Sample records for m6a adult pure

  1. Adults Studying Pure Mathematics in Adult Tertiary Preparation.

    ERIC Educational Resources Information Center

    Bennison, Anne

    2002-01-01

    Investigated the experiences of a group of adults enrolled in the Pure Mathematics module of the Certificate IV in Adult Tertiary Preparation in 2000 at one of the Institutes of TAFE in Brisbane, Australia. Classroom learning experiences, exposure to technology, and the impact of returning to study on other facets of students' lives were…

  2. Radiation effects on beta 10.6 of pure and europium doped KCl

    NASA Technical Reports Server (NTRS)

    Grimes, H. H.; Maisel, J. E.; Hartford, R. H.

    1975-01-01

    Changes in the optical absorption coefficient as a result of X-ray and electron bombardment of pure KCl (monocrystalline and polycrystalline), and divalent europium doped polycrystalline KCl were determined. The optical absorption coefficients were measured by a constant heat flow calorimetric method. Both 300 KV X-irradiation and 2 MeV electron irradiation produced significant increases in beta 10.6, measured at room temperature. The X-irradiation of pure moncrystalline KCl increased beta 10.6 by 0.005/cm for a 113 MR dose. For an equivalent dose, 2 MeV electrons were found less efficient in changing beta 10.6. However, electron irradiation of pure and Eu-doped polycrystalline KCl produced marked increases in adsorption. Beta increased to over 0.25/cm in Eu-doped material for a 30 x 10 to the 14th power electrons/sq cm dose, a factor of 20 increase over unirradiated material. Moreover, bleaching the electron irradiated doped KCl with 649 m light produced and additional factor of 1.5 increase. These findings will be discussed in light of known defect-center properties in KCl.

  3. Pure Erythroleukemia (Variant Acute Myeloid Leukemia-vAML-M6) with Deletion of Chromosome 20, Mainly Presenting as Late Erythroblasts, a Unique Case Report with Review of Literature.

    PubMed

    Rasool, Javid; Geelani, Sajad; Khursheed; Yasir; Lone, Mohd Suhail; Shaban, Mohd

    2014-03-01

    Acute erythroleukemia is characterized by a predominant immature erythroid population and accounts for approximately 2-5 % of all cases of acute leukemia. Two subtypes are recognized based on the presence or absence of a significant myeloid component: erythroleukemia and pure erythroid leukemia. Erythroleukemia is predominantly a disease of adults, while pure erythroid leukemia can be seen in any age including children. Here is a case of pure erythroleukemia presenting mainly as late erythroblasts which was diagnosed on bone marrow examination, cytochemistry and was confirmed on immunophenotyping. Possibly this is the only case so for demonstrating deletion of long arm of chromosome 20 in pure erythroleukemia.

  4. Validation of the Omron M6 (HEM-7001-E) upper-arm blood pressure measuring device according to the International Protocol in adults and obese adults.

    PubMed

    Altunkan, Sekip; Ilman, Nevzat; Kayatürk, Nur; Altunkan, Erkan

    2007-08-01

    Electronic blood pressure (BP) measurement devices are the preferred choice of patients owing to their user-friendly nature; however, there is a requirement to investigate the accuracy and reliability of these devices. The objective of this study is to evaluate the accuracy of the Omron M6 upper-arm BP device against the mercury sphygmomanometer in adults and obese adults according to the International Protocol criteria. One hundred and twenty-one patients, older than 30 years of age, were studied and classified on the basis of the range of the International Protocol. BP measurements at the upper arm with the Omron M6 were compared with the results obtained by two trained observers using a mercury sphygmomanometer. Nine sequential BP measurements were taken. A total of 33 participants were selected for each validation study. During the validation study, 99 measurements were performed on 33 participants for comparison. The first phase was performed on 15 participants, and if the device passed this phase, 18 more participants were selected. Having a two-fold purpose, this study was conducted on both adult and obese adult patients. Mean discrepancies and standard deviations of the monitor-mercury sphygmomanometer were 1.1+/-4.0 mmHg for systolic BP (SBP) and -0.5+/-3.5 mmHg for diastolic BP (DBP) in the adult group. The device passed phase 1 in 15 participants. In phase 2.1, out of a total of 99 comparisons, 88, 96, and 97 for SBP, and 88, 98, and 99 for DBP were <5, <10, and <15 mmHg, respectively. Mean discrepancies and standard deviations of the monitor-mercury sphygmomanometer were 1.7+/-4.8 mmHg for SBP and -0.8+/-4.3 mmHg for DBP in the obese adult group. The device passed phase 1 in 15 participants. In phase 2.1, out of a total of 99 comparisons, 82, 90, and 97 for SBP, and 80, 97, and 99 for DBP were <5, <10, and <15 mmHg, respectively. It was found that the Omron M6 automatic monitor, which measures BP at the upper arm, produced results in accordance with the

  5. M-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is the product of a late muscle differentiation gene.

    PubMed

    Vandoolaeghe, P; Gueuning, M A; Rousseau, G G

    1999-06-07

    Genes that are expressed in adult muscle, but not in myotubes, are useful markers of the last steps of muscle maturation. We have investigated at what stage of differentiation the muscle-specific (M) promoter of a gene that codes for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2) becomes functional. M-PFK2 mRNA, which is present in adult muscle, did not appear during differentiation of L6 myoblasts into myotubes induced by growth factor withdrawal and hormonal treatment, even when this differentiation was stimulated by expression of transgenes coding for myf-5 or Rb. A comparison with the expression pattern of muscle genes showed that M-PFK2 is a marker of mature skeletal muscle. We also found that M-PFK2 is expressed in both types (slow-twitch and fast-twitch) of adult muscle. Thus, the M-PFK2 promoter is a novel model for studying the transcriptional control of the final steps of muscle differentiation that are common to the two types of myofibers. Copyright 1999 Academic Press.

  6. m6A-Driver: Identifying Context-Specific mRNA m6A Methylation-Driven Gene Interaction Networks

    PubMed Central

    Zhang, Song-Yao; Zhang, Shao-Wu; Liu, Lian; Huang, Yufei

    2016-01-01

    As the most prevalent mammalian mRNA epigenetic modification, N6-methyladenosine (m6A) has been shown to possess important post-transcriptional regulatory functions. However, the regulatory mechanisms and functional circuits of m6A are still largely elusive. To help unveil the regulatory circuitry mediated by mRNA m6A methylation, we develop here m6A-Driver, an algorithm for predicting m6A-driven genes and associated networks, whose functional interactions are likely to be actively modulated by m6A methylation under a specific condition. Specifically, m6A-Driver integrates the PPI network and the predicted differential m6A methylation sites from methylated RNA immunoprecipitation sequencing (MeRIP-Seq) data using a Random Walk with Restart (RWR) algorithm and then builds a consensus m6A-driven network of m6A-driven genes. To evaluate the performance, we applied m6A-Driver to build the context-specific m6A-driven networks for 4 known m6A (de)methylases, i.e., FTO, METTL3, METTL14 and WTAP. Our results suggest that m6A-Driver can robustly and efficiently identify m6A-driven genes that are functionally more enriched and associated with higher degree of differential expression than differential m6A methylated genes. Pathway analysis of the constructed context-specific m6A-driven gene networks further revealed the regulatory circuitry underlying the dynamic interplays between the methyltransferases and demethylase at the epitranscriptomic layer of gene regulation. PMID:28027310

  7. Production of pure 133mXe for CTBTO

    NASA Astrophysics Data System (ADS)

    Peräjärvi, K.; Eronen, T.; Gorelov, D.; Hakala, J.; Jokinen, A.; Kettunen, H.; Kolhinen, V.; Laitinen, M.; Moore, I. D.; Penttilä, H.; Rissanen, J.; Saastamoinen, A.; Toivonen, H.; Turunen, J.; Äystö, J.

    2014-01-01

    Underground nuclear weapon detonations release gaseous species into the atmosphere. The most interesting isotopes/isomers from the detection point of view are 131mXe, 133mXe, 133Xe and 135Xe. We have developed a method that employs high-precision Penning trap mass spectrometry at the JYFLTRAP facility, the University of Jyväskylä, to produce pure calibration samples of these isotopes/isomers. Among developments this work required a new mass resolution record of a few parts-per-million. Here the status and future plans of the project are reviewed.

  8. m6A level and isoform characterization sequencing (m6A-LAIC-seq) reveals the census and complexity of the m6A epitranscriptome

    PubMed Central

    Molinie, Benoit; Wang, Jinkai; Lim, Kok-Seong; Hillebrand, Roman; Lu, Zhi-xiang; Van Wittenberghe, Nicholas; Howard, Benjamin D.; Daneshvar, Kaveh; Mullen, Alan C.; Dedon, Peter

    2017-01-01

    N6-Methyladenosine (m6A) is a widespread, reversible chemical modification of RNA molecules, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (‘m6A levels’) or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A-level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of nonstoichiometric m6A levels with cell-type specificity. At the level of isoform characterization, we discovered widespread differences in the use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3′ untranslated regions, while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications. PMID:27376769

  9. Pure spinor superspace action for D = 6, N = 1 super-Yang-Mills theory

    NASA Astrophysics Data System (ADS)

    Cederwall, Martin

    2018-05-01

    A Batalin-Vilkovisky action for D = 6, N = 1 super-Yang-Mills theory, including coupling to hypermultiplets, is given. The formalism involves pure spinor superfields. The geometric properties of the D = 6, N = 1 pure spinors (which differ from Cartan pure spinors) are examined. Unlike the situation for maximally supersymmetric models, the fields and antifields (including ghosts) of the vector multiplet reside in separate superfields. The formalism provides an off-shell superspace formulation for matter hypermultiplets, which in a traditional treatment are on-shell.

  10. m6ASNP: a tool for annotating genetic variants by m6A function.

    PubMed

    Jiang, Shuai; Xie, Yubin; He, Zhihao; Zhang, Ya; Zhao, Yuli; Chen, Li; Zheng, Yueyuan; Miao, Yanyan; Zuo, Zhixiang; Ren, Jian

    2018-05-01

    Large-scale genome sequencing projects have identified many genetic variants for diverse diseases. A major goal of these projects is to characterize these genetic variants to provide insight into their function and roles in diseases. N6-methyladenosine (m6A) is one of the most abundant RNA modifications in eukaryotes. Recent studies have revealed that aberrant m6A modifications are involved in many diseases. In this study, we present a user-friendly web server called "m6ASNP" that is dedicated to the identification of genetic variants that target m6A modification sites. A random forest model was implemented in m6ASNP to predict whether the methylation status of an m6A site is altered by the variants that surround the site. In m6ASNP, genetic variants in a standard variant call format (VCF) are accepted as the input data, and the output includes an interactive table that contains the genetic variants annotated by m6A function. In addition, statistical diagrams and a genome browser are provided to visualize the characteristics and to annotate the genetic variants. We believe that m6ASNP is a very convenient tool that can be used to boost further functional studies investigating genetic variants. The web server "m6ASNP" is implemented in JAVA and PHP and is freely available at [60].

  11. Regulation of mTOR and S6K1 Activation by the nPKC isoforms, PKCε and PKCδ, in Adult Cardiac Muscle Cells

    PubMed Central

    Moschella, Phillip C.; Rao, Vijay U.; McDermott, Paul J.; Kuppuswamy, Dhandapani

    2007-01-01

    SUMMARY Activation of both mTOR and its downstream target, S6K1 (p70 S6 kinase) have been implicated to affect cardiac hypertrophy. Our earlier work, in a feline model of 1–48 h pressure overload, demonstrated that mTOR/S6K1 activation occurred primarily through a PKC/c-Raf pathway. To further delineate the role of specific PKC isoforms on mTOR/S6K1 activation, we utilized primary cultures of adult feline cardiomyocytes in vitro and stimulated with endothelin-1 (ET-1), phenylephrine (PE), TPA, or insulin. All agonist treatments resulted in S2248 phosphorylation of mTOR and T389 and S421/T424 phosphorylation of S6K1, however only ET-1 and TPA-stimulated mTOR/S6K1 activation was abolished with infection of a dominant negative adenoviral c-Raf (DN-Raf) construct. Expression of DN-PKCε blocked ET-1-stimulated mTOR S2448 and S6K1 S421/T424 and T389 phosphorylation but had no effect on insulin-stimulated S6K1 phosphorylation. Expression of DN-PKCδ or pretreatment of cardiomyocytes with rottlerin, a PKCδ specific inhibitor, blocked both ET-1 and insulin stimulated mTOR S2448 and S6K1 T389 phosphorylation. However, treatment with Gö6976, a specific classical PKC (cPKC) inhibitor did not affect mTOR/S6K1 activation. These data indicate that: (i) PKCε is required for ET-1-stimulated T421/S424 phosphorylation of S6K1, (ii) both PKCε and PKCδ are required for ET-1-stimulated mTOR S2448 and S6K1 T389 phosphorylation, (iii) PKCδ is also required for insulin-stimulated mTOR S2448 and S6K1 T389 phosphorylation. Together, these data delineate both distinct and combinatorial roles of specific PKC isoforms on mTOR and S6K1 activation in adult cardiac myocytes following hypertrophic stimulation. PMID:17976640

  12. Regulation of mTOR and S6K1 activation by the nPKC isoforms, PKCepsilon and PKCdelta, in adult cardiac muscle cells.

    PubMed

    Moschella, Phillip C; Rao, Vijay U; McDermott, Paul J; Kuppuswamy, Dhandapani

    2007-12-01

    Activation of both mTOR and its downstream target, S6K1 (p70 S6 kinase) have been implicated to affect cardiac hypertrophy. Our earlier work, in a feline model of 1-48 h pressure overload, demonstrated that mTOR/S6K1 activation occurred primarily through a PKC/c-Raf pathway. To further delineate the role of specific PKC isoforms on mTOR/S6K1 activation, we utilized primary cultures of adult feline cardiomyocytes in vitro and stimulated with endothelin-1 (ET-1), phenylephrine (PE), TPA, or insulin. All agonist treatments resulted in S2248 phosphorylation of mTOR and T389 and S421/T424 phosphorylation of S6K1, however only ET-1 and TPA-stimulated mTOR/S6K1 activation was abolished with infection of a dominant negative adenoviral c-Raf (DN-Raf) construct. Expression of DN-PKC(epsilon) blocked ET-1-stimulated mTOR S2448 and S6K1 S421/T424 and T389 phosphorylation but had no effect on insulin-stimulated S6K1 phosphorylation. Expression of DN-PKC(delta) or pretreatment of cardiomyocytes with rottlerin, a PKC(delta) specific inhibitor, blocked both ET-1 and insulin stimulated mTOR S2448 and S6K1 T389 phosphorylation. However, treatment with Gö6976, a specific classical PKC (cPKC) inhibitor did not affect mTOR/S6K1 activation. These data indicate that: (i) PKC(epsilon) is required for ET-1-stimulated T421/S424 phosphorylation of S6K1, (ii) both PKC(epsilon) and PKC(delta) are required for ET-1-stimulated mTOR S2448 and S6K1 T389 phosphorylation, (iii) PKC(delta) is also required for insulin-stimulated mTOR S2448 and S6K1 T389 phosphorylation. Together, these data delineate both distinct and combinatorial roles of specific PKC isoforms on mTOR and S6K1 activation in adult cardiac myocytes following hypertrophic stimulation.

  13. A role for the membrane protein M6 in the Drosophila visual system.

    PubMed

    Zappia, María Paula; Bernabo, Guillermo; Billi, Silvia C; Frasch, Alberto C; Ceriani, María Fernanda; Brocco, Marcela Adriana

    2012-07-04

    Members of the proteolipid protein family, including the four-transmembrane glycoprotein M6a, are involved in neuronal plasticity in mammals. Results from our group previously demonstrated that M6, the only proteolipid protein expressed in Drosophila, localizes to the cell membrane in follicle cells. M6 loss triggers female sterility, which suggests a role for M6 in follicular cell remodeling. These results were the basis of the present study, which focused on the function and requirements of M6 in the fly nervous system. The present study identified two novel, tissue-regulated M6 isoforms with variable N- and C- termini, and showed that M6 is the functional fly ortholog of Gpm6a. In the adult brain, the protein was localized to several neuropils, such as the optic lobe, the central complex, and the mushroom bodies. Interestingly, although reduced M6 levels triggered a mild rough-eye phenotype, hypomorphic M6 mutants exhibited a defective response to light. Based on its ability to induce filopodium formation we propose that M6 is key in cell remodeling processes underlying visual system function. These results bring further insight into the role of M6/M6a in biological processes involving neuronal plasticity and behavior in flies and mammals.

  14. Effect of Midmorning Puree Snacks on Subjective Appetite, Food Intake, and Glycemic and Insulin Responses in Healthy Adults.

    PubMed

    Guo, Qing; Totosy de Zepetnek, Julia; Chang, Jennifer; Hayden, Julia; Crozier, Stephen J; Mongia, Gagan; Rousseau, Dérick; Bellissimo, Nick

    2018-04-27

    Dietary pattern changes, as a part of a healthy lifestyle, may improve weight management. The objective of this study was to examine the effect of midmorning puree snacks varying in macronutrient composition and energy content on subjective appetite, food intake, and glycemic and insulin responses in healthy adults. In a randomized, repeated measures crossover design, 6 treatments (snack skipping and purees: control [186 kcal], maltodextrin [272 kcal], whey protein [201 kcal], oat [276 kcal], and coconut oil [276 kcal]) were administered to 23 normal weight adults (n = 14 males, n = 9 females). Subjective appetite, blood glucose, and insulin responses were measured at regular intervals for 2 hours immediately followed by an ad libitum pizza lunch. In vitro digestion experiments were conducted to corroborate results of the human trial. Compared to snack skipping, all snack treatments similarly reduced subjective average appetite (net area under the curve), but only oat (p < 0.032) and coconut oil (p < 0.031) purees significantly decreased test meal food intake. However, caloric compensation did not differ among snack treatments (p < 0.73). Both blood glucose (incremental area under the curve [iAUC]; p < 0.0001) and serum insulin (iAUC; p < 0.0001) were affected by treatment. A positive correlation was found between blood glucose iAUC and in vitro glucose release (r = 0.993, p < 0.0001). The release of free fatty acids (FFAs) was sustained, and oats were difficult to disintegrate during in vitro digestion. Compared with snack skipping, coconut oil and oat puree snacks suppressed short-term food intake, which was likely due to the sustained release of FFA and slowly digestible oats, respectively. Our in vitro digestion model predicted the relative differences in the glycemic response in vivo.

  15. A role for the membrane protein M6 in the Drosophila visual system

    PubMed Central

    2012-01-01

    Background Members of the proteolipid protein family, including the four-transmembrane glycoprotein M6a, are involved in neuronal plasticity in mammals. Results from our group previously demonstrated that M6, the only proteolipid protein expressed in Drosophila, localizes to the cell membrane in follicle cells. M6 loss triggers female sterility, which suggests a role for M6 in follicular cell remodeling. These results were the basis of the present study, which focused on the function and requirements of M6 in the fly nervous system. Results The present study identified two novel, tissue-regulated M6 isoforms with variable N- and C- termini, and showed that M6 is the functional fly ortholog of Gpm6a. In the adult brain, the protein was localized to several neuropils, such as the optic lobe, the central complex, and the mushroom bodies. Interestingly, although reduced M6 levels triggered a mild rough-eye phenotype, hypomorphic M6 mutants exhibited a defective response to light. Conclusions Based on its ability to induce filopodium formation we propose that M6 is key in cell remodeling processes underlying visual system function. These results bring further insight into the role of M6/M6a in biological processes involving neuronal plasticity and behavior in flies and mammals. PMID:22762289

  16. Earthquake rupture properties of the 2016 Kumamoto earthquake foreshocks ( M j 6.5 and M j 6.4) revealed by conventional and multiple-aperture InSAR

    NASA Astrophysics Data System (ADS)

    Kobayashi, Tomokazu

    2017-01-01

    By applying conventional cross-track InSAR and multiple-aperture InSAR (MAI) techniques with ALOS-2 SAR data to foreshocks of the 2016 Kumamoto earthquake, ground displacement fields in range (line-of-sight) and azimuth components have been successfully mapped. The most concentrated crustal deformation with ground displacement exceeding 15 cm is located on the western side of the Hinagu fault zone. A locally distributed displacement which appears along the strike of the Futagawa fault can be identified in and around Mashiki town, suggesting that a different local fault slip also contributed toward foreshocks. Inverting InSAR, MAI, and GNSS data, distributed slip models are obtained that show almost pure right-lateral fault motion on a plane dipping west by 80° for the Hinagu fault and almost pure normal fault motion on a plane dipping south by 70° for the local fault beneath Mashiki town. The slip on the Hinagu fault reaches around the junction of the Hinagu and Futagawa faults. The slip in the north significantly extends down to around 10 km depth, while in the south the slip is concentrated near the ground surface, perhaps corresponding to the M j 6.5 and the M j 6.4 events, respectively. The focal mechanism of the distributed slip model for the Hinagu fault alone shows pure right-lateral motion, which is inconsistent with the seismically estimated mechanism that includes a significant non-double couple component. On the other hand, when taking the contribution of normal fault motion into account, the focal mechanism appears similar to that of the seismic analysis. This result may suggest that local fault motion occurred just beneath Mashiki town, simultaneously with the M j 6.5 event, thereby increasing the degree of damage to the town.[Figure not available: see fulltext.

  17. Acute guttate psoriasis patients have positive streptococcus hemolyticus throat cultures and elevated antistreptococcal M6 protein titers.

    PubMed

    Zhao, Guang; Feng, Xiaoling; Na, Aihua; Yongqiang, Jiang; Cai, Qing; Kong, Jian; Ma, Huijun

    2005-02-01

    To further study the role of Streptococci hemolyticus infection and streptococcal M6 protein in the pathogenesis of acute guttate psoriasis, streptococcal cultures were taken from the throats of 68 patients with acute guttate psoriasis. PCR technique was applied to detect M6 protein encoding DNA from those cultured streptococci. Pure M6 protein was obtained by Sephacry/S-200HR and Mono-Q chromatography from proliferated Streptococcus hemolyticus. Antistreptococcal M6 protein titers were measured in the serum of patients with acute guttate psoriasis, plaque psoriasis and healthy controls by ELISA. A high incidence of Streptococcus hemolyticus culture was observed in the guttate psoriatic group compared with the plaque psoriasis and control groups. Fourteen strains of Streptococcus hemolyticus were cultured from the throats of 68 acute guttate psoriasis patients. Of these, 5 strains contain DNA encoding the M6 protein gene as confirmed by PCR technique. More than 85% purification of M6 protein was obtained from Streptococcus pyogenes. Applying our pure M6 protein with the ELISA methods, we found that the titer of antistreptococcal M6 protein was significantly higher in the serum of guttate psoriasis patients than in the control or plaque psoriasis groups (P < 0.01). We verified that patients of acute guttate psoriasis have a high incidence of Streptococcus hemolyticus in their throats and raised titers of antistreptococcal M6 protein in their sera.

  18. Nighttime kidney transplantation is associated with less pure technical graft failure.

    PubMed

    Brunschot, Denise M D Özdemir-van; Hoitsma, Andries J; van der Jagt, Michel F P; d'Ancona, Frank C; Donders, Rogier A R T; van Laarhoven, Cees J H M; Hilbrands, Luuk B; Warlé, Michiel C

    2016-07-01

    To minimize cold ischemia time, transplantations with kidneys from deceased donors are frequently performed during the night. However, sleep deprivation of those who perform the transplantation may have adverse effects on cognitive and psychomotor performance and may cause reduced cognitive flexibility. We hypothesize that renal transplantations performed during the night are associated with an increased incidence of pure technical graft failure. A retrospective analysis of data of the Dutch Organ Transplant Registry concerning all transplants from deceased donors between 2000 and 2013 was performed. Nighttime surgery was defined as the start of the procedure between 8 p.m. and 8 a.m. The primary outcome measure was technical graft failure, defined as graft loss within 10 days after surgery without signs of (hyper)acute rejection. Of 4.519 renal transplantations in adult recipients, 1.480 were performed during the night. The incidence of pure technical graft failure was 1.0 % for procedures started during the night versus 2.6 % for daytime surgery (p = .001). In a multivariable model, correcting for relevant donor, recipient and graft factors, daytime surgery was an independent predictor of pure technical graft failure (p < .001). Limitation of this study is mainly to its retrospective design, and the influence of some relevant variables, such as the experience level of the surgeon, could not be assessed. We conclude that nighttime surgery is associated with less pure technical graft failures. Further research is required to explore factors that may positively influence the performance of the surgical team during the night.

  19. Outcomes of transient evoked otoacoustic emission testing in 6-year-old school children: a comparison with pure tone screening and tympanometry.

    PubMed

    Driscoll, C; Kei, J; McPherson, B

    2001-01-01

    (1) To establish test performance measures for Transient Evoked Otoacoustic Emission testing of 6-year-old children in a school setting; (2) To investigate whether Transient Evoked Otoacoustic Emission testing provides a more accurate and effective alternative to a pure tone screening plus tympanometry protocol. Pure tone screening, tympanometry and transient evoked otoacoustic emission data were collected from 940 subjects (1880 ears), with a mean age of 6.2 years. Subjects were tested in non-sound-treated rooms within 22 schools. Receiver operating characteristics curves along with specificity, sensitivity, accuracy and efficiency values were determined for a variety of transient evoked otoacoustic emission/pure tone screening/tympanometry comparisons. The Transient Evoked Otoacoustic Emission failure rate for the group was 20.3%. The failure rate for pure tone screening was found to be 8.9%, whilst 18.6% of subjects failed a protocol consisting of combined pure tone screening and tympanometry results. In essence, findings from the comparison of overall Transient Evoked Otoacoustic Emission pass/fail with overall pure tone screening pass/fail suggested that use of a modified Rhode Island Hearing Assessment Project criterion would result in a very high probability that a child with a pass result has normal hearing (true negative). However, the hit rate was only moderate. Selection of a signal-to-noise ratio (SNR) criterion set at > or =1 dB appeared to provide the best test performance measures for the range of SNR values investigated. Test performance measures generally declined when tympanometry results were included, with the exception of lower false alarm rates and higher positive predictive values. The exclusion of low frequency data from the Transient Evoked Otoacoustic Emission SNR versus pure tone screening analysis resulted in improved performance measures. The present study poses several implications for the clinical implementation of Transient Evoked

  20. m6aViewer: software for the detection, analysis, and visualization of N6-methyladenosine peaks from m6A-seq/ME-RIP sequencing data.

    PubMed

    Antanaviciute, Agne; Baquero-Perez, Belinda; Watson, Christopher M; Harrison, Sally M; Lascelles, Carolina; Crinnion, Laura; Markham, Alexander F; Bonthron, David T; Whitehouse, Adrian; Carr, Ian M

    2017-10-01

    Recent methods for transcriptome-wide N 6 -methyladenosine (m 6 A) profiling have facilitated investigations into the RNA methylome and established m 6 A as a dynamic modification that has critical regulatory roles in gene expression and may play a role in human disease. However, bioinformatics resources available for the analysis of m 6 A sequencing data are still limited. Here, we describe m6aViewer-a cross-platform application for analysis and visualization of m 6 A peaks from sequencing data. m6aViewer implements a novel m 6 A peak-calling algorithm that identifies high-confidence methylated residues with more precision than previously described approaches. The application enables data analysis through a graphical user interface, and thus, in contrast to other currently available tools, does not require the user to be skilled in computer programming. m6aViewer and test data can be downloaded here: http://dna2.leeds.ac.uk/m6a. © 2017 Antanaviciute et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  1. Synthesis of Cis, syndiotactic A -alt-B Copolymers from Two Enantiomerically Pure Trans -2,3-Disubstituted-5,6-Norbornenes

    DOE PAGES

    Jang, Eun Sil; John, Jeremy M.; Schrock, Richard R.

    2016-09-06

    Cis,syndiotactic A-alt-B copolymers, where A and B are two enantiomerically pure trans-2,3-disubstituted-5,6-norbornenes with “opposite” chiralities, can be prepared with stereogenic-at-metal initiators of the type M(NR)(CHR')(OR”)(pyrrolide). Formation of a high percentage of alternating AB copolymer linkages relies on an inversion of chirality at the metal with each propagating step and a relatively fast formation of an AB sequence as a consequence of a preferred diastereomeric relationship between the chirality at the metal and the chirality of the monomer. Finally, this approach to formation of an alternating AB copolymer contrasts dramatically with the principle of forming AB copolymers from achiral monomers andmore » catalysts.« less

  2. mRNA Traffic Control Reviewed: N6-Methyladenosine (m6 A) Takes the Driver's Seat.

    PubMed

    Visvanathan, Abhirami; Somasundaram, Kumaravel

    2018-01-01

    Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Our understanding about the landscape of RNA modifications is still rudimentary in contrast to DNA and histone modifications. The major obstacle has been the lack of sensitive detection methods since they are non-editing events. However, with the advent of next-generation sequencing techniques, RNA modifications are being identified precisely at single nucleotide resolution. In recent years, methylation at the N6 position of adenine (m 6 A) has gained the attention of RNA biologists. The m 6 A modification has a set of writers (methylases), erasers (demethylases), and readers. Here, we provide a summary of interesting facts, conflicting findings, and recent advances in the technical and functional aspects of the m 6 A epitranscriptome. © 2017 WILEY Periodicals, Inc.

  3. TLR7 imidazoquinoline ligand 3M-019 is a potent adjuvant for pure protein prototype vaccines.

    PubMed

    Johnston, Dean; Zaidi, Bushra; Bystryn, Jean-Claude

    2007-08-01

    Cancer vaccines, while theoretically attractive, present difficult challenges that must be overcome to be effective. Cancer vaccines are often poorly immunogenic and may require augmentation of immunogenicity through the use of adjuvants and/or immune response modifiers. Toll-like receptor (TLR) ligands are a relatively new class of immune response modifiers that may have great potential in inducing and augmenting both cellular and humoral immunity to vaccines. TLR7 ligands produce strong cellular responses and specific IgG2a and IgG2b antibody responses to protein immunogens. This study shows that a new TLR7 ligand, 3M-019, in combination with liposomes produces very strong immune responses to a pure protein prototype vaccine in mice. Female C57BL/6 mice were immunized subcutaneously with ovalbumin (OVA, 0.1 mg/dose) weekly 4x. Some groups were immunized to OVA plus 3M-019 or to OVA plus 3M-019 encapsulated in liposomes. Both antibody and cellular immune responses against OVA were measured after either two or four immunizations. Anti-OVA IgG antibody responses were significantly increased after two immunizations and were substantially higher after four immunizations in mice immunized with OVA combined with 3M-019. Encapsulation in liposomes further augmented antibody responses. IgM responses, on the other hand, were lowered by 3M-019. OVA-specific IgG2a levels were increased 625-fold by 3M-019 in liposomes compared to OVA alone, while anti-OVA IgG2b levels were over 3,000 times higher. In both cases encapsulation of 3M-019 in liposomes was stronger than either liposomes alone or 3M-019 without liposomes. Cellular immune responses were likewise increased by 3M-019 but further enhanced when it was encapsulated in liposomes. The lack of toxicity also indicates that this combination may by safe, effective method to boost immune response to cancer vaccines.

  4. Rethinking m6A Readers, Writers, and Erasers

    PubMed Central

    Meyer, Kate D.; Jaffrey, Samie R.

    2018-01-01

    In recent years, m6A has emerged as an abundant and dynamically regulated modification throughout the transcriptome. Recent technological advances have enabled the transcriptome-wide identification of m6A residues, which in turn has provided important insights into the biology and regulation of this pervasive regulatory mark. Also central to our current understanding of m6A are the discovery and characterization of m6A readers, writers, and erasers. Over the last few years, studies into the function of these proteins have led to important discoveries about the regulation and function of m6A. However, during this time our understanding of these proteins has also evolved considerably, sometimes leading to the reversal of early conceptions regarding the reading, writing and erasing of m6A. In this review, we summarize recent advances in m6A research, and we highlight how these new findings have reshaped our understanding of how m6A is regulated in the transcriptome. PMID:28759256

  5. Dissolution rates of pure methane hydrate and carbon-dioxide hydrate in undersaturated seawater at 1000-m depth

    USGS Publications Warehouse

    Rehder, G.; Kirby, S.H.; Durham, W.B.; Stern, L.A.; Peltzer, E.T.; Pinkston, J.; Brewer, P.G.

    2004-01-01

    To help constrain models involving the chemical stability and lifetime of gas clathrate hydrates exposed at the seafloor, dissolution rates of pure methane and carbon-dioxide hydrates were measured directly on the seafloor within the nominal pressure-temperature (P/T) range of the gas hydrate stability zone. Other natural boundary conditions included variable flow velocity and undersaturation of seawater with respect to the hydrate-forming species. Four cylindrical test specimens of pure, polycrystalline CH4 and CO2 hydrate were grown and fully compacted in the laboratory, then transferred by pressure vessel to the seafloor (1028 m depth), exposed to the deep ocean environment, and monitored for 27 hours using time-lapse and HDTV cameras. Video analysis showed diameter reductions at rates between 0.94 and 1.20 ??m/s and between 9.0 and 10.6 ?? 10-2 ??m/s for the CO2 and CH4 hydrates, respectively, corresponding to dissolution rates of 4.15 ?? 0.5 mmol CO2/m2s and 0.37 ?? 0.03 mmol CH4/m2s. The ratio of the dissolution rates fits a diffusive boundary layer model that incorporates relative gas solubilities appropriate to the field site, which implies that the kinetics of the dissolution of both hydrates is diffusion-controlled. The observed dissolution of several mm (CH4) or tens of mm (CO2) of hydrate from the sample surfaces per day has major implications for estimating the longevity of natural gas hydrate outcrops as well as for the possible roles of CO2 hydrates in marine carbon sequestration strategies. ?? 2003 Elsevier Ltd.

  6. Training older adults on Theory of Mind (ToM): transfer on metamemory.

    PubMed

    Lecce, Serena; Bottiroli, Sara; Bianco, Federica; Rosi, Alessia; Cavallini, Elena

    2015-01-01

    Research on aging has shown a significant decline in ToM after 65 years of age. Despite these age-related difficulties, no study has yet investigated the possibility to improve ToM in older adults. To address this gap we tested the efficacy of a conversation-based ToM training with age-appropriate ToM tasks and its transfer effects on metamemory. We examined 72 older adults (Mage=67.61 years, SD=6.39 years) assigned to three training conditions: a ToM training, a physical-conversation training and a social-contact group. All participants took part in two 2-h testing and to two 2-h training sessions. Results showed that after the intervention, older adults in the ToM training group improved their mental states' understanding significantly more than participants in the physical-conversation training and in the social-contact groups. Crucially, the positive effect of the ToM intervention generalized to metamemory knowledge. This is the first study investigating the efficacy of a ToM training and its transfer effect on metacognition in older adults. From a theoretical point of view, it supports the relation between ToM and metamemory. Practical implications of these data are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Strain dependent effects of conditioned fear in adult C57Bl/6 and Balb/C mice following postnatal exposure to chlorpyrifos: relation to expression of brain acetylcholinesterase mRNA

    PubMed Central

    Oriel, Sarit; Kofman, Ora

    2015-01-01

    Following reports of emotional psychopathology in children and adults exposed to organophosphates, the effects of postnatal chlorpyrifos (CPF) on fear-conditioning and depression-like behaviors were tested in adult mice. Concomitant changes in expression of mRNA for synaptic and soluble splice variants of acetylcholinesterase (AChE) were examined in mouse pups and adults of the Balb/C and C57Bl/6 (B6) strains, which differ in their behavioral and hormonal stress response. Mice were injected subcutaneously with 1 mg/kg CPF on postnatal days 4–10 and tested as adults for conditioned fear, sucrose preference, and forced swim. Acetylcholinesterase activity was assessed in the brains of pups on the first and last day of treatment. Expression of soluble and synaptic AChE mRNA was assessed in brains of treated pups and fear-conditioned adults using real-time PCR. Adult Balb/C mice exposed postnatally to CPF showed exacerbated fear-conditioning and impaired active avoidance. Adult B6 mice exposed postnatally to CPF showed a more specific fear response to tones and less freezing in the inter-tone intervals, in contrast to the vehicle-pretreated mice. Chlorpyrifos also attenuated sweet preference and enhanced climbing in the forced swim test. Chlorpyrifos-treated mice had increased expression of both synaptic and readthrough AChE transcripts in the hippocampus of Balb/C mice and decreased expression in the amygdala following fear-conditioning. In conclusion, postnatal CPF had long-term effects on fear and depression, as well as on expression of AChE mRNA. These changes may be related to alteration in the interaction between hippocampus and amygdala in regulating negative emotions. PMID:25972795

  8. High-throughput m6A-seq reveals RNA m6A methylation patterns in the chloroplast and mitochondria transcriptomes of Arabidopsis thaliana.

    PubMed

    Wang, Zegang; Tang, Kai; Zhang, Dayong; Wan, Yizhen; Wen, Yan; Lu, Quanyou; Wang, Lei

    2017-01-01

    This study is the first to comprehensively characterize m6A patterns in the Arabidopsis chloroplast and mitochondria transcriptomes based on our open accessible data deposited in NCBI's Gene Expression Omnibus with GEO Series accession number of GSE72706. Over 86% of the transcripts were methylated by m6A in the two organelles. Over 550 and 350 m6A sites were mapped, with ~5.6 to ~5.8 and ~4.6 to ~4.9 m6A sites per transcript, to the chloroplast and mitochondria genome, respectively. The overall m6A methylation extent in the two organelles was greatly higher than that in the nucleus. The m6A motif sequences in the transcriptome of two organelles were similar to the nuclear motifs, suggesting that selection of the m6A motifs for RNA methylation was conserved between the nucleus and organelle transcriptomes. The m6A patterns of rRNAs and tRNAs in the organelle were similar to those in the nucleus. However, the m6A patterns in coding RNAs were distinct between the nucleus and the organelle, suggesting that that regulation of the m6A methylation patterns may be different between the nuclei and the organelles. The extensively methylated transcripts in the two organelles were mainly associated with rRNA, ribosomal proteins, photosystem reaction proteins, tRNA, NADH dehydrogenase and redox. On average, 64% and 79% of the transcripts in the two organelles showed differential m6A methylation across three organs of the leaves, flowers and roots. The m6A methylation extent in the chloroplast was higher than that in the mitochondria. This study provides deep insights into the m6A methylation topology and differentiation in the plant organelle transcriptomes.

  9. Ethnoveterinary application of Morinda citrifolia fruit puree on a commercial heifer rearing facility with endemic salmonellosis.

    PubMed

    Brooks, V J; De Wolfe, T J; Paulus, T J; Xu, J; Cai, J; Keuler, N S; Godbee, R G; Peek, S F; McGuirk, S M; Darien, B J

    2012-01-01

    We have previously reported that Morinda citrifolia (noni) puree modulates neonatal calves developmental maturation of the innate and adaptive immune system. In this study, the effect of noni puree on respiratory and gastrointestinal (GI), health in preweaned dairy calves on a farm with endemic salmonellosis was examined. Two clinical trials were conducted whereby each trial evaluated one processing technique of noni puree. Trials 1 and 2 tested noni versions A and B, respectively. Puree analysis and trial methods were identical to each other, with the calf as the experimental unit. Calves were designated to 1 of 3 treatment groups in each trial and received either: 0, 15 or 30 mL every 12 hr of noni supplement for the first 3 weeks of life. Health scores, weaning age, weight gain from admission to weaning, and weaned by 6 weeks, were used as clinical endpoints for statistical analysis. In trial 1, calves supplemented with 15 mL noni puree of version A every 12 hr had a higher probability of being weaned by 6 weeks of age than control calves (P = 0.04). In trial 2, calves receiving 30 mL of version B every 12 hr had a 54.5% reduction in total medical treatments by 42 days of age when compared to controls (P = 0.02). There was a trend in reduced respiratory (61%), and GI (52%) medical treatments per calf when compared to controls (P = 0.06 and 0.08, respectively). There were no differences in weight gain or mortality for any treatment group in either trial.

  10. M553 sphere forming experiment: Pure nickel specimen evaluation

    NASA Technical Reports Server (NTRS)

    Johnson, P. C.; Peters, E. T.

