which they correspond. In this article we derive a new approach that allows one to obtain many classes of nonseparable, spatio-temporal stationary covariance functions and fit several such classes to spatio-temporal data on wind speed over a region in the tropical western Pacific ocean.
679 citations
TL;DR: Results of further studies suggest that suppression of transcriptional activation of COX-2 and iNOS by apigenin might mainly be mediated through inhibition of IkB kinase activity.
Abstract: Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of carcinogenesis and inflammation. In this study, we investigated the effect of various flavonoids and (-)-epigallocatechin-3-gallate on the activities of inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Apigenin, genistein and kaempferol were markedly active inhibitors of transcriptional activation of COX-2, with IC(50) < 15 microM. In addition, apigenin and kaempferol were also markedly active inhibitors of transcriptional activation of iNOS, with IC(50) < 15 microM. Of those compounds tested, apigenin was the most potent inhibitor of transcriptional activation of both COX-2 and iNOS. Western and northern blot analyses demonstrated that apigenin significantly blocked protein and mRNA expression of COX-2 and iNOS in LPS-activated macrophages. Transient transfection experiments showed that LPS caused an approximately 4-fold increase in both COX-2 and iNOS promoter activities, these increments were suppressed by apigenin. Moreover, electrophoretic mobility shift assay (EMSA) experiments indicated that apigenin blocked the LPS-induced activation of nuclear factor-kB (NF-kB). The inhibition of NF-kB activation occurs through the prevention of inhibitor kB (IkB) degradation. Transient transfection experiments also showed that apigenin inhibited NF-kB-dependent transcriptional activity. Finally, we showed that apigenin could inhibit the IkB kinase activity induced by LPS or interferon-gamma. The results of further studies suggest that suppression of transcriptional activation of COX-2 and iNOS by apigenin might mainly be mediated through inhibition of IkB kinase activity. This study suggests that modulation of COX-2 and iNOS by apigenin and related flavonoids may be important in the prevention of carcinogenesis and inflammation.
581 citations
TL;DR: Results indicate that in addition to being a low-affinity nitrate transporter, as previously recognized, CHL1 is also involved in both the inducible and constitutive phases of high-affination nitrate uptake in Arabidopsis.
Abstract: Higher plants have both high- and low-affinity nitrate uptake systems. These systems are generally thought to be genetically distinct. Here, we demonstrate that a well-known low-affinity nitrate uptake mutant of Arabidopsis, chl1 , is also defective in high-affinity nitrate uptake. Two to 3 hr after nitrate induction, uptake activities of various chl1 mutants at 250 μM nitrate (a high-affinity concentration) were only 18 to 30% of those of wild-type plants. In these mutants, both the inducible phase and the constitutive phase of high-affinity nitrate uptake activities were reduced, with the inducible phase being severely reduced. Expressing a CHL1 cDNA driven by the cauliflower mosaic virus 35S promoter in a transgenic chl1 plant effectively recovered the defect in high-affinity uptake for the constitutive phase but not for the induced phase, which is consistent with the constitutive level of CHL1 expression in the transgenic plant. Kinetic analysis of nitrate uptake by CHL1 -injected Xenopus oocytes displayed a biphasic pattern with a Michaelis–Menten K m value of ~50 μM for the high-affinity phase and ~4 mM for the low-affinity phase. These results indicate that in addition to being a low-affinity nitrate transporter, as previously recognized, CHL1 is also involved in both the inducible and constitutive phases of high-affinity nitrate uptake in Arabidopsis.
473 citations
TL;DR: In this paper, a plane-wave pseudopotential method is used to calculate the second-harmonic generation (SHG) coefficients at the independent-particle level with a formalism originally given by Aversa and Sipe [Phys. Rev. B 52, 14 636 (1995)] and later rearranged by Rashkeev et al. [Rev.
