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Find video protocols related to scientific articles indexed in Pubmed.
JOINT IDENTIFICATION OF IMAGING AND PROTEOMICS BIOMARKERS OF ALZHEIMER'S DISEASE USING NETWORK-GUIDED SPARSE LEARNING.
Proc IEEE Int Symp Biomed Imaging
PUBLISHED: 11-20-2014
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Identification of biomarkers for early detection of Alzheimer's disease (AD) is an important research topic. Prior work has shown that multimodal imaging and biomarker data could provide complementary information for prediction of cognitive or AD status. However, the relationship among multiple data modalities are often ignored or oversimplified in prior studies. To address this issue, we propose a network-guided sparse learning model to embrace the complementary information and inter-relationships between modalities. We apply this model to predict cognitive outcome from imaging and proteomic data, and show that the proposed model not only outperforms traditional ones, but also yields stable multimodal biomarkers across cross-validation trials.
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A novel structure-aware sparse learning algorithm for brain imaging genetics.
Med Image Comput Comput Assist Interv
PUBLISHED: 10-17-2014
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Brain imaging genetics is an emergent research field where the association between genetic variations such as single nucleotide polymorphisms (SNPs) and neuroimaging quantitative traits (QTs) is evaluated. Sparse canonical correlation analysis (SCCA) is a bi-multivariate analysis method that has the potential to reveal complex multi-SNP-multi-QT associations. Most existing SCCA algorithms are designed using the soft threshold strategy, which assumes that the features in the data are independent from each other. This independence assumption usually does not hold in imaging genetic data, and thus inevitably limits the capability of yielding optimal solutions. We propose a novel structure-aware SCCA (denoted as S2CCA) algorithm to not only eliminate the independence assumption for the input data, but also incorporate group-like structure in the model. Empirical comparison with a widely used SCCA implementation, on both simulated and real imaging genetic data, demonstrated that S2CCA could yield improved prediction performance and biologically meaningful findings.
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Human connectome module pattern detection using a new multi-graph MinMax cut model.
Med Image Comput Comput Assist Interv
PUBLISHED: 10-17-2014
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Many recent scientific efforts have been devoted to constructing the human connectome using Diffusion Tensor Imaging (DTI) data for understanding the large-scale brain networks that underlie higher-level cognition in human. However, suitable computational network analysis tools are still lacking in human connectome research. To address this problem, we propose a novel multi-graph min-max cut model to detect the consistent network modules from the brain connectivity networks of all studied subjects. A new multi-graph MinMax cut model is introduced to solve this challenging computational neuroscience problem and the efficient optimization algorithm is derived. In the identified connectome module patterns, each network module shows similar connectivity patterns in all subjects, which potentially associate to specific brain functions shared by all subjects. We validate our method by analyzing the weighted fiber connectivity networks. The promising empirical results demonstrate the effectiveness of our method.
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Proton energy optimization and reduction for intensity-modulated proton therapy.
Phys Med Biol
PUBLISHED: 10-08-2014
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Intensity-modulated proton therapy (IMPT) is commonly delivered via the spot-scanning technique. To 'scan' the target volume, the proton beam is controlled by varying its energy to penetrate the patient's body at different depths. Although scanning the proton beamlets or spots with the same energy can be as fast as 10-20?m?s(-1), changing from one proton energy to another requires approximately two additional seconds. The total IMPT delivery time thus depends mainly on the number of proton energies used in a treatment. Current treatment planning systems typically use all proton energies that are required for the proton beam to penetrate in a range from the distal edge to the proximal edge of the target. The optimal selection of proton energies has not been well studied. In this study, we sought to determine the feasibility of optimizing and reducing the number of proton energies in IMPT planning. We proposed an iterative mixed-integer programming optimization method to select a subset of all available proton energies while satisfying dosimetric criteria. We applied our proposed method to six patient datasets: four cases of prostate cancer, one case of lung cancer, and one case of mesothelioma. The numbers of energies were reduced by 14.3%-18.9% for the prostate cancer cases, 11.0% for the lung cancer cases and 26.5% for the mesothelioma case. The results indicate that the number of proton energies used in conventionally designed IMPT plans can be reduced without degrading dosimetric performance. The IMPT delivery efficiency could be improved by energy layer optimization leading to increased throughput for a busy proton center in which a delivery system with slow energy switch is employed.
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Highly-flexible, low-cost, all stainless steel mesh-based dye-sensitized solar cells.
Nanoscale
PUBLISHED: 09-26-2014
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Highly-flexible, ITO-free dye-sensitized solar cells (DSSCs) are fabricated in a simple, all-solution-based, facile, and controllable way. A double mesh structure is applied to DSSCs, and the design principles, especially scale parameters, are analyzed delicately to ensure the power conversion efficiency and mechanical flexibility of the device. The good flexibility of mesh-based DSSCs is verified by systematic bending tests compared to conventional flexible DSSCs based on PET/ITO or metal foil substrates. Commercial carbon ink is used as a counter electrode material, and it is proved to be low-cost and efficient. The double mesh structure design provides an attractive strategy toward the development of flexible and wearable electrochemical energy supplies.
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Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear cell renal cell carcinoma progression.
Mol. Cancer Ther.
PUBLISHED: 09-23-2014
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PTENP1 is a pseudogene of the PTEN tumor suppression gene (TSG). The functions of PTENP1 in clear cell renal cell carcinoma (ccRCC) have not yet been studied. We found that PTENP1 is down-regulated in ccRCC tissues and cells due to methylation. PTENP1 and PTEN are direct targets of microRNA miR-21 and their expression is suppressed by miR-21 in ccRCC cell lines. miR-21 expression promotes ccRCC cell proliferation, migration, invasion in vitro and tumor growth and metastasis in vivo. Overexpression of PTENP1 in cells expressing miR-21 reduces cell proliferation, invasion, tumor growth and metastasis, recapitulating the phenotypes induced by PTEN expression. Overexpression of PTENP1 in ccRCC cells sensitizes these cells to cisplatin and gemcitabine treatments in vitro and in vivo. In clinical samples, the expression of PTENP1 and PTEN is correlated, and both expressions are inversely correlated with miR-21 expression. ccRCC patients with no PTENP1 expression have a lower survival rate. These results suggest that PTENP1 functions as a competing endogenous RNA (ceRNA) in ccRCC to suppress cancer progression.
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Claims, liabilities, injures and compensation payments of medical malpractice litigation cases in China from 1998 to 2011.
BMC Health Serv Res
PUBLISHED: 09-11-2014
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Although China experienced great improvement in their health system, disputes between patients and doctors have increasingly intensified, reaching an unprecedented level. Retrospective analysis of medical malpractice litigation can discover the characteristics and fundamental cause of these disagreements.
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A single-field integrated boost treatment planning technique for spot scanning proton therapy.
Radiat Oncol
PUBLISHED: 09-05-2014
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Intensity modulated proton therapy (IMPT) plans are normally generated utilizing multiple field optimization (MFO) techniques. Similar to photon based IMRT, MFO allows for the utilization of a simultaneous integrated boost in which multiple target volumes are treated to discrete doses simultaneously, potentially improving plan quality and streamlining quality assurance and treatment delivery. However, MFO may render plans more sensitive to the physical uncertainties inherent to particle therapy. Here we present clinical examples of a single-field integrated boost (SFIB) technique for spot scanning proton therapy based on single field optimization (SFO) treatment-planning techniques.
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Preparation and identification of monoclonal antibodies against ?-conotoxin MVIIA.
Monoclon Antib Immunodiagn Immunother
PUBLISHED: 08-30-2014
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?-Conotoxins MVIIA (?-CTX MVIIA) is a peptide with 25 amino acid residues. It is a selective and reversible N-type voltage-gated calcium channel blocker, which could be used as an analgesic for pain. To date, there are no monoclonal antibodies (MAb) for immunoassay against ?-conotoxin MVIIA. In this study, an MAb against ?-conotoxin MVIIA was prepared. The conotoxin-coding DNA sequence was chemically synthesized and cloned into expression vector pGEX-6p-1 and pET32a (+), respectively. The fusion protein GST-CTX was expressed and purified, and was used to immunize BALB/c mice for preparing the anti-CTX antibody. The spleen cells were fused with SP2/0 myeloma cells after the titer of antiserum was detected and qualified. After being screened by indirect ELISA and cloned by limiting dilution, a hybridoma named 4A12, which produces monoclonal antibody specifically against ?-CTX MVIIA, was successfully obtained. It was found that there are 102 chromosomes in the 4A12 cell, and the subclass for the MAb is IgM. The MAb affinity against ?-CTX MVIIA was 7.33×10(9) L/mol, and the cross-reaction test showed that the MAb specifically bound ?-CTX MVIIA. The MAb could be used as a specific antagonist for ?-CTX MVIIA in the physiological study on the CaV channels in the nervous system.