    1973-01-01

    A region or cap of very fine two-dimensional surface growth structure was observed at the top of three of the six pure nickel flight specimens. Such two-dimensional surface growth structures have been observed both on the ground-based specimens and on other surface areas of the flight specimens. However, the fine structures observed on the three flight samples are at least an order of magnitude finer than those previously observed, and resemble similar localized, fine, two-dimensional surface structures observed in both ground and flight specimens for the nickel alloys. The two-dimensional growth areas consist primarily of fine equiaxed grains, specimen SL-2.6, fine dendrites, specimen SL-2.5, or a core of fine equiaxed grains surrounded by a ring of fine dendrites, specimen SL-1.9.

  11. Lymphocyte proliferative responses of goats vaccinated with Brucella melitensis 16M or a delta purE201 strain.

    PubMed Central

    Olsen, S C; Cheville, N F; Stevens, M G; Houng, H H; Drazek, E S; Hadfield, T L; Warren, R L; Hoover, D L

    1997-01-01

    The response to a Brucella melitensis purEK deletion mutant, delta purE201 (referred to as strain 201), was compared with the response to its parental strain, 16M, in juvenile goats. Proliferative responses to gamma-irradiated bacteria were detected earlier in strain 201-infected goats. Lymphocytes from strain 16M- or 201-infected goats proliferated in response to one-dimensional polyacrylamide gel electrophoresis-separated proteins of similar mass isolated from strain 16M or Brucella abortus RB51. Data from this study suggest that some antigens stimulating cell-mediated responses are conserved among Brucella species, as 201- and 16M-infected goats recognized similar proteins expressed by RB51 and 16M. PMID:9199478

  12. mRNA N6-methyladenosine methylation of postnatal liver development in pig.

    PubMed

    He, Shen; Wang, Hong; Liu, Rui; He, Mengnan; Che, Tiandong; Jin, Long; Deng, Lamei; Tian, Shilin; Li, Yan; Lu, Hongfeng; Li, Xuewei; Jiang, Zhi; Li, Diyan; Li, Mingzhou

    2017-01-01

    N6-methyladenosine (m6A) is a ubiquitous reversible epigenetic RNA modification that plays an important role in the regulation of post-transcriptional protein coding gene expression. Liver is a vital organ and plays a major role in metabolism with numerous functions. Information concerning the dynamic patterns of mRNA m6A methylation during postnatal development of liver has been long overdue and elucidation of this information will benefit for further deciphering a multitude of functional outcomes of mRNA m6A methylation. Here, we profile transcriptome-wide m6A in porcine liver at three developmental stages: newborn (0 day), suckling (21 days) and adult (2 years). About 33% of transcribed genes were modified by m6A, with 1.33 to 1.42 m6A peaks per modified gene. m6A was distributed predominantly around stop codons. The consensus motif sequence RRm6ACH was observed in 78.90% of m6A peaks. A negative correlation (average Pearson's r = -0.45, P < 10-16) was found between levels of m6A methylation and gene expression. Functional enrichment analysis of genes consistently modified by m6A methylation at all three stages showed genes relevant to important functions, including regulation of growth and development, regulation of metabolic processes and protein catabolic processes. Genes with higher m6A methylation and lower expression levels at any particular stage were associated with the biological processes required for or unique to that stage. We suggest that differential m6A methylation may be important for the regulation of nutrient metabolism in porcine liver.

  13. Arabidopsis m6A demethylase activity modulates viral infection of a plant virus and the m6A abundance in its genomic RNAs

    PubMed Central

    Martínez-Pérez, Mireya; Aparicio, Frederic; López-Gresa, Maria Pilar; Bellés, Jose María; Sánchez-Navarro, Jesus A.

    2017-01-01

    N6-methyladenosine (m6A) is an internal, reversible nucleotide modification that constitutes an important regulatory mechanism in RNA biology. Unlike mammals and yeast, no component of the m6A cellular machinery has been described in plants at present. m6A has been identified in the genomic RNAs of diverse mammalian viruses and, additionally, viral infection was found to be modulated by the abundance of m6A in viral RNAs. Here we show that the Arabidopsis thaliana protein atALKBH9B (At2g17970) is a demethylase that removes m6A from single-stranded RNA molecules in vitro. atALKBH9B accumulates in cytoplasmic granules, which colocalize with siRNA bodies and associate with P bodies, suggesting that atALKBH9B m6A demethylase activity could be linked to mRNA silencing and/or mRNA decay processes. Moreover, we identified the presence of m6A in the genomes of two members of the Bromoviridae family, alfalfa mosaic virus (AMV) and cucumber mosaic virus (CMV). The demethylation activity of atALKBH9B affected the infectivity of AMV but not of CMV, correlating with the ability of atALKBH9B to interact (or not) with their coat proteins. Suppression of atALKBH9B increased the relative abundance of m6A in the AMV genome, impairing the systemic invasion of the plant, while not having any effect on CMV infection. Our findings suggest that, as recently found in animal viruses, m6A modification may represent a plant regulatory strategy to control cytoplasmic-replicating RNA viruses. PMID:28923956

  14. Recovery of Patients with Pure Diffuse Axonal Injury Who Remained in a Coma for 6 Hours or More.

    PubMed

    Almeida Vieira, Rita de Cássia; Paiva, Wellingson Silva; de Oliveira, Daniel Vieira; de Paula Guirado, Vinícius Monteiro; Caetano Lança, Ellen de Fátima; de Sousa, Regina Márcia Cardoso

    2018-01-01

    Diffuse axonal injury (DAI) is a traumatic brain injury and one of the most common causes of unfavorable outcome and death. The aim of this study was to investigate the recovery of patients with pure DAI who remained in a coma for 6 hours or longer after brain injury. This was a follow-up study of 75 patients diagnosed with pure DAI, aged 18-60 years, with a Glasgow Coma Scale score ≤8 at hospital admission. Patient data were collected at hospital admission, hospital discharge, and 3 and 6 months after DAI. Recovery was assessed by score changes in the Katz Index of Independence in Activities of Daily Living and Extended Glasgow Outcome Scale. The percentage of patients in a coma for 6-24 hours, >24 hours without brainstem signs, and >24 hours with brainstem signs was 42.7%, 20%, and 37.3%, respectively. The 6-month mortality rate was 32.0%, and the mean Extended Glasgow Outcome Scale score among survivors decreased from 3.8 at discharge (SD = 1.2) to 2.1 at 3 months (SD = 1.6) and 1.2 at 6 months (SD = 1.6). The mean Katz Index of Independence in Activities of Daily Living scores were 8.5 (SD = 5.5), 3.5 (SD = 5.8), and 1.8 (SD = 4.5) at discharge and 3 and 6 months after trauma, respectively. Statistically significant differences were observed among the 3 evaluation periods. Mortality was high among patients with DAI, but almost all survivors had favorable outcomes at 6 months. Functional improvement was more pronounced in the first 3 months. Copyright © 2017. Published by Elsevier Inc.

  15. The m6A pathway facilitates sex determination in Drosophila

    PubMed Central

    Kan, Lijuan; Grozhik, Anya V.; Vedanayagam, Jeffrey; Patil, Deepak P.; Pang, Nan; Lim, Kok-Seong; Huang, Yi-Chun; Joseph, Brian; Lin, Ching-Jung; Despic, Vladimir; Guo, Jian; Yan, Dong; Kondo, Shu; Deng, Wu-Min; Dedon, Peter C.; Jaffrey, Samie R.; Lai, Eric C.

    2017-01-01

    The conserved modification N6-methyladenosine (m6A) modulates mRNA processing and activity. Here, we establish the Drosophila system to study the m6A pathway. We first apply miCLIP to map m6A across embryogenesis, characterize its m6A ‘writer’ complex, validate its YTH ‘readers’ CG6422 and YT521-B, and generate mutants in five m6A factors. While m6A factors with additional roles in splicing are lethal, m6A-specific mutants are viable but present certain developmental and behavioural defects. Notably, m6A facilitates the master female determinant Sxl, since multiple m6A components enhance female lethality in Sxl sensitized backgrounds. The m6A pathway regulates Sxl processing directly, since miCLIP data reveal Sxl as a major intronic m6A target, and female-specific Sxl splicing is compromised in multiple m6A pathway mutants. YT521-B is a dominant m6A effector for Sxl regulation, and YT521-B overexpression can induce female-specific Sxl splicing. Overall, our transcriptomic and genetic toolkit reveals in vivo biologic function for the Drosophila m6A pathway. PMID:28675155

  16. Dynamic m(6)A mRNA methylation directs translational control of heat shock response.

    PubMed

    Zhou, Jun; Wan, Ji; Gao, Xiangwei; Zhang, Xingqian; Jaffrey, Samie R; Qian, Shu-Bing

    2015-10-22

    The most abundant mRNA post-transcriptional modification is N(6)-methyladenosine (m(6)A), which has broad roles in RNA biology. In mammalian cells, the asymmetric distribution of m(6)A along mRNAs results in relatively less methylation in the 5' untranslated region (5'UTR) compared to other regions. However, whether and how 5'UTR methylation is regulated is poorly understood. Despite the crucial role of the 5'UTR in translation initiation, very little is known about whether m(6)A modification influences mRNA translation. Here we show that in response to heat shock stress, certain adenosines within the 5'UTR of newly transcribed mRNAs are preferentially methylated. We find that the dynamic 5'UTR methylation is a result of stress-induced nuclear localization of YTHDF2, a well-characterized m(6)A 'reader'. Upon heat shock stress, the nuclear YTHDF2 preserves 5'UTR methylation of stress-induced transcripts by limiting the m(6)A 'eraser' FTO from demethylation. Remarkably, the increased 5'UTR methylation in the form of m(6)A promotes cap-independent translation initiation, providing a mechanism for selective mRNA translation under heat shock stress. Using Hsp70 mRNA as an example, we demonstrate that a single m(6)A modification site in the 5'UTR enables translation initiation independent of the 5' end N(7)-methylguanosine cap. The elucidation of the dynamic features of 5'UTR methylation and its critical role in cap-independent translation not only expands the breadth of physiological roles of m(6)A, but also uncovers a previously unappreciated translational control mechanism in heat shock response.

  17. Casting of Ti-6Al-4V alloy compared with pure Ti in an Ar-arc casting machine.

    PubMed

    Syverud, M; Okabe, T; Herø, H

    1995-10-01

    Dental prostheses of Ti are normally cast in pure Ti. Some appliances, however, require higher yield strength. Casting of Ti alloys is of interest in such cases. The objective of the present work was to study the quality of castings made of Ti-6Al-4V compared with those made of pure Ti. Casting was made into a mold kept at room temperature using a MgO-Al2O3 investment. A standardized five-unit bridge was cast, consisting of two cylindrical crowns with sharp margins and three pontics. The overall mold filling was satisfactory. The margins of the casting alloys were, however, more rugged and incomplete than those of pure Ti. The most likely reason for this difference is the increased formation of dendrites in the alloy and thus more resistance to fluid flow. Furthermore, the sprue of the alloy was also found to contain some spherical, internal pores. Such pores were rare in the pure Ti castings. The surface reactions were found to be minimal for both of the materials. Increased casting deficiencies observed in the cast bridges of the Ti-6Al-4V alloy, compared with pure Ti, were: 1) the margins of the crowns in the bridge were less complete and 2) there was a tendency to an increased internal porosity, particularly in the sprues.

  18. Post-transcriptional m6A editing of HIV-1 mRNAs enhances viral gene expression

    PubMed Central

    Kennedy, Edward M.; Bogerd, Hal P.; Kornepati, Anand V. R.; Kang, Dong; Ghoshal, Delta; Marshall, Joy B.; Poling, Brigid C.; Tsai, Kevin; Gokhale, Nandan S.; Horner, Stacy M.; Cullen, Bryan R.

    2016-01-01

    Summary Covalent addition of a methyl group to the adenosine N6 (m6A) is an evolutionarily conserved and common RNA modification that is thought to modulate several aspects of RNA metabolism. While the presence of multiple m6A editing sites on diverse viral RNAs was reported starting almost 40 years ago, how m6A editing affects virus replication has remained unclear. Here, we used photo-crosslinking-assisted m6A sequencing techniques to precisely map several m6A editing sites on the HIV-1 genome and report that they cluster in the HIV-1 3’ untranslated region (3'UTR). Viral 3'UTR m6A sites or analogous cellular m6A sites strongly enhanced mRNA expression in cis by recruiting the cellular YTHDF m6A “reader” proteins. Reducing YTHDF expression inhibited, while YTHDF overexpression enhanced, HIV-1 protein and RNA expression, and virus replication in CD4+ T cells. These data identify m6A editing, and the resultant recruitment of YTHDF proteins, as major positive regulators of HIV-1 mRNA expression. PMID:27117054

  19. Tris[(6S)-6-hy-droxy-4-epi-shikimic acid] monohydrate: an enanti-omerically pure hy-droxy-lated shikimic acid derived from methyl shikimate.

    PubMed

    Griesbeck, Axel G; Miara, Claus; Neudörfl, Jörg-M

    2012-11-01

    The title compound, 3C(7)H(10)O(6)·H(2)O, is the enanti-omerically pure product of a multi-step synthesis from the enanti-omerically pure natural shikimic acid. The asymmetric unit contains three mol-ecules of the acid and one mol-ecule of water. The cyclo-hexene rings of the acids have half-chair conformations. The carboxyl-ate, the four hydroxide groups and the additional water mol-ecule form a complex three-dimensional hydrogen-bonding network.

  20. Emission of a pulsed purely rotational transition chemical H{sub 2}-F{sub 2} laser

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Molevich, N E; Pichugin, S Yu

    2008-04-30

    The possibility of obtaining efficient emission at purely rotational transitions of HF molecules in a pulsed chemical hydrogen fluoride laser is studied theoretically. The operation of a H{sub 2}-F{sub 2} laser with a gas pressure of 1.1 atm emitting at the v, j {yields} v, j - 1 (v = 1 - 6, j = 10 - 14) transitions is simulated taking into account resonance VR processes. The total specific laser energy release calculated over all the vibrational levels is 5.5 J L{sup -1} on purely rotational transitions at {lambda}{approx}17 {mu}m (j = 14), 3.5 J L{sup -1} at {lambda}{approx}18.5more » {mu}m (j = 13), and 2.5 J L{sup -1} at {lambda}{approx}20 {mu}m (j = 12). (lasers and amplifiers)« less

  1. Reduced m6A mRNA methylation is correlated with the progression of human cervical cancer

    PubMed Central

    Kong, Beihua; Song, Chen; Cong, Jianglin; Hou, Jianqing; Wang, Shaoguang

    2017-01-01

    The m6A mRNA methylation involves in mRNA splicing, degradation and translation. Recent studies have revealed that reduced m6A mRNA methylation might promote cancer development. However, the role of m6A mRNA methylation in cervical cancer development remains unknown. Therefore, we investigated the role of m6A methylation in cervical cancer in the current study. We first evaluated the m6A mRNA methylation level in 286 pairs of cervical cancer samples and their adjacent normal tissues by dot blot assay. Then the role of m6A on patient survival rates and cervical cancer progression were assessed. The m6A level was significantly reduced in the cervical cancer when comparing with the adjacent normal tissue. The m6A level reduction was significantly correlated with the FIGO stage, tumor size, differentiation, lymph invasion and cancer recurrence. It was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with cervical cancer. Reducing m6A level via manipulating the m6A regulators expression promoted cervical cancer cell proliferation. And increasing m6A level significantly suppressed tumor development both in vitro and in vivo. Our results showed that the reduced m6A level is tightly associated with cervical cancer development and m6A mRNA methylation might be a potential therapeutic target in cervical cancer. PMID:29228737

  2. Comparison of adult age differences in verbal and visuo-spatial memory: the importance of 'pure', parallel and validated measures.

    PubMed

    Kemps, Eva; Newson, Rachel

    2006-04-01

    The study compared age-related decrements in verbal and visuo-spatial memory across a broad elderly adult age range. Twenty-four young (18-25 years), 24 young-old (65-74 years), 24 middle-old (75-84 years) and 24 old-old (85-93 years) adults completed parallel recall and recognition measures of verbal and visuo-spatial memory from the Doors and People Test (Baddeley, Emslie & Nimmo-Smith, 1994). These constituted 'pure' and validated indices of either verbal or visuo-spatial memory. Verbal and visuo-spatial memory declined similarly with age, with a steeper decline in recall than recognition. Unlike recognition memory, recall performance also showed a heightened decline after the age of 85. Age-associated memory loss in both modalities was largely due to working memory and executive function. Processing speed and sensory functioning (vision, hearing) made minor contributions to memory performance and age differences in it. Together, these findings demonstrate common, rather than differential, age-related effects on verbal and visuo-spatial memory. They also emphasize the importance of using 'pure', parallel and validated measures of verbal and visuo-spatial memory in memory ageing research.

  3. Engineering of a DNA Polymerase for Direct m6 A Sequencing.

    PubMed

    Aschenbrenner, Joos; Werner, Stephan; Marchand, Virginie; Adam, Martina; Motorin, Yuri; Helm, Mark; Marx, Andreas

    2018-01-08

    Methods for the detection of RNA modifications are of fundamental importance for advancing epitranscriptomics. N 6 -methyladenosine (m 6 A) is the most abundant RNA modification in mammalian mRNA and is involved in the regulation of gene expression. Current detection techniques are laborious and rely on antibody-based enrichment of m 6 A-containing RNA prior to sequencing, since m 6 A modifications are generally "erased" during reverse transcription (RT). To overcome the drawbacks associated with indirect detection, we aimed to generate novel DNA polymerase variants for direct m 6 A sequencing. Therefore, we developed a screen to evolve an RT-active KlenTaq DNA polymerase variant that sets a mark for N 6 -methylation. We identified a mutant that exhibits increased misincorporation opposite m 6 A compared to unmodified A. Application of the generated DNA polymerase in next-generation sequencing allowed the identification of m 6 A sites directly from the sequencing data of untreated RNA samples. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  4. The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.

    PubMed

    Feng, Jie; Hao, Shuyu; Pan, Changcun; Wang, Yu; Wu, Zhen; Zhang, Junting; Yan, Hai; Zhang, Liwei; Wan, Hong

    2015-11-01

    Brainstem and thalamic gliomas are rare, and they are poorly understood in adults. Genetic aberrations that occur in these tumors are still unknown. In this study, we investigated whether thalamic gliomas have different genetic aberrations and clinical outcomes compared with brainstem gliomas in adults. Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%. High-grade gliomas in the thalamus were statistically significantly more numerous than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a significantly shorter overall survival than patients with wild-type tumors (P = .020) by Cox regression after adjustment for other independent risk factors. However, there was no statistical tendency toward a poorer overall survival in thalamic gliomas containing the K27M mutation compared with wild-type tumors. The presence of the K27M mutation significantly corresponded with mutations in TP53 in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with mutations in IDH1, which was detected only in brainstem gliomas. The microarray data identified 86 differentially expressed genes between brainstem and thalamic gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which plays an important role in cancer pathways, was found to be differentially expressed between brainstem and thalamic gliomas with K27M mutations. Although the K27M mutation was frequently observed in adult brainstem and thalamic gliomas, this mutation tended to be associated with a poorer prognosis in brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present different genetic aberrations from thalamic gliomas. These differences may provide guidance for therapeutic decisions for the treatment of adult brainstem and thalamic gliomas, which may have different molecular targets. Copyright © 2015. Published by Elsevier Inc.

  5. N-Substituted cis-4a-(3-Hydroxyphenyl)-8a-methyloctahydroisoquinolines Are Opioid Receptor Pure Antagonists

    PubMed Central

    Carroll, F. Ivy; Chaudhari, Sachin; Thomas, James B.; Mascarella, S. Wayne; Gigstad, Kenneth M.; Deschamps, Jeffrey; Navarro, Hernán A.

    2008-01-01

    N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a–g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctahydroisoquinolines 6a–g can exist in conformations where the 3-hydroxyphenyl substituent is either axial or equatorial similar to the (3-hydroxyphenyl)piperidines 4. The 3-hydroxyphenyl equatorial conformation is responsible for the antagonist activity observed in the (3-hydroxyphenyl)piperidine antagonists. Single crystal X-ray analysis of 6a shows that the 3-hydroxyphenyl equatorial conformation is favored in the solid state. Molecular modeling studies also suggest that the equatorial conformation has the lower potential energy relative to the axial conformation. Evaluation of compounds 6a–g in the [35S]GTP-γ-S in vitro functional assay showed that they were opioid receptor pure antagonists. N-[4a-(3-Hydroxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinoline-6-yl]-3-(piperidin-1-yl)propionamide (6d) with a Ke of 0.27 nM at the κ opioid receptor with 154- and 46-fold selectively relative to the μ and δ receptors, respectively, possessed the best combination of κ potency and selectivity. PMID:16366600

  6. Amplified spontaneous emission of Rhodamine 6G embedded in pure deoxyribonucleic acid

    NASA Astrophysics Data System (ADS)

    Rau, Ileana; Szukalski, Adam; Sznitko, Lech; Miniewicz, Andrzej; Bartkiewicz, Stanislaw; Kajzar, Francois; Sahraoui, Bouchta; Mysliwiec, Jaroslaw

    2012-10-01

    Deoxyribonucleic acid (DNA) is commonly viewed as a genetic information carrier. However, now it is recognized as a nanomaterial, rather than as a biological material, in the research field of nanotechnology. Here, we show that using pure DNA, doped with rhodamine 6G, we are able to observe amplified spontaneous emission (ASE) phenomenon. Moderate ASE threshold, photodegradation, and reasonable gain coefficient observed in this natural host gives some perspectives for practical applications of this system in biophotonics. Obtained results open the way and will be leading to construction of truly bio-lasers using nature made luminophores, such as anthocyanins.

  7. UV Irradiation Effects in Pure and Tin-Doped Amorphous AsSe Films

    DTIC Science & Technology

    2001-06-01

    during irradiation did not exceed 40 ’C. 304 M. Popescu, M. lovu, W. Hloyer, 0. Shpotyuk , F. Sava, A. L6rinczi 3. Results Pure and tin-doped AsSe filns...9000 ,- ,, ---, ,, - ,, - 9000 .... ... .-.. .. r111h) (222) Illuminated 8000 8000 - 7000 7000 lie (220) 6000 6000 5000 O 5000 4000 - 4000 3000 .L...Popescu, M. lovu, W. Hoyer, 0. Shpotyuk , F. Sava, A. L6rinczi the effective thickness of the layers and, possibly, the correlation length. The photo

  8. Treatment for Relapsed/Refractory AML Based on a High Throughput Drug Sensitivity Assay

    ClinicalTrials.gov

    2018-04-11

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  9. Pure transvaginal appendectomy versus traditional laparoscopic appendectomy for acute appendicitis: a prospective cohort study.

    PubMed

    Roberts, Kurt E; Solomon, Daniel; Mirensky, Tamar; Silasi, Dan-Arin; Duffy, Andrew J; Rutherford, Tom; Longo, Walter E; Bell, Robert L

    2012-02-01

    This report describes the first cohort study comparing pure transvaginal appendectomies (TVAs) to traditional 3-port laparoscopic appendectomies (LAs). Between August 2008 and August 2010, 42 patients were offered a pure TVA. Patients who did not wish to undergo a TVA underwent a LA and served as the control group. Demographic data, operative time, length of stay, patient controlled analgesia (PCA) 12-hour-morphine utilization, complications, return to normal activity, and return to work were recorded. Eighteen of 40 enrolled patients underwent a pure TVA. Two patients refused to participate in this study. Mean age (TVA: 31.3 ± 2.5 years vs. LA: 28.2 ± 2.3 years, P = 0.36), mean body mass index (TVA: 23.7 ± 1.2 kg/m2 vs. LA: 23.6 ± 0.7 kg/m2, P = 0.96) mean operative time (TVA: 44.4 ± 4.5 minutes vs. LA: 39.8 ± 2.6 minutes, P = 0.38), and mean length of hospital stay (TVA: 1.1 ± 0.1 days vs. LA: 1.2 ± 0.1 days, P = 0.53) were not statistically significant. However, mean postoperative morphine-use (TVA: 8.7 ± 2.0 mg vs. LA: 23.0 ± 3.4 mg, P < 0.01), return to normal activity (TVA: 3.3 ± 0.4 days vs. LA: 9.7 ± 1.6 days, P < 0.01), and return to work (TVA: 5.4 ± 1.1 days vs. LA: 10.7 ± 1.5 days, P = 0.01) were statistically significant. One conversion in the TVA group to a LA was necessary because of inability to maintain adequate pneumoperitoneum. Four complications were observed: 1 intraabdominal abscess and 1 case of urinary retention in the TVA group; 1 early postoperative bowel obstruction and 1 case of urinary retention in the LA group. Pure TVA is a safe and well-tolerated procedure with significantly less pain and faster recovery compared to traditional LA.

  10. Regulatory Role of N6 -methyladenosine (m6 A) Methylation in RNA Processing and Human Diseases.

    PubMed

    Wei, Wenqiang; Ji, Xinying; Guo, Xiangqian; Ji, Shaoping

    2017-09-01

    N 6 -methyladenosine (m 6 A) modification is an abundant and conservative RNA modification in bacterial and eukaryotic cells. m 6 A modification mainly occurs in the 3' untranslated regions (UTRs) and near the stop codons of mRNA. Diverse strategies have been developed for identifying m 6 A sites in single nucleotide resolution. Dynamic regulation of m 6 A is found in metabolism, embryogenesis, and developmental processes, indicating a possible epigenetic regulation role along RNA processing and exerting biological functions. It has been known that m 6 A editing involves in nuclear RNA export, mRNA degradation, protein translation, and RNA splicing. Deficiency of m 6 A modification will lead to kinds of diseases, such as obesity, cancer, type 2 diabetes mellitus (T2DM), infertility, and developmental arrest. Some specific inhibitors against methyltransferase and demethylase have been developed to selectively regulate m 6 A modification, which may be advantageous for treatment of m 6 A related diseases. J. Cell. Biochem. 118: 2534-2543, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. [Ag2M(Te2O5)2]SO4 (M = CeIV or ThIV): A New Purely Inorganic d/f-Heterometallic Cationic Material.

    PubMed

    Poe, Todd N; White, Frankie D; Proust, Vanessa; Villa, Eric M; Polinski, Matthew J

    2018-05-07

    Two new isotypic d/f-heterometallic purely inorganic cationic materials, [Ag 2 M(Te 2 O 5 ) 2 ]SO 4 (M = Ce IV or Th IV ), were synthesized using the metal oxides (MO 2 and TeO 2 ), silver nitrate, and sulfuric acid under mild hydrothermal conditions. The prepared materials were characterized via single-crystal X-ray diffraction, which revealed that the materials possess a 3D framework of corner-sharing Te 2 O 5 2- units. The tellurite framework creates four unique pores, three of which are occupied by the M IV and Ag I metal centers. The tellurite network, metal coordination, and total charge yield a cationic framework, which is charge-balanced by electrostatically bound sulfate anions residing in the largest of the four framework pores. These materials also possess Ag I in a ligand-imposed linear geometry.

  12. Pure MW Data for v=0-6 of PbI Give Vibrational Spacings and a Full Analytic Potential Energy Function

    NASA Astrophysics Data System (ADS)

    Yoo, Ji Ho (Chris); Evans, Corey; Walker, Nick; Le Roy, Robert J.

    2015-06-01

    At last year's ISMS meeting, Zaleski et al. reported new broadband MW spectroscopy measurements of pure rotational transitions in the v=0-6 levels of the ^2Π1/2 ground electronic state of PbI. The analysis presented at that time was a conventional v-level by v-level `band-constant' analysis performed using the PGopher program. That level-by-level PGopher analysis yielded values of B_v, D_v and five spin-splitting parameters for each vibrational level of each isotopologue. Ignoring the spin-splitting information, the B_v and D_v values were used to generate a set of synthetic pure R(0) transitions for each level that were taken to represent the ``mechanical'' information about the molecule contained in these spectra. A standard direct-potential-fit (DPF) analysis was then used to fit these data to an ``Expanded Morse Oscillator'' (EMO) potential function form. The well-depth parameter D_e was fixed at the literature value, while values of the equilibrium distance r_e and three EMO exponent-coefficient expansion `potential shape' parameters are determined from the fits. The best fits to the data yield potentials whose fundamental vibrational spacings are in excellent agreement with experiment together with reliable predictions for the first five overtone energies. D.P. Zaleski, H. Köckert, S.L. Stephens, N. Walker, L.-M. Dickens, and C. Evans, paper RE08 at the 69th International Symposium on Molecular Spectroscopy, University of Illinois (2014). PGopher - a Program for Simulating Rotational Structure, C. M. Western, University of Bristol, http://pgopher.chm.bris.ac.uk DPotFit 2.0: A Computer Program for fitting Diatomic Molecule Spectra to Potential Energy Functions, R.J. Le Roy, J. Seto and Y. Huang, University of Waterloo Chemical Physics Research Report CP-667 (2013); see http://leroy.uwaterloo.ca/programs/. K. Ziebarth, R. Breidohr, O. Shestakov and E.H. Fink, Chem. Phys. Lett. 190, 271 (1992).

  13. RNA epitranscriptomics: Regulation of infection of RNA and DNA viruses by N6 -methyladenosine (m6 A).

    PubMed

    Tan, Brandon; Gao, Shou-Jiang

    2018-04-26

    N 6 -methyladenosine (m 6 A) was discovered 4 decades ago. However, the functions of m 6 A and the cellular machinery that regulates its changes have just been revealed in the last few years. m 6 A is an abundant internal mRNA modification on cellular RNA and is implicated in diverse cellular functions. Recent works have demonstrated the presence of m 6 A in the genomes of RNA viruses and transcripts of a DNA virus with either a proviral or antiviral role. Here, we first summarize what is known about the m 6 A "writers," "erasers," "readers," and "antireaders" as well as the role of m 6 A in mRNA metabolism. We then review how the replications of numerous viruses are enhanced and restricted by m 6 A with emphasis on the oncogenic DNA virus, Kaposi sarcoma-associated herpesvirus (KSHV), whose m 6 A epitranscriptome was recently mapped. In the context of KSHV, m 6 A and the reader protein YTHDF2 acts as an antiviral mechanism during viral lytic replication. During viral latency, KSHV alters m 6 A on genes that are implicated in cellular transformation and viral latency. Lastly, we discuss future studies that are important to further delineate the functions of m 6 A in KSHV latent and lytic replication and KSHV-induced oncogenesis. Copyright © 2018 John Wiley & Sons, Ltd.

  14. The Role of Dynamic m6 A RNA Methylation in Photobiology.

    PubMed

    Robinson, Myles; Shah, Palak; Cui, Yan-Hong; He, Yu-Ying

    2018-05-04

    N 6 -methyladenosine (m 6 A) is the most abundant internal RNA modification among numerous post-transcriptional modifications identified in eukaryotic mRNA. m 6 A modification of RNA is catalyzed by the "writer" m 6 A methyltransferase enzyme complex, consisting of METTL3, METTL14, WTAP and KIAA1429. The m 6 A modification is reversible and can be removed by "eraser" m 6 A demethylase enzymes, namely, FTO and ALKBH5. The biological function of m 6 A modification on RNA is carried out by RNA-binding effector proteins called "readers." Varied functions of the reader proteins regulate mRNA metabolism by affecting stability, translation, splicing or nuclear export. The epitranscriptomic gene regulation by m 6 A RNA methylation regulates various pathways, which contribute to basic cellular processes essential for cell maintenance, development and cell fate, and affect response to external stimuli and stressors. In this review, we summarize the recent advances in the regulation and function of m 6 A RNA methylation, with a focus on UV-induced DNA damage response and the circadian clock machinery. Insights into the mechanisms of m 6 A RNA regulation and post-transcriptional regulatory function in these biological processes may facilitate the development of new preventive and therapeutic strategies for various diseases related to dysregulation of UV damage response and circadian rhythm. © 2018 The American Society of Photobiology.

  15. A Self-Diagnostic System for the M6 Accelerometer

    NASA Technical Reports Server (NTRS)

    Flanagan, Patrick M.; Lekki, John

    2001-01-01

    The design of a Self-Diagnostic (SD) accelerometer system for the Space Shuttle Main Engine is presented. This retrofit system connects diagnostic electronic hardware and software to the current M6 accelerometer system. This paper discusses the general operation of the M6 accelerometer SD system and procedures for developing and evaluating the SD system. Signal processing techniques using M6 accelerometer diagnostic data are explained. Test results include diagnostic data responding to changing ambient temperature, mounting torque and base mounting impedance.

  16. Pure erythroid leukemia following precursor B-cell lymphoblastic leukemia.

    PubMed

    Xu, Min; Finn, Laura S; Tsuchiya, Karen D; Thomson, Blythe; Pollard, Jessica; Rutledge, Joe

    2012-01-01

    Therapy-related acute myeloid leukemia is an unfortunate sequel to current multimodal intensive chemotherapy. The patient described was diagnosed with pure erythroleukemia, AML-M6b, during therapy for precursor B-cell acute lymphoblastic leukemia. To the best of our knowledge, this is the first report of this unusual association.

  17. Osteolytic Bone Lesions - A Rare Presentation of AML M6.

    PubMed

    Geetha, N; Sreelesh, K P; Priya, M J; Lali, V S; Rekha, N

    2015-01-01

    Acute myeloid leukemia (AML) M6 is a rare form of AML accounting for < 5 % of all AML. Extramedullary involvement is very rarely seen in this entity. Skeletal lesion has not been described in AML M6 before. We discuss the case of a 17 year old boy with AML M6, who presented with osteolytic lesion of right humerus. He was treated with induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  18. Dissecting limiting factors of the Protein synthesis Using Recombinant Elements (PURE) system

    PubMed Central

    Li, Jun; Zhang, Chi; Huang, Poyi; Kuru, Erkin; Forster-Benson, Eliot T. C.; Church, George M.

    2017-01-01

    ABSTRACT Reconstituted cell-free protein synthesis systems such as the Protein synthesis Using Recombinant Elements (PURE) system give high-throughput and controlled access to in vitro protein synthesis. Here we show that compared with the commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has less mRNA degradation and produces up to ∼6-fold full-length proteins. However the majority of polypeptides PURE produces are partially translated or inactive since the signal from firefly luciferase (Fluc) translated in PURE is only ∼2/3rd of that measured using the RTS 100 E. coli HY S30 system. Both of the 2 batch systems suffer from low ribosome recycling efficiency when translating proteins from 82 kD to 224 kD. A systematic fed-batch analysis of PURE shows replenishment of 6 small molecule substrates individually or in combination before energy depletion increased Fluc protein yield by ∼1.5 to ∼2-fold, while creatine phosphate and magnesium have synergistic effects when added to the PURE system. Additionally, while adding EF-P to PURE reduced full-length protein translated, it increased the fraction of functional protein and reduced partially translated protein probably by slowing down the translation process. Finally, ArfA, rather than YaeJ or PrfH, helped reduce ribosome stalling when translating Fluc and improved system productivity in a template-dependent fashion. PMID:28702280

  19. Dissecting limiting factors of the Protein synthesis Using Recombinant Elements (PURE) system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Jun; Zhang, Chi; Huang, Poyi

    Reconstituted cell-free protein synthesis systems such as the Protein synthesis Using Recombinant Elements (PURE) system give high-throughput and controlled access to in vitro protein synthesis. Here we show that compared with the commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has less mRNA degradation and produces up to ~6-fold full-length proteins. However the majority of polypeptides PURE produces are partially translated or inactive since the signal from firefly luciferase (Fluc) translated in PURE is only ~2/3 rd of that measured using the RTS 100 E. coli HY S30 system. Both of the 2 batchmore » systems suffer from low ribosome recycling efficiency when translating proteins from 82 k D to 224 k D. A systematic fed-batch analysis of PURE shows replenishment of 6 small molecule substrates individually or in combination before energy depletion increased Fluc protein yield by ~1.5 to ~2-fold, while creatine phosphate and magnesium have synergistic effects when added to the PURE system. Additionally, while adding EF-P to PURE reduced full-length protein translated, it increased the fraction of functional protein and reduced partially translated protein probably by slowing down the translation process. Finally, ArfA, rather than YaeJ or PrfH, helped reduce ribosome stalling when translating Fluc and improved system productivity in a template-dependent fashion.« less

  20. Dissecting limiting factors of the Protein synthesis Using Recombinant Elements (PURE) system

    DOE PAGES

    Li, Jun; Zhang, Chi; Huang, Poyi; ...

    2017-05-09

    Reconstituted cell-free protein synthesis systems such as the Protein synthesis Using Recombinant Elements (PURE) system give high-throughput and controlled access to in vitro protein synthesis. Here we show that compared with the commercial S30 crude extract based RTS 100 E. coli HY system, the PURE system has less mRNA degradation and produces up to ~6-fold full-length proteins. However the majority of polypeptides PURE produces are partially translated or inactive since the signal from firefly luciferase (Fluc) translated in PURE is only ~2/3 rd of that measured using the RTS 100 E. coli HY S30 system. Both of the 2 batchmore » systems suffer from low ribosome recycling efficiency when translating proteins from 82 k D to 224 k D. A systematic fed-batch analysis of PURE shows replenishment of 6 small molecule substrates individually or in combination before energy depletion increased Fluc protein yield by ~1.5 to ~2-fold, while creatine phosphate and magnesium have synergistic effects when added to the PURE system. Additionally, while adding EF-P to PURE reduced full-length protein translated, it increased the fraction of functional protein and reduced partially translated protein probably by slowing down the translation process. Finally, ArfA, rather than YaeJ or PrfH, helped reduce ribosome stalling when translating Fluc and improved system productivity in a template-dependent fashion.« less

  1. A cross-sectional study of differences in 6-min walk distance in healthy adults residing at high altitude versus sea level

    PubMed Central

    2014-01-01

    Background We sought to determine if adult residents living at high altitude have developed sufficient adaptation to a hypoxic environment to match the functional capacity of a similar population at sea level. To test this hypothesis, we compared the 6-min walk test distance (6MWD) in 334 residents living at sea level vs. at high altitude. Methods We enrolled 168 healthy adults aged ≥35 years residing at sea level in Lima and 166 individuals residing at 3,825 m above sea level in Puno, Peru. Participants completed a 6-min walk test, answered a sociodemographics and clinical questionnaire, underwent spirometry, and a blood test. Results Average age was 54.0 vs. 53.8 years, 48% vs. 43% were male, average height was 155 vs. 158 cm, average blood oxygen saturation was 98% vs. 90%, and average resting heart rate was 67 vs. 72 beats/min in Lima vs. Puno. In multivariable regression, participants in Puno walked 47.6 m less (95% CI -81.7 to -13.6 m; p < 0.01) than those in Lima. Other variables besides age and height that were associated with 6MWD include change in heart rate (4.0 m per beats/min increase above resting heart rate; p < 0.001) and percent body fat (-1.4 m per % increase; p = 0.02). Conclusions The 6-min walk test predicted a lowered functional capacity among Andean high altitude vs. sea level natives at their altitude of residence, which could be explained by an incomplete adaptation or a protective mechanism favoring neuro- and cardioprotection over psychomotor activity. PMID:24484777

  2. Minimally differentiated erythroleukaemia (AML M6 'variant'): a rare subset of AML distinct from AML M6. Groupe Français d'Hématologie Cellulaire.

    PubMed

    Garand, R; Duchayne, E; Blanchard, D; Robillard, N; Kuhlein, E; Fenneteau, O; Salomon-Nguyen, F; Grange, M J; Rousselot, P; Demur, C

    1995-08-01

    We describe eight cases of erythroleukaemia distinct from FAB-AML M6, which demonstrate minimal erythroid differentiation not associated with a myeloblastic component. Three infants (including a Down's syndrome) and two adults presented with a de novo leukaemia. One case was preceded by an untreated refractory anaemia with excess of blasts and one by polycythaemia vera. One case presented with an inaugural blast crisis of chronic myeloid leukaemia. In four patients the leukaemic cells showed a proerythroblast-like morphology. The four other were initially classified as undifferentiated AL (two cases) or AML MO (two cases) because of the immature aspect of the cells, their lack of myeloperoxidase activity and the absence of B, T lymphoid and myeloid (My) marker expressions apart from the CD33 antigen. Immunophenotyping in three cases showed an immature erythroblast profile (glycophorins A and B+, spectrin+). In the five others the erythroid nature was recognized by the expression of ABH blood group system on fresh cells (four cases) and glycophorin A on cells after 3 d in vitro culture with erythropoietin (EPO) + IL3 (two cases). Moreover, an erythroid colony growth of leukaemic origin was observed in three patients. In conclusion, the study of erythroid marker expression is of particular importance when immunophenotyping leukaemic cells with a proerythroblast-like morphology or an undifferentiated aspect and a HLA DR-, CD36++, B-, T-, My- (CD33 +/-) phenotype. We propose the term AML M6 'variant' for this rare type of AML.