Abstract: Electronic structure calculations of $\ensuremath{\beta}\ensuremath{-}{\mathrm{BaB}}_{2}{\mathrm{O}}_{4}$ from first principles are performed based on a plane-wave pseudopotential method, and the linear optical properties are then obtained. The static second-harmonic generation (SHG) coefficients are calculated at the independent-particle level with a formalism originally given by Aversa and Sipe [Phys. Rev. B 52, 14 636 (1995)] and later rearranged by Rashkeev et al. [Phys. Rev. B 57, 3905 (1998)] to explicitly show Kleinman's symmetry. The formalism is improved to be more efficient in reducing the $k$ points necessary for convergence. A real-space atom-cutting method is suggested to analyze the respective contributions of various transitions among ions and ion groups to optical response. The contribution of the cation Ba to SHG effects is found to be not important but non-negligible, while its contribution to birefringence is negligible.
410 citations
TL;DR: It is suggested that the presence of the gallate group at the 3 position plays the most important role in their free radical-scavenging abilities and an additional insertion of the hydroxylgroup at the 5' position in the B ring also contributes to their scavenging activities.
405 citations
TL;DR: In this article, the RANSAC-based DARCES method is proposed to solve the partially overlapping 3D registration problem without any initial estimation, which can be used even for the case that there are no local features in the 3D data sets.
Abstract: In this paper, we propose a new method, the RANSAC-based DARCES method (data-aligned rigidity-constrained exhaustive search based on random sample consensus), which can solve the partially overlapping 3D registration problem without any initial estimation. For the noiseless case, the basic algorithm of our method can guarantee that the solution it finds is the true one, and its time complexity can be shown to be relatively low. An extra characteristic is that our method can be used even for the case that there are no local features in the 3D data sets.
399 citations
TL;DR: Four populations of the rare, highly clonal grass Calamagrostis porteri ssp.
Abstract: Four populations of the rare, highly clonal grass Calamagrostis porteri ssp. insperata were examined using allozymes and the two polymerase chain reaction (PCR)‐based markers, random amplified polymorphic DNA (RAPD) and intersimple sequence repeat (ISSR) bands. Only one of the 15 allozyme loci was variable and two alleles were detected, both of which were found in two populations, while only one genotype was detected in the other two populations. ISSR and RAPD markers detected more genotypes within populations than did allozymes. ISSR markers detected more diversity than RAPD markers in three of the four populations examined. In one population, no RAPD diversity was found whereas eight different genotypes were found among the 10 plants with ISSR markers. This diversity is present despite rare flowering, no documented occurrence of seed set in natural populations and very low seed set with experimental pollinations, all of which suggest that sexual reproduction rarely occurs. The subspecies is self‐compatible, but seed initiation is lower in selfed ovules; also, there is high embryo abortion regardless of pollen source. Variation detected by RAPD and ISSR primers may reflect higher levels of sexual reproduction in the past, very rare sexual reproduction in extant populations, somatic mutations, or a combination of the three. Although the PCR‐based markers identify several multilocus genotypes within populations, it is not known whether these all represent distinct genets generated by sexual reproduction or result from somatic mutations in the old, perennial and highly clonal plants.
395 citations
TL;DR: In this paper, an ethnographic study examines parental beliefs and practices with respect to shame, as well as young children's participation in shaming events, revealing that the socialization of shame was well underway by age two-and-a-half.
Abstract: In an effort to understand shame in Chinese terms, this ethnographic study examines parental beliefs and practices with respect to shame, as well as young children's participation in shaming events. Nine middle-class Taiwanese families participated in this study. Interviews with the primary caregivers and longitudinal observations of spontaneous home interactions revealed that the socialization of shame was well underway by age two-and-a-half. Two types of events were identified, most incidents of which were playful and involved the child's active participation.The child's rudimentary sense of shame was manipulated in order to teach right from wrong and to motivate the child to amend. These events were vivid illustrations of the practice of opportunity education.