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Transcriptome-guided amyloid imaging genetic analysis via a novel structured sparse learning algorithm.
Bioinformatics
PUBLISHED: 08-28-2014
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Imaging genetics is an emerging field that studies the influence of genetic variation on brain structure and function. The major task is to examine the association between genetic markers such as single-nucleotide polymorphisms (SNPs) and quantitative traits (QTs) extracted from neuroimaging data. The complexity of these datasets has presented critical bioinformatics challenges that require new enabling tools. Sparse canonical correlation analysis (SCCA) is a bi-multivariate technique used in imaging genetics to identify complex multi-SNP-multi-QT associations. However, most of the existing SCCA algorithms are designed using the soft thresholding method, which assumes that the input features are independent from one another. This assumption clearly does not hold for the imaging genetic data. In this article, we propose a new knowledge-guided SCCA algorithm (KG-SCCA) to overcome this limitation as well as improve learning results by incorporating valuable prior knowledge.
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Enhanced biotransformation of dehydroepiandrosterone to 3?,7?,15?-trihydroxy-5-androsten-17-one with Gibberella intermedia CA3-1 by natural oils addition.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 08-22-2014
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Dihydroxylation of dehydroepiandrosterone (DHEA) is an essential step in the synthesis of many important pharmaceutical intermediates. However, the solution to the problem of low biohydroxylation conversion in the biotransformation of DHEA has yet to be found. The effects of natural oils on the course of dihydroxylation of DHEA to 3?,7?,15?-trihydroxy-5-androsten-17-one (7?,15?-diOH-DHEA) were studied. With rapeseed oil (2 %, v/v) addition, the bioconversion efficiency was improved, and the 7?,15?-diOH-DHEA yield was increased by 40.8 % compared with that of the control at DHEA concentration of 8.0 g/L. Meantime, the ratio of 7?,15?-diOH-DHEA to 7?-OH-DHEA was also increased by 4.5 times in the rapeseed oil-containing system. To explain the mechanism underlying the increase of 7?,15?-diOH-DHEA yield, the effects of rapeseed oil on the pH of the bioconversion system, the cell growth and integrity of Gibberella intermedia CA3-1, as well as the membrane composition were systematically studied. The addition of rapeseed oil enhanced the substrate dispersion and maintained the pH of the system during bioconversion. Cells grew better with favorable integrity. The fatty acid profile of G. intermedia cells revealed that rapeseed oil changed the cell membrane composition and improved cell membrane permeability for lipophilic substrates.
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Fast construction of FM-index for long sequence reads.
Bioinformatics
PUBLISHED: 08-08-2014
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We present a new method to incrementally construct the FM-index for both short and long sequence reads, up to the size of a genome. It is the first algorithm that can build the index while implicitly sorting the sequences in the reverse (complement) lexicographical order without a separate sorting step. The implementation is among the fastest for indexing short reads and the only one that practically works for reads of averaged kilobases in length.
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Ancient human genomes suggest three ancestral populations for present-day Europeans.
Iosif Lazaridis, Nick Patterson, Alissa Mittnik, Gabriel Renaud, Swapan Mallick, Karola Kirsanow, Peter H Sudmant, Joshua G Schraiber, Sergi Castellano, Mark Lipson, Bonnie Berger, Christos Economou, Ruth Bollongino, Qiaomei Fu, Kirsten I Bos, Susanne Nordenfelt, Heng Li, Cesare de Filippo, Kay Prüfer, Susanna Sawyer, Cosimo Posth, Wolfgang Haak, Fredrik Hallgren, Elin Fornander, Nadin Rohland, Dominique Delsate, Michael Francken, Jean-Michel Guinet, Joachim Wahl, George Ayodo, Hamza A Babiker, Graciela Bailliet, Elena Balanovska, Oleg Balanovsky, Ramiro Barrantes, Gabriel Bedoya, Haim Ben-Ami, Judit Bene, Fouad Berrada, Claudio M Bravi, Francesca Brisighelli, George B J Busby, Francesco Cali, Mikhail Churnosov, David E C Cole, Daniel Corach, Larissa Damba, George van Driem, Stanislav Dryomov, Jean-Michel Dugoujon, Sardana A Fedorova, Irene Gallego Romero, Marina Gubina, Michael Hammer, Brenna M Henn, Tor Hervig, Ugur Hodoglugil, Aashish R Jha, Sena Karachanak-Yankova, Rita Khusainova, Elza Khusnutdinova, Rick Kittles, Toomas Kivisild, William Klitz, Vaidutis Kučinskas, Alena Kushniarevich, Leila Laredj, Sergey Litvinov, Theologos Loukidis, Robert W Mahley, Bela Melegh, Ene Metspalu, Julio Molina, Joanna Mountain, Klemetti Näkkäläjärvi, Desislava Nesheva, Thomas Nyambo, Ludmila Osipova, Jüri Parik, Fedor Platonov, Olga Posukh, Valentino Romano, Francisco Rothhammer, Igor Rudan, Ruslan Ruizbakiev, Hovhannes Sahakyan, Antti Sajantila, Antonio Salas, Elena B Starikovskaya, Ayele Tarekegn, Draga Toncheva, Shahlo Turdikulova, Ingrida Uktveryte, Olga Utevska, René Vasquez, Mercedes Villena, Mikhail Voevoda, Cheryl A Winkler, Levon Yepiskoposyan, Pierre Zalloua, Tatijana Zemunik, Alan Cooper, Cristian Capelli, Mark G Thomas, Andrés Ruiz-Linares, Sarah A Tishkoff, Lalji Singh, Kumarasamy Thangaraj, Richard Villems, David Comas, Rem Sukernik, Mait Metspalu, Matthias Meyer, Evan E Eichler, Joachim Burger, Montgomery Slatkin, Svante Pääbo, Janet Kelso, David Reich, Johannes Krause.
Nature
PUBLISHED: 07-11-2014
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We sequenced the genomes of a ?7,000-year-old farmer from Germany and eight ?8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ?44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
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Screening, identification and culture optimization of a newly isolated aromatic nitrilase-producing bacterium--Pseudomonas putida CGMCC3830.
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 07-11-2014
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Microbial nitrilases have attracted increasing attention in nitrile hydrolysis for carboxylic acid production in recent years. A bacterium with nitrilase activity was isolated and identified as Pseudomonas putida CGMCC3830 based on its morphology, physiological and biochemical characteristics, as well as 16S rRNA gene sequence. The nitrilase production was optimized by varying culture conditions using the one-factor-at-a-time method and response surface methodology. Glycerol 13.54 g/L, tryptone 11.59 g/L, yeast extract 5.21 g/L, KH2PO4 1 g/L, NaCl 1 g/L, urea 1 g/L, initial pH 6.0 and culture temperature 30 degrees C were proved to be the optimal culture conditions. It resulted in the maximal nitrilase production of 36.12 U/mL from 2.02 U/mL. Investigations on substrate specificity demonstrate P. putida nitrilase preferentially hydrolyze aromatic nitriles. When applied in nicotinic acid synthesis, 2 mg/mL P. putida cells completely hydrolyzed 20.8 g/L 3-cyanopyridine into nicotinic acid in 90 min. The results indicated P. putida CGMCC3830 displayed potential for industrial production of nicotinic acid.
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Toward better understanding of artifacts in variant calling from high-coverage samples.
Bioinformatics
PUBLISHED: 06-27-2014
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Whole-genome high-coverage sequencing has been widely used for personal and cancer genomics as well as in various research areas. However, in the lack of an unbiased whole-genome truth set, the global error rate of variant calls and the leading causal artifacts still remain unclear even given the great efforts in the evaluation of variant calling methods.
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Egr-1 participates in abnormally high gdnf gene transcription mediated by histone hyperacetylation in glioma cells.