  3. A Preliminary Exploration of the Effects of a 6-week Interactive Video Dance Exercise Program in an Adult Population

    PubMed Central

    Fruth, Stacie J; Clifford, Anne; Hine, Stephanie; Huckstep, Jeremy; Merkel, Heidi; Wilkinson, Hilary; Yoder, Jason

    2011-01-01

    Purpose: The purpose of this study was to determine the effects of a 6-week interactive video dance game (IVDG) program on adult participants’ cardiorespiratory status and body mass index (BMI). Methods: Twenty-seven healthy adult participants attended IVDG sessions over a 6-week period. Participants completed pre- and post-testing consisting of a submaximal VO2 treadmill test, assessment of resting heart rate (RHR) and blood pressure (BP), BMI, and general health questionnaires. Data were analyzed using descriptives, paired t-tests to assess pre-to post-testing differences, and one-way ANOVAs to analyze variables among select groups of participants. Questionnaire data was manually coded and assessed. Results: Twenty participants attended at least 75% of available sessions and were used in data analysis. Mean BMI decreased significantly (from 26.96 kg/m2 to 26.21 kg/m2; 2.87%) and cardiorespiratory fitness measured by peak VO2 increased significantly (from 20.63 ml/kg/min to 21.69 ml/kg/min; 5.14%). Most participants reported that the IVDG program was a good workout, and that they were encouraged to continue or start an exercise routine. Forty percent reported improvements in sleep, and nearly half stated they had or were considering purchasing a home version of a video dance game. Conclusions: Interactive video dance game is an effective and enjoyable exercise program for adults who wish to decrease their BMI and improve components of cardiorespiratory fitness. PMID:22163175

  4. Radiation effects on beta /10.6/ of pure and europium doped KCl

    NASA Technical Reports Server (NTRS)

    Grimes, H. H.; Maisel, J. E.; Hartford, R. H.

    1975-01-01

    Changes in the optical absorption coefficient as the result of X-ray and electron bombardment of pure monocrystalline and polycrystalline KCl and of divalent europium doped polycrystalline KCl were determined. A constant heat flow calorimetric method was used to measure the optical absorption coefficients. Both 300 kV X-ray irradiation and 2 MeV electron irradiation produced increases in the optical absorption coefficient at room temperature. X-ray irradiation produced more significant changes in pure monocrystalline KCl than equivalent amounts of electron irradiation. Electron irradiation of pure and Eu-doped polycrystalline KCl produced increases in the absorption by as much as a factor of 20 over untreated material. Bleaching of the electron-irradiated doped KCl with 649 millimicron light produced a further increase.

  5. FTO, m6 Am , and the hypothesis of reversible epitranscriptomic mRNA modifications.

    PubMed

    Mauer, Jan; Jaffrey, Samie R

    2018-05-12

    The fate of mRNA is regulated by epitranscriptomic nucleotide modifications, the most abundant of which is N 6 -methyladenosine (m 6 A). Although the pattern and distribution of m 6 A in mRNA is mediated by specific methyltransferases, a recent hypothesis is that specific demethylases or 'erasers' allow m 6 A to be dynamically reversed by signaling pathways. In this Review, we discuss the data in support and against this model. New insights into the function of fat mass and obesity-associated protein (FTO), the original enzyme thought to be an m 6 A eraser, reveal that its physiologic target is not m 6 A, but instead is N 6 ,2'-O-dimethyladenosine (m 6 A m ). Another m 6 A demethylase, ALKBH5, appears to have functions limited to sperm development in normal mice. Overall, the majority of the data suggest that m 6 A is generally not reversible, although m 6 A may be susceptible to demethylation in pathophysiological states such as cancer. © 2018 Federation of European Biochemical Societies.

  6. Pure zero-dimensional Cs4PbBr6 single crystal rhombohedral microdisks with high luminescence and stability.

    PubMed

    Zhang, Haihua; Liao, Qing; Wu, Yishi; Chen, Jianwei; Gao, Qinggang; Fu, Hongbing

    2017-11-08

    Zero-dimensional (0D) perovskite Cs 4 PbBr 6 has been speculated to be an efficient solid-state emitter, exhibiting strong luminescense on achieving quantum confinement. Although several groups have reported strong green luminescence from Cs 4 PbBr 6 powders and nanocrystals, doubts that the origin of luminescence comes from Cs 4 PbBr 6 itself or CsPbBr 3 impurities have been a point of controversy in recent investigations. Herein, we developed a facile one-step solution self-assembly method to synthesize pure zero-dimensional rhombohedral Cs 4 PbBr 6 micro-disks (MDs) with a high PLQY of 52% ± 5% and photoluminescence full-width at half maximum (FWHM) of 16.8 nm. The obtained rhombohedral MDs were high quality single-crystalline as demonstrated by XRD and SAED patterns. We demonstrated that Cs 4 PbBr 6 MDs and CsPbBr 3 MDs were phase-separated from each other and the strong green emission comes from Cs 4 PbBr 6 . Power and temperature dependence spectra evidenced that the observed strong green luminescence of pure Cs 4 PbBr 6 MDs originated from direct exciton recombination in the isolated octahedra with a large binding energy of 303.9 meV. Significantly, isolated PbBr 6 4- octahedra separated by a Cs + ion insert in the crystal lattice is beneficial to maintaining the structural stability, depicting superior thermal and anion exchange stability. Our study provides an efficient approach to obtain high quality single-crystalline Cs 4 PbBr 6 MDs with highly efficient luminescence and stability for further optoelectronic applications.

  7. A continuous arc delivery optimization algorithm for CyberKnife m6.

    PubMed

    Kearney, Vasant; Descovich, Martina; Sudhyadhom, Atchar; Cheung, Joey P; McGuinness, Christopher; Solberg, Timothy D

    2018-06-01

    This study aims to reduce the delivery time of CyberKnife m6 treatments by allowing for noncoplanar continuous arc delivery. To achieve this, a novel noncoplanar continuous arc delivery optimization algorithm was developed for the CyberKnife m6 treatment system (CyberArc-m6). CyberArc-m6 uses a five-step overarching strategy, in which an initial set of beam geometries is determined, the robotic delivery path is calculated, direct aperture optimization is conducted, intermediate MLC configurations are extracted, and the final beam weights are computed for the continuous arc radiation source model. This algorithm was implemented on five prostate and three brain patients, previously planned using a conventional step-and-shoot CyberKnife m6 delivery technique. The dosimetric quality of the CyberArc-m6 plans was assessed using locally confined mutual information (LCMI), conformity index (CI), heterogeneity index (HI), and a variety of common clinical dosimetric objectives. Using conservative optimization tuning parameters, CyberArc-m6 plans were able to achieve an average CI difference of 0.036 ± 0.025, an average HI difference of 0.046 ± 0.038, and an average LCMI of 0.920 ± 0.030 compared with the original CyberKnife m6 plans. Including a 5 s per minute image alignment time and a 5-min setup time, conservative CyberArc-m6 plans achieved an average treatment delivery speed up of 1.545x ± 0.305x compared with step-and-shoot plans. The CyberArc-m6 algorithm was able to achieve dosimetrically similar plans compared to their step-and-shoot CyberKnife m6 counterparts, while simultaneously reducing treatment delivery times. © 2018 American Association of Physicists in Medicine.

  8. AthMethPre: a web server for the prediction and query of mRNA m6A sites in Arabidopsis thaliana.

    PubMed

    Xiang, Shunian; Yan, Zhangming; Liu, Ke; Zhang, Yaou; Sun, Zhirong

    2016-10-18

    N 6 -Methyladenosine (m 6 A) is the most prevalent and abundant modification in mRNA that has been linked to many key biological processes. High-throughput experiments have generated m 6 A-peaks across the transcriptome of A. thaliana, but the specific methylated sites were not assigned, which impedes the understanding of m 6 A functions in plants. Therefore, computational prediction of mRNA m 6 A sites becomes emergently important. Here, we present a method to predict the m 6 A sites for A. thaliana mRNA sequence(s). To predict the m 6 A sites of an mRNA sequence, we employed the support vector machine to build a classifier using the features of the positional flanking nucleotide sequence and position-independent k-mer nucleotide spectrum. Our method achieved good performance and was applied to a web server to provide service for the prediction of A. thaliana m 6 A sites. The server also provides a comprehensive database of predicted transcriptome-wide m 6 A sites and curated m 6 A-seq peaks from the literature for query and visualization. The AthMethPre web server is the first web server that provides a user-friendly tool for the prediction and query of A. thaliana mRNA m 6 A sites, which is freely accessible for public use at .

  9. Addition of m6A to SV40 late mRNAs enhances viral structural gene expression and replication

    PubMed Central

    Courtney, David G.

    2018-01-01

    Polyomaviruses are a family of small DNA tumor viruses that includes several pathogenic human members, including Merkel cell polyomavirus, BK virus and JC virus. As is characteristic of DNA tumor viruses, gene expression in polyomaviruses is temporally regulated into an early phase, consisting of the viral regulatory proteins, and a late phase, consisting of the viral structural proteins. Previously, the late transcripts expressed by the prototypic polyomavirus simian virus 40 (SV40) were reported to contain several adenosines bearing methyl groups at the N6 position (m6A), although the precise location of these m6A residues, and their phenotypic effects, have not been investigated. Here, we first demonstrate that overexpression of the key m6A reader protein YTHDF2 induces more rapid viral replication, and larger viral plaques, in SV40 infected BSC40 cells, while mutational inactivation of the endogenous YTHDF2 gene, or the m6A methyltransferase METTL3, has the opposite effect, thus suggesting a positive role for m6A in the regulation of SV40 gene expression. To directly test this hypothesis, we mapped sites of m6A addition on SV40 transcripts and identified two m6A sites on the viral early transcripts and eleven m6A sites on the late mRNAs. Using synonymous mutations, we inactivated the majority of the m6A sites on the SV40 late mRNAs and observed that the resultant viral mutant replicated more slowly than wild type SV40. Alternative splicing of SV40 late mRNAs was unaffected by the reduction in m6A residues and our data instead suggest that m6A enhances the translation of viral late transcripts. Together, these data argue that the addition of m6A residues to the late transcripts encoded by SV40 plays an important role in enhancing viral gene expression and, hence, replication. PMID:29447282

  10. Anesthetic efficacy of 1.8 mL versus 3.6 mL of 4% articaine with 1:100,000 epinephrine as a primary buccal infiltration of the mandibular first molar.

    PubMed

    Martin, Matthew; Nusstein, John; Drum, Melissa; Reader, Al; Beck, Mike

    2011-05-01

    No study has compared 1.8 mL and 3.6 mL 4% articaine with 1:100,000 epinephrine in a mandibular buccal infiltration of the first molar. The authors conducted a prospective, randomized, single-blind, crossover study comparing the degree of pulpal anesthesia obtained with 1.8 mL and 3.6 mL 4% articaine with 1:100,000 epinephrine as a primary infiltration in the mandibular first molar. Eighty-six asymptomatic adult subjects randomly received a primary mandibular buccal first molar infiltration of 1.8 mL or 3.6 mL 4% articaine with 1:100,000 epinephrine in two separate appointments. The authors used an electric pulp tester to test the first molar for anesthesia in 3-minute cycles for 90 minutes after the injections. Compared with the 1.8-mL volume of 4% articaine with 1:100,000 epinephrine, the 3.6-mL volume showed a statistically higher success rate (70% vs 50%). The anesthetic efficacy of 3.6 mL 4% articaine with 1:100,000 epinephrine is better than 1.8 mL of the same anesthetic solution in a primary mandibular buccal infiltration of the first molar. However, the success rate of 70% is not high enough to support its use as a primary injection technique in the mandibular first molar. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Tris[(6S)-6-hy­droxy-4-epi-shikimic acid] monohydrate: an enanti­omerically pure hy­droxy­lated shikimic acid derived from methyl shikimate

    PubMed Central

    Griesbeck, Axel G.; Miara, Claus; Neudörfl, Jörg-M.

    2012-01-01

    The title compound, 3C7H10O6·H2O, is the enanti­omerically pure product of a multi-step synthesis from the enanti­omerically pure natural shikimic acid. The asymmetric unit contains three mol­ecules of the acid and one mol­ecule of water. The cyclo­hexene rings of the acids have half-chair conformations. The carboxyl­ate, the four hydroxide groups and the additional water mol­ecule form a complex three-dimensional hydrogen-bonding network. PMID:23284468

  12. Danger and loss events and the incidence of anxiety and depressive disorders: a prospective-longitudinal community study of adolescents and young adults.

    PubMed

    Asselmann, E; Wittchen, H-U; Lieb, R; Höfler, M; Beesdo-Baum, K

    2015-01-01

    There are inconclusive findings regarding whether danger and loss events differentially predict the onset of anxiety and depression. A community sample of adolescents and young adults (n = 2304, age 14-24 years at baseline) was prospectively followed up in up to four assessments over 10 years. Incident anxiety and depressive disorders were assessed at each wave using the DSM-IV/M-CIDI. Life events (including danger, loss and respectively mixed events) were assessed at baseline using the Munich Event List (MEL). Logistic regressions were used to reveal associations between event types at baseline and incident disorders at follow-up. Loss events merely predicted incident 'pure' depression [odds ratio (OR) 2.4 per standard deviation, 95% confidence interval (CI) 1.5-3.9, p < 0.001] whereas danger events predicted incident 'pure' anxiety (OR 2.3, 95% CI 1.1-4.6, p = 0.023) and 'pure' depression (OR 2.5, 95% CI 1.7-3.5, p < 0.001). Mixed events predicted incident 'pure' anxiety (OR 2.9, 95% CI 1.5-5.7, p = 0.002), 'pure' depression (OR 2.4, 95% CI 1.6-3.4, p < 0.001) and their co-morbidity (OR 3.6, 95% CI 1.8-7.0, p < 0.001). Our results provide further evidence for differential effects of danger, loss and respectively mixed events on incident anxiety, depression and their co-morbidity. Since most loss events referred to death/separation from significant others, particularly interpersonal loss appears to be highly specific in predicting depression.

  13. Coordination of m6A mRNA methylation and gene transcription by ZFP217 regulates pluripotency and reprogramming

    PubMed Central

    Aguilo, Francesca; Zhang, Fan; Sancho, Ana; Fidalgo, Miguel; Di Cecilia, Serena; Vashisht, Ajay; Lee, Dung-Fang; Chen, Chih-Hung; Rengasamy, Madhumitha; Andino, Blanca; Jahouh, Farid; Roman, Angel; Krig, Sheryl R.; Wang, Rong; Zhang, Weijia; Wohlschlegel, James A.; Wang, Jianlong; Walsh, Martin J.

    2015-01-01

    SUMMARY Epigenetic and epitranscriptomic networks have important functions in maintaining pluripotency of embryonic stem cells (ESCs) and somatic cell reprogramming. However the mechanisms integrating the actions of these distinct networks are only partially understood. Here, we show that the chromatin-associated zinc finger protein 217 (ZFP217) coordinates epigenetic and epitranscriptomic regulation. ZFP217 interacts with several epigenetic regulators, activates transcription of key pluripotency genes, and modulates N6-methyladenosine (m6A) deposition on their transcripts by sequestering the enzyme m6A methyltransferase-like 3 (METTL3). Consistently, Zfp217 depletion compromises ESC self-renewal and somatic cell reprogramming, globally increases m6A RNA levels, and enhances m6A modification of Nanog, Sox2, Klf4, and c-Myc mRNAs, promoting their degradation. ZFP217 binds its own target gene mRNAs, which are also METTL3-associated, and is enriched at promoters of m6A-modified transcripts. Collectively, these findings shed light on how a transcription factor can tightly couple gene transcription to m6A RNA modification to insure ESC identity. PMID:26526723

  14. ThermoData Engine Database - Pure Compounds and Binary Mixtures

    National Institute of Standards and Technology Data Gateway

    SRD 103b NIST ThermoData Engine Version 6.0 - Pure CompoThermoData Engine Database - Pure Compounds and Binary Mixtures (PC database for purchase)   This database contains property data for more than 21,000 pure compounds, 37,500 binary mixtures, 10,000 ternary mixtures, and 6,000 chemical reactions.

  15. Synthesis and biological activity of M6-P and M6-P analogs on fibroblast and keratinocyte proliferation.

    PubMed

    Clavel, Caroline; Barragan-Montero, Véronique; Garric, Xavier; Molès, Jean-Pierre; Montero, Jean-Louis

    2005-09-01

    A new synthetic route to obtain the carboxylate analog of mannose 6-phosphate (M6-P) is presented. The effects of the M6-P, the carboxylate and two other analogs (the phosphonate and the alpha,beta ethylenic carboxylate) on the proliferation of human keratinocytes and dermal fibroblasts as well as on the proliferation of a murine fibroblast cell line, 3T3-J2 are tested. We observed that M6-P is a potent inhibitor of proliferation of both fibroblasts and keratinocytes. Among its analogs, the phosphonate showed a similar effect on human dermal fibroblasts but not on keratinocytes.

  16. Immunoglobulin M nephropathy nephropathy in adults and adolescents in India: a single-center study of natural history.

    PubMed

    Singhai, A M; Vanikar, A V; Goplani, K R; Kanodia, K V; Patel, R D; Suthar, K S; Patel, H V; Gumber, M R; Shah, P R; Trivedi, H L

    2011-01-01

    Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis (GN) usually presenting clinically as steroid resistant/dependent nephrotic syndrome (NS) with pathology of mesangial proliferative GN or focal and segmental glomerulosclerosis with diffuse predominant mesangial IgM deposits. Not much information is available about its natural history. This is the first Indian study to our knowledge on IgMN in adults and adolescents. We evaluated renal biopsies performed at our center between January,'04 to September,'09. Biopsies of all adolescents and adults were evaluated for IgMN and we studied their age, gender distribution, blood pressure (BP), disease duration, steroid/immunosuppressive management and serial serum creatinine (SCr), urinary proteins, and BP values. Patients with other systemic diseases/infections and children were excluded. IgMN constituted 4.3% of 2702 adult renal biopsies. No significant gender predilection was noted. Males presented at average age of 23.1 years, females at 30 years. Steroid-dependent NS was the commonest presentation noted in 75% followed by steroid-resistant NS. Hypertension was noted in 10% patients. Mesangial proliferative GN (MePGN) was commonest histopathological finding noted in 74.4%, followed by focal segmental glomerulosclerosis (FSGS) in 16.2%, and minimal change disease (MCD) in 9.4% biopsies. Sole IgM deposits were noted in 88.5%. All MCD, 35.6% MePGN reached remission, FSGS progressed to renal failure by 1 year. Hypertension, proteinuria, interstitial fibrosis, and FSGS were bad prognosticators. This is the first Indian study of IgMN in adults and adolescents carried out over a period of 5.8 years, which has shown that hypertension, proteinuria, and interstitial fibrosis at presentation have bad prognosis.

  17. Social inequalities in pure-tone hearing assessed using occupational stratification schemes.

    PubMed

    von Gablenz, Petra; Holube, Inga

    2017-07-01

    The objective of this study is to analyse the performance of two occupational stratification approaches and the impact of social position on adult hearing. The prevalence of hearing impairment, pure-tone averages (PTA) and prevalence ratios (PR) for relative hearing loss, which focuses on the position of one's PTA in the age- and gender-specific distribution, were compared in groups defined by ISCO Skill Level and the International Socio-Economic Index (ISEI). About 1571 subjects aged 30-89, including 677 highly screened adults, from the cross-sectional study HÖRSTAT. ISCO Skill Level and ISEI yielded qualitatively the same results. The prevalence difference between the socially least and most advantaged group ranges between 10 and 16%, varying with the scheme applied. Low- and high-frequency PTA and PR for relative hearing loss confirm the gradient. Screening reduced, but did not negate the social differences. The prevalence difference dropped to 6-7% in the otologically normal subsample. Social groups defined by hierarchical, occupational measures differ in their pure-tone hearing, even if the main risk factors are controlled for. This underlines the need for population-based sampling, the relevance of reporting the study group's social composition and the importance of advancing the discussion on appropriate social measures in hearing research.

  18. [((H)L)2Fe6(NCMe)m]n+ (m = 0, 2, 4, 6; n = -1, 0, 1, 2, 3, 4, 6): an electron-transfer series featuring octahedral Fe6 clusters supported by a hexaamide ligand platform.

    PubMed

    Zhao, Qinliang; Harris, T David; Betley, Theodore A

    2011-06-01

    Using a trinucleating hexaamide ligand platform, the all-ferrous hexanuclear cluster ((H)L)(2)Fe(6) (1) is obtained from reaction of 3 equiv of Fe(2)(Mes)(4) (Mes = 2,4,6-Me(3)C(6)H(2)) with 2 equiv of the ligand ((H)L)H(6). Compound 1 was characterized by X-ray diffraction analysis, (57)Fe Mössbauer, SQUID magnetometry, mass spectrometry, and combustion analysis, providing evidence for an S=6 ground state and delocalized electronic structure. The cyclic voltammogram of [((H)L)(2)Fe(6)](n+) in acetonitrile reveals a rich redox chemistry, featuring five fully reversible redox events that span six oxidation states ([((H)L)(2)Fe(6)](n+), where n=-1→4) within a 1.3 V potential range. Accordingly, each of these species is readily accessed chemically to provide the electron-transfer series [((H)L)(2)Fe(6)(NCMe)(m)][PF(6)](n) (m=0, n=-1 (2); m=2, n=1 (3); m=4, n=2 (4); m=6, n=3 (5); m=6, n=4 (6)). Compounds 2-6 were isolated and characterized by X-ray diffraction, (57)Fe Mössbauer and multinuclear NMR spectroscopy, and combustion analysis. Two-electron oxidation of the tetracationic cluster in 6 by 2 equiv of [NO](+) generates the thermally unstable hexacationic cluster [((H)L)(2)Fe(6)(NCMe)(m)](6+), which is characterized by NMR and (57)Fe Mössbauer spectroscopy. Importantly, several stepwise systematic metrical changes accompany oxidation state changes to the [Fe(6)] core, namely trans ligation of solvent molecules and variation in Mössbauer spectra, spin ground state, and intracluster Fe-Fe separation. The observed metrical changes are rationalized by considering a qualitative, delocalized molecular orbital description, which provides a set of frontier orbitals populated by Fe 3d electrons. © 2011 American Chemical Society

  19. Using mHealth Technology in a Self-Management Intervention to Promote Physical Activity Among Adults With Chronic Disabling Conditions: Randomized Controlled Trial.

    PubMed

    Plow, Matthew; Golding, Meghan

    2017-12-01

    Physical activity is considered a comprehensive approach for managing limitations in physical function among adults with chronic disabling conditions. However, adults with chronic disabling conditions often face many barriers to engaging in physical activity. A strategy to promote physical activity among adults with chronic disabling conditions is to encourage the use of mobile health (mHealth) apps. The objective of this pilot study was to examine the potential benefits of using commercially available mHealth apps in a self-management intervention among 46 adults with musculoskeletal or neurological conditions. Participants were randomized to one of 3 intervention groups: (1) mHealth-based self-management intervention, (2) paper-based self-management intervention, and (3) contact-control intervention. Participants in all 3 groups met in person once and received 3 follow-up phone calls with a trained graduate assistant. Participants in the mHealth-based and paper-based groups received a computer tablet or a paper diary, respectively, to facilitate goal setting, self-monitoring, and action planning. Participants in the contact-control group received information on healthy behaviors without being taught skills to change behaviors. The following outcomes were measured at baseline and at the 7th week: physical activity (Physical Activity and Disability Survey-revised), psychosocial factors (self-efficacy, self-regulation, and social support), and physical function (Patient Report Outcomes Measurement Information System, 6-min walk test, 1-min chair stands, and 1-min arm curls). Repeated-measures multivariate analysis of variance (MANOVA) indicated significant differences between groups in physical activity levels (Wilks λ=0.71, F 6,76 =2.34, P=.04). Both the mHealth-based and paper-based groups had large effect size increases in planned exercise and leisure-time physical activity compared with the contact-control group (Cohen d=1.20 and d=0.82, respectively). Repeated

  20. Chromosomal mapping of the human M6 genes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Olinsky, S.; Loop, B.T.; DeKosky, A.

    1996-05-01

    M6 is a neuronal membrane glycoprotein that may have an important role in neural development. This molecule was initially defined by a monoclonal antibody that affected the survival of cultured cerebellar neurons and the outgrowth of neurites. The nature of the antigen was discovered by expression cDNA cloning using this monoclonal antibody. Two distinct murine M6 cDNAs (designated M6a and M6b) whose deduced amino acid sequences were remarkably similar to that of the myelin proteolipid protein human cDNA and genomic clones encoding M6a and M6b and have characterized them by restriction mapping, Southern hybridization with cDNA probes, and sequence analysis.more » We have localized these genes within the human genome by FISH (fluorescence in situ hybridization). The human M6a gene is located at 4q34, and the M6b gene is located at Xp22.2 A number of human neurological disorders have been mapped to the Xp22 region, including Aicardi syndrome (MIM 304050), Rett syndrome (MIM 312750), X-linked Charcot-Marie-Tooth neuropathy (MIM 302801), and X-linked mental retardation syndromes (MRX1, MIM 309530). This raises the possibility that a defect in the M6b gene is responsible for one of these neurological disorders. 8 refs., 3 figs.« less

  1. M6-C artificial disc placement.

    PubMed

    Coric, Domagoj; Parish, John; Boltes, Margaret O

    2017-01-01

    There has been a steady evolution of cervical total disc replacement (TDR) devices over the last decade resulting in surgical technique that closely mimics anterior cervical discectomy and fusion as well as disc design that emphasizes quality of motion. The M6-C TDR device is a modern-generation artificial disc composed of titanium endplates with tri-keel fixation as well as a polyethylene weave with a polyurethane core. Although not yet approved by the FDA, M6-C has finished a pilot and pivotal US Investigational Device Exemption (IDE) study. The authors present the surgical technique for implantation of a 2-level M6-C cervical TDR device. The video can be found here: https://youtu.be/rFEAqINLRCo .

  2. Reversible methylation of m6Am in the 5′ cap controls mRNA stability

    PubMed Central

    Mauer, Jan; Luo, Xiaobing; Blanjoie, Alexandre; Jiao, Xinfu; Grozhik, Anya V.; Patil, Deepak P.; Linder, Bastian; Pickering, Brian F.; Vasseur, Jean-Jacques; Chen, Qiuying; Gross, Steven S.; Elemento, Olivier; Debart, Françoise; Kiledjian, Megerditch; Jaffrey, Samie R.

    2017-01-01

    Internal bases in mRNA can be subjected to modifications that influence the fate of mRNA in cells. One of the most prevalent modified bases is found at the 5′ end of mRNA, at the first encoded nucleotide adjacent to the 7-methylguanosine cap. Here we show that this nucleotide, N6,2′-O-dimethyladenosine (m6Am), is a reversible modification that influences cellular mRNA fate. Using a transcriptome-wide map of m6Am we find that m6Am-initiated transcripts are markedly more stable than mRNAs that begin with other nucleotides. We show that the enhanced stability of m6Am-initiated transcripts is due to resistance to the mRNA-decapping enzyme DCP2. Moreover, we find that m6Am is selectively demethylated by fat mass and obesity-associated protein (FTO). FTO preferentially demethylates m6Am rather than N6-methyladenosine (m6A), and reduces the stability of m6Am mRNAs. Together, these findings show that the methylation status of m6Am in the 5′ cap is a dynamic and reversible epitranscriptomic modification that determines mRNA stability. PMID:28002401

  3. A Simple Protein Synthesis Model for the PURE System Operation.

    PubMed

    Mavelli, Fabio; Marangoni, Roberto; Stano, Pasquale

    2015-06-01

    The encapsulation of transcription-translation (TX-TL) cell-free machinery inside lipid vesicles (liposomes) is a key element in synthetic cell technology. The PURE system is a TX-TL kit composed of well-characterized parts, whose concentrations are fine tunable, which works according to a modular architecture. For these reasons, the PURE system perfectly fulfils the requirements of synthetic biology and is widely used for constructing synthetic cells. In this work, we present a simplified mathematical model to simulate the PURE system operations. Based on Michaelis-Menten kinetics and differential equations, the model describes protein synthesis dynamics by using 9 chemical species, 6 reactions and 16 kinetic parameters. The model correctly predicts the time course for messenger RNA and protein production and allows quantitative predictions. By means of this model, it is possible to foresee how the PURE system species affect the mechanism of proteins synthesis and therefore help in understanding scenarios where the concentration of the PURE system components has been modified purposely or as a result of stochastic fluctuations (for example after random encapsulation inside vesicles). The model also makes the determination of response coefficients for all species involved in the TX-TL mechanism possible and allows for scrutiny on how chemical energy is consumed by the three PURE system modules (transcription, translation and aminoacylation).

  4. Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults.

    PubMed

    Ng, Yi Shiau; Grady, John P; Lax, Nichola Z; Bourke, John P; Alston, Charlotte L; Hardy, Steven A; Falkous, Gavin; Schaefer, Andrew G; Radunovic, Aleksandar; Mohiddin, Saidi A; Ralph, Matilda; Alhakim, Ali; Taylor, Robert W; McFarland, Robert; Turnbull, Douglass M; Gorman, Gráinne S

    2016-08-21

    To provide insight into the mechanism of sudden adult death syndrome (SADS) and to give new clinical guidelines for the cardiac management of patients with the most common mitochondrial DNA mutation, m.3243A>G. These studies were initiated after two young, asymptomatic adults harbouring the m.3243A>G mutation died suddenly and unexpectedly. The m.3243A>G mutation is present in ∼1 in 400 of the population, although the recognized incidence of mitochondrial DNA (mtDNA) disease is ∼1 in 5000. Pathological studies including histochemistry and molecular genetic analyses performed on various post-mortem samples including cardiac tissues (atrium and ventricles) showed marked respiratory chain deficiency and high levels of the m.3243A>G mutation. Systematic review of cause of death in our m.3243A>G patient cohort showed the person-time incidence rate of sudden adult death is 2.4 per 1000 person-years. A further six cases of sudden death among extended family members have been identified from interrogation of family pedigrees. Our findings suggest that SADS is an important cause of death in patients with m.3243A>G and likely to be due to widespread respiratory chain deficiency in cardiac muscle. The involvement of asymptomatic relatives highlights the importance of family tracing in patients with m.3243A>G and the need for specific cardiac arrhythmia surveillance in the management of this common genetic disease. In addition, these findings have prompted the derivation of cardiac guidelines specific to patients with m.3243A>G-related mitochondrial disease. Finally, due to the prevalence of this mtDNA point mutation, we recommend inclusion of testing for m.3243A>G mutations in the genetic autopsy of all unexplained cases of SADS. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  5. A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine.

    PubMed

    Gerich, Mark E; Quiros, J Antonio; Marcin, James P; Tennyson, Linda; Henthorn, Maria; Prindiville, Thomas P

    2010-11-01

    6-mercaptopurine (6-MP) is used for the induction and maintenance of remission of inflammatory bowel disease (IBD). 6-MP is converted into 6-methylmercaptopurine (6-MMP) or 6-thioguanine nucleotides (6-TGN) intracellularly. Treatment response in IBD patients correlates with 6-TGN levels. This study prospectively evaluated the effect of allopurinol on 6-MP metabolites in adult and pediatric IBD patients. Additionally, we quantified the prevalence of preferential metabolism towards 6-MMP through a retrospective analysis of IBD patients. Twenty patients (10 adult; 10 pediatric) with evidence of preferential metabolism towards 6-MMP, (6-TGN<250 pmol/8×10⁸ RBCs and 6-MMP>5000 pmol/8×10⁸ RBCs) were prospectively treated with allopurinol 100 mg daily and up to 100 mg of 6-MP. 6-MP dose was adjusted after a 3-week metabolite measurement. The median dose of 6-MP for adults decreased from 100mg daily (range: 37.5-150 mg) to 25mg daily (range: 12.5-50 mg). The median dose of 6-MP for pediatric patients decreased from 50 mg (range: 25-50 mg) to 10.7 mg (range: 10.7 to 21.4 mg). Mean 6-TGN levels in all subjects increased from 197.4 (± 59) to 284.8 (± 107) pmol/8×10⁸ RBCs (p=0.0005). Mean 6-MMP levels in all subjects decreased from a mean of 7719.8 (± 4716) to 404.8 (± 332) pmol/8×10⁸ RBCs (p=0.0004). There were no complications associated with allopurinol therapy. Eighty-eight (30.9%) of 285 IBD patients had evidence of preferential metabolism towards 6-MMP. The proportion of preferential metabolism was equal in adults and pediatric patients. Our results indicate that the addition of allopurinol safely shifts metabolite production in both adult and pediatric IBD patients and that there is a high prevalence of preferential metabolism towards 6-MMP among IBD patients. Published by Elsevier B.V.

  6. Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation.

    PubMed

    Geula, Shay; Moshitch-Moshkovitz, Sharon; Dominissini, Dan; Mansour, Abed AlFatah; Kol, Nitzan; Salmon-Divon, Mali; Hershkovitz, Vera; Peer, Eyal; Mor, Nofar; Manor, Yair S; Ben-Haim, Moshe Shay; Eyal, Eran; Yunger, Sharon; Pinto, Yishay; Jaitin, Diego Adhemar; Viukov, Sergey; Rais, Yoach; Krupalnik, Vladislav; Chomsky, Elad; Zerbib, Mirie; Maza, Itay; Rechavi, Yoav; Massarwa, Rada; Hanna, Suhair; Amit, Ido; Levanon, Erez Y; Amariglio, Ninette; Stern-Ginossar, Noam; Novershtern, Noa; Rechavi, Gideon; Hanna, Jacob H

    2015-02-27

    Naïve and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N(6)-methyladenosine (m(6)A) transferase, as a regulator for terminating murine naïve pluripotency. Mettl3 knockout preimplantation epiblasts and naïve embryonic stem cells are depleted for m(6)A in mRNAs, yet are viable. However, they fail to adequately terminate their naïve state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m(6)A predominantly and directly reduces mRNA stability, including that of key naïve pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naïve and primed pluripotency in an opposing manner. Copyright © 2015, American Association for the Advancement of Science.

  7. Experimental and numerical investigations of the turbulent wake flow of a generic space launcher at $M_infty =3 M ∞ = 3 and M_infty =6$ M ∞ = 6

    NASA Astrophysics Data System (ADS)

    Statnikov, V.; Stephan, S.; Pausch, K.; Meinke, M.; Radespiel, R.; Schröder, W.

    2016-06-01

    The turbulent wake of a generic space launcher wind tunnel model with an underexpanded nozzle jet is investigated experimentally and numerically to gain insight into the variation of intricate wake flow phenomena of space vehicles at higher stages of the flight trajectory with increasing Mach number. The experiments are carried out at M_∞ =3 and M_∞ =6 in the Ludwieg tube test facility at the Institute of Fluid Mechanics at the Technische Universität Braunschweig, while the corresponding time-resolved computations are performed by the Institute of Aerodynamics at RWTH Aachen University using a zonal RANS-LES approach. A strong alteration of the wake topology with increasing Mach number due to the changing pressure ratio at the nozzle exit is found. At M_∞ =3 the moderate underexpansion rate of p_e/p_∞ ≈ 5 leads to a formation of a recirculation region with an elongated triangular cross-section reaching to the nozzle exit. At M_∞ =6 a substantially stronger afterexpansion of the jet plume (p_e/p_∞ ≈ 100) causes the formation of a cavity region with a quadrangular cross-section. The stronger deflection towards the nozzle at M_∞ =3 results in lower mean and rms wall pressure ratios than at M_∞ =6. However, due to the higher freestream pressure value at the lower Mach number the relation of absolute values is reciprocal, making the lower supersonic regime more critical with respect to dynamic structural loads. This observation is confirmed by an overall good agreement between numerical and experimental data at characteristic positions on the base and nozzle wall. Furthermore, it was shown that undesired effects of the strut support in the wake are present along the whole circumference. For M_∞ =3 the strut influence is found to be particularly intense. The spectral analysis of wall pressure fluctuations reveals fundamental differences in the dynamic behavior of the two investigated wake flow regimes. At M_∞ =3, a dominant frequency range around

  8. Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-04

    Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  9. Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

    ClinicalTrials.gov

    2015-01-22

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  10. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Geographical segregation and IL-6: a marker of chronic inflammation in older adults.

    PubMed

    Purser, Jama L; Kuchibhatla, Maragatha N; Miranda, Marie L; Blazer, Dan G; Cohen, Harvey J; Fillenbaum, Gerda G

    2008-01-01

    AIM: To examine environmental sociodemographic risks of high IL-6, a marker of chronic inflammation in older adults. METHODS: We spatially linked 1990 USA Census tract demographic and economic measures to a prospective cohort study of representative community residents aged 71 years and older, from over 1700 of whom a cytokine protein and biological marker of chronic inflammation. IL-6, was collected. Using generalized interactive mixed models, we modeled 1989-1990 individual and census level risk factors for the dependent variable high IL-6 between 1992-1993 (high IL-6 = upper quartile: >2.96 pg/ml). RESULTS: After individual health risk adjustment, IL-6 remained elevated in communities with greater densities of poor older adults (odd ratio [OR]: 1.25 per 10% increase in exposure. 95% confidence interval [CI]: 1.05, 1.48) and in racially segregated communities (OR: 1.14 per 10% increase in exposure. 95% CI: 1.04, 1.25). CONCLUSIONS: Socially disadvantaged environments may influence IL-6, a biomarker of age-associated inflammation.

  12. Vitamin B6 deficiency: a potential cause of refractory seizures in adults.

    PubMed

    Gerlach, Anthony T; Thomas, Sheela; Stawicki, Stanislaw P; Whitmill, Melissa L; Steinberg, Steven M; Cook, Charles H

    2011-03-01

    In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. Case series. Tertiary care surgical intensive care unit. In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. Intravenous pyridoxine followed by oral pyridoxine. In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration. Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.

  13. High performance direct absorption spectroscopy of pure and binary mixture hydrocarbon gases in the 6-11 μm range

    NASA Astrophysics Data System (ADS)

    Heinrich, Robert; Popescu, Alexandru; Hangauer, Andreas; Strzoda, Rainer; Höfling, Sven

    2017-08-01

    The availability of accurate and fast hydrocarbon analyzers, capable of real-time operation while enabling feedback-loops, would lead to a paradigm change in the petro-chemical industry. Primarily gas chromatographs measure the composition of hydrocarbon process streams. Due to sophisticated gas sampling, these analyzers are limited in response time. As hydrocarbons absorb in the mid-infrared spectral range, the employment of fast spectroscopic systems is highly attractive due to significantly reduced maintenance costs and the capability to setup real-time process control. New developments in mid-infrared laser systems pave the way for the development of high-performance analyzers provided that accurate spectral models are available for multi-species detection. In order to overcome current deficiencies in the availability of spectroscopic data, we developed a laser-based setup covering the 6-11 μm wavelength range. The presented system is designated as laboratory reference system. Its spectral accuracy is at least 6.6× 10^{-3} cm^{-1} with a precision of 3× 10^{-3} cm^{-1}. With a "per point" minimum detectable absorption of 1.3× 10^{-3} cm^{-1} Hz^{{-}{1/2}} it allows us to perform systematic measurements of hydrocarbon spectra of the first 7 alkanes under conditions which are not tabulated in spectroscopic database. We exemplify the system performance with measured direct absorption spectra of methane, propane, iso-butane, and a mixture of methane and propane.

  14. Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

    ClinicalTrials.gov

    2015-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  15. Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-04-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  16. Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-04-25

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  17. Otoacoustic emissions in the general adult population of Nord-Trøndelag, Norway: III. Relationships with pure-tone hearing thresholds.

