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Biomedical subjects

Y Han

Publications and source records attributed to Y Han.

At least 19 recordsLinked to original sources
PubMed2006

Label-free detection of single nucleotide polymorphisms utilizing the differential transfer function of field-effect transistors.

We present a label-free method for the detection of DNA hybridization, which is monitored by non-metallized silicon field-effect transistors (FET) in a microarray approach. The described method enables a fast and fully electronic readout of ex situ binding assays. The label-free detection utilizing the field-effect is based on the intrinsic charge of the DNA molecules and/or on changes of the solid-liquid interface impedance, when biomolecules bind to the sensor surface. With our sensor system, usually a time-resolved, dc readout is used. In general, this FET signal suffers from sensor drift, temperature drift, changes in electrolyte composition or pH value, influence of the reference electrode, etc. In this article, we present a differential ac readout concept for FET microarrays, which enables a stable operation of the sensor against many of these side-parameters, reliable readout and a possibility for a quick screening of large sensor arrays. We present the detection of point mutations in short DNA samples with this method in an ex situ binding assay.

Biosensing Techniques↗
PubMed2006

Brownian motion of an ellipsoid.

We studied the Brownian motion of isolated ellipsoidal particles in water confined to two dimensions and elucidated the effects of coupling between rotational and translational motion. By using digital video microscopy, we quantified the crossover from short-time anisotropic to long-time isotropic diffusion and directly measured probability distributions functions for displacements. We confirmed and interpreted our measurements by using Langevin theory and numerical simulations. Our theory and observations provide insights into fundamental diffusive processes, which are potentially useful for understanding transport in membranes and for understanding the motions of anisotropic macromolecules.

Journal Article↗
PubMed2006

Field-effect sensors with charged macromolecules: characterisation by capacitance-voltage, constant-capacitance, impedance spectroscopy and atomic-force microscopy methods.

Field-effect-based capacitive electrolyte-insulator-semiconductor (EIS) sensors have been utilised for the deoxyribonucleic acid (DNA) immobilisation and hybridisation detection as well as for monitoring the layer-by-layer adsorption of polyelectrolytes (anionic poly(sodium 4-styrene sulfonate) (PSS) and cationic poly(allylamine hydrochloride) (PAH)). The EIS sensors with charged macromolecules have been systematically characterised by capacitance-voltage, constant-capacitance, impedance spectroscopy and atomic-force microscopy methods. The effect of the number and polarity of the polyelectrolyte layers on the shift of the capacitance-voltage curves has been investigated. Alternating potential shifts of about 30-90 mV have been observed after the adsorption of each polyanion and polycation layer, respectively. The DNA immobilisation and hybridisation signals were 35-55 and 24-33 mV, respectively. The possible mechanisms for the sensor responses are discussed.

DNA↗
PubMed2006

Restoration of shp1 expression by 5-AZA-2'-deoxycytidine is associated with downregulation of JAK3/STAT3 signaling in ALK-positive anaplastic large cell lymphoma.

Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK+ ALCL) is characterized by constitutive activation of the Janus kinase (JAK)3/signal transducers and activators of transcription 3 (STAT3) signaling pathway. SHP1, a tyrosine phosphatase that negatively regulates JAK/STAT, is frequently absent in ALK+ ALCL owing to gene methylation. To test the hypothesis that loss of SHP1 contributes to JAK3/STAT3 activation in ALK+ ALCL cells, we induced SHP1 expression using 5-aza-2'-deoxycytidine (5-AZA), an inhibitor of DNA methyltransferase, in ALK+ ALCL cell lines, and correlated with changes in the JAK3/STAT3 pathway. 5-AZA gradually restored SHP1 expression in Karpas 299 and SU-DHL-1 cells over 5 days. The initially low level of SHP1 expression did not result in significant changes to the expression or tyrosine phosphorylation of JAK3 and STAT3. However, higher levels of SHP1 seen subsequently correlated with substantial decreases in JAK3 and pJAK3, followed by pSTAT3 (but not STAT3). Importantly, the decrease in JAK3 was abrogated by MG132, a proteasome inhibitor. 5-AZA induced no significant increase in apoptosis but it sensitized ALCL cells to doxorubicin-induced apoptosis. Our findings support the concept that loss of SHP1 contributes to the constitutive activation of JAK3/STAT3 in ALK+ ALCL cells. SHP1 appears to downregulate JAK3 by two mechanisms: tyrosine dephosphorylation and increased degradation via the proteasome pathway.