388 citations
TL;DR: A phylogenetic tree of the Brassicaceae species under study was constructed and showed that the rate of nucleotide substitution in the first intron of the mitochondrial (mt) gene for NADH subunit 4 (nad4) is very low, about 0.16–0.23 × 10−9 substitution per site per year, which is about half of the silent rate in exons of nad4
Abstract: We obtained 16 nucleotide sequences ( approximately 1400 bp each) of the first intron of the mitochondrial (mt) gene for NADH subunit 4 (nad4) from 10 species of Brassicaceae. Using these new sequences and five published sequences from GenBank, we constructed a phylogenetic tree of the Brassicaceae species under study and showed that the rate of nucleotide substitution in the first intron of nad4 is very low, about 0.16-0.23 x 10(-9) substitution per site per year, which is about half of the silent rate in exons of nad4. The ratios of substitution rates in this intron, ITS, and IGS are approximately 1:23:73, where ITS is the nuclear intergenic spacer between 18S and 25S rRNA genes and IGS is the intergenic spacer of 5S rRNA genes. A segment (335 bp) in the first intron of nad4 in Brassicaceae species that is absent in wheat was considered as a nonfunctional sequence and used to estimate the neutral rate (the rate of mutation) in mtDNA to be 0.5-0.7 x 10(-9) substitution per site per year, which is about three times higher than the substitution rate in the rest of the first intron of nad4. We estimated that the dates of divergence are 170-235 million years (Myr) for the monocot-dicot split, 112-156 Myr for the Brassicaceae-Lettuce split, 14.5-20.4 Myr for the Brassica-Arabidopsis split, and 14.5-20.4 Myr for the Arabidopsis-Arabideae split.
377 citations
TL;DR: It is suggested that both PI3-K/Akt-dependent and -independent pathways contribute to the IL-3 activation of mcl-1 gene expression.
Abstract: mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3) signaling pathways and plays an important role in the viability response of these cytokines In this study, we demonstrated that cytokine stimulation of mcl-1 mRNA and protein expression were attenuated by pretreatment of cells with phosphatidylinositol 3-kinase (PI3-K) inhibitors Reporter gene assays further showed that the PI3-K/Akt signaling pathway was involved in IL-3 activation of mcl-1 gene transcription Analysis of the mcl-1 promoter revealed that both promoter elements, SIE at position -87 and CRE-2 at -70, contribute to IL-3 stimulation of mcl-1 gene expression Although either the SIE site or the CRE-2 site alone was sufficient to confer IL-3 inducibility on a heterologous promoter, only IL-3 activation of the CRE-2 reporter was mediated via the PI3-K/Akt pathway The SIE binding activity was constitutively high in cells deprived of or stimulated by IL-3 In contrast, the CRE-2 binding activity was low in cytokine-starved cells and was strongly induced within 1 h following cytokine treatment of cells In addition, cytokine induction of the CRE-2 but not of the SIE binding activity was dependent on activation of the PI3-K/Akt signaling pathway Lastly, we showed that CREB was one component of the CRE-2 binding complex and played a role in IL-3 activation of the mcl-1 reporter gene Taken together, our results suggest that both PI3-K/Akt-dependent and -independent pathways contribute to the IL-3 activation of mcl-1 gene expression Activation of mcl-1 by the PI3-K/Akt-dependent pathway is through a transcription factor complex containing CREB
TL;DR: Cl cloning and characterization of a CHL1 homolog, AtNRT1:2 (originally named NTL1), are reported, with data to indicate that this gene encodes a constitutive component of low-affinity nitrate uptake.
Abstract: The Arabidopsis CHL1 ( AtNRT1 ) gene encodes an inducible component of low-affinity nitrate uptake, which necessitates a “two-component” model to account for the constitutive low-affinity uptake observed in physiological studies. Here, we report the cloning and characterization of a CHL1 homolog, AtNRT1:2 (originally named NTL1 ), with data to indicate that this gene encodes a constitutive component of low-affinity nitrate uptake. Transgenic plants expressing antisense AtNRT1:2 exhibited reduced nitrate-induced membrane depolarization and nitrate uptake activities in assays with 10 mM nitrate. Furthermore, transgenic plants expressing antisense AtNRT1:2 in the chl1-5 background exhibited an enhanced resistance to chlorate (7 mM as opposed to 2 mM for the chl1-5 mutant). Kinetic analysis of AtNRT1:2 -injected Xenopus oocytes yielded a K m for nitrate of ∼5.9 mM. In contrast to CHL1 , AtNRT1:2 was constitutively expressed before and after nitrate exposure (it was repressed transiently only when the level of CHL1 mRNA started to increase significantly), and its mRNA was found primarily in root hairs and the epidermis in both young (root tips) and mature regions of roots. We conclude that low-affinity systems of nitrate uptake, like high-affinity systems, are composed of inducible and constitutive components and that with their distinct functions, they are part of an elaborate nitrate uptake network in Arabidopsis.