Biochim. Biophys. Acta
PUBLISHED: 06-26-2014
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Abnormally high transcription of the glial cell-line derived neurotrophic factor (gdnf) gene in glioma cells is related to the hyperacetylation of histone H3 lysine 9 (H3K9) in its promoter region II, but the mechanism remains unclear. There are three consecutive putative binding sites for the transcription factor early growth response protein 1(Egr-1) in promoter region II of the gdnf gene, and Egr-1 participates in gdnf gene transcription activation. Here we show that the acetylation level of H3K9 at Egr-1 binding sites in gdnf gene promoter region II in rat C6 astroglioma cells was significantly higher than that in normal astrocytes, and the binding capacity was also significantly higher. In C6 astroglioma cells, gdnf gene transcription significantly decreased after Egr-1 knock-down. In addition, the deletion or mutation of the Egr-1 binding site also significantly down-regulated the activity of promoter region II of this gene in vitro. When curcumin decreased the acetylation level of H3K9 at the Egr-1 binding site, the binding of Egr-1 to promoter region II and GDNF mRNA levels significantly decreased. In contrast, trichostatin A treatment significantly increased H3K9 acetylation at the Egr-1 binding site, which significantly increased both the binding of Egr-1 with promoter region II and GDNF mRNA levels. In this context, knocking down Egr-1 significantly reduced the elevation in gdnf gene transcription. Collectively, our results demonstrate that the hyperacetylation of H3K9 at Egr-1 binding sites in promoter region II of the gdnf gene can up-regulate the binding of Egr-1 to increase gdnf gene transcription in glioma cells.
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Development and application of a quantitative fluorescence-based immunochromatographic assay for fumonisin b1 in maize.
J. Agric. Food Chem.
PUBLISHED: 06-26-2014
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A fluorescence-based immunochromatographic assay (ICA) for fumonisin B1 (FB1) that employs conjugates of fluorescent microspheres and monoclonal antibodies (FM-mAbs) as detection reporters is described. The ICA is based on the competitive reaction between FB1-bovine serum albumin (BSA; test line) and the target FB1 for binding to the FM-mAb conjugates. A limit of detection (LOD) for FB1 of 0.12 ng/mL was obtained, with an analytical working range of 0.25-2.0 ng/mL (corresponding to 250-2000 ?g/kg in maize flour samples, according to the extraction procedure). The recoveries of the ICA to detect FB1 in maize samples ranged from 91.4 to 118.2%. A quantitative comparison of the fluorescence-based ICA and HPLC-MS/MS analysis of naturally contaminated maize samples indicated good agreement between the two methods (r(2) = 0.93). By replacing the target of interest, the FM-based ICA can easily be extended to other chemical contaminants and thus represents a versatile strategy for food safety analysis.
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Astrocyte-like cells differentiated from a novel population of CD45-positive cells in adult human peripheral blood.
Cell Biol. Int.
PUBLISHED: 06-11-2014
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We have previously reported a novel CD45-positive cell population called peripheral blood insulin-producing cells (PB-IPCs) and its unique potential for releasing insulin in vitro. Despite the CD45-positive phenotype and self-renewal ability, PB-IPCs are distinguished from hemopoietic and endothelial progenitor cells (EPCs) by some characteristics, such as a CD34-negative phenotype and different culture conditions. We have further identified the gene profiles of the embryonic and neural stem cells, and these profiles include Sox2, Nanog, c-Myc, Klf4, Notch1 and Mash1. After treatment with all-trans retinoic acid (ATRA) in vitro, most PB-IPCs exhibited morphological changes that included the development of elongated and branched cell processes. In the process of induction, the mRNA expression of Hes1 was robustly upregulated, and a majority of cells acquired some astrocyte-associated specific phenotypes including anti-glial fibrillary acidic protein (GFAP), CD44, Glutamate-aspartate transporter (GLAST) and S100?. In spite of the deficiency of glutamate uptaking, the differentiated cells significantly relaxed the regulation of the expression of brain-derived neurotrophic factor (BDNF) mRNA. This finding demonstrates that PB-IPCs could be induced into a population of astrocyte-like cells and enhanced the neurotrophic potential when the state of proliferation was limited by ATRA, which implies that this unique CD45+ cell pool may have a protective role in some degenerative diseases of the central nervous system (CNS).
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Laparoscopic renal cryoablation versus laparoscopic partial nephrectomy for the treatment of small renal masses: a systematic review and meta-analysis of comparative studies.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 06-11-2014
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For small renal masses (SRMs), open partial nephrectomy represents the therapeutic standard of care, and laparoscopic partial nephrectomy (LPN) has provided encouraging outcomes. Laparoscopic renal cryoablation (LRC) could be regarded as an alternative to surgical excision in selected patients, if perioperative complication rates and oncologic results are comparable. However, the short- and long-term outcomes of LRC versus LPN have not been adequately assessed. This study evaluated the safety and efficacy of LRC compared with LPN in the treatment of SRMs.
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Work stress, work motivation and their effects on job satisfaction in community health workers: a cross-sectional survey in China.
BMJ Open
PUBLISHED: 06-07-2014
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It is well documented that both work stress and work motivation are key determinants of job satisfaction. The aim of this study was to examine levels of work stress and motivation and their contribution to job satisfaction among community health workers in Heilongjiang Province, China.
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Fibulin-1 is epigenetically down-regulated and related with bladder cancer recurrence.
BMC Cancer
PUBLISHED: 06-02-2014
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Bladder cancer is one of the most common cancers worldwide. Fibulin-1, a multi-functional extracellular matrix protein, has been demonstrated to be involved in many kinds of cancers, while its function in bladder cancer remains unclear. So here we investigated the expression and function of fibulin-1 in Bladder cancer.
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Dosimetric effects caused by couch tops and immobilization devices: report of AAPM Task Group 176.
Med Phys
PUBLISHED: 06-01-2014
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The dosimetric impact from devices external to the patient is a complex combination of increased skin dose, reduced tumor dose, and altered dose distribution. Although small monitor unit or dose corrections are routinely made for blocking trays, ion chamber correction factors, e.g., accounting for temperature and pressure, or tissue inhomogeneities, the dose perturbation of the treatment couch top or immobilization devices is often overlooked. These devices also increase skin dose, an effect which is also often ignored or underestimated. These concerns have grown recently due to the increased use of monolithic carbon fiber couch tops which are optimal for imaging for patient position verification but cause attenuation and increased skin dose compared to the "tennis racket" style couch top they often replace. Also, arc delivery techniques have replaced stationary gantry techniques which cause a greater fraction of the dose to be delivered from posterior angles. A host of immobilization devices are available and used to increase patient positioning reproducibility, and these also have attenuation and skin dose implications which are often ignored. This report of Task Group 176 serves to present a survey of published data that illustrates the magnitude of the dosimetric effects of a wide range of devices external to the patient. The report also provides methods for modeling couch tops in treatment planning systems so the physicist can accurately compute the dosimetric effects for indexed patient treatments. Both photon and proton beams are considered. A discussion on avoidance of high density structures during beam planning is also provided. An important aspect of this report are the recommendations the authors make to clinical physicists, treatment planning system vendors, and device vendors on how to make measurements of surface dose and attenuation and how to report these values. For the vendors, an appeal is made to work together to provide accurate couch top models in planning systems.
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Relationships between actual and desired workplace characteristics and job satisfaction for community health workers in China: a cross-sectional study.
BMC Fam Pract
PUBLISHED: 05-27-2014
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BackgroundCommunity health workers are the main providers of community health services in China and have been important in the process of health system reform that has been in place since 2009. Therefore, it is critical that healthcare managers and policy decision makers motivate current staff and improve their job satisfaction. This study examined workplace characteristics and their contribution to job satisfaction in community health workers in Heilongjiang Province, China.MethodsA cross-sectional survey of 448 community health workers, from three cities in Heilongjiang province, was conducted between October 1, 2012 and December 31, 2012. Multistage sampling procedures were used to measure socioeconomic and demographic status, job satisfaction, and both actual and desired workplace characteristics. Factor analysis was conducted to determine the main factors contributing to workplace characteristics, and multiple linear regression analysis was performed to assess the key determinants of job satisfaction.ResultsEight groups of factors were identified as the most important workplace characteristics. These comprised system and policy; fringe benefits; work itself; work relationships; professional development; recognition; work environment; and remuneration. In all cases, all desired workplace characteristics were higher than the associated actual workplace characteristics. The main determinants of job satisfaction were occupation, years worked in health service institution, and five subscales representing the gap between desired and actual workplace characteristics, which were system and policy; fringe benefits; working relationship; professional development; and remuneration.ConclusionsThese findings suggested that managers wishing to enhance job satisfaction should assess workplace characteristics comprehensively and design mechanisms that reduce the gap between actual and desired workplace characteristics.
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miRNA-34a Suppresses Cell Proliferation and Metastasis by Targeting CD44 in Human Renal Carcinoma Cells.
J. Urol.
PUBLISHED: 05-19-2014
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We investigated the potential functions of miR-34a in CD44 transcriptional complexes in renal cell carcinoma.