    PubMed

    Engdahl, Bo; Tambs, Kristian; Borchgrevink, Hans M; Hoffman, Howard J

    2005-01-01

    This study aims to describe the association between otoacoustic emissions (OAEs) and pure-tone hearing thresholds (PTTs) in an unscreened adult population (N =6415), to determine the efficiency by which TEOAEs and DPOAEs can identify ears with elevated PTTs, and to investigate whether a combination of DPOAE and TEOAE responses improves this performance. Associations were examined by linear regression analysis and ANOVA. Test performance was assessed by receiver operator characteristic (ROC) curves. The relation between OAEs and PTTs appeared curvilinear with a moderate degree of non-linearity. Combining DPOAEs and TEOAEs improved performance. Test performance depended on the cut-off thresholds defining elevated PTTs with optimal values between 25 and 45 dB HL, depending on frequency and type of OAE measure. The unique constitution of the present large sample, which reflects the general adult population, makes these results applicable to population-based studies and screening programs.

  18. Epigallocatechin gallate targets FTO and inhibits adipogenesis in an mRNA m6A-YTHDF2-dependent manner.

    PubMed

    Wu, Ruifan; Yao, Yongxi; Jiang, Qin; Cai, Min; Liu, Qing; Wang, Yizhen; Wang, Xinxia

    2018-05-24

    N 6 -methyladenosine (m 6 A) modification of mRNA plays a role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, plays a critical role in anti-obesity and anti-adipogenesis. High-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HPLC-QqQ-MS/MS) was performed to determine the m 6 A levels in 3T3-L1 preadipocytes. The effects of EGCG on the m 6 A levels in specific genes were determined by methylated RNA immunoprecipitation coupled with quantitative real-time PCR (meRIP-qPCR). Several adipogenesis makers and cell cycle genes were analyzed by quantitative real-time PCR (qPCR) and western blotting. Lipid accumulation was evaluated by oil red O staining. All measurements were performed at least for three times. Here we showed that EGCG inhibited adipogenesis by blocking the mitotic clonal expansion (MCE) at the early stage of adipocyte differentiation. Exposing 3T3-L1 cells to EGCG reduced the expression of fat mass and obesity-associated (FTO) protein, an m 6 A demethylase, which led to increased overall levels of RNA m 6 A methylation. Cyclin A2 (CCNA2) and cyclin dependent kinase 2 (CDK2) play vital roles in MCE. The m 6 A levels of CCNA2 and CDK2 mRNA were dramatically enhanced by EGCG. Interestingly, EGCG increased the expression of YTH N 6 -methyladenosine RNA binding protein 2 (YTHDF2), which recognized and decayed methylated mRNAs, resulting in decreased protein levels of CCNA2 and CDK2. As a result, MCE was blocked and adipogenesis was inhibited. FTO overexpression and YTHDF2 knockdown in 3T3-L1 cells significantly increased CCNA2 and CDK2 protein levels and ameliorated the EGCG-induced adipogenesis inhibition. Thus, m 6 A-dependent CCNA2 and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition. Our findings provide mechanistic insights into how m 6 A is involved in the

  19. Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory AML and MDS

    ClinicalTrials.gov

    2017-02-14

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  20. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-07-25

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. AML Therapy With Irradiated Allogeneic Cells

    ClinicalTrials.gov

    2017-02-01

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-14

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-05-16

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  4. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-06-27

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  5. Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-05-30

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  6. Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-02-01

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-01-02

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  8. Czochralski and modified Bridgman-Stockbarger growth of pure, Cd 2+ and Nd 3+ doped benzil single crystals

    NASA Astrophysics Data System (ADS)

    Aggarwal, M. D.; Wang, W. S.; Tambwe, M.

    1993-03-01

    Pure, Cd2+ and Nd3+-doped benzil C6H5COCOC6H5 have been grown from melt using the Czochralski and modified Bridgman-Stockbarger methods. Angle-tuned second harmonic generation of pure benzil from Nd:YAG laser radiation of λ = 1.06 μm with a conversion efficiency η = I2w/Iw = 0.4% has been demonstrated. We have used a Nd:YAG pulse laser to measure the radiation damage threshold as 15.9 MW/cm2 (c-axis) and 23.9 MW/cm2 (a-axis) under the conditions that laser pulse width is 10 ns. Under the same conditions, the conversion efficiency of Nd3+ and Cd2+-doped benzil, η= I2w/Iw = 1.1%, has been demonstrated. The radiation threshold is higher than for pure benzil crystals.

  9. Abnormal glomerular filtration rate in children, adolescents and young adults starts below 75 mL/min/1.73 m(2).

    PubMed

    Pottel, Hans; Hoste, Liesbeth; Delanaye, Pierre

    2015-05-01

    The chronic kidney disease (CKD) classification system for children is similar to that for adults, with both mainly based on estimated glomerular filtration rate (eGFR) combined with fixed cut-off values. The main cut-off eGFR value used to define CKD is 60 mL/min/1.73 m(2), a value that is also applied for children older than 2 years of age, adolescents and young adults. Based on a literature search, we evaluated inclusion criteria for eGFR in clinical trials or research studies on CKD for children. We also collected information on direct measurements of GFR (mGFR) in children and adolescents, with the aim to estimate the normal reference range for GFR. Using serum creatinine (Scr) normal reference values and Scr-based eGFR-equations, we also evaluated the correspondence between Scr normal reference values and (e)GFR normal reference values. Based on our literature search, the inclusion of children in published CKD studies has been based on cut-off values for eGFR of >60 mL/min/1.73 m(2). The lower reference limits for mGFR far exceed this adult threshold. Using eGFR values calculated using Scr-based formulas, we found that abnormal Scr levels in children already correspond to eGFR values that are below a cut-off of 75 mL/min/1.73 m(2). Abnormal GFR in children, adolescents and young adults starts below 75 mL/min/1.73 m(2), and as abnormality is a sign of disease, we recommend referring children, adolescents and young adults with an (e)GFR of <75 mL/min/1.73 m(2) for further clinical assessment.

  10. Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-07-03

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study.

    PubMed

    Leong, Darryl P; Teo, Koon K; Rangarajan, Sumathy; Kutty, V Raman; Lanas, Fernando; Hui, Chen; Quanyong, Xiang; Zhenzhen, Qian; Jinhua, Tang; Noorhassim, Ismail; AlHabib, Khalid F; Moss, Sarah J; Rosengren, Annika; Akalin, Ayse Arzu; Rahman, Omar; Chifamba, Jephat; Orlandini, Andrés; Kumar, Rajesh; Yeates, Karen; Gupta, Rajeev; Yusufali, Afzalhussein; Dans, Antonio; Avezum, Álvaro; Lopez-Jaramillo, Patricio; Poirier, Paul; Heidari, Hosein; Zatonska, Katarzyna; Iqbal, Romaina; Khatib, Rasha; Yusuf, Salim

    2016-12-01

    The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25 th -75 th percentile) 50 kg (43-56 kg) in men <40 years from Europe/North America to 18 kg (14-20 kg) in women >60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported. Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges.

  12. High-intensity exercise training does not influence body weight but improves lipid oxidation in obese adults: a 6-week RCT.

    PubMed

    Jabbour, Georges; Iancu, Horia-Daniel

    2017-01-01

    This study examined the effects of 6 weeks of high-intensity training (HIT) on lipid oxidation (LO) rates during incremental exercises in obese adults. Twenty-four obese adults were randomised into a no-exercise control group (n=12; body mass index=33.3 (4.8) kg.m -2 ) and a HIT group (18 sessions of 6×6 s of supramaximal cycling and 2 min passive intervals; n=12; body mass index=33.2 (2.8)kg.m -2 ). The percentage of LO contribution was computed at rest and for all workloads (25, 50, 75, 100 and 125 W) in both groups before and after training via a graded maximal cycling test. After training, the HIT group showed significantly higher LO at rest and at 25, 50 and 75 W compared with baseline (p<0.01) and the control group (p<0.01). Moreover, for the training group, the homoeostasis model assessment of insulin resistance (HOMA-IR) index decreased significantly from the baseline value (p<0.01) and the control group value (p<0.01). The increases in LO observed at rest and stages 25, 50 and 75 W were positively correlated with the declines in the HOMA-IR index (r=0.87, r=0.83, r=0.91 and r=0.88; p<0.01). In obese adults, HIT increased lipid contributions to energy release at rest and in response to incremental exercise, while there were no changes in participants' aerobic capacity. This supports the hypothesis that metabolic changes rather than improved aerobic capacity are important to improve LO. ISRCTN66508384. Stage: post-results.

  13. An m6A-YTH Module Controls Developmental Timing and Morphogenesis in Arabidopsis.

    PubMed

    Arribas-Hernández, Laura; Bressendorff, Simon; Hansen, Mathias Henning; Poulsen, Christian; Erdmann, Susanne; Brodersen, Peter

    2018-04-11

    Methylation of N6-adenosine (m6A) in mRNA is an important post-transcriptional gene regulatory mechanism in eukaryotes. m6A provides a binding site for effector proteins ("readers") that influence pre-mRNA splicing, mRNA degradation or translational efficiency. YT521-B homology (YTH) domain proteins are important m6A readers with established functions in animals. Plants contain more YTH domain proteins than other eukaryotes, but their biological importance remains unknown. Here, we show that the cytoplasmic Arabidopsis thaliana YTH domain proteins EVOLUTIONARILY CONSERVED C-TERMINAL REGION2/3 (ECT2/3) are required for the correct timing of leaf formation and for normal leaf morphology. These functions depend fully on intact m6A binding sites of ECT2 and ECT3, indicating that they function as m6A readers. Mutation of the close ECT2 homolog, ECT4, enhances the delayed leaf emergence and leaf morphology defects of ect2/ect3 mutants, and all three ECT proteins are expressed at leaf formation sites in the shoot apex of young seedlings and in the division zone of developing leaves. ECT2 and ECT3 are also highly expressed at early stages of trichome development and are required for trichome morphology, as previously reported for m6A itself. Overall, our study establishes the relevance of a cytoplasmic m6A-YTH regulatory module in the timing and execution of plant organogenesis. © 2018 American Society of Plant Biologists. All rights reserved.

  14. Pure Maple Syrup: Nutritive Value.

    PubMed

    Leaf, A L

    1964-02-28

    Variations in concentrations of sugar, nitrogen, phosphorus, potassium, calcium, and magnesium of sap from sugar maple (Acer saccharum, Marsh.) trees are related to the time of sap collection and result in variation of the same components in pure maple syrup. Thirty milliliters (one fluid ounce) of pure maple syrup may contain 3 to 6 mg of phosphorus, 10 to 30 mg of potassium, 40 to 80 mg of calcium, and 4 to 25 mg of magnesium.

  15. Beneficial impacts of regular exercise on platelet function in sedentary older adults: Evidence from a randomized 6-month walking trial.

    PubMed

    Haynes, Andrew; Linden, Matthew D; Robey, Elisa; Naylor, Louise H; Ainslie, Philip N; Cox, Kay L; Lautenschlager, Nicola T; Green, Daniel J

    2018-04-12

    Platelet activation, including the formation of monocyte platelet aggregates (MPAs), contributes to atherosclerosis, thrombus formation and acute coronary syndromes. Regular participation in exercise can lower cardiovascular risk, but little is known regarding the impact of exercise training on platelet function. We investigated the effect of 6 months of walking exercise on platelet function in sedentary older adults without significant cardiovascular disease. Twenty-seven participants were randomly allocated to 6 months of either: no-exercise (n=13) or 3 x 50 mins/wk of supervised centre-based walking (n=14). Circulating and agonist induced MPAs were assessed using flow cytometry before (month 0 0M) and after (month 6 6M) the intervention. Circulating MPAs increased from 0M (3.7 {plus minus} 1.0%) to 6M (4.7 {plus minus} 1.6%) in the no-exercise group (P = 0.009), whereas a non-significant decrease was observed in the walking group (0M 4.3 {plus minus} 1.7% vs 6M 3.7 {plus minus} 1.2, P = 0.052). The change in MPAs between groups was significant (P = 0.001). There were no differences between groups in platelet responses to agonists across the interventions (all P > 0.05). Collectively, these data suggest that the absence of regular exercise may increase MPAs, which are cellular mediators involved in atherosclerosis, whilst regular walking inhibits such increases. The thrombotic function of platelets appear to be relatively unaltered by exercise training. This study provides novel data related to the cardio-protective effects associated with participation in exercise.

  16. Association of Hearing Impairment With Incident Frailty and Falls in Older Adults

    PubMed Central

    Kamil, Rebecca J.; Betz, Joshua; Powers, Becky Brott; Pratt, Sheila; Kritchevsky, Stephen; Ayonayon, Hilsa N.; Harris, Tammy B.; Helzner, Elizabeth; Deal, Jennifer A.; Martin, Kathryn; Peterson, Matthew; Satterfield, Suzanne; Simonsick, Eleanor M.; Lin, Frank R.

    2017-01-01

    Objective We aimed to determine whether hearing impairment (HI) in older adults is associated with the development of frailty and falls. Method Longitudinal analysis of observational data from the Health, Aging and Body Composition study of 2,000 participants aged 70 to 79 was conducted. Hearing was defined by the pure-tone-average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better hearing ear. Frailty was defined as a gait speed of <0.60 m/s and/or inability to rise from a chair without using arms. Falls were assessed annually by self-report. Results Older adults with moderate-or-greater HI had a 63% increased risk of developing frailty (adjusted hazard ratio [HR] = 1.63, 95% confidence interval [CI] = [1.26, 2.12]) compared with normal-hearing individuals. Moderate-or-greater HI was significantly associated with a greater annual percent increase in odds of falling over time (9.7%, 95% CI = [7.0, 12.4] compared with normal hearing, 4.4%, 95% CI = [2.6, 6.2]). Discussion HI is independently associated with the risk of frailty in older adults and with greater odds of falling over time. PMID:26438083

  17. Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

  18. Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-01

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-04

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  20. Differential sensitivity of aerobic gram-positive and gram-negative microorganisms to 2,4,6-trinitrotoluene (TNT) leads to dissimilar growth and TNT transformation: Results of soil and pure culture studies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fuller, M.E.; Manning, J.F. Jr.

    1996-07-30

    The effects of 2,4,6-trinitrotoluene (TNT) on indigenous soil populations and pure bacterial cultures were examined. The number of colony-forming units (CFU) appearing when TNT-contaminated soil was spread on 0.3% molasses plates decreased by 50% when the agar was amended with 67 {mu}g TNT mL{sup -1}, whereas a 99% reduction was observed when uncontaminated soil was plated. Furthermore, TNT-contaminated soil harbored a greater number of organisms able to grow on plates amended with greater than 10 {mu}g TNT mL{sup -1}. The percentage of gram-positive isolates was markedly less in TNT-contaminated soil (7%; 2 of 30) than in uncontaminated soil (61%; 20more » of 33). Pseudomonas aeruginosa, Pseudomonas corrugate, Pseudomonasfluorescens and Alcaligenes xylosoxidans made up the majority of the gram-negative isolates from TNT-contaminated soil. Gram-positive isolates from both soils demonstrated marked growth inhibition when greater than 8-16 {mu}g TNT mL{sup -1} was present in the culture media. Most pure cultures of known aerobic gram-negative organisms readily degraded TNT and evidenced net consumption of reduced metabolites. However, pure cultures of aerobic gram-positive bacteria were sensitive to relatively low concentrations of TNT as indicated by the 50% reduction in growth and TNT transformation which was observed at approximately 10 {mu}g TNT mL{sup -1}. Most non-sporeforming gram-positive organisms incubated in molasses media amended with 80 {mu}g TNT mL{sup -1} or greater became unculturable, whereas all strains tested remained culturable when incubated in mineral media amended with 98 {mu}g TNT mL{sup -1}, indicating that TNT sensitivity is likely linked to cell growth. These results indicate that gram-negative organisms are most likely responsible for any TNT transformation in contaminated soil, due to their relative insensitivity to high TNT concentrations and their ability to transform TNT.« less

  1. Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML

    ClinicalTrials.gov

    2017-09-12

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

    ClinicalTrials.gov

    2015-02-05

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  3. Steam tables for pure water as an ActiveX component in Visual Basic 6.0

    NASA Astrophysics Data System (ADS)

    Verma, Mahendra P.

    2003-11-01

    The IAPWS-95 formulation for the thermodynamic properties of pure water was implemented as an ActiveX component ( SteamTables) in Visual Basic 6.0. For input parameters as temperature ( T=190-2000 K) and pressure ( P=3.23×10 -8-10,000 MPa) the program SteamTables calculates the following properties: volume ( V), density ( D), compressibility factor ( Z0), internal energy ( U), enthalpy ( H), Gibbs free energy ( G), Helmholtz free energy ( A), entropy ( S), heat capacity at constant pressure ( Cp), heat capacity at constant volume ( Cv), coefficient of thermal expansion ( CTE), isothermal compressibility ( Ziso), velocity of sound ( VelS), partial derivative of P with T at constant V (d Pd T), partial derivative of T with V at constant P (d Td V), partial derivative of V with P at constant T (d Vd P), Joule-Thomson coefficient ( JTC), isothermal throttling coefficient ( IJTC), viscosity ( Vis), thermal conductivity ( ThrmCond), surface tension ( SurfTen), Prandtl number ( PrdNum) and dielectric constant ( DielCons) for the liquid and vapor phases of pure water. It also calculates T as a function of P (or P as a function of T) along the sublimation, saturation and critical isochor curves, depending on the values of P (or T). The SteamTables can be incorporated in a program in any computer language, which supports object link embedding (OLE) in the Windows environment. An application of SteamTables is illustrated in a program in Visual Basic 6.0 to tabulate the values of the thermodynamic properties of water and vapor. Similarly, four functions, Temperature(Press), Pressure(Temp), State(Temp, Press) and WtrStmTbls(Temp, Press, Nphs, Nprop), where Temp, Press, Nphs and Nprop are temperature, pressure, phase number and property number, respectively, are written in Visual Basic for Applications (VBA) to use the SteamTables in a workbook in MS-Excel.

  4. RNA N6-adenosine methylation (m6A) steers epitranscriptomic control of herpesvirus replication

    PubMed Central

    Ye, Fengchun

    2017-01-01

    Latency is a hallmark of all herpesviruses, during which the viral genomes are silenced through DNA methylation and suppressive histone modifications. When latent herpesviruses reactivate to undergo productive lytic replication, the suppressive epigenetic marks are replaced with active ones to allow for transcription of viral genes. Interestingly, by using Kaposi’s sarcoma-associated herpesvirus (KSHV) as a model, we recently demonstrated that the newly transcribed viral RNAs are also subjected to post-transcriptional N6-adenosine methylation (m6A). Blockade of this post-transcriptional event abolishes viral protein expression and halts virion production. We found that m6A modification controls RNA splicing, stability, and protein translation to regulate viral lytic gene expression and replication. Thus, our finding for the first time reveals a critical role of this epitranscriptomic mechanism in the control of herpesviral replication, which shall shed lights on development of novel strategies for the control of herpesviral infection. PMID:29082271

  5. Rehabilitation of pure alexia: A review

    PubMed Central

    Starrfelt, Randi; Ólafsdóttir, Rannveig Rós; Arendt, Ida-Marie

    2013-01-01

    Acquired reading problems caused by brain injury (alexia) are common, either as a part of an aphasic syndrome, or as an isolated symptom. In pure alexia, reading is impaired while other language functions, including writing, are spared. Being in many ways a simple syndrome, one would think that pure alexia was an easy target for rehabilitation efforts. We review the literature on rehabilitation of pure alexia from 1990 to the present, and find that patients differ widely on several dimensions, such as alexia severity and associated deficits. Many patients reported to have pure alexia in the reviewed studies, have associated deficits such as agraphia or aphasia and thus do not strictly conform to the diagnosis. Few studies report clear and generalisable effects of training, none report control data, and in many cases the reported findings are not supported by statistics. We can, however, tentatively conclude that Multiple Oral Re-reading techniques may have some effect in mild pure alexia where diminished reading speed is the main problem, while Tacile-Kinesthetic training may improve letter identification in more severe cases of alexia. There is, however, still a great need for well-designed and controlled studies of rehabilitation of pure alexia. PMID:23808895

  6. A DFT study of pure and lithium doped gold clusters

    NASA Astrophysics Data System (ADS)

    Rani, Babita

    2018-05-01

    First principles calculations on Aun and Aun-1Li (n=1-6) clusters are performed to understand the effect of size and composition on their structural and energy parameters. It has been found that binding energy increases continuously with increase in the size of pure Aun and doped Aun-1Li clusters and attains its maximum at n=6. Also, Li doping results in the improvement of relative stabilities of pure gold clusters, owing to higher bond strength (i.e. shorter bond length) of Au- Li bond as compared to Au-Au bonds. Moreover, Aun-1Li clusters are found to be more compact. Structural transformations are observed in case of gold clusters doped with Li atom which may affect their application in the field of catalysis.

  7. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2018-05-24

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  8. Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-05

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-12-07

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Reliability and validity of the 6-min walk test in adults and seniors with intellectual disabilities.

    PubMed

    Guerra-Balic, Myriam; Oviedo, Guillermo R; Javierre, Casimiro; Fortuño, Jesús; Barnet-López, Silvia; Niño, Oscar; Alamo, Juan; Fernhall, Bo

    2015-12-01

    Adults with intellectual disabilities (ID) have significantly lower rates of physical activity and fitness than adults without ID. The 6-min walk test (6 MWT) is an inexpensive and simple way to test mobility and submaximal work capacity. To evaluate the test-retest reliability and validity of the 6 MWT in adults and seniors with ID and explore factors contributing to the 6 MWT distance (6 MWD). 46 participants with mild, moderate and severe ID levels (age=41 ± 11 years) performed the 6 MWT three times (T1; T2; T3) to determine test-retest reliability. To test validity, peak oxygen uptake (VO2 peak) was measured using a treadmill protocol. To analyze factors contributing to the 6 MWD, sex, height, fat mass % and fat free mass %, ID level, isometric leg strength and relative VO2 peak were also measured. The walking distances for T1, T2 and T3 were 460.3 ± 76.9; 489.4 ± 81.2 and 491.4 ± 77.9 m, respectively. The 6 MWDs between T1-T2 and T1-T3 were significantly different (p<0.001), but T2 and T3 were not different. The intraclass correlation coefficient between T2 and T3 was 0.96 indicating high reliability. Relative VO2 peak and isometric leg strength significantly contributed to the 6 MWD (R(2)=0.55). The 6 MWT is an easy, inexpensive, reliable and valid test in adults and seniors with ID. Familiarization is necessary to obtain reliable values. Relative VO2 peak and leg strength have significant impact on the distance walked. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Correlation between ZBED6 Gene Upstream CpG Island methylation and mRNA expression in cattle.

    PubMed

    Huang, Yong-Zhen; Zhang, Zi-Jing; He, Hua; Cao, Xiu-Kai; Song, Cheng-Chuang; Liu, Kun-Peng; Lan, Xian-Yong; Lei, Chu-Zhao; Qi, Xing-Lei; Bai, Yue-Yu; Chen, Hong

    2017-04-03

    DNA methylation is essential for the regulation of gene expression and important roles in muscle development. To assess the extent of epigenetic modifications and gene expression on the differentially methylated region (DMR) in ZBED6, we simultaneously examined DNA methylation and expression in six tissues from two different developmental stages (fetal bovine and adult bovine). The DNA methylation pattern was compared using bisulfite sequencing polymerase chain reaction (BSP) and combined bisulfite restriction analysis (COBRA). The result of quantitative real-time PCR (qPCR) analysis showed that ZBED6 has a broad tissue distribution and is highly expressed in adult bovine (P < 0.05 or P < 0.01). The DNA methylation level was significantly different in liver, lung and spleen between the two cattle groups (P < 0.05 or P < 0.01). The adult bovine group exhibited a significantly higher mRNA level and lower DNA methylation level than the fetal bovine group in liver, lung, and spleen. No significant association was detected between DNA methylation level and muscle, heart, and kidney at two different stages. In this study, the statistical analyses indicated that DNA methylation patterns are associated with mRNA level in some tissues, these results may be a useful parameter to investigate muscle developmental in cattle and as a model for studies in other species, potentially contributing to an improvement of growth performance selection in beef cattle breeding program.

  12. Genome-wide maps of m6A circRNAs identify widespread and cell-type-specific methylation patterns that are distinct from mRNAs

    PubMed Central

    Zhou, Chan; Molinie, Benoit; Daneshvar, Kaveh; Pondick, Joshua V.; Wang, Jinkai; Van Wittenberghe, Nicholas O.; Xing, Yi; Giallourakis, Cosmas C.; Mullen, Alan C.

    2017-01-01

    Summary N6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that together with depletion of ribosomal RNA and m6A immunoprecipitation defined thousands of m6A-circRNAs, with cell-type-specific expression. The presence of m6A-circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A-circRNAs are frequently derived from exons that are not methylated in mRNAs, while mRNAs that are methylated on the same exons that compose m6A-circRNAs exhibit less stability, in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification. PMID:28854373

  13. Transient thermal analysis during friction stir welding between AA2014-T6 and pure copper

    NASA Astrophysics Data System (ADS)

    Gadhavi, A. R.; Ghetiya, N. D.; Patel, K. M.

    2018-04-01

    AA2xxx-Cu alloys showed larger applications in the defence sectors and in aerospace industries due to high strength to weight ratio and toughness. FSW in a butt joint configuration was carried out between AA2014-T6 and pure Copper placing AA2014 on AS and Cu on RS. Temperature profiles were observed by inserting K-type thermocouples in the mid-thickness at various locations of the plate. A sharp decrease in temperature profiles was observed on Copper side due to its higher thermal conductivity. A thermal numerical model was prepared in ANSYS to compare the simulated temperature profiles with the experimental temperature profiles and both the temperature profiles were found to be in good agreement.

  14. Maintaining a Class M 5.5 environment in a Class M 6.5 cleanroom

    NASA Astrophysics Data System (ADS)

    Hughes, David W.; Hedgeland, Randy J.; Geer, Wayne C.; Greenberg, Barry N.

    1994-10-01

    During Kennedy Space Center processing of the Hubble Space Telescope First Servicing Mission, critical optical components were integrated in a Class 100,000 (M 6.5 at 0.5 micrometers and 5.0 micrometers , per Fed-Std 209E) cleanroom. A Class 10,000 (M 5.5) environment was mandated by the 400B (per Mil-Std 1246B) surface cleanliness requirement of the Scientific Instruments. To maintain a Class M 5.5 environment, a contamination control plan was implemented which addressed personnel constraints, operations, and site management. This plan limited personnel access, imposed strict gowning requirements, and increased cleanroom janitorial operations, prohibited operations known to generate contamination while sensitive hardware was exposed to the environment, and controlled roadwork, insecticide spraying, and similar activities. Facility preparations included a ceiling to floor cleaning, sealing of vents and doors, and revising the garment change room entry patterns. The cleanroom was successfully run below Class 5000 while the instruments were present; certain operations, however, were observed to cause local contamination levels to increase above Class M 5.5.

  15. m6A RNA Degradation Products are Catabolized by an Evolutionarily Conserved N6-methyl-AMP Deaminase in Plant and Mammalian Cells.

    PubMed

    Chen, Mingjia; Urs, Mounashree J; Sánchez-González, Ismael; Olayioye, Monilola A; Herde, Marco; Witte, Claus-Peter

    2018-06-08

    N6-methylated adenine (m6A) is the most frequent posttranscriptional modification in eukaryotic mRNA. Turnover of RNA generates N6-methylated AMP (N6-mAMP), which has an unclear metabolic fate. We show that Arabidopsis thaliana and human cells require an N6-mAMP deaminase (ADAL, renamed MAPDA) to catabolize N6-mAMP to inosine monophosphate (IMP) in vivo by hydrolytically removing the aminomethyl group. A phylogenetic, structural, and biochemical analysis revealed that many fungi partially or fully lack MAPDA, which coincides with a minor role of N6A-RNA methylation in these organisms. MAPDA likely protects RNA from m6A mis-incorporation. This is required because eukaryotic RNA polymerase can use N6-mATP as a substrate. Upon abrogation of MAPDA, root growth is slightly reduced, and the N6-methyladenosine, N6-mAMP, and N6-mATP concentrations are increased in Arabidopsis. Although this will potentially lead to m6A mis-incorporation into RNA, we show that the frequency is too low to be reliably detected in vivo. Since N6-mAMP was several fold more abundant than N6-mATP in MAPDA mutants, we speculate that additional molecular filters suppress the generation of N6-mATP. Enzyme kinetic data indicate that adenylate kinases represent such filters being highly selective for AMP versus N6-mAMP phosphorylation. We conclude that a multilayer molecular protection system is in place preventing N6-mAMP accumulation and salvage. © 2018 American Society of Plant Biologists. All rights reserved.

  16. Expression of fructose-1,6-bisphosphatase mRNA isoforms in normal and basal forebrain cholinergic lesioned rat brain.

    PubMed

    Löffler, T; Al-Robaiy, S; Bigl, M; Eschrich, K; Schliebs, R

    2001-06-01

    Fructose-1,6-bisphosphatase is one of the key enzymes in the gluconeogenic pathway predominantly occurring in liver, kidney and muscle. In the brain, fructose-1,6-bisphosphatase has been suggested to be an astrocyte-specific enzyme but the functional importance of glyconeogenesis in the brain is still unclear. To further elucidate the cellular source of fructose-1,6-bisphosphatase in the brain, non-radioactive in situ hybridizations were performed using digoxigenin-labeled RNA probes based on the sequence of recently cloned rat liver and muscle fructose-1,6-bisphosphatase cDNAs. In situ hybridization using a riboprobe for the liver isoform revealed a location of the hybridization signal mainly in neurons, while rat muscle fructose-1,6-bisphosphatase mRNA was detected in both neurons and astrocytes in the hippocampal formation and in layer I of the cerebral cortex.RT-PCR using RNA preparations of rat astrocytes, neurons, and adult whole brain demonstrated a localization of liver fructose-1,6-bisphosphatase mRNA isoform in neurons but not in astrocytes. The muscle fructose-1,6-bisphosphatase mRNA isoform could be detected by RT-PCR in total rat brain, astrocytic, and neuronal mRNA preparations. The isoforms of fructose-1,6-bisphosphatase mRNA seemingly demonstrate a distinct cellular expression pattern in rat brain suggesting a role of glyconeogenesis in both neurons and glial cells.

  17. Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-08-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Enzymatic preparation of optically pure (+)-2-azabicyclo[2.2.1]hept-5-en-3-one by (-)-γ-lactamase from Bradyrhizobium japonicum USDA 6.

    PubMed

    Zhu, Shaozhou; Ren, Lu; Yu, Songzhu; Gong, Cuiyu; Song, Dawei; Zheng, Guojun

    2014-10-15

    Whole cells of Bradyrhizobium japonicum USDA 6 showed both (+)-γ-lactamase activity and (-)-γ-lactamase activity. Insight into the genome of B. japonicum USDA 6 revealed two potential γ-lactamases: a type I (+)-γ-lactamase and a (-)-γ-lactamase, making it the first strain to contain two totally different enantioselective lactamases. Both recombinant enzymes could easily be used to prepare either optically pure (+)-γ-lactam ((+)-2-azabicyclo[2.2.1]hept-5-en-3-one) or optically pure (-)-γ-lactam ((-)-2-azabicyclo[2.2.1]hept-5-en-3-one), which are versatile synthetic building blocks for the synthesis of various carbocyclic nucleosides and carbocyclic sugar analogues. Bioinformatic analysis showed that the type I (+)-γ-lactamase belongs to the amidase signature family, with 504 amino acids; the (-)-γ-lactamase, which consists of 274 amino acids, belongs to the hydrolase family. Here, we report that B. japonicum USDA contains a (-)-γ-lactamase in addition to a (+)-γ-lactamase, and it is the (-)-γ-lactamase from this strain that is examined in detail in this Letter. Enzymatic synthesis of optically pure (+)-γ-lactam with nearly 50% isolated yield and >99% ee was achieved. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Pure white OLED based on an organic small molecule: 2,6-Di(1H-benzo[d]imidazol-2-yl)pyridine

    NASA Astrophysics Data System (ADS)

    Liu, Jian

    2015-10-01

    2,6-Di(1H-benzo[d]imidazol-2-yl)pyridine (DBIP) was synthesized. The single-crystal structure of DBIP was resolved. DBIP-based OLED was fabricated. The electroluminescence for the device corresponds to a pure white emission. In addition, thermal stability, UV-vis, photoluminescence and electrochemical behaviors of DBIP were investigated as well.

  20. Underwater localization of pure tones by harbor seals (Phoca vitulina).

    PubMed

    Bodson, Anaïs; Miersch, Lars; Dehnhardt, Guido

    2007-10-01

    The underwater sound localization acuity of harbor seals (Phoca vitulina) was measured in the horizontal plane. Minimum audible angles (MAAs) of pure tones were determined as a function of frequency from 0.2 to 16 kHz for two seals. Testing was conducted in a 10-m-diam underwater half circle using a right/left psychophysical procedure. The results indicate that for both harbor seals, MAAs were large at high frequencies (13.5 degrees and 17.4 degrees at 16 kHz), transitional at intermediate frequencies (9.6 degrees and 10.1 degrees at 4 kHz), and particularly small at low frequencies (3.2 degrees and 3.1 degrees at 0.2 kHz). Harbor seals seem to be able to utilize both binaural cues, interaural time differences (ITDs) and interaural intensity differences (IIDs), but a significant decrease in the sound localization acuity with increasing frequency suggests that IID cues may not be as robust as ITD cues under water. These results suggest that the harbor seal can be regarded as a low-frequency specialist. Additionally, to obtain a MAA more representative of the species, the horizontal underwater MAA of six adult harbor seals was measured at 2 kHz under identical conditions. The MAAs of the six animals ranged from 8.8 degrees to 11.7 degrees , resulting in a mean MAA of 10.3 degrees .

  1. A Randomized, Controlled Safety, and Immunogenicity Trial of the M72/AS01 Candidate Tuberculosis Vaccine in HIV-Positive Indian Adults.

    PubMed

    Kumarasamy, Nagalingeswaran; Poongulali, Selvamuthu; Bollaerts, Anne; Moris, Philippe; Beulah, Faith Esther; Ayuk, Leo Njock; Demoitié, Marie-Ange; Jongert, Erik; Ofori-Anyinam, Opokua

    2016-01-01

    Human immunodeficiency virus (HIV)-associated tuberculosis is a major public health threat. We evaluated the safety and immunogenicity of the candidate tuberculosis vaccine M72/AS01 in HIV-positive and HIV-negative Indian adults.Randomized, controlled observer-blind trial (NCT01262976).We assigned 240 adults (1:1:1) to antiretroviral therapy (ART)-stable, ART-naive, or HIV-negative cohorts. Cohorts were randomized 1:1 to receive M72/AS01 or placebo following a 0, 1-month schedule and followed for 12 months (time-point M13). HIV-specific and laboratory safety parameters, adverse events (AEs), and M72-specific T-cell-mediated and humoral responses were evaluated.Subjects were predominantly QuantiFERON-negative (60%) and Bacille Calmette-Guérin-vaccinated (73%). Seventy ART-stable, 73 ART-naive, and 60 HIV-negative subjects completed year 1. No vaccine-related serious AEs or ART-regimen adjustments, or clinically relevant effects on laboratory parameters, HIV-1 viral loads or CD4 counts were recorded. Two ART-naive vaccinees died of vaccine-unrelated diseases. M72/AS01 induced polyfunctional M72-specific CD4 T-cell responses (median [interquartile range] at 7 days postdose 2: ART-stable, 0.9% [0.7-1.5]; ART-naive, 0.5% [0.2-1.0]; and HIV-negative, 0.6% [0.4-1.1]), persisting at M13 (0.4% [0.2-0.5], 0.09% [0.04-0.2], and 0.1% [0.09-0.2], respectively). Median responses were higher in the ART-stable cohort versus ART-naive cohort from day 30 onwards (P ≤ 0.015). Among HIV-positive subjects (irrespective of ART-status), median responses were higher in QuantiFERON-positive versus QuantiFERON-negative subjects up to day 30 (P ≤ 0.040), but comparable thereafter. Cytokine-expression profiles were comparable between cohorts after dose 2. At M13, M72-specific IgG responses were higher in ART-stable and HIV-negative vaccinees versus ART-naive vaccinees (P ≤ 0.001).M72/AS01 was well-tolerated and immunogenic in this population of ART-stable and ART-naive HIV

  2. A Randomized, Controlled Safety, and Immunogenicity Trial of the M72/AS01 Candidate Tuberculosis Vaccine in HIV-Positive Indian Adults

    PubMed Central

    Kumarasamy, Nagalingeswaran; Poongulali, Selvamuthu; Bollaerts, Anne; Moris, Philippe; Beulah, Faith Esther; Ayuk, Leo Njock; Demoitié, Marie-Ange; Jongert, Erik; Ofori-Anyinam, Opokua

    2016-01-01

    Abstract Human immunodeficiency virus (HIV)-associated tuberculosis is a major public health threat. We evaluated the safety and immunogenicity of the candidate tuberculosis vaccine M72/AS01 in HIV-positive and HIV-negative Indian adults. Randomized, controlled observer-blind trial (NCT01262976). We assigned 240 adults (1:1:1) to antiretroviral therapy (ART)-stable, ART-naive, or HIV-negative cohorts. Cohorts were randomized 1:1 to receive M72/AS01 or placebo following a 0, 1-month schedule and followed for 12 months (time-point M13). HIV-specific and laboratory safety parameters, adverse events (AEs), and M72-specific T-cell-mediated and humoral responses were evaluated. Subjects were predominantly QuantiFERON-negative (60%) and Bacille Calmette–Guérin-vaccinated (73%). Seventy ART-stable, 73 ART-naive, and 60 HIV-negative subjects completed year 1. No vaccine-related serious AEs or ART-regimen adjustments, or clinically relevant effects on laboratory parameters, HIV-1 viral loads or CD4 counts were recorded. Two ART-naive vaccinees died of vaccine-unrelated diseases. M72/AS01 induced polyfunctional M72-specific CD4+ T-cell responses (median [interquartile range] at 7 days postdose 2: ART-stable, 0.9% [0.7–1.5]; ART-naive, 0.5% [0.2–1.0]; and HIV-negative, 0.6% [0.4–1.1]), persisting at M13 (0.4% [0.2–0.5], 0.09% [0.04–0.2], and 0.1% [0.09–0.2], respectively). Median responses were higher in the ART-stable cohort versus ART-naive cohort from day 30 onwards (P ≤ 0.015). Among HIV-positive subjects (irrespective of ART-status), median responses were higher in QuantiFERON-positive versus QuantiFERON-negative subjects up to day 30 (P ≤ 0.040), but comparable thereafter. Cytokine-expression profiles were comparable between cohorts after dose 2. At M13, M72-specific IgG responses were higher in ART-stable and HIV-negative vaccinees versus ART-naive vaccinees (P ≤ 0.001). M72/AS01 was well-tolerated and immunogenic in this population of

  3. m6A RNA Methylation Controls Neural Development and Is Involved in Human Diseases.

    PubMed

    Du, Kunzhao; Zhang, Longbin; Lee, Trevor; Sun, Tao

    2018-06-16

    RNA modifications are involved in many aspects of biological functions. N6-methyladenosine (m 6 A) is one of the most important forms of RNA methylation and plays a vital role in regulating gene expression, protein translation, cell behaviors, and physiological conditions in many species, including humans. The dynamic and reversible modification of m 6 A is conducted by three elements: methyltransferases ("writers"), such as methyltransferase-like protein 3 (METTL3) and METTL14; m 6 A-binding proteins ("readers"), such as the YTH domain family proteins (YTHDFs) and YTH domain-containing protein 1 (YTHDC1); and demethylases ("erasers"), such as fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5). In this review, we summarize the current knowledge on mapping mRNA positions of m 6 A modification and revealing molecular processes of m 6 A. We further highlight the biological significance of m 6 A modification in neural cells during development of the nervous system and its association with human diseases. m 6 A RNA methylation is becoming a new frontier in neuroscience and should help us better understand neural development and neurological diseases from a novel point of view.

