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Find video protocols related to scientific articles indexed in Pubmed.
Modified Landweber algorithm for robust particle sizing by using Fraunhofer diffraction.
Appl Opt
PUBLISHED: 10-17-2014
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In this paper, a robust modified Landweber algorithm was proposed to retrieve the particle size distributions from Fraunhofer diffraction. Three typical particle size distributions, i.e., Rosin-Rammler, lognormal, and bimodal normal distributions for particles ranging from 4.8 to 96 ?m, were employed to verify the performance of the algorithm. To show its merits, the proposed algorithm was compared with the Tikhonov regularization algorithm and the ?1-norm-based algorithm. Simulation results showed that, for noise-free data, both the modified Landweber algorithm and the ?1-norm-based algorithm were better than the Tikhonov regularization algorithm in terms of accuracy. When the data was noise-contaminated, the modified Landweber algorithm was superior to the other two algorithms in both accuracy and speed. An experimental setup was also established and the results validated the feasibility and effectiveness of the proposed method.
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Scale-Invariant Quantum Anomalous Hall Effect in Magnetic Topological Insulators beyond the Two-Dimensional Limit.
Phys. Rev. Lett.
PUBLISHED: 09-26-2014
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We investigate the quantum anomalous Hall effect (QAHE) and related chiral transport in the millimeter-size (Cr_{0.12}Bi_{0.26}Sb_{0.62})_{2}Te_{3} films. With high sample quality and robust magnetism at low temperatures, the quantized Hall conductance of e^{2}/h is found to persist even when the film thickness is beyond the two-dimensional (2D) hybridization limit. Meanwhile, the Chern insulator-featured chiral edge conduction is manifested by the nonlocal transport measurements. In contrast to the 2D hybridized thin film, an additional weakly field-dependent longitudinal resistance is observed in the ten-quintuple-layer film, suggesting the influence of the film thickness on the dissipative edge channel in the QAHE regime. The extension of the QAHE into the three-dimensional thickness region addresses the universality of this quantum transport phenomenon and motivates the exploration of new QAHE phases with tunable Chern numbers. In addition, the observation of scale-invariant dissipationless chiral propagation on a macroscopic scale makes a major stride towards ideal low-power interconnect applications.
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Resting state cortical oscillations of PD patients without and with Subthalamic deep brain stimulation, a MEG study.
J Clin Neurophysiol
PUBLISHED: 09-19-2014
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In this study, we investigate the modification to cortical oscillations of Parkinson's disease (PD) patients by subthalamic deep brain stimulation (STN-DBS).
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MiR-497 downregulation contributes to the malignancy of pancreatic cancer and associates with a poor prognosis.
Oncotarget
PUBLISHED: 08-24-2014
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Chemoresistance is one of the causes of poor prognosis in pancreatic cancer patients. However, the mechanisms of resistance remain unclear. Here we screened miRNAs associated with drug resistance in pancreatic cancer, and identified a panel of miRNAs dysregulated in gemcitabine-resistance pancreatic cancer cells, including 13 downregulated miRNAs and 20 upregulated miRNAs. Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples (P=0.000). Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer (P=0.01, hazard ratio=2.762, 95% confidence interval: 1.159-6.579). Together these results indicate that miR-497 could be a new therapeutic target and prognostic marker of pancreatic cancer.
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[Association between polymorphism of ATP2B1 gene, its interaction with smoking and essential hypertension -a case-control study].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 07-26-2014
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To investigate the association between polymorphism of ATP2B1 gene, its interaction with smoking and susceptibility of essential hypertension.
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Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease.
PLoS Genet.
PUBLISHED: 07-01-2014
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The majority of the heritability of coronary artery disease (CAD) remains unexplained, despite recent successes of genome-wide association studies (GWAS) in identifying novel susceptibility loci. Integrating functional genomic data from a variety of sources with a large-scale meta-analysis of CAD GWAS may facilitate the identification of novel biological processes and genes involved in CAD, as well as clarify the causal relationships of established processes. Towards this end, we integrated 14 GWAS from the CARDIoGRAM Consortium and two additional GWAS from the Ottawa Heart Institute (25,491 cases and 66,819 controls) with 1) genetics of gene expression studies of CAD-relevant tissues in humans, 2) metabolic and signaling pathways from public databases, and 3) data-driven, tissue-specific gene networks from a multitude of human and mouse experiments. We not only detected CAD-associated gene networks of lipid metabolism, coagulation, immunity, and additional networks with no clear functional annotation, but also revealed key driver genes for each CAD network based on the topology of the gene regulatory networks. In particular, we found a gene network involved in antigen processing to be strongly associated with CAD. The key driver genes of this network included glyoxalase I (GLO1) and peptidylprolyl isomerase I (PPIL1), which we verified as regulatory by siRNA experiments in human aortic endothelial cells. Our results suggest genetic influences on a diverse set of both known and novel biological processes that contribute to CAD risk. The key driver genes for these networks highlight potential novel targets for further mechanistic studies and therapeutic interventions.
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Seed-weighted random walk ranking for cancer biomarker prioritisation: a case study in leukaemia.
Int J Data Min Bioinform
PUBLISHED: 05-29-2014
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A central focus of clinical proteomics for cancer is to identify protein biomarkers with diagnostic and therapeutic application potential. Network-based analyses have been used in computational disease-related gene prioritisation for several years. The Random Walk Ranking (RWR) algorithm has been successfully applied to prioritising disease-related gene candidates by exploiting global network topology in a Protein-Protein Interaction (PPI) network. Increasing the specificity and sensitivity ofbiomarkers may require consideration of similar or closely-related disease phenotypes and molecular pathological mechanisms shared across different disease phenotypes. In this paper, we propose a method called Seed-Weighted Random Walk Ranking (SW-RWR) for prioritizing cancer biomarker candidates. This method uses the information of cancer phenotype association to assign to each gene a disease-specific, weighted value to guide the RWR algorithm in a global human PPI network. In a case study of prioritizing leukaemia biomarkers, SW-RWR outperformed a typical local network-based analysis in coverage and also showed better accuracy and sensitivity than the original RWR method (global network-based analysis). Our results suggest that the tight correlation among different cancer phenotypes could play an important role in cancer biomarker discovery.
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Proximity induced high-temperature magnetic order in topological insulator--ferrimagnetic insulator heterostructure.
Nano Lett.
PUBLISHED: 05-23-2014
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Introducing magnetic order in a topological insulator (TI) breaks time-reversal symmetry of the surface states and can thus yield a variety of interesting physics and promises for novel spintronic devices. To date, however, magnetic effects in TIs have been demonstrated only at temperatures far below those needed for practical applications. In this work, we study the magnetic properties of Bi2Se3 surface states (SS) in the proximity of a high Tc ferrimagnetic insulator (FMI), yttrium iron garnet (YIG or Y3Fe5O12). Proximity-induced butterfly and square-shaped magnetoresistance loops are observed by magneto-transport measurements with out-of-plane and in-plane fields, respectively, and can be correlated with the magnetization of the YIG substrate. More importantly, a magnetic signal from the Bi2Se3 up to 130 K is clearly observed by magneto-optical Kerr effect measurements. Our results demonstrate the proximity-induced TI magnetism at higher temperatures, an important step toward room-temperature application of TI-based spintronic devices.
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Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis.
Hum. Mol. Genet.
