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Biomedical subjects

T Zhu

Publications and source records attributed to T Zhu.

At least 19 recordsLinked to original sources
PubMed2007

All-fiber dynamic gain equalizer based on a twisted long-period grating written by high-frequency CO2 laser pulses.

A novel dynamic gain equalizer for flattening Er-doped fiber amplifiers based on a twisted long-period fiber grating (LPFG) induced by high-frequency CO(2) laser pulses is reported for the first time to our knowledge. Experimental results show that its transverse-load sensitivity is up to 0.34 dB/(g.mm(-1)), while the twist ratio of the twisted LPFG is approximately 20 rad/m, which is 7 times higher than that of a torsion-free LPFG. In addition, it is found that the strong orientation dependence of the transverse-load sensitivity of the torsion-free LPFG reported previously has been weakened considerably. Therefore such a dynamic gain equalizer based on the unique transverse-load characteristics of the twisted LPFG provides a much larger adjustable range and makes packaging of the gain equalizer much easier. A demonstration has been carried out to flatten an Er-doped fiber amplifier to +/-0.5 dB over a 32 nm bandwidth.

Journal Article↗
PubMed2007

HOXA1-stimulated oncogenicity is mediated by selective upregulation of components of the p44/42 MAP kinase pathway in human mammary carcinoma cells.

Expression of homeobox A1 (HOXA1) results in oncogenic transformation of immortalized human mammary epithelial cells with aggressive tumor formation in vivo. However, the mechanisms by which HOXA1 mediates oncogenic transformation is not well defined. To identify molecules that could potentially be involved in HOXA1-mediated oncogenic transformation, microarray analysis was utilized to characterize and compare the gene expression pattern in response to forced expression or depletion of HOXA1 in human mammary carcinoma cells. Gene expression profiling identified that genes involved in the p44/42 mitogen-activated protein (MAP) kinase activation pathway (GRB2, MAP kinase kinase (MEK1) and SDFR1) or p44/42 MAP kinase-regulated genes (IER3, EPAS1, PCNA and catalase) are downstream expression targets of HOXA1. Forced expression of HOXA1 increased GRB2 and MEK1 mRNA and protein expression and increased p44/42 MAP kinase phosphorylation, activity and Elk-1-mediated transcription. Use of a MEK1 inhibitor demonstrated that increased p44/42 MAP kinase activity is required for the HOXA1-mediated increase in cell proliferation, survival, oncogenicity and oncogenic transformation. Thus, modulation of the p44/42 MAP kinase pathway is one mechanism by which HOXA1 mediates oncogenic transformation of the human mammary epithelial cell.

Breast Neoplasms↗
PubMed2006

Phellinus linteus sensitises apoptosis induced by doxorubicin in prostate cancer.

It has been demonstrated that the Phellinus linteus (PL) mushroom, which mainly consists of polysaccharides, possesses antitumour activity. The mechanisms of PL against malignant growth remain unknown. The anticancer drug doxorubicin (Dox) has been shown to induce apoptosis via initiating a caspase cascade. In this investigation, we tested the effect of PL on Dox-induced apoptosis in prostate cancer LNCaP cells. We showed that PL or Dox, at relatively low doses, does not induce apoptosis in the cells. However, combination treatment with low doses of PL and Dox results in a synergistic effect on the induction of apoptosis. In this apoptotic process, caspases 8, 3 and BID are cleaved, and the addition of caspase inhibitor z-VADfmk completely blocks apoptosis. In addition, JNK is activated in response to PL or the combination treatment in LNCaP cells. The suppression of JNK partially inhibits the induction of apoptosis elicited by the co-treatment. These findings indicate that PL has a synergistic effect with Dox to activate caspases in prostate cancer LNCaP cells. Our study also suggests that PL has therapeutic potential to augment the magnitude of apoptosis induced by antiprostate cancer drugs.

Agaricales↗
PubMed2006

Downregulation of cAMP-dependent protein kinase inhibitor gamma is required for BMP-2-induced osteoblastic differentiation.

