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Find video protocols related to scientific articles indexed in Pubmed.
Durability, inactivation and regeneration of silver tetratantalate in photocatalytic H2 evolution.
Phys Chem Chem Phys
PUBLISHED: 11-20-2014
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The prepared Ag2Ta4O11 photocatalyst exhibits durable activity for H2 production from water. We investigated the durability, inactivation and regeneration mechanism in depth. This work provides a new perspective and makes an important step for the research on Ag-based photocatalysts.
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MeT-DB: a database of transcriptome methylation in mammalian cells.
Nucleic Acids Res.
PUBLISHED: 11-08-2014
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Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. The MethylTranscriptome DataBase (MeT-DB, http://compgenomics.utsa.edu/methylation/) is the first comprehensive resource for N6-methyladenosine (m(6)A) in mammalian transcriptome. It includes a database that records publicaly available data sets from methylated RNA immunoprecipitation sequencing (MeRIP-Seq), a recently developed technology for interrogating m(6)A methyltranscriptome. MeT-DB includes ?300k m(6)A methylation sites in 74 MeRIP-Seq samples from 22 different experimental conditions predicted by exomePeak and MACS2 algorithms. To explore this rich information, MeT-DB also provides a genome browser to query and visualize context-specific m(6)A methylation under different conditions. MeT-DB also includes the binding site data of microRNA, splicing factor and RNA binding proteins in the browser window for comparison with m(6)A sites and for exploring the potential functions of m(6)A. Analysis of differential m(6)A methylation and the related differential gene expression under two conditions is also available in the browser. A global perspective of the genome-wide distribution of m(6)A methylation in all the data is provided in circular ideograms, which also act as a navigation portal. The query results and the entire data set can be exported to assist publication and additional analysis.
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Fas signaling promotes chemoresistance in gastrointestinal cancer by up-regulating P-glycoprotein.
Oncotarget
PUBLISHED: 10-22-2014
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Fas signaling promotes metastasis of gastrointestinal (GI) cancer cells by inducing epithelial-mesenchymal transition (EMT), and EMT acquisition has been found to cause cancer chemoresistance. Here, we demonstrated that the response to chemotherapy of GI cancer patients with higher expression of FasL was significantly worse than patients with lower expression. Fas-induced activation of the ERK1/2-MAPK pathway decreased the sensitivity of GI cancer cells to chemotherapeutic agents and promoted the expression of P-glycoprotein (P-gp). FasL promoted chemoresistance of GI cancer cell via upregulation of P-gp by increasing ?-catenin and decreasing miR-145. ?-catenin promoted P-gp gene transcription by binding with P-gp promoter while miR-145 suppressed P-gp expression by interacting with the mRNA 3'UTR of P-gp. Immunostaining and qRT-PCR analysis of human GI cancer samples revealed a positive association among FasL, ?-catenin, and P-gp, but a negative correlation between miR-145 and FasL or P-gp. Altogether, our results showed Fas signaling could promote chemoresistance in GI cancer through modulation of P-gp expression by ?-catenin and miR-145. Our findings suggest that Fas signaling-based cancer therapies should be administered cautiously, as activation of this pathway may not only lead to apoptosis but also induce chemoresistance.
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Large-scale assessment of missed opportunity risks in a complex hospital setting.
Inform Health Soc Care
PUBLISHED: 10-18-2014
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In this research, we apply a large-scale logistic regression analysis to assess the patient missed opportunity risks at a complex VA (US Department of Veterans Affairs) hospital in three categories, namely, no-show alone, no-show combined with late patient cancellation and no-show combined with late patient and clinic cancellations. The analysis includes unique explanatory variables related to VA patients for predicting missed opportunity risks. Furthermore, we develop two aggregated weather indices by combining many weather measures and include them as explanatory variables. The results indicate that most of the explanatory variables considered are significant factors for predicting the missed opportunity risks. Patients with afternoon appointment, higher percentage service connected, and insurance, married patients, shorter lead time and appointments with longer appointment length are consistently related to lower risks of missed opportunity. Furthermore, the VA patient-related factors and the two proposed weather indices are useful predictors for the risks of no-show and patient cancellation. More importantly, this research presents an effective procedure for VA hospitals and clinics to analyze the missed opportunity risks within the complex VA information technology system, and help them to develop proper interventions to mitigate the adverse effects caused by the missed opportunities.
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Spectroscopic properties and continuous-wave laser operation of Yb:Bi4Si3O12 crystal.
Opt Express
PUBLISHED: 10-17-2014
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Yb3+:Bi4Si3O12 single crystal with Yb3+ concentration of 5.7 at.% has been grown successfully by the Czochralski method. The energy level positions of Yb3+ in Bi4Si3O12 crystal were determined based on the absorption and fluorescence spectra. The peak absorption cross-section is 0.98 × 10-20 cm2 at 976 nm and the peak emission cross-section is 0.57 × 10-20 cm2 at 1035 nm. The fluorescence lifetime of the excited multiplet is 1.26 ms. Diode-pumped continuous-wave laser operation around 1038 nm has been demonstrated in the Yb3+:Bi4Si3O12 crystal with a slope efficiency of 27% and maximum output power of 240 mW.
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PDGF-BB and bFGF ameliorate radiation-induced intestinal progenitor/stem cell apoptosis via AKT/p53 signaling in mice.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 10-11-2014
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Radiation-induced gastrointestinal (GI) syndrome, so far, has no effective prophylactic and therapeutical treatment. Previous studies and our data have demonstrated the critical role of p53 in acute radiation-induced GI syndrome in mice. Many cytokines, such as tumor necrosis factor- and fibroblast growth factor (bFGF), have been found to protect against radiation-induced intestinal injury, although the underlying mechanisms remain to be identified. Here, we report blockage of p53 through a protein kinase B (AKT) pathway in intestinal progenitor/stem cells (ISCs) or crypt cells as a novel molecular mechanism of growth-factor-mediated intestinal radioprotection. Treatment with platelet-derived growth factor (PDGF-BB) and bFGF activated intestinal crypt AKT of phosphorylation, lessened intestinal crypt p53 expression, decreased radiation-induced apoptosis in mouse intestinal progenitor/stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)-positive cells by 50% in average, and thereby significantly increased the survival rate of mice with abdominal radiation by three days in average. Conversely, AKT inhibitor perifosine obstructed growth-factor-simulated AKT phosphorylation while promoted radiation-induced p53 expression in intestinal crypt. Importantly, reduced AKT phosphorylation and elevated p53 expression by AKT inhibitor perifosine impaired intestinal progenitor/stem cells radioprotection provided by PDGF-BB and bFGF. Consistently, PDGF-BB and bFGF both upregulated AKT activation, suppressed radiation-evoked p53 expression, and abrogated radiation-induced apoptosis in IEC-6 cells, although p53 overexpression in IEC-6 cells could partially counteract radioprotection of PDGF-BB and bFGF. Our data strongly suggest that intestinal crypt radioprotection by PDGF-BB and bFGF is dependent on regulation of AKT/p53 signaling.
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Annexin A2 complexes with S100 proteins: structure, function and pharmacological manipulation.
Br. J. Pharmacol.
PUBLISHED: 10-05-2014
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Annexin A2 (AnxA2) was originally identified as a substrate of the pp60v-src oncoprotein in transformed chicken embryonic fibroblasts (Cooper et al., 1982; Erikson et al., 1984; Gerke et al., 1984). It is an abundant protein that associates with biological membranes as well as the actin cytoskeleton (Harder et al., 1994; Thiel et al., 1992), and has been implicated in intracellular vesicle fusion, the organisation of membrane domains, lipid rafts and membrane-cytoskeleton contacts (Gerke et al., 2005). In addition to an intracellular role, AnxA2 has been reported to participate in processes localised to the cell surface including extracellular protease regulation and cell cell interactions (Bharadwaj et al., 2013; Luo et al., 2013). There are many reports showing that AnxA2 is differentially expressed between normal and malignant tissue and potentially involved in tumour progression. An important aspect of AnxA2 function relates to its interaction with small Ca(2+) dependent adaptor proteins called S100 proteins, which is the topic of this review. The interaction between AnxA2 and S100A10 has been very well characterised historically; more recently other S100 proteins have been shown to interact with AnxA2 as well. The biochemical evidence for the occurrence of these protein interactions will be discussed, as well as their function. Recent studies aiming to generate inhibitors of S100 protein interactions will be described and the potential of these inhibitors to further our understanding of AnxA2 S100 protein interactions will be discussed.