PUBLISHED: 05-15-2014
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Adolescent idiopathic scoliosis (AIS) causes spinal deformity in 3% of children. Despite a strong genetic basis, few genes have been associated with AIS and the pathogenesis remains poorly understood. In a genome-wide rare variant burden analysis using exome sequence data, we identified fibrillin-1 (FBN1) as the most significantly associated gene with AIS. Based on these results, FBN1 and a related gene, fibrillin-2 (FBN2), were sequenced in a total of 852 AIS cases and 669 controls. In individuals of European ancestry, rare variants in FBN1 and FBN2 were enriched in severely affected AIS cases (7.6%) compared with in-house controls (2.4%) (OR = 3.5, P = 5.46 × 10(-4)) and Exome Sequencing Project controls (2.3%) (OR = 3.5, P = 1.48 × 10(-6)). Scoliosis severity in AIS cases was associated with FBN1 and FBN2 rare variants (P = 0.0012) and replicated in an independent Han Chinese cohort (P = 0.0376), suggesting that rare variants may be useful as predictors of curve progression. Clinical evaluations revealed that the majority of AIS cases with rare FBN1 variants do not meet diagnostic criteria for Marfan syndrome, though variants are associated with tall stature (P = 0.0035) and upregulation of the transforming growth factor beta pathway. Overall, these results expand our definition of fibrillin-related disorders to include AIS and open up new strategies for diagnosing and treating severe AIS.
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PIM kinases: an overview in tumors and recent advances in pancreatic cancer.
Future Oncol
PUBLISHED: 05-07-2014
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The PIM kinases represent a family of serine/threonine kinases, which is composed of three different members (PIM1, PIM2 and PIM3). Aberrant expression of PIM kinases is observed in variety of tumors, including pancreatic cancer. The PIM kinases play pivotal roles in the regulation of cell cycle, apoptosis, properties of stem cells, metabolism, autophagy, drug resistance and targeted therapy. The roles of PIM kinases in pancreatic cancer include the regulation of proliferation, apoptosis, cell cycle, formation, angiogenesis and prediction prognosis. Blocking the activities of PIM kinases could prevent pancreatic cancer development. PIM kinases may be a novel target for cancer therapy.
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CHIP is a novel tumor suppressor in pancreatic cancer through targeting EGFR.
Oncotarget
PUBLISHED: 04-12-2014
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Carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is an E3 ubiquitin ligase that is involved in protein quality control and mediates several tumor-related proteins in many cancers, but the function of CHIP in pancreatic cancer is not known. Here we show that CHIP interacts and ubiquitinates epidermal growth factor receptor (EGFR) for proteasome-mediated degradation in pancreatic cancer cells, thereby inhibiting the activation of EGFR downstream pathway. CHIP suppressed cell proliferation, anchor-independent growth, invasion and migration, as well as enhanced apoptosis induced by erlotinib in vitro and in vivo. The expression of CHIP was decreased in pancreatic cancer tissues or sera. Low CHIP expression in tumor tissues was correlated with tumor differentiation and shorter overall survival. These observations indicate that CHIP serves as a novel tumor suppressor by down-regulating EGFR pathway in pancreatic cancer cells, decreased expression of CHIP was associated with poor prognosis in pancreatic cancer.
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The cystathionine ?-lyase/hydrogen sulfide system maintains cellular glutathione status.
Biochem. J.
PUBLISHED: 04-09-2014
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Hydrogen sulfide (H2S) has been implicated to exhibit antioxidative properties in many models. CSE (cystathionine ?-lyase) is an important enzyme responsible for endogenous H2S production in mammalian systems, but little is known about the modulation of endogenous H2S production and its antioxidative activity. We found that inhibiting CSE activity with PAG (propargylglycine) or silencing CSE expression using an siRNA approach resulted in a greater reduction in cell viability under exposure to the oxidizing agent hydrogen peroxide (H2O2). Cellular oxidative stress also increased significantly upon PAG inhibition or CSE knockdown. Further experiments using an activity-null Y60A mutant, a hyperactive E339A mutant and a control E349A mutant demonstrated that modulation of CSE catalytic activity altered its antioxidative activity. The increased sensitivity towards H2O2-induced cytotoxicity in CSE-siRNA-transfected cells was associated with a decreased glutathione concentration (GSH) and glutathione ratio (GSH/GSSG). Incubation of cells with exogenous H2S increased the GSH concentration and GSH/GSSG ratio. Moreover, exogenous H2S preserved the cellular glutathione status under BSO (buthionine sulfoximine)-induced glutathione depletion. Taken together, the results of the present study provide molecular insights into the antioxidative activity of CSE and highlights the importance of the CSE/H2S system in maintaining cellular glutathione status.
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New method of thrombus preparation using a fluid model for evaluation of thrombectomy devices in a swine model.
Thromb. Res.
PUBLISHED: 04-04-2014
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Mechanical thrombectomy is a promising new modality of interventional stroke treatment. Preparation of thrombus is a very important step for the evaluation of the mechanical thrombectomy devices. The objective of this study was to explore a new method of thrombus preparation with fluid model (FM) for assessment of thrombectomy devices used in the recanalization of acute ischemic stroke.
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Magnetization switching through giant spin-orbit torque in a magnetically doped topological insulator heterostructure.
Nat Mater
PUBLISHED: 04-02-2014
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Recent demonstrations of magnetization switching induced by in-plane current in heavy metal/ferromagnetic heterostructures (HMFHs) have drawn great attention to spin torques arising from large spin-orbit coupling (SOC). Given the intrinsic strong SOC, topological insulators (TIs) are expected to be promising candidates for exploring spin-orbit torque (SOT)-related physics. Here we demonstrate experimentally the magnetization switching through giant SOT induced by an in-plane current in a chromium-doped TI bilayer heterostructure. The critical current density required for switching is below 8.9 × 10(4) A cm(-2) at 1.9 K. Moreover, the SOT is calibrated by measuring the effective spin-orbit field using second-harmonic methods. The effective field to current ratio and the spin-Hall angle tangent are almost three orders of magnitude larger than those reported for HMFHs. The giant SOT and efficient current-induced magnetization switching exhibited by the bilayer heterostructure may lead to innovative spintronics applications such as ultralow power dissipation memory and logic devices.
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Electric-field control of ferromagnetism in Mn-doped ZnO nanowires.
Nano Lett.
PUBLISHED: 03-05-2014
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In this Letter, the electric-field control of ferromagnetism was demonstrated in a back-gated Mn-doped ZnO (Mn-ZnO) nanowire (NW) field-effect transistor (FET). The ZnO NWs were synthesized by a thermal evaporation method, and the Mn doping of 1 atom % was subsequently carried out in a MBE system using a gas-phase surface diffusion process. Detailed structural analysis confirmed the single crystallinity of Mn-ZnO NWs and excluded the presence of any precipitates or secondary phases. For the transistor, the field-effect mobility and n-type carrier concentration were estimated to be 0.65 cm(2)/V·s and 6.82 × 10(18) cm(-3), respectively. The magnetic hysteresis curves measured under different temperatures (T = 10-350 K) clearly demonstrate the presence of ferromagnetism above room temperature. It suggests that the effect of quantum confinements in NWs improves Tc, and meanwhile minimizes crystalline defects. The magnetoresistace (MR) of a single Mn-ZnO NW was observed up to 50 K. Most importantly, the gate modulation of the MR ratio was up to 2.5 % at 1.9 K, which implies the electric-field control of ferromagnetism in a single Mn-ZnO NW.
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Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and their clinical subtypes.
Lung Cancer
PUBLISHED: 01-30-2014
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Lung cancer is one of the most common human cancers worldwide. Among all lung cancer cases, non-small cell lung cancer (NSCLC) accounts for approximately 85%. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts that have been shown to play important roles in tumourigenesis and tumor progression. To reveal novel tumor-related lncRNAs in NSCLC and their associations with clinical subtypes, we herein identified 2935 probe sets mapped to lncRNAs on Affymetrix HG-U133 Plus 2.0 array with an lncRNA classification pipeline. We found 47 lncRNAs differentially expressed between normal lung tissues and tumor samples and 19 lncRNAs differed in expression between SCC and AC, two subtypes of NSCLC, after analyses of the gene expression profiles of five datasets downloaded from the gene expression omnibus (GEO) with a leave one dataset out validation process. The different lncRNA expression profiles between NSCLC and normal tissue and between the subtypes of NSCLC may have potential implications in the pathogenesis of this cancer. lncRNAs screening may be beneficial in the diagnosis, subclassification, and the personalized treatment of NSCLC.
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RASSF10 is epigenetically inactivated and induces apoptosis in lung cancer cell lines.