Osteoblasts, normally derived from undifferentiated mesenchymal precursor cells, acquire their characteristic phenotypes when induced by various regulatory factors, one of which is bone morphogenetic protein-2 (BMP-2). Our recent studies suggest that expression of cAMP-dependent protein kinase (PKA) inhibitor G (PKIG) is down-regulated as human mesenchymal stromal cells (MSCs) undergo BMP-2-induced osteoblastic differentiation. This raises our hypothesis that the PKA pathway is involved in osteogenesis. In this report, we demonstrated that PKIG in human MSCs and its murine homologue PKA inhibitor gamma (PKIgamma) in murine pre-myoblast C2C12 cells were down-regulated when these cells were treated with BMP-2. On the contrary, the PKA activity of C2C12 cells was increased upon BMP-2 treatment. Overexpression of PKIgamma in C2C12 cells was shown to repress mRNA expression of early osteoblastic markers osterix and type I collagen while inhibiting the PKA activity. This correlated with decreased alkaline phosphatase (ALP) activities. Furthermore, inhibition of the PKA activity using its specific inhibitor KT5720 was found to have the similar effect, whereas 8-Br-cAMP, a specific PKA activator, accelerated BMP-2-induced ALP activities. Finally, this study showed that BMP-2 treatment promoted activities of transcription regulatory elements including cAMP response element (CRE) and activating protein-1 (AP1). This effect of BMP-2 was diminished in PKIgamma-overexpressed C2C12 cells. Taken together, our results indicate that the activation of the PKA pathway may be one of key BMP-2-activated signaling events that lead to osteogenesis and that downregulation of PKIgamma may be prerequisite for the PKA activation during the osteoblastic differentiation of precursor cells.

Alkaline Phosphatase↗
PubMed2006

Demodulation algorithm for spatial-frequency-division-multiplexed fiber-optic Fizeau strain sensor networks.

A demodulation algorithm for spatial-frequency-division-multiplexed fiber-optic Fizeau strain sensor networks with a large number of sensors is proposed to effectively reduce the cross talk between any two adjacent sensors and hence substantially enhance the multiplexing capability of the network, which is based on the Pisarenko algorithm. The cross talk between two fiber-optic Fizeau sensors is investigated experimentally. The experimental results show that a strain accuracy of better than +/-10 micro permittivity can be achieved even when the cavity length difference is approximately 100 microm. It was demonstrated that the multiplexing capability of the spatial-frequency-division-multiplexed fiber-optic Fizeau sensor network can be approximately 5 times greater than that of the conventional fast-Fourier-transform algorithm, and this can lead to achievement of a sensing network with a multiplexing capability of as many as 1000 Fizeau sensors.

Journal Article↗
PubMed2006

Inhibition of telomerase enhances apoptosis induced by sodium butyrate via mitochondrial pathway.

Telomerase activation represents an early step in carcinogenesis. Increased telomerase activity in cervical cancer suggests a potential target for the development of novel therapeutic drugs. The aim of this study is to investigate the impact of telomerase activity on the biological features of HeLa cells and the possible mechanisms of enhanced apoptosis rate induced by sodium butyrate after telomerase inhibition. We introduced vectors encoding dominate negative (DN)-hTERT, wild-type (WT)-hTERT, or a control vector expressing only a drug-resistance marker into HeLa cells. Thus we assessed the biological effects of telomerase activity on telomere length, cell proliferation, chemosensitivity and radiosensitivity. In order to understand the mechanisms in which DN-hTERT enhances the apoptosis induced by sodium butyrate, we detected the release status of cytochrome c and apoptosis inducing factor (AIF) from mitochondria. Ectopic expression of DN-hTERT resulted in inhibition of telomerase activity, reduction of telomere length, decreased colony formation ability, and loss of tumorigenicity in nude mice. Moreover, DN-hTERT transfected HeLa cells with shortened telomeres were more susceptible to multiple chemotherapeutic agents and radiation. WT-hTERT transfected HeLa cells with longer telomeres exhibited resistance to radiation and chemotherapeutic agents. Our data demonstrate that elevated release level of cytochrome c and AIF from mitochondria might contribute to the enhanced apoptosis in DN-hTERT transfected HeLa cells after treatment with sodium butyrate. Inhibition of telomerase might serve as a promising adjunctive therapy combined with conventional therapy in cervical cancer.

Animals↗
PubMed2006

Observation of organochlorine pesticides in the air of the Mt. Everest region.