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An advanced Ag-based photocatalyst Ag2Ta4O11 with outstanding activity, durability and universality for removing organic dyes.
Phys Chem Chem Phys
PUBLISHED: 10-03-2014
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Constructing Ag-based photocatalysts by the incorporation of Ag(+) ions into metal/nonmetal oxides for removing organic pollutants is a recently developed strategy, but overcoming their own photocorrosion is still a tremendous challenge. In this work, an advanced Ag-based photocatalyst Ag2Ta4O11 is obtained by this strategy, which exhibits improved photocatalytic activity compared with Ta2O5 and the universality for degrading several organic dyes. Importantly, the Ag2Ta4O11 photocatalyst has outstanding durability and reusability, which indicates that it has potential application prospects for organic wastewater treatment in the printing and dyeing industry.
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AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.
N. Engl. J. Med.
PUBLISHED: 09-03-2014
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The androgen-receptor isoform encoded by splice variant 7 lacks the ligand-binding domain, which is the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of androgen-receptor splice variant 7 messenger RNA (AR-V7) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone.
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QT restitution properties during exercise in male patients with coronary artery disease.
Ann Noninvasive Electrocardiol
PUBLISHED: 08-29-2014
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The hypothesis of action potential duration restitution (APDR) suggests that wave break is mainly determined by the steepness of APDR curve. The purpose of this study was to investigate the QT restitution properties by a noninvasive method, exercise ECG test, in patients with and without left anterior descending coronary artery disease (CAD).
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Calcium/calmodulin?dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor??B and Akt?mediated matrix metalloproteinase?9 production.
Mol Med Rep
PUBLISHED: 08-28-2014
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Calcium/calmodulin?dependent protein kinase II (CaMKII) is a multi-functional serine/threonine protein kinase, involved in processes that cause tumor progression, including cell cycle regulation, apoptosis and differentiation. However, the role of CaMKII in cancer cell metastasis has not been fully elucidated. In the present study, the function of CaMKII in gastric cancer cell metastasis is reported. Firstly, it was demonstrated that the overexpression of H282R (constitutively active CaMKII) enhanced gastric cancer cell migration and invasion, and the inhibition of CaMKII activity by KN?62 decreased gastric cancer cell metastasis. Furthermore, H282R upregulated matrix metalloproteinase?9 (MMP?9) expression and production, which were dependent on CaMKII?mediated increase in nuclear factor (NF)??B and Akt activation. Finally, CaMKII activation, through phosphorylation of the Thr 286 site, was significantly increased in the metastatic gastric cancer tissues compared with non?metastatic tissues, suggesting that CaMKII has an important function in the regulation of gastric cancer cell metastasis. Collectively, the present study demonstrated that CaMKII promotes gastric cancer cell metastasis by NF??B and Akt?mediated?MMP?9 production. These findings suggest a novel function of CaMKII in the control of gastric cancer metastasis, offering a promising target for future therapeutics to treat and prevent gastric cancer metastases via the inhibition of CaMKII activity.
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A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis.
Tumour Biol.
PUBLISHED: 08-07-2014
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Cancer cells exhibit the ability to metabolise glucose to lactate even under aerobic conditions for energy. This phenomenon is known as the Warburg effect and can be a potential target to kill cancer cells. Several studies have shown evidence for interplay between microRNAs and key metabolic enzyme effecters, which can facilitate the Warburg effect in cancer cells. In the present study, a microRNA sponge forcibly expressed using a lentiviral vector was utilised to knock down miR-21 expression in vitro. qPCR and Western blot assays were performed to evaluate the expression of a regulatory factor related to aerobic glycolysis and the signalling pathway it regulates. In bladder cancer specimens, expression levels of glycolysis-related genes [glucose transporter (GLUT)1, GLUT3, lactic dehydrogenase (LDH)A, LDHB, hexokinase (HK)1, HK2, pyruvate kinase type M (PKM) and hypoxia-inducible factor 1-alpha (HIF-1?)] were higher in tumour tissues than in adjacent tissues, suggesting the role of glycolysis in bladder cancer. miR-21 inhibition in bladder cancer cell lines resulted in reduction in tumour aerobic glycolysis. Decrease in glucose uptake and lactate production was observed upon expression of the miR-21 sponge, which promoted phosphatase and tensin homologue (PTEN) expression, decreased phosphorylated AKT and deactivated mTOR. Furthermore, messenger RNA (mRNA) and protein expression levels of glycolysis-related genes were also lower in miR-21 sponge cells compared to miR-21 control cells. Our findings suggest that miR-21 acts as a molecular switch to regulate aerobic glycolysis in bladder cancer cells via the PTEN/phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Blocking miR-21 function can be an effective diagnostic and therapeutic approach either by itself or in combination with existing methods to treat bladder cancer.
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Gold(I)-Catalyzed Highly Diastereo- and Enantioselective Alkyne Oxidation/Cyclopropanation of 1,6-Enynes.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-29-2014
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A highly enantioselective oxidative cyclopropanation of 1,6-enynes catalyzed by cationic Au(I) /chiral phophoramidite complexes is presented. The new method provides convenient access to densely functionalized bicyclo[3.1.0]hexanes bearing three contiguous quaternary and tertiary stereogenic centers with high enantioselectivity (up to e.r. 98:2). Control experiments suggest that the quinoline moiety of the ?-gold vinyloxyquinolinium intermediate in the reaction plays an important role in promoting good enantioselectivity through a transitional auxiliary effect in the transition state.
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Clinical significance of tumor-derived IL-1? and IL-18 in localized renal cell carcinoma: Associations with recurrence and survival.
Urol. Oncol.
PUBLISHED: 07-20-2014
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Interleukin-1? (IL-1?) and IL-18 are products of activated inflammasomes that play central roles in innate immunity and inflammation. This study was aimed to determine the effect of tumor-derived IL-1? and IL-18 on recurrence and survival of patients with localized clear cell renal cell carcinoma (ccRCC) following surgery.
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Lineage of origin in rhabdomyosarcoma informs pharmacological response.
Genes Dev.
PUBLISHED: 07-18-2014
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Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1.
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Association of serum vaspin and adiponectin levels with renal function in patients with or without type 2 diabetes mellitus.
J Diabetes Res
PUBLISHED: 07-15-2014
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Vaspin and adiponectin are two adipocytokines with antidiabetic effects. Some studies reported that levels of adiponectin and vaspin were correlated with decreased glomerular filtration rate (FGR) and increased albuminuria. We therefore evaluated the vaspin and adiponectin levels in renal insufficiency (RI) patients with or without T2DM. Serum vaspin, adiponectin levels were measured in 416 subjects with or without T2DM. Analysis was made between groups divided by these subjects presence or absence of RI. We found that serum adiponectin level was significantly higher in nondiabetic patients with RI than in nondiabetic subjects without RI; however, there were no statistical differences between the diabetic patients with RI and without RI. In all the subjects, the serum adiponectin level was also higher in 50 individuals with RI than that in 366 subjects without RI. The serum vaspin levels showed no significant differences between the diabetic patients or nondiabetics subjects with RI and without RI. Contrary to adiponectin, the serum vaspin level was lower in 169 patients with T2DM than in 247 individuals without T2DM. Our data suggested that both of T2DM and renal insufficiency were correlated with the serum level of adiponectin. However, the serum vaspin levels showed no significant difference between the individuals with renal insufficiency and without renal insufficiency.
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Telecom-band degenerate-frequency photon pair generation in silicon microring cavities.
Opt Lett
PUBLISHED: 07-01-2014
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In this Letter, telecom-band degenerate-frequency photon pairs are generated in a specific mode of a silicon microring cavity by the nondegenerate spontaneous four-wave mixing (SFWM) process, under two continuous-wave pumps at resonance wavelength of two different cavity modes. The ratio of coincidence to accidental coincidence is up to 100 under a time bin width of 5 ns, showing their characteristics of quantum correlation. Their quantum interference in balanced and unbalanced Mach-Zehnder interferometers is investigated theoretically and experimentally, and the results show potential in quantum metrology and quantum information.