Biomed. Pharmacother.
PUBLISHED: 01-18-2014
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Ras-association domain family 10 (RASSF10), the latest member of the RASSF family with Ras effector function, has been frequently inactivated by aberrant promoter hypermethylation in several human cancers. However, its role in lung cancer has remained unclear. In this study, we investigated the methylation status of RASSF10 by combined bisulfate restriction analysis (COBRA) and examined its preliminary function in lung cancer cell lines. RASSF10 was methylated in four out of six lung cancer cell lines, including NCI-H157, NCI-460, SPCA-1 and NCI-H446. Treatment with a DNA methylation inhibitor, 5-aza-2'-deoxycytiding (5-aza-DC), restored RASSF10 mRNA expression and the restoration of RASSF10 increased cell apoptosis in a dose dependent manner, whereas knockdown of RASSF10 improved cell proliferation ability and inhibited cell apoptosis rate significantly. Immunofluorescence revealed that RASSF10 protein was located in the cell membrane. Taken together, our data for the first time demonstrates the frequent epigenetic inactivation of RASSF10 in lung cancer cell lines. RASSF10 induces cell apoptosis and might function as a tumor suppressor gene in lung cancer.
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Discovery of novel P-glycoprotein-mediated multidrug resistance inhibitors bearing triazole core via click chemistry.
Chem Biol Drug Des
PUBLISHED: 01-09-2014
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A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors bearing a triazol-phenethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 5 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity (IC50s > 100 ?m). Compared with VRP, compound 5 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 5 persisted longer chemo-sensitizing effect (>24 h) than VRP (<6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent reversal activity, compound 5 may represent a promising candidate for developing P-gp-mediated MDR inhibitor.
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Critical roles of mitochondria in brain activities of torpid Myotis ricketti bats revealed by a proteomic approach.
J Proteomics
PUBLISHED: 01-04-2014
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Bats are the only mammals that fly and hibernate. Little is known about their overall metabolism in the brain during hibernation. In this study, brain proteins of torpid and active Myotis ricketti bats were fractionated and compared using a proteomic approach. Results showed that 21% (23 proteins) of identified proteins with significant expression changes were associated with amino acid metabolism and proteostasis. The expression levels of proteins involved in energy metabolism (15 proteins), cytoskeletal structure (18 proteins), and stress response (13 proteins) were also significantly altered in torpid bats. Over 30% (34 proteins) of differentially expressed proteins were associated with mitochondrial functions. Various post-translational modifications (PTMs) on PDHB, DLD, and ARG1 were detected, suggesting that bats use PTMs to regulate protein functions during torpor. Antioxidation and stress responses in torpid bats were similar to those of hibernated squirrels, suggesting a common strategy adopted by small hibernators against brain dysfunction. Since many amino acids that metabolize in mitochondria modulate neuronal transmissions, results of this study reveal pivotal roles of mitochondria in neural communication, metabolic regulation, and brain cell survival during bat hibernation. This article is part of a Special Issue entitled: Proteomics of non-model organisms.
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Joint Testing of Genotypic and Gene-Environment Interaction Identified Novel Association for BMP4 with Non-Syndromic CL/P in an Asian Population Using Data from an International Cleft Consortium.
PLoS ONE
PUBLISHED: 01-01-2014
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Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered.
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Analysis of interleukin-8 gene variants reveals their relative importance as genetic susceptibility factors for chronic periodontitis in the Han population.
PLoS ONE
PUBLISHED: 01-01-2014
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Interleukin (IL)-8, an important chemokine that regulates the inflammatory response, plays an important role in periodontitis. Previous studies indicate that certain IL-8 gene polymorphisms are associated with periodontitis susceptibility in some populations. However, the literature is somewhat contradictory, and not all IL-8 polymorphisms have been examined, particularly in Han Chinese individuals. The aim of this study was to investigate the association of every IL-8 SNP with chronic periodontitis in Han Chinese individuals. We analyzed 23 SNPs with minor allele frequency (MAF)?0.01, which were selected from 219 SNPs in the NCBI dbSNP and preliminary HapMap data analyses from a cohort of 400 cases and 750 controls from genetically independent Han Chinese individuals. Single SNP, haplotype and gender-specific associations were performed. We found that rs4073 and rs2227307 were significantly associated with chronic periodontitis. Further haplotype analysis indicated that a haplotype block (rs4073-rs2227307-rs2227306) that spans the promoter and exon1 of IL-8 was highly associated with chronic periodontitis. Additionally, the ATC haplotype in this block was increased 1.5-fold in these cases. However, when analyzing the samples by gender, no significant gender-specific associations in IL-8 were observed, similar to the results of haplotype association analyses in female and male subgroups. Our results provide further evidence that IL-8 is associated with chronic periodontitis in Han Chinese individuals. Furthermore, our results confirm previous reports suggesting the intriguing possibilities that IL-8 plays a role in the pathogenesis of chronic periodontitis and that this gene may be involved in the etiology of this condition.
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Relaxed evolution in the tyrosine aminotransferase gene tat in old world fruit bats (chiroptera: pteropodidae).
PLoS ONE
PUBLISHED: 01-01-2014
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Frugivorous and nectarivorous bats fuel their metabolism mostly by using carbohydrates and allocate the restricted amounts of ingested proteins mainly for anabolic protein syntheses rather than for catabolic energy production. Thus, it is possible that genes involved in protein (amino acid) catabolism may have undergone relaxed evolution in these fruit- and nectar-eating bats. The tyrosine aminotransferase (TAT, encoded by the Tat gene) is the rate-limiting enzyme in the tyrosine catabolic pathway. To test whether the Tat gene has undergone relaxed evolution in the fruit- and nectar-eating bats, we obtained the Tat coding region from 20 bat species including four Old World fruit bats (Pteropodidae) and two New World fruit bats (Phyllostomidae). Phylogenetic reconstructions revealed a gene tree in which all echolocating bats (including the New World fruit bats) formed a monophyletic group. The phylogenetic conflict appears to stem from accelerated TAT protein sequence evolution in the Old World fruit bats. Our molecular evolutionary analyses confirmed a change in the selection pressure acting on Tat, which was likely caused by a relaxation of the evolutionary constraints on the Tat gene in the Old World fruit bats. Hepatic TAT activity assays showed that TAT activities in species of the Old World fruit bats are significantly lower than those of insectivorous bats and omnivorous mice, which was not caused by a change in TAT protein levels in the liver. Our study provides unambiguous evidence that the Tat gene has undergone relaxed evolution in the Old World fruit bats in response to changes in their metabolism due to the evolution of their special diet.
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Sex- and age-interacting eQTLs in human complex diseases.
Hum. Mol. Genet.
PUBLISHED: 11-15-2013
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Many complex human diseases exhibit sex or age differences in gene expression. However, the presence and the extent of genotype-specific variations in gene regulation are largely unknown. Here, we report results of a comprehensive analysis of expression regulation of genetic variation related to 11 672 complex disease-associated SNPs as a function of sex and age in whole-blood-derived RNA from 5254 individuals. At false discovery rate <0.05, we identified 14 sex- and 10 age-interacting expression quantitative trait loci (eQTLs). We show that these eQTLs are also associated with many sex- or age-associated traits. These findings provide important context regarding the regulation of phenotypes by genotype-environment interaction.
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Regulation of drought tolerance by the F-box protein MAX2 in Arabidopsis.
Plant Physiol.