TL;DR: In this article, the authors discuss the recent advances in process technology with special focus on improvements of para-isomer selectivity and catalyst stability, and provide perspective trends in related research and development.
Abstract: Disproportionation and transalkylation are important processes for the interconversion of mono-, di-, and tri-alkylbenzenes. In this review, we discuss the recent advances in process technology with special focus on improvements of para-isomer selectivity and catalyst stability. Extensive patent search and discussion on technology development are presented. The key criteria for process development are identified. The working principles of para-isomer selectivity improvements involve the reduction of diffusivity and the inactivation of external surface. In conjunction with the fundamental research, various practical modification aspects particularly the pre-coking and the silica deposition techniques, are extensively reviewed. The impact of para-isomer selective technology on process economics and product recovery strategy is discussed. Furthermore, perspective trends in related research and development are provided.
TL;DR: One application of the analysis is to improve genome-wide marker-assisted selection, particularly when the information about epistasis is used for selection with mating, as well as other areas that require further investigation.
Abstract: Understanding and estimating the structure and parameters associated with the genetic architecture of quantitative traits is a major research focus in quantitative genetics. With the availability of a well-saturated genetic map of molecular markers, it is possible to identify a major part of the structure of the genetic architecture of quantitative traits and to estimate the associated parameters. Multiple interval mapping, which was recently proposed for simultaneously mapping multiple quantitative trait loci (QTL), is well suited to the identification and estimation of the genetic architecture parameters, including the number, genomic positions, effects and interactions of significant QTL and their contribution to the genetic variance. With multiple traits and multiple environments involved in a QTL mapping experiment, pleiotropic effects and QTL by environment interactions can also be estimated. We review the method and discuss issues associated with multiple interval mapping, such as likelihood analysis, model selection, stopping rules and parameter estimation. The potential power and advantages of the method for mapping multiple QTL and estimating the genetic architecture are discussed. We also point out potential problems and difficulties in resolving the details of the genetic architecture as well as other areas that require further investigation. One application of the analysis is to improve genome-wide marker-assisted selection, particularly when the information about epistasis is used for selection with mating.
TL;DR: Phylogenetic analysis indicates that, among known theropods with integumentary filaments or feathers, Dromaeosauridae is the most bird-like, and is more closely related to birds than is Troodontidae.
Abstract: Dromaeosaurids, despite their notoriety, are poorly characterized meat-eating dinosaurs, and were previously known only from disarticulated or fragmentary specimens1. Many studies have denied their close relationship to birds2,3. Here we report the best represented and probably the earliest dromaeosaurid yet discovered, Sinornithosaurus millenii gen. et sp. nov., from Sihetun, the famous Mesozoic fish–dinosaur–bird locality in China4,5. Sinornithosaurus not only greatly increases our knowledge of Dromaeosauridae but also provides evidence for a filamentous integument in this group. It is remarkably similar to early birds postcranially. The shoulder girdle shows that terrestrial dromaeosaurids had attained the prerequisites for powered, flapping flight6, supporting the idea that bird flight originated from the ground up7,8. The discovery of Sinornithosaurus widens the distribution of integumentary filaments among non-avian theropods5,9,10. Phylogenetic analysis indicates that, among known theropods with integumentary filaments or feathers2,5, Dromaeosauridae is the most bird-like, and is more closely related to birds than is Troodontidae.
TL;DR: The findings suggest that salicylate exerts its antiinflammatory action in part by suppressing COX-2 induction, thereby reducing the synthesis of proinflammatory prostaglandins.