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Endoplasmic reticulum stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) protects against pressure overload-induced heart failure and lung remodeling.
Hypertension
PUBLISHED: 06-23-2014
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Studies have reported that development of congestive heart failure is associated with increased endoplasmic reticulum stress. Double stranded RNA-activated protein kinase R-like endoplasmic reticulum kinase (PERK) is a major transducer of the endoplasmic reticulum stress response and directly phosphorylates eukaryotic initiation factor 2?, resulting in translational attenuation. However, the physiological effect of PERK on congestive heart failure development is unknown. To study the effect of PERK on ventricular structure and function, we generated inducible cardiac-specific PERK knockout mice. Under unstressed conditions, cardiac PERK knockout had no effect on left ventricular mass, or its ratio to body weight, cardiomyocyte size, fibrosis, or left ventricular function. However, in response to chronic transverse aortic constriction, PERK knockout mice exhibited decreased ejection fraction, increased left ventricular fibrosis, enhanced cardiomyocyte apoptosis, and exacerbated lung remodeling in comparison with wild-type mice. PERK knockout also dramatically attenuated cardiac sarcoplasmic reticulum Ca(2+)-ATPase expression in response to aortic constriction. Our findings suggest that PERK is required to protect the heart from pressure overload-induced congestive heart failure.
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DNA methylation is developmentally regulated for genes essential for cardiogenesis.
J Am Heart Assoc
PUBLISHED: 06-21-2014
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DNA methylation is a major epigenetic mechanism altering gene expression in development and disease. However, its role in the regulation of gene expression during heart development is incompletely understood. The aim of this study is to reveal DNA methylation in mouse embryonic hearts and its role in regulating gene expression during heart development.
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A novel manganese complex LMnAc selectively kills cancer cells by induction of ROS-triggered and mitochondrial-mediated cell death.
Sci China Life Sci
PUBLISHED: 06-16-2014
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We previously identified a novel synthesized metal compound, LMnAc ([L2Mn2(Ac)(H2O)2](Ac) (L=bis(2-pyridylmethyl) amino-2-propionic acid)). This compound exhibited significant inhibition on cancer cell proliferation and was more selective against cancer cells than was the popular chemotherapeutic reagent cisplatin. In this study, we further investigated the underlying molecular mechanisms of LMnAc-induced cancer cell death. We found that LMnAc achieved its selectivity against cancer cells through the transferrin-transferrin receptor system, which is highly expressed in tumor cells. LMnAc triggered cancer cells to commit autophagy and apoptosis, which was mediated by the mitochondrial pathway. Moreover, LMnAc disrupted mitochondrial function, resulting in mitochondrial membrane potential collapse and ATP reduction. In addition, LMnAc induced intracellular Ca(2+) overload and reactive oxygen species generation. Interestingly, its anticancer effect was significantly reduced following pretreatment with the antioxidant N-acetyl cysteine, indicating that reactive oxygen species triggered cell death. Altogether, our data suggest that LMnAc appears to be a selectively promising anticancer drug candidate.
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Aluminum plasmonic nanoparticles enhanced dye sensitized solar cells.
Opt Express
PUBLISHED: 06-13-2014
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We present an investigation on utilizing plasmonic aluminium (Al) nanoparticles (NPs) to enhance the optical absorption of dye-sensitized solar cells (DSCs). The Al NPs exhibit not only the light absorption enhancement in solar cells with localized surface plasmon (LSP) effect but also the chemical stability to iodide/triiodide electrolyte. Besides, the lower work function (~4.06 eV), compared with that of TiO? (~4.6 eV), may suppress the quenching processes, such as charge transfer to metal NPs, to reduce the loss. Thus, high concentration of Al NPs could be incorporated into the TiO? anodes, and the power conversion efficiency (PCE) of DSCs is improved by nearly 13%. Moreover, electrochemical impedance spectroscopy (EIS) characterization also indicates that the plasmonic DSCs with Al NPs present better electrochemical performance than regular ones, which contributes to the improvement of PCE of the device.
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Integrated silicon modulator based on microring array assisted MZI.
Opt Express
PUBLISHED: 06-13-2014
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A silicon modulator with microring array assisted MZI is experimentally demonstrated on silicon-on-insulator wafer through CMOS-compatible process. The footprint of the whole modulator is about 600 ?m(2). With forward-biased current-driven p-n junction, the 3-dB modulation bandwidth is ~2GHz. Furthermore, the impact of ambient temperature is minified with the help of MZI. Within temperature range of 10 - 70 °C, the maximum divergence of modulation curve is less than ~3 dB.
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Diode-pumped 1.5-1.6 ?m laser operation in Er³? doped YbAl?(BO?)? microchip.
Opt Express
PUBLISHED: 06-13-2014
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Er3+ doped YbAl3(BO3)4 crystal with large absorption coefficient of 184 cm(-1) at pump wavelength of 976 nm is a promising microchip gain medium of 1.5-1.6 ?m laser. End-pumped by a 976 nm diode laser, 1.5-1.6 ?m continuous-wave laser with maximum output power of 220 mW and slope efficiency of 8.1% was obtained at incident pump power of 4.54 W in a c-cut 200-?m-thick Er:YbAl3(BO3)4 microchip. When a Co2+:Mg0.4Al2.4O4 crystal was used as the saturable absorber, 1521 nm passively Q-switched pulse laser with about 0.19 ?J energy, 265 ns duration, and 96 kHz repetition rate was realized.
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Early gene expression in salivary gland after isoproterenol treatment.
J. Cell. Biochem.
PUBLISHED: 06-10-2014
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Isoproterenol, a ?-adrenergic agonist, has been shown to induce salivary gland hyperplasia. However, the mechanism involved in this pharmacological phenomenon is not well understood. To gain a better understanding of the underlying changes, including genes, networks and pathways altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60?min after isoproterenol injection. After isoproterenol treatment, the number of differentially expressed genes was increased in a time-dependent manner. Pathway analysis showed that cell hyperplasia, p38(MAPK) , and IGF-1 were the most altered function, network and pathway, respectively. The balanced regulation of up- and down-expression of genes related to cell proliferation/survival may provide a better understanding of the mechanism of isoproterenol-induced parotid gland enlargement without tumor transformation. J. Cell. Biochem. © 2014 Wiley Periodicals, Inc.
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Novel Garnet-structure Ca(2)GdZr(2)(AlO(4))3:Ce(3+) phosphor and its structural tuning of optical properties.
Inorg Chem
PUBLISHED: 06-10-2014
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Aluminate garnet phosphors Ca2GdZr2(AlO4)3:Ce(3+) (CGZA:Ce(3+)) for solid-state white lighting sources are reported. The crystal structure and Mulliken bonding population of the CGZA:Ce(3+) have been analyzed. The larger 5d ((2)D) barycenter shift ?c and smaller phenomenological parameter 10Dq of Ce(3+) in CGZA are related to the larger covalent character of Ce-O. The tuning spectral properties of the Ce(3+)-doped CGZA-based isostructural phosphors are presented. The splitting of cubic crystal field energy level (2)Eg in Ca2REZr2(AlO4)3:Ce(3+) (CREZA:Ce(3+)) (RE = Lu, Y, and Gd) increases as the radius of RE(3+) increases, and the splitting of (2)Eg may dominate the difference of spectroscopic red-shift D(A) in CREZA:Ce(3+). The splitting of the (2)Eg in CaGd2ZrSc(AlO4)3:Ce(3+) (CGZSA:Ce(3+)) phosphors increases seemly due to the decreasing of the covalent character of Ce-O. Thermal quenching properties of Ce(3+)-doped CGZA-based isostructural phosphors are also presented and analyzed. For CREZA:Ce(3+) phosphors, the increasing of the radius of RE(3+) results in an enhancement of thermal quenching. The quenching of CGZSA:Ce(3+) is obviously stronger mainly due to the smaller energy difference between the lowest 5d excited state and 4f ground state.
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An insight into advances in the pathogenesis and therapeutic strategies of spinocerebellar ataxia type 3.