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Genome sequence of a 45,000-year-old modern human from western Siberia.
Nature
PUBLISHED: 05-15-2014
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We present the high-quality genome sequence of a ?45,000-year-old modern human male from Siberia. This individual derives from a population that lived before-or simultaneously with-the separation of the populations in western and eastern Eurasia and carries a similar amount of Neanderthal ancestry as present-day Eurasians. However, the genomic segments of Neanderthal ancestry are substantially longer than those observed in present-day individuals, indicating that Neanderthal gene flow into the ancestors of this individual occurred 7,000-13,000 years before he lived. We estimate an autosomal mutation rate of 0.4 × 10(-9) to 0.6 × 10(-9) per site per year, a Y chromosomal mutation rate of 0.7 × 10(-9) to 0.9 × 10(-9) per site per year based on the additional substitutions that have occurred in present-day non-Africans compared to this genome, and a mitochondrial mutation rate of 1.8 × 10(-8) to 3.2 × 10(-8) per site per year based on the age of the bone.
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[Optimization of hydroxylating DHEA to 7alpha,15alpha-diOH-DHEA by compound mutation and fermentation optimization].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 05-14-2014
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Combined with method of ketoconazole resistance screening, a 7alpha,15alpha-diOH-DHEA high-producing mutant Colletotrichum lini ST-1 was obtained by compound mutation of NTG and low energy N+ ion beam implantation. With the substrate concentration of 10 g/L DHEA, the molar yield of 7alpha,15alpha-diOH-DHEA reached 34.2%, increased by 46.2% than that of the original strain. Then we optimized the medium. First, Plackett-Burman design was used to evaluate the effects of medium components on molar yield of the product. Results show that glucose, yeast extract and MgSO4 x 7H2O were the important parameters for the biotransformation process. Subsequently, the path of steepest ascent was used to approach the optimal levels. To obtain the optimal levels, central composite design and response surface analysis were carried out. The optimal medium was as follows (g/L): glucose 26.34, yeast extract 12.15, corn flour 3.00, FeSO4 x 7H2O 0.015, MgSO4 x 7H2O 0.14, KH2PO4 0.90. Under the optimal conditions, the molar yield of 7alpha,15alpha-diOH-DHEA reached 49.3%, which was 44.2% higher than that of using the medium before optimization.
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Improving the catalytic potential and substrate tolerance of Gibberella intermedia nitrilase by whole-cell immobilization.
Bioprocess Biosyst Eng
PUBLISHED: 05-08-2014
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Comparative studies of immobilized and free cells of Gibberella intermedia CA3-1 in bioconversion of 3-cyanopyridine to nicotinic acid were performed. Entrapping method was chosen based on the advantages in enzymatic activity recovery, mechanical strength and preparation procedure. Four entrapment matrices were investigated and sodium alginate was screened to be the most suitable material. Maximal nitrilase activity of alginate immobilized cells was obtained under conditions of 2 % alginate, 0.6 % CaCl2, 0.4 g cell/g alginate, 1.8 mm bead size. The immobilized cells showed excellent substrate tolerance even when the 3-cyanopyridine concentration was 700 mM. The half-lives of immobilized cells at 30, 40 and 50 °C were 315, 117.5 and 10.9 h, respectively, correspondingly 1.4, 1.6 and 1.7-fold compared with that of the free cells. Efficient reusability of immobilized cells up to 28 batches was achieved and 205.7 g/(g dcw) nicotinic acid was obtained with 80.55 % enzyme activity preserved.
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Clinical Implementation of Intensity Modulated Proton Therapy for Thoracic Malignancies.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 05-01-2014
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Intensity modulated proton therapy (IMPT) can improve dose conformality and better spare normal tissue over passive scattering techniques, but range uncertainties complicate its use, particularly for moving targets. We report our early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance.
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Is there a clinical benefit with a smooth compensator design compared with a plunged compensator design for passive scattered protons?
Med Dosim
PUBLISHED: 04-30-2014
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In proton therapy, passive scattered proton plans use compensators to conform the dose to the distal surface of the planning volume. These devices are custom made from acrylic or wax for each treatment field using either a plunge-drilled or smooth-milled compensator design. The purpose of this study was to investigate if there is a clinical benefit of generating passive scattered proton radiation treatment plans with the smooth compensator design. We generated 4 plans with different techniques using the smooth compensators. We chose 5 sites and 5 patients for each site for the range of dosimetric effects to show adequate sample. The plans were compared and evaluated using multicriteria (MCA) plan quality metrics for plan assessment and comparison using the Quality Reports [EMR] technology by Canis Lupus LLC. The average absolute difference for dosimetric metrics from the plunged-depth plan ranged from -4.7 to +3.0 and the average absolute performance results ranged from -6.6% to +3%. The manually edited smooth compensator plan yielded the best dosimetric metric, +3.0, and performance, + 3.0% compared to the plunged-depth plan. It was also superior to the other smooth compensator plans. Our results indicate that there are multiple approaches to achieve plans with smooth compensators similar to the plunged-depth plans. The smooth compensators with manual compensator edits yielded equal or better target coverage and normal tissue (NT) doses compared with the other smooth compensator techniques. Further studies are under investigation to evaluate the robustness of the smooth compensator design.
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[Value of modified Allis technique in closed reduction of posteriorly dislocated hip with Pipkin I/II fracture].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-29-2014
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To explore the value of modified Allis technique in closed reduction of posteriorly dislocated hip.
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Evaluation of the systematic error in using 3D dose calculation in scanning beam proton therapy for lung cancer.
J Appl Clin Med Phys
PUBLISHED: 04-28-2014
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The objective of this study was to evaluate and understand the systematic error between the planned three-dimensional (3D) dose and the delivered dose to patient in scanning beam proton therapy for lung tumors. Single-field and multifield optimized scanning beam proton therapy plans were generated for ten patients with stage II-III lung cancer with a mix of tumor motion and size. 3D doses in CT datasets for different respiratory phases and the time-weighted average CT, as well as the four-dimensional (4D) doses were computed for both plans. The 3D and 4D dose differences for the targets and different organs at risk were compared using dose-volume histogram (DVH) and voxel-based techniques, and correlated with the extent of tumor motion. The gross tumor volume (GTV) dose was maintained in all 3D and 4D doses, using the internal GTV override technique. The DVH and voxel-based techniques are highly correlated. The mean dose error and the standard deviation of dose error for all target volumes were both less than 1.5% for all but one patient. However, the point dose difference between the 3D and 4D doses was up to 6% for the GTV and greater than 10% for the clinical and planning target volumes. Changes in the 4D and 3D doses were not correlated with tumor motion. The planning technique (single-field or multifield optimized) did not affect the observed systematic error. In conclusion, the dose error in 3D dose calculation varies from patient to patient and does not correlate with lung tumor motion. Therefore, patient-specific evaluation of the 4D dose is important for scanning beam proton therapy for lung tumors.
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[Preliminary study on general regulations for processing of different processing procedures of prepared slices of Chinese crude drugs in China].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 04-24-2014
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General regulations for the processing are the important part of processing procedures of prepared slices of Chinese crude drugs. It has an important significance on enhancing the operability of actual production, regulating production of prepared slices of Chinese crude drugs, improving quality and establishing drug safety. The article could provides suggestions and reference for future compilation work on "National processing procedures of prepared slices of Chinese crude drugs" by comparative analysis and summary on general regulations for the processing of different processing procedures of prepared slices of Chinese crude drugs in China.
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[Descriptive epidemiological study on disabilities attributed to non-dementia organic mental disorder in China].
Beijing Da Xue Xue Bao
PUBLISHED: 04-19-2014
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To describe the prevalence rates of disabilities attributed to non-dementia organic mental disorder and their demographic and regional distributions in China for supporting policy maker to prevent mental disabilities.
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[Descriptive epidemiological study on mental disabilities in China].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 04-18-2014
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To describe the prevalence and characteristics of mental disabilities in China.
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The Efficient Production of 3?,7?,15?-Trihydroxy-5-Androsten-17-One from Dehydroepiandrosterone by Gibberella intermedia.
Appl. Biochem. Biotechnol.
