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Biomedical subjects

Quan Chen

Publications and source records attributed to Quan Chen.

At least 37 records · Page 2Linked to original sources

Compact molten globule-like state of hUBF HMG Box1 at extremely low pH.

Using far and near-UV CD, ANS fluorescence and 2D NMR spectroscopy, an acid-induced partly folded state (A state) at extremely low pH for hUBF HMG Box1 was identified and characterized. As compared to the native state (N), the A state has similar secondary structure, less compact pack with larger amounts of exposed hydrophobic surface, and narrower chemical shift dispersion in (1)H-(15)N HSQC spectrum, which implies that it is a molten globule (MG)-like species. On the other hand, substantial tertiary contacts and cooperative thermal denaturing transition indicate that the A state is closer-relative to the classic MG-to the native folded state. In addition, when the solution pH is adjusted to neutrality, the protein in the A state refolds to the native state easily. All these data suggest that the A state of hUBF HMG Box1 could represent a potential folding intermediate on protein folding pathway.

Anilino Naphthalenesulfonates↗

The internal magnetic field distribution, and single exponential magnetic resonance free induction decay, in rocks.

When fluid saturated porous media are subjected to an applied uniform magnetic field, an internal magnetic field, inside the pore space, is induced due to magnetic susceptibility differences between the pore-filling fluid and the solid matrix. The microscopic distribution of the internal magnetic field, and its gradients, was simulated based on the thin-section pore structure of a sedimentary rock. The simulation results were verified experimentally. We show that the 'decay due to diffusion in internal field' magnetic resonance technique may be applied to measure the pore size distribution in partially saturated porous media. For the first time, we have observed that the internal magnetic field and its gradients in porous rocks have a Lorentzian distribution, with an average gradient value of zero. The Lorentzian distribution of internal magnetic field arises from the large susceptibility contrast and an intrinsic disordered pore structure in these porous media. We confirm that the single exponential magnetic resonance free induction decay commonly observed in fluid saturated porous media arises from a Lorentzian internal field distribution. A linear relationship between the magnetic resonance linewidth, and the product of the susceptibility difference in the porous media and the applied magnetic field, is observed through simulation and experiment.

Journal Article↗

Centric scan SPRITE for spin density imaging of short relaxation time porous materials.

The single-point ramped imaging with T1 enhancement (SPRITE) imaging technique has proven to be a very robust and flexible method for the study of a wide range of systems with short signal lifetimes. As a pure phase encoding technique, SPRITE is largely immune to image distortions generated by susceptibility variations, chemical shift and paramagnetic impurities. In addition, it avoids the line width restrictions on resolution common to time-based sampling, frequency encoding methods. The standard SPRITE technique is however a longitudinal steady-state imaging method; the image intensity is related to the longitudinal steady state, which not only decreases the signal-to-noise ratio, but also introduces many parameters into the image signal equation. A centric scan strategy for SPRITE removes the longitudinal steady state from the image intensity equation and increases the inherent image intensity. Two centric scan SPRITE methods, that is, Spiral-SPRITE and Conical-SPRITE, with fast acquisition and greatly reduced gradient duty cycle, are outlined. Multiple free induction decay (FID) points may be acquired during SPRITE sampling for signal averaging to increase signal-to-noise ratio or for T2* and spin density mapping without an increase in acquisition time. Experimental results show that most porous sedimentary rock and concrete samples have a single exponential T2* decay due to susceptibility difference-induced field distortion. Inhomogeneous broadening thus dominates, which suggests that spin density imaging can be easily obtained by SPRITE.

Geologic Sediments↗

A general solution for catheter position effects for strain estimation in intravascular elastography.

Intravascular ultrasound (US) elastography reveals the elastic properties of vascular tissue and plaque. However, misalignment of the US catheter in the vessel lumen can cause incorrect strain estimation in intravascular US elastography caused by strain projection artifacts. In this paper, we present a general theoretical solution where the impact of catheter eccentricity, tilt and noncoplanar errors on the strain estimates are derived. Appropriate corrections to strain estimates can then be applied with prior knowledge of the catheter position information to reduce the strain projection artifacts. Simulations using a frequency-domain-based algorithm that models intravascular US imaging before and after a specified deformation are presented. The simulations are used to verify the theoretical derivations for two displacement situations (linear and nonlinear) under intraluminal pressure, with and without stress decay. The linear displacement case demonstrates that the correction factor is dependent only on the angle between the US beam and the cross-sectional plane of the vessel. For the nonlinear displacement case, where a l/r stress decay in the displacement is modeled, the correction factor becomes a more complicated function of the azimuthal angle.