  4. Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism.

    PubMed

    Yang, Ying; Hsu, Phillip J; Chen, Yu-Sheng; Yang, Yun-Gui

    2018-05-22

    N 6 -methyladenosine (m 6 A) is a chemical modification present in multiple RNA species, being most abundant in mRNAs. Studies on enzymes or factors that catalyze, recognize, and remove m 6 A have revealed its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. This review describes the current understanding of the m 6 A modification, particularly the functions of its writers, erasers, readers in RNA metabolism, with an emphasis on its role in regulating the isoform dosage of mRNAs.

  5. A new perylenequinone from a halotolerant fungus, Alternaria sp. M6.

    PubMed

    Zhang, Song-Ya; Li, Zhan-Lin; Bai, Jiao; Wang, Yu; Zhang, Li-Min; Wu, Xin; Hua, Hui-Ming

    2012-01-01

    To study the metabolites of a halotolerant fungus Alternaria sp. M6. The metabolites were isolated and purified by various chromatographic techniques. Their structures were determined on the basis of physical properties and spectroscopic data. Nine compounds were isolated and identified as 8β-chloro-3, 6aα, 7β, 9β, 10-pentahydroxy-9, 8, 7, 6a-tetrahydroperylen-4(6aH)-one (1), alterperylenol (2), dihydroalterperylenol (3), adenine (4), adenosine (5), deoxyadenosine (6), guanosine (7), tryptophan (8), and hexadecanoic acid (9). Compound 1 is a new perylenequinone. Copyright © 2012 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  6. Structure and stability of M6N8 clusters (M = Si, Ge, Sn, Ti).

    PubMed

    Davydova, Elena I; Timoshkin, Alexey Y; Frenking, Gernot

    2010-06-10

    The structures and stabilities of the M(6)N(8) clusters (M = Si, Ge, Sn, Ti) have been theoretically studied at DFT and ab initio levels of theory. Two new isomers have been considered: cage-like molecules and propeller-like molecules. It is shown that only for M = Si are both isomers true minima on the potential energy surface. The thermodynamics of the dissociation process (1/6)M(6)N(8) --> (1/3)M(3)N(4) is discussed. For each M(3)N(4) molecule, four structures with different multiplicity are considered. The thermodynamic analysis shows that independently of the multiplicity of M(3)N(4) nitrides all M(6)N(8) clusters are stable in the gas phase in a wide temperature range and could be potential intermediates in chemical vapor deposition of the nitride materials.

  7. Influencing factors of the 6-min walk distance in adult Arab populations: a literature review.

    PubMed

    Joobeur, Samah; Rouatbi, Sonia; Latiri, Imed; Sfaxi, Raoudha; Ben Saad, Helmi

    2016-05-01

    Background Walk tests, especially the 6-min walk-test (6MWT), are commonly used in order to evaluate submaximal exercise capacity. The primary outcome of the 6MWT is the 6-min walk-distance (6MWD). Numerous demographic, physiological and anthropometric factors can influence the 6MWD in healthy adults. Objective The purpose of the present review is to highlight and discuss the 6MWD influencing factors in healthy of the healthy adult Arab populations. Methods It is a review including a literature search, from 1970 to September 31th 2015 using the PubMed, the Science Direct databases and the World Wide Web on Google search engine. Reference lists of retrieved English/French articles were searched for any additional references. Results Six studies, conducted in Tunisia (n=2), Saudi Arabia (n=3) and Algeria (n=1) were included. All studies were conducted according to the 2002-American-thoracic-society guidelines for the 6MWT. In addition to anthropometric data (sex, age, height, weight, body mass index, lean mass), the following data were recognized as 6MWD influencing factors: schooling and socioeconomic levels, urban origin, parity, physical activity score or status, metabolic equivalent task for moderate activity, spirometric data, end-walk heart-rate, resting diastolic blood pressure, dyspnoea Borg value and niqab-wearing. Conclusion The 6MWD influencing factors in adult Arab populations are numerous and include some specific predictors such as parity, physical activity level and niqab-wearing.

  8. A new corrective technique for adolescent idiopathic scoliosis: convex manipulation using 6.35 mm diameter pure titanium rod followed by concave fixation using 6.35 mm diameter titanium alloy

    PubMed Central

    2015-01-01

    Background It has been thought that corrective posterior surgery for adolescent idiopathic scoliosis (AIS) should be started on the concave side because initial convex manipulation would increase the risk of vertebral malrotation, worsening the rib hump. With the many new materials, implants, and manipulation techniques (e.g., direct vertebral rotation) now available, we hypothesized that manipulating the convex side first is no longer taboo. Methods Our technique has two major facets. (1) Curve correction is started from the convex side with a derotation maneuver and in situ bending followed by concave rod application. (2) A 6.35 mm diameter pure titanium rod is used on the convex side and a 6.35 mm diameter titanium alloy rod on the concave side. Altogether, 52 patients were divided into two groups. Group N included 40 patients (3 male, 37 female; average age 15.9 years) of Lenke type 1 (23 patients), type 2 (2), type 3 (3), type 5 (10), type 6 (2). They were treated with a new technique using 6.35 mm diameter different-stiffness titanium rods. Group C included 12 patients (all female, average age 18.8 years) of Lenke type 1 (6 patients), type 2 (3), type 3 (1), type 5 (1), type 6 (1). They were treated with conventional methods using 5.5 mm diameter titanium alloy rods. Radiographic parameters (Cobb angle/thoracic kyphosis/correction rates) and perioperative data were retrospectively collected and analyzed. Results Preoperative main Cobb angles (groups N/C) were 56.8°/60.0°, which had improved to 15.2°/17.1° at the latest follow-up. Thoracic kyphosis increased from 16.8° to 21.3° in group N and from 16.0° to 23.4° in group C. Correction rates were 73.2% in group N and 71.7% in group C. There were no significant differences for either parameter. Mean operating time, however, was significantly shorter in group N (364 min) than in group C (456 min). Conclusion We developed a new corrective surgical technique for AIS using a 6.35 mm diameter pure titanium

  9. Identification of factors required for m6 A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI.

    PubMed

    Růžička, Kamil; Zhang, Mi; Campilho, Ana; Bodi, Zsuzsanna; Kashif, Muhammad; Saleh, Mária; Eeckhout, Dominique; El-Showk, Sedeer; Li, Hongying; Zhong, Silin; De Jaeger, Geert; Mongan, Nigel P; Hejátko, Jan; Helariutta, Ykä; Fray, Rupert G

    2017-07-01

    N6-adenosine methylation (m 6 A) of mRNA is an essential process in most eukaryotes, but its role and the status of factors accompanying this modification are still poorly understood. Using combined methods of genetics, proteomics and RNA biochemistry, we identified a core set of mRNA m 6 A writer proteins in Arabidopsis thaliana. The components required for m 6 A in Arabidopsis included MTA, MTB, FIP37, VIRILIZER and the E3 ubiquitin ligase HAKAI. Downregulation of these proteins led to reduced relative m 6 A levels and shared pleiotropic phenotypes, which included aberrant vascular formation in the root, indicating that correct m 6 A methylation plays a role in developmental decisions during pattern formation. The conservation of these proteins amongst eukaryotes and the demonstration of a role in writing m 6 A for the E3 ubiquitin ligase HAKAI is likely to be of considerable relevance beyond the plant sciences. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  10. Redefining dermatomyositis: a description of new diagnostic criteria that differentiate pure dermatomyositis from overlap myositis with dermatomyositis features.

    PubMed

    Troyanov, Yves; Targoff, Ira N; Payette, Marie-Pier; Raynauld, Jean-Pierre; Chartier, Suzanne; Goulet, Jean-Richard; Bourré-Tessier, Josiane; Rich, Eric; Grodzicky, Tamara; Fritzler, Marvin J; Joyal, France; Koenig, Martial; Senécal, Jean-Luc

    2014-11-01

    Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM.Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival.Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high

  11. Shunting arc plasma source for pure carbon ion beam

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koguchi, H.; Sakakita, H.; Kiyama, S.

    2012-02-15

    A plasma source is developed using a coaxial shunting arc plasma gun to extract a pure carbon ion beam. The pure carbon ion beam is a new type of deposition system for diamond and other carbon materials. Our plasma device generates pure carbon plasma from solid-state carbon material without using a hydrocarbon gas such as methane gas, and the plasma does not contain any hydrogen. The ion saturation current of the discharge measured by a double probe is about 0.2 mA/mm{sup 2} at the peak of the pulse.

  12. Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2017-10-16

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia

  13. Shunting arc plasma source for pure carbon ion beam.

    PubMed

    Koguchi, H; Sakakita, H; Kiyama, S; Shimada, T; Sato, Y; Hirano, Y

    2012-02-01

    A plasma source is developed using a coaxial shunting arc plasma gun to extract a pure carbon ion beam. The pure carbon ion beam is a new type of deposition system for diamond and other carbon materials. Our plasma device generates pure carbon plasma from solid-state carbon material without using a hydrocarbon gas such as methane gas, and the plasma does not contain any hydrogen. The ion saturation current of the discharge measured by a double probe is about 0.2 mA∕mm(2) at the peak of the pulse.

  14. Older adults are mobile too!Identifying the barriers and facilitators to older adults' use of mHealth for pain management.

    PubMed

    Parker, Samantha J; Jessel, Sonal; Richardson, Joshua E; Reid, M Cary

    2013-05-06

    Mobile health (mHealth) is a rapidly emerging field with the potential to assist older adults in the management of chronic pain (CP) through enhanced communication with providers, monitoring treatment-related side effects and pain levels, and increased access to pain care resources. Little is currently known, however, about older adults' attitudes and perceptions of mHealth or perceived barriers and facilitators to using mHealth tools to improve pain management. We conducted six focus groups comprised of 41 diverse older adults (≥60 years of age) with CP. Participants were recruited from one primary care practice and two multiservice senior community day-visit centers located in New York City that serve older adults in their surrounding neighborhoods. Focus group discussions were recorded and transcribed, and transcriptions were analyzed using direct content analysis to identify and quantify themes. Focus group discussions generated 38 individual themes pertaining to the use of mHealth to help manage pain and pain medications. Participants had low prior use of mHealth (5% of participants), but the vast majority (85%) were highly willing to try the devices. Participants reported that mHealth devices might help them reach their healthcare provider more expeditiously (27%), as well as help to monitor for falls and other adverse events in the home (15%). Barriers to device use included concerns about the cost (42%) and a lack of familiarity with the technology (32%). Facilitators to device use included training prior to device use (61%) and tailoring devices to the functional needs of older adults (34%). This study suggests that older adults with CP are interested and willing to use mHealth to assist in the management of pain. Participants in our study reported important barriers that medical professionals, researchers, and mHealth developers should address to help facilitate the development and evaluation of age-appropriate, and function-appropriate, m

  15. Corrosion-fatigue life of commercially pure titanium and Ti-6Al-4V alloys in different storage environments.

    PubMed

    Zavanelli, R A; Pessanha Henriques, G E; Ferreira, I; De Almeida Rollo, J M

    2000-09-01

    Removable partial dentures are affected by fatigue because of the cyclic mechanism of the masticatory system and frequent insertion and removal. Titanium and its alloys have been used in the manufacture of denture frameworks; however, preventive agents with fluorides are thought to attack titanium alloy surfaces. This study evaluated, compared, and analyzed the corrosion-fatigue life of commercially pure titanium and Ti-6Al-4V alloy in different storage environments. For each metal, 33 dumbbell rods, 2.3 mm in diameter at the central segment, were cast in the Rematitan system. Corrosion-fatigue strength test was carried out through a universal testing machine with a load 30% lower than the 0.2% offset yield strength and a combined influence of different environments: in air at room temperature, with synthetic saliva, and with fluoride synthetic saliva. After failure, the number of cycles were recorded, and fracture surfaces were examined with an SEM. ANOVA and Tukey's multiple comparison test indicated that Ti-6Al-4V alloy achieved 21,269 cycles (SD = 8,355) against 19,157 cycles (SD = 3, 624) for the commercially pure Ti. There were no significant differences between either metal in the corrosion-fatigue life for dry specimens, but when the solutions were present, the fatigue life was significantly reduced, probably because of the production of corrosion pits caused by superficial reactions.

  16. Metabolites associated with circulating interleukin-6 in older adults

    USDA-ARS?s Scientific Manuscript database

    Background: Circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) levels are elevated in older adults, but mechanisms are unclear. In the current study, we used an untargeted metabolomic approach to develop an improved understanding about mechanisms related to circulating IL-6 in ...

  17. Altered GPM6A/M6 dosage impairs cognition and causes phenotypes responsive to cholesterol in human and Drosophila.

    PubMed

    Gregor, Anne; Kramer, Jamie M; van der Voet, Monique; Schanze, Ina; Uebe, Steffen; Donders, Rogier; Reis, André; Schenck, Annette; Zweier, Christiane

    2014-12-01

    Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient-derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient-derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long-term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes. © 2014 WILEY PERIODICALS, INC.

  18. Profiling of m6A RNA modifications identified an age-associated regulation of AGO2 mRNA stability.

    PubMed

    Min, Kyung-Won; Zealy, Richard W; Davila, Sylvia; Fomin, Mikhail; Cummings, James C; Makowsky, Daniel; Mcdowell, Catherine H; Thigpen, Haley; Hafner, Markus; Kwon, Sang-Ho; Georgescu, Constantin; Wren, Jonathan D; Yoon, Je-Hyun

    2018-06-01

    Gene expression is dynamically regulated in a variety of mammalian physiologies. During mammalian aging, there are changes that occur in protein expression that are highly controlled by the regulatory steps in transcription, post-transcription, and post-translation. Although there are global profiles of human transcripts during the aging processes available, the mechanism(s) by which transcripts are differentially expressed between young and old cohorts remains unclear. Here, we report on N6-methyladenosine (m6A) RNA modification profiles of human peripheral blood mononuclear cells (PBMCs) from young and old cohorts. An m6A RNA profile identified a decrease in overall RNA methylation during the aging process as well as the predominant modification on proteincoding mRNAs. The m6A-modified transcripts tend to be more highly expressed than nonmodified ones. Among the many methylated mRNAs, those of DROSHA and AGO2 were heavily methylated in young PBMCs which coincided with a decreased steady-state level of AGO2 mRNA in the old PBMC cohort. Similarly, downregulation of AGO2 in proliferating human diploid fibroblasts (HDFs) also correlated with a decrease in AGO2 mRNA modifications and steady-state levels. In addition, the overexpression of RNA methyltransferases stabilized AGO2 mRNA but not DROSHA and DICER1 mRNA in HDFs. Moreover, the abundance of miRNAs also changed in the young and old PBMCs which are possibly due to a correlation with AGO2 expression as observed in AGO2-depleted HDFs. Taken together, we uncovered the role of mRNA methylation on the abundance of AGO2 mRNA resulting in the repression of miRNA expression during the process of human aging. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  19. Scintillation characterization of the pure Tl2LiGdBr6 single crystal

    NASA Astrophysics Data System (ADS)

    Jang, Jonghun; Rooh, Gul; Kim, Sunghwan; Kim, HongJoo

    2018-05-01

    A pure Tl2LiGdBr6 (TLGB) single crystal was developed. This scintillator was grown by the two-zone vertical Bridgman technique. Owing to the improvement in the crystal quality of TLGB, excellent scintillation properties were observed. The characterization of this scintillation material was carried out under X- and γ-ray excitations. In the X-ray excitation emission spectrum, the Tl+ ion emission band was observed between 390 and 550 nm and peaked at 435 nm. Under 662 keV γ-ray excitation, the energy resolution and light yield of the grown sample were measured to be 7.2% (FWHM) and 27,000 ± 2,700 ph/MeV, respectively. In addition, under the same γ-ray excitation, scintillation decay time was also measured at room temperature. Three decay time components were found to be 56 ns (24%), 105 ns (53%), and 1.5 µs (23%). Further improvements in scintillation properties are expected with the good quality crystal of this compound.

  20. Effects of chronic overload on muscle hypertrophy and mTOR signaling in adult and aged rats

    USDA-ARS?s Scientific Manuscript database

    We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two-thirds of the gas...

  1. Structure and expression of MHC class Ib genes of the central M region in rat and mouse: M4, M5, and M6.

    PubMed

    Lambracht-Washington, Doris; Moore, Yuki F; Wonigeit, Kurt; Lindahl, Kirsten Fischer

    2008-04-01

    The M region at the telomeric end of the murine major histocompatibility complex (MHC) contains class I genes that are highly conserved in rat and mouse. We have sequenced a cosmid clone of the LEW rat strain (RT1 haplotype) containing three class I genes, RT1.M6-1, RT1.M4, and RT1.M5. The sequences of allelic genes of the BN strain (RT1n haplotype) were obtained either from cDNAs or genomic clones. For the coding parts of the genes few differences were found between the two RT1 haplotypes. In LEW, however, only RT1.M5 and RT1.M6 have open reading frames; whereas in BN all three genes were intact. In line with the findings in BN, transcription was found for all three rat genes in several tissues from strain Sprague Dawley. Protein expression in transfectants could be demonstrated for RT1.M6-1 using the monoclonal antibody OX18. By sequencing of transcripts obtained by RT-PCR, a second, transcribed M6 gene, RT1.M6-2, was discovered, which maps next to RT1.M6-1 outside of the region covered by the cosmid. In addition, alternatively spliced forms for RT1.M5 and RT1.M6 were detected. Of the orthologous mouse genes, H2-M4, H2-M5, and H2-M6, only H2-M5 has an open reading frame. Other important differences between the corresponding parts of the M region of the two species are insertion of long LINE repeats, duplication of RT1.M6, and the inversion of RT1.M5 in the rat. This demonstrates substantial evolutionary dynamics in this region despite conservation of the class I gene sequences themselves.

  2. Pure white OLED based on an organic small molecule: 2,6-Di(1H-benzo[d]imidazol-2-yl)pyridine.

    PubMed

    Liu, Jian

    2015-10-05

    2,6-Di(1H-benzo[d]imidazol-2-yl)pyridine (DBIP) was synthesized. The single-crystal structure of DBIP was resolved. DBIP-based OLED was fabricated. The electroluminescence for the device corresponds to a pure white emission. In addition, thermal stability, UV-vis, photoluminescence and electrochemical behaviors of DBIP were investigated as well. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. M6 membrane protein plays an essential role in Drosophila oogenesis.

    PubMed

    Zappia, María Paula; Brocco, Marcela Adriana; Billi, Silvia C; Frasch, Alberto C; Ceriani, María Fernanda

    2011-01-01

    We had previously shown that the transmembrane glycoprotein M6a, a member of the proteolipid protein (PLP) family, regulates neurite/filopodium outgrowth, hence, M6a might be involved in neuronal remodeling and differentiation. In this work we focused on M6, the only PLP family member present in Drosophila, and ortholog to M6a. Unexpectedly, we found that decreased expression of M6 leads to female sterility. M6 is expressed in the membrane of the follicular epithelium in ovarioles throughout oogenesis. Phenotypes triggered by M6 downregulation in hypomorphic mutants included egg collapse and egg permeability, thus suggesting M6 involvement in eggshell biosynthesis. In addition, RNAi-mediated M6 knockdown targeted specifically to follicle cells induced an arrest of egg chamber development, revealing that M6 is essential in oogenesis. Interestingly, M6-associated phenotypes evidenced abnormal changes of the follicle cell shape and disrupted follicular epithelium in mid- and late-stage egg chambers. Therefore, we propose that M6 plays a role in follicular epithelium maintenance involving membrane cell remodeling during oogenesis in Drosophila.

  4. M6 Membrane Protein Plays an Essential Role in Drosophila Oogenesis

    PubMed Central

    Zappia, María Paula; Brocco, Marcela Adriana; Billi, Silvia C.; Frasch, Alberto C.; Ceriani, María Fernanda

    2011-01-01

    We had previously shown that the transmembrane glycoprotein M6a, a member of the proteolipid protein (PLP) family, regulates neurite/filopodium outgrowth, hence, M6a might be involved in neuronal remodeling and differentiation. In this work we focused on M6, the only PLP family member present in Drosophila, and ortholog to M6a. Unexpectedly, we found that decreased expression of M6 leads to female sterility. M6 is expressed in the membrane of the follicular epithelium in ovarioles throughout oogenesis. Phenotypes triggered by M6 downregulation in hypomorphic mutants included egg collapse and egg permeability, thus suggesting M6 involvement in eggshell biosynthesis. In addition, RNAi-mediated M6 knockdown targeted specifically to follicle cells induced an arrest of egg chamber development, revealing that M6 is essential in oogenesis. Interestingly, M6-associated phenotypes evidenced abnormal changes of the follicle cell shape and disrupted follicular epithelium in mid- and late-stage egg chambers. Therefore, we propose that M6 plays a role in follicular epithelium maintenance involving membrane cell remodeling during oogenesis in Drosophila. PMID:21603606

  5. Undergraduate Research Possibilities with a 0.6m Telescope

    NASA Astrophysics Data System (ADS)

    Carini, M. T.; Barnaby, D.; Gelderman, R.; Marchenko, S.; McGruder, C. H., III; Strolger, L.

    2005-12-01

    We present a discussion of the research projects that are being carried out by undergraduate students with the 0.6m telescope at the Bell Observatory, operated by Western Kentucky University. As a primarily undergraduate institution, our goal is to provide a meaningful undergraduate educational experience through both quality instruction and engagement of students in mentored research activities. Such activities not only enhance the student's educational experience, but also prepare them to be competitive in graduate school and/or the workplace. Using our modernized 0.6m telescope, our students pursue research projects which investigate a variety of astrophysically interesting problems: variability of Blazars, eclipsing binary stars, Gamma-ray burst identifications and follow up, photometric searches for extra-solar planets, supernova monitoring and survey programs, the relationship between morphological disturbances and activity in Seyfert nuclei, and variability in Wolf Rayet stars. We discuss the instrumentation, projects and results obtained by our undergraduate students, and the impact this has had on their undergraduate experience.

  6. Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

    PubMed

    Dermaut, B; Seneca, S; Dom, L; Smets, K; Ceulemans, L; Smet, J; De Paepe, B; Tousseyn, S; Weckhuysen, S; Gewillig, M; Pals, P; Parizel, P; De Bleecker, J L; Boon, P; De Meirleir, L; De Jonghe, P; Van Coster, R; Van Paesschen, W; Santens, P

    2010-01-01

    m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

  7. The Cultivation of Pure Altruism via Gratitude: A Functional MRI Study of Change with Gratitude Practice

    PubMed Central

    Karns, Christina M.; Moore, William E.; Mayr, Ulrich

    2017-01-01

    Gratitude is an emotion and a trait linked to well-being and better health, and welcoming benefits to oneself is instrumentally valuable. However, theoretical and empirical work highlights that gratitude is more fully understood as an intrinsically valuable moral emotion. To understand the role of neural reward systems in the association between gratitude and altruistic motivations we tested two hypotheses: First, whether self-reported propensity toward gratitude relates to fMRI-derived indicators of “pure altruism,” operationalized as the neural valuation of passive, private transfers to a charity versus to oneself. In young adult female participants, self-reported gratitude and altruism were associated with “neural pure altruism” in ventromedial prefrontal cortex (VMPFC) and nucleus accumbens. Second, whether neural pure altruism can be increased through practicing gratitude. In a double-blind study, we randomly assigned participants to either a gratitude-journal or active-neutral control journal group for 3 weeks. Relative to pre-test levels, gratitude journaling increased the neural pure altruism response in the VMPFC. We posit that as a context-dependent value-sensitive cortical region, the VMPFC supports change with gratitude practice, a change that is larger for benefits to others versus oneself. PMID:29375336

  8. The Cultivation of Pure Altruism via Gratitude: A Functional MRI Study of Change with Gratitude Practice.

    PubMed

    Karns, Christina M; Moore, William E; Mayr, Ulrich

    2017-01-01

    Gratitude is an emotion and a trait linked to well-being and better health, and welcoming benefits to oneself is instrumentally valuable. However, theoretical and empirical work highlights that gratitude is more fully understood as an intrinsically valuable moral emotion. To understand the role of neural reward systems in the association between gratitude and altruistic motivations we tested two hypotheses: First, whether self-reported propensity toward gratitude relates to fMRI-derived indicators of "pure altruism," operationalized as the neural valuation of passive, private transfers to a charity versus to oneself. In young adult female participants, self-reported gratitude and altruism were associated with "neural pure altruism" in ventromedial prefrontal cortex (VMPFC) and nucleus accumbens. Second, whether neural pure altruism can be increased through practicing gratitude. In a double-blind study, we randomly assigned participants to either a gratitude-journal or active-neutral control journal group for 3 weeks. Relative to pre-test levels, gratitude journaling increased the neural pure altruism response in the VMPFC. We posit that as a context-dependent value-sensitive cortical region, the VMPFC supports change with gratitude practice, a change that is larger for benefits to others versus oneself.

  9. Microtubule-dependent distribution of mRNA in adult cardiocytes.

    PubMed

    Scholz, Dimitri; Baicu, Catalin F; Tuxworth, William J; Xu, Lin; Kasiganesan, Harinath; Menick, Donald R; Cooper, George

    2008-03-01

    Synthesis of myofibrillar proteins in the diffusion-restricted adult cardiocyte requires microtubule-based active transport of mRNAs as part of messenger ribonucleoprotein particles (mRNPs) to translation sites adjacent to nascent myofibrils. This is especially important for compensatory hypertrophy in response to hemodynamic overloading. The hypothesis tested here is that excessive microtubule decoration by microtubule-associated protein 4 (MAP4) after cardiac pressure overloading could disrupt mRNP transport and thus hypertrophic growth. MAP4-overexpressing and pressure-overload hypertrophied adult feline cardiocytes were infected with an adenovirus encoding zipcode-binding protein 1-enhanced yellow fluorescent protein fusion protein, which is incorporated into mRNPs, to allow imaging of these particles. Speed and distance of particle movement were measured via time-lapse microscopy. Microtubule depolymerization was used to study microtubule-based transport and distribution of mRNPs. Protein synthesis was assessed as radioautographic incorporation of [3H]phenylalanine. After microtubule depolymerization, mRNPs persist only perinuclearly and apparent mRNP production and protein synthesis decrease. Reestablishing microtubules restores mRNP production and transport as well as protein synthesis. MAP4 overdecoration of microtubules via adenovirus infection in vitro or following pressure overloading in vivo reduces the speed and average distance of mRNP movement. Thus cardiocyte microtubules are required for mRNP transport and structural protein synthesis, and MAP4 decoration of microtubules, whether directly imposed or accompanying pressure-overload hypertrophy, causes disruption of mRNP transport and protein synthesis. The dense, highly MAP4-decorated microtubule network seen in severe pressure-overload hypertrophy both may cause contractile dysfunction and, perhaps even more importantly, may prevent a fully compensatory growth response to hemodynamic overloading.

  10. NSUN2-Mediated m5C Methylation and METTL3/METTL14-Mediated m6A Methylation Cooperatively Enhance p21 Translation.

    PubMed

    Li, Qiu; Li, Xiu; Tang, Hao; Jiang, Bin; Dou, Yali; Gorospe, Myriam; Wang, Wengong

    2017-09-01

    N6-methyladenosine (m6A) and m5C methylation are two major types of RNA methylation, but the impact of joint modifications on the same mRNA is unknown. Here, we show that in p21 3'UTR, NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Interestingly, methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2-mediated m5C and METTL3/METTL14-mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress-induced cellular senescence. Our findings on p21 mRNA methylation and expression reveal that joint m6A and m5C modification of the same RNA may influence each other, coordinately affecting protein expression patterns. J. Cell. Biochem. 118: 2587-2598, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. DDAH2 mRNA expression is inversely associated with some cardiovascular risk-related features in healthy young adults.

    PubMed

    Puchau, Blanca; Hermsdorff, Helen Hermana M; Zulet, M Angeles; Martínez, J Alfredo

    2009-01-01

    The purpose of this study was to evaluate whether the mRNA expression profiles of three genes (PRMT1, DDAH2 and NOS3) are related to ADMA metabolism and signalling, and the potential relationships with anthropometrical, biochemical, lifestyle and inflammatory indicators in healthy young adults. An emphasis on the putative effect of different mRNA expression on cardiovascular risk-related features was paid. Anthropometrical measurements as well as lifestyle features were analyzed in 120 healthy young adults. Fasting blood samples were collected for the measurement of glucose and lipid profiles as well as the concentrations of selected inflammatory markers. Profiles of mRNA expression were assessed for PRMT1, DDAH2 and NOS3 genes from peripheral blood mononuclear cells. Regarding inflammatory biomarkers, DDAH2 was inversely associated with IL-6 and TNF-alpha. Moreover, subjects in the highest quintile of DDAH2 mRNA expression showed a reduced risk to have higher values of waist circumference, and to be more prone to show higher values of HDL-c. Interestingly, DDAH2 gene expression seemed to be related with some anthropometrical, biochemical, lifestyle and inflammatory indicators linked to cardiovascular risk in apparently healthy young adults, emerging as a potential disease marker.

  12. Long-term Durability of Immune Responses After Hepatitis A Vaccination Among HIV-Infected Adults

    PubMed Central

    Wilkins, Kenneth; Lee, Andrew W.; Grosso, Anthony; Landrum, Michael L.; Weintrob, Amy; Ganesan, Anuradha; Maguire, Jason; Klopfer, Stephanie; Brandt, Carolyn; Bradley, William P.; Wallace, Mark R.; Agan, Brian K.

    2011-01-01

    Background.  Vaccination provides long-term immunity to hepatitis A virus (HAV) among the general population, but there are no such data regarding vaccine durability among human immunodeficiency virus (HIV)–infected adults. Methods.  We retrospectively studied HIV-infected adults who had received 2 doses of HAV vaccine. We analyzed blood specimens taken at 1 year, 3 years, and, when available, 6–10 years postvaccination. HAV immunoglobulin G (IgG) values of ≥10 mIU/mL were considered seropositive. Results.  We evaluated specimens from 130 HIV-infected adults with a median age of 35 years and a median CD4 cell count of 461 cells/mm3 at or before time of vaccination. Of these, 49% had an HIV RNA load <1000 copies/mL. Initial vaccine responses were achieved in 89% of HIV-infected adults (95% confidence interval [CI], 83%–94%), compared with 100% (95% CI, 99%–100%) of historical HIV-uninfected adults. Among initial HIV-infected responders with available specimens, 90% (104 of 116; 95% CI, 83%–95%) remained seropositive at 3 years and 85% (63 of 74; 95% CI, 75%–92%) at 6–10 years. Geometric mean concentrations (GMCs) among HIV-infected adults were 154, 111, and 64 mIU/mL at 1, 3, and 6–10 years, respectively, compared with 1734, 687, and 684 mIU/mL among HIV-uninfected persons. Higher GMCs over time among HIV-infected adults were associated with lower log10 HIV RNA levels (β = −.12, P = .04). Conclusions.  Most adults with well-controlled HIV infections had durable seropositive responses up to 6–10 years after HAV vaccination. Suppressed HIV RNA levels are associated with durable HAV responses. PMID:21606540

  13. Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-09

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  14. Clinical features of pure obsessive-compulsive disorder.

    PubMed

    Torres, Albina R; Shavitt, Roseli G; Torresan, Ricardo C; Ferrão, Ygor A; Miguel, Euripedes C; Fontenelle, Leonardo F

    2013-10-01

    Psychiatric comorbidity is the rule in obsessive-compulsive disorder (OCD); however, very few studies have evaluated the clinical characteristics of patients with no co-occurring disorders (non-comorbid or "pure" OCD). The aim of this study was to estimate the prevalence of pure cases in a large multicenter sample of OCD patients and compare the sociodemographic and clinical characteristics of individuals with and without any lifetime axis I comorbidity. A cross-sectional study with 955 adult patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Assessment instruments included the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, The USP-Sensory Phenomena Scale and the Brown Assessment of Beliefs Scale. Comorbidities were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders. Bivariate analyses were followed by logistic regression. Only 74 patients (7.7%) presented pure OCD. Compared with those presenting at least one lifetime comorbidity (881, 92.3%), non-comorbid patients were more likely to be female and to be working, reported less traumatic experiences and presented lower scores in the Y-BOCS obsession subscale and in total DY-BOCS scores. All symptom dimensions except contamination-cleaning and hoarding were less severe in non-comorbid patients. They also presented less severe depression and anxiety, lower suicidality and less previous treatments. In the logistic regression, the following variables predicted pure OCD: sex, severity of depressive and anxious symptoms, previous suicidal thoughts and psychotherapy. Pure OCD patients were the minority in this large sample and were characterized by female sex, less severe depressive and anxious symptoms, less suicidal thoughts and less use of psychotherapy as a treatment modality. The implications of these findings for clinical practice are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Effectiveness of mobile health (mHealth) interventions for promoting healthy eating in adults: A systematic review.

    PubMed

    McCarroll, Rebecca; Eyles, Helen; Ni Mhurchu, Cliona

    2017-12-01

    Unhealthy eating is a major risk factor for chronic disease. However, many current strategies to promote healthy eating are not sustainable over the longer-term. More cost-effective wide-reaching initiatives are urgently needed. Mobile health (mHealth) interventions, delivered via mobile devices, could provide a solution. This systematic review summarized the evidence on the effect of mHealth interventions for promoting healthy eating in adults. A comprehensive systematic search of five scientific databases was conducted using methods adapted from the Cochrane Handbook. Eligible studies were randomized controlled trials (RCTs), published up to 1 July 2016, which examined healthy eating interventions delivered via mobile device. Of 879 articles identified, 84 full text articles were potentially eligible and further assessed, and 23 included. Narrative review results indicated small positive effects of mHealth interventions on healthy eating (5/8 trials) and weight loss (5/13 trials). However, the current evidence base is insufficient (studies are of poor quality) to determine conclusive positive effects. More rigorous RCTs with longer-term (>6months) follow-up are warranted to determine if effects are maintained. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia.

    PubMed

    Kwok, Chau-To; Marshall, Amy D; Rasko, John E J; Wong, Justin J L

    2017-02-02

    Methylation of N 6 adenosine (m 6 A) is known to be important for diverse biological processes including gene expression control, translation of protein, and messenger RNA (mRNA) splicing. However, its role in the development of human cancers is poorly understood. By analyzing datasets from the Cancer Genome Atlas Research Network (TCGA) acute myeloid leukemia (AML) study, we discover that mutations and/or copy number variations of m 6 A regulatory genes are strongly associated with the presence of TP53 mutations in AML patients. Further, our analyses reveal that alterations in m 6 A regulatory genes confer a worse survival in AML. Our work indicates that genetic alterations of m 6 A regulatory genes may cooperate with TP53 and/or its regulator/downstream targets in the pathogenesis and/or maintenance of AML.

  17. Physical performance in recently aged adults after 6 weeks traditional Thai dance: a randomized controlled trial.

    PubMed

    Janyacharoen, Taweesak; Laophosri, Maneepun; Kanpittaya, Jaturat; Auvichayapat, Paradee; Sawanyawisuth, Kittisak

    2013-01-01

    Exercise has been shown to be effective in cardiovascular endurance in the elderly. We studied the effect of Thai dancing on physical performance of Thai elderly. This was an open-labeled, randomized intervention study. The Thai dancing group exercised for 40 minutes three times a week for 6 weeks. Physical performance ability was the primary outcome, including a 6-minute walk test (6MWT), five-times sit-to-stand (FTSST), and a sit-and-reach test measured before and after 6 weeks of intervention. There were 42 subjects enrolled in the study, and 38 female subjects completed (20 in Thai dance group, 18 controls), with an average age of 65.8 ± 5.1 years. The Thai dance group had significantly better physical performance in all measurements at the end of the study. The 6MWT was longer (416.7 ± 58.7 versus 345.7 ± 55.1 m; P = 0.011), FTSST was quicker (10.2 ± 1.5 versus 14.4 ± 3.3 seconds; P < 0.001), and flexibility was higher (14.9 ± 3.5 versus 11.1 ± 5.7 cm; P = 0.002) in the Thai dance group than the control group. Thai dance can improve physical performance in recently aged (elderly) female adults.

  18. Uniform and accelerated degradation of pure iron patterned by Pt disc arrays

    PubMed Central

    Huang, Tao; Zheng, Yufeng

    2016-01-01

    Pure iron has been confirmed as a promising biodegradable metal. However, the degradation rate of pure iron should be accelerated to meet the clinical requirements. In this work, two different designs of platinum disc arrays, including sizes of Φ20 μm × S5 μm and Φ4 μm × S4 μm, have been coated on the surface of pure iron. Corrosion tests showed the platinum discs formed plenty of galvanic cells with the iron matrix which significantly accelerated the degradation of pure iron. Simultaneously, due to the designability of the shape, size as well as distribution of Pt discs, the degradation rate as well as degradation uniformity of pure iron can be effectively controlled by coating with platinum discs. The cytotoxicity test results unveiled that Pt discs patterned pure iron exhibited almost no toxicity to human umbilical vein endothelial cells, but a significant inhibition on proliferation of vascular smooth muscle cells. In addition, the hemolysis rate of Pt discs patterned pure iron was lower than 1%. Moreover, Pt discs also effectively reduced the number of adhered platelets. All these results indicated that Pt discs patterning is an effective way to accelerate degradation and improve biocompatibility of pure iron. PMID:27033380

  19. The burden of pure anisometropic amblyopia: a cross-sectional study on 2800 Iranians.

    PubMed

    Akbarzadeh, Siamak; Vahabi, Reihaneh; Bazzazi, Nooshin; Roshanaei, Ghodratollah; Heydarian, Samira; Fouladi, Daniel F

    2018-02-01

    To assess the proportion of pure anisometropic amblyopia in a sample Iranian (white) population. A total of 2800 consecutive individuals who presented at a referral eye clinic for any reason were examined for the presence of pure anisometropic amblyopia. Anisometropia was reported when a spherical equivalent refraction difference of at least 1.0 D with or without a cylinder refraction difference of at least 1.0 D was present between the two eyes. Amblyopia was defined as the best-corrected visual acuity of 20/30 or worse or a two-line interocular visual acuity difference between eyes that could not be attributed to any structural ocular pathology or visual pathway abnormality. Subjects were 1528 females and 1272 males with a mean age of 30.25 ± 14.93 years (range, 5-65). Amblyopia was diagnosed in 192 cases (6.9%), significantly more frequent among females (7.9 vs. 5.7%, p = 0.02). Pure anisometropic amblyopia was present in 6.1% of the study population, significantly more common in patients with spherical hyperopic anisometropia (37.7%) compared to patients with spherical myopic anisometropia (21.3%), cylindrical myopic anisometropia (4.1%), and cylindrical hyperopic anisometropia (15%) (p < 0.001). Pure anisometropic amblyopia is a common finding in Caucasians seeking eye care, particularly when anisometropia is of spherical hyperopic subtype.

  20. Efficiency in hydrocarbon degradation and biosurfactant production by Joostella sp. A8 when grown in pure culture and consortia.

    PubMed

    Rizzo, Carmen; Rappazzo, Alessandro Ciro; Michaud, Luigi; De Domenico, Emilio; Rochera, Carlos; Camacho, Antonio; Lo Giudice, Angelina

    2018-05-01

    Joostella strains are emerging candidates for biosurfactant production. Here such ability was analyzed for Joostella strain A8 in comparison with Alcanivorax strain A53 and Pseudomonas strain A6, all previously isolated from hydrocarbon enrichment cultures made of polychaete homogenates. In pure cultures Joostella sp. A8 showed the highest stable emulsion percentage (78.33%), hydrophobicity rate (62.67%), and an optimal surface tension reduction during growth in mineral medium supplemented with diesel oil (reduction of about 12mN/m), thus proving to be highly competitive with Alcanivorax and Pseudomonas strains. During growth in pure culture different level of biodegradation were detected for Alcanivorax strain A53 (52.7%), Pseudomonas strain A6 (38.2%) and Joostella strain A8 (26.8%). When growing in consortia, isolates achieved similar abundance values, with the best efficiency that was observed for the Joostella-Pseudomonas co-culture. Gas-chromatographic analysis revealed an increase in the biodegradation efficiency in co-cultures (about 90%), suggesting that the contemporary action of different bacterial species could improve the process. Results were useful to compare the efficiencies of well-known biosurfactant producers (i.e. Pseudomonas and Alcanivorax representatives) with a still unknown biosurfactant producer, i.e. Joostella, and to confirm them as optimal biosurfactant-producing candidates. Copyright © 2017. Published by Elsevier B.V.