PUBLISHED: 04-16-2014
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The biotransformation of dehydroepiandrosterone (DHEA) by Gibberella intermedia was investigated. The formation of the main products was monitored by high-performance liquid chromatography (HPLC). Products were purified and identified as 3?,7?-dihydroxy-5-androsten-17-one (7?-OH-DHEA) and 3?,7?,15?-trihydroxy-5-androsten-17-one (7?,15?-diOH-DHEA) using mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses. 7?,15?-DiOH-DHEA is a key intermediate for the synthesis of pharmacologically active steroids. A biotransformation process was optimized to obtain a high concentration of 7?,15?-diOH-DHEA. The results showed the optimal biotransformation process under the following conditions: a culture medium containing 15 g/L glucose, 16 g/L yeast extract, 12 g/L corn steep liquor, and 0.15 g/L ferrous sulfate; an initial pH of 6.5; culture temperature of 30 °C; inoculum size of 4 %; 40 mL volume of the culture medium in 250 mL flasks; the addition of 1 % Tween 80 as co-solvent; and the transformation period of 78 h. After optimization, the molar yield of 7?,15?-diOH-DHEA from 5 g/L substrate DHEA was 77.4 %, which was increased by 115 % than the yield obtained in the original bioconversion process.
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Thermal-triggerd proteinquake leads to disassembly of DegP hexamer as an imperative activation step.
Sci Rep
PUBLISHED: 04-11-2014
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The Escherichia coli DegP has been reported to function both as molecular chaperone and protease for the quality control of outer membrane protein biogenesis. Activation of the inactive DegP hexamers was believed to occur via their disassembly into trimeric units and subsequent reassembly into larger oligomers (12-mers and 24-mers). Here, we analyzed the thermal stability and the unfolding dynamics of the different secondary structure components of the DegP hexamers using Fourier transform infrared spectroscopy and temperature-jump nanosecond time-resolved IR difference absorbance spectroscopy. We found that the interfacial secondary structure components possess a degreed thermal stability, with the disassembly of the DegP hexamers follows a "proteinquake" manner, such that the fully exposed parts of the interfacial ?-sheets serving as the temperature sensor and epicenter to drive the sequential unfolding/disassembly process that finishes within about 134?ns at room temperature.
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Wilcoxon's signed-rank statistic: what null hypothesis and why it matters.
Pharm Stat
PUBLISHED: 04-04-2014
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In statistical literature, the term 'signed-rank test' (or 'Wilcoxon signed-rank test') has been used to refer to two distinct tests: a test for symmetry of distribution and a test for the median of a symmetric distribution, sharing a common test statistic. To avoid potential ambiguity, we propose to refer to those two tests by different names, as 'test for symmetry based on signed-rank statistic' and 'test for median based on signed-rank statistic', respectively. The utility of such terminological differentiation should become evident through our discussion of how those tests connect and contrast with sign test and one-sample t-test. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
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[Clinical characters of culture-negative prosthetic joint infection].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 04-04-2014
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To explore the clinical characters and histopathologic differences between patients with culture-positive and culture-negative prosthetic joint infection (PJI).
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Lung nodule classification with multilevel patch-based context analysis.
IEEE Trans Biomed Eng
PUBLISHED: 03-25-2014
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In this paper, we propose a novel classification method for the four types of lung nodules, i.e., well-circumscribed, vascularized, juxta-pleural, and pleural-tail, in low dose computed tomography scans. The proposed method is based on contextual analysis by combining the lung nodule and surrounding anatomical structures, and has three main stages: an adaptive patch-based division is used to construct concentric multilevel partition; then, a new feature set is designed to incorporate intensity, texture, and gradient information for image patch feature description, and then a contextual latent semantic analysis-based classifier is designed to calculate the probabilistic estimations for the relevant images. Our proposed method was evaluated on a publicly available dataset and clearly demonstrated promising classification performance.
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Enhancement of steroid hydroxylation yield from dehydroepiandrosterone by cyclodextrin complexation technique.
Steroids
PUBLISHED: 03-08-2014
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The cyclodextrins (CDs) complexation technique was performed for the enhancement of hydroxylation yield from dehydroepiandrosterone (DHEA) by Colletotrichum lini ST-1. Using DHEA/methyl-?-cyclodextrin (M-?-CD) or DHEA/hydroxypropyl-?-cyclodextrin (HP-?-CD) inclusion complexes as substrate (10g/L), the hydroxylation yields were increased by 14.98% and 20.54% respectively, and the biotransformation course was shortened by 12h. X-ray diffractometry, differential scanning calorimetry, and phase solubility analyses showed an inclusion complex was formed between CDs and DHEA at a molar ratio of 1:1, which remarkably increased the solubility of DHEA, and then improved substrate biotransformation efficiency and hydroxylation yield. Meanwhile, results of thermodynamic parameters (?G, ?H, ?S and Ks) analysis revealed the complexation process was spontaneous and DHEA/CDs inclusion complex was stable. Scanning electron microscopy and transmission electron microscopy showed that the enhancement of DHEA hydroxylation yield also depended on the improvement of cell permeability through interaction between cytomembrane and CDs. These results suggested that the CDs complexation technique was a promising method to enhance steroids hydroxylation yield by increasing steroids solubility and decreasing membrane resistance of substrate and product during biotransformation process.
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Evaluation and mitigation of the interplay effects of intensity modulated proton therapy for lung cancer in a clinical setting.
Pract Radiat Oncol
PUBLISHED: 02-19-2014
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The primary aim of this study was to evaluate the impact of the interplay effects of intensity modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of isolayered rescanning to mitigate these interplay effects.
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Femoral stress and strain changes post-hip, -knee and -ipsilateral hip/knee arthroplasties: a finite element analysis.
Orthop Surg
PUBLISHED: 02-19-2014
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To identify the optimal ratio of free femur for minimizing the risks of periprosthetic fracture.
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The inter-monomer interface of the major light-harvesting chlorophyll a/b complexes of photosystem II (LHCII) influences the chlorophyll triplet distribution.
J. Plant Physiol.
PUBLISHED: 02-04-2014
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Under strong light conditions, long-lived chlorophyll triplets ((3)Chls) are formed, which can sensitize singlet oxygen, a species harmful to the photosynthetic apparatus of plants. Plants have developed multiple photoprotective mechanisms to quench (3)Chl and scavenge singlet oxygen in order to sustain the photosynthetic activities. The lumenal loop of light-harvesting chlorophyll a/b complex of photosystem II (LHCII) plays important roles in regulating the pigment conformation and energy dissipation. In this study, site-directed mutagenesis analysis was applied to investigate triplet-triplet energy transfer and quenching of (3)Chl in LHCII. We mutated the amino acid at site 123 located in this region to Gly, Pro, Gln, Thr and Tyr, respectively, and recorded fluorescence excitation spectra, triplet-minus-singlet (TmS) spectra and kinetics of carotenoid triplet decay for wild type and all the mutants. A red-shift was evident in the TmS spectra of the mutants S123T and S123P, and all of the mutants except S123Y showed a decrease in the triplet energy transfer efficiency. We propose, on the basis of the available structural information, that these phenomena are related to the involvement, due to conformational changes in the lumenal region, of a long-wavelength lutein (Lut2) involved in quenching (3)Chl.
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In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC.
Asian Pac J Trop Med
PUBLISHED: 01-15-2014
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To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.
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Dosimetric benefits of robust treatment planning for intensity modulated proton therapy for base-of-skull cancers.
Pract Radiat Oncol
PUBLISHED: 01-14-2014
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The clinical advantage of intensity modulated proton therapy (IMPT) may be diminished by range and patient setup uncertainties. We evaluated the effectiveness of robust optimization that incorporates uncertainties into the treatment planning optimization algorithm for treatment of base of skull cancers.
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Intramolecular C-F and C-H bond cleavage promoted by butadienyl heavy Grignard reagents.
Nat Commun
PUBLISHED: 01-03-2014
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Organomagnesium compounds (Grignard reagents) are among the most useful organometallic reagents and have greatly accelerated the advancement of synthetic chemistry and related sciences. Nevertheless, heavy Grignard reagents based on the metals calcium, strontium or barium are not widely used, mainly due to their rather inert heavy alkaline-earth metals and extremely high reactivity of their corresponding Grignard-type reagents. Here we report the generation and reaction chemistry of butadienyl heavy Grignard reagents whose extremely high reactivity is successfully tamed. Facile synthesis of perfluoro-?-extended pentalene and naphthalene derivatives is realized by the in situ generated heavy Grignard reagents via intramolecular C-F/C-H bond cleavage. These obtained perfluorodibenzopentalene and perfluorodinaphthopentalene derivatives show low-lying LUMO levels, with one being the lowest value so far among all pentalene derivatives. Our results set an exciting example for the meaningful synthetic application of heavy Grignard reagents.
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Integrative analysis of multi-dimensional imaging genomics data for Alzheimer's disease prediction.