Artifacts↗

Cytotoxic activities of new jadomycin derivatives.

Cytotoxic activities of jadomycin B and five new jadomycin derivatives against four cancer cell lines (HepG2, IM-9, IM-9/Bcl-2 and H460) were evaluated. Jadomycin S was most potent against HepG2, IM-9 and IM-9/Bcl-2 while jadomycin F was most potent against H460. Their potencies correlated with the degrees of apoptosis induced. Structure-activity-relationship analyses clearly demonstrate that the side chains of the oxazolone ring derived from the incorporated amino acids make a significant impact on biological activity. Therefore, jadomycin offers an ideal scaffold to manipulate structure and could be exploited to make many novel bioactive compounds with altered activities.

Antibiotics, Antineoplastic↗

The role of Akt on arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation.

The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARgamma and C/EBPalpha and disrupting the interaction between PPARgamma and RXRalpha, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARgamma . Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.

3T3-L1 Cells↗

Correlation of RF signals during angular compounding.

A theoretical analysis of the correlation between radio-frequency (RF) echo signal data acquired from the same location but at different angles is presented. The accuracy of the theoretical results is verified with computer simulations. Refinements to previous analyses of the correlation of RF signals originating from the same spatial location at different angular positions are made. We extend the analysis to study correlation of RF signals coming from different spatial locations and eventually correlation of RF signal segments that intersect at the same spatial location. The theory predicts a faster decorrelation with a change in the insonification angle for longer RF echo signal segments. As the RF signal segment becomes shorter, the decorrelation rate with angle is slower and approaches the limit corresponding to the correlation of RF signals originating from the same spatial location. Theoretical results provide a clear understanding of angular compounding techniques used to improve the signal-to-noise ratio in ultrasonic parametric imaging and in elastography.

Algorithms↗

Optimization of angular and frequency compounding in ultrasonic attenuation estimations.

Previous reports have shown that the variance in ultrasound attenuation measurements is reduced when spatial and frequency compounding were applied in data acquisition and analysis. This paper investigates factors affecting the efficiency of compound attenuation imaging methods. A theoretical expression is derived that predicts the correlation between attenuation versus frequency slope (beta) estimates as a function of the increment between measurement frequencies (deltaf ) and the angular separation between beam lines (Delta (theta)). Theoretical results are compared with those from attenuation measurements on tissue-mimicking phantoms and from simulation data. Both predictions and measurement results show that the correlation between beta estimates as a function of (Delta f ) is independent of the length of the radio frequency (rf) data segment over which beta is derived. However, it decreases with an increase in the length of the data segment used in power spectra estimates. In contrast, the correlation between beta estimates as a function of delta(theta) decreases when the rf data segment length is longer or the frequency of the signal is higher. O 2005 Acoustical Society of America.

Acoustics↗

Ultrasonic noninvasive temperature estimation using echoshift gradient maps: simulation results.

Percutaneous ultrasound-image-guided radiofrequency (rf) ablation is an effective treatment for patients with hepatic malignancies that are excluded from surgical resection due to other complications. However, ablated regions are not clearly differentiated from normal untreated regions using conventional ultrasound imaging due to similar echogenic tissue properties. In this paper, we investigate the statistics that govern the relationship between temperature elevation and the corresponding temperature map obtained from the gradient of the echoshifts obtained using consecutive ultrasound radiofrequency signals. A relationship derived using experimental data on the sound speed and tissue expansion variations measured on canine liver tissue samples at different elevated temperatures is utilized to generate ultrasound radiofrequency simulated data. The simulated data set is then utilized to statistically estimate the accuracy and precision of the temperature distributions obtained. The results show that temperature increases between 37 and 67 degrees C can be estimated with standard deviations of +/- 3 degrees C. Our results also indicate that the correlation coefficient between consecutive radiofrequency signals should be greater than 0.85 to obtain accurate temperature estimates.

Animals↗

[Therapeutic effects of DNA vaccines in a murine model of Mycobacterium tuberculosis infection].