Rev Neurosci
PUBLISHED: 06-08-2014
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Abstract Spinocerebellar ataxia type 3 (SCA3) is the most common type of spinocerebellar ataxia, which are inherited neurodegenerative diseases. CAG repeat expansions that translate into an abnormal length of glutamine residues are considered to be the disease-causing mutation. The pathological mechanisms of SCA3 are not fully elucidated but may include aggregate or inclusion formation, imbalance of cellular protein homeostasis, axonal transportation dysfunction, translation dysregulation, mitochondrial damage and oxidative stress, abnormal neural signaling pathways, etc. Currently, symptom relief is the only available therapeutic route; however, promising therapeutic targets have been discovered, such as decreasing the mutant protein through RNA interference (RNAi) and antisense oligonucleotides (AONs) and replacement therapy using stem cell transplantation. Other potential targets can inhibit the previously mentioned pathological mechanisms. However, additional efforts are necessary before these strategies can be used clinically.
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A nonapoptotic role for CASP2/caspase 2: modulation of autophagy.
Autophagy
PUBLISHED: 06-01-2014
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CASP2/caspase 2 plays a role in aging, neurodegeneration, and cancer. The contributions of CASP2 have been attributed to its regulatory role in apoptotic and nonapoptotic processes including the cell cycle, DNA repair, lipid biosynthesis, and regulation of oxidant levels in the cells. Previously, our lab demonstrated CASP2-mediated modulation of autophagy during oxidative stress. Here we report the novel finding that CASP2 is an endogenous repressor of autophagy. Knockout or knockdown of CASP2 resulted in upregulation of autophagy in a variety of cell types and tissues. Reinsertion of Caspase-2 gene (Casp2) in mouse embryonic fibroblast (MEFs) lacking Casp2 (casp2(-/-)) suppresses autophagy, suggesting its role as a negative regulator of autophagy. Loss of CASP2-mediated autophagy involved AMP-activated protein kinase, mechanistic target of rapamycin, mitogen-activated protein kinase, and autophagy-related proteins, indicating the involvement of the canonical pathway of autophagy. The present study also demonstrates an important role for loss of CASP2-induced enhanced reactive oxygen species production as an upstream event in autophagy induction. Additionally, in response to a variety of stressors that induce CASP2-mediated apoptosis, casp2(-/-) cells demonstrate a further upregulation of autophagy compared with wild-type MEFs, and upregulated autophagy provides a survival advantage. In conclusion, we document a novel role for CASP2 as a negative regulator of autophagy, which may provide important insight into the role of CASP2 in various processes including aging, neurodegeneration, and cancer.
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Targeting RPL39 and MLF2 reduces tumor initiation and metastasis in breast cancer by inhibiting nitric oxide synthase signaling.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-29-2014
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We previously described a gene signature for breast cancer stem cells (BCSCs) derived from patient biopsies. Selective shRNA knockdown identified ribosomal protein L39 (RPL39) and myeloid leukemia factor 2 (MLF2) as the top candidates that affect BCSC self-renewal. Knockdown of RPL39 and MLF2 by specific siRNA nanoparticles in patient-derived and human cancer xenografts reduced tumor volume and lung metastases with a concomitant decrease in BCSCs. RNA deep sequencing identified damaging mutations in both genes. These mutations were confirmed in patient lung metastases (n = 53) and were statistically associated with shorter median time to pulmonary metastasis. Both genes affect the nitric oxide synthase pathway and are altered by hypoxia. These findings support that extensive tumor heterogeneity exists within primary cancers; distinct subpopulations associated with stem-like properties have increased metastatic potential.
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[Efficacy and prognostic factors of preoperative radiation therapy of elbow arthrolysis].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 05-24-2014
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To assess the efficacy and prognostic factors of preoperative radiation therapy in patients of elbow arthrolysis.
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An update on complex I assembly: the assembly of players.
J. Bioenerg. Biomembr.
PUBLISHED: 05-16-2014
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Defects in Complex I assembly is one of the emerging underlying causes of severe mitochondrial disorders. The assembly of Complex I has been difficult to understand due to its large size, dual genetic control and the number of proteins involved. Mutations in Complex I subunits as well as assembly factors have been reported to hinder its assembly and give rise to a range of mitochondria disorders. In this review, we summarize the recent progress made in understanding the Complex I assembly pathway. In particularly, we focus on the known as well as novel assembly factors and their role in assembly of Complex I and human disease.
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Snail predicts recurrence and survival of patients with localized clear cell renal cell carcinoma after surgical resection.
Urol. Oncol.
PUBLISHED: 05-15-2014
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Snail (known as SNAI1), a zinc-finger transcription factor, is best known for the induction of epithelial-to-mesenchymal transition, which has emerged as a recognized mechanism underlying epithelial cancer progression. Herein, the aim is to determine the effect of Snail expression on recurrence and survival of patients with localized clear cell renal cell carcinoma (ccRCC) following surgery.
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A high-content morphological screen identifies novel microRNAs that regulate neuroblastoma cell differentiation.
Oncotarget
PUBLISHED: 05-10-2014
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Neuroblastoma, the most common extracranial solid tumor of childhood, arises from neural crest cell precursors that fail to differentiate. Inducing cell differentiation is an important therapeutic strategy for neuroblastoma. We developed a direct functional high-content screen to identify differentiation-inducing microRNAs, in order to develop microRNA-based differentiation therapy for neuroblastoma. We discovered novel microRNAs, and more strikingly, three microRNA seed families that induce neuroblastoma cell differentiation. In addition, we showed that microRNA seed families were overrepresented in the identified group of fourteen differentiation-inducing microRNAs, suggesting that microRNA seed families are functionally more important in neuroblastoma differentiation than microRNAs with unique sequences. We further investigated the differentiation-inducing function of the microRNA-506-3p/microRNA-124-3p seed family, which was the most potent inducer of differentiation. We showed that the differentiation-inducing function of microRNA-506-3p/microRNA-124-3p is mediated, at least partially, by down-regulating expression of their targets CDK4 and STAT3. We further showed that expression of miR-506-3p, but not miR-124-3p, is dramatically upregulated in differentiated neuroblastoma cells, suggesting the important role of endogenous miR-506-3p in differentiation and tumorigenesis. Overall, our functional screen on microRNAs provided the first comprehensive analysis on the involvements of microRNA species in neuroblastoma cell differentiation and identified novel differentiation-inducing microRNAs. Further investigations are certainly warranted to fully characterize the function of the identified microRNAs in order to eventually benefit neuroblastoma therapy.
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Lipid-lowering therapy and lipid goal attainment in patients with metabolic syndrome in China: Subgroup analysis of the Dyslipidemia International Study-China (DYSIS-China).
Atherosclerosis
PUBLISHED: 05-07-2014
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To objectively evaluate lipid-lowering therapy and low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment in metabolic syndrome (MetS) patients in China.
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One-stage dorsal inlay oral mucosa graft urethroplasty for anterior urethral stricture.
BMC Urol
PUBLISHED: 05-01-2014
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Anterior urethral stricture remains a great challenge. We reported our clinical technique and results by using inlay dorsal buccal mucosal graft urethroplasty for repair of anterior urethral stricture.
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Phosphorylation of a WRKY transcription factor by MAPKs is required for pollen development and function in Arabidopsis.
PLoS Genet.
PUBLISHED: 05-01-2014
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Plant male gametogenesis involves complex and dynamic changes in gene expression. At present, little is known about the transcription factors involved in this process and how their activities are regulated. Here, we show that a pollen-specific transcription factor, WRKY34, and its close homolog, WRKY2, are required for male gametogenesis in Arabidopsis thaliana. When overexpressed using LAT52, a strong pollen-specific promoter, epitope-tagged WRKY34 is temporally phosphorylated by MPK3 and MPK6, two mitogen-activated protein kinases (MAPKs, or MPKs), at early stages in pollen development. During pollen maturation, WRKY34 is dephosphorylated and degraded. Native promoter-driven WRKY34-YFP fusion also follows the same expression pattern at the protein level. WRKY34 functions redundantly with WRKY2 in pollen development, germination, and pollen tube growth. Loss of MPK3/MPK6 phosphorylation sites in WRKY34 compromises the function of WRKY34 in vivo. Epistasis interaction analysis confirmed that MPK6 belongs to the same genetic pathway of WRKY34 and WRKY2. Our study demonstrates the importance of temporal post-translational regulation of WRKY transcription factors in the control of developmental phase transitions in plants.