  1. A hierarchical model for clustering m(6)A methylation peaks in MeRIP-seq data.

    PubMed

    Cui, Xiaodong; Meng, Jia; Zhang, Shaowu; Rao, Manjeet K; Chen, Yidong; Huang, Yufei

    2016-08-22

    The recent advent of the state-of-art high throughput sequencing technology, known as Methylated RNA Immunoprecipitation combined with RNA sequencing (MeRIP-seq) revolutionizes the area of mRNA epigenetics and enables the biologists and biomedical researchers to have a global view of N (6)-Methyladenosine (m(6)A) on transcriptome. Yet there is a significant need for new computation tools for processing and analysing MeRIP-Seq data to gain a further insight into the function and m(6)A mRNA methylation. We developed a novel algorithm and an open source R package ( http://compgenomics.utsa.edu/metcluster ) for uncovering the potential types of m(6)A methylation by clustering the degree of m(6)A methylation peaks in MeRIP-Seq data. This algorithm utilizes a hierarchical graphical model to model the reads account variance and the underlying clusters of the methylation peaks. Rigorous statistical inference is performed to estimate the model parameter and detect the number of clusters. MeTCluster is evaluated on both simulated and real MeRIP-seq datasets and the results demonstrate its high accuracy in characterizing the clusters of methylation peaks. Our algorithm was applied to two different sets of real MeRIP-seq datasets and reveals a novel pattern that methylation peaks with less peak enrichment tend to clustered in the 5' end of both in both mRNAs and lncRNAs, whereas those with higher peak enrichment are more likely to be distributed in CDS and towards the 3'end of mRNAs and lncRNAs. This result might suggest that m(6)A's functions could be location specific. In this paper, a novel hierarchical graphical model based algorithm was developed for clustering the enrichment of methylation peaks in MeRIP-seq data. MeTCluster is written in R and is publicly available.

  2. Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6.

    PubMed

    Hasserjian, R P; Howard, J; Wood, A; Henry, K; Bain, B

    2001-03-01

    Classic erythroleukaemia (acute myeloid leukaemia M6, or M6 AML) is defined as an excess of myeloblasts in an erythroid predominant background. Leukaemia variants in which the primitive blast cells are demonstrably erythroid are extremely rare and poorly characterised. Variably referred to as "true erythroleukaemia" or "acute erythremic myelosis", they are often included within the M6 AML category even though they do not meet strict criteria for this type of AML. Two cases of acute erythroid neoplasia are presented with clinical, morphological, immunophenotypic, and cytogenetic analysis. Both patients presented with profound anaemia, one in a setting of long standing myelodysplasia. Bone marrow examination revealed a predominant population of highly dysplastic erythroid cells in both cases. In one case, the liver was infiltrated by neoplastic erythroid cells. Both patients died within four months of diagnosis. This report illustrates that cases of acute leukaemia occur in which the dominant neoplastic cell is a primitive erythroid cell without an accompanying increase in myeloblasts. This does not preclude the neoplastic clone originating in a multipotent haemopoietic stem cell, as suggested by cases arising in patients with myelodysplasia. Acute erythremic myelosis should be recognised as a distinct variant of M6 AML.

  3. The association of body size in early to mid-life with adult urinary 6-sulfatoxymelatonin levels among night shift health care workers.

    PubMed

    Ramin, Cody A; Massa, Jennifer; Wegrzyn, Lani R; Brown, Susan B; Pierre-Paul, Jeffrey; Devore, Elizabeth E; Hankinson, Susan E; Schernhammer, Eva S

    2015-05-06

    Adult body mass index (BMI) has been associated with urinary melatonin levels in humans; however, whether earlier-life body size is associated with melatonin, particularly among night shift workers, remains unknown. We evaluated associations of birth weight, body shape (or somatotype) at ages 5 and 10, BMI at age 18 and adulthood, weight change since age 18, waist circumference, waist to hip ratio, and height with creatinine-adjusted morning urinary melatonin (6-sulfatoxymelatonin, aMT6s) levels among 1,343 healthy women (aged 32-53 at urine collection, 1996-1999) in the Nurses' Health Study (NHS) II cohort. Using multivariable linear regression, we computed least-square mean aMT6s levels across categories of body size, and evaluated whether these associations were modified by night shift work. Adult BMI was inversely associated with aMT6s levels (mean aMT6s levels = 34 vs. 50 ng/mg creatinine, comparing adult BMI ≥ 30 vs. <20 kg/m(2); P trend < 0.0001); however, other measures of body size were not related to aMT6s levels after accounting for adult BMI. Night shifts worked prior to urine collection, whether recent or cumulatively over time, did not modify the association between adult BMI and aMT6s levels (e.g., P interaction = 0.72 for night shifts worked within two weeks of urine collection). Our results suggest that adult BMI, but not earlier measures of body size, is associated with urinary aMT6s levels in adulthood. These observations did not vary by night shift work status, and suggest that adult BMI may be an important mechanism by which melatonin levels are altered and subsequently influence chronic disease risk.

  4. Pure versus mixed electrosurgical current for endoscopic biliary sphincterotomy: a meta-analysis of adverse outcomes.

    PubMed

    Verma, Dharmendra; Kapadia, Asha; Adler, Douglas G

    2007-08-01

    Endoscopic biliary sphincterotomy (ES) can cause bleeding, pancreatitis, and perforation. This has, in part, been attributed to the type of electrosurgical current used for ES. No consensus exists on the optimal type of electrosurgical current for ES to maximize safety. To compare the rates of complications in patients undergoing ES via pure current versus mixed current. A systematic review of published, prospective, randomized trials that compared pure current with mixed current for ES. Patients undergoing ES, with random assignment to either current group. Data were standardized for pancreatitis and postsphincterotomy bleeding. There were insufficient data to analyze perforation risk. A random-effects model was used. Bleeding, pancreatitis, and perforation. A total of 804 patients from 4 trials that compared pure current to mixed current were analyzed. The aggregated rate of pancreatitis was 3.8%, 95% confidence interval (CI) 1.0%-6.6%, for the pure-current group versus 7.9%, 95% CI 3.1%-12.7%, for the mixed-current group; the difference was not statistically significant. The rate of bleeding (all severity groups) for the pure-current group was 37.3% (95% CI 27.3%, 47.3%), which was significantly higher than that of the mixed-current group (12.2% [95% CI 4.1%, 20.3%]). Mild bleeding was significantly more frequent with pure current (28.9% [95% CI 16.3, 41.4]) compared with mixed current (9.4% [95% CI 2.1%, 16.8%]). Variables, including endoscopist skill and cannulation difficulty, were difficult to measure. The rate of pancreatitis in patients who underwent ES when using pure current was not significantly different from those when using mixed current. Pure current was associated with more episodes of bleeding, primarily mild bleeding. Data were insufficient to analyze the perforation risk.

  5. m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells

    PubMed Central

    Cui, Qi; Shi, Hailing; Ye, Peng; Li, Li; Qu, Qiuhao; Sun, Guoqiang; Sun, Guihua; Lu, Zhike; Huang, Yue; Yang, Cai-Guang; Riggs, Arthur D.

    2017-01-01

    Summary RNA modifications play critical roles in important biological processes. However, the functions of N6-methyladenosine (m6A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m6A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal. Moreover, inhibition of FTO suppresses tumor progression and prolongs lifespan of GSC-grafted mice substantially. m6A sequencing reveals that knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., ADAM19) with critical biological functions in GSCs. In summary, this study identifies the m6A mRNA methylation machinery as promising therapeutic targets for glioblastoma. PMID:28297667

  6. Differential effect of pure isoflavones and soymilk on estrogen receptor activity in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rando, Gianpaolo; Ramachandran, Balaji; Rebecchi, Monica

    2009-06-15

    Background: Because of the complexity of estrogen receptor (ER) physiological activity, the interaction of pure isoflavones or soy-based diets on ER needs to be clearly demonstrated. Objectives: To investigate the effects of the administration of isoflavones as a pure compound or as a component of diet on the ER transcriptional activity in adult mice. Methods: Effects of acute (6 h) and chronic (21 days) oral administration of soy milk, pure genistein and a mix of genistein and daidzein was studied in living ERE-Luc mice. In this animal model, the synthesis of luciferase is under the state of ER transcriptional activity.more » Luciferase activity was measured in living mice by daily bioluminescence imaging sessions and in tissue extracts by enzymatic assay. Results: Acute, oral administration of genistein or soymilk caused a significant increase of ER activity in liver. In a 20 day long treatment, soymilk was more potent than genistein in liver and appeared to extend its influence on ER transcriptional activity in other tissues, such as the digestive tract. A mixture of pure genistein and daidzein at the same concentration as in soymilk failed to induce significant changes during acute and chronic studies suggesting an important, uncharacterized role of the soymilk matrix. Consistent with this observation, synergistic effects of the matrix plus isoflavones were observed in MCF-7 cells stably transfected with the ERE-luc construct. Conclusions: This study underlines the limitations of the analysis of single food components in the evaluation of their effects on estrogen receptor activity and advocates the necessity to use complex organisms for the full comprehension of the effects of compounds altering the endocrine balance.« less

  7. The effect of ultrasound on particle size, color, viscosity and polyphenol oxidase activity of diluted avocado puree.

    PubMed

    Bi, Xiufang; Hemar, Yacine; Balaban, Murat O; Liao, Xiaojun

    2015-11-01

    The effect of ultrasound treatment on particle size, color, viscosity, polyphenol oxidase (PPO) activity and microstructure in diluted avocado puree was investigated. The treatments were carried out at 20 kHz (375 W/cm(2)) for 0-10 min. The surface mean diameter (D[3,2]) was reduced to 13.44 μm from an original value of 52.31 μm by ultrasound after 1 min. A higher L(∗) value, ΔE value and lower a(∗) value was observed in ultrasound treated samples. The avocado puree dilution followed pseudoplastic flow behavior, and the viscosity of diluted avocado puree (at 100 s(-1)) after ultrasound treatment for 1 min was 6.0 and 74.4 times higher than the control samples for dilution levels of 1:2 and 1:9, respectively. PPO activity greatly increased under all treatment conditions. A maximum increase of 25.1%, 36.9% and 187.8% in PPO activity was found in samples with dilution ratios of 1:2, 1:5 and 1:9, respectively. The increase in viscosity and measured PPO activity might be related to the decrease in particle size. The microscopy images further confirmed that ultrasound treatment induced disruption of avocado puree structure. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position-Specific Nucleotide Propensities and a Support Vector Machine.

    PubMed

    Li, Guang-Qing; Liu, Zi; Shen, Hong-Bin; Yu, Dong-Jun

    2016-10-01

    As one of the most ubiquitous post-transcriptional modifications of RNA, N 6 -methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A.

  9. Genetic manipulation of iron biomineralization enhances MR relaxivity in a ferritin-M6A chimeric complex.

    PubMed

    Radoul, Marina; Lewin, Limor; Cohen, Batya; Oren, Roni; Popov, Stanislav; Davidov, Geula; Vandsburger, Moriel H; Harmelin, Alon; Bitton, Ronit; Greneche, Jean-Marc; Neeman, Michal; Zarivach, Raz

    2016-05-23

    Ferritin has gained significant attention as a potential reporter gene for in vivo imaging by magnetic resonance imaging (MRI). However, due to the ferritin ferrihydrite core, the relaxivity and sensitivity for detection of native ferritin is relatively low. We report here on a novel chimeric magneto-ferritin reporter gene - ferritin-M6A - in which the magnetite binding peptide from the magnetotactic bacteria magnetosome-associated Mms6 protein was fused to the C-terminal of murine h-ferritin. Biophysical experiments showed that purified ferritin-M6A assembled into a stable protein cage with the M6A protruding into the cage core, enabling magnetite biomineralisation. Ferritin-M6A-expressing C6-glioma cells showed enhanced (per iron) r2 relaxivity. MRI in vivo studies of ferritin-M6A-expressing tumour xenografts showed enhanced R2 relaxation rate in the central hypoxic region of the tumours. Such enhanced relaxivity would increase the sensitivity of ferritin as a reporter gene for non-invasive in vivo MRI-monitoring of cell delivery and differentiation in cellular or gene-based therapies.

  10. The OFP-6M transport jet

    NASA Technical Reports Server (NTRS)

    Alexander, Kelly; Heneghan, Brian; Holmes, Joules; Hughes, Bret; Kettering, Mark; Wells, Jennifer; Whelan, Todd

    1994-01-01

    This report presents a preliminary design of a commercial jet transport that meets the criteria of the Request For Proposal presented by the American Institute of Aeronautics and Astronauts (AIAA). The proposal requires an innovative design of a low cost domestic commercial transport that will reduce operating costs for airline companies while still meeting present and future requirements of the Federal Aviation Regulations for this type of aircraft. Specifications for the design include a mixed class, 153 passenger aircraft, traveling a range of 3000 nm. The intent of the project is to identify factors that reduce cost and to design within the limits of these constraints. The project includes techniques or options that incorporate new technologies but do not override practicality, alternative design approaches, and a comparison between the new design and current aircraft in its class. The OFP-6M is an alternative design approach to the conventional commercial transport jet and is geared towards customer satisfaction through efficiency and reliability. The goals of the OFP-6M transport design are to provide original, sensible, and practical solutions by combining essential preliminary design factors with growing technology. The design focus of the OFP-6M reduces costs by simplifying systems where significant weight or maintenance savings can be achieved, and by integrating advanced technology for improved performance. Key aspects of the OFP-6M design are efficient use of materials like composites, and efficient advanced ducted high bypass turbofan engines. The high bypass engines lower fuel consumption and aid in reducing costs and meeting future noise emission restrictions. Composites are used for most structural components, including flooring and wing box. Although composites are an emerging technology and presently, a high maintenance material, they can be cost effective and an alternative to aluminum structures when correct manufacturing and design strategies

  11. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  12. Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study.

    PubMed

    Gillard, Paul; Yang, Pan-Chyr; Danilovits, Manfred; Su, Wei-Juin; Cheng, Shih-Lung; Pehme, Lea; Bollaerts, Anne; Jongert, Erik; Moris, Philippe; Ofori-Anyinam, Opokua; Demoitié, Marie-Ange; Castro, Marcela

    2016-09-01

    Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed post-M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov: NCT01424501. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

  13. Superposing pure quantum states with partial prior information

    NASA Astrophysics Data System (ADS)

    Dogra, Shruti; Thomas, George; Ghosh, Sibasish; Suter, Dieter

    2018-05-01

    The principle of superposition is an intriguing feature of quantum mechanics, which is regularly exploited in many different circumstances. A recent work [M. Oszmaniec et al., Phys. Rev. Lett. 116, 110403 (2016), 10.1103/PhysRevLett.116.110403] shows that the fundamentals of quantum mechanics restrict the process of superimposing two unknown pure states, even though it is possible to superimpose two quantum states with partial prior knowledge. The prior knowledge imposes geometrical constraints on the choice of input states. We discuss an experimentally feasible protocol to superimpose multiple pure states of a d -dimensional quantum system and carry out an explicit experimental realization for two single-qubit pure states with partial prior information on a two-qubit NMR quantum information processor.

  14. Successful treatment of congenital acute myeloid leukemia (AML-M6) in a premature infant.

    PubMed

    van Dongen, Joyce C A; Dalinghaus, Michiel; Kroon, Andre A; de Vries, Andrica C H; van den Heuvel-Eibrink, Marry M

    2009-11-01

    Congenital acute myeloid leukemia (AML), and especially AML-M6 is a rare disease with a poor prognosis. Moreover, reports of treatment outcome of congenital AML-M6 in premature infants are not available. We report the first treated case of congenital AML-M6 in a premature girl, who received a full AML protocol. She presented with blueberry-muffin spots, anemia, high white blood cell count, and serious cardiopulmonary distress. Peripheral blood smears showed AML-M6 blasts. After treatment with a sequential low-dose cytarabine after birth and full-dose AML treatment according to the MRC-12 protocol at the age of 2 months, she now is in continuous complete remission for 4 years.

  15. A 18 m 2 cylindrical tracking detector made of 2.6 m long, stereo mylar straw tubes with 100 μm resolution

    NASA Astrophysics Data System (ADS)

    Benussi, L.; Bertani, M.; Bianco, S.; Fabbri, F. L.; Gianotti, P.; Giardoni, M.; Ghezzo, A.; Guaraldo, C.; Lanaro, A.; Locchi, P.; Lu, J.; Lucherini, V.; Mecozzi, A.; Pace, E.; Passamonti, L.; Qaisar, N.; Ricciardi, A.; Sarwar, S.; Serdyouk, V.; Trasatti, L.; Volkov, A.; Zia, A.

    1998-12-01

    An array of 2424 2.6 m-long, 15 mm-diameter mylar straw tubes, arranged in two axial and four stereo layers, has been assembled. The array covers a cylindrical tracking surface of 18 m 2 and provides coordinate measurement in the drift direction and along the wire. A correction of the systematic effects which are introduced by gravitational sag and electrostatics, thus dominating the detector performance especially with long straws, allows to determine wire position from drift-time distribution. The correction has been applied to reach a space resolution of 40 μm with DME, 100 μm with Ar+C 2H 6, and 100-200 μm with CO 2. Such a resolution is the best ever obtained for straws of these dimensions. A study of the gas leakage for the straw system has been performed, and results are reported. The array is being commissioned as a subdetector of the FINUDA spectrometer, and tracking performances are being studied with cosmic rays.

  16. Normative data for the Words-in-Noise Test for 6- to 12-year-old children.

    PubMed

    Wilson, Richard H; Farmer, Nicole M; Gandhi, Avni; Shelburne, Emily; Weaver, Jamie

    2010-10-01

    To establish normative data for children on the Words-in-Noise Test (WIN; R. H. Wilson, 2003; R. H. Wilson & R. McArdle, 2007). Forty-two children in each of 7 age groups, ranging in age from 6 to 12 years (n=294), and 24 young adults (age range: 18-27 years) with normal hearing for pure tones participated. All listeners were screened at 15 dB HL (American National Standards Institute, 2004) with the octave interval between 500 and 4000 Hz. Randomizations of WIN Lists 1, 2, and 1 or WIN Lists 2, 1, and 2 were presented with the noise fixed at 70 dB SPL, followed by presentation at 90 dB SPL of the 70 Northwestern University Auditory Test No. 6 (T. W. Tillman & R. Carhart, 1966) words used in the WIN. Finally, the Peabody Picture Vocabulary Test-Revised (L. M. Dunn & L. M. Dunn, 1981) was administered. Testing was conducted in a quiet room. There were 3 main findings: (a) The biggest change in recognition performance occurred between the ages of 6 and 7 years; (b) from 9 to 12 years, recognition performance was stable; and (c) performance by young adults (18-27 years) was slightly better (1-2 dB) than performance by the older children. The WIN can be used with children as young as 6 years of age; however, age-specific ranges of normal recognition performance must be used.

  17. The use of e-health and m-health tools in health promotion and primary prevention among older adults: a systematic literature review.

    PubMed

    Kampmeijer, Ramon; Pavlova, Milena; Tambor, Marzena; Golinowska, Stanisława; Groot, Wim

    2016-09-05

    The use of e-health and m-health technologies in health promotion and primary prevention among older people is largely unexplored. This study provides a systematic review of the evidence on the scope of the use of e-health and m-health tools in health promotion and primary prevention among older adults (age 50+). A systematic literature review was conducted in October 2015. The search for relevant publications was done in the search engine PubMed. The key inclusion criteria were: e-health and m-health tools used, participants' age 50+ years, focus on health promotion and primary prevention, published in the past 10 years, in English, and full-paper can be obtained. The text of the publications was analyzed based on two themes: the characteristics of e-health and m-health tools and the determinants of the use of these tools by older adults. The quality of the studies reviewed was also assessed. The initial search resulted in 656 publications. After we applied the inclusion and exclusion criteria, 45 publications were selected for the review. In the publications reviewed, various types of e-health/m-health tools were described, namely apps, websites, devices, video consults and webinars. Most of the publications (60 %) reported studies in the US. In 37 % of the publications, the study population was older adults in general, while the rest of the publications studied a specific group of older adults (e.g. women or those with overweight). The publications indicated various facilitators and barriers. The most commonly mentioned facilitator was the support for the use of the e-health/m-health tools that the older adults received. E-health and m-health tools are used by older adults in diverse health promotion programs, but also outside formal programs to monitor and improve their health. The latter is hardly studied. The successful use of e-health/m-health tools in health promotion programs for older adults greatly depends on the older adults' motivation and support

  18. Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development.

    PubMed

    Storer, Mekayla A; Gallagher, Denis; Fatt, Michael P; Simonetta, Jaclin V; Kaplan, David R; Miller, Freda D

    2018-05-08

    Circulating systemic factors can regulate adult neural stem cell (NSC) biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6), since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Cognitive-Behaviorally-Oriented Group Rehabilitation of Adults with ADHD: Results of a 6-Month Follow-Up

    ERIC Educational Resources Information Center

    Salakari, Anita; Virta, Maarit; Gronroos, Nina; Chydenius, Esa; Partinen, Markku; Vataja, Risto; Kaski, Markus; Iivanainen, Matti

    2010-01-01

    Objective: Recently, novel psychological treatments for adult ADHD have been reported with promising results. However, studies about long-term treatment effects are scanty. The authors study effects of cognitive-behaviorally-oriented group rehabilitation during a 6-month follow-up. Method: Participating in the rehabilitation were 29 adults, of…

  20. The first reference equations for the 6-minute walk distance over a 10 m course.

    PubMed

    Beekman, Emmylou; Mesters, Ilse; Gosselink, Rik; Klaassen, Mariska P M; Hendriks, Erik J M; Van Schayck, Onno C P; de Bie, Rob A

    2014-09-01

    As primary care practice space is mostly limited to 10 m, the 6-minute walk test (6MWT) over a 10 m course is a frequently used alternative to evaluate patients' performance in COPD. Considering that course length significantly affects distance walked in 6 minutes (6MWD), this study aims to develop appropriate reference equations for the 10 m 6MWT. 181 healthy subjects, aged 40-90 years, performed two standardised 6MWTs over a straight 10 m course in a cross-sectional study. Average distance achieved was 578±108 m and differed between males and females (p<0.001). Resulting sex-specific reference equations from multiple regression analysis included age, body mass index and change in heart rate, explaining 62% of the variance in 6MWD for males and 71% for females. The presented reference equations are the first to evaluate 6MWD over a 10 m course and expand the usefulness of the 6MWT. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5

    PubMed Central

    Huang, Yue; Yan, Jingli; Li, Qi; Li, Jiafei; Gong, Shouzhe; Zhou, Hu; Gan, Jianhua; Jiang, Hualiang; Jia, Gui-Fang; Luo, Cheng; Yang, Cai-Guang

    2015-01-01

    Two human demethylases, the fat mass and obesity-associated (FTO) enzyme and ALKBH5, oxidatively demethylate abundant N6-methyladenosine (m6A) residues in mRNA. Achieving a method for selective inhibition of FTO over ALKBH5 remains a challenge, however. Here, we have identified meclofenamic acid (MA) as a highly selective inhibitor of FTO. MA is a non-steroidal, anti-inflammatory drug that mechanistic studies indicate competes with FTO binding for the m6A-containing nucleic acid. The structure of FTO/MA has revealed much about the inhibitory function of FTO. Our newfound understanding, revealed herein, of the part of the nucleotide recognition lid (NRL) in FTO, for example, has helped elucidate the principles behind the selectivity of FTO over ALKBH5. Treatment of HeLa cells with the ethyl ester form of MA (MA2) has led to elevated levels of m6A modification in mRNA. Our collective results highlight the development of functional probes of the FTO enzyme that will (i) enable future biological studies and (ii) pave the way for the rational design of potent and specific inhibitors of FTO for use in medicine. PMID:25452335

  2. Improving Appointment Adherence among Young Adults with HIV in Peru with an mHealth Intervention: a Feasibility Study

    PubMed Central

    Prochazka, Mateo; Batey, D Scott; Zinski, Anne; Dionne-Odom, Jodie; Otero, Larissa; Rodriguez, J Martin; González, Elsa

    2017-01-01

    Abstract Background Mobile Health (mHealth) interventions, including short message services (SMS) reminders and motivational messages, are associated with improved HIV appointment adherence, though feasibility is context-dependent. We assessed the feasibility of an mHealth intervention to improve appointment adherence among young adults with HIV in Lima, Peru. Methods Between November 2016 and April 2017, we implemented a one-way mHealth pilot intervention in an outpatient hospital without electronic medical records. We enrolled young adults (age 18–29) entering HIV care in a 3-component intervention: (i) reminder SMS prior to scheduled appointments (provider, laboratory, pharmacy); (ii) motivational SMS after each visit; and (iii) phone call following a missed visit. Feasibility evaluation included enrollment acceptance, visit tracking (information captured in the study database within 3 days of attendance), and proportion of intervention delivery (threshold >90%). We performed a qualitative assessment to identify implementation challenges reviewing staff field notes and meeting minutes. Results We enrolled 80/94 (85.1%) eligible participants. The median age was 25 years and 83% were male. The median time of follow-up after enrollment was 115 [interquartile range (IQR): 84–141] days, and participants had a median of 10 (IQR: 8–14) visits during the study period. Among 850 total participant visits, study personnel tracked 751 (88.4%); most (80.8%) untracked visits were pharmacy pickups. Of all tracked visits, most (78.7%) were scheduled appointments and 160 (21.3%) were unscheduled walk-ins. Intervention delivery reached 556/591 (94.1%) for reminder SMS; 733/751 (97.6%) for motivational messages, and 169/170 (99.4%) phone calls for missed visits, 127 (75.1%) of which were answered. Qualitative assessment revealed 2 major themes: real-time appointment tracking in a paper-based system consumed most staff time and resources, and meticulous in-person coordination

  3. Can mHealth Revolutionize the Way We Manage Adult Obesity?

    PubMed

    Bhardwaj, Niharika N; Wodajo, Bezawit; Gochipathala, Keerthi; Paul, David P; Coustasse, Alberto

    2017-01-01

    Obesity is the largest driver of chronic preventable diseases, accounting for an estimated $147 billion or 10 percent of total US healthcare costs in 2008. It has been forecasted that 42 percent of Americans will be obese by 2030. Mobile health (mHealth) technologies target and may modify the behavioral factors that lead to obesity to promote a healthy lifestyle. These technologies could potentially reduce the cost and the morbidity and mortality burden of obesity because of their inexpensive and portable nature. This study aimed to analyze the efficacy and cost-effectiveness of mHealth interventions for adult obesity in the United States. The methodology used in this study was a literature review of 54 articles. Weight, body mass index (BMI), waist circumference reductions, and favorable lifestyle behavior changes were noted across most studies. Existing data and research on efficacy and linked costs indicated that mHealth technologies were more effective than other methods and could be inexpensively delivered remotely to manage adult obesity, offering significant benefits over conventional care. Further studies on the costs and benefits of adapting such mHealth interventions in clinical settings are needed.

  4. [Pure Amnesia].

    PubMed

    Tagawa, Koichi; Tokida, Haruki

    2017-06-01

    Pure amnesia (amnesic syndrome) is an organic brain syndrome characterized by impairment in episodic memory, with either an anterograde or sometimes retrograde loss of memories. Although episodic memory is impaired, semantic memory, immediate memory, and procedural memory are preserved. The Papez circuit is a network of nerve fibers and nerve centers that starts and ends in the hippocampus travelling by way of the fornix, mammillary bodies, anterior thalamic nuclei, cingulate gyrus, and parahippocampal gyrus. A lesion restricted to this circuit often produces pure amnesia. Regions concerned with the Yakovlev circuit also have an important role in memory. Clinical cases of pure amnesia caused by cerebrovascular disease presented following brain imaging and resulted from various different lesions. The cases identified were predominantly thalamic amnesia and hippocampal amnesia. Thalamic amnesia often resulted from an infarction in the territory of the thalamotuberal artery and paramedian thalamic artery although thalamic hemorrhage in medial portion of thalamus also produced pure amnesia. Hippocampal amnesia usually occurred following an infarction in the temporal branches of posterior cerebral artery. Cases of retrosplenial amnesia caused by subcortical hematoma and infarction in the retrosplenial region are also described. In addition, cases of pure amnesia resulting from an infarction in the fornix, mammillary body hemorrhage, and caudate hemorrhage are also shown.

  5. Physical performance in recently aged adults after 6 weeks traditional Thai dance: a randomized controlled trial

    PubMed Central

    Janyacharoen, Taweesak; Laophosri, Maneepun; Kanpittaya, Jaturat; Auvichayapat, Paradee; Sawanyawisuth, Kittisak

    2013-01-01

    Background Exercise has been shown to be effective in cardiovascular endurance in the elderly. We studied the effect of Thai dancing on physical performance of Thai elderly. Methods This was an open-labeled, randomized intervention study. The Thai dancing group exercised for 40 minutes three times a week for 6 weeks. Physical performance ability was the primary outcome, including a 6-minute walk test (6MWT), five-times sit-to-stand (FTSST), and a sit-and-reach test measured before and after 6 weeks of intervention. Results There were 42 subjects enrolled in the study, and 38 female subjects completed (20 in Thai dance group, 18 controls), with an average age of 65.8 ± 5.1 years. The Thai dance group had significantly better physical performance in all measurements at the end of the study. The 6MWT was longer (416.7 ± 58.7 versus 345.7 ± 55.1 m; P = 0.011), FTSST was quicker (10.2 ± 1.5 versus 14.4 ± 3.3 seconds; P < 0.001), and flexibility was higher (14.9 ± 3.5 versus 11.1 ± 5.7 cm; P = 0.002) in the Thai dance group than the control group. Conclusion Thai dance can improve physical performance in recently aged (elderly) female adults. PMID:23950640

  6. Hepatoblastoma with pure fetal epithelial differentiation in a 10-year-old boy

    PubMed Central

    Zhong, Shanshan; Zhao, Yang; Fan, Chuifeng

    2018-01-01

    Abstract Rationale: Hepatoblastoma is a rare malignant embryonal tumor that only accounts for approximately 1% of all pediatric cancers and mostly develops in children younger than 5 years old. Moreover, the occurrence of hepatoblastoma in adults is extremely rare. Patient concerns: Herein, we present a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy.Pathological examination was performed. The tumor was 15 cm × 15 cm in size with clear margins. The cut surface was multiple nodular and grey-yellow. Histologically, the small cuboidal tumor cells were arranged in trabeculae with 2–3 cell layers. The tumor cells had eosinophilic or clear cytoplasm, formed dark and light areas, and were positive for alpha-fetoprotein, CK, CK8/18, CD10, hepatocyte, and GPC3. CD34 staining revealed that the sinusoids were lined by endothelial cells in the tumor tissues. The Ki67 index was approximately 20%. Diagnoses: Based on these findings, the case was diagnosed as hepatoblastoma with pure fetal epithelial differentiation. Interventions: The tumor was completely removed. Outcomes: No recurrence was found 3 months after the operation. Lessons: Hepatoblastoma with pure epithelial differentiation can also occur in older children. Children rarely notice and report any physical abnormality, and this may be among the primary reasons for the late diagnosis of the tumor. Annual heath checks may be beneficial in the detection of these rare tumors and improvement of patient outcomes. PMID:29480877

  7. Innovatively Continuous Mass Production Couette-taylor Flow: Pure Inorganic Green-Emitting Cs4PbBr6 Perovskite Microcrystal for display technology.

    PubMed

    Song, Young Hyun; Choi, Seung Hee; Park, Won Kyu; Yoo, Jin Sun; Kwon, Seok Bin; Kang, Bong Kyun; Park, Sang Ryul; Seo, Young Soo; Yang, Woo Seok; Yoon, Dae Ho

    2018-01-31

    We report for the first time the mass production of Cs 4 PbBr 6 perovskite microcrystal with a Couette-Taylor flow reactor in order to enhance the efficiency of the synthesis reaction. We obtained a pure Cs 4 PbBr 6 perovskite solid within 3 hrs that then realized a high photoluminescence quantum yield (PLQY) of 46%. Furthermore, the Cs 4 PbBr 6 perovskite microcrystal is applied with red emitting K 2 SiF 6 phosphor on a blue-emitting InGaN chip, achieving a high-performance luminescence characteristics of 9.79 lm/W, external quantum efficiency (EQE) of 2.9%, and correlated color temperature (CCT) of 2976 K; therefore, this perovskite is expected to be a promising candidate material for applications in optoelectronic devices.

  8. Gastrointestinal and urinary complaints in adults with hereditary spastic paraparesis.

    PubMed

    Kanavin, Øivind J; Fjermestad, Krister W

    2018-04-16

    Hereditary spastic paraparesis (HSP) is a group of rare genetic disorders affecting the central nervous system. Pure HSP is limited to lower limb spasticity and urinary voiding dysfunction. Complex HSP involves additional neurological features. Beyond the described core symptoms, knowledge about the burden of disease for adults with HSP is limited, particularly regarding gastrointestinal functions, fecal incontinence, and urinary symptoms. We conducted a cross-sectional self-report survey with 108 adult HSP patients (M age  = 57.7 years, SD = 11.5, range 30 to 81; 54.2% females) recruited from a national HSP user group association and a national (non-clinical) advisory unit for rare disorders. HSP data was compared to data from a Norwegian population study, HUNT-3 (N = 46,293). The HSP group reported more gastrointestinal and urinary complaints compared to controls. Gastrointestinal complaints included at least "much" complaints with constipation (14.6%) and alternating constipation/diarrhea (8.0%), and at least daily uncontrollable flatulence (47.6%), fecal incontinence (11.6%), and inability to hold back stools (38.5%). Urinary complaints included frequent urination (27.4% > 8 times daily), sudden urge (51.9%) and urinary incontinence (30.5% at least daily/nightly). This survey of adults with HSP recruited from non-clinical settings showed constipation, alternate constipation and diarrhea, fecal incontinence, and voiding dysfunction represent considerable problems for many persons with HSP. Health care providers should screen and manage often unrecognized gastrointestinal and fecal incontinence complaints among HSP patients.

  9. Sustained glycaemic control and less nocturnal hypoglycaemia with insulin glargine 300U/mL compared with glargine 100U/mL in Japanese adults with type 1 diabetes (EDITION JP 1 randomised 12-month trial including 6-month extension).

    PubMed

    Matsuhisa, Munehide; Koyama, Masayoshi; Cheng, Xi; Sumi, Mariko; Riddle, Matthew C; Bolli, Geremia B; Hirose, Takahisa

    2016-12-01

    To evaluate the efficacy and safety of insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in adults with type 1 diabetes in Japan over 12months. EDITION JP 1 was a multicentre, randomised, open-label phase 3 study. Following a 6-month on-treatment period, participants continued to receive Gla-300 or Gla-100 once daily, plus mealtime insulin, over a 6-month open-label extension phase. HbA1c, hypoglycaemia, body weight and adverse events were assessed. Overall, 114/122 (93%) and 114/121 (94%) of participants in the Gla-300 and Gla-100 group, respectively, completed the 6-month extension phase. Glycaemic control was sustained in both groups up to month 12 (mean HbA1c: Gla-300, 7.9% [62mmol/mol]; Gla-100, 7.8% [62mmol/mol]). Annualised rates of hypoglycaemia were lower with Gla-300 versus Gla-100; significantly for nocturnal confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia (2.39 and 3.85 events per participant-year; rate ratio: 0.62 [0.39-0.97]). No between-treatment differences in mean body weight change or adverse events were observed. Over 12months' treatment, participants with type 1 diabetes receiving Gla-300 achieved sustained glycaemic control and experienced less nocturnal hypoglycaemia that was confirmed (<3.0mmol/L [<54mg/dL]) or severe compared with Gla-100, supporting the 6-month results. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Update: Mechanisms underlying N6-methyladenosine modification of eukaryotic mRNA

    PubMed Central

    Wang, Yang; Zhao, Jing Crystal

    2016-01-01

    Summary Eukaryotic messenger RNA (mRNA) undergoes chemical modification both at the 5′cap [1, 2] and internally [3–14]. Among internal modifications, m6A, by far the most abundant, is present in all eukaryotes examined, including mammals [3–6], flies [15], plants [16, 17] and yeast [18, 19]. m6A modification plays an essential role in diverse biological processes. Over the past few years, our knowledge relevant to establishment and function of this modification has grown rapidly. This review focuses on technologies that have facilitated m6A detection in mRNAs, identification of m6A methylation enzymes and binding proteins, and potential functions of the modification at the molecular level. Regarding m6A function at cellular or organismal levels or in disease, please refer to other recent reviews [20–23]. PMID:27793360

  11. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-11-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  12. [CrIII(NCMe)6]3+--a labile CrIII source enabling formation of Cr[M(CN)6] (M=V, Cr, Mn, Fe) Prussian blue-type magnetic materials.

    PubMed

    Nelson, Kendric J; Daniels, Matthew C; Reiff, William M; Troff, Shayla A; Miller, Joel S

    2007-11-26

    The kinetic inertness of the hexaaquachromium(III) (kH2O=2.4x10(-6) s(-1)) has led to challenges with respect to incorporating CrIII ions into Prussian blue-type materials; however, hexakis(acetonitrile)chromium(III) was shown to be substantially more labile (approximately 10(4) times) and enables a new synthetic route for the synthesis of these materials via nonaqueous solvents. The synthesis, spectroscopic, and physical properties of Cr[M(CN)6] (M=V, Cr, Mn, Fe) Prussian blue analogues synthesized from [CrIII(NCMe)6]3+ and the corresponding [MIII(CN)6]3- are described. All these compounds {(NEt4)0.02CrIII[VIII(CN)6]0.98(BF4)(0.08).0.10MeCN (1), CrIII[CrIII(CN)6].0.16MeCN (2), CrIII[MnIII(CN)6].0.10MeCN (3), and (NEt4)0.04CrIII0.64CrIV0.40[FeII(CN)6]0.40[FeIII(CN)6]0.60(BF4)(0.16).1.02MeCN (4)} are ferrimagnets exhibiting cluster-glass behavior. Strong antiferromagnetic coupling was observed for M=V, Cr, and Mn with Weiss constants (theta) ranging from -132 to -524 K; and in 2, where the strongest coupling is observed (theta=-524 K), the highest Tc (110 K) value was observed. Weak antiferromagnetic coupling was observed for M=Fe (theta=-12 K) leading to the lowest Tc (3 K) value in this series. Weak coupling and the low Tc value observed in 4 were additionally contributed by the presence of both [FeII(CN)6]4- and [FeIII(CN)6]3- as confirmed by 57Fe-Mössbauer spectroscopy.

  13. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. Membrane glycoprotein M6a interacts with the micro-opioid receptor and facilitates receptor endocytosis and recycling.

    PubMed

    Wu, Dai-Fei; Koch, Thomas; Liang, Ying-Jian; Stumm, Ralf; Schulz, Stefan; Schröder, Helmut; Höllt, Volker

    2007-07-27

    Using a yeast two-hybrid screen, the neuronal membrane glycoprotein M6a, a member of the proteolipid protein family, was identified to be associated with the mu-opioid receptor (MOPr). Bioluminescence resonance energy transfer and co-immunoprecipitation experiments confirmed that M6a interacts agonist-independently with MOPr in human embryonic kidney 293 cells co-expressing MOPr and M6a. Co-expression of MOPr with M6a, but not with M6b or DM20, exists in many brain regions, further supporting a specific interaction between MOPr and M6a. After opioid treatment M6a co-internalizes and then co-recycles with MOPr to cell surface in transfected human embryonic kidney 293 cells. Moreover, the interaction of M6a and MOPr augments constitutive and agonist-dependent internalization as well as the recycling rate of mu-opioid receptors. On the other hand, overexpression of a M6a-negative mutant prevents mu-opioid receptor endocytosis, demonstrating an essential role of M6a in receptor internalization. In addition, we demonstrated the interaction of M6a with a number of other G protein-coupled receptors (GPCRs) such as the delta-opioid receptor, cannabinoid receptor CB1, and somatostatin receptor sst2A, suggesting that M6a might play a general role in the regulation of certain GPCRs. Taken together, these data provide evidence that M6a may act as a scaffolding molecule in the regulation of GPCR endocytosis and intracellular trafficking.