Front Aging Neurosci
PUBLISHED: 01-01-2014
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In this paper, we explore the effects of integrating multi-dimensional imaging genomics data for Alzheimer's disease (AD) prediction using machine learning approaches. Precisely, we compare our three recent proposed feature selection methods [i.e., multiple kernel learning (MKL), high-order graph matching based feature selection (HGM-FS), sparse multimodal learning (SMML)] using four widely-used modalities [i.e., magnetic resonance imaging (MRI), positron emission tomography (PET), cerebrospinal fluid (CSF), and genetic modality single-nucleotide polymorphism (SNP)]. This study demonstrates the performance of each method using these modalities individually or integratively, and may be valuable to clinical tests in practice. Our experimental results suggest that for AD prediction, in general, (1) in terms of accuracy, PET is the best modality; (2) Even though the discriminant power of genetic SNP features is weak, adding this modality to other modalities does help improve the classification accuracy; (3) HGM-FS works best among the three feature selection methods; (4) Some of the selected features are shared by all the feature selection methods, which may have high correlation with the disease. Using all the modalities on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, the best accuracies, described as (mean ± standard deviation)%, among the three methods are (76.2 ± 11.3)% for AD vs. MCI, (94.8 ± 7.3)% for AD vs. HC, (76.5 ± 11.1)% for MCI vs. HC, and (71.0 ± 8.4)% for AD vs. MCI vs. HC, respectively.
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Laparoscopic versus open radical cystectomy in bladder cancer: a systematic review and meta-analysis of comparative studies.
PLoS ONE
PUBLISHED: 01-01-2014
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More recently laparoscopic radical cystectomy (LRC) has increasingly been an attractive alternative to open radical cystectomy (ORC) and many centers have reported their early experiences in the treatment of bladder cancer. Evaluate the safety and efficacy of LRC compared with ORC in the treatment of bladder cancer.
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Patient-specific quantification of respiratory motion-induced dose uncertainty for step-and-shoot IMRT of lung cancer.
Med Phys
PUBLISHED: 12-11-2013
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Purpose: The objective of this study was to quantify respiratory motion-induced dose uncertainty at the planning stage for step-and-shoot intensity-modulated radiation therapy (IMRT) using an analytical technique.Methods: Ten patients with stage II?III lung cancer who had undergone a planning four-dimensional (4D) computed tomographic scan and step-and-shoot IMRT planning were selected with a mix of motion and tumor size for this retrospective study. A step-and-shoot IMRT plan was generated for each patient. The maximum and minimum doses with respiratory motion were calculated for each plan, and the mean deviation from the 4D dose was calculated, taking delivery time, fractionation, and patient breathing cycle into consideration.Results: For all patients evaluated in this study, the mean deviation from the 4D dose in the planning target volume (PTV) was <2.5%, with a standard deviation <1.2%, and maximum point dose variation from the 4D dose was <6.2% in the PTV assuming delivery dose rate of 200 MU?min and patient breathing cycle of 8 s. The motion-induced dose uncertainty is a function of motion, fractionation, MU (plan modulation), dose rate, and patient breathing cycle.Conclusions: Respiratory motion-induced dose uncertainty varies from patient to patient. Therefore, it is important to evaluate the dose uncertainty on a patient-specific basis, which could be useful for plan evaluation and treatment strategy determination for selected patients.
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Improving spot-scanning proton therapy patient specific quality assurance with HPlusQA, a second-check dose calculation engine.
Med Phys
PUBLISHED: 12-11-2013
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Purpose: The purpose of this study was to validate the use of HPlusQA, spot-scanning proton therapy (SSPT) dose calculation software developed at The University of Texas MD Anderson Cancer Center, as second-check dose calculation software for patient-specific quality assurance (PSQA). The authors also showed how HPlusQA can be used within the current PSQA framework.Methods: The authors compared the dose calculations of HPlusQA and the Eclipse treatment planning system with 106 planar dose measurements made as part of PSQA. To determine the relative performance and the degree of correlation between HPlusQA and Eclipse, the authors compared calculated with measured point doses. Then, to determine how well HPlusQA can predict when the comparisons between Eclipse calculations and the measured dose will exceed tolerance levels, the authors compared gamma index scores for HPlusQA versus Eclipse with those of measured doses versus Eclipse. The authors introduce the ??? transformation as a way to more easily compare gamma scores.Results: The authors compared measured and calculated dose planes using the relative depth, z?R × 100%, where z is the depth of the measurement and R is the proton beam range. For relative depths than less than 80%, both Eclipse and HPlusQA calculations were within 2 cGy of dose measurements on average. When the relative depth was greater than 80%, the agreement between the calculations and measurements fell to 4 cGy. For relative depths less than 10%, the Eclipse and HPlusQA dose discrepancies showed a negative correlation, -0.21. Otherwise, the correlation between the dose discrepancies was positive and as large as 0.6. For the dose planes in this study, HPlusQA correctly predicted when Eclipse had and had not calculated the dose to within tolerance 92% and 79% of the time, respectively. In 4 of 106 cases, HPlusQA failed to predict when the comparison between measurement and Eclipses calculation had exceeded the tolerance levels of 3% for dose and 3 mm for distance-to-agreement.Conclusions: The authors found HPlusQA to be reasonably effective (79% ± 10%) in determining when the comparison between measured dose planes and the dose planes calculated by the Eclipse treatment planning system had exceeded the acceptable tolerance levels. When used as described in this study, HPlusQA can reduce the need for patient specific quality assurance measurements by 64%. The authors believe that the use of HPlusQA as a dose calculation second check can increase the efficiency and effectiveness of the QA process.
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Cancer-derived mutations in KEAP1 impair NRF2 degradation but not ubiquitination.
Cancer Res.
PUBLISHED: 12-09-2013
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NRF2 is a transcription factor that mediates stress responses. Oncogenic mutations in NRF2 localize to one of its two binding interfaces with KEAP1, an E3 ubiquitin ligase that promotes proteasome-dependent degradation of NRF2. Somatic mutations in KEAP1 occur commonly in human cancer, where KEAP1 may function as a tumor suppressor. These mutations distribute throughout the KEAP1 protein but little is known about their functional impact. In this study, we characterized 18 KEAP1 mutations defined in a lung squamous cell carcinoma tumor set. Four mutations behaved as wild-type KEAP1, thus are likely passenger events. R554Q, W544C, N469fs, P318fs, and G333C mutations attenuated binding and suppression of NRF2 activity. The remaining mutations exhibited hypomorphic suppression of NRF2, binding both NRF2 and CUL3. Proteomic analysis revealed that the R320Q, R470C, G423V, D422N, G186R, S243C, and V155F mutations augmented the binding of KEAP1 and NRF2. Intriguingly, these super-binder mutants exhibited reduced degradation of NRF2. Cell-based and in vitro biochemical analyses demonstrated that despite its inability to suppress NRF2 activity, the R320Q superbinder mutant maintained the ability to ubiquitinate NRF2. These data strengthen the genetic interactions between KEAP1 and NRF2 in cancer and provide new insight into KEAP1 mechanics.
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Rapid Detection of Mycobacterium tuberculosis and Pyrazinamide Susceptibility Related to pncA Mutations in Sputum Specimens through an Integrated Gene-to-Protein Function Approach.
J. Clin. Microbiol.
PUBLISHED: 11-13-2013
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Testing the pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis isolates is challenging. In a previous paper, we described the development of a rapid colorimetric test for the PZA susceptibility of M. tuberculosis by a PCR-based in vitro-synthesized-pyrazinamidase (PZase) assay. Here, we present an integrated approach to detect M. tuberculosis and PZA susceptibility directly from sputum specimens. M. tuberculosis was detected first, using a novel long-fragment quantitative real-time PCR (LF-qPCR), which amplified a fragment containing the whole pncA gene. Then, the positive amplicons were sequenced to find mutations in the pncA gene. For new mutations not found in the Tuberculosis Drug Resistance Mutation Database (www.tbdreamdb.com), the in vitro PZase assay was used to test the PZA resistance. This approach could detect M. tuberculosis within 3 h with a detection limit of 7.8 copies/reaction and report the PZA susceptibility within 2 days. In an initial testing of 213 sputum specimens, the LF-qPCR found 53 positive samples with 92% sensitivity and 97% specificity compared to the culture test for M. tuberculosis detection. DNA sequencing of the LF-qPCR amplicons revealed that 49 samples were PZA susceptible and 1 was PZA resistant. In the remaining 3 samples, with new pncA mutations, the in vitro PZase assay found that 1 was PZA susceptible and 2 were PZA resistant. This integrated approach provides a rapid, efficient, and relatively low-cost solution for detecting M. tuberculosis and PZA susceptibility without culture.