Abstract: The pharmacological action of salicylate cannot be explained by its inhibition of cyclooxygenase (COX) activity. In this report, the effects of aspirin and sodium salicylate on COX-2 expressions in human umbilical vein endothelial cells and foreskin fibroblasts were evaluated. Aspirin and sodium salicylate at therapeutic concentrations equipotently blocked COX-2 mRNA and protein levels induced by interleukin-1β and phorbol 12-myristate 13-acetate. The suppressing effect was more pronounced in cultured cells deprived of fetal bovine serum for 24 h, suggesting that it may be cell cycle related. Salicylate inhibited nascent COX-2 transcript synthesis but had no effect on COX-2 mRNA stability. It inhibited COX-2 promoter activity in a concentration-dependent manner. In mice pretreated with aspirin (10 and 30 mg/kg), followed by challenge with lipopolysaccharide, COX-2 mRNA expression in peritoneal macrophages was markedly suppressed. These findings suggest that salicylate exerts its antiinflammatory action in part by suppressing COX-2 induction, thereby reducing the synthesis of proinflammatory prostaglandins.
TL;DR: The study of chemical reaction dynamics has now advanced to the stage where even comparatively weak van der Waals interactions can no longer be neglected in calculations of the potential energy surfaces of chemical reactions.
Abstract: The van der Waals forces in the entrance valley of the Cl + HD reaction are shown here to play a decisive role in the reaction9s dynamics. Exact quantum mechanical calculations of reactive scattering on a potential energy surface without Cl–HD van der Waals forces predict that the HCl and DCl products will be produced almost equally, whereas the same calculations on a new ab initio potential energy surface with van der Waals forces show a strong preference for the production of DCl. This preference is also seen in crossed molecular beam experiments on the reaction. The study of chemical reaction dynamics has now advanced to the stage where even comparatively weak van der Waals interactions can no longer be neglected in calculations of the potential energy surfaces of chemical reactions.
TL;DR: Viral envelope protein D8L, that binds to chondroitin sulfate on cells, interferes with the adsorption of wild-type vaccinia virions to cells, indicating a role in virus entry.
Abstract: We previously showed that an envelope A27L protein of intracellular mature virions (IMV) of vaccinia virus binds to cell surface heparan sulfate during virus infection. In the present study we identified another viral envelope protein, D8L, that binds to chondroitin sulfate on cells. Soluble D8L protein interferes with the adsorption of wild-type vaccinia virions to cells, indicating a role in virus entry. To explore the interaction of cell surface glycosaminoglycans and vaccinia virus, we generated mutant viruses from a control virus, WR32-7/Ind14K (A27L + D8L + ) to be defective in expression of either the A27L or the D8L gene (A27L + D8L − or A27L − D8L + ) or both (A27L − D8L − ). The A27L + D8L + and A27L − D8L + mutants grew well in BSC40 cells, consistent with previous observations. However, the IMV titers of A27L + D8L − and A27L − D8L − viruses in BSC40 cells were reduced, reaching only 10% of the level for the control virus. The data suggested an important role for D8L protein in WR32-7/Ind14K virus growth in cell cultures. A27L protein, on the other hand, could not complement the functions of D8L protein. The low titers of the A27L + D8L − and A27L − D8L − mutant viruses were not due to defects in the morphogenesis of IMV, and the mutant virions demonstrated a brick shape similar to that of the control virions. Furthermore, the infectivities of the A27L + D8L − and A27L − D8L − mutant virions were 6 to 10% of that of the A27L + D8L + control virus. Virion binding assays revealed that A27L + D8L − and A27L − D8L − mutant virions bound less well to BSC40 cells, indicating that binding of viral D8L protein to cell surface chondroitin sulfate could be important for vaccinia virus entry.
TL;DR: Examination of the relationship between the chemical structure and inhibitory effects of eight flavonoids reveal that the double bond between C2 and C3 in ring C and the OH groups on C3′ and C4′ in ring B are critical for the biological activities.