High mountains have been suggested to play an important role in the global transport of persistent organic pollutants, yet observation of these pollutants in high mountains is very limited. In the summer of 2002, air samples were collected at Dingri at a height of 4400 m above sea level (m a.s.l.) and at Rongbuk Valley (4976 m a.s.l.) in the Mt. Everest region and analyzed using large volume injection gas chromatography tandem mass spectrometry. The mean concentrations of organochlorine pesticides (OCPs) in the samples were 19.2, 11.2, 7.7, 8.9, 10.4, 27.6, 5.1, 5.1, and 3.7 pg m(-3) for alpha-HCH, beta-HCH, gamma-HCH, HCB, heptachlor, alpha-endosulfan, p,p'-DDE, o,p'-DDT, and p,p'-DDT, respectively. Backward trajectories were used to assess the association between source regions, transport paths, and observed OCP concentrations. During the sampling period, the o,p'-DDT/p,p'-DDT concentration ratios were observed to be between 1.23 and 1.41, much higher than that of technical DDT, indicating the existence of a DDT source other than technical DDTs in the source regions.

Air Pollutants↗
PubMed2006

Heterogeneous decomposition of indoor ammonia in a photoreactor with TiO2-finished cotton fabrics.

Addition of urea-based antifreeze admixtures during cement mixing can make it possible to concrete cement in construction of buildings in cold weather. This, however has led to increasing indoor air pollution due to continuous transformation and emission from urea to gaseous ammonia in indoor concrete walls. In order to control ammonia from indoor concrete walls, aqueous dispersion of nano-titanium dioxide (TiO2) was prepared and mixed with silicone additive to establish a treating bath. Cotton fabrics were finished with this treating bath by using pad-dry-cure process and then characterized by X-Ray Diffractometer, Infrared Fourier Transform Spectrometer and Scanning Electron Microscope. The gaseous ammonia was derived from an environmental condition simulated chamber. The heterogeneous decomposition of gaseous ammonia by UV/TiO2 process in an annular photoreactor fixed with the TiO2-coated cotton fabric was studied under various dosages of aqueous nano-TiO2 dispersion, initial ammonia concentration, relative humidity and gas flow rate. A design equation of surface catalytic kinetics was developed for describing the decomposition of ammonia in air streams by UV/TiO2 process at given operating conditions. Experimental results indicated that increasing dosage of aqueous nano-TiO2 dispersion improved the ammonia decomposition of cotton fabric, which was prepared. At a constant temperature of 25 degrees C, ammonia in the air stream was effective removed by decreasing initial ammonia concentration and gas flow rate. For moisture in the range of 15-65%, when the relatively humidity level was increased to 45%, the decomposition of ammonia was remarkably enhanced, and the decomposition of ammonia could be inhibited by excessive moisture.

Air Pollutants↗
PubMed2006

Effects of number of diffusion gradient directions on derived diffusion tensor imaging indices in human brain.

BACKGROUND AND PURPOSE: The effects of a number of diffusion-encoding gradient directions (NDGD) on diffusion tensor imaging (DTI) indices have been studied previously with theoretic analysis and numeric simulations. In this study, we made in vivo measurements in the human brain to compare different clinical scan protocols and to evaluate their effects on the calculated DTI indices. METHODS: Fifteen healthy volunteers were scanned with a 1.5T MR scanner. Single-shot DTI images were acquired using 3 protocols different in NDGD and number of excitations (NEX) for each direction (NDGD/NEX = 6/10, 21/3, 31/2). Means and standard error of mean (SEM) were calculated and compared in 6 regions of interest (ROIs) for mean diffusivity (D), fractional anisotropy (FA), diffusion tensor eigenvalues (lambda(1), lambda(2), and lambda(3)), and correlation coefficients (r) of these indices among the 3 DTI protocols. RESULTS: At the ROI level, no significant differences were found for the mean and SEM of D and FA among protocols (P > .05). The 6-NDGD protocol, however, yielded higher values for lambda(1) and lambda(2) and lower values for lambda(3) in most ROIs (P < .05) compared with the other protocols. At the voxel level, the correlation between the protocols r(21-31) were higher than r(6-21) and r(6-31) in most ROIs. The correlation of FA among 3 protocols also increased with increasing anisotropy. CONCLUSION: For ROI analyses, different NDGDs lead to similar values of FA and D but different eigenvalues. However, different NDGDs at the voxel level provide varying values. The selection of the NDGD, therefore, should depend on the focus of different DTI applications.

Adult↗
PubMed2005

Emission of ammonia from indoor concrete wall and assessment of human exposure.