OBJECTIVE: To study the effects and mechanisms of DNA vaccines encoding Mycobacterium tuberculosis antigens on murine Mycobacterium tuberculosis infection. METHODS: C57BL/J6 mice infected with Mycobacterium tuberculosis were treated with normal saline (NS), pCDNA3.1, psIL-12, pcD85B, pcDMPT64, pcD85B + pcDMPT64, and pcD85B + psIL-12 respectively. The numbers of viable bacteria in the lung and the spleen were counted. The levels of IFN-gamma, IL-4 and TNF-alpha of spleen lymphocytes stimulated with PPD were detected with ELISA. Lungs and spleens were prepared for pathological analysis. RESULTS: The pcD85B group (6.99 +/- 0.40 in lung, 5.17 +/- 0.33 in spleen), the psIL-12 group (7.41 +/- 0.50 in lung, 5.31 +/- 0.21 in spleen)and the pcD85B + psIL-12 group (7.64 +/- 0.28 in lung, 5.49 +/- 0.31 in spleen) showed significantly reduced number of colony forming units (lg(-1) CFU/g, x +/- s) in lungs and spleens compared with the control mice (5.76 +/- 0.16 in saline, 5.88 +/- 0.21 in pCDNA3.1), but the difference between the pcD85B group and the pcD85B + psIL-12 group was not significant. pcD85B vaccination induced high levels of IFN-gamma and TNF-alpha. No change of IL-4 was found in all groups. The pathological changes in lungs of the pcD85B group were localized, while those in the control group were extensive. There was no significant changes in the spleen of all groups. CONCLUSIONS: Ag85B DNA vaccination had immunotherapeutic effects, which were associated with a switch to Th1 response and enhanced production of cytokines TNF-alpha and INF-gamma. psIL-12 alone showed therapeutic effect, but it didn't enhance the therapeutic effect of single Ag85B DNA vaccination.

Animals↗

Aggregation behavior of single-walled carbon nanotubes in dilute aqueous suspension.

The aggregation behavior of colloidal single-walled carbon nanotubes (SWNT) in dilute aqueous suspensions was investigated using a novel light scattering measurement technique. The aggregation of SWNT in three suspensions was examined: (1) nanotubes after acid treatment; (2) as-received nanotubes stabilized by a nonionic surfactant; and (3) acid-treated nanotubes with nonionic surfactant. Continuous light scattering measurements of the SWNT suspensions (probing the 38-436 nm length scale) made over two weeks showed that the nanotubes in each sample formed networks with fractal-like structures. The as-received nanotubes were stable over the measurement period, while the acid-treated nanotube suspension showed greater dispersion variability over time, yielding looser structures at large length scales and more compact structures at smaller length scales. The addition of surfactant to the acid-treated suspension significantly enhanced nanotube dispersion.

Journal Article↗

[The estimation of protective efficacy of the fusion gene vaccine encoding tubercle antigen 85B and MPT64 in mice challenged with Mycobacterium tuberculosis].

OBJECTIVE: To evaluate the protective efficacy of the fusion DNA vaccine (AM) encoding tubercle Ag85B and MPT64 in mice infected with Mycobacterium tuberculosis. METHODS: C57BL/6 mice were intramuscularly immunized with the DNA vaccines. The mice were challenged with 10(6) CFU H37Rv via lateral tail vein 35 days later after the third immunization for DNA vaccine groups and 100 days later for BCG vaccinated group. The mice in vaccinated groups and control groups were sacrificed 42 days later following challenge. The lungs and spleens were removed respectively, and the number of CFU in organs and histopathologic changes was determined. The antibody level, IFN-gamma, IL-4 and the survival time in all of the mice were evaluated. RESULTS: Antibody titer of pcDNA/Ag85B + pcDNA/MPT64 group and pcDNA/AM group was higher than that of other groups (P < 0.05). The level of IFN-gamma produced by spleen lymphocytes and spleen lymphocyte proliferation from BCG group, pcDNA/Ag85B, pcDNA/Ag85B + pcDNA/MPT64 group and pcDNA/AM group was higher than that of other groups (P < 0.05). No IL-4 was found in all groups. The number of bacterial colonies in the lungs and spleens was significantly decreased at 6th week postchallenge in all the vaccinated groups (P < 0.05), especially in BCG group (P < 0.01). The pulmonary histopathological changes were observed 6 weeks later following challenge with M. tuberculosis H37Rv. In PBS and pcDNA3.1 groups, the lesion was characterized by seroplastic inflammatory infiltration and lung tissue necrosis, in BCG group by granulomas and numerous macrophages, lymphocytes and a few epithelioid cells. The lesion in pcDNA/Ag85B groups was characterized by seroplastic inflammatory infiltration and a few macrophages, in pcDNA/Ag85B + pcDNA/MPT64 group and pcDNA/AM group, by granulomas, numerous macrophages and lymphocytes. The lesion in spleen was different from the lung and characterized by proliferative lymphocytes and inflammatory infiltration. The results in spleen were similar to those in lung. The survival time of BCG vaccinated mice after challenge with M. tuberculosis H37Rv was longer than that of other groups. The survival time of AM group was longer than that of other DNA vaccine groups. CONCLUSION: The pcDNA/AM can improve the protective efficacy in immunized mice against M. tuberculosis.