Abstract: 1. Flavonoids display a wide range of pharmacological properties including anti-inflammatory. Anti-mutagenic, anti-carcinogenic and anti-cancer effects. Here, we evaluated the effects of eight flavonoids on the tumour cell proliferation, cellular protein phosphorylation, and matrix metalloproteinase (MMPs) secretion. 2. Of the flavonoids examined, luteolin (Lu) and quercetin (Qu) were the two most potent agents, and significantly inhibited A431 cell proliferation with IC50 values of 19 and 21 micronM, respectively. 3. The epidermal growth factor (EGF) (10 nM) promoted growth of A431 cells (+25+/-4.6%) and mediated epidermal growth factor receptor (EGFR) tyrosine kinase activity and autophosphorylation of EGFR were inhibited by Lu and Qu. At concentration of 20 micronM, both Lu and Qu markedly decreased the levels of phosphorylation of A431 cellular proteins, including EGFR. 4. A431 cells treated with Lu or Qu exhibited protuberant cytoplasmic blebs and progressive shrinkage morphology. Lu and Qu also time-dependently induced the appearance of a ladder pattern of DNA fragmentation, and this effect was abolished by EGF treatment. 5. The addition of EGF only marginally diminished the inhibitory effect of luteolin and quercetin on the growth rate of A431 cells, treatment of cellular proteins with EGF and luteolin or quercetin greatly reduced protein phosphorylation, indicating Lu and Qu may act effectively to inhibit a wide range of protein kinases, including EGFR tyrosine kinase. 6. EGF increased the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), while Lu and Qu appeared to suppress the secretion of these two MMPs in A431 cells. 7. Examination of the relationship between the chemical structure and inhibitory effects of eight flavonoids reveal that the double bond between C2 and C3 in ring C and the OH groups on C3' and C4' in ring B are critical for the biological activities. 8. This study demonstrates that the inhibitory effects of Lu and Qu, and the stimulatory effects of EGF, on tumour cell proliferation, cellular protein phosphorylation, and MMP secretion may be mediated at least partly through EGFR. This study supports the idea that Lu and Qu may have potential as anti-cancer and anti-metastasis agents.
TL;DR: In this article, the authors proposed that the oblique collision may have played an important role in the late Paleozoic closing of the southern Tianshan oceanic basin in the Tien Shan Range, and they integrated their results with the existing Chinese and international literature on sedimentology, geochemistry, isotopic geochronology, paleontonology and paleomagnetism.
Journal Article•
TL;DR: Although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the twoliposomal drug groups.
Abstract: Sterically stabilized liposome is characterized by a surface coating of polyethylene glycol (PEG) or other polymers that can reduce opsonization of the liposome by plasma proteins. It has a higher plasma area under the concentration-time curve (AUC), which is believed to correlate with better therapeutic efficacy. However, the presence of large molecules on the liposomal surface may reduce the interactions of liposomes with cells and hinder entry of liposomes into the tumor tissue. Using a stable liposomal system composed of distearoyl phosphatidylcholine/cholesterol, we examined the effect of PEG (Mr 2000) on the pharmacokinetics and on the efficacy of liposomal doxorubicin with C-26 syngeneic tumor model in BALB/c mice. The plasma AUC of liposomal doxorubicin with 6 mol-% PEG-modified distearoyl phosphatidylethanolamine (PEG-DSPE) was approximately twice that of liposomal doxorubicin without PEG at various dosages, regardless of whether the mice were tumor-bearing. Paradoxically, the group of mice treated with liposomal doxorubicin without PEG had higher tumor doxorubicin concentrations. The 72-h tumor AUC was 1.44 times that of liposomal doxorubicin with 6% PEG-DSPE. The tumor-accumulation efficiency (AUC(Tumor)/AUC(Plasma)) of liposomal doxorubicin without PEG was 0.87, and this was more than twice that of the liposomal doxorubicin with 6% PEG-DSPE (0.31). At a dose of 10 mg/kg, although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the two liposomal drug groups. In this stable liposome system, surface coating with PEG offered no benefit for liposomal doxorubicin in the C-26 tumor model. To enhance the therapeutic index of liposomal doxorubicin, simply increasing plasma AUC by surface coating with PEG may not be satisfactory.