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Vacuum Rabi Splitting of Exciton-Polariton Emission in an AlN Film.
Sci Rep
PUBLISHED: 10-14-2013
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The vacuum Rabi splitting of exciton-polariton emission is observed in cathodoluminescence (CL) and photoluminescence spectra of an AlN epitaxial film. Atomic force microscopy and CL measurements show that the film has an atomically flat surface, high purity, and high crystal quality. By changing the temperature, anticrossing behavior between the upper and lower polariton branch can be obtained in low temperature with a Rabi splitting of 44?meV, in agreement with the calculation. This large energy splitting is caused by strong oscillator strength, intrinsically pure polarization in wurtzite AlN semiconductor, and high fraction of free exciton in the sample. These properties indicate that AlN can be a potential semiconductor for the further development of polariton physics and polariton-based novel devices.
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Even Four Minutes of Poor Quality of CPR Compromises Outcome in a Porcine Model of Prolonged Cardiac Arrest.
Biomed Res Int
PUBLISHED: 10-04-2013
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Objective. Untrained bystanders usually delivered suboptimal chest compression to victims who suffered from cardiac arrest in out-of-hospital settings. We therefore investigated the hemodynamics and resuscitation outcome of initial suboptimal quality of chest compressions compared to the optimal ones in a porcine model of cardiac arrest. Methods. Fourteen Yorkshire pigs weighted 30?±?2?kg were randomized into good and poor cardiopulmonary resuscitation (CPR) groups. Ventricular fibrillation was electrically induced and untreated for 6?mins. In good CPR group, animals received high quality manual chest compressions according to the Guidelines (25% of animals anterior-posterior thoracic diameter) during first two minutes of CPR compared with poor (70% of the optimal depth) compressions. After that, a 120-J biphasic shock was delivered. If the animal did not acquire return of spontaneous circulation, another 2?mins of CPR and shock followed. Four minutes later, both groups received optimal CPR until total 10?mins of CPR has been finished. Results. All seven animals in good CPR group were resuscitated compared with only two in poor CPR group (P < 0.05). The delayed optimal compressions which followed 4 mins of suboptimal compressions failed to increase the lower coronary perfusion pressure of five non-survival animals in poor CPR group. Conclusions. In a porcine model of prolonged cardiac arrest, even four minutes of initial poor quality of CPR compromises the hemodynamics and survival outcome.
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Approach to multiparticle parallel tracking in thick samples with three-dimensional nanoresolution.
Opt Lett
PUBLISHED: 10-02-2013
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This Letter proposes a method referred to as distorted grating (DG) and double-helix point spread function (DH-PSF) combination microscopy (DDCM), which is capable of multiparticle parallel localization and tracking in a transparent sample thicker than 10 ?m, the thickness of cells. A special phase mask, combining the field depth extension capabilities of DG with the three-dimensional (3D) nanolocalization capabilities of the DH-PSF, is designed for multiparticle parallel localization. Time-lapse tracking of one particle moving along the z axis and parallel tracking of two particles are simulated. Results demonstrate that, with only a single snapshot, particles can be localized, tracking with 3D nanoresolution wherever they are. The theoretical localization precisions of DDCM, DH-PSF, and multifocus microscopy are compared. DDCM results in almost constant localization precisions in all three dimensions for a depth of field larger than 10 ?m. DDCM is expected to become a tool in investigations of important dynamic events in living cells.
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[Screening and condition optimization of a strain for efficiently biotransformation of saponins in Dioscorea zingiberensis into diosgenin].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 09-26-2013
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Diosgenin is an important raw material in steroid hormone and widely used in pharmaceutical industry. The traditional method for diosgenin production is acidolysis, which causes serious pollution. In order to obtain a cleaner and more efficient approach of diosgenin production, a strain of Gibberella intermedia WX12 (the sexual stage of Fusarium proliferatum) was screened from the strains deposited in our laboratory. This strain converted saponins in Dioscorea zingiberensis C.H. Wright (DZW) into diosgenin. The conversion medium was optimized by statistical experimental design. The optimized conversion medium was as follows (g/L): glucose 20.6, yeast extract 5.0, NaCl 1, K2PO4 3, ZnSO4 x 7H2O 1.5 and saponins 3. Under the optimal conditions, the yield of diosgenin achieved to (31 +/- 0.3) mg/g DZW, which was 3 times higher than that of the original medium.
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The complete genome sequence of a Neanderthal from the Altai Mountains.
Nature
PUBLISHED: 09-05-2013
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We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.
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Epigenetic Inactivation of KLF4 is Associated with Urothelial Cancer Progression and Early Recurrence.
J. Urol.
PUBLISHED: 08-27-2013
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KLF4 is a transcription factor with divergent functions in different malignancies. We analyzed KLF4 expression and DNA methylation, and their clinical relevance and biological function in urothelial cancer.
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Quality of chest compressions during compression-only CPR: a comparative analysis following the 2005 and 2010 American Heart Association guidelines.
Am J Emerg Med
PUBLISHED: 08-08-2013
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The latest guidelines both increased the requirements of chest compression rate and depth during cardiopulmonary resuscitation (CPR), which may make it more difficult for the rescuer to provide high-quality chest compression. In this study, we investigated the quality of chest compressions during compression-only CPR under the latest 2010 American Heart Association (AHA) guidelines (AHA 2010) and its effect on rescuer fatigue.
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Role of microRNA-mediated MMP regulation in the treatment and diagnosis of malignant tumors.
Cancer Biol. Ther.
PUBLISHED: 08-05-2013
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Matrix metalloproteinases (MMPs) play important roles in tumor cell proliferation and apoptosis and contribute to tumor growth, angiogenesis, migration, and invasion primarily via extracellular matrix (ECM) degradation and/or the activation of pre-pro-growth factors. Recently, there has been considerable interest in the posttranscriptional regulation of MMPs via microRNAs (miRs). In this review, we highlight the complicated interactive network comprised of different MMPs and their regulating microRNAs, as well as the ways in which these interactions influence cancer development, including tumor angiogenesis, growth, invasion, and metastasis. Based on the conclusive roles that microRNAs play in the regulation of MMPs during cancer progression, we discuss the potential use of microRNA-mediated MMP regulation in the diagnosis and treatment of tumors from the clinical perspective. In particular, microRNA-mediated MMP regulation may lead to the development of promising new MMP inhibitors that target MMPs more selectively, and this approach may also target multiple molecules in a network, leading to the efficient regulation of distinct biological processes relevant to malignant tumors. A thorough understanding of the mechanisms underlying microRNA-mediated MMP regulation during tumor progression will help to provide new insights into the diagnosis and treatment of malignant tumors.
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The cyclophilin CYP20-2 modulates the conformation of BRASSINAZOLE-RESISTANT1, which binds the promoter of FLOWERING LOCUS D to regulate flowering in Arabidopsis.
Plant Cell
PUBLISHED: 07-29-2013
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Brassinosteroids (BRs) regulate many physiological processes during plant development, including flowering. However, little is known about the components of BR signaling that mediate flowering. Here, we report that BRASSINAZOLE-RESISTANT1 (BZR1), the conformation of which is altered by a cyclophilin (CYP20-2), binds cis-elements in the FLOWERING LOCUS D (FLD) promoter to regulate flowering. Both bzr1-1D and fld-4 showed delayed flowering. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed that BZR1 bound to a putative BR response cis-element and suppressed the expression of FLD. Overexpression of FLD partially rescued the late flowering of pBZR1:mBZR1(Pro234-Leu)-CFP (mx3). Yeast two-hybrid and pull-down assays demonstrated that BZR1 interacts with CYP20-2. Arabidopsis thaliana CYP20-2 had greater peptidyl-prolyl cis-trans isomerase activity than did wheat (Triticum aestivum) CYP20-2. Fourier transform infrared spectroscopy revealed conformation changes in BZR1, dependent on interaction with CYP20-2. Due to differences in activity and substrate preference between CYP20-2 proteins from wheat and Arabidopsis, At-CYP20-2-overexpressing lines showed earlier flowering, whereas Ta CYP20-2 lines flowered later. Immunoblot and chromatin immunoprecipitation assays showed that histone H3 trimethyl Lys4 and H3 acetylation levels were negatively correlated with the transcription of FLD (a putative histone demethylase) in various lines. Therefore, a conformational change of BZR1 mediated by CYP20-2 causes altered flowering through modulation of FLD expression.