PUBLISHED: 11-06-2013
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MAX2 (More AXillary growth 2) has been shown to regulate diverse biological processes, including plant architecture, photomorphogenesis, senescence and karrikin signaling. Although karrikin is a smoke-derived abiotic signal, a role for MAX2 in abiotic stress response pathways is least investigated. Here, we show that the max2 mutant is strongly hypersensitive to drought stress compared to wild type. Stomatal closure of max2 was less sensitive to ABA than that of wild type. Cuticle thickness of max2 is significantly thinner than that of wild type. Both of these phenotypes of max2 mutant plants correlate with the increased water loss and drought sensitive phenotype. qRT-PCR analyses showed that the expression of stress responsive genes and ABA biosynthesis, catabolism, transport and signaling genes was impaired in max2 compared to wild type seedlings in response to drought stress. Double mutant analysis of max2 with ABA-insensitive mutants abi3 and abi5 indicated that MAX2 may function upstream of these genes. The expression of ABA-regulated genes was enhanced in imbibed max2 seeds. In addition, max2 mutant seedlings are hypersensitive to ABA and osmotic stress including NaCl, Mannitol and Glucose. Interestingly, ABA, osmotic stress and drought sensitive phenotypes were restricted to max2, and the strigolactone biosynthetic pathway mutants, max1, max3 and max4, did not display any defects in these responses. Taken together, these results uncover an important role for MAX2 in plant responses to abiotic stress conditions.
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Interplay between different magnetisms in Cr-doped topological insulators.
ACS Nano
PUBLISHED: 09-30-2013
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Breaking the time-reversal-symmetry of topological insulators through magnetic doping has led to exotic physical discoveries. Here, we report the gate-dependent magneto-transport measurements on the Cr-doped (BixSb1-x)2Te3 thin films. With effective top-gate modulations, we demonstrate the presence of both the hole-mediated RKKY coupling and carrier-independent van Vleck magnetism in the magnetic TI systems. Most importantly, by varying the Cr doping concentrations from 2% to 20%, we unveil the interplay between the two magnetic orders and establish the valid approach to either enhance or suppress each individual contribution. The electric-field-controlled ferromagnetisms identified in the Cr-doped TI materials will serve as the fundamental step to further explore the TRS-breaking TI systems, and it may also help to expand the functionality of TI-based device for spintronics applications.
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Evidence of the two surface states of (Bi0.53Sb0.47)2Te3 films grown by van der Waals epitaxy.
Sci Rep
PUBLISHED: 09-19-2013
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The discovery of topological insulators (TIs) has led to numerous exciting opportunities for studying topological states of quantum physics and for exploring spintronic applications due to the new physics arising from their robust metallic surface states. Here, we report the high-quality topological insulator (BixSb1-x)2Te3 thin films using a single van der Waals GaSe buffer layer. As a result, ultra-low surface carrier density of 1.3 × 10(12)?cm(-2) and a high Hall mobility of 3100?cm(2)/Vs have been achieved for (Bi0.53Sb0.47)2Te3. The high-quality films enable us to observe quantum oscillations associated with the top and bottom surface states and to manipulate the Dirac electrons and bulk holes conduction properties. The observation of the two surface states may lead to a path towards the implementation of TIs in spintronics.
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Manipulating surface-related ferromagnetism in modulation-doped topological insulators.
Nano Lett.
PUBLISHED: 09-12-2013
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A new class of devices based on topological insulators (TI) can be achieved by the direct engineering of the time-reversal-symmetry (TRS) protected surface states. In the meantime, a variety of interesting phenomena are also expected when additional ferromagnetism is introduced to the original topological order. In this Letter, we report the magnetic responses from the magnetically modulation-doped (Bi(z)Sb(1-z))2Te3/Cr(x)(Bi(y)Sb(1-y))2Te3 bilayer films. By electrically tuning the Fermi level across the Dirac point, we show that the top TI surface carriers can effectively mediate the magnetic impurities and generate robust ferromagnetic order. More importantly, such surface magneto-electric effects can be either enhanced or suppressed, depending on the magnetic interaction range inside the TI heterostructures. The manipulation of surface-related ferromagnetism realized in our modulation-doped TI device is important for the realization of TRS-breaking topological physics, and it may also lead to new applications of TI-based multifunctional heterostructures.
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Interventional therapy for the treatment of severe hemobilia after percutaneous transhepatic cholangial drainage: a case series.
Int Surg
PUBLISHED: 08-27-2013
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Abstract From May 2003 to May 2010, a total of 9 patients with severe hemobilia after percutaneous transhepatic cholangial drainage (PTCD) were diagnosed using superselective angiography and cholangiography, and then were treated with interventional procedures. Two patients with hepatic arterio-biliary fistula underwent proximal and distal arterial embolization of the responsible vessel. Six patients with pseudoaneurysm had pseudoaneurysm occlusion with proximal and distal embolization. Another patient with biliary-portal vein fistula received a biliary fully covered stent placement. The effects in these patients were evaluated using superselective angiography immediately after the intervention and at 3- and 6-month follow-up. In all patients, hemobilia was stopped right after the treatment and no sign of recurrence was noted at 3- and 6-month follow-up after the interventional therapy. Our findings demonstrate that interventional therapy is a simple, minimally invasive, and safe approach for treating severe hemobilia in patients receiving PTCD.
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Electrical spin injection and detection in Mn5Ge3/Ge/Mn5Ge3 nanowire transistors.
Nano Lett.
PUBLISHED: 08-16-2013
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In this Letter, we report the electrical spin injection and detection in Ge nanowire transistors with single-crystalline ferromagnetic Mn5Ge3 as source/drain contacts formed by thermal reactions. Degenerate indium dopants were successfully incorporated into as-grown Ge nanowires as p-type doping to alleviate the conductivity mismatch between Ge and Mn5Ge3. The magnetoresistance (MR) of the Mn5Ge3/Ge/Mn5Ge3 nanowire transistor was found to be largely affected by the applied bias. Specifically, negative and hysteretic MR curves were observed under a large current bias in the temperature range from T = 2 K up to T = 50 K, which clearly indicated the electrical spin injection from ferromagnetic Mn5Ge3 contacts into Ge nanowires. In addition to the bias effect, the MR amplitude was found to exponentially decay with the Ge nanowire channel length; this fact was explained by the dominated Elliot-Yafet spin-relaxation mechanism. The fitting of MR further revealed a spin diffusion length of lsf = 480 ± 13 nm and a spin lifetime exceeding 244 ps at T = 10 K in p-type Ge nanowires, and they showed a weak temperature dependence between 2 and 50 K. Ge nanowires showed a significant enhancement in the measured spin diffusion length and spin lifetime compared with those reported for bulk p-type Ge. Our study of the spin transport in the Mn5Ge3/Ge/Mn5Ge3 nanowire transistor points to a possible realization of spin-based transistors; it may also open up new opportunities to create novel Ge nanowire-based spintronic devices. Furthermore, the simple fabrication process promises a compatible integration into standard Si technology in the future.
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Single universal primer multiplex ligation-dependent probe amplification with sequencing gel electrophoresis analysis.
Anal. Biochem.
PUBLISHED: 07-27-2013
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In this study, a novel single universal primer multiplex ligation-dependent probe amplification (SUP-MLPA) technique that uses only one universal primer to perform multiplex polymerase chain reaction (PCR) was developed. Two reversely complementary common sequences were designed on the 5 or 3 end of the ligation probes (LPs), which allowed the ligation products to be amplified through only a single universal primer (SUP). SUP-MLPA products were analyzed on sequencing gel electrophoresis with extraordinary resolution. This method avoided the high expenses associated with capillary electrophoresis, which was the commonly used detection instrument. In comparison with conventional multiplex PCR, which suffers from low sensitivity, nonspecificity, and amplification disparity, SUP-MLPA had higher specificity and sensitivity and a low detection limit of 0.1 ng for detecting single crop species when screening the presence of genetically modified crops. We also studied the effect of different lengths of stuffer sequences on the probes for the first time. Through comparing the results of quantitative PCR, the LPs with different stuffer sequences did not affect the ligation efficiency, which further increased the multiplicity of this assay. The improved SUP-MLPA and sequencing gel electrophoresis method will be useful for food and animal feed identification, bacterial detection, and verification of genetic modification status of crops.
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Atrial natriuretic peptide is negatively regulated by microRNA-425.
J. Clin. Invest.
PUBLISHED: 05-17-2013
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Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3 untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.
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Clinical characteristics and prognosis of primary leiomyosarcoma of the pancreas: a systematic review.
