1,183 research outputs found

    A Critical Heat Generation for Safe Nuclear Fuels after a LOCA

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    This study applies a thermo-elasto-plastic-creep finite element procedure to the analysis of an accidental behavior of nuclear fuel as well as normal behavior. The result will be used as basic data for the robust design of nuclear power plant and fuels. We extended the range of mechanical strain from small or medium to large adopting the Hencky logarithmic strain measure in addition to the Green-Lagrange strain and Almansi strain measures, for the possible large strain situation in accidental environments. We found that there is a critical heat generation after LOCA without ECCS (event category 5), under which the cladding of fuel sustains the internal pressure and temperature for the time being for the rescue of the power plant. With the heat generation above the critical value caused by malfunctioning of the control rods, the stiffness of cladding becomes zero due to the softening by high temperature. The weak position of cladding along the length continuously bulges radially to burst and to discharge radioactive substances. This kind of cases should be avoid by any means

    Highly sensitive near-infrared SERS nanoprobes for in vivo imaging using gold-assembled silica nanoparticles with controllable nanogaps

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    Abstract Background To take advantages, such as multiplex capacity, non-photobleaching property, and high sensitivity, of surface-enhanced Raman scattering (SERS)-based in vivo imaging, development of highly enhanced SERS nanoprobes in near-infrared (NIR) region is needed. A well-controlled morphology and biocompatibility are essential features of NIR SERS nanoprobes. Gold (Au)-assembled nanostructures with controllable nanogaps with highly enhanced SERS signals within multiple hotspots could be a breakthrough. Results Au-assembled silica (SiO2) nanoparticles (NPs) (SiO2@Au@Au NPs) as NIR SERS nanoprobes are synthesized using the seed-mediated growth method. SiO2@Au@Au NPs using six different sizes of Au NPs (SiO2@Au@Au50–SiO2@Au@Au500) were prepared by controlling the concentration of Au precursor in the growth step. The nanogaps between Au NPs on the SiO2 surface could be controlled from 4.16 to 0.98nm by adjusting the concentration of Au precursor (hence increasing Au NP sizes), which resulted in the formation of effective SERS hotspots. SiO2@Au@Au500 NPs with a 0.98-nm gap showed a high SERS enhancement factor of approximately 3.8 × 106 under 785-nm photoexcitation. SiO2@Au@Au500 nanoprobes showed detectable in vivo SERS signals at a concentration of 16μg/mL in animal tissue specimen at a depth of 7mm. SiO2@Au@Au500 NPs with 14 different Raman label compounds exhibited distinct SERS signals upon subcutaneous injection into nude mice. Conclusions SiO2@Au@Au NPs showed high potential for in vivo applications as multiplex nanoprobes with high SERS sensitivity in the NIR region. Graphical Abstrac

    Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

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    The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

    Computational Prediction of O-linked Glycosylation Sites That Preferentially Map on Intrinsically Disordered Regions of Extracellular Proteins

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    O-glycosylation of mammalian proteins is one of the important posttranslational modifications. We applied a support vector machine (SVM) to predict whether Ser or Thr is glycosylated, in order to elucidate the O-glycosylation mechanism. O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically. Therefore, we developed two types of SVMs for predicting clustered and isolated sites separately. We found that the amino acid composition was effective for predicting the clustered type, whereas the site-specific algorithm was effective for the isolated type. The highest prediction accuracy for the clustered type was 74%, while that for the isolated type was 79%. The existence frequency of amino acids around the O-glycosylation sites was different in the two types: namely, Pro, Val and Ala had high existence probabilities at each specific position relative to a glycosylation site, especially for the isolated type. Independent component analyses for the amino acid sequences around O-glycosylation sites showed the position-specific existences of the identified amino acids as independent components. The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions. This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability

    Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

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    Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

    Transcription of nuclear organellar DNA in a model plant system

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    Endosymbiotic gene transfer from cytoplasmic organelles (chloroplasts and mitochondria) to the nucleus is an ongoing process in land plants. Although the frequency of organelle DNA migration is high, functional gene transfer is rare because a nuclear promoter is thought necessary for activity in the nucleus. Here we show that a chloroplast promoter, 16S rrn, drives nuclear transcription, suggesting that a transferred organellar gene may become active without obtaining a nuclear promoter. Examining the chromatin status of a known de novo chloroplast integrant indicates that plastid DNA inserts into open chromatin and that this relaxed condition is maintained after integration. Transcription of nuclear organelle DNA integrants was explored at the whole genome level by analyzing RNA-seq data of Oryza sativa subsp. japonica, and utilizing sequence polymorphisms to unequivocally discriminate nuclear organelle DNA transcripts from those of bona fide cytoplasmic organelle DNA. Nuclear copies of organelle DNA that are transcribed show a spectrum of transcriptional activity but at comparatively low levels compared with the majority of other nuclear genes.Dong Wang, Zhipeng Qu, David L. Adelson, Jian-Kang Zhu, and Jeremy N. Timmi

    Survey of childhood empyema in Asia: Implications for detecting the unmeasured burden of culture-negative bacterial disease