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Prevalence of dyslipidaemia in patients treated with lipid-lowering agents in China: results of the DYSlipidemia International Study (DYSIS).
Atherosclerosis
PUBLISHED: 04-15-2014
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Despite clear guideline recommendations, there is a paucity of data regarding the prevalence and type of persistent lipid profile abnormalities in patients on stable lipid-lowering therapy in China.
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GALNT4 Predicts Clinical Outcome in Patients with Clear Cell Renal Cell Carcinoma.
J. Urol.
PUBLISHED: 04-15-2014
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We investigated the clinical significance of GALNT4 expression in patients with clear cell renal cell carcinoma.
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Diode-pumped passively Q-switched Er3+:Yb3+:Sr3Lu2(BO3)4 laser at 1534 nm.
Opt Express
PUBLISHED: 04-11-2014
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End-pumped by a 970 nm diode laser, 1534 nm pulse laser with about 16 ?J energy, 48 ns duration, and 21 kHz repetition rate was obtained at absorbed pump power of 11.8 W in a Z-cut 1.08-mm-thick Er(3+):Yb(3+):Sr(3)Lu(2)(BO(3))(4) crystal passively Q-switched by a Co(2+):Mg(0.4)Al(2.4)O(4) crystal. The effects of absorbed pump power and resonator cavity length on output performances of the pulse laser were investigated. Compared with that of the Er(3+):Yb(3+):LuAl(3)(BO(3))(4) laser in a similar experimental condition, higher pulse energy realized in the Er(3+):Yb(3+):Sr(3)Lu(2)(BO(3))(4) crystal may be originated from its smaller stimulated-emission cross section at 1534 nm and longer fluorescence lifetime of the (4)I(13/2) upper laser level of Er(3+) ions.
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Nursing for the complete VATS lobectomy performed with non-tracheal intubation.
J Thorac Dis
PUBLISHED: 04-10-2014
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Video-assisted thoracoscopic surgery (VATS) has without doubt been the most important advance in thoracic surgery. The general anesthesia before the tracheal intubation for VATS was often accompanied with tracheal mucosa and lung injuries, which were typically manifested as painful throat, nausea, vomiting, and other symptoms. However, the non-intubated anesthesia VATS can avoid these shortcomings due to its shorter anesthesia time, simpler steps, and quicker post-operative recovery. A total of 63 patients underwent VATS lobectomy under non-intubated anesthesia from July 2012 to July 2013. Good teamwork, proper pre-operative visit, and comfortable intra-operative position had ensured the success of these operations. In conclusion, adequate pre-operative preparation, careful nursing, and close cooperation can achieve a successful non-intubated anesthesia VATS.
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Astrocyte elevated gene-1 (AEG-1) and c-Myc cooperate to promote hepatocarcinogenesis.
Hepatology
PUBLISHED: 04-10-2014
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Astrocyte elevated gene-1 (AEG-1) and c-Myc are overexpressed in human hepatocellular carcinoma (HCC) functioning as oncogenes. AEG-1 is transcriptionally regulated by c-Myc and AEG-1 itself induces c-Myc by activating Wnt/?-catenin signaling pathway. We now document cooperation of AEG-1 and c-Myc in promoting hepatocarcinogenesis by analyzing hepatocyte-specific transgenic mice expressing either AEG-1 (Alb/AEG-1), c-Myc (Alb/c-Myc) or both (Alb/AEG-1/c-Myc). WT and Alb/AEG-1 mice did not develop spontaneous HCC. Alb/c-Myc mice developed spontaneous HCC without distant metastasis while Alb/AEG-1/c-Myc mice developed highly aggressive HCC with frank metastasis to the lungs. Induction of carcinogenesis by N-nitrosodiethylamine (DEN) significantly accelerated the kinetics of tumor formation in all groups. However, in Alb/AEG-1/c-Myc the effect was markedly pronounced with lung metastasis. In vitro analysis showed that Alb/AEG-1/c-Myc hepatocytes acquired increased proliferation and transformative potential with sustained activation of pro-survival and epithelial-mesenchymal transition (EMT) signaling pathways. RNA-sequencing analysis identified a unique gene signature in livers of Alb/AEG-1/c-Myc mice that was not observed when either AEG-1 or c-Myc was overexpressed. Specifically Alb/AEG-1/c-Myc mice overexpressed maternally imprinted non-coding RNAs, such as Rian, Meg-3 and Migr, which are implicated in hepatocarcinogenesis. Knocking down these ncRNAs significantly inhibited proliferation and invasion by Alb/AEG-1/c-Myc hepatocytes. Conclusion: Our studies reveal a novel cooperative oncogenic effect of AEG-1 and c-Myc that might explain the mechanism of aggressive HCC. Alb/AEG-1/c-Myc mice provide a useful model to understand the molecular mechanism of cooperation between these two oncogenes and other molecules involved in hepatocarcinogenesis. This model might also be of use for evaluating novel therapeutic strategies targeting HCC. (Hepatology 2014;).
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Generation of 1.5 ?m discrete frequency-entangled two-photon state in polarization-maintaining fibers.
Opt Lett
PUBLISHED: 04-02-2014
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In this Letter, the generation of a 1.5 ?m discrete frequency-entangled two-photon state is realized based on a piece of commercial polarization-maintaining fiber (PMF). It is connected with a polarization beam splitter to realize a modified Sagnac fiber loop (MSFL). Correlated two-photon states are generated through a spontaneous four-wave-mixing process along the two propagation directions of the MSFL, and output from the MSFL with orthogonal polarizations. Their quantum interference is realized through a 45° polarization collimation between polarization axes of PMFs inside and outside the MSFL, while their phase difference is controlled by the polarization state of the pump light. The frequency-entangled property of the two-photon state is demonstrated by a spatial quantum beating experiment with a fringe visibility of 98.2±1.3%, without subtracting the accidental coincidence counts. The proposed scheme generates a 1.5 ?m discrete frequency-entangled two-photon state in a polarization-maintaining way, which is desired in practical quantum light sources.
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A protocol for RNA methylation differential analysis with MeRIP-Seq data and exomePeak R/Bioconductor package.
Methods
PUBLISHED: 03-28-2014
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Despite the prevalent studies of DNA/Chromatin related epigenetics, such as, histone modifications and DNA methylation, RNA epigenetics has not drawn deserved attention until a new affinity-based sequencing approach MeRIP-Seq was developed and applied to survey the global mRNA N6-methyladenosine (m(6)A) in mammalian cells. As a marriage of ChIP-Seq and RNA-Seq, MeRIP-Seq has the potential to study the transcriptome-wide distribution of various post-transcriptional RNA modifications. We have previously developed an R/Bioconductor package 'exomePeak' for detecting RNA methylation sites under a specific experimental condition or the identifying the differential RNA methylation sites in a case control study from MeRIP-Seq data. Compared with other relatively well studied data types such as ChIP-Seq and RNA-Seq, the study of MeRIP-Seq data is still at very early stage, and existing protocols are not optimized for dealing with the intrinsic characteristic of MeRIP-Seq data. We therein provide here a detailed and easy-to-use protocol of using exomePeak R/Bioconductor package along with other software programs for analysis of MeRIP-Seq data, which covers raw reads alignment, RNA methylation site detection, motif discovery, differential RNA methylation analysis, and functional analysis. Particularly, the rationales behind each processing step as well as the specific method used, the best practice, and possible alternative strategies are briefly discussed. The exomePeak R/Bioconductor package is freely available from Bioconductor: http://www.bioconductor.org/packages/release/bioc/html/exomePeak.html.
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The impact of nonlinear losses in the silicon micro-ring cavities on CW pumping correlated photon pair generation.
Opt Express
PUBLISHED: 03-26-2014
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In this paper, 1.5 ?m correlated photon pairs are generated under continuous wave (CW) pumping in a silicon micro-ring cavity with a Q factor of 8.1 × 10(4). The ratio of coincidences to accidental coincidences (CAR) is up to 200 under a coincidence time bin width of 5 ns. The experiment result of single side photon count shows that the generation rate does not increase as the square of the pump level due to the nonlinear losses in the cavity which reduce the Q factor and impact the field enhancement effect in the cavity under high pump level. Theoretical analysis shows that the photon pair generation rate in the cavity is proportional to the seventh power of the Q factor, which agrees well with the experiment result. It provides a way to analyze the performance of CW pumping correlated photon pair generation in silicon micro-ring cavities under high pump levels.