Anaplastic Lymphoma Kinase↗
PubMed2006

Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis.

It has been shown that acetylcholinesterase (AChE) expression was induced during apoptosis and the anti-sense oligonucleotides and siRNA of AChE may prevent apoptosis in various cell types. However, the mechanisms underlying AChE upregulation remain elusive. We demonstrated here that c-Jun NH2-terminal kinase (JNK) could mediate AChE expression. In this study, both etoposide and excisanin A, two anticancer agents, induced apoptosis in colon cancer cell line SW620 as determined by Annexin V staining, the cleavage of caspase-3 and the proteolytic degradation of poly (ADP-ribose) polymerase (PARP). The results showed that both the agents upregulated AChE in SW620 cells. In the meantime, JNK was also activated and the expression and phosphorylation of c-Jun increased in SW620 cells exposed to the two agents. The induced AChE mRNA and protein expression could be blocked by SP600125, a specific inhibitor of SAPK/JNK, and small interfering RNA directed against JNK1/2. Transfection with adenovirus-mediated dominant negative c-Jun also blocked the upregulation of AChE expression. Together, these results suggest that AChE expression may be mediated by the activation of JNK pathway during apoptosis through a c-Jun-dependent mechanism.

Acetylcholinesterase↗
PubMed2006

Anomalous decrease in groundwater radon before the Taiwan M6.8 Chengkung earthquake.

On December 10, 2003, an earthquake of magnitude (M) 6.8, the strongest since 1951, occurred near the Chengkung area in eastern Taiwan. Approximately 65 d prior to the 2003 Chengkung earthquake, precursory changes in the groundwater radon concentration were observed at the Antung radon-monitoring station located 20 km from the epicenter. The radon anomaly was a decrease from a background level of 28.9 BqL(-1) to a minimum of 12.2 BqL(-1). Observations at the Antung hot spring suggest that the groundwater radon, when observed under suitable geological conditions, can be a sensitive tracer for strain changes in the crust preceding an earthquake.

Disasters↗
PubMed2006

N-acetylphytosphingosine-induced apoptosis of Jurkat cells is mediated by the conformational change in Bak.

N-acetylphytosphingosine (NAPS), a sphingolipid derivative, is one of the well-known signal molecules that mediates various cellular functions, including cell growth, differentiation, and apoptosis. In this study, we demonstrated that NAPS induces apoptosis of Jurkat cells by activating Bak, but not Bax, which are both members of a proapoptotic subfamily of the Bcl-2 proteins. NAPS activated caspase-8 in a FADD-independent manner, but the lack of caspase-8 did not suppress the activation of caspase-3 and -9 and cell death, indicating that caspase-8 activation does not play an important role in NAPS-induced cell death. The overexpression of Bcl-xL, an anti-apoptotic protein, completely inhibited the activation of the caspases and apoptosis, assuming that NAPS-induced apoptosis was initiated by the mitochondria. The expression levels of pro- and anti-apoptotic Bcl-2 family members were not changed by the NAPS treatment. However, Bad was translocated from the cytosol into the mitochondria, where it bound to Bcl-xL, and Bak was dissociated from Bcl-xL and conformationally changed. Taken together, these findings indicate that NAPS induced apoptosis of Jurkat cells in a mitochondria-dependent manner that was controlled by the translocation of Bad and the conformational change in Bak.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Obesity risk associated with the K121Q polymorphism of the glycoprotein PC-1 gene.