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    <p>Abstract</p> <p>Background</p> <p>Parapneumonic empyema continues to be a disease of significant morbidity and mortality among children despite recent advances in medical management. To date, only a limited number of studies have assessed the burden of empyema in Asia.</p> <p>Methods</p> <p>We surveyed medical records of four representative large pediatric hospitals in China, Korea, Taiwan and Vietnam using <it>ICD</it>-10 diagnostic codes to identify children <16 years of age hospitalized with empyema or pleural effusion from 1995 to 2005. We also accessed microbiology records of cultured empyema and pleural effusion specimens to describe the trends in the epidemiology and microbiology of empyema.</p> <p>Results</p> <p>During the study period, we identified 1,379 children diagnosed with empyema or pleural effusion (China, n = 461; Korea, n = 134; Taiwan, n = 119; Vietnam, n = 665). Diagnoses of pleural effusion (n = 1,074) were 3.5 times more common than of empyema (n = 305), although the relative proportions of empyema and pleural effusion noted in hospital records varied widely between the four sites, most likely because of marked differences in coding practices. Although pleural effusions were reported more often than empyema, children with empyema were more likely to have a cultured pathogen. In addition, we found that median age and gender distribution of children with these conditions were similar across the four countries. Among 1,379 empyema and pleural effusion specimens, 401 (29%) were culture positive. <it>Staphylococcus aureus </it>(n = 126) was the most common organism isolated, followed by <it>Streptococcus pneumoniae </it>(n = 83), <it>Pseudomonas aeruginosa </it>(n = 37) and <it>Klebsiella </it>(n = 35) and <it>Acinetobacter </it>species (n = 34).</p> <p>Conclusion</p> <p>The age and gender distribution of empyema and pleural effusion in children in these countries are similar to the US and Western Europe. <it>S. pneumoniae </it>was the second leading bacterial cause of empyema and pleural effusion among Asian children. The high proportion of culture-negative specimens among patients with pleural effusion or empyema suggests that culture may not be a sufficiently sensitive diagnostic method to determine etiology in the majority of cases. Future prospective studies in different countries would benefit from standardized case definitions and coding practices for empyema. In addition, more sensitive diagnostic methods would improve detection of pathogens and could result in better prevention, treatment and outcomes of this severe disease.</p

    Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication

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    Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that are considered to be the root cause of tumor heterogeneity, because of their ability to generate the full rep- ertoire of cancer cell types. Moreover, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. As such, targeting CSCs may be a useful strategy to improve the effectiveness of classical anticancer therapies. Recently, metabolism has been considered as a relevant player in CSC biology, and indeed, onco- genic alterations trigger the metabolite-driven dissemination of CSCs. More interestingly, the action of metabolic pathways in CSC maintenance might not be merely a conse- quence of genomic alterations. Indeed, certain metabotypic phenotypes may play a causative role in maintaining the stem traits, acting as an orchestrator of stemness. Here, we review the current studies on the metabolic features of CSCs, focusing on the bio- chemical energy pathways involved in CSC maintenance and propagation. We provide a detailed overview of the plastic metabolic behavior of CSCs in response to microenvironment changes, genetic aberrations, and pharmacological stressors. In addition, we describe the potential of comprehensive metabolic approaches to identify and selectively eradicate CSCs, together with the possibility to ‘force’ CSCs within certain metabolic dependences, in order to effectively target such metabolic biochemical inflexibilities. Finally, we focus on targeting mitochondria to halt CSC dissemination and effectively eradicate cancer

    Nucleic acid-based fluorescent probes and their analytical potential

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    It is well known that nucleic acids play an essential role in living organisms because they store and transmit genetic information and use that information to direct the synthesis of proteins. However, less is known about the ability of nucleic acids to bind specific ligands and the application of oligonucleotides as molecular probes or biosensors. Oligonucleotide probes are single-stranded nucleic acid fragments that can be tailored to have high specificity and affinity for different targets including nucleic acids, proteins, small molecules, and ions. One can divide oligonucleotide-based probes into two main categories: hybridization probes that are based on the formation of complementary base-pairs, and aptamer probes that exploit selective recognition of nonnucleic acid analytes and may be compared with immunosensors. Design and construction of hybridization and aptamer probes are similar. Typically, oligonucleotide (DNA, RNA) with predefined base sequence and length is modified by covalent attachment of reporter groups (one or more fluorophores in fluorescence-based probes). The fluorescent labels act as transducers that transform biorecognition (hybridization, ligand binding) into a fluorescence signal. Fluorescent labels have several advantages, for example high sensitivity and multiple transduction approaches (fluorescence quenching or enhancement, fluorescence anisotropy, fluorescence lifetime, fluorescence resonance energy transfer (FRET), and excimer-monomer light switching). These multiple signaling options combined with the design flexibility of the recognition element (DNA, RNA, PNA, LNA) and various labeling strategies contribute to development of numerous selective and sensitive bioassays. This review covers fundamentals of the design and engineering of oligonucleotide probes, describes typical construction approaches, and discusses examples of probes used both in hybridization studies and in aptamer-based assays
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