World J Surg Oncol
PUBLISHED: 05-10-2013
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Primary pancreatic leiomyosarcoma (PLMS) is rare. The clinical characteristics and prognosis is still not completely understood. The aim of the present study is to identify the clinical characteristics and long-term outcomes of PLMS from the existing reported cases in different scientific literature.
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Enucleation of pancreatic lesions: indications, outcomes, and risk factors for clinical pancreatic fistula.
J. Gastrointest. Surg.
PUBLISHED: 04-24-2013
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There are few large samples and single-center series that focus on the outcomes of pancreatic enucleation and risk factors for clinical pancreatic fistula (PF). This study aimed to evaluate the indications, short- and long-term results, and risk factors for clinical PF after pancreatic enucleation.
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Gene expression signatures of coronary heart disease.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 03-28-2013
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To identify transcriptomic biomarkers of coronary heart disease (CHD) in 188 cases with CHD and 188 age- and sex-matched controls who were participants in the Framingham Heart Study.
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A systems biology framework identifies molecular underpinnings of coronary heart disease.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 03-28-2013
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Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD.
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Comparison of daily versus nondaily image-guided radiotherapy protocols for patients treated with intensity-modulated radiotherapy for head and neck cancer.
Head Neck
PUBLISHED: 03-20-2013
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The purpose of this study was to determine the feasibility of nondaily image-guided radiotherapy (RT) strategies with intensity-modulated radiotherapy (IMRT) for head and neck cancer.
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Perioperative Complications of Recanalization and Stenting for Symptomatic Nonacute Vertebrobasilar Artery Occlusion.
Ann Vasc Surg
PUBLISHED: 03-18-2013
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Endovascular recanalization and stenting has been used to treat patients with symptomatic nonacute intracranial vertebrobasilar artery occlusion (VBAO) refractory to aggressive medical treatment. This study was performed to analyze the perioperative complications of the procedures.
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Preliminary findings of recanalization and stenting for symptomatic vertebrobasilar artery occlusion lasting more than 24h: a retrospective analysis of 21 cases.
Eur J Radiol
PUBLISHED: 02-19-2013
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To evaluate the technical feasibility, safety and short-term treatment effects of recanalization and stenting for intracranial symptomatic vertebrobasilar artery occlusion (VBAO) lasting more than 24h.
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Control of Hes7 expression by Tbx6, the Wnt pathway and the chemical Gsk3 inhibitor LiCl in the mouse segmentation clock.
PLoS ONE
PUBLISHED: 01-09-2013
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The mouse segmentation is established from somites, which are iteratively induced every two hours from the presomitic mesoderm (PSM) by a system known as the segmentation clock. A crucial component of the segmentation clock is the gene Hes7, which is regulated by the Notch and Fgf/Mapk pathways, but its relation to other pathways is unknown. In addition, chemical alteration of the Wnt pathway changes the segmentation clock period but the mechanism is unclear.To clarify these questions, we have carried out Hes7 promoter analysis in transgenic mouse embryos and have identified an essential 400 bp region, which contains binding sites of Tbx6 and the Wnt signaling effector Lef1. We have found that the Hes7 promoter is activated by Tbx6, and normal activity of the Hes7 promoter in the mouse PSM requires Tbx6 binding sites. Our results demonstrate that Wnt pathway molecules activate the Hes7 promoter cooperatively with Tbx6 in cell culture and are necessary for its proper expression in the mouse PSM. Furthermore, it is shown that the chemical Gsk3 inhibitor LiCl lengthens the oscillatory period of Hes7 promoter activity.Our data suggest that Tbx6 and the Wnt pathway cooperatively regulate proper Hes7 expression. Furthermore, proper Hes7 promoter activity and expression is important for the normal pace of oscillation.
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A novel beaded filament structural protein 1 (BFSP1) gene mutation associated with autosomal dominant congenital cataract in a Chinese family.
Mol. Vis.
PUBLISHED: 01-01-2013
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To identify the disease-causing mutation in a five-generation Chinese family affected with bilateral congenital nuclear cataract.
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The FGF and FGFR Gene Family and Risk of Cleft Lip With or Without Cleft Palate.
Cleft Palate Craniofac. J.
PUBLISHED: 11-10-2011
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Background : Isolated, nonsyndromic cleft lip with or without cleft palate is a common human congenital malformation with a complex and heterogeneous etiology. Genes coding for fibroblast growth factors and their receptors (FGF/FGFR genes) are excellent candidate genes. Methods : We tested single-nucleotide polymorphic markers in 10 FGF/FGFR genes (including FGFBP1, FGF2, FGF10, FGF18, FGFR1, FGFR2, FGF19, FGF4, FGF3, and FGF9) for genotypic effects, interactions with one another, and with common maternal environmental exposures in 221 Asian and 76 Maryland case-parent trios ascertained through a child with isolated, nonsyndromic cleft lip with or without cleft palate. Results : Both FGFR1 and FGF19 yielded evidence of linkage and association in the transmission disequilibrium test, confirming previous evidence. Haplotypes of three single-nucleotide polymorphisms in FGFR1 were nominally significant among Asian trios. Estimated odds ratios for individual single-nucleotide polymorphic markers and haplotypes of multiple markers in FGF19 ranged from 1.31 to 1.87. We also found suggestive evidence of maternal genotypic effects for markers in FGF2 and FGF10 among Asian trios. Tests for gene-environment (G × E) interaction between markers in FGFR2 and maternal smoking or multivitamin supplementation yielded significant evidence of G × E interaction separately. Tests of gene-gene (G × G) interaction using Cordells method yielded significant evidence between single-nucleotide polymorphisms in FGF9 and FGF18, which was confirmed in an independent sample of trios from an international consortium. Conclusion : Our results suggest several genes in the FGF/FGFR family may influence risk for isolated, nonsyndromic cleft lip with or without cleft palate through distinct biological mechanisms.
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Domain combination of the vertebrate-like TLR gene family: implications for their origin and evolution.
J. Genet.
PUBLISHED: 10-13-2011
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Domain shuffling, which is an important mechanism in the evolution of multi-domain proteins, has shaped the evolutionary development of the immune system in animals. Toll and Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate and adaptive immune systems. Draft genome sequences provide the opportunity to compare the Toll/TLR gene repertoire among representative metazoans. In this study, we investigated the combination of Toll/interleukin-1 receptor (TIR) and leucine-rich repeat (LRR) domains of metazoan Toll/TLRs. Before Toll with both domains occurred in Cnidaria (sea anemone, Nematostella vectensis), through domain combinations, TIR-only and LRR-only proteins had already appeared in sponges (Amphimedon queenslandica). Although vertebrate-like TIR (V-TIR) domain already appeared in Cnidaria, the vertebrate-like TLR (V-TLR) with both domains appeared much later. The first combination between V-TIR domain and vertebrate-like LRR (V-LRR) domain for V-TLR may have occurred after the divergence of Cnidaria and bilateria. Then, another combination for V-TLR, a recombination of both domains, possibly occurred before or during the evolution of primitive vertebrates. Taken together, two rounds of domain combinations may thus have co-shaped the vertebrate TLRs.
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[Determination of ethyl glucuronide in human urine by solid phase extraction-gas chromatography-mass spectrometry].
Se Pu
PUBLISHED: 05-24-2011
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A solid phase extraction (SPE) and gas chromatography (GC) with mass spectrometry (MS) method for determination of ethyl glucuronide (EtG) in human urine was established. One mL urine sample was deproteinated by 100 microL 3 mol/L hydrochloric acid and cleaned up through a solid phase extraction column. The target analytes were eluted from an NH2-column with 4% ammonia solution and then treated with bis (trimethylsilyl) trifluoroacetamide (BSTFA) + trimethylchlorosilane (TMCS) (99:1) for derivatization. The derivatized samples were analyzed by GC-MS. Data were acquired in the selected ion monitoring (SIM) mode and the quantitation of EtG was done through internal standard method. Good linearity was obtained at the mass concentration range of 0.1 - 3.2 mg/L with a correlation coefficient (r) of 0.9921. The limit of detection (LOD) was 28.4 microg/L. The range of recoveries was 92.5% - 108.7%, and the relative standard deviations (RSDs) of intra-day and inter-day were all less than 5%. This method is sensitive, specific, accurate and can be applied to the determination of EtG for medicolegal identification and clinical laboratory.