  15. Research on M23C6 precipitation of 690 alloy

    NASA Astrophysics Data System (ADS)

    Zhigang, Song; han, Feng; Wenjie, Zheng; Lihong, Zhang; Mingjuan, Ma; Weijun, Sang

    Precipitation M23C6 of 690 alloy was studied in this paper. Firstly, M23C6 precipitation and evolution of chromium-depleted zone of 690 alloy during TT were studied. Evolution of chromium-depleted zone of 690 alloy was affected markedly by TT.The test results showed that the lowest chromium concentration in chromium-depleted zone raised dramatically after TT for 10 20h because of chromium backfill.The morphology of M23C6 in 690 alloy specimens changed obviously during different TT temperatures of 650 850°C. 690 alloy could get good M23C6 morphology though TT at 700 725°C and there appeared coarse M23C6 presenting multiple layer morphology when TT temperature reached 750 850°C. When treated for TT different time at 715°C, the M23C6 amount increased with extension of TT time and M23C6 could precipitate adequately while the TT time reached 15h.

  16. A missense mutation in Grm6 reduces but does not eliminate mGluR6 expression or rod depolarizing bipolar cell function.

    PubMed

    Peachey, Neal S; Hasan, Nazarul; FitzMaurice, Bernard; Burrill, Samantha; Pangeni, Gobinda; Karst, Son Yong; Reinholdt, Laura; Berry, Melissa L; Strobel, Marge; Gregg, Ronald G; McCall, Maureen A; Chang, Bo

    2017-08-01

    GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction and underlie the human condition autosomal recessive complete congenital stationary night blindness. Mouse mutants for Grm6 are important models for this condition. Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen of mice maintained at The Jackson Laboratory. The Grm6 nob8 mouse has a reduced-amplitude b-wave component of the ERG, which reflects light-evoked DBC activity. Sequencing identified a missense mutation that converts a highly conserved methionine within the ligand binding domain to leucine (p.Met66Leu). Consistent with prior studies of Grm6 mutant mice, the laminar size and structure in the Grm6 nob8 retina were comparable to control. The Grm6 nob8 phenotype is distinguished from other Grm6 mutants that carry a null allele by a reduced but not absent ERG b-wave, decreased but present expression of mGluR6 at DBC dendritic tips, and mislocalization of mGluR6 to DBC somas. Consistent with a reduced but not absent b-wave, there were a subset of retinal ganglion cells whose responses to light onset have times to peak within the range of those in control retinas. These data indicate that the p.Met66Leu mutant mGluR6 is trafficked less than control. However, the mGluR6 that is localized to the DBC dendritic tips is able to initiate DBC signal transduction. The Grm6 nob8 mouse extends the Grm6 allelic series and will be useful for elucidating the role of mGluR6 in DBC signal transduction and in human disease. NEW & NOTEWORTHY This article describes a mouse model of the human disease complete congenital stationary night blindness in which the mutation reduces but does not eliminate GRM6 expression and bipolar cell function, a distinct phenotype from that seen in other Grm6 mouse models.

  17. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  18. Production of fermented chestnut purees by lactic acid bacteria.

    PubMed

    Blaiotta, G; Di Capua, M; Coppola, R; Aponte, M

    2012-09-03

    The objective of this study was to develop a new chestnut-based puree, in order to seasonally adjust the offer and use the surplus of undersized production, providing, at the same time, a response to the growing demand for healthy and environmentally friendly products. Broken dried chestnuts have been employed to prepare purees to be fermented with six different strains of Lactobacillus (Lb.) rhamnosus and Lactobacillus casei. The fermented purees were characterized by a technological and sensorial point of view, while the employed strains were tested for their probiotic potential. Conventional in vitro tests have indicated the six lactobacilli strains as promising probiotic candidates; moreover, being the strains able to grow and to survive in chestnut puree at a population level higher than 8 log₁₀ CFU/mL along 40 days of storage at 4 °C, the bases for the production of a new food, lactose-free and with reduced fat content, have been laid. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Compact objects in pure Lovelock theory

    NASA Astrophysics Data System (ADS)

    Dadhich, Naresh; Hansraj, Sudan; Chilambwe, Brian

    For static fluid interiors of compact objects in pure Lovelock gravity (involving only one Nth order term in the equation), we establish similarity in solutions for the critical odd and even d = 2N + 1, 2N + 2 dimensions. It turns out that in critical odd d = 2N + 1 dimensions, there cannot exist any bound distribution with a finite radius, while in critical even d = 2N + 2 dimensions, all solutions have similar behavior. For exhibition of similarity, we would compare star solutions for N = 1, 2 in d = 4 Einstein and d = 6 in Gauss-Bonnet theory, respectively. We also obtain the pure Lovelock analogue of the Finch-Skea model.

  20. Validation of a Spanish translation of the Gratitude Questionnaire (GQ-6) with a Chilean sample of adults and high schoolers.

    PubMed

    Langer, Álvaro I; Ulloa, Valentina G; Aguilar-Parra, José M; Araya-Véliz, Claudio; Brito, Gonzalo

    2016-03-31

    Recent studies have associated positive emotions with several variables such as learning, coping strategies or assertive behaviour. The concept of gratitude has been specifically defined as a tendency to recognise and respond to people or situations with grateful emotion. Unfortunately in Latin America, no validated measures of gratitude on different populations are available. The aim of this study was to analyse the psychometric properties of the Gratitude Questionnaire (GQ-6) in two Chilean samples. Two studies were conducted: the first with 668 high school adolescents (390 women and 278 men, with ages ranging between 12 and 20, and a mean age 15.54 ± 1.22) and the second with 331 adults (231 women and 100 men, with an average age of 37.59 ± 12.6). An analysis of the psychometric properties of the GQ-6 scale to determine the validity and reliability of the instrument in Chilean adolescents and adults was performed. Bivariate correlations, multiple regression analyses, exploratory factor analysis (EFA) and Monte Carlo simulations were carried out. Finally, a confirmatory factor analysis (CFA) was performed. A single-factor solution was found in both studies, a 5 item version for the adolescents and 6 items for adults. This factorial solution was invariant across genders. Reliability of the GQ was adequate in both samples (using Cronbach's alpha coefficient). In addition convergent and discriminate validity were assessed. Additionally, a negative correlation between the GQ-5 and depression in adolescents and a positive correlation between the GQ-6 and happiness in adults was found. The GQ is a suitable measure for evaluating a person's disposition toward gratitude in Chilean adolescents and adults. This instrument may contribute to the advancement of the study of positive emotions in Latin America.

  1. MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

    ClinicalTrials.gov

    2017-06-16

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Simplified method to isolate highly pure canine pancreatic islets.

    PubMed

    Woolcott, Orison O; Bergman, Richard N; Richey, Joyce M; Kirkman, Erlinda L; Harrison, L Nicole; Ionut, Viorica; Lottati, Maya; Zheng, Dan; Hsu, Isabel R; Stefanovski, Darko; Kabir, Morvarid; Kim, Stella P; Catalano, Karyn J; Chiu, Jenny D; Chow, Robert H

    2012-01-01

    The canine model has been used extensively to improve the human pancreatic islet isolation technique. At the functional level, dog islets show high similarity to human islets and thus can be a helpful tool for islet research. We describe and compare 2 manual isolation methods, M1 (initial) and M2 (modified), and analyze the variables associated with the outcomes, including islet yield, purity, and glucose-stimulated insulin secretion (GSIS). Male mongrel dogs were used in the study. M2 (n = 7) included higher collagenase concentration, shorter digestion time, faster shaking speed, colder purification temperature, and higher differential density gradient than M1 (n = 7). Islet yield was similar between methods (3111.0 ± 309.1 and 3155.8 ± 644.5 islets/g, M1 and M2, respectively; P = 0.951). Pancreas weight and purity together were directly associated with the yield (adjusted R(2) = 0.61; P = 0.002). Purity was considerably improved with M2 (96.7% ± 1.2% vs 75.0% ± 6.3%; P = 0.006). M2 improved GSIS (P = 0.021). Independently, digestion time was inversely associated with GSIS. We describe an isolation method (M2) to obtain a highly pure yield of dog islets with adequate β-cell glucose responsiveness. The isolation variables associated with the outcomes in our canine model confirm previous reports in other species, including humans.

  3. Revival of pure titanium for dynamically loaded porous implants using additive manufacturing.

    PubMed

    Wauthle, Ruben; Ahmadi, Seyed Mohammad; Amin Yavari, Saber; Mulier, Michiel; Zadpoor, Amir Abbas; Weinans, Harrie; Van Humbeeck, Jan; Kruth, Jean-Pierre; Schrooten, Jan

    2015-09-01

    Additive manufacturing techniques are getting more and more established as reliable methods for producing porous metal implants thanks to the almost full geometrical and mechanical control of the designed porous biomaterial. Today, Ti6Al4V ELI is still the most widely used material for porous implants, and none or little interest goes to pure titanium for use in orthopedic or load-bearing implants. Given the special mechanical behavior of cellular structures and the material properties inherent to the additive manufacturing of metals, the aim of this study is to investigate the properties of selective laser melted pure unalloyed titanium porous structures. Therefore, the static and dynamic compressive properties of pure titanium structures are determined and compared to previously reported results for identical structures made from Ti6Al4V ELI and tantalum. The results show that porous Ti6Al4V ELI still remains the strongest material for statically loaded applications, whereas pure titanium has a mechanical behavior similar to tantalum and is the material of choice for cyclically loaded porous implants. These findings are considered to be important for future implant developments since it announces a potential revival of the use of pure titanium for additively manufactured porous implants. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Dietary Levels of Pure Flavonoids Improve Spatial Memory Performance and Increase Hippocampal Brain-Derived Neurotrophic Factor

    PubMed Central

    Rendeiro, Catarina; Vauzour, David; Rattray, Marcus; Waffo-Téguo, Pierre; Mérillon, Jean Michel; Butler, Laurie T.; Williams, Claire M.; Spencer, Jeremy P. E.

    2013-01-01

    Evidence suggests that flavonoid-rich foods are capable of inducing improvements in memory and cognition in animals and humans. However, there is a lack of clarity concerning whether flavonoids are the causal agents in inducing such behavioral responses. Here we show that supplementation with pure anthocyanins or pure flavanols for 6 weeks, at levels similar to that found in blueberry (2% w/w), results in an enhancement of spatial memory in 18 month old rats. Pure flavanols and pure anthocyanins were observed to induce significant improvements in spatial working memory (p = 0.002 and p = 0.006 respectively), to a similar extent to that following blueberry supplementation (p = 0.002). These behavioral changes were paralleled by increases in hippocampal brain-derived neurotrophic factor (R = 0.46, p<0.01), suggesting a common mechanism for the enhancement of memory. However, unlike protein levels of BDNF, the regional enhancement of BDNF mRNA expression in the hippocampus appeared to be predominantly enhanced by anthocyanins. Our data support the claim that flavonoids are likely causal agents in mediating the cognitive effects of flavonoid-rich foods. PMID:23723987

  5. Cracks growth behaviors of commercial pure titanium under nanosecond laser irradiation for formation of nanostructure-covered microstructures (with sub-5-μm)

    NASA Astrophysics Data System (ADS)

    Pan, A. F.; Wang, W. J.; Mei, X. S.; Zheng, B. X.; Yan, Z. X.

    2016-11-01

    This study reported on the formation of sub-5-μm microstructures covered on titanium by cracks growth under 10-ns laser radiation at the wavelength of 532 nm and its induced light modification for production of nanostructures. The electric field intensity and laser power density absorbed by commercial pure titanium were computed to investigate the self-trapping introduced by cracks and the effect of surface morphology on laser propagation characteristics. It is found that nanostructures can form at the surface with the curvature radius below 20 μm. Meanwhile, variable laser fluences were applied to explore the evolution of cracks on commercial pure titanium with or without melt as spot overlap number increased. Experimental study was first performed at the peak laser fluence of 1.063 J/cm2 to investigate the microstructures induced only by cracks growth. The results demonstrated that angular microstructures with size between 1.68 μm and 4.74 μm was obtained and no nanostructure covered. Then, at the peak laser fluence of 2.126 J/cm2, there were some nanostructures covered on the melt-induced curved microstructured surface. However, surface molten material submerged in the most of cracks at the spot overlap number of 744, where the old cracks disappeared. The results indicated that there was too much molten material and melting time at the peak laser fluence of 2.126 J/cm2, which was not suitable for obtainment of perfect micro-nano structures. On this basis, peak laser fluence was reduced down to 1.595 J/cm2 and the sharp sub-5 μm microstructures with nanostructures covered was obtained at spot overlap number of 3720.

  6. Pure single-port laparoscopic distal gastrectomy for early gastric cancer: comparative study with multi-port laparoscopic distal gastrectomy.

    PubMed

    Ahn, Sang-Hoon; Son, Sang-Yong; Jung, Do Hyun; Park, Do Joong; Kim, Hyung-Ho

    2014-11-01

    The purpose of this study was to show the feasibility and safety of pure single-port laparoscopic distal gastrectomy (SDG) by comparing its short-term outcomes with those of conventional multiport totally laparoscopic distal gastrectomy (TLDG). Prospectively collected data of 50 gastric cancer patients who underwent pure SDG from November 2011 through October 2013 were compared with the matched data of 50 TLDG patients. Mean operation time (144.5 vs 140.3 minutes; p = 0.561) and number of harvested lymph nodes (51.7 ± 16.3 vs 52.4 ± 17.9; p = 0.836) were comparable. Estimated blood loss was lower in the SDG patients (50.5 ± 31.5 mL vs 87.5 ± 79.6 mL; p = 0.007). Postoperative recovery was faster in the SDG patients in terms of lower maximum pain score on the operative day (6.1 ± 1.4 vs 6.9 ± 1.5; p = 0.015) and postoperative day 1 (4.6 ± 1.0 vs 5.5 ± 1.4; p < 0.001), less use of parenteral analgesics (0.8 ± 1.0 vs 1.4 ± 1.0; p = 0.020), and less increase in C-reactive protein level on postoperative day 5 (4.57 ± 6.26 mg/L vs 8.51 ± 5.25 mg/L; p = 0.008). Postoperative morbidity occurred in 6 (12%) and 5 (10%) patients in the SDG and TLDG group, respectively. This study showed that pure SDG is both safe and feasible for early gastric cancer, with similar operation time and better short-term outcomes than TLDG in terms of postoperative pain, estimated blood loss, inflammatory reaction, and cosmetic result. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  7. A pure inorganic 1D chain based on {Mo8O28} clusters and Mn(II) ions: [Mn(H2O)2Mo8O28 ] n 6 n -

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaofen; Yan, Yonghong; Wu, Lizhou; Yu, Chengxin; Dong, Xinbo; Hu, Huaiming; Xue, Ganglin

    2016-01-01

    A new pure inorganic polymer, (NH4)6n[Mn(H2O)2Mo8O28)]n(H2O)2n(1), has been synthesized and characterized by elemental analyses, IR spectrum, UV-vis absorption spectra, TG-DSC and electrochemical studies. In 1, [Mo8O28]8- anions act as tetradentate ligands and are alternately linked by Mn(H2O)2 2 + ions into a one-dimensional chain structure. It is interesting that 1 represents the first example of pure inorganic-inorganic hybrid based on octamolybdate and transition metal ions. Moreover, it was indicated that 1 had definite catalytic activities on the probe reaction of benzyl alcohol oxidation to benzaldehyde with H2O2.

  8. Transnasal endoscopic evaluation of swallowing: a bedside technique to evaluate ability to swallow pureed diets in elderly patients with dysphagia.

    PubMed

    Sakamoto, Torao; Horiuchi, Akira; Nakayama, Yoshiko

    2013-08-01

    Endoscopic evaluation of swallowing (EES) is not commonly used by gastroenterologists to evaluate swallowing in patients with dysphagia. To use transnasal endoscopy to identify factors predicting successful or failed swallowing of pureed foods in elderly patients with dysphagia. EES of pureed foods was performed by a gastroenterologist using a small-calibre transnasal endoscope. Factors related to successful versus unsuccessful swallowing of pureed foods were analyzed with regard to age, comorbid diseases, swallowing activity, saliva pooling, vallecular residues, pharyngeal residues and airway penetration⁄aspiration. Unsuccessful swallowing was defined in patients who could not eat pureed foods at bedside during hospitalization. Logistic regression analysis was used to identify independent predictors of swallowing of pureed foods. During a six-year period, 458 consecutive patients (mean age 80 years [range 39 to 97 years]) were considered for the study, including 285 (62%) men. Saliva pooling, vallecular residues, pharyngeal residues and penetration⁄aspiration were found in 240 (52%), 73 (16%), 226 (49%) and 232 patients (51%), respectively. Overall, 247 patients (54%) failed to swallow pureed foods. Multivariate logistic regression analysis demonstrated that the presence of pharyngeal residues (OR 6.0) and saliva pooling (OR 4.6) occurred significantly more frequently in patients who failed to swallow pureed foods. Pharyngeal residues and saliva pooling predicted impaired swallowing of pureed foods. Transnasal EES performed by a gastroenterologist provided a unique bedside method of assessing the ability to swallow pureed foods in elderly patients with dysphagia.

  9. Transnasal endoscopic evaluation of swallowing: A bedside technique to evaluate ability to swallow pureed diets in elderly patients with dysphagia

    PubMed Central

    Sakamoto, Torao; Horiuchi, Akira; Nakayama, Yoshiko

    2013-01-01

    BACKGROUND: Endoscopic evaluation of swallowing (EES) is not commonly used by gastroenterologists to evaluate swallowing in patients with dysphagia. OBJECTIVE: To use transnasal endoscopy to identify factors predicting successful or failed swallowing of pureed foods in elderly patients with dysphagia. METHODS: EES of pureed foods was performed by a gastroenterologist using a small-calibre transnasal endoscope. Factors related to successful versus unsuccessful swallowing of pureed foods were analyzed with regard to age, comorbid diseases, swallowing activity, saliva pooling, vallecular residues, pharyngeal residues and airway penetration/aspiration. Unsuccessful swallowing was defined in patients who could not eat pureed foods at bedside during hospitalization. Logistic regression analysis was used to identify independent predictors of swallowing of pureed foods. RESULTS: During a six-year period, 458 consecutive patients (mean age 80 years [range 39 to 97 years]) were considered for the study, including 285 (62%) men. Saliva pooling, vallecular residues, pharyngeal residues and penetration/aspiration were found in 240 (52%), 73 (16%), 226 (49%) and 232 patients (51%), respectively. Overall, 247 patients (54%) failed to swallow pureed foods. Multivariate logistic regression analysis demonstrated that the presence of pharyngeal residues (OR 6.0) and saliva pooling (OR 4.6) occurred significantly more frequently in patients who failed to swallow pureed foods. CONCLUSIONS: Pharyngeal residues and saliva pooling predicted impaired swallowing of pureed foods. Transnasal EES performed by a gastroenterologist provided a unique bedside method of assessing the ability to swallow pureed foods in elderly patients with dysphagia. PMID:23936875

  10. Effects of a 6-month multimodal training intervention on retention of functional fitness in older adults: a randomized-controlled cross-over design.

    PubMed

    Gudlaugsson, Janus; Gudnason, Vilmundur; Aspelund, Thor; Siggeirsdottir, Kristin; Olafsdottir, Anna S; Jonsson, Palmi V; Arngrimsson, Sigurbjorn A; Harris, Tamara B; Johannsson, Erlingur

    2012-09-10

    Older adults have the highest rates of disability, functional dependence and use of healthcare resources. Training interventions for older individuals are of special interest where regular physical activity (PA) has many health benefits. The main purpose of this study was to assess the immediate and long-term effects of a 6-month multimodal training intervention (MTI) on functional fitness in old adults. For this study, 117 participants, 71 to 90 years old, were randomized in immediate intervention group and a control group (delayed intervention group). The intervention consisted of daily endurance and twice-a-week strength training. The method was based on a randomized-controlled cross-over design. Short Physical Performance Battery (SPPB), 8 foot up-and-go test, strength performance, six min walking test (6 MW), physical activity, BMI and quality of life were obtained at baseline, after a 6-month intervention- and control phase, again after 6-month crossover- and delayed intervention phase, and after anadditional 6-month follow-up. After 6 months of MTI, the intervention group improved in physical performance compared with the control group via Short Physical Performance Battery (SPPB) score (mean diff = 0.6, 95 % CI: 0.1, 1.0) and 8-foot up-and-go test (mean diff = -1.0 s, 95 % CI: -1.5, -0.6), and in endurance performance via 6-minute walking test (6 MW) (mean diff = 44.2 meters, 95 % CI: 17.1, 71.2). In strength performance via knee extension the intervention group improved while control group declined (mean diff = 55.0 Newton, 95 % CI: 28.4, 81.7), and also in PA (mean diff = 125.9 cpm, 95 % CI: 96.0, 155.8). Long-term effects of MTI on the particpants was assesed by estimating the mean difference in the variables measured between time-point 1 and 4: SPPB (1.1 points, 95 % CI: 0.8, 1.4); 8-foot up-and-go (-0.9 s, 95 % CI: -1.2, -0.6); 6 MW (18.7 m, 95 % CI: 6.5, 31.0); knee extension (4.2 Newton, 95 % CI: -10.0, 18.3); hand grip (6.7 Newton, 95 % CI: -4.4, 17

  11. Facile Isolation of Adsorbent-Free Long and Highly-Pure Chirality-Selected Semiconducting Single-Walled Carbon Nanotubes Using A Hydrogen-bonding Supramolecular Polymer.

    PubMed

    Toshimitsu, Fumiyuki; Nakashima, Naotoshi

    2015-12-14

    The ideal form of semiconducting-single-walled carbon nanotubes (sem-SWNTs) for science and technology is long, defect-free, chirality pure and chemically pure isolated narrow diameter tubes. While various techniques to solubilize and purify sem-SWNTs have been developed, many of them targeted only the chiral- or chemically-purity while sacrificing the sem-SWNT intrinsic structural identities by applying strong ultra-sonication and/or chemical modifications. Toward the ultimate purification of the sem-SWNTs, here we report a mild-conditioned extraction of the sem-SWNTs using removable supramolecular hydrogen-bonding polymers (HBPs) that are composed of dicarboxylic- or diaminopyridyl-fluorenes with ~70%-(8,6)SWNT selective extraction. Replacing conventional strong sonication techniques by a simple shaking using HPBs was found to provide long sem-SWNTs (>2.0 μm) with a very high D/G ratio, which was determined by atomic force microscopy observations. The HBPs were readily removed from the nanotube surfaces by an outer stimulus, such as a change in the solvent polarities, to provide chemically pure (8,6)-enriched sem-SWNTs. We also describe molecular mechanics calculations to propose possible structures for the HBP-wrapped sem-SWNTs, furthermore, the mechanism of the chiral selectivity for the sorted sem-SWNTs is well explained by the relationship between the molecular surface area and mass of the HBP/SWNT composites.

  12. Defense Mechanisms in "Pure" Anxiety and "Pure" Depressive Disorders.

    PubMed

    Colovic, Olga; Lecic Tosevski, Dusica; Perunicic Mladenovic, Ivana; Milosavljevic, Maja; Munjiza, Ana

    2016-10-01

    Our study was intended to test whether there are any differences in the way defense mechanisms are used by patients suffering from pure anxiety and those with pure depressive disorders. The sample size was as follows: depressive disorders without psychotic symptoms 30, anxiety disorders 30, and the healthy control group 30. The assessment of defense mechanisms was made using the DSQ-40 questionnaire. Our findings show that "pure" anxiety disorders differ from "pure" depressive disorders only in the use of immature defense mechanisms. The group with depressive disorders was significantly more prone to use immature defense mechanisms than the group with anxiety disorders (p = 0.005), primarily projection (p = 0.001) and devaluation (p = 0.003). These defense mechanisms may therefore be used both to differentiate between anxiety and depressive disorders and also to determine which symptoms (anxiety or depressive disorders) are dominant at any given stage of treatment.

  13. Facilitators of and Barriers to mHealth Adoption in Older Adults With Heart Failure.

    PubMed

    Cajita, Maan Isabella; Hodgson, Nancy A; Lam, Katherine Wai; Yoo, Sera; Han, Hae-Ra

    2018-05-04

    The purpose of this descriptive, exploratory study was to assess the perceptions of older adults with heart failure regarding the use of mobile technology and to identify potential facilitators of and barriers to mHealth adoption. Semistructured interviews were used to collect data. Transcripts were analyzed using qualitative content analysis. The findings indicated that older adults do not base their intention to use mHealth solely on perceived ease of use and perceived usefulness, as outlined in the Technology Acceptance Model. The following themes emerged from the content analysis: facilitators included previous experience with mobile technology, willingness to learn mHealth, ease of use, presence of useful features, adequate training, free equipment, and doctor's recommendation; barriers included lack of knowledge regarding how to use mHealth, decreased sensory perception, lack of need for technology, poorly designed interface, cost of technology, and limited/fixed income. Overall, the findings suggest that older adults are willing to use mobile health technology, albeit with reservations. Future researchers who seek to implement mHealth-based interventions should address person-related, technology-related, and contextual barriers, and simultaneously capitalize on the influence of potential facilitators, such as a physician's recommendation, to promote mHealth adoption.

  14. Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and Guidance.

    PubMed

    Mita, Sakura; de Monasterio-Schrader, Patricia; Fünfschilling, Ursula; Kawasaki, Takahiko; Mizuno, Hidenobu; Iwasato, Takuji; Nave, Klaus-Armin; Werner, Hauke B; Hirata, Tatsumi

    2015-11-01

    The function of mature neurons critically relies on the developmental outgrowth and projection of their cellular processes. It has long been postulated that the neuronal glycoproteins M6a and M6b are involved in axon growth because these four-transmembrane domain-proteins of the proteolipid protein family are highly enriched on growth cones, but in vivo evidence has been lacking. Here, we report that the function of M6 proteins is required for normal axonal extension and guidance in vivo. In mice lacking both M6a and M6b, a severe hypoplasia of axon tracts was manifested. Most strikingly, the corpus callosum was reduced in thickness despite normal densities of cortical projection neurons. In single neuron tracing, many axons appeared shorter and disorganized in the double-mutant cortex, and some of them were even misdirected laterally toward the subcortex. Probst bundles were not observed. Upon culturing, double-mutant cortical and cerebellar neurons displayed impaired neurite outgrowth, indicating a cell-intrinsic function of M6 proteins. A rescue experiment showed that the intracellular loop of M6a is essential for the support of neurite extension. We propose that M6 proteins are required for proper extension and guidance of callosal axons that follow one of the most complex trajectories in the mammalian nervous system. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Intonation Facilitates Contrast Resolution: Evidence from Japanese Adults and 6-Year Olds

    ERIC Educational Resources Information Center

    Ito, Kiwako; Jincho, Nobuyuki; Minai, Utako; Yamane, Naoto; Mazuka, Reiko

    2012-01-01

    Two eye-tracking experiments tested how pitch prominence on a prenominal adjective affects contrast resolution in Japanese adult and 6-year old listeners. Participants located two animals in succession on displays with multiple colored animals. In Experiment 1, adults' fixations to the contrastive target (pink cat [right arrow] GREEN cat) were…

  16. Herbicidal activity of pure compound isolated from rhizosphere inhabiting Aspergillus flavus.

    PubMed

    Khattak, Saeed Ullah; Lutfullah, Ghosia; Iqbal, Zafar; Rehman, Irshad Ur; Ahmad, Jamshaid; Khan, Abid Ali

    2018-05-01

    In the quest for bioactive natural products of fungal origin, Aspergillus flavus was isolated from rhizosphere of Mentha piperita using Potato Dextrose Agar (PDA) and Czapec Yeast Broth (CYB) nutrient media for metabolites production. In total, three different metabolites were purified using HPLC/LCMS and the structures were established using 500 Varian NMR experiments. Further the isolated metabolites in different concentrations (10, 100, 1000 μg/mL) were tested for herbicidal activity using Completely Randomized design (CRD) against the seeds of Silybum marianum and Avena fatua which are major threats to wheat crop in Pakistan. Among the isolated metabolites, one compound was found active against the test weed species whose activity is reported in the present work. The chemical name of the compound is 2-(1, 4-dihydroxybutan-2-yl)-1, 3-dihydroxy-6, 8-dimethoxyanthracene-9, 10(4aH, 9aH)-dione with mass of 388. Results showed that all seeds germinated in control treatment; however, with the metabolite treated, the growth was retarded to different levels in all parts of the weeds. At a dose of 1000 μg/mL of the pure compound, 100% seeds of S. marianum and 60% seeds of A. fatua were inhibited. Interestingly, the pure compound exhibited less inhibition of 10% towards the seeds of common wheat (Triticum aestivum).

  17. Rabbit Neonates and Human Adults Perceive a Blending 6-Component Odor Mixture in a Comparable Manner

    PubMed Central

    Sinding, Charlotte; Thomas-Danguin, Thierry; Chambault, Adeline; Béno, Noelle; Dosne, Thibaut; Chabanet, Claire; Schaal, Benoist; Coureaud, Gérard

    2013-01-01

    Young and adult mammals are constantly exposed to chemically complex stimuli. The olfactory system allows for a dual processing of relevant information from the environment either as single odorants in mixtures (elemental perception) or as mixtures of odorants as a whole (configural perception). However, it seems that human adults have certain limits in elemental perception of odor mixtures, as suggested by their inability to identify each odorant in mixtures of more than 4 components. Here, we explored some of these limits by evaluating the perception of three 6-odorant mixtures in human adults and newborn rabbits. Using free-sorting tasks in humans, we investigated the configural or elemental perception of these mixtures, or of 5-component sub-mixtures, or of the 6-odorant mixtures with modified odorants' proportion. In rabbit pups, the perception of the same mixtures was evaluated by measuring the orocephalic sucking response to the mixtures or their components after conditioning to one of these stimuli. The results revealed that one mixture, previously shown to carry the specific odor of red cordial in humans, was indeed configurally processed in humans and in rabbits while the two other 6-component mixtures were not. Moreover, in both species, such configural perception was specific not only to the 6 odorants included in the mixture but also to their respective proportion. Interestingly, rabbit neonates also responded to each odorant after conditioning to the red cordial mixture, which demonstrates their ability to perceive elements in addition to configuration in this complex mixture. Taken together, the results provide new insights related to the processing of relatively complex odor mixtures in mammals and the inter-species conservation of certain perceptual mechanisms; the results also revealed some differences in the expression of these capacities between species putatively linked to developmental and ecological constraints. PMID:23341948

  18. [Current anatomical and etiological aspects of chronic or subacute, surgical, pure mitral valve insufficiency in adults. Apropos of 75 medicosurgical cases].

    PubMed

    Penther, P; Boschat, J; Etienne, Y; Jobic, Y

    1991-04-01

    Seventy five medico-surgical cases (52 men, with a mean age at surgery of 59, and 23 women, with a mean age at surgery of 59) collected between 1983 and 1989, in an ethnically homogeneous and geographically stable population (West Brittany) confirmed that the current anatomical and etiological aspects of chronic (or subacute) pure mitral incompetence (MI) have changed radically. While rates for bacterial and ischemic etiologies remain stable, the share of rheumatic MI (14 cases) has fallen considerably, to the advantage of degenerative MI (51 cases) with a heavy male predominance (39 men) with in 33 cases rupture of the main chordae, and tending to affect the lesser mitral cusp more often. A precise diagnosis in terms of lesions and etiology is possible in almost all cases on the basis of clinical history and echocardiographic findings. In a perfectly homogeneous population, chronic surgical pure MI is currently essentially a male disease, of dystrophic origin, in patients in the 6th and 7th decades of life.

  19. Alcohol-dependent patients with comorbid phobic disorders: a comparison between comorbid patients, pure alcohol-dependent and pure phobic patients.

    PubMed

    Schadé, Annemiek; Marquenie, Loes A; Van Balkom, Anton J L M; Koeter, Maarten W J; De Beurs, Edwin; Van Den Brink, Wim; Van Dyck, Richard

    2004-01-01

    Patients with a double diagnosis of alcohol dependence and phobic disorders are a common phenomenon in both alcohol and anxiety disorder clinics. If we are to provide optimum treatment we need to know more about the clinical characteristics of this group of comorbid patients. To answer the following questions. (1). What are the clinical characteristics of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder? (2). Are alcohol dependence and other clinical characteristics of comorbid patients different from those of 'pure' alcohol-dependent patients? (3). Are the anxiety symptoms and other clinical characteristics of comorbid patients different from those of 'pure' phobic patients? Three groups of treatment-seeking patients were compared on demographic and clinical characteristics: alcohol dependent patients with a comorbid phobic disorder (n = 110), alcohol-dependent patients (n = 148) and patients with social phobia or agoraphobia (n = 106). In order to diagnose the comorbid disorders validly, the assessment took place at least 6 weeks after detoxification. Comorbid patients have high scores on depressive symptoms and general psychopathology: 25% of patients have a current and 52% a lifetime depressive disorder. The majority have no partner and are unemployed, they have a high incidence of other substance use (benzodiazepine, cocaine, cannabis) and a substantial proportion of comorbid patients have been emotionally, physically and sexually abused. They do not have a more severe, or different type of alcohol dependence or anxiety disorder than 'pure' alcohol-dependent patients and phobic patients respectively. Comorbid patients constitute a complex part of the treatment-seeking population in alcohol clinics and psychiatric hospitals. These findings should be taken into account when diagnosing and treating alcohol-dependent patients with a comorbid phobic disorder.

  20. Faithful teleportation with arbitrary pure or mixed resource states

    NASA Astrophysics Data System (ADS)

    Zhao, Ming-Jing; Li, Zong-Guo; Fei, Shao-Ming; Wang, Zhi-Xi; Li-Jost, Xianqing

    2011-05-01

    We study faithful teleportation systematically with arbitrary entangled states as resources. The necessary conditions of mixed states to complete perfect teleportation are proved. Based on these results, the necessary and sufficient conditions of faithful teleportation of an unknown state |phirang in { C}^d with an entangled resource ρ in { C}^m \\otimes { C}^d and { C}^d \\otimes { C}^n are derived. It is shown that for ρ in { C}^m \\otimes { C}^d, ρ must be a maximally entangled state, while for ρ in { C}^d \\otimes { C}^n, ρ must be a pure maximally entangled state. Moreover, we show that the sender's measurements must be all projectors of maximally entangled pure states. The relations between the entanglement of the formation of the resource states and faithful teleportation are also discussed.

  1. Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development.

    PubMed

    Kasowitz, Seth D; Ma, Jun; Anderson, Stephen J; Leu, N Adrian; Xu, Yang; Gregory, Brian D; Schultz, Richard M; Wang, P Jeremy

    2018-05-25

    The N6-methyladenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotes. The majority of m6A sites are found in the last exon and 3' UTRs. Here we show that the nuclear m6A reader YTHDC1 is essential for embryo viability and germline development in mouse. Specifically, YTHDC1 is required for spermatogonial development in males and for oocyte growth and maturation in females; Ythdc1-deficient oocytes are blocked at the primary follicle stage. Strikingly, loss of YTHDC1 leads to extensive alternative polyadenylation in oocytes, altering 3' UTR length. Furthermore, YTHDC1 deficiency causes massive alternative splicing defects in oocytes. The majority of splicing defects in mutant oocytes are rescued by introducing wild-type, but not m6A-binding-deficient, YTHDC1. YTHDC1 is associated with the pre-mRNA 3' end processing factors CPSF6, SRSF3, and SRSF7. Thus, YTHDC1 plays a critical role in processing of pre-mRNA transcripts in the oocyte nucleus and may have similar non-redundant roles throughout fetal development.

  2. Corrosion of pure aluminium and aluminium alloy: a comparative study using a slow positron beam

    NASA Astrophysics Data System (ADS)

    Wu, Y. C.; Li, P. H.; Xue, X. D.; Wang, S. J.; Kallis, A.; Coleman, P. G.; Zhai, T.

    2011-01-01

    Corrosion-related defects in pure Al and AA 2037 Al alloy have been investigated by positron beam-based Doppler broadening energy spectroscopy. Defect profiles have been analyzed by measuring the S parameter as a function of incident positron energy up to 30 keV. When pure Al samples are immersed in 1M NaOH for various times, a significant increase in the S parameter near the surface is observed. This implies that the corrosion process involves the creation of defects and nanometer voids. In contrast, a significant decrease in the S parameter is observed after the corrosion of water-quenched Al alloy by the same method, which is interpreted as being a result of Cu enrichment near the metal-oxide interface layer.

  3. Low level of efavirenz in HIV-1-infected Thai adults is associated with the CYP2B6 polymorphism.

    PubMed

    Sukasem, C; Manosuthi, W; Koomdee, N; Santon, S; Jantararoungtong, T; Prommas, S; Chamnanphol, M; Puangpetch, A; Sungkanuparph, S

    2014-06-01

    Human immunodeficiency virus type 1 (HIV-1) infections with a plasma efavirenz concentration of <1,000 ng/mL appear to have a high risk for the emergence of drug resistance. In the present study, we assessed the influence of the CYP2B6 polymorphism on the plasma efavirenz level. CYP2B6 T18492C (rs2279345) in 149 HIV-infected Thai adults were genotyped. Plasma efavirenz concentrations 12 h after dosing were measured using a validated high-performance liquid chromatography. The relationship between the plasma efavirenz level and the CYP2B6 T18492C polymorphism were analysed. Among the 149 patients, the frequency of T18492C heterozygous (T/C) and homozygous mutant (C/C) was 38.26 % (n = 57) and 6.04 % (n = 9), respectively. In the entire cohort, the median efavirenz plasma concentration was 2,410 ng/mL [interquartile range (IQR) 1,460-4,120 ng/mL]. The plasma efavirenz concentration for patients with 18492CC (1,200 ng/mL, IQR 1,050-1,990 ng/mL) or 18492TC (1,900 ng/mL, IQR 1,320-2,510 ng/mL) genotypes were significantly lower than those with homozygous wild type (3,380 ng/mL, IQR 2,040-5,660 ng/mL), P-value < 0.001. The CYP2B6 T18492C polymorphism was significantly associated with lower efavirenz concentrations compared to those with homozygous wild type in HIV-1 infections. The genetic polymorphism CYP2B6 T18492C may be useful for the optimised efavirenz dose. Further studies in the clinical setting will need to be conducted before such an approach can be recommended for widespread use.

  4. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    ClinicalTrials.gov

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  5. The 2001 January 13th M {W}7.7 and February 13th M {W}6.6 El Salvador Earthquakes: Deformation and Stress Triggering

    NASA Astrophysics Data System (ADS)

    Hreinsdóttir, S.; Freymueller, J. T.

    2001-12-01

    On the 13th of January 2001, an M {W} 7.7 normal fault earthquake occurred offshore El Salvador. The earthquake occurred in the subducting Cocos plate and was followed by high seismic activity and several earthquakes exceeding magnitude 5. On the 13th of February, an M {W} 6.6 strike slip earthquake occurred in the overriding Caribbean plate, about 75 km NNW from the epicenter of the large January earthquake. Deformation due to these earthquakes was observed at six continuous CORS GPS stations in Central America. In the M {W} 7.7 earthquake about 10 mm displacement was measured at GPS stations in El Salvador and Honduras. A smaller but significant dispacement was also observed at GPS stations in Nicaragua, more then 200 km from the earthquake's epicenter. In the M {W} 6.6 earthquake 41+/- 1 mm displacement in direction N111oE was measured at the GPS station in San Salvador, El Salvador. Other CORS GPS stations were not affected by that earthquake. A postsesmic signal is detectable at the San Salvador GPS station, strongest right after the earthquake and then decays. On average we see 0.3 +/- 0.1 mm/day of SSW motion of the station in the first twenty days following the earthquake. Using seismic and geodetic data, we calculated Coulomb stress changes following the January 13th, M {W} 7.7 earthquake. Of special interest were six 5.4 <= {M} {W}<=5.8 thrust events that presumably occurred on the interface between the Caribean and Cocos plate, and the M {W} 6.6 strike slip earthquake that occurred in the overriding Caribean plate. The location and focal mechanism of these earthquakes correlate with areas of calculated increase in static stress thus indicating stress triggering. The thrust events occurred 2 to 20 days after the M {W} 7.7 earthquake, in increasing distance from the M {W} 7.7 event with time.