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Short-term rapamycin treatment in mice has few effects on the transcriptome of white adipose tissue compared to dietary restriction.
Mech. Ageing Dev.
PUBLISHED: 03-24-2014
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Rapamycin, a drug that has been shown to increase lifespan in mice, inhibits the target of rapamycin (TOR) pathway, a major pathway that regulates cell growth and energy status. It has been hypothesized that rapamycin and dietary restriction (DR) extend lifespan through similar mechanisms/pathways. Using microarray analysis, we compared the transcriptome of white adipose tissue from mice fed rapamycin or DR-diet for 6 months. Multidimensional scaling and heatmap analyses showed that rapamycin had essentially no effect on the transcriptome as compared to DR. For example, only six transcripts were significantly altered by rapamycin while mice fed DR showed a significant change in over 1000 transcripts. Using ingenuity pathway analysis, we found that stearate biosynthesis and circadian rhythm signaling were significantly changed by DR. Our findings showing that DR, but not rapamycin, has an effect on the transcriptome of the adipose tissue, suggesting that these two manipulations increase lifespan through different mechanisms/pathways.
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Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4.
Nat. Genet.
PUBLISHED: 02-28-2014
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Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT cases in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.
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Reactive oxygen species in signalling the transcriptional activation of WIPK expression in tobacco.
Plant Cell Environ.
PUBLISHED: 02-13-2014
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Plant mitogen-activated protein kinases represented by tobacco WIPK (wounding-induced protein kinase) and its orthologs in other species are unique in their regulation at transcriptional level in response to stress and pathogen infection. We previously demonstrated that transcriptional activation of WIPK is essential for induced WIPK activity, and activation of salicylic acid-induced protein kinase (SIPK) by the constitutively active NtMEK2(DD) is sufficient to induce WIPK gene expression. Here, we report that the effect of SIPK on WIPK gene expression is mediated by reactive oxygen species (ROS). Using a combination of pharmacological and gain-of-function transgenic approaches, we studied the relationship among SIPK activation, WIPK gene activation in response to fungal cryptogein, light-dependent ROS generation in chloroplasts, and ROS generated via NADPH oxidase. In the conditional gain-of-function GVG-NtMEK2(DD) transgenic tobacco, induction of WIPK expression is dependent on the ROS generation in chloroplasts. Consistently, methyl viologen, an inducer of ROS generation in chloroplasts, highly activated WIPK expression. In addition to chloroplast-originated ROS, H(2)O(2) generated from the cell-surface NADPH oxidase could also activate WIPK gene expression, and inhibition of cryptogein-induced ROS generation also abolished WIPK gene activation. Our data demonstrate that WIPK gene activation is mediated by ROS, which provides a mechanism by which ROS influence cellular signalling processes in plant stress/defence response.
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Energy-time entanglement generation in optical fibers under CW pumping.
Opt Express
PUBLISHED: 02-12-2014
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In this paper, the energy-time entangled photon-pairs at 1.5 ?m are generated by the spontaneous four wave mixing (SFWM) in optical fibers under continuous wave (CW) pumping. The energy-time entanglement property is demonstrated experimentally through an experiment of Franson-type interference. Although the generation rates of the noise photons are one order of magnitude higher than that of the photon-pairs under CW pumping, the impact of noise photons can be highly suppressed in the measurement by a narrow time domain filter supported by superconducting nanowire single photon detectors with low timing jitters and time correlated single photon counting (TCSPC) module with high time resolution. The experiment results show that the SFWM in optical fibers under CW pumping provides a simple and practical way to generate energy-time entanglement at 1.5 ?m, which has great potential for long-distance quantum information applications over optical fibers.
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Pubertal bisphenol A exposure alters murine mammary stem cell function leading to early neoplasia in regenerated glands.
Cancer Prev Res (Phila)
PUBLISHED: 02-11-2014
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Perinatal exposure to bisphenol A (BPA) has been shown to cause aberrant mammary gland morphogenesis and mammary neoplastic transformation. Yet, the underlying mechanism is poorly understood. We tested the hypothesis that mammary glands exposed to BPA during a susceptible window may lead to its susceptibility to tumorigenesis through a stem cell-mediated mechanism. We exposed 21-day-old Balb/c mice to BPA by gavage (25 ?g/kg/d) during puberty for 3 weeks, and a subset of animals were further challenged with one oral dose (30 mg/kg) of 7,12-dimethylbenz(a)anthracene (DMBA) at 2 months of age. Primary mammary cells were isolated at 6 weeks, and 2 and 4 months of age for murine mammary stem cell (MaSC) quantification and function analysis. Pubertal exposure to the low-dose BPA increased lateral branches and hyperplasia in adult mammary glands and caused an acute increase of MaSC in 6-week-old glands and a delayed increase of luminal progenitors in 4-month-old adult gland. Most importantly, pubertal BPA exposure altered the function of MaSC from different age groups, causing early neoplastic lesions in their regenerated glands similar to those induced by DMBA exposure, which indicates that MaSCs are susceptible to BPA-induced transformation. Deep sequencing analysis on MaSC-enriched mammospheres identified a set of aberrantly expressed genes associated with early neoplastic lesions in patients with human breast cancer. Thus, our study for the first time shows that pubertal BPA exposure altered MaSC gene expression and function such that they induced early neoplastic transformation.
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Porcine reproductive and respiratory syndrome virus induces IL-1? production depending on TLR4/MyD88 pathway and NLRP3 inflammasome in primary porcine alveolar macrophages.
Mediators Inflamm.
PUBLISHED: 02-10-2014
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Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. Previous studies have reported that PRRSV infection induced the production of IL-1 ? . However, the cellular sensors and signaling pathways involved in this process have not been elucidated yet. Here, we studied the mechanisms responsible for the production of IL-1 ? in response to highly pathogenic PRRSV. Upon PRRSV infection of primary porcine alveolar macrophages, both mRNA expression and secretion of IL-1 ? were significantly increased in a time- and dose-dependent manner. We also investigated the role of several pattern-recognition receptors and adaptor molecules in this response and showed that the TLR4/MyD88 pathway and its downstream signaling molecules, NF- ? B, ERK1/2, and p38 MAPKs, were involved in IL-1 ? production during PRRSV infection. Treatment with specific inhibitors or siRNA knockdown assays demonstrated that components of the NLRP3 inflammasome were crucial for IL-1 ? secretion but not for IL-1 ? mRNA expression. Furthermore, TLR4/MyD88/NF- ? B signaling pathway was involved in PRRSV-induced expression of NLRP3 inflammasome components. Together, our results deciphered the pathways leading from recognition of PRRSV to the production and release of IL-1 ? , providing a deeper knowledge of the mechanisms of PRRSV-induced inflammation responses.
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A two-stage exon recognition model based on synergetic neural network.
Comput Math Methods Med
PUBLISHED: 01-30-2014
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Exon recognition is a fundamental task in bioinformatics to identify the exons of DNA sequence. Currently, exon recognition algorithms based on digital signal processing techniques have been widely used. Unfortunately, these methods require many calculations, resulting in low recognition efficiency. In order to overcome this limitation, a two-stage exon recognition model is proposed and implemented in this paper. There are three main works. Firstly, we use synergetic neural network to rapidly determine initial exon intervals. Secondly, adaptive sliding window is used to accurately discriminate the final exon intervals. Finally, parameter optimization based on artificial fish swarm algorithm is used to determine different species thresholds and corresponding adjustment parameters of adaptive windows. Experimental results show that the proposed model has better performance for exon recognition and provides a practical solution and a promising future for other recognition tasks.
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Negative elongation factor controls energy homeostasis in cardiomyocytes.
Cell Rep
PUBLISHED: 01-23-2014
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Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor ? (PPAR?), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPAR?-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes.
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PELP1 oncogenic functions involve alternative splicing via PRMT6.