Animals↗

Essential role of the voltage-dependent anion channel (VDAC) in mitochondrial permeability transition pore opening and cytochrome c release induced by arsenic trioxide.

The precise molecular mechanism underlying arsenic trioxide (As(2)O(3))-induced apoptosis is a subject of extensive study. Here, we show that clinically relevant doses of As(2)O(3) can induce typical apoptosis in IM-9, a multiple myeloma cell line, in a Bcl-2 inhibitable manner. We confirmed that As(2)O(3) directly induced cytochrome c (cyto c) release from isolated mouse liver mitochondria via the mitochondrial permeability transition pore, and we further identified the voltage-dependent anion channel (VDAC) as a biological target of As(2)O(3) responsible for eliciting cyto c release in apoptosis. First, pretreatment of the isolated mitochondria with an anti-VDAC antibody specifically prevented As(2)O(3)-induced cyto c release. Second, in proteoliposome experiments, VDAC by itself was sufficient to mediate As(2)O(3)-induced cyto c release, which could be specifically inhibited by Bcl-X(L). Third, As(2)O(3) induced mitochondria membrane potential (DeltaPsim) reduction and cyto c release only in the VDAC-expressing, but not in the VDAC-deficient yeast strain. Finally, we found that As(2)O(3) induced the increased expression and homodimerization of VDAC in IM-9 cells, but not in Bcl-2 overexpressing cells, suggesting that VDAC homodimerization could potentially determine its gating capacity to cyto c, and Bcl-2 blockage of VDAC homodimerization represents a novel mechanism for its inhibition of apoptosis.

Animals↗

Simulation study of effects of speed of sound and attenuation on ultrasound lateral resolution.

Experiments have shown that the lateral profile of a point target measured with a clinical ultrasound scanner is wider when the target is embedded in a urethane phantom than when it is in a traditional gel phantom. The behavior has been attributed to the low speed of sound in the urethane material, with the possibility that some of the broadening is caused by increased attenuation in this material. In this paper we apply a computer simulation model to study this behavior. Lateral beam profiles modeled for targets within a medium having a speed of sound and an attenuation matching that of urethane are compared with profiles for targets in a water-based gel. Simulations yield results that agree qualitatively with published experimental results. The lateral profile broadening in urethane is caused by the 6 % mismatch between speed of sound in this material and the speed of sound assumed in the receive focusing and beam forming. Attenuation plays a lesser role than the mismatch of the speed of sound.

Algorithms↗

Mechanical stretch induces mitochondria-dependent apoptosis in neonatal rat cardiomyocytes and G2/M accumulation in cardiac fibroblasts.