Addition of urea-based antifreeze admixtures during cement mixing can make it possible to produce concrete cement in construction of buildings in cold weather; this, however, has led to increasing indoor air pollution due to continuous transformation and emission from urea to gaseous ammonia in indoor concrete wall. It is believed that ammonia is harmful to human body and exposure to ammonia can cause some serious symptoms such as headaches, burns, and even permanent damage to the eyes and lungs. In order to understand the emission of ammonia from indoor concrete wall in civil building and assess the health risk of people living in these buildings, the experimental pieces of concrete wall were first prepared by concreting cement and urea-based antifreeze admixtures to simulate the indoor wall in civil building in this work. Then environmental chamber was adopted for studying the effect of temperature, relative humility and air exchange rate on emission of ammonia from experimental pieces of concrete wall. Also the field experiment was made at selected rooms in given civil buildings. Exposure and potential dose of adult and children exposed to indoor/outdoor ammonia in summer and in winter are calculated and evaluated by using Scenario Evaluation Approach. The results indicated that high air exchange rate leads to decreased ammonia concentration, and elevation of temperature causes increasing ammonia concentration and volatilizing rate in chamber. The complete emission of ammonia from the wall containing urea-based antifreeze admixtures needs more than 10 years in general. Ventilating or improving air exchange can play a significant role in reducing ammonia concentration in actual rooms in field experiments. Urea-based antifreeze admixtures in concrete wall can give rise to high exposure and potential dose, especially in summer. Generally, adults have a high potential dose than children, while children have personal average dose rate beyond adults in the same conditions.

Adult↗
PubMed2005

Tissue factor enhances protease-activated receptor-2-mediated factor VIIa cell proliferative properties.

In addition to its hemostatic functions, factor (F)VIIa exhibits cell proliferative properties as seen in angiogenesis and tumor growth. A role for tissue factor (TF) and protease-activated receptors (PAR)-1 and -2 in cell proliferation remain to be clarified. We tested the hypothesis that FVIIa induces cell proliferation by a mechanism involving TF and PAR-2. Human recombinant FVIIa induced cell proliferation of human BOSC23 cells transfected with plasmid containing human TF DNA sequence. Because DNA primase 1 (PRIM1) plays an essential role in cell proliferation, we used the cloned PRIM1 promoter upstream of the reporter gene chloramphenicol acetyl transferase (CAT) to elucidate the mode of action of FVIIa. FVIIa evoked a dose-dependent increase in cell proliferation and PRIM1 induction, which were markedly potentiated (4-5-fold) by the presence of TF and abrogated by TF antisense oligonucleotide. PRIM1 induction by FVIIa was also abolished by PAR-2 but not by PAR-1 antisense. In contrast, thrombin induced a small increase in CAT activity which was unaffected by TF, but was prevented only by PAR-1 antisense as well as the thrombin inhibitor hirudin. Proliferative properties of FVIIa were associated with a TF-dependent increase in intracellular calcium and were mediated by a concordant phosphorylation of p44/42 MAP kinase. In conclusion, data reveal that FVIIa induces PRIM1 and ensuing cellular proliferation via a TF- and of the PARs entirely PAR-2-dependent pathway, in distinction to that of thrombin which is PAR-1-dependent and TF-independent. We speculate that FVIIa-TF-PAR-2 inhibitors may be effective in suppressing cell proliferation.

Blotting, Northern↗
PubMed2005

Engineering of Bacillus subtilis for enhanced total synthesis of folic acid.

We investigated whether the yield of the B vitamin folic acid could be elevated in Bacillus subtilis. Strategies for increasing the folic acid yield were investigated by employing computer-aided flux analysis and mutation. Controlling the activity of the enzyme pyruvate kinase by placing it under inducible control was one strategy devised to elevate yield while insuring that a rapid growth rate results. Other single mutation strategies included amplifying the expression of the genes in the folate operon and overexpressing the Escherichia coli aroH gene, which encodes 2-dehydro-3-deoxyphosphoheptonate aldolase. The latter could conceivably elevate the abundance of the folic acid precursor, para-aminobenzoic acid. Strains that combined two or more mutations were also constructed. Overall, a strain possessing inducible pyruvate kinase, overexpressed aroH, and increased transcription and translation of genes from the folic operon exhibited the best yield. The yield was eightfold higher than that displayed by the parent B. subtilis 168 strain.

Bacillus subtilis↗
PubMed2003

Effect of simulated microgravity on aged pea seed vigour and related physiological properties.