Mol Oncol
PUBLISHED: 01-23-2014
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Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a proto-oncogene that functions as coactivator of the estrogen receptor and is an independent prognostic predictor of shorter survival of breast cancer patients. The dysregulation of PELP1 in breast cancer has been implicated in oncogenesis, metastasis, and therapy resistance. Although several aspects of PELP1 have been studied, a complete list of PELP1 target genes remains unknown, and the molecular mechanisms of PELP1 mediated oncogenesis remain elusive. In this study, we have performed a whole genome analysis to profile the PELP1 transcriptome by RNA-sequencing and identified 318 genes as PELP1 regulated genes. Pathway analysis revealed that PELP1 modulates several pathways including the molecular mechanisms of cancer, estrogen signaling, and breast cancer progression. Interestingly, RNA-seq analysis also revealed that PELP1 regulates the expression of several genes involved in alternative splicing. Accordingly, the PELP1 regulated genome includes several uniquely spliced isoforms. Mechanistic studies show that PELP1 binds RNA with a preference to poly-C, co-localizes with the splicing factor SC35 at nuclear speckles, and participates in alternative splicing. Further, PELP1 interacts with the arginine methyltransferase PRMT6 and modifies PRMT6 functions. Inhibition of PRMT6 reduced PELP1-mediated estrogen receptor activation, cellular proliferation, and colony formation. PELP1 and PRMT6 are co-recruited to estrogen receptor target genes, PELP1 knockdown affects the enrichment of histone H3R2 di-methylation, and PELP1 and PRMT6 coordinate to regulate the alternative splicing of genes involved in cancer. Collectively, our data suggest that PELP1 oncogenic functions involve alternative splicing leading to the activation of unique pathways that support tumor progression and that the PELP1-PRMT6 axis may be a potential target for breast cancer therapy.
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Prognostic Significance of p21-activated Kinase 6 Expression in Patients with Clear Cell Renal Cell Carcinoma.
Ann. Surg. Oncol.
PUBLISHED: 01-18-2014
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To investigate prognostic values of intratumoral p21-activated kinase 6 (PAK6) expression in patients with clear cell renal cell carcinoma (ccRCC).
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Transcriptional regulation of abscisic acid signal core components during cucumber seed germination and under Cu²?, Zn²?, NaCl and simulated acid rain stresses.
Plant Physiol. Biochem.
PUBLISHED: 01-09-2014
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Abscisic acid (ABA) is an important phytohormone that regulates lots of physiological and biochemical processes in plant life cycle, especially in seed germination and stress responses. For exploring the transcriptional regulation of ABA signal transduction during cucumber (Cucumis sativus L.) seed germination and under Cu(2+), Zn(2+), NaCl and simulated acid rain stresses, nine CsPYLs, three group A CsPP2Cs and two subclass III CsSnRK2s were identified from cucumber genome, which respectively showed high sequence similarities and highly conserved domains with homologous genes in Arabidopsis. Based on Real-time PCR analysis, most of the tested genes' expression decreased during cucumber seed germination, which was in accordance with the ABA level variation. In addition, according to the absolute expression, CsPYL1, CsPYL3, CsPP2C5, CsABI1, CsSnRK2.3 and CsSnRK2.4 were highly expressed, indicating that they may play more important roles in ABA signaling during cucumber seed germination. Moreover, most of these highly expressed genes, except CsPYL3, were up-regulated by ABA treatment. Meanwhile, most of the tested genes' expression dramatically changed at the initial water uptake phase, indicating that this period may be critical in the regulation of ABA on seed germination. Under Cu(2+), Zn(2+), NaCl and simulated acid rain stresses, cucumber seed germination percentage decreased and ABA content increased. Meanwhile, the expression of ABA signal transduction core components genes showed specific response to a particular stress and was not always consist with ABA variation. Generally, the expression of CsPYL1, CsPYL3, CsABI1, CsSnRK2.3 and CsSnRK2.4 was sensitive to 120 mM NaCl and 0.5 mM Cu(2+) treatments.
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The role of mitochondria in T-2 toxin-induced human chondrocytes apoptosis.
PLoS ONE
PUBLISHED: 01-01-2014
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T-2 toxin, a mycotoxin produced by Fusarium species, has been shown to cause diverse toxic effects in animals and is also a possible pathogenic factor of Kashin-Beck disease (KBD). The role of mitochondria in KBD is recognized in our recent research. The aim of this study was to evaluate the role of mitochondria in T-2 toxin-induced human chondrocytes apoptosis to understand the pathogenesis of KBD. T-2 toxin decreased chondrocytes viabilities in concentration- and time-dependent manners. Exposure to T-2 toxin can reduce activities of mitochondrial complexes III, IV and V, ??m and the cellular ATP, while intracellular ROS increased following treatment with T-2 toxin. Furthermore, mitochondrial cytochrome c release, caspase-9 and 3 activation and chondrocytes apoptosis were also obviously observed. Interestingly, Selenium (Se) can partly block T-2 toxin -induced mitochondria dysfunction, oxidative damage and chondrocytes apoptosis. These results suggest that the effect of T-2 toxin on human chondrocytes apoptosis may be mediated by a mitochondrial pathway, which is highly consistent with the chondrocytes changes in KBD.
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IL-17A promotes the migration and invasiveness of cervical cancer cells by coordinately activating MMPs expression via the p38/NF-?B signal pathway.
PLoS ONE
PUBLISHED: 01-01-2014
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IL-17A plays an important role in many inflammatory diseases and cancers. We aimed to examine the effect of IL-17A on the invasion of cervical cancer cells and study its related mechanisms.
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Interleukin 17A promotes gastric cancer invasiveness via NF-?B mediated matrix metalloproteinases 2 and 9 expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Interleukin 17A (IL-17A), as a pro-inflammatory cytokine, is involved in pathology of inflammatory diseases and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the invasiveness of gastric cancer (GC). In the study, we found that IL-17A could promote the migration and invasion of GC cells. Furthermore, after treated with IL-17A, the expressions and activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated, while the expressions of TIMP-1 and TIMP-2 were downregulated. Moreover, the nuclear/overall fractions of p65 and p50 were dramatically elevated by IL-17A. Pretreatment with helenalin, a nuclear factor-?B (NF-?B) inhibitor, was proved to abolish the promoting effect of IL-17A on the invasion ability of GC cells and upregulation of MMP-2 and MMP-9. In conclusion, our findings illustrated that IL-17A could promote the invasion of GC cells by activating NF-?B pathway, and subsequently upregulating the expression of MMP-2 and MMP-9. These results may lead to the identification of new diagnostic markers and therapeutic targets of GC.
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Effects of early blood pressure lowering on early and long-term outcomes after acute stroke: an updated meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Hypertension is common after acute stroke onset. Previous studies showed controversial effects of early blood pressure (BP) lowering on stroke outcomes. The aim of this study is to assess the effects of early BP lowering on early and long-term outcomes after acute stroke.
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Meta-analysis reveals a lack of association between UGT2B17 deletion polymorphism and tumor susceptibility.
PLoS ONE
PUBLISHED: 01-01-2014
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UGT2B17 is a vital member of the UGT2 family and functions as a detoxification enzyme which catalyzes the glucuronidation of lipophilic compounds. Accumulating evidences implicates that it may contribute to the susceptibility of tumor risk. Identification of a UGT2B17 deletion polymorphism has attracted studies to evaluate the association between the UGT2B17 deletion polymorphism and tumor risk in diverse populations. However, the available results are conflicting.
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Long-term effect of agricultural reclamation on soil chemical properties of a coastal saline marsh in Bohai Rim, northern China.
PLoS ONE
PUBLISHED: 01-01-2014
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Over the past six decades, coastal wetlands in China have experienced rapid and extensive agricultural reclamation. In the context of saline conditions, long-term effect of cultivation after reclamation on soil chemical properties has not been well understood. We studied this issue using a case of approximately 60-years cultivation of a coastal saline marsh in Bohai Rim, northern China. The results showed that long-term reclamation significantly decreased soil organic carbon (SOC) (-42.2%) and total nitrogen (TN) (-25.8%) at surface layer (0-30 cm) as well as their stratification ratios (SRs) (0-5 cm:50-70 cm and 5-10 cm:50-70 cm). However, there was no significant change in total phosphorus (TP) as well as its SRs under cultivation. Cultivation markedly reduced ratios of SOC to TN, SOC to TP and TN to TP at surface layer (0-30 cm) and their SRs (0-5 cm:50-70 cm). After cultivation, electrical conductivity and salinity significantly decreased by 60.1% and 55.3% at 0-100 cm layer, respectively, suggesting a great desalinization. In contrast, soil pH at 20-70 cm horizons notably increased as an effect of reclamation. Cultivation also changed compositions of cations at 0-10 cm layer and anions at 5-100 cm layer, mainly decreasing the proportion of Na+, Cl- and SO4(2-). Furthermore, cultivation significantly reduced the sodium adsorption ratio and exchangeable sodium percentage in plow-layer (0-20 cm) but not residual sodium carbonate, suggesting a reduction in sodium harm.