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Neuronal control of Drosophila courtship song.
Neuron
PUBLISHED: 01-18-2011
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The courtship song of the Drosophila male serves as a genetically tractable model for the investigation of the neural mechanisms of decision-making, action selection, and motor pattern generation. Singing has been causally linked to the activity of the set of neurons that express the sex-specific fru transcripts, but the specific neurons involved have not been identified. Here we identify five distinct classes of fru neuron that trigger or compose the song. Our data suggest that P1 and pIP10 neurons in the brain mediate the decision to sing, and to act upon this decision, while the thoracic neurons dPR1, vPR6, and vMS11 are components of a central pattern generator that times and shapes the songs pulses. These neurons are potentially connected in a functional circuit, with the descending pIP10 neuron linking the brain and thoracic song centers. Sexual dimorphisms in each of these neurons may explain why only males sing.
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Dwell position inaccuracy in the Varian GammaMed HDR ring applicator.
J Appl Clin Med Phys
PUBLISHED: 07-26-2010
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Varian has issued two Product Notification Letters warning of known inaccuracies in dwell positions for their GammaMed HDR ring applicator. This inaccuracy was measured for two sets of applicators. Autoexposed radiographs were taken of the HDR source at different dwell positions and analyzed per Varian recommendations using tools within the BrachyVision treatment planning program. Comparison between programmed and actual dwell positions showed the actual positions shifted distally by an average of 0.34 cm (0.17 cm-0.59 cm) across all positions in all rings. A correction method was developed and tested. During planning, the tip of the ring was extrapolated distally beyond its actual position in the patient image set and a proximal offset of the same distance was applied to the dwell positions. A global shift of 0.3 mm corrected all but the most proximal actual dwell position to within +2 mm of the planned position.
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Prolonged survival of human hepatocarcinoma cells in the liver of newborn C57BL/6 mice and resulting cellular xenorejection, especially the activation of hepatic natural killer T cells.
Pathobiology
PUBLISHED: 05-28-2010
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To investigate the fate of human hepatocellular carcinoma (HCC) in the livers of newborn mice and the resulting cellular rejection.
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Comparison of intensity-modulated radiotherapy using helical tomotherapy and segmental multileaf collimator-based techniques for nasopharyngeal carcinoma: dosimetric analysis incorporating quality assurance guidelines from RTOG 0225.
Technol. Cancer Res. Treat.
PUBLISHED: 05-06-2010
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Intensity-modulated radiotherapy (IMRT) treatment plans generated by segmental multileaf collimator (SMLC) and helical tomotherapy (HT) techniques for patients with nasopharyngeal carcinoma were compared using standardized criteria proposed by Radiation Therapy Oncology Group (RTOG) protocol 0225. The goal was to deliver a prescribed dose of 70 Gy to at least 95% of the planning target volume (PTV) encompassing gross tumor, and 59.4 Gy and 50.4 Gy, respectively, to areas at high and low risk for microscopic disease, over 33 treatments while respecting constraints to organs at risk (OAR). HT-IMRT significantly reduced dose to the contralateral parotid gland and improved dose homogeneity to the PTVs. Mean doses to the inner and middle ears were also reduced by 18% and 24%, respectively, on the ipsilateral side, and 24%, and 35%, respectively, on the contralateral side using HT-IMRT compared to SMLC-IMRT. Additionally, HT-IMRT reduced mean doses to brainstem (p = 0.02), larynx (p = 0.03), and oral cavity (p = 0.03). These findings suggest that HT-IMRT may be of improve the therapeutic ratio in the radiotherapeutic treatment of nasopharyngeal carcinoma.
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Systems biology visualization tools for drug target discovery.
Expert Opin Drug Discov
PUBLISHED: 04-19-2010
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Importance of the field: Post-genome drug development has been driven by the need to study biological perturbations at the molecular system level. Systems biology visualization tools can help researchers extract hidden patterns from complex and large Omics data sets, model disease molecular mechanisms, and identify drug targets and drugs with good pharmacological and toxicological profiles. Areas covered in this review: This review covers basic concepts in developing and applying information visualization tools to systems biology. We describe a framework and basic data representation schemes for visual data analysis in systems biology. We review major application areas of these visualization tools within drug discovery by focusing on early-stage drug discovery tasks such as disease biology modeling, target identifications and lead identification. We also show case studies and summarize our experience using visualization tools as lessons to our readers. What the reader will gain: The reader will understand what visualization tools are available for diverse types of systems biology studies in drug discovery and understand how these tools can help advance drug development. Take home message: In spite of the complexity inherent in systems biology, proper use of information visualization tools may reveal emerging properties hidden in the data and enhance chances of success for drug discovery.
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Enhanced photoluminescence due to lateral ordering of GeSi quantum dots on patterned Si(001) substrates.
Nanotechnology
PUBLISHED: 04-01-2010
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Multilayer ordered GeSi quantum dots (QDs) with thin Si spacers were obtained via self-assembly on pit-patterned Si(001) substrates. The lateral ordering of GeSi QDs predetermined by the periodic pit pattern results in remarkably improved size uniformity in comparison with random QDs on flat substrates. A much stronger and narrower photoluminescence (PL) peak from ordered QDs were observed than that from random ones, particularly at high excitation power. Such enhanced PL signal was attributed to the high density of states and the uniform distribution of excitons in the ordered and uniform QDs, which can efficiently suppress the Auger effect and the Coulomb screening effect. Moreover, anomalous narrowing of the PL peak from the ordered QDs with the excitation power was observed, which was explained in terms of distributed feedback associated with the periodic stacked GeSi QDs.
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Warfarin anticoagulation before angioplasty relieves thrombus burden in Budd-Chiari syndrome caused by inferior vena cava anatomic obstruction.
J. Vasc. Surg.
PUBLISHED: 03-18-2010
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Pulmonary embolism (PE) is one of the major complications after percutaneous balloon angioplasty (PTBA) for Budd-Chiaris syndrome (BCS). The purpose of this study was to investigate the role of warfarin pre-treatment in the prevention of PE after PTBA in patients with large inferior vena cava (IVC) thrombus.
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Vector analysis of prostate patient setup with image-guided radiation therapy via kV cone beam computed tomography.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-23-2010
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To analyze the daily setup variations in a cohort of intensity-modulated radiation therapy (IMRT) prostate cancer patients who had received daily image-guided RT without the use of fiducial markers to determine if daily image guidance is necessary.
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[Chemical constituents and antitumor activity on leukemia K562 cell of Leonurus heterophyllus].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 11-10-2009
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The chemical constituents of Leonurus heterophyllus were separated and purified by repeated column chromatography on silica gel, HPD 100, Sephadex LH-20, and PHPLC. Each compound was characterized by spectroscopic and physical data. Eight compounds have been purified and identified to be quercetin 3-O-robinobioside (1), rutin (2), isoquerci trin (3), hyperoside (4), quercetin (5), apigenin (6), genkwanin (7), and benzoic acid (8). Among them, compounds 2, 5-7 were isolated from L. heterophyllus for the first time; Compounds 1, 3, 4, 8 were obtained for the first time from the genus Leonurus. The in vitro activities against leukemia K562 Cells of pure components were evaluated by testing their IC50. Compounds 1-6, 8 exhibited in-vitro inhibitory activities against leukemia K562 cells in different extent.
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HAPPI: an online database of comprehensive human annotated and predicted protein interactions.
BMC Genomics
PUBLISHED: 07-07-2009
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Human protein-protein interaction (PPIs) data are the foundation for understanding molecular signalling networks and the functional roles of biomolecules. Several human PPI databases have become available; however, comparisons of these datasets have suggested limited data coverage and poor data quality. Ongoing collection and integration of human PPIs from different sources, both experimentally and computationally, can enable disease-specific network biology modelling in translational bioinformatics studies.