  6. Differential effects of chronic overload-induced muscle hypertrophy on mTOR and MAPK signaling pathways in adult and aged rats

    USDA-ARS?s Scientific Manuscript database

    We examined activation of the mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signaling pathways in adult (Y; 6 mo old; n = 16) and aged (O; 30 mo old; n = 16) male rats (Fischer 344 x Brown Norway) subjected to chronic overload-induced muscle hypertrophy of the plan...

  7. Simplified Method to Isolate Highly Pure Canine Pancreatic Islets

    PubMed Central

    Woolcott, Orison O.; Bergman, Richard N.; Richey, Joyce M.; Kirkman, Erlinda L.; Harrison, L. Nicole; Ionut, Viorica; Lottati, Maya; Zheng, Dan; Hsu, Isabel R.; Stefanovski, Darko; Kabir, Morvarid; Kim, Stella P.; Catalano, Karyn J.; Chiu, Jenny D.; Chow, Robert H.

    2015-01-01

    Objectives The canine model has been used extensively to improve the human pancreatic islet isolation technique. At the functional level, dog islets show high similarity to human islets and thus can be a helpful tool for islet research. We describe and compare 2 manual isolation methods, M1 (initial) and M2 (modified), and analyze the variables associated with the outcomes, including islet yield, purity, and glucose-stimulated insulin secretion (GSIS). Methods Male mongrel dogs were used in the study. M2 (n = 7) included higher collagenase concentration, shorter digestion time, faster shaking speed, colder purification temperature, and higher differential density gradient than M1 (n = 7). Results Islet yield was similar between methods (3111.0 ± 309.1 and 3155.8 ± 644.5 islets/g, M1 and M2, respectively; P = 0.951). Pancreas weight and purity together were directly associated with the yield (adjusted R2 = 0.61; P = 0.002). Purity was considerably improved with M2 (96.7% ± 1.2% vs 75.0% ± 6.3%; P = 0.006). M2 improved GSIS (P = 0.021). Independently, digestion time was inversely associated with GSIS. Conclusions We describe an isolation method (M2) to obtain a highly pure yield of dog islets with adequate β-cell glucose responsiveness. The isolation variables associated with the outcomes in our canine model confirm previous reports in other species, including humans. PMID:21792087

  8. A case report of adult cerebellar high-grade glioma with H3.1 K27M mutation: a rare example of an H3 K27M mutant cerebellar tumor.

    PubMed

    Funata, Nobuaki; Nobusawa, Sumihito; Nakata, Satoshi; Yamazaki, Tatsuya; Takabagake, Kazuhiko; Koike, Tsukasa; Maegawa, Tatsuya; Yamada, Ryoji; Shinoura, Nobusada; Mine, Yutaka

    2018-01-01

    Diffuse midline glioma, H3 K27M mutant, is newly recognized as a distinct category, which usually arises in the brain stem, thalamus or spinal cord of children, and young adults. The oncogenic H3 K27M mutation involves H3.3 (encoded by H3F3A) or H3.1 (encoded by HIST1H3B/HIST1H3C), and the incidence of each mutation differs among the primary sites. Recently, several papers have reported that cerebellar high-grade gliomas in both children and adults also harbor H3 K27 mutation. With the exception of one pediatric case, all of the cases carried the mutation in H3.3. We herein present the case of an adult cerebellar high-grade astrocytic tumor with H3.1 K27M mutation in a 45-year-old man, which also involvedTP53 mutation and was immunonegative for ATRX. Some groups have reported that H3.3 and H3.1 K27M mutations define subgroups of diffuse intrinsic pontine gliomas (DIPGs) with different phenotypes as well as genetic alterations. On comparing the findings of the present case, particularly TP53 mutation status and ATRX expression, to the findings of the previous studies on DIPGs, our case seems unusual among the H3.1 K27M mutant subgroup. Further studies are needed to clarify the exact frequency, clinicopathological characteristics, and genomic alterations of cerebellar gliomas harboring H3 K27M mutation.

  9. Pure-quartic solitons

    PubMed Central

    Blanco-Redondo, Andrea; Martijn, de Sterke C.; Sipe, J.E.; Krauss, Thomas F.; Eggleton, Benjamin J.; Husko, Chad

    2016-01-01

    Temporal optical solitons have been the subject of intense research due to their intriguing physics and applications in ultrafast optics and supercontinuum generation. Conventional bright optical solitons result from the interaction of anomalous group-velocity dispersion and self-phase modulation. Here we experimentally demonstrate a class of bright soliton arising purely from the interaction of negative fourth-order dispersion and self-phase modulation, which can occur even for normal group-velocity dispersion. We provide experimental and numerical evidence of shape-preserving propagation and flat temporal phase for the fundamental pure-quartic soliton and periodically modulated propagation for the higher-order pure-quartic solitons. We derive the approximate shape of the fundamental pure-quartic soliton and discover that is surprisingly Gaussian, exhibiting excellent agreement with our experimental observations. Our discovery, enabled by precise dispersion engineering, could find applications in communications, frequency combs and ultrafast lasers. PMID:26822758

  10. Whole-body and multispectral photoacoustic imaging of adult zebrafish

    NASA Astrophysics Data System (ADS)

    Huang, Na; Xi, Lei

    2016-10-01

    Zebrafish is a top vertebrate model to study developmental biology and genetics, and it is becoming increasingly popular for studying human diseases due to its high genome similarity to that of humans and the optical transparency in embryonic stages. However, it becomes difficult for pure optical imaging techniques to volumetric visualize the internal organs and structures of wild-type zebrafish in juvenile and adult stages with excellent resolution and penetration depth. Even with the establishment of mutant lines which remain transparent over the life cycle, it is still a challenge for pure optical imaging modalities to image the whole body of adult zebrafish with micro-scale resolution. However, the method called photoacoustic imaging that combines all the advantages of the optical imaging and ultrasonic imaging provides a new way to image the whole body of the zebrafish. In this work, we developed a non-invasive photoacoustic imaging system with optimized near-infrared illumination and cylindrical scanning to image the zebrafish. The lateral and axial resolution yield to 80 μm and 600 μm, respectively. Multispectral strategy with wavelengths from 690 nm to 930 nm was employed to image various organs inside the zebrafish. From the reconstructed images, most major organs and structures inside the body can be precisely imaged. Quantitative and statistical analysis of absorption for organs under illumination with different wavelengths were carried out.

  11. Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's Option B+ Program: Results From the PURE Malawi Study.

    PubMed

    Hosseinipour, Mina; Nelson, Julie A E; Trapence, Clement; Rutstein, Sarah E; Kasende, Florence; Kayoyo, Virginia; Kaunda-Khangamwa, Blessings; Compliment, Kara; Stanley, Christopher; Cataldo, Fabian; van Lettow, Monique; Rosenberg, Nora E; Tweya, Hannock; Gugsa, Salem; Sampathkumar, Veena; Schouten, Erik; Eliya, Michael; Chimbwandira, Frank; Chiwaula, Levison; Kapito-Tembo, Atupele; Phiri, Sam

    2017-06-01

    In 2011, Malawi launched Option B+, a program of universal antiretroviral therapy (ART) treatment for pregnant and lactating women to optimize maternal health and prevent pediatric HIV infection. For optimal outcomes, women need to achieve HIVRNA suppression. We report 6-month HIVRNA suppression and HIV drug resistance in the PURE study. PURE study was a cluster-randomized controlled trial evaluating 3 strategies for promoting uptake and retention; arm 1: Standard of Care, arm 2: Facility Peer Support, and arm 3: Community Peer support. Pregnant and breastfeeding mothers were enrolled and followed according to Malawi ART guidelines. Dried blood spots for HIVRNA testing were collected at 6 months. Samples with ART failure (HIVRNA ≥1000 copies/ml) had resistance testing. We calculated odds ratios for ART failure using generalized estimating equations with a logit link and binomial distribution. We enrolled 1269 women across 21 sites in Southern and Central Malawi. Most enrolled while pregnant (86%) and were WHO stage 1 (95%). At 6 months, 950/1269 (75%) were retained; 833/950 (88%) had HIVRNA testing conducted, and 699/833 (84%) were suppressed. Among those with HIVRNA ≥1000 copies/ml with successful amplification (N = 55, 41% of all viral loads > 1000 copies/ml), confirmed HIV resistance was found in 35% (19/55), primarily to the nonnucleoside reverse transcriptase inhibitor class of drugs. ART failure was associated with treatment default but not study arm, age, WHO stage, or breastfeeding status. Virologic suppression at 6 months was <90% target, but the observed confirmed resistance rates suggest that adherence support should be the primary approach for early failure in option B+.

  12. [Allelopathic effects of the humus soils from Betula platyphylla and Quercus liaotungensis pure plantations on 9 kinds of common shrubs and herbs].

    PubMed

    Huang, Liang-Jia; Liu, Zeng-wen; Zhu, Bo-Chao; Bing, Yuan-Hao; Zhang, Xiao-Xi; Lü, Chen

    2014-06-01

    The humus soils were collected from Betula platyphylla and Quercus liaotungensis pure plantations and woodless land separately where the site conditions were basically the same, and taken as medium for potting culture test of 9 kinds of shrubs or herbs in plastic greenhouse to assess the allelopathic effects of humus soils of pure plantations on shrubs or herbs. Humus soils from B. platyphylla plantation significantly inhibited the seed germinations of Medicago sativa and Melilotus officinalis, decreased the catalase (CAT) activity of M. officinalis, Coronilla varia, M. sativa and Lespedeza davurica, and improved malondialdehyde (MDA) contents in seedlings of Caragana kor-shinskii, C. varia and Astragalus adsurgens. The biomass growths of C. varia, Amorpha fruticosa, M. sativa, M. officinalis and A. adsurgens in humus soils from B. platyphylla plantation were significantly decreased by 48.2%, 45.1%, 44.3%, 37.3% and 36.0%, respectively. In addition, humus soil of Q. liaotungensis plantation significantly decreased the germination rates of M. sativa and A. adsurgens, the chlorophyll contents of Vicia villosa, A. fruticosa and M. sativa, and improved malondialdehyde (MDA) contents in seedlings of Lespedeza davurica, Caragana korshinskii, M. officinalis and A. adsurgens. The biomass growths of A. adsurgens, M. sativa, M. officinalis and A. fruticosa were significantly decreased by 52.6% , 43.8%, 35.5% and 34.6%, respective- ly. B. platyphylla plantation humus soil had obvious inhibition effects on M. sativa, M. officinalis and A. fruticosa, while Q. liaotungensis plantation humus soil had obvious inhibition effects on M. sativa, A. adsurgens and A. fruticosa.

  13. Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development

    PubMed Central

    Leu, N. Adrian; Xu, Yang; Schultz, Richard M.

    2018-01-01

    The N6-methyladenosine (m6A) modification is the most prevalent internal RNA modification in eukaryotes. The majority of m6A sites are found in the last exon and 3’ UTRs. Here we show that the nuclear m6A reader YTHDC1 is essential for embryo viability and germline development in mouse. Specifically, YTHDC1 is required for spermatogonial development in males and for oocyte growth and maturation in females; Ythdc1-deficient oocytes are blocked at the primary follicle stage. Strikingly, loss of YTHDC1 leads to extensive alternative polyadenylation in oocytes, altering 3’ UTR length. Furthermore, YTHDC1 deficiency causes massive alternative splicing defects in oocytes. The majority of splicing defects in mutant oocytes are rescued by introducing wild-type, but not m6A-binding-deficient, YTHDC1. YTHDC1 is associated with the pre-mRNA 3’ end processing factors CPSF6, SRSF3, and SRSF7. Thus, YTHDC1 plays a critical role in processing of pre-mRNA transcripts in the oocyte nucleus and may have similar non-redundant roles throughout fetal development. PMID:29799838

  14. Comparative analysis of Six 3 and Six 6 distribution in the developing and adult mouse brain.

    PubMed

    Conte, Ivan; Morcillo, Julian; Bovolenta, Paola

    2005-11-01

    Six 3 and Six 6 genes are two closely related members of the Six/sine oculis family of homeobox containing transcription factors. Their expression and function at early stages of embryonic development has been widely addressed in a variety of species. However, their mRNA distribution during late embryonic, postnatal, and adult brain barely has been analyzed. Here, we show that despite their initial overlap in the anterior neural plate, the expression of Six 3 and Six 6 progressively segregates to different regions during mammalian brain development, maintaining only few areas of partial overlap in the thalamic and hypothalamic regions. Six 3, but not Six 6, is additionally expressed in the olfactory bulb, cerebral cortex, hippocampus, midbrain, and cerebellum. These distinct patterns support the idea that Six 3 and Six 6 are differentially required during forebrain development. Developmental Dynamics 234:718-725, 2005. (c) 2005 Wiley-Liss, Inc.

  15. Low temperature processing of ultra-pure cellulose fibers into nylon 6 and other thermoplastics

    Treesearch

    Rod Jacobson; Dan Caulfield; Karl Sears; John Underwood

    2002-01-01

    The objective of this research was to develop a stable process for compound ultra-pure cellulose fibers into polyamides. This has been a difficult procedure and has taken years of trial and error to understand the viscosity shear heating effects associated with compounding cellulose into high-melting point engineering thermoplastics. The evolution of the low...

  16. Teaching Adult Students Mathematical Investigations-6.

    ERIC Educational Resources Information Center

    Angiama, R. O.

    Teaching Adult Students Mathematical Investigation is based on the continuing research work carried out for the last ten years of teaching on the Foundation Course in Mathematics at Goldsmiths, University of London. Teaching Mathematical Investigation to adult students is a very challenging and often rewarding experience for adult educators as…

  17. A Comprehensive Assessment of the Effects of Transgenic Cry1Ac/Cry1Ab Rice Huahui 1 on Adult Micraspis discolor (Fabricius) (Coleoptera: Coccinellidae)

    PubMed Central

    Zhou, Xia; Guo, Yunling; Kong, Hua; Zuo, Jiao; Huang, Qixing; Jia, Ruizong; Guo, Anping; Xu, Lin

    2016-01-01

    Micraspis discolor (Fabricius) (Coleoptera: Coccinellidae) is a widely distributed coleoptera predator in southern Asia in rice ecosystem, and adult M. discolor feed on both rice pollen and soft-bodied arthropods. Bitrophic bioassay and tritrophic bioassay were conducted to evaluate the potential impact of Cry1Ac/Cry1Ab-expressing rice Huahui 1 and its non-transgenic counterpart Minghui 63 on fitness parameters of adult M. discolor. The results showed that the survival, and fecundity of this beetle’ adults were not different when they fed on Bt rice or non-Bt rice pollen or Nilaparvata lugens (Stål) reared on Bt rice or non-Bt rice. Toxicity assessment to ensure M. discolor adults were not sensitive to Cry1Ab or Cry1Ac protein independent from the pollen background, M. discolor adults were fed with an artificial diet containing Cry1Ac, Cry1Ab or both protein approximately 10 times higher concentration than in Huahui 1 rice pollen. No difference was detected for any of the life-table parameters tested between Cry protein-containing and pure diet. Artificial diet containing E-64 (N-(trans-Epoxysuccinyl)-L-leucine 4-guanidinobutylamide) was included as a positive control. In contrast, the pre-oviposition and fecundity of M. discolor were significantly adversely affected by feeding on E-64-containing diet. In both bioassays, the uptakes of Cry protein by adult M. discolor were tested by ELISA measurements. These results indicated that adults of M. discolor are not affected by Cry1Ab- or Cry1Ac-expressing rice pollen and are not sensitive to Cry protein at concentrations exceeding the levels in rice pollen in Huahui1. This suggests that M. discolor adults would not be harmed by Cry1Ac/Cry1Ab rice if Bt rice Huahui 1 were commercialized. PMID:26914608

  18. Structural Testing of a 6m Hypersonic Inflatable Aerodynamic Decelerator System

    NASA Technical Reports Server (NTRS)

    Swanson, G. T.; Kazemba, C. D.; Johnson, R. K.; Hughes, S. J.; Calomino, A. M.

    2015-01-01

    NASA is developing low ballistic coefficient technologies to support the Nations long-term goal of landing humans on Mars. Current entry, decent, and landing technologies are not practical for this class of payloads due to geometric constraints dictated by current and future launch vehicle fairing limitations. Hypersonic Inflatable Aerodynamic Decelerators (HIADs) are being developed to circumvent this limitation and are now considered a leading technology to enable landing of heavy payloads on Mars. At the beginning of 2014, a 6m diameter HIAD inflatable structure with an integrated flexible thermal protection system (TPS) was subjected to a static load test series to verify its structural performance under flight-relevant loads. The inflatable structure was constructed into a 60 degree sphere-cone configuration using nine inflatable torus segments composed of fiber-reinforced thin films. The inflatable tori were joined together using adhesives and high-strength textile woven structural straps. These straps help distribute the load throughout the inflatable structure. The 6m flexible TPS was constructed using multiple layers of high performance materials that are designed to protect the inflatable structure from heat loads that would be seen in flight during atmospheric entry. A custom test fixture was constructed to perform the static load test series. The fixture consisted of a round structural tub with enough height and width to allow for displacement of the HIAD test article as loads were applied. The bottom of the tub rim had an airtight seal with the floor. The rigid centerbody of the HIAD was mounted to a pedestal in the center of the structural tub. Using an impermeable membrane draped over the HIAD test article, an airtight seal was created with the top rim of the static load tub. This seal allowed partial vacuum to be pulled beneath the HIAD resulting in a uniform static pressure load applied to the outer surface. Using this technique, the test article

  19. Far-infrared laser diagnostics on the HT-6M tokamak

    NASA Astrophysics Data System (ADS)

    Gao, X.; Lu, H. J.; Guo, Q. L.; Wan, Y. X.; Tong, X. D.

    1995-01-01

    A multichannel far-infrared (FIR) hydrogen cyanide (HCN) laser interferometer was developed to measure plasma electron density profile on the HT-6M tokamak. The structure of the seven-channel FIR laser interferometer is described. The laser source used in the interferometer was a continuous-wave glow discharge HCN laser with a cavity length of 3.4 m and power output of about 100 mW at 337 μm. The detection sensitivity was 1/15 fringe with a temporal resolution of 0.1 ms. Experimental results were measured by the seven-channel FIR HCN laser interferometer with edge Ohmic heating, a pumping limiter, and ion cyclotron resonant heating on the HT-6M tokamak are reported.

  20. Physiological effects of positive pressure breathing with pure oxygen and a low oxygen gas mixture.

    PubMed

    Liu, Xiaopeng; Xiao, Huajun; Shi, Weiru; Wen, Dongqing; Yu, Lihua; Chen, Jianzhang

    2015-01-01

    Positive pressure breathing (PPB) can cause circulatory dysfunction due to peripheral pooling of blood. This study explored a better way at ground level to simulate pure oxygen PPB at 59,055 ft (18,000 m) by comparing the physiological changes during PPB with pure oxygen and low oxygen at ground level. Six subjects were exposed to 3 min of 69-mmHg PPB and 3 min of 59-mmHg PPB with pure oxygen and low oxygen while wearing the thoracic counterpressure jerkin inflated to 1× breathing pressure and G-suit inflated to 3 and 4× breathing pressure. Stroke volume (SV), cardiac output (CO), heart rate (HR), and peripheral oxygen saturation (Spo2) were measured. Subjects completed a simulating flying task (SFT) during 3-min PPB and scores were recorded. HR and SV responses differed significantly between breathing pure oxygen and low oxygen. CO response was not significantly different for pure oxygen and low oxygen, the two levels of PPB, and the two levels of G-suit pressure. Spo2 declined as a linear function of time during low-oxygen PPB and there was a significant difference in Spo2 response for the two levels of PPB. The average score of SFT during pure oxygen PPB was 3970.5 ± 1050.4, which was significantly higher than 2708.0 ± 702.7 with low oxygen PPB. Hypoxia and PPB have a synergistic negative effect on both the cardiovascular system and SFT performance. PPB with low oxygen was more appropriate at ground level to investigate physiological responses during PPB and evaluate the protective performance of garments. Liu X, Xiao H, Shi W, Wen D, Yu L, Chen J. Physiological effects of positive pressure breathing with pure oxygen and a low oxygen gas mixture.

  1. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring

    PubMed Central

    Rossini, Kamila Fernanda; de Oliveira, Camila Andrea; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-01-01

    Background The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. Results LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. Conclusion GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. PMID:28678925

  2. Magnetic ground states in the three O s6 + (5 d2 ) double perovskites B a2M Os O6 (M =Mg ,Zn,and Cd) from Néel order to its suppression

    NASA Astrophysics Data System (ADS)

    Marjerrison, C. A.; Thompson, C. M.; Sharma, A. Z.; Hallas, A. M.; Wilson, M. N.; Munsie, T. J. S.; Flacau, R.; Wiebe, C. R.; Gaulin, B. D.; Luke, G. M.; Greedan, J. E.

    2016-10-01

    Three closely related double perovskites (DP) based on the 5 d2 ion, O s6 +,B a2M Os O6 , with M =Mg , Zn, and Cd have been prepared and characterized using x-ray (XRD) and neutron diffraction (ND), dc magnetization, heat capacity, and muon spin relaxation (μ SR ) techniques. All three are cubic, Fm-3 m , at ambient temperature from XRD with Δ d /d ˜5 ×10-4 resolution. For both M =Mg and Zn, ND data at 3.5 K and lower, Δ d /d =2 ×10-3 , resolution show no signs of a distortion. The results are compared with the known DP material, B a2CaOs O6 , which shows antiferromagnetic (AF) order below TN=49 K and a moderate frustration index, f ˜4 , (f =| θCW|/ TN ), where θCW is the Curie-Weiss temperature. B a2MgOs O6 with a unit cell constant a0=8.0757 (1 ) Å , 3% smaller than for B a2CaOs O6 , also shows Néel order below TN=51 K with f ˜2 . However, B a2ZnOs O6,a0=8.0975 (1 ) Å , 0.27% larger than B a2MgOs O6 , does not show Néel order from either heat capacity or μ SR data. A zero field cooled/field cooled (ZFC/FC) irreversibility occurs near 30 K and a broad heat capacity anomaly is detected at a similar temperature. The μ SR data are consistent with a weak spin ordering with an onset below 28 K but with a coexisting dynamic component. B a2CdOs O6 with a0=8.3190 (1 ) Å , 0.5% smaller than B a2CaOs O6 , shows no evidence for any type of order/spin freezing to 0.47 K from any of the measurement techniques applied. The results for M =Zn and Cd appear to lie outside of the mean field theory of Chen and Balents [Phys. Rev. B 84, 094420 (2011), 10.1103/PhysRevB.84.094420] for cubic d2 DP with strong spin orbit coupling, but B a2MgOs O6 , along with B a2CaOs O6 , is likely one of the three predicted AF phases. The remarkable contrast between the doppelgänger pairs M =Mg /Zn and M =Ca /Cd may be traceable to differences in electronic structure of the diamagnetic M ions. All of the super-super exchange pathways in these DP materials involve Os-O-M -O-Os linkages.

  3. Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts

    PubMed Central

    Gurtan, Allan M.; Ravi, Arvind; Rahl, Peter B.; Bosson, Andrew D.; JnBaptiste, Courtney K.; Bhutkar, Arjun; Whittaker, Charles A.; Young, Richard A.; Sharp, Phillip A.

    2013-01-01

    MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to derepression of let-7 targets at levels that exceed 10-fold to 100-fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 (E3.5) and the induction of let-7 upon differentiation at E10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor-suppressive function. PMID:23630078

  4. Pulmonary Responses in Healthy Young Adults Exposed to Low Concentration of Ozone for 6.6 Hours with Mild Exercise

    EPA Science Inventory

    Rational: Recent studies have shown small but significant decreases in lung function following a prolonged exposure (6.6 hour) of healthy young adults to levels of ozone (0.08 ppm) near the current 8 hour standard. It is unclear, however, if such effects may be extended to concen...

  5. Pure-tone Audiometer

    NASA Astrophysics Data System (ADS)

    Kapul, A. A.; Zubova, E. I.; Torgaev, S. N.; Drobchik, V. V.

    2017-08-01

    The research focuses on a pure-tone audiometer designing. The relevance of the study is proved by high incidence of an auditory analyser in older people and children. At first, the article provides information about subjective and objective audiometry methods. Secondly, we offer block-diagram and basic-circuit arrangement of device. We decided to base on STM32F407VG microcontroller and use digital pot in the function of attenuator. Third, we implemented microcontroller and PC connection. C programming language is used for microcontroller’s program and PC’s interface. Fourthly, we created the pure-tone audiometer prototype. In the future, we will implement the objective method ASSR in addition to pure-tone audiometry.

  6. Prenatal diagnosis and molecular cytogenetic characterization of de novo pure partial trisomy 6p associated with microcephaly, craniosynostosis and abnormal maternal serum biochemistry.

    PubMed

    Chen, Chih-Ping; Chen, Ming; Chen, Chen-Yu; Chern, Schu-Rern; Wu, Peih-Shan; Chang, Shun-Ping; Kuo, Yu-Ling; Chen, Wen-Lin; Pan, Chen-Wen; Wang, Wayseen

    2014-02-25

    We present prenatal diagnosis and molecular cytogenetic characterization of de novo pure trisomy 6p22.3 → p25.3 encompassing BMP6 in a fetus associated with microcephaly and craniosynostosis on prenatal ultrasound, abnormal maternal serum biochemistry of a low PAPP-A level in the first-trimester combined test, and a karyotype of 46,XX,der(22)t(6;22)(p22.3;p13)dn. The present case demonstrates the usefulness of rapid prenatal identification of the origin of the extra chromosome material on the short arm of an acrocentric chromosome by spectral karyotyping, fluorescence in situ hybridization and array comparative genomic hybridization. We review the phenotypic abnormality of craniosynostosis in previously reported patients with partial trisomy 6p. We discuss the genotype-phenotype correlation of the involved gene of BMP6 in this case. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Corneal tissue ablation using 6.1 μm quantum cascade laser

    NASA Astrophysics Data System (ADS)

    Huang, Yong; Kang, Jin U.

    2012-03-01

    High absorption property of tissues in the IR range (λ> 2 μm) results in effective tissue ablation, especially near 3 μm. In the mid-infrared range, wavelengths of 6.1 μm and 6.45 μm fall into the absorption bands of the amide protein groups Amide-I and Amide-II, respectively. They also coincide with the deformation mode of water, which has an absorption peak at 6.1 μm. This coincidence makes 6.1 μm laser a better ablation tool that has promising effectiveness and minimum collateral damages than 3 μm lasers. In this work, we performed bovine corneal ablation test in-vitro using high-power 6.1μm quantum cascade laser (QCL) operated at pulse mode. Quantum cascade laser has the advantages of low cost, compact size and tunable wavelength, which makes it great alternative Mid-IR light source to conventional tunable free-electron lasers (FEL) for medical applications. Preliminary results show that effective corneal stroma craters were achieved with much less collateral damage in corneal tissue that contains less water. Future study will focus on optimizing the control parameters of QCL to attain neat and precise ablation of corneal tissue and development of high peak power QCL.

  8. Characterization of a 6×6-mm2 75-μm cell MPPC suitable for the Cherenkov Telescope Array project

    NASA Astrophysics Data System (ADS)

    Romeo, G.; Bonanno, G.; Garozzo, S.; Grillo, A.; Marano, D.; Munari, M.; Timpanaro, M. C.; Catalano, O.; Giarrusso, S.; Impiombato, D.; La Rosa, G.; Sottile, G.

    2016-08-01

    This paper presents the latest characterization results of a novel Low Cross-Talk (LCT) large-area (6×6-mm2) Multi-Pixel Photon Counter (MPPC) detector manufactured by Hamamatsu, belonging to the recent LCT5 family and achieving a fill-factor enhancement and cross-talk reduction. In addition, the newly adopted resin coating is demonstrated to yield improved photon detection capabilities in the 290-350 nm spectral range, making the new LCT MPPC particularly suitable for emerging applications like Cherenkov Telescopes. For a 3×3-mm2 version of the new MPPC under test, a comparative analysis of the large pixel pitch (75-μm) detector versus the smaller pixel pitch (50-μm) detector is also undertaken. Furthermore, measurements of the 6×6-mm2 MPPC response versus the angle of incidence are provided for the characterized device.

  9. Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation.

    PubMed

    Yoon, Sung-Han; Schmidt, Tobias; Bleiziffer, Sabine; Schofer, Niklas; Fiorina, Claudia; Munoz-Garcia, Antonio J; Yzeiraj, Ermela; Amat-Santos, Ignacio J; Tchetche, Didier; Jung, Christian; Fujita, Buntaro; Mangieri, Antonio; Deutsch, Marcus-Andre; Ubben, Timm; Deuschl, Florian; Kuwata, Shingo; De Biase, Chiara; Williams, Timothy; Dhoble, Abhijeet; Kim, Won-Keun; Ferrari, Enrico; Barbanti, Marco; Vollema, E Mara; Miceli, Antonio; Giannini, Cristina; Attizzani, Guiherme F; Kong, William K F; Gutierrez-Ibanes, Enrique; Jimenez Diaz, Victor Alfonso; Wijeysundera, Harindra C; Kaneko, Hidehiro; Chakravarty, Tarun; Makar, Moody; Sievert, Horst; Hengstenberg, Christian; Prendergast, Bernard D; Vincent, Flavien; Abdel-Wahab, Mohamed; Nombela-Franco, Luis; Silaschi, Miriam; Tarantini, Giuseppe; Butter, Christian; Ensminger, Stephan M; Hildick-Smith, David; Petronio, Anna Sonia; Yin, Wei-Hsian; De Marco, Federico; Testa, Luca; Van Mieghem, Nicolas M; Whisenant, Brian K; Kuck, Karl-Heinz; Colombo, Antonio; Kar, Saibal; Moris, Cesar; Delgado, Victoria; Maisano, Francesco; Nietlispach, Fabian; Mack, Michael J; Schofer, Joachim; Schaefer, Ulrich; Bax, Jeroen J; Frerker, Christian; Latib, Azeem; Makkar, Raj R

    2017-12-05

    Limited data exist about safety and efficacy of transcatheter aortic valve replacement (TAVR) in patients with pure native aortic regurgitation (AR). This study sought to compare the outcomes of TAVR with early- and new-generation devices in symptomatic patients with pure native AR. From the pure native AR TAVR multicenter registry, procedural and clinical outcomes were assessed according to VARC-2 criteria and compared between early- and new-generation devices. A total of 331 patients with a mean STS score of 6.7 ± 6.7 underwent TAVR. The early- and new-generation devices were used in 119 patients (36.0%) and 212 patients (64.0%), respectively. STS score tended to be lower in the new-generation device group (6.2 ± 6.7 vs. 7.6 ± 6.7; p = 0.08), but transfemoral access was more frequently used in the early-generation device group (87.4% vs. 60.8%; p < 0.001). Compared with the early-generation devices, the new-generation devices were associated with a significantly higher device success rate (81.1% vs. 61.3%; p < 0.001) due to lower rates of second valve implantation (12.7% vs. 24.4%; p = 0.007) and post-procedural AR ≥ moderate (4.2% vs. 18.8%; p < 0.001). There were no significant differences in major 30-day endpoints between the 2 groups. The cumulative rates of all-cause and cardiovascular death at 1-year follow-up were 24.1% and 15.6%, respectively. The 1-year all-cause mortality rate was significantly higher in the patients with post-procedural AR ≥ moderate compared with those with post-procedural AR ≤ mild (46.1% vs. 21.8%; log-rank p = 0.001). On multivariable analysis, post-procedural AR ≥ moderate was independently associated with 1-year all-cause mortality (hazard ratio: 2.85; 95% confidence interval: 1.52 to 5.35; p = 0.001). Compared with the early-generation devices, TAVR using the new-generation devices was associated with improved procedural outcomes in treating patients with pure native AR. In patients with pure native AR

  10. Can a pure vector gravitational wave mimic a pure tensor one?

    NASA Astrophysics Data System (ADS)

    Allen, Bruce

    2018-06-01

    In the general theory of relativity, gravitational waves have two possible polarizations, which are transverse and traceless with helicity ±2 . Some alternative theories contain additional helicity 0 and helicity ±1 polarization modes. Here, we consider a hypothetical "pure vector" theory in which gravitational waves have only two possible polarizations, with helicity ±1 . We show that if these polarizations are allowed to rotate as the wave propagates, then for certain source locations on the sky, the strain outputs of three ideal interferometric gravitational wave detectors can exactly reproduce the strain outputs predicted by general relativity.

  11. A new surfactant-introduction strategy for separating the pure single-phase of metal-organic frameworks.

    PubMed

    Zhao, Jun; Wang, Yenan; Dong, Wenwen; Wu, Yapan; Li, Dongsheng; Liu, Bin; Zhang, Qichun

    2015-06-11

    By introducing different surfactants into a reaction system, two previous mixed-phase Ni(II)-MOFs constructed from an undeveloped pyridyl-tetracarboxylate and Ni(II) salts were successfully isolated to obtain two pure products. Compound 1 exhibits a 3D H-bonded network with (3,8)-connected {4.5(2)}2{4(2).5(6).6(14).7(2).8(4)} topology, while 2 features a 3D 2-fold interpenetrating framework with a self-penetrating (3,4,4)-connected {6(2).10(3).12}{6(3)}2{6(4).8.10}2 topological net.

  12. [The corrosion of pure iron in five different mediums].

    PubMed

    Xu, Li; Zhu, Shengfa; Huang, Nan; Li, Xinchang; Zhang, Yu

    2009-08-01

    The sectional test was adopted in this study to investigate the corrosion of pure iron in 0.15 mol/L NaCl solution, Ringer solution, PBS(-) solution, SBF solution and M199 cell culture medium at three different times. The result shows that different mediums have different corrosion effects on pure iron. The arrangement according to the medium's corrosion ability from the strongest to weakest is 0.15 mol/L NaCl solution (Ringer solution), PBS(-) solution, SBF solution and M199 cell culture medium. The results of scanning electron microscopy and energy dispersive X-ray spectrum analyses show that the addition of HPO4(2-), H2POC4-, Ca2+, Mg2+, SO4(2-) and the organic component can inhibit the corrosion to some degree.

  13. Role of loop L5-6 connecting transmembrane segments M5 and M6 in biogenesis and functioning of yeast Pma1 H+-ATPase.

    PubMed

    Petrov, V V

    2015-01-01

    The L5-6 loop is a short extracytoplasmic stretch (714-DNSLDID) connecting transmembrane segments M5 and M6 and forming along with segments M4 and M8 the core through which cations are transported by H+-, Ca2+-, K+,Na+-, H+,K+-, and other P2-ATPases. To study structure-function relationships within this loop of the yeast plasma membrane Pma1 H+-ATPase, alanine- and cysteine-scanning mutagenesis has been employed. Ala and Cys substitutions for the most conserved residue (Leu717) led to complete block in biogenesis preventing the enzyme from reaching secretory vesicles. The Ala replacement at Asp714 led to five-fold decrease in the mutant expression and loss of its activity, while the Cys substitution blocked biogenesis completely. Replacements of other residues did not lead to loss of enzymatic activity. Additional replacements were made for Asp714 and Asp720 (Asp®Asn/Glu). Of the substitutions made at Asp714, only D714N partially restored the mutant enzyme biogenesis and functioning. However, all mutant enzymes with substituted Asp720 were active. The expressed mutants (34-95% of the wild-type level) showed activity high enough (35-108%) to be analyzed in detail. One of the mutants (I719A) had three-fold reduced coupling ratio between ATP hydrolysis and H+ transport; however, the I719C mutation was rather indistinguishable from the wild-type enzyme. Thus, substitutions at two of the seven positions seriously affected biogenesis and/or functioning of the enzyme. Taken together, these results suggest that the M5-M6 loop residues play an important role in protein stability and function, and they are probably responsible for proper arrangement of transmembrane segments M5 and M6 and other domains of the enzyme. This might also be important for the regulation of the enzyme.

  14. Pure laparoscopic hepatectomy in semiprone position for right hepatic major resection.

    PubMed

    Ikeda, Tetsuo; Mano, Yohei; Morita, Kazutoyo; Hashimoto, Naotaka; Kayashima, Hirohito; Masuda, Atsuro; Ikegami, Toru; Yoshizumi, Tomoharu; Shirabe, Ken; Maehara, Yoshihiko

    2013-02-01

    Pure laparoscopic liver resection is technically difficult for tumors located in the dorsal anterior and posterior sectors. We have developed a maneuver to perform pure laparoscopic hepatectomy in the semiprone position which was developed for resecting tumors located in these areas. The medical records have been reviewed retrospectively in 30 patients who underwent laparoscopic liver resection in the semiprone position for carcinoma in the dorsal anterior or posterior sectors of the right liver between 2008 and 2011. Seventeen liver tumors were primary liver tumors and 13 were colorectal metastases. Of the 30 patients, 11 (36.6 %) underwent major hepatectomy [right hemihepatectomy in 7 (23.3 %) and posterior sectionectomy in 4 (13.3 %)]. Anatomical minor resection, such as S6 or S7 segmentectomy, was performed in five patients (16.6 %). Five patients with liver metastasis underwent a simultaneous laparoscopic resection. There was no mortality, reoperation, or conversion to open procedures. There were no hepatectomy-related complications such as postoperative bleeding, bile leakage, or liver failure. Pure laparoscopic hepatectomy in the semiprone position for tumors present in the dorsal anterior and posterior sectors is feasible and safe. This method expands the indications for laparoscopic liver resection for tumors.

  15. Human herpesvirus 6 encephalitis followed by acute disseminated encephalomyelitis in an immunocompetent adult.

    PubMed

    Horie, Junichi; Suzuki, Keisuke; Nakamura, Toshiki; Okamura, Madoka; Iwasaki, Akio; Hirata, Koichi

    2017-04-28

    A 26-year-old, otherwise healthy man presented with visual abnormality followed by loss of consciousness and convulsion. The patient then developed headache and fever 14 days later. Brain MRI showed hyperintensities in the left cingulate cortex. The cerrebrospinal fluid examinations showed mononuclear pleocytosis and positive PCR results for human herpesvirus 6 (HHV-6). A diagnosis of HHV-6 encephalitis and symptomatic epilepsy was made. The patient's clinical symptoms improved promptly following acyclovir treatment. However, 3 months later the patient noticed dysesthesia in the trunk, the left upper limb and the right lower limb. Brain and spine MRI showed multiple brain white matter lesions, the middle cerebellar peduncle and cervical spinal lesions. The symptoms resolved following methylprednisolone pulse therapy only. We report an adult patient with HHV-6 encephalitis followed by acute disseminated encephalomyelitis whose initial presentation was epilepsy. HHV-6 encephalitis should be included in the differential diagnosis of encephalitis of unknown etiology in an immunocompetent adult.

  16. Sociodemographic factors associated with IgG and IgM seroprevalence for human cytomegalovirus infection in adult populations of Pakistan: a seroprevalence survey.

    PubMed

    Ibrahim, Saira; Siddiqui, Anwar A; Siddiqui, Amna R; Ahmed, Waquaruddin; Moss, Paul A H; Lalani, El-Nasir M A

    2016-10-22

    The seroprevalence of human cytomegalovirus (HCMV) infection ranges from 30 to 90 % in developed countries. Reliable estimates of HCMV seroprevalence are not available for Pakistan. This study determined the seroprevalence and sociodemographic factors associated with HCMV infection in adult populations of Karachi, Pakistan. A seroprevalence survey was conducted on 1000 adults, including residents of two semi-urban communities, and visitors to a government and a private hospital. Questionnaire-based interviews were conducted. Sera were analysed for HCMV-specific IgG and IgM. Chi-square or Fisher's exact test was used for comparing sociodemographic variables against seropositivity of HCMV-IgG or IgM. Multiple logistic regression modeling was performed for IgG seroprevalence and adjusted odds ratios were computed. The seroprevalence of HCMV-IgG and IgM was 93.2 and 4.3 % respectively. 95.3 % of individuals who were IgM seropositive were also seropositive for IgG. Around 6 % (15/250) of women of childