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W Liu

Publications and source records attributed to W Liu.

At least 19 recordsLinked to original sources
PubMed2007

Pooling batches in drug stability study by using constant-width simultaneous confidence bands.

One important study objective in drug stability studies is to estimate the shelf-life of a drug. A key statistical problem involved in this is how to assess the practical equivalence of different batches of the same drug so that different batches can be subgrouped to produce a single shelf-life for the drug. In this paper constant-width simultaneous confidence bands are proposed to quantify the magnitude of difference between different batches, with a particular view to establish the practical equivalence of different batches. This approach is suitable for the situation that the intercepts and slopes of the regression lines for the batches cannot be assumed to be equal. It is shown how constant-width simultaneous confidence bands can be easily constructed for the multiple comparison of several general linear regression models. In particular, it is shown that constant-width simultaneous confidence bands have a better chance to establish the equivalence than, and so are preferable to, the hyperbola-shaped simultaneous confidence bands considered.

Drug Stability↗
PubMed2007

Purification, characterization, and crystallization of the components of a biphenyl dioxygenase system from Sphingobium yanoikuyae B1.

Sphingobium yanoikuyae B1 initiates the catabolism of biphenyl by adding dioxygen to the aromatic nucleus to form (+)-cis-(2R, 3S)-dihydroxy-1-phenylcyclohexa-4,6-diene. The present study focuses on the biphenyl 2,3-dioxygenase system, which catalyzes the dioxygenation reaction. This enzyme has been shown to have a broad substrate range, catalyzing the dioxygenation of not only biphenyl, but also three- and four-ring polycyclic aromatic hydrocarbons. Extracts prepared from biphenyl-grown B1 cells contained three protein components that were required for the oxidation of biphenyl. The genes encoding the three components (bphA4, bphA3 and bphA1f,A2f) were expressed in Escherichia coli. Biotransformations of biphenyl, naphthalene, phenanthrene, and benzo[a]pyrene as substrates using the recombinant E. coli strain resulted in the formation of the expected cis-dihydrodiol products previously shown to be produced by biphenyl-induced strain B1. The three protein components were purified to apparent homogeneity and characterized in detail. The reductase component (bphA4), designated reductase(BPH-B1), was a 43 kD monomer containing one mol FAD/mol reductase(BPH-B1). The ferredoxin component (bphA3), designated ferredoxin(BPH-B1), was a 12 kD monomer containing approximately 2 g-atoms each of iron and acid-labile sulfur. The oxygenase component (bphA1f,A2f), designated oxygenase(BPH-B1), was a 217 kD heterotrimer consisting of alpha and beta subunits (approximately 51 and 21 kD, respectively). The iron and acid-labile sulfur contents of oxygenase(BPH-B1) per alphabeta were 2.4 and 1.8 g-atom per mol, respectively. Reduced ferredoxin(BPH-B1) and oxygenase(BPH-B1) each gave EPR signals typical of Rieske [2Fe-2S] proteins. Crystals of reductase(BPH-B1), ferredoxin(BPH-B1) and oxygenase(BPH-B1 )diffracted to 2.5 A, 2.0 A and 1.75 A, respectively. The structures of the three proteins are currently being determined.

Amino Acid Sequence↗
PubMed2007

Construction and characterization of efficient, stable and safe replication-deficient foamy virus vectors.

As serious side effects affected recent virus-mediated gene transfer studies, novel vectors with improved safety profiles are urgently needed. In the present study, replication-deficient retroviral vectors based on feline foamy virus (FFV) were constructed and analyzed. The novel FFV vectors are devoid of almost the complete env gene plus the internal promoter - accessory bel gene cassette including the gene for the viral transcriptional transactivator Bel1/Tas. In these Bel1/Tas-independent vectors, expression of the lacZ (beta-galactosidase) marker gene is directed by the heterologous, constitutively active human ubiquitin C promoter (ubi). Env-transcomplemented vectors have un-concentrated titers of more than 10(5) transducing units/ml. The vectors allow efficient transduction of a broad array of diverse target cells, which can be increased by repeated vector exposure. However, the number of lacZ marker gene expressing cells decreased slightly upon serial passages of the transduced cells. Vectors carrying a self-inactivating (SIN) deletion of the TATA box and most parts of the viral promoter were not rescued by wt FFV whereas those with the intact or a partially deleted promoter were readily reactivated. This finding indicates that the viral promoters are in fact non-functional, pointing to a highly advantageous safety profile of these new FFV-ubi-lacZ-SIN vectors.

Animals↗
PubMed2007

Anti-CD45RB monoclonal antibody prolongs renal allograft survival in cynomolgus monkeys.

Previously, an anti-CD45RB monoclonal antibody (mAb) has been shown to induce murine allograft tolerance. The present study was performed to assess the ability of an anti-human CD45RB mAb to prevent rejection in a monkey MHC-mismatched kidney transplant model. The recipients were allocated into the following treatment groups: (1) isotype control IgG; (2) mouse anti-human CD45RB IgG1 (6G3); (3) human-mouse chimeric anti-CD45RB-IgG1 (C6G3-IgG1); (4) human-mouse chimeric anti-CD45RB-IgG2 (C6G3-IgG2); (5) tacrolimus at a subtherapeutic dose and (6) tacrolimus and C6G3-IgG1 in combination. Monotherapy with anti-CD45RB mAb significantly prolonged renal allograft survival to a median survival of 21 days. Adding a subtherapeutic dose of tacrolimus improved the efficacy of the anti-CD45RB mAb, achieving a median survival of 85 days, whereas a subtherapeutic dose of tacrolimus alone only moderately prolonged survival to 27 days. Treatment with anti-CD45RB mAb resulted in an alteration of the CD45RB(hi) : CD45RB(lo) cell ratio in the peripheral blood. We have, for the first time, demonstrated that an anti-human CD45RB mAb (6G3) can prolong graft survival. Induction with an anti-CD45RB mAb improves the efficacy of tacrolimus in the prevention of rejection. These encouraging results indicate that an anti-CD45RB mAb may be valuable in future clinical transplantation.

Animals↗
PubMed2006

CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases.

CEACAM1, also known as biliary glycoprotein (BGP), CD66a, pp120 and C-CAM1, is a member of the CEA immunoglobulin superfamily. CEACAM1 is a putative tumor suppressor based on diminished expression in some solid neoplasms such as colorectal carcinoma. However, CEACAM1 is overexpressed in some tumors such as non-small cell lung cancer. To clarify the mechanism of action of this cell adhesion molecule, we studied thyroid carcinoma that has a spectrum of morphologies and variable behavior allowing separation of proliferation from invasion and metastasis. CEACAM1 is expressed in thyroid carcinoma cell lines derived from tumors that exhibit aggressive behavior. Introduction of CEACAM1 into endogenously deficient WRO cells resulted in reduced cell cycle progression associated with p21 upregulation and diminished Rb phosphorylation. Forced CEACAM1 expression enhanced cell-matrix adhesion and migration and promoted tumor invasiveness. Conversely, small interfering RNA (siRNA)-mediated downregulation of CEACAM1 expression in MRO cells accelerated cell cycle progression and significantly enhanced tumor size in xenografted mice. CEACAM1 is not appreciably expressed in normal thyroid tissue or benign thyroid tumors. In a human thyroid tissue array, CEACAM1 reactivity was associated with metastatic spread but not with increased tumor size. These findings identify CEACAM1 as a unique mediator that restricts tumor growth whereas increasing metastatic potential. Our data highlight a complex repertoire of actions providing a putative mechanism underlying the spectrum of biologic behaviors associated with thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed2006

In meso structure of the cobalamin transporter, BtuB, at 1.95 A resolution.

Crystals of the apo form of the vitamin B12 and colicin receptor, BtuB, that diffract to 1.95 A have been grown by the membrane-based in meso technique. The structure of the protein differs in several details from that of its counterpart grown by the more traditional, detergent-based (in surfo) method. Some of these differences include (i) the five N-terminal residues are resolved in meso, (ii) residues 57-62 in the hatch domain and residues 574-581 in loop 21-22 are disordered in meso and are ordered in surfo, (iii) residues 278-287 in loop 7-8 are resolved in meso, (iv) residues 324-331 in loop 9-10, 396-411 in loop 13-14, 442-458 in loop 15-16 and 526-541 in loop 19-20 have large differences in position between the two crystal forms, as have residues 86-96 in the hatch domain, and (v) the conformation of residues 6 and 7 in the Ton box (considered critical to signal transduction and substrate transport) are entirely different in the two structures. Importantly, the in meso orientation of residues 6 and 7 is similar to that of the vitamin B12-charged state. These data suggest that the "substrate-induced" 180 degrees -rotation of residues 6 and 7 reported in the literature may not be a unique signalling event. The extent to which these findings agree with structural, dynamic and functional insights gleaned from site-directed spin labelling and electron paramagnetic resonance measurements is evaluated. Packing in in meso grown crystals is dense and layered, consistent with the current model for crystallogenesis of membrane proteins in lipidic mesophases. Layered packing has been used to locate the transmembrane hydrophobic surface of the protein. Generally, this is consistent with tryptophan, tyrosine, lipid and CalphaB-factor distributions in the protein, and with predictions based on transfer free energy calculations.

Amino Acids↗
PubMed2006

ErbB receptor regulation by dexamethasone in mouse type II epithelial cells.

Glucocorticoids stimulate foetal surfactant synthesis. Therefore, they are used in impending pre-term birth. One mechanism of action on surfactant synthesis is through the induction of neuregulin (NRG) secretion by foetal lung fibroblasts. The direct effects on signalling pathways, and specifically on erbB receptors in foetal type II cell surfactant synthesis, are less well understood. The present authors studied the effect of known promoters of foetal surfactant synthesis (namely dexamethasone and mature (i.e. NRG-containing) fibroblast-conditioned medium (FCM)) on erbB receptor activation, protein content and dimerisation patterns in foetal mouse lung type II cells. Dexamethasone inhibited surfactant synthesis in immature type II cells at day (d)16 of gestation, while the mature FCM had stimulatory effects. Both treatments directly stimulated surfactant synthesis in more mature (d17) cells. At this gestational day, dexamethasone had only a small effect on phosphorylation, but it stimulated the protein levels of all four erbB receptors. Dexamethasone effects were distinct from those of mature FCM, which stimulated both protein content and phosphorylation of all erbB receptors and of the signalling intermediate phospholipase Cgamma. Dexamethasone modulated erbB receptor dimerisation patterns, such that erbB2 became the main dimerisation partner for erbB4. In conclusion, dexamethasone signalling involves erbB receptors in foetal type II cells, in a manner similar to, but distinct from, neuregulin-containing fibroblast-conditioned medium signalling.

Animals↗
PubMed2006

Fibrin fibers have extraordinary extensibility and elasticity.

Blood clots perform an essential mechanical task, yet the mechanical behavior of fibrin fibers, which form the structural framework of a clot, is largely unknown. By using combined atomic force-fluorescence microscopy, we determined the elastic limit and extensibility of individual fibers. Fibrin fibers can be strained 180% (2.8-fold extension) without sustaining permanent lengthening, and they can be strained up to 525% (average 330%) before rupturing. This is the largest extensibility observed for protein fibers. The data imply that fibrin monomers must be able to undergo sizeable, reversible structural changes and that deformations in clots can be accommodated by individual fiber stretching.

Blood Coagulation↗
PubMed2006

Genetic variation in the COX-2 gene and the association with prostate cancer risk.

COX-2 is a key enzyme in the conversion of arachidonic acid to prostaglandins. The prostaglandins produced by COX-2 are involved in inflammation and pain response in different tissues in the body. Accumulating evidence from epidemiologic studies, chemical carcinogen-induced rodent models and clinical trials indicate that COX-2 plays a role in human carcinogenesis and is overexpressed in prostate cancer tissue. We examined whether sequence variants in the COX-2 gene are associated with prostate cancer risk. We analyzed a large population-based case-control study, cancer prostate in Sweden (CAPS) consisting of 1,378 cases and 782 controls. We evaluated 16 single nucleotide polymorphisms (SNPs) spanning the entire COX-2 gene in 94 subjects of the control group. Five SNPs had a minor allele frequency of more than 5% in our study population and these were genotyped in all case patients and control subjects and gene-specific haplotypes were constructed. A statistically significant difference in allele frequency between cases and controls was observed for 2 of the SNPs (+3100 T/G and +8365 C/T), with an odds ratio of 0.78 (95% CI=0.64-0.96) and 0.65 (95% CI=0.45-0.94) respectively. In the haplotype analysis, 1 haplotype carrying the variant allele from both +3100 T/G and +8365 C/T, with a population frequency of 3%, was also significantly associated with decreased risk of prostate cancer (p=0.036, global simulated p-value=0.046). This study supports the hypothesis that inflammation is involved in prostate carcinogenesis and that sequence variation within the COX-2 gene influence the risk of prostate cancer.

Aged↗
PubMed2006

Preventing renal ischemia-reperfusion injury using small interfering RNA by targeting complement 3 gene.

The complement system is one of the important mediators of renal ischemia-reperfusion injury (IRI). We hypothesized that efficient silencing of C3, which is the central component on which all complement activation pathways converge, could be achieved using small interfering RNA (siRNA), and that this would result in overall inhibition of complement activation, thereby preventing IRI in kidneys. A series of experiments was conducted, using a mouse model of IRI and vector-delivered C3-specific siRNA. We demonstrated the following: (1) renal expression of C3 increases as a result of IRI; (2) by incorporation into a pRNAT U6.1 vector, siRNA can be delivered to renal cells in vivo; (3) systemically delivered siRNA is effective in reducing the expression of C3 in an experimentally induced mouse kidney model of IRI; (4) similarly, siRNA reduces complement-mediated IRI-related effects, both in terms of renal injury (as evidenced by renal function and histopathology examination) and mouse mortality and (5) silencing the production of C3 diminishes in vivo production of TNF-alpha. This study implies that siRNA represents a novel approach to preventing IRI in kidneys and might be used in a variety of clinical settings, including transplantation and acute tubular necrosis.

Animals↗
PubMed2006

Arabidopsis thaliana fatty acid alpha-dioxygenase-1: evaluation of substrates, inhibitors and amino-terminal function.

Plant alpha dioxygenases (PADOX) convert fatty acids to 2-hydroperoxy products that are important in plant signaling pathways. The PADOX amino-terminal domain is distinct from that in other myeloperoxidase-family hemoproteins, and the positional specificity and prosthetic group of PADOX distinguish them from the non-heme iron plant lipoxygenases. The constraints of the PADOX active site on potential substrates are poorly understood and only limited structure-function and mechanistic information is available for these enzymes. We developed several bacterial and insect cell systems for expression of recombinant Arabidopsis thaliana PADOX1 and evaluated the enzyme's substrate and inhibitor profiles and explored the functional role of the amino-terminal domain. Substrate specificity studies gave the following relative oxygenase activity values: linolenate, 1.00; linoleate, 0.95; oleate, 0.84; palmitoleate, 0.69; myristate, 0.23; palmitate, 0.17; and gamma-linolenate, 0.16. Methyl esters of myristate, linoleate and linolenate were not oxygenated. 3-Thiamyristate was the only oxygenase substrate that produced pronounced enzyme self-inactivation during catalysis. 3,4-Dehydromyristate inactivated the oxygenase without appreciable oxygen consumption. Several compounds inhibited oxygenase activity, including catechol (K(i) approximately 90 microM), divalent zinc ion (K(i) approximately 50 microM), N,N,N',N'-tetramethyl-p-phenylenediamine (K(i) approximately 20 microM) and cyanide ion (K(i) approximately 5 microM). Zinc ion did not change the K(m) values for linoleate or oxygen, or the K(i) value for cyanide, indicating that zinc acts at a distinct site from the other compounds. Gel-filtration chromatography revealed considerable variation in oligomeric state of recombinant PADOX1 produced in the various expression systems, but oligomeric state was not correlated with activity. Deletion of the first eight or fourteen PADOX1 residues in a NuSA-PADOX1 fusion protein led to 13 and 83% decreases in activity, respectively, indicating the N-terminal region is important for normal catalytic activity.

Arabidopsis↗
PubMed2006

Laser ultrasonic characterization of adhesive bonds between epoxy coating and aluminum substrate.

Nanosecond pulsed laser irradiation through transparent epoxy bonded to aluminum substrate excites wide-band ultrasonic waves at the bonded interface. The normal displacements on the rear surface of aluminum produced by the direct and multi-reflected longitudinal waves in the coating layer are detected by a laser interferometer. The amplitude of the reflected signal depends on the properties of the coating/substrate interface, which is described by terms of the interfacial stiffness using a spring boundary model. The waveforms at the epicenter versus interfacial stiffness are simulated and found to be in good agreement with experimental results. The relation between the interfacial stiffness and the amplitude ratio of the reflected and direct waves is thus established. An image of amplitude ratio of a specimen (null 10 mm) is obtained from the epicenter waveforms recorded by a laser ultrasonic scanning system, which shows the distribution of bond quality on the bonding interface.

Journal Article↗
PubMed2006

Characteristics of calcaneus quantitative ultrasound normative data in Chinese mainland men and women.

INTRODUCTION: Quantitative ultrasound (QUS) assessment at the calcaneus, as a safe and reliable method for evaluating skeletal status, is rapidly gaining in popularity. Assessment by QUS provides three parameters of skeletal status: broadband ultrasound attenuation (BUA), speed of sound (SOS) and derived data-stiffness index (STI). The objective of the present study was firstly to determine the normative QUS data on healthy Chinese mainland men and women and secondly to investigate the effects of sex, age and body size on these three QUS parameters. METHODS: A study cohort consisting of 725 healthy Chinese women and 568 men aged 10-83 years participated in this investigation. The three QUS parameters all exhibited a characteristic mild rise-then-fall pattern with increasing age in both sexes. Younger men and women had similar QUS values, while older women had lower values than older men. Age-related differences were more pronounced among females. Pearson's correlation and regression analysis showed that weight was a major determinant of QUS in both sexes, along with age. RESULTS: There were some discrepancies between our data and results from other populations, even when the same type of QUS instrument was used, probably as a result of various factors, including ethnic, life-style environment and diet, among others. CONCLUSIONS: These normative data will be useful for comparing the results of individual studies, predicting fracture risk of Chinese men and women and determining diagnostic criteria of osteoporosis by QUS.

Adolescent↗
PubMed2006

Remote time-resolved filament-induced breakdown spectroscopy of biological materials.

We report, for what we believe to be the first time, on the feasibility of remote time-resolved filament-induced breakdown spectroscopy (FIBS) of biological materials. The fluorescence from egg white and yeast powder, induced by femtosecond laser pulse filamentation in air, was detected in the backward direction with targets located 3.5 m away from the detection system. The remarkably distinct spectra of egg white and yeast allow us to propose that this technique, time-resolved FIBS, could be potentially useful for remote detection and identification of harmful biological agents.

Connective Tissue↗
PubMed2006

Assessment of low quantitative ultrasound values of calcaneus in Chinese mainland women.

Calcaneus quantitative ultrasound (QUS) assessment is a safe and reliable method for evaluating skeletal status. Until now, considerable data have been accumulated on the distribution of QUS in Caucasian populations, whereas such data are still insufficient in Asian populations, especially in Chinese mainland. The present study aimed to obtain the distribution characteristic of calcaneus QUS in healthy Chinese women, and to further investigate the distribution of low bone mass by QUS stiffness index (SI). This study included 2,498 healthy Chinese females aged 10-87 yr. The QUS exhibited a characteristic mild rise and then fall pattern with increasing age. Age, body height, and weight were significant influencing factors on SI, especially age and weight. The prevalence of osteoporosis detected using instrument-derived T-score or internal T-score was different from that calculated according to calcaneus bone mass density (BMD) previously reported. Furthermore, between instrument-derived T-scores and internal T-scores, there were also significant differences. We concluded that the World Health Organization criteria from BMD may not be appropriate for QUS, and the instrument-derived T-score may also not be appropriate for the studied population. The results will be useful for predicting fracture risk of Chinese women and determining diagnostic criteria of osteoporosis by QUS.

Adolescent↗
PubMed2006

Single molecule mechanical probing of the SNARE protein interactions.

Exocytotic release of neurotransmitters is mediated by the ternary soluble N-ethyl maleimide-sensitive fusion protein attachment protein receptors (SNAREs) complex, comprised of syntaxin (Sx), synaptosome-associated protein of 25 kDa (SNAP25), and synaptobrevin 2 (Sb2). Since exocytosis involves the nonequilibrium process of association and dissociation of bonds between molecules of the SNARE complex, dynamic measurements at the single molecule level are necessary for a detailed understanding of these interactions. To address this issue, we used the atomic force microscope in force spectroscopy mode to show from single molecule investigations of the SNARE complex, that Sx1A and Sb2 are zippered throughout their entire SNARE domains without the involvement of SNAP25. When SNAP25B is present in the complex, it creates a local interaction at the 0 (ionic) layer by cuffing Sx1A and Sb2. Force loading rate studies indicate that the ternary complex interaction is more stable than the Sx1A-Sb2 interaction.

Animals↗
PubMed2006

The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance.

Birt-Hogg-Dubé syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The BHD locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene (BHD) were identified in a panel of BHD families. Using RNA interference to decrease expression of the Drosophila BHD homolog (DBHD), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of DBHD gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either unpaired (upd) or decapentaplegic (dpp). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human.

Amino Acid Sequence↗