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Initial clinical experience with helical tomotherapy for head and neck cancer.
Head Neck
PUBLISHED: 05-01-2009
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To report a single-institutional experience with the use of helical tomotherapy (HT)-based intensity-modulated radiotherapy (IMRT) for head and neck cancer.
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Feasibility and midterm outcomes of percutaneous transhepatic balloon angioplasty for symptomatic Budd-Chiari syndrome secondary to hepatic venous obstruction.
J. Vasc. Surg.
PUBLISHED: 04-05-2009
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This study evaluated the feasibility and outcomes of percutaneous transhepatic balloon angioplasty (PTBA) of the hepatic vein in the management of Budd-Chiari syndrome (BCS) secondary to hepatic venous outflow obstruction.
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Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract.
Hum. Mutat.
PUBLISHED: 03-24-2009
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Congenital cataracts (CCs) are clinically and genetically heterogeneous. Mutations in the same gene may lead to CCs differing in inheritance, morphology and severity. Loci for autosomal dominant posterior polar CC and total CC have both been mapped to the chromosomal 1p36 region harboring the EPHA2 receptor tyrosine kinase gene. Here, we report mutations of EPHA2 in three CC families from different ancestral groups. In a Chinese family with posterior polar CC, we identified a missense mutation, c.2819C>T (p.T940I), replacing a critical amino acid that functions at the receptor oligomerization interface. In a British family with posterior polar CC and an Australian family with total CC, we found a frameshift mutation (c.2915_2916delTG) and a splicing mutation (c.2826-9G>A), respectively. These two mutations are predicted to produce novel C-terminal polypeptides with 39 identical amino acids. Yeast two-hybrid analysis showed stronger interaction between the total CC-associated mutant EPHA2 and low molecular weight protein-tyrosine phosphatase, a negative regulator of EPHA2 signaling. Our results implicate the Eph-ephrin signaling system in development of human cataract and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCs.
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Utility of megavoltage fan-beam CT for treatment planning in a head-and-neck cancer patient with extensive dental fillings undergoing helical tomotherapy.
Med Dosim
PUBLISHED: 02-10-2009
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The purpose of this study was to demonstrate the potential utility of megavoltage fan-beam computed tomography (MV-FBCT) for treatment planning in a patient undergoing helical tomotherapy for nasopharyngeal carcinoma in the presence of extensive dental artifact. A 28-year-old female with locally advanced nasopharyngeal carcinoma presented for radiation therapy. Due to the extensiveness of the dental artifact present in the oral cavity kV-CT scan acquired at simulation, which made treatment planning impossible on tomotherapy planning system, MV-FBCT imaging was obtained using the HI-ART tomotherapy treatment machine, with the patient in the treatment position, and this information was registered with her original kV-CT scan for the purposes of structure delineation, dose calculation, and treatment planning. To validate the feasibility of the MV-FBCT-generated treatment plan, an electron density CT phantom (model 465, Gammex Inc., Middleton, WI) was scanned using MV-FBCT to obtain CT number to density table. Additionally, both a "cheese" phantom (which came with the tomotherapy treatment machine) with 2 inserted ion chambers and a generic phantom called Quasar phantom (Modus Medical Devices Inc., London, ON, Canada) with one inserted chamber were used to confirm dosimetric accuracy. The MV-FBCT could be used to clearly visualize anatomy in the region of the dental artifact and provide sufficient soft-tissue contrast to assist in the delineation of normal tissue structures and fat planes. With the elimination of the dental artifact, the MV-FBCT images allowed more accurate dose calculation by the tomotherapy system. It was confirmed that the phantom material density was determined correctly by the tomotherapy MV-FBCT number to density table. The ion chamber measurements agreed with the calculations from the MV-FBCT generated phantom plan within 2%. MV-FBCT may be useful in radiation treatment planning for nasopharyngeal cancer patients in the setting of extensive dental artifacts.
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Finding fractal patterns in molecular interaction networks: a case study in Alzheimers disease.
Int J Comput Biol Drug Des
PUBLISHED: 01-04-2009
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The identification of molecular entities involved in human diseases has been a primary focus of post-genomic biomedicine for pursuing the clinical goals of diagnosis and therapeutic treatment. An emerging perspective in systems biology is that the essential biological roles of molecular entities seem to be well correlated with general molecular network properties. Several types of biological complex networks, including protein interaction networks, have a feature of scale-free networks that relates to fractals (multi-scale self-similarity). Using Alzheimers Disease (AD) as a case study, we constructed an AD-relevant protein interaction subnetwork. We further developed a computational framework based on Ant Colony Optimisation (ACO) to rank disease network relevant nodes. In this framework, the task of ranking nodes is represented as the problem of finding optimal density distributions of ant colonies on all nodes of the network. Our results also revealed fractal-like properties of the network.
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Characterization of sFRP2-like in amphioxus: insights into the evolutionary conservation of Wnt antagonizing function.
Evol. Dev.
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Wnt signaling plays a key role in embryonic patterning and morphogenetic movements. The secreted Frizzled-related proteins (sFRPs) antagonize Wnt signaling, but their roles in development are poorly understood. To determine whether function of sFRPs is conserved between amphioxus and vertebrates, we characterized sFRP2-like function in the amphioxus, Branchiostoma belcheri tsingtauense (B. belcheri). As in other species of Branchiostome, in B. belcheri, expression of sFRP2-like is restricted to the mesendoderm during gastrulation and to the anterior mesoderm and endoderm during neurulation. Functional analyses in frog (Xenopus laevis) indicate that amphioxus sFRP2-like potently inhibits both canonical and non-canonical Wnts. Thus, sFRP-2 probably functions in amphioxus embryos to inhibit Wnt signaling anteriorly. Moreover, dorsal overexpression of amphioxus sFRP2-like in Xenopus embryos, like inhibition of Wnt11, blocks gastrulation movements. This implies that sFRP2-like may also modulate Wnt signaling during gastrulation movements in amphioxus.
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Regulation of estradiol and progesterone production by CRH-R1 and -R2 is through divergent signaling pathways in cultured human placental trophoblasts.
Endocrinology
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CRH and its related peptides urocortins (UCN) have been identified in placenta and implicated to play pivotal roles in the regulation of pregnancy and parturition in humans. The objectives of present study were to investigate the effects of endogenous CRH and its related peptides in the regulation of steroid production in placenta. Placental trophoblasts were isolated from term placenta tissues and cultured for 72 h. Estradiol (E(2)) and progesterone (P(4)) contents in culture media were determined by radioimmunoassay. Treatment of cultured trophoblasts with CRH or UCNI antibody showed decreased E(2), whereas increased P(4) production. Treatment of cells with CRH receptor type 1 antagonist antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased E(2) but increased P(4) production. Knockdown of CRH receptor type 1 or CRH-R2 cells showed a decrease in E(2) production and an increase in P(4) production. In CRH-R2 knockdown cells, CRH stimulated GTP-bound G?s protein and phosphorylated phospholipase C-?3. Adenylyl cyclase and protein kinase A inhibitors blocked CRH-induced increased E(2) production but not decreased P(4) production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine blocked the effects of CRH on E(2) and P(4) production in CRH-R2 knockdown cells. UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound G?i protein and phosphorylated phospholipase C-?3 expression. Both U73122 and chelerythrine blocked UCNIII-induced increased E(2) production and decreased P(4) production. We suggest that CRH and its related peptides might be involved in changes in the progesterone to estrogen ratio during human pregnancy.
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Multifunctional ZnPc-loaded mesoporous silica nanoparticles for enhancement of photodynamic therapy efficacy by endolysosomal escape.