We used simulated microgravity to treat aged pea seeds, in order to observe its effect on seed vigour and related physiological properties. The result shows that microgravity obviously promotes the germination rate, vitality index, germination index, and keeps the activity of protective enzyme, with conductivity and the content of MDA decreased. These effects gradually disappeared for a certain period after the microgravity administration.

Fabaceae↗
PubMed2003

Phosphorylation of protein kinase C sites in NBD1 and the R domain control CFTR channel activation by PKA.

Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) channel by protein kinase A (PKA) is enhanced by protein kinase C (PKC). However, the mechanism of modulation is not known and it remains uncertain whether PKC acts directly on CFTR or through phosphorylation of an ancillary protein. Using excised patches that had been pre-treated with phosphatases, we found that PKC exposure results in much larger PKA-activated currents and shifts the PKA concentration dependence. To examine if these effects are mediated by direct PKC phosphorylation of CFTR, a mutant was constructed in which serines or threonines at nine PKC consensus sequences on CFTR were replaced by alanines (i.e. the '9CA' mutant T582A/T604A/S641A/T682A/S686A/S707A/S790A/T791A/S809A). In excised patches, 9CA channels had greatly reduced responses to PKA (i.e. 5-10 % that of wild-type), which were not enhanced by PKC pre-treatment, although the mutant channels were still functional according to iodide efflux assays. Stimulation of iodide efflux by chlorophenylthio-cAMP (cpt-cAMP) was delayed in cells expressing 9CA channels, and a similar delay was observed when cells expressing wild-type CFTR were treated with the PKC inhibitor chelerythrine. This suggests that weak activation by PKA in excised patches and slow stimulation of iodide efflux from intact cells are specifically due to the loss of PKC phosphorylation. Finally, PKC caused a slight activation of wild-type channels when added to excised patches after phosphatase pre-treatment but had no effect on the mutant. We conclude that direct phosphorylation of CFTR at one or more of the nine sites mutated in 9CA is required for both the partial activation by PKC and for its modulation of CFTR responses to PKA.

Alkaloids↗
PubMed2003

A metabolic network analysis & NMR experiment design tool with user interface-driven model construction for depth-first search analysis.

A Windows program for metabolic engineering analysis and experimental design has been developed. A graphical user interface enables the pictorial, "on-screen" construction of a metabolic network. Once a model is composed, balance equations are automatically generated. Model construction, modification and information exchange between different users is thus considerably simplified. For a given model, the program can then be used to predict all the extreme point flux distributions that optimize an objective function while satisfying balances and constraints by using a depth-first search strategy. One can also find the minimum reaction set that satisfies different conditions. Based on the identified flux distributions or linear combinations, the user can simulate the NMR and GC/MS spectra of selected signal molecules. Alternately, spectra vectorization allows for the automated optimization of labeling experiments that are intended to distinguish between different, yet plausible flux extreme point distributions. The example provided entails predicting the flux distributions associated with deleting pyruvate kinase and designing 13C NMR experiments that can maximally discriminate between the flux distributions.

Computer Simulation↗
PubMed2003

Efficient and long-term intracardiac gene transfer in delta-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectors.

Intracardiac gene transfer and gene therapy have been investigated with different vector systems. Here we used adeno-associated virus (AAV) vectors to deliver either a reporter gene or a therapeutic gene into the heart of golden Syrian hamsters. The method of gene delivery was direct infusion of the AAV2 vectors into the coronary artery ex vivo in a heterotopically transplanted heart. When an AAV2 vector carrying the Lac-Z gene driven by CMV promoter was delivered into the heart of healthy hamsters, effective gene transfer was achieved in up to 90% of the cardiomyocytes. Lac-Z gene expression persisted for more than 1 year without immune rejection or promoter shutoff. Furthermore, when an AAV2 vector carrying human delta-sarcoglycan gene was similarly delivered into the heart of Bio14.6 Syrian hamster, a congestive heart failure and limb girdle muscular dystrophy animal model, widespread therapeutic gene transfer was achieved in a majority of the cardiomyocytes. Efficient expression of the human delta-sarcoglycan gene in the dystrophic hamster hearts restored the entire sarcoglycan complex that was missing due to the primary deficiency of delta-sarcoglycan. Transgene expression persisted for 4 months (the duration of the study) without immune rejection or promoter shutoff. These results indicate that AAV is a promising vector system for cardiac gene therapy.

Animals↗