BACKGROUND: Obesity is considered to be a multifactorial trait resulting from the combined influence of genetic and environmental determinants. Insulin resistance plays an important role in the development of obesity. Plasma-cell membrane differentiation antigene-1 (PC-1) inhibits insulin receptor signalling when overexpressed and thus causes insulin resistance. PC-1 gene polymorphism might be associated with adipocyte metabolism disturbance and energy imbalance. The purpose of this study was to determine whether K121Q polymorphism in PC-1 gene is involved in obesity susceptibility in Chinese Han population. METHODS: The genotype of the polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism analysis for 338 unrelated subjects of Beijing, China. Their Body mass index (BMI), plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL), free fatty acid (FFA) and insulin level were measured. Chi-square analyses were applied to test the significance differences in genotypic and allelic frequencies. Association studies were undertaken using the t-test and logistic regression analyses. RESULTS: The obese had significantly higher frequency of KQ/QQ genotype or Q allele than non-obese in females (26.7% vs. 10.9%, p = 0.014 and 13.3% vs. 5.5%, p = 0.021). Significant elevation of insulin amongst the Q121 carrier women in obesity individuals and higher FFA level of Q121 carrier men in non-obese controls (BMI < or = 23 kg/m2) were observed. Binary logistic regression analysis revealed that PC-1 genotype together with higher glucose, total cholesterol, triglyceride and serum HDL were independently associated with the presence of obesity. CONCLUSIONS: The observed genotype distributions revealed a significant association of PC-1 K121Q with obesity. PC-1 Q121 carriers are more likely to be insulin-resistant or get fatter in respect to KK subjects and carriers of the Q allele are at higher risk for the development of obesity in female.

Adult↗
PubMed2006

Application and utilization of chemoinformatics tools in lead generation and optimization.

The process of Drug Discovery is a complex and high risk endeavor that requires focused attention on experimental hypotheses, the application of diverse sets of technologies and data to facilitate high quality decision-making. All is aimed at enhancing the quality of the chemical development candidate(s) through clinical evaluation and into the market. In support of the lead generation and optimization phases of this endeavor, high throughput technologies such as combinatorial/high throughput synthesis and high throughput and ultra-high throughput screening, have allowed the rapid analysis and generation of large number of compounds and data. Today, for every analog synthesized 100 or more data points can be collected and captured in various centralized databases. The analysis of thousands of compounds can very quickly become a daunting task. In this article we present the process we have developed for both analyzing and prioritizing large sets of data starting from diversity and focused uHTS in support of lead generation and secondary screens supporting lead optimization. We will describe how we use informatics and computational chemistry to focus our efforts on asking relevant questions about the desired attributes of a specific library, and subsequently in guiding the generation of more information-rich sets of analogs in support of both processes.

Chemistry, Pharmaceutical↗
PubMed2004

Protein crystal growth on board Shenzhou 3: a concerted effort improves crystal diffraction quality and facilitates structure determination.

The crystallization of 16 proteins was carried out using 60 wells on board Shenzhou 3 in 2002. Although the mission was only 7 days, careful and concerted planning at all stages made it possible to obtain crystals of improved quality compared to their ground controls for some of the proteins. Significantly improved resolutions were obtained from diffracted crystals of 4 proteins. A complete data set from a space crystal of the PEP carboxykinase yielded significantly higher resolution (1.46A vs. 1.87A), I/sigma (22.4 vs. 15.5), and a lower average temperature factor (29.2A(2) vs. 42.9A(2)) than the best ground-based control crystal. The 3-D structure of the enzyme is well improved with significant ligand density. It has been postulated that the reduced convection and absence of macromolecule sedimentation under microgravity have advantages/benefits for protein crystal growth. Improvements in experimental design for protein crystal growth in microgravity are ongoing.

Crystallization↗
PubMed2004

Coulomb sink: a novel coulomb effect on coarsening of metal nanoclusters on semiconductor surfaces.

We propose the concept of a "Coulomb sink" to elucidate the effect of Coulomb charging on coarsening of metal mesas grown on semiconductor surfaces. We show that a charged mesa, due to its reduced chemical potential, acts as a Coulomb sink and grows at the expense of neighboring neutral mesas. The theory explains qualitatively the most salient features of coarsening of charged Pb mesas on the Si(111) surface, as observed by a scanning tunneling microscope. It provides a potentially useful method for controlled fabrication of metal nanostructures.

Journal Article↗
PubMed2004

Insulin inhibits AMPA-induced neuronal damage via stimulation of protein kinase B (Akt).