TL;DR: In this paper, the authors investigated sedimentation dynamics in the East China Sea based on profiles and inventories of 210 Pb, 137 Cs and ex 239,240 Pu in sediment cores collected from various settings in this marginal sea.
TL;DR: DsbC, a periplasmic disulfide isomerase of Gram-negative bacteria, shows more pronounced chaperone activity than does PDI in promoting the in vitroreactivation and suppressing aggregation of denaturedd-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) during refolding.
TL;DR: This paper uses the non-update-in-place scheme to implement a flash memory server and proposes a new cleaning policy that uses a fine-grained method to effectively cluster hot data and cold data in order to reduce cleaning overhead.
TL;DR: This new taxon from the Yixian Formation provides fresh evidence that therizinosauroids are nested within the coelurosaurian theropods, and supports the hypothesis that the filamentous integumentary structures may be homologous to the feathers of birds.
Abstract: Therizinosauroidea (‘segnosaurs’) are little-known group of Asian dinosaurs with an unusual combination of features that, until recently, obscured their evolutionary relationships. Suggested affinities include Ornithischia1, Sauropodomorpha2,3, Theropoda4,5,6,7,8,9,10,11 and Saurischia sedis mutabilis12. Here we describe a new therizinosauroid from the Yixian Formation (Early Cretaceous, Liaoning, China)13. This new taxon provides fresh evidence that therizinosauroids are nested within the coelurosaurian theropods8,9,10,11. Our analysis suggests that several specialized therizinosauroid characters, such as the Sauropodomorpha-like tetradactyl pes1,2, evolved independently within this group. Most interestingly, this new dinosaur has integumentary filaments as in Sinosauropteryx14,15. This indicates that such feather-like structures may have a broad distribution among non-avian theropods, and supports the hypothesis that the filamentous integumentary structures may be homologous to the feathers of birds14,15.
TL;DR: In this paper, a series of carbonaceous adsorbents including PAN-based activated carbon fibers, coal activated carbon and pitch carbon bead were analyzed using Density Functional Theory (DFT).
TL;DR: Sugars play multiple roles in all aspects of plant life, and provide the main respiratory substrates for the generation of energy and metabolic intermediates that drive photosynthesis.
Abstract: Photosynthesis converts solar energy to chemical energy, which then drives the synthesis of sugars from carbon dioxide and water. Sugars play multiple roles in all aspects of plant life. First, they provide the main respiratory substrates for the generation of energy and metabolic intermediates that
TL;DR: A novel method was introduced to predict protein subcellular locations from sequences using sequence data, and this method achieved a prediction accuracy higher than previous methods based on the amino acid composition.
TL;DR: In this paper, the authors considered a general second-order hyperbolic equation defined on an open bounded domain with variable coefficients in both the elliptic principal part and in the first-order terms as well.
TL;DR: It is demonstrated that the combination of nylon microarrays with(33)P-labelled radioactive probes provides 100-fold better sensitivity, making it possible to perform expression profiling experiments using submicrogram amounts of unamplified total RNA from small biological samples.
Abstract: DNA or oligonucleotide arrays are widely used for large-scale expression measurements, using various implementations: macroarrays in which DNA is spotted onto nylon membranes of relatively large dimensions (with radioactive detection) on the one hand; microarrays on glass slides and oligonucleotide chips, both used with fluorescent probes, on the other hand. Nylon micro-arrays with colourimetric detection have also been described recently. The small physical dimensions of miniaturized systems allow small hybridization volumes (2-100 microl) and provide high probe concentrations, in contrast to macroarrays. We show, however, that actual sensitivity (defined as the amount of sample necessary for detection of a given mRNA species) is in fact similar for all these systems and that this is mostly due to the very different amounts of target material present on the respective arrays. We then demonstrate that the combination of nylon microarrays with(33)P-labelled radioactive probes provides 100-fold better sensitivity, making it possible to perform expression profiling experiments using submicrogram amounts of unamplified total RNA from small biological samples. This has important implications in basic and clinical research and makes this alternative approach particularly suitable for groups operating in an academic context.