Heart remodeling is associated with the loss of cardiomyocytes and increase of fibrous tissue owing to abnormal mechanical load in a number of heart disease conditions. In present study, a well-described in vitro sustained stretch model was employed to study mechanical stretch-induced responses in both neonatal cardiomyocytes and cardiac fibroblasts. Cardiomyocytes, but not cardiac fibroblasts, underwent mitochondria-dependent apoptosis as evidenced by cytochrome c (cyto c) and Smac/DIABLO release from mitochondria into cytosol accompanied by mitochondrial membrane potential (Deltapsi(m)) reduction, indicative of mitochondrial permeability transition pore (PTP) opening. Cyclosporin A, an inhibitor of PTP, inhibited stretch-induced cyto c release, Deltapsi(m) reduction and apoptosis, suggesting an important role of mitochondrial PTP in stretch-induced apoptosis. The stretch also resulted in increased expression of the pro-apoptotic Bcl-2 family proteins, including Bax and Bad, in cardiomyocytes, but not in fibroblasts. Bax was accumulated in mitochondria following stretch. Cell permeable Bid-BH3 peptide could induce and facilitate stretch-induced apoptosis and Deltapsi(m) reduction in cardiomyocytes. These results suggest that Bcl-2 family proteins play an important role in coupling stretch signaling to mitochondrial death machinery, probably by targeting to PTP. Interestingly, the levels of p53 were increased at 12 h after stretch although we observed that Bax upregulation and apoptosis occurred as early as 1 h. Adenovirus delivered dominant negative p53 blocked Bax upregulation in cardiomyocytes but showed partial effect on preventing stretch-induced apoptosis, suggesting that p53 was only partially involved in mediating stretch-induced apoptosis. Furthermore, we showed that p21 was upregulated and cyclin B1 was downregulated only in cardiac fibroblasts, which may be associated with G2/M accumulation in response to mechanical stretch.

Adenoviridae↗

Elastographic versus x-ray CT imaging of radio frequency ablation coagulations: an in vitro study.

Techniques to image elasticity parameters (i.e., elastography) have recently become of great interest to researchers. In this paper we use conventional ultrasound elastography and x-ray CT to image radio frequency (RF) ablation sites of excised canine liver enclosed in gelatin. Thermal coagulations of different sizes were produced by applying the RF procedure for various times and end point temperatures. Dimensions, areas and volumes computed from CT and elastography were compared with those on whole mount pathology specimens. Ultrasound elastography exhibited high contrast for the thermal coagulations and performed better than CT. The correlation between pathology and elastography for this sample set of 40 thermal coagulations (r = 0.94 for volume estimation, r = 0.87 for area estimation) is better than the correlation between pathology and CT (r = 0.89 for volume estimation, r = 0.82 for area estimation).

Animals↗

Correlation of ultrasonic scatterer size estimates for the statistical analysis and optimization of angular compounding.

Ultrasonic scatterer size estimates generally have large variances due to the inherent noise of spectral estimates used to calculate size. Compounding partially correlated size estimates associated with the same tissue, but produced with data acquired from different angles of incidence, is an effective way to reduce the variance without making dramatic sacrifices in spatial resolution. This work derives theoretical approximations for the correlation between these size estimates, and the coherence between their associated spectral estimates, as functions of ultrasonic system parameters. A Gaussian spatial autocorrelation function is assumed to adequately model scatterer shape. Both approximations compare favorably with simulation results, which consider validation near the focus. Utilization of the correlation/coherence expressions for statistical analysis and optimization is discussed. Approximations, such as the invariance of phase and amplitude terms with angle, are made to obtain closed-form solutions to the derived spectral coherence near the focus and permit analytical optimization analysis. Results indicate that recommended parameter adjustments for performance improvement generally depend upon whether, for the system under consideration, the primary source of change in total coherence with rotation is phase term variation due to the change in the relative position of scattering sites, or field amplitude term variation due to beam movement.

Analysis of Variance↗

Harmonic ultrasound fields through layered liquid media.

Harmonic field generation through a layered liquid media is studied experimentally and theoretically. Lateral and axial beam profiles of the fundamental to the 4th harmonic component of the field from a focused, 19-mm diameter transducer were measured using a calibrated hydrophone in a water tank. Measurements were performed before and after the insertion of a cylindrical phantom containing vegetable oil. A frequency domain numerical solution to the "KZK" equation was used to calculate the beam profile, taking into account the acoustic properties of the medium and phantom. Effects of nonlinear propagation, diffraction, attenuation, and reflection are include in the calculation. Agreement within 5% was obtained between measurements and theoretical predictions throughout the mid- and far-field of the transducer for both the uniform path and the layered media. Measurements also were carried out using an unfocused transducer as a receiver. The shape of the axial beam profile using this receiver agreed very well with the theoretical prediction using the "KZK" equation, after accounting for phase variations over the finite-sized detector in the calculated field.

Algorithms↗