We designed a series of experiments to explore the neuroprotective effects of insulin. Insulin significantly inhibited the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced neuronal cell damage as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) assay. However, insulin had little affect on the AMPA-induced glial cell damage. To determine whether insulin inhibits AMPA-induced excitotoxicity, we performed grease-gap recording assays using rat brain slices. In these experiments, insulin also significantly inhibited AMPA-induced depolarization. Flow cytometry and DNA fragmentation assays showed that insulin inhibits AMPA-induced apoptosis and DNA fragmentation, respectively. Insulin stimulated protein kinase B (Akt) activity, whereas AMPA pretreatment did not alter the insulin-stimulated Akt activity. On the contrary, insulin blocked induction of SAPK/JNK, which AMPA stimulated. Taken together, these results suggest that insulin exerts neuroprotective effects by inhibiting AMPA-induced excitotoxicity and apoptosis, possibly by activating Akt and blocking SAPK/JNK.

Animals↗
PubMed2004

Geometric constant defining shape transitions of carbon nanotubes under pressure.

We demonstrate that when a single-walled carbon nanotube is under pressure it undergoes a series of shape transitions, first transforming from a circle to an oval and then from an oval to a peanut. Most remarkably, the ratio of the area of the tube cross sections at the second transition over that at the first transition appears as a constant, independent of the tube radius. Its accurate value is computed to be G=0.819 469, by formulating a variational geometry problem to represent single-walled carbon nanotubes with a family of closed plane curves of fixed length and minimum bending energy. The implications of such a geometric constant in designing nanotube electromechanical pressure sensors are discussed.

Journal Article↗
PubMed2004

Surface analyses of micro-arc oxidized and hydrothermally treated titanium and effect on osteoblast behavior.

Osteoblast adhesion on the implant material surface is essential for the success of any implant in which osteointegration is required. Surface properties of implant material have a critical role in the cell adhesion progress. Titanium and its alloys are widespread and increasingly used as implant material in dentistry and orthopedics because of their excellent biocompatibility, which is attributed to a passive layer of TiO2 on the surface. In this study, the micro-arc oxidizing (MAO) and hydrothermally synthesizing (HS) methods were used to modify the TiO2 layer on the titanium surface. The surface microstructure was observed by scanning electron microscopy. The surface energy was assessed. The mouse osteoblastic cell line (MC3T3-E1) was seeded on the treated surfaces to evaluate their effect on cell behavior. This included cell adhesion kinetics, cell proliferation, cell morphology, and cytoskeletal organization. The surface structure of MAO samples exhibited micropores with a diameter of 1-3 microm, whereas the MAO-HS-treated samples showed additional multiple crystalline microparticles on the microporous surface. The surface energy of MAO and MAO-HS was higher than that of titanium. The cell adhesion rate was higher on the MAO-HS surface than on the MAO and titanium surface, but without any significant difference between them. After 3 days of culture, cells proliferated significantly more on the MAO and titanium surface than on the MAO-HS surface. The cytoskeletal organization was analyzed by actin and vinculin staining on all the samples. We conclude that the MAO and MAO-HS methods change the surface energy of TiO2 layer on the titanium surface. This may have an influence on the initial cell attachment. Other surface characteristics may be involved in the cell proliferation, which is different from cell attachment on the sample surface. A longer-duration cell experiment should be conducted to see the effect on cell differentiation. Future in vivo evaluation may give further evidence to optimize the surface character of this kind of implant material.

Actins↗
PubMed2004

Small-bowel displacement system for the sparing of small bowel in three-dimensional conformal radiotherapy for cervical cancer.