Biomaterials
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The cellular uptake and localization of photosensitizer-loaded nanoparticles have significant impact on photodynamic therapy (PDT) efficacy due to short lifetime and limited action radius of singlet oxygen. Herein, we develop poly(ethylene glycol) (PEG)- and polyethylenimine (PEI)-functionalized zinc(II) phthalocyanine (ZnPc)-loaded mesoporous silica nanoparticles (MSNs), which are able to distribute in the cytosol by endolysosomal escape. In this photosensitizer-carrier system (PEG-PEI-MSNs/ZnPc), ZnPc is a PDT agent; MSNs are the nanocarrier for encapsulating ZnPc; PEI facilitates endosomal escape; and PEG enhances biocompatibility. The as-synthesized PEG-PEI-MSNs/ZnPc have a high escape efficiency from the lysosome to the cytosol due to the "proton sponge" effect of PEI. Compared with the ZnPc-loaded MSNs, the phototoxicity of the PEG-PEI-MSNs/ZnPc is greatly enhanced in vitro. By measuring the mitochondrial membrane potential, a significant loss of >80% ??m after treatment with PEG-PEI-MSNs/ZnPc-PDT is observed. It is further demonstrated that the ultra-efficient passive tumor targeting and excellent PDT efficacy are achieved in tumor-bearing mice upon intravenous injection of PEG-PEI-MSNs/ZnPc and the followed light exposure. We present here a strategy for enhancement of PDT efficacy by endolysosomal escape and highlight the promise of using multifunctional MSNs for cancer therapy.
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Fabrication of crystal ?-Si?N?/Si-SiOx core-shell/Au-SiOx peapod-like axial double heterostructures for optoelectronic applications.
Nanotechnology
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Novel crystal ?-Si(3)N(4)/Si-SiO(x) core-shell/Au-SiO(x) peapod-like axial double heterostructural nanowires were obtained by directly annealing a Au covered SiO(2) thin film on a Si substrate. Our extensive electron microscopic investigation revealed that the ?-Si(3)N(4) sections with a mathematical left angle bracket 101 mathematical right angle bracket growth direction were grown first, followed by growth of the Si-SiO(x) core-shell sections and finally growth of the Au-SiO(x) peapod-like sections. Through a series of systematically comparative experiments, a temperature-dependent multi-step vapor-liquid-solid growth mechanism is proposed. Room temperature photoluminescence measurement of individual nanowires reveals two emission peaks (410 and 515 nm), indicating their potential applications in light sources, laser or light emitting display devices.
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A simple electrochemical aptasensor for ultrasensitive protein detection using cyclic target-induced primer extension.
Biosens Bioelectron
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A simple electrochemical aptasensor was developed for ultrasensitive protein detection by combining a novel strategy of cyclic target-induced primer extension (CTIPE) with an aptamer-hairpin probe and enzyme-amplified electrochemical readout. In the presence of protein target, the immobilized aptamer-hairpin probe recognized the protein to trigger primer extension reaction by target-induced conformational transition, which released the protein from replicated DNA duplex. The released target could cyclically bind with other aptamer-hairpin probes and trigger new primer extension, leading to formation of numerous biotin-tagged DNA duplex, which significantly amplified the protein recognition event and facilitated the subsequent enzymatic signal enhancement, leading to an ultrasensitive electrochemical aptasensor. Using human vascular endothelial growth factor as a model protein, the designed aptasensor could detect protein down to 0.82 pg mL(-1) with a linear range from 1 pg mL(-1) to 1 ng mL(-1). The proposed aptasensor was amenable to quantification of protein in complex biological matrixes, and would become a simple and powerful tool for bioanalysis and clinic diagnostic application.
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BMP4 was associated with NSCL/P in an Asian population.
PLoS ONE
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The Bone Morphogenetic Protein 4 gene (BMP4) is located in chromosome 14q22-q23 which has shown evidence of linkage for isolated nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a genome wide linkage analysis of human multiplex families. BMP4 has been shown to play crucial roles in lip and palatal development in animal models. Several candidate gene association analyses also supported its potential risk for NSCL/P, however, results across these association studies have been inconsistent. The aim of the current study was to test for possible association between markers in and around the BMP4 gene and NSCL/P in Asian and Maryland trios.
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Label-free and high-sensitive detection of Salmonella using a surface plasmon resonance DNA-based biosensor.
J. Biotechnol.
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A method based on surface plasmon resonance (SPR) DNA biosensor has been developed for label-free and high-sensitive detection of Salmonella. A biotinylated single-stranded oligonucleotide probe was designed to target a specific sequence in the invA gene of Salmonella and then immobilized onto a streptavidin coated dextran sensor surface. The invA gene was isolated from bacterial cultures and amplified using a modified semi-nested asymmetric polymerase chain reaction (PCR) technique. In order to investigate the hybridization detection, experiments with different concentration of synthetic target DNA sequences have been performed. The calibration curve of synthetic target DNA had good linearity from 5 nM to 1000 nM with a detection limit of 0.5 nM. The proposed method was applied successfully to the detection of single-stranded invA amplicons from three serovars of Salmonella, i.e., Typhimurium, Enterica and Derby, and the responses to PCR products were related to different S. typhimurium concentrations in the range from 10(2) to 10(10) CFU mL(-1). While with this system to detect E. coli and S. aureus, no significant signal was observed, demonstrating good selectivity of the method. In addition, the hybridization can be completed within 15 min, and the excellent sensor surface regeneration allows at least 300 assay cycles without obvious loss of performance.
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Electrochemical immunosensor for competitive detection of neuron specific enolase using functional carbon nanotubes and gold nanoprobe.
Talanta
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An electrochemical immunosensor for detection of neuron specific enolase (NSE) was designed by immobilizing NSE covalently functionalized single-walled carbon nanotubes (NSE-SWNTs) on a glassy carbon electrode. The NSE-SWNTs not only enhanced electrochemical signal but also presented abundant antigen domains for competitive immunological recognition to anti-NSE primary antibody and then gold nanoprobes labeled with alkaline phosphatase conjugated secondary antibody (AP-anti-IgG/AuNPs). The AP-anti-IgG/AuNPs exhibited highly catalytic activity toward enzyme substrate and significantly amplified the amperometric signal for target molecule detection. Based on the dual signal amplification of SWNTs and gold nanoprobe, the immunosensor could response down to 0.033 ng mL(-1) NSE with a linear range from 0.1 ng mL(-1) to 2 ?g mL(-1), and showed acceptable precision and reproducibility. The designed immunosensor was amenable to direct quantification of target protein with a wide range of concentration in complex clinical serum specimens. The assay results were in a good agreement with the reference values. The proposed electrochemical immunosensor provided a pragmatic platform for convenient detection of tumor markers in clinical diagnosis.
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Development of a standardized method for contouring the lumbosacral plexus: a preliminary dosimetric analysis of this organ at risk among 15 patients treated with intensity-modulated radiotherapy for lower gastrointestinal cancers and the incidence of rad
Int. J. Radiat. Oncol. Biol. Phys.
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To generate a reproducible step-wise guideline for the delineation of the lumbosacral plexus (LSP) on axial computed tomography (CT) planning images and to provide a preliminary dosimetric analysis on 15 representative patients with rectal or anal cancers treated with an intensity-modulated radiotherapy (IMRT) technique.
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Benefit of enactment over oral repetition of verbal instruction does not require additional working memory during encoding.
Psychon Bull Rev
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For this research, we used a dual-task approach to investigate the involvement of working memory in following written instructions. In two experiments, participants read instructions to perform a series of actions on objects and then recalled the instructions either by spoken repetition or performance of the action sequence. Participants engaged in concurrent articulatory suppression, backward-counting, and spatial-tapping tasks during the presentation of the instructions, in order to disrupt the phonological-loop, central-executive, and visuospatial-sketchpad components of working memory, respectively. Recall accuracy was substantially disrupted by all three concurrent tasks, indicating that encoding and retaining verbal instructions depends on multiple components of working memory. The accuracy of recalling the instructions was greater when the actions were performed than when the instructions were repeated, and this advantage was unaffected by the concurrent tasks, suggesting that the benefit of enactment over oral repetition does not cost additional working memory resources.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.