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Prediction of nodal involvement in primary rectal carcinoma without invasion to pelvic structures: accuracy of preoperative CT, MR, and DWIBS assessments relative to histopathologic findings.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate the accuracy of preoperative computed tomography (CT), magnetic resonance (MR) imaging and diffusion-weighted imaging with background body signal suppression (DWIBS) in the prediction of nodal involvement in primary rectal carcinoma patients in the absence of tumor invasion into pelvic structures.
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Role of mtDNA haplogroups in the prevalence of knee osteoarthritis in a southern Chinese population.
Int J Mol Sci
PUBLISHED: 01-01-2014
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Mitochondrial DNA (mtDNA) has been implicated in various human degenerative diseases. However, the role of mtDNA in Osteoarthritis (OA) is less known. To investigate whether mtDNA haplogroups contribute to the prevalence of knee OA, we have carried out a comprehensive case-control study on 187 knee OA patients and 420 geographically matched controls in southern China. OA patients were classified on the Kellgren/Lawrence scale from two to four for the disease severity study and the data were analyzed by adjusting for age and sex. We found that patients with haplogroup G (OR = 3.834; 95% CI 1.139, 12.908; p = 0.03) and T16362C (OR = 1.715; 95% CI 1.174, 2.506; p = 0.005) exhibited an increased risk of OA occurrence. Furthermore, patients carrying haplogroup G had a higher severity progression of knee OA (OR = 10.870; 95% CI 1.307, 90.909; p = 0.007). On the other hand, people with haplogroup B/B4 (OR = 0.503; 95% CI 0.283, 0.893; p = 0.019)/(OR = 0.483; 95% CI 0.245, 0.954; p = 0.036) were less susceptible for OA occurrence. Interestingly, we found OA patients also exhibited a general increase in mtDNA content. Our study indicates that the mtDNA haplogroup plays a role in modulating OA development.
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Effects of climatic factors and ecosystem responses on the inter-annual variability of evapotranspiration in a coniferous plantation in subtropical China.
PLoS ONE
PUBLISHED: 01-01-2014
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Because evapotranspiration (ET) is the second largest component of the water cycle and a critical process in terrestrial ecosystems, understanding the inter-annual variability of ET is important in the context of global climate change. Eight years of continuous eddy covariance measurements (2003-2010) in a subtropical coniferous plantation were used to investigate the impacts of climatic factors and ecosystem responses on the inter-annual variability of ET. The mean and standard deviation of annual ET for 2003-2010 were 786.9 and 103.4 mm (with a coefficient of variation of 13.1%), respectively. The inter-annual variability of ET was largely created in three periods: March, May-June, and October, which are the transition periods between seasons. A set of look-up table approaches were used to separate the sources of inter-annual variability of ET. The annual ETs were calculated by assuming that (a) both the climate and ecosystem responses among years are variable (Vcli-eco), (b) the climate is variable but the ecosystem responses are constant (Vcli), and (c) the climate is constant but ecosystem responses are variable (Veco). The ETs that were calculated under the above assumptions suggested that the inter-annual variability of ET was dominated by ecosystem responses and that there was a negative interaction between the effects of climate and ecosystem responses. These results suggested that for long-term predictions of water and energy balance in global climate change projections, the ecosystem responses must be taken into account to better constrain the uncertainties associated with estimation.
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Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
PLoS ONE
PUBLISHED: 01-01-2014
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Rapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (<300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (>4,500) changed significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a change in gene expression (>4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity.
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Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver.
Aging Cell
PUBLISHED: 10-15-2013
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Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone.
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Self-supporting polymer pipes for low loss single-mode THz transmission.
Opt Express
PUBLISHED: 10-10-2013
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In this paper, a self-supporting polymer pipe is proposed and investigated for THz wave transmission. Utilizing fiber drawing technique for polymer fiber, self-supporting pipes with wall thickness of several tens micrometers can be fabricated using polymethylmethacrylate (PMMA). The guiding mechanism and transmission characteristics of the self-supporting pipes are investigated theoretically, showing that it can support single-mode transmission at THz band. The self-supporting pipe samples with different structure parameters are fabricated and measured experimentally, showing that it can support single HE(11) mode transmission. Theoretical analysis and experimental results show that this self-supporting polymer pipe is a promising candidate for low loss THz fibers.
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Variable optical attenuator based on photonic crystal waveguide with low-group-index tapers.
Appl Opt
PUBLISHED: 10-03-2013
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We demonstrate a compact thermo-optic variable optical attenuator (VOA) based on the cutoff effect of W1 photonic crystal waveguide (PCW). In experiment, a variable attenuation range of 29 dB is achieved with a device length of only 16.8 ?m. The coupling loss is also reduced by 7.5±2.5 dB through introducing low-group-index tapers between the W1 PCW and strip waveguide. This VOA provides the largest variable attenuation range in the reported tunable PCW device to our knowledge.
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Comparative study on the acousto-optic Q-switched pulse performances of 1520 and 1560 nm lasers in Er:Yb:RAl3(BO3)4 (R = Y and Lu) crystals.
Opt Express
PUBLISHED: 08-14-2013
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1520 and 1560 nm acousto-optic Q-switched pulse lasers with high peak power and narrow width were respectively realized in Er:Yb:RAl(3)(BO(3))(4) (R = Y and Lu) crystals end-pumped by a 970 nm diode laser. For Er:Yb:LuAl(3)(BO(3))(4) crystal, 1520 nm laser with 350 ?J energy, 32 ns width and 10.9 kW peak power, and 1560 nm laser with 520 ?J energy, 67 ns width and 7.8 kW peak power were respectively obtained at pulse repetition frequency of 1 kHz. For Er:Yb:YAl(3)(BO(3))(4) crystal, 1520 nm laser with 210 ?J energy, 45 ns width and 4.7 kW peak power, and 1560 nm laser with 380 ?J energy, 102 ns width and 3.7 kW peak power were respectively obtained at pulse repetition frequency of 1 kHz. Pulse performances of 1520 and 1560 nm lasers were compared and the narrower pulse width of 1520 nm laser was ascribed to the higher stimulated emission cross-section.
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miR-23a inhibits E-cadherin expression and is regulated by AP-1 and NFAT4 complex during Fas-induced EMT in gastrointestinal cancer.
Carcinogenesis
PUBLISHED: 08-08-2013
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Fas signaling has been shown to induce the epithelial-mesenchymal transition (EMT) to promote gastrointestinal (GI) cancer metastasis, but the involvement of microRNA in this mechanism remains unknown. We found that Fas ligand (FasL) treatment inhibited E-cadherin expression and promoted cell invasion by upregulation of miR-23a, but overexpression of the miR-23a inhibitor could partially block this activity. FasL-induced extracellular signal-regulated kinase/mitogen-activated protein kinase signaling activated the activator protein 1 (AP-1) complex and repressed glycogen synthase kinase-3? activity, which contributed to nuclear translocation of AP-1 and nuclear factor of activated T cells (NFAT4). Nuclear accumulation and interaction of AP-1 and NFAT4 and subsequent binding to the miR-23a promoter led to increased miR-23a expression. Inhibition of Fas signaling by downregulation of the Fas receptor led to a decrease in miR-23a expression and cell invasion ability in vivo and in vitro, as well as an increase in E-cadherin. Evaluation of human GI precancerous and cancer specimens showed that the expression of FasL and miR-23a increased, whereas the expression of E-cadherin decreased during GI cancer progression. A significant correlation was noted between any two of these three molecules. An EMT phenotype was shown to correlate with an advanced cancer stage and worse prognosis. Taken together, our results show that miR-23a participates in the mechanism of the FasL-induced EMT process and may serve as a potential therapeutic target for cancer metastasis.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.