AIMS: The efficacy of the small-bowel displacement system (SBDS) in three-dimensional conformal radiotherapy (3-D CRT) planning for sparing the volume of small bowel is presented for cervical cancer. MATERIALS AND METHODS: Ten consecutive patients, who received pelvic radiation therapy for uterine cervical cancer with the SBDS from January to March 2003, were included in this study. The SBDS consists of a customised Styrofoam compression device, which can displace the small bowel out of the radiation fields, and an individualised immobilisation board. With oral contrast before scanning, computed tomography was taken in the prone position with and without the SBDS. 3-D conformal planning was carried out, and dose distribution was compared in the target volumes and in the organs-at-risk with and without the SBDS. RESULTS: In all patients, the SBDS significantly reduced the small-bowel volume within radiation fields. The median small-bowel volume with SBDS was reduced by 56.4% compared with the small-bowel volume without SBDS (from 491 to 214 cm3; P = 0.004). Among the 10 patients, the highest small-bowel volume reduction was 70.2% (from 544 to 62 cm3). At the prescription dose, the median volume of small bowel irradiated was reduced significantly with SBDS (9.8% vs 1.2%; P = 0.005). Differences in the dose-volume histogram for the rectum and the bladder between the 3-D CRT plans with and without SBDS were not statistically significant (P > 0.1). All patients completed radiotherapy without a break in treatment. CONCLUSION: The SBDS is a novel method that can be used to displace the small bowel away from the 3-D CRT fields effectively, and reduce radiation therapy morbidity.

Adult↗
PubMed2004

Catalytic activity of caspase-3 is required for its degradation: stabilization of the active complex by synthetic inhibitors.

The activation of caspase-3 represents a critical step in the pathways leading to the biochemical and morphological changes that underlie apoptosis. Upon induction of apoptosis, the large (p17) and small (p12) subunits, comprising active caspase-3, are generated via proteolytic processing of a latent proenzyme dimer. Two copies of each individual subunit are generated to form an active heterotetramer. The tetrameric form of caspase-3 cleaves specific protein substrates within the cell, thereby producing the apoptotic phenotype. In contrast to the proenzyme, once activated in HeLa cells, caspase-3 is difficult to detect due to its rapid degradation. Interestingly, however, enzyme stability and therefore detection of active caspase-3 by immunoblot analysis can be restored by treatment of cells with a peptide-based caspase-3 selective inhibitor, suggesting that the active form can be stabilized through protein-inhibitor interaction. The heteromeric active enzyme complex is necessary for its stabilization by inhibitors, as expression of the large subunit alone is not stabilized by the presence of inhibitors. Our results show for the first time, that synthetic caspase inhibitors not only block caspase activity, but may also increase the stability of otherwise rapidly degraded mature caspase complexes. Consistent with these findings, experiments with a catalytically inactive mutant of caspase-3 show that rapid turnover is dependent on the activity of the mature enzyme. Furthermore, turnover of otherwise stable active site mutants of capase-3 is rescued by the presence of the active enzyme suggesting that turnover can be mediated in trans.

Apoptosis↗
PubMed2004

Towards optimal filtering of "standard" multifocal electroretinogram (mfERG) recordings: findings in normal and diabetic subjects.

AIMS: To study the effects of two commonly used pre-amplifier filtering bandwidths on normal multifocal electroretinogram (mfERG) responses and their comparative abilities to detect retinal disease. METHODS: 103 standard mfERGs were recorded simultaneously in two channels with different pre-amplifier settings (10-100 Hz and 10-300 Hz) from one eye of each of 20 normal subjects, 17 diabetics with non-proliferative diabetic retinopathy (NPDR), and 12 diabetics without retinopathy. Signal to noise ratios (SNR) of the normal subjects' first order mfERGs were compared between channels. All subjects' amplitudes and implicit times were derived using a "template stretching" method. For comparison, implicit time was also measured using a "template sliding" method. mfERG amplitudes and implicit times were compared between the channels and among subject groups. RESULTS: Normal mean amplitudes and implicit times were similar for the two channels. However, normal 10-100 Hz recordings had significantly higher SNR and lower intersubject variability than 10-300 Hz recordings. In NPDR, the 10-100 Hz channel identified significantly more implicit time and amplitude abnormalities. In the diabetics without retinopathy, 10-100 Hz filtering identified significantly more implicit time abnormalities than 10-300 Hz filtering. For both filter settings, diabetic implicit times were more often abnormal than amplitudes. The 10-100 Hz channel was superior for both implicit time measurements. CONCLUSION: Standard mfERGs recorded from normal eyes and filtered 10-100 Hz contain less noise, higher SNR, and less intersubject variability than those filtered at 10-300 Hz. This underlies the finding that the 10-100 Hz filter setting identifies more retinal dysfunction than the 10-300 Hz setting.

Adult↗