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Mechanistic insights into 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a key enzyme of the MEP terpenoid biosynthetic pathway.
FEBS J.
PUBLISHED: 07-14-2013
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The binding mode of 1-deoxy-D-xylulose 5-phosphate (DXP) to 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) (EC 1.1.1.267) from Escherichia coli was investigated via (18) O isotope exchange experiments and determination of the kinetic parameters of the reaction. The results support a C3-C4 substrate binding mode in which DXP chelates a DXR-bound divalent cation via its hydroxyl groups at C3 and C4. Based on this binding mode and the early results, a catalytic cycle for the conversion of DXP to 2-methyl-D-erythritol 4-phosphate mediated by DXR including a pseudo-single molecule transition state of the retro-aldol intermediates is proposed. Taking into account the binding mode of DXP and the catalytic cycle of DXR, the mechanistic insights of DXR are disclosed and the current discrepancies concerning the catalysis of this enzyme are interpreted within the accepted retro-aldol/aldol sequence.
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Purification and characterisation of a bifunctional alginate lyase from novel Isoptericola halotolerans CGMCC 5336.
Carbohydr Polym
PUBLISHED: 07-06-2013
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A novel halophilic alginate-degrading microorganism was isolated from rotten seaweed and identified as Isoptericola halotolerans CGMCC5336. The lyase from the strain was purified to homogeneity by combining of ammonium sulfate fractionation and anion-exchange chromatography with a specific activity of 8409.19 U/ml and a recovery of 25.07%. This enzyme was a monomer with a molecular mass of approximately 28 kDa. The optimal temperature and pH were 50 °C and pH 7.0, respectively. The lyase maintained stability at neutral pH (7.0-8.0) and temperatures below 50 °C. Metal ions including Na(+), Mg(2+), Mn(2+), and Ca(2+) notably increased the activity of the enzyme. With sodium alginate as the substrate, the Km and Vmax were 0.26 mg/ml and 1.31 mg/ml min, respectively. The alginate lyase had substrate specificity for polyguluronate and polymannuronate units in alginate molecules, indicating its bifunctionality. These excellent characteristics demonstrated the potential applications in alginate oligosaccharides production with low polymerisation degrees.
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Pseudo-Sanger sequencing: massively parallel production of long and near error-free reads using NGS technology.
BMC Genomics
PUBLISHED: 06-28-2013
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Usually, next generation sequencing (NGS) technology has the property of ultra-high throughput but the read length is remarkably short compared to conventional Sanger sequencing. Paired-end NGS could computationally extend the read length but with a lot of practical inconvenience because of the inherent gaps. Now that Illumina paired-end sequencing has the ability of read both ends from 600 bp or even 800 bp DNA fragments, how to fill in the gaps between paired ends to produce accurate long reads is intriguing but challenging.
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Clinicopathological characteristics and prognosis of Chinese patients with sarcomatoid carcinoma of the bladder.
Histol. Histopathol.
PUBLISHED: 06-27-2013
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The purpose of this study was to retrospectively analyze the clinicopathological features and prognosis of Chinese patients diagnosed with sarcomatoid carcinoma (SC) of the bladder.
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Tacrolimus as rescue therapy for adult-onset refractory minimal change nephrotic syndrome with reversible acute renal failure.
Nephrol. Dial. Transplant.
PUBLISHED: 06-19-2013
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Some adult patients with minimal change nephrotic syndrome (MCNS) who are refractory to steroid treatment or combination with immunosuppressive drug developed reversible acute renal failure (ARF) due to persistent severe hypoalbuminemia and proteinuria. It is a challenge to find rescue therapies that are effective and safe in treating such difficult patients.
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Carbon monoxide releasing molecule?2 attenuated ischemia/reperfusion?induced apoptosis in cardiomyocytes via a mitochondrial pathway.
Mol Med Rep
PUBLISHED: 06-02-2013
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Carbon monoxide (CO) is an endogenous gaseous transmitter that exerts multi?protection in ischemia/reperfusion (I/R) injury, but few experimental studies regarding CO on myocardial I/R?induced apoptosis, as well as its underlying mechanism have been conducted. The present study was designed to investigate whether CO released from CO?releasing molecule?2 (CORM?2) is capable of ameliorating myocardial I/R?induced apoptosis via a mitochondrial apoptotic pathway. Primary cultures of neonatal rat cardiomyocytes were randomly distributed into four groups: Control, I/R (cultured cardiomyocytes were subjected to 2 h simulated ischemia followed by 4 h reperfusion), CORM?2 and inactive CORM?2 (iCORM?2) groups (20 µM CORM?2 and 20 µM iCORM?2 were administered at the beginning of reperfusion following ischemia, respectively). Flow cytometric analysis showed that CORM?2 treatment significantly decreased apoptosis of cardiomyocytes triggered by simulated I/R. CORM?2 partially recovered mitochondrial respiration and ultrastructure alteration, and lowered caspase?3 expression and the release of cytochrome c. Furthermore, CORM?2 partly reduced BAK/BAX expression in mitochondria, as well as the BAX level in the cytoplasm. Cardioprotection is lost when CORM?2 is replaced by iCORM?2. CORM?2 treatment, at the time of reperfusion, was concluded to attenuate myocardial I/R?induced apoptosis. The protection mechanisms may be targeted to the mitochondria and involved in the inhibition of the BAK/BAX?mediated intrinsic pathway.
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Epigenetic alterations of Krüppel-like factor 4 and its tumor suppressor function in renal cell carcinoma.
Carcinogenesis
PUBLISHED: 05-30-2013
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Krüppel-like factor 4 (KLF4) is a transcription factor that can have divergent functions in different malignancies. The expression and role of KLF4 in renal cell cancer remain unclear. The purpose of this study is to determine epigenetic alterations and possible roles of KLF4 in renal cell carcinoma. The KLF4 expression in primary renal cell cancer tissues and case-matched normal renal tissues was determined by protein and messenger RNA analyses. The epigenetic alterations were detected by methylation-specific PCR and Sequenom MassARRAY. Kaplan-Meier curves and the log-rank test were used for the survival analysis. The effects of KLF4 on cell growth and epithelial-to-mesenchymal transition (EMT) were determined in renal cancer cell lines after viral-based and RNA activation-mediated overexpression of KLF4. In vivo antitumor activity of KLF4 was evaluated by using stably KLF4-transfected renal cancer cells. KLF4 expression was dramatically decreased in various pathological types of renal cancer and associated with poor survival after nephrectomy. Hypermethylation of KLF4 promoter mainly contributed to its expression suppression. In vitro assays indicated that KLF4 overexpression inhibited renal cancer cell growth and survival. KLF4 overexpression also suppressed renal cancer cell migration and invasion by altering the EMT-related factors. In vivo assay showed that ectopic expression of KLF4 also inhibited tumorigenicity and metastasis of renal cancer. Our results suggest that KLF4 is a putative tumor suppressor gene epigenetically silenced in renal cell cancers by promoter CpG methylation and that it has prognostic value for renal cell progression.
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Maternal administration of the herbal medicine toki-shakuyaku-san promotes fetal growth and placental gene expression in normal mice.
Am. J. Chin. Med.
PUBLISHED: 05-29-2013
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Toki-shakuyaku-san (TSS), an herbal formula based on traditional Chinese medicine, is commonly used in obstetrics. To examine the effects of TSS on the normal mouse fetus and placenta, TSS was administered to normal pregnant mice and their placentas and fetuses were studied. First, the effects of maternal TSS treatment on implantation were investigated. Administration of TSS from gestation day 0.5 (G0.5) to G6.5 showed that litter size was not altered at embryonic day 11.5 (E11.5), but the number of resorbed fetuses was slightly decreased. Then, to investigate effects on fetal and placental growths after implantation, TSS was administered from G5.5. At E14.5, the body weight of fetuses from TSS-treated dams was significantly increased. Gene expression of insulin-like growth factor 2 (Igf2), one of the most important modulators of fetal growth, was significantly increased in the placentas and fetuses of TSS-treated dams. In addition, the expression of particular placental developmental genes and nutrient transporter genes was significantly increased in TSS-treated placentas. At E18.5, after longer-term administration of TSS, fetal and placental weights were not altered, but the expression of the placental developmental and nutrient transporter genes remained elevated compared with controls. These results suggest that maternal TSS treatment in normal mice enhances the expression of Igf2, placental developmental genes and nutrient transporter genes, resulting in increased fetal weight. No obvious changes were observed in the expression of these genes after longer-term maternal TSS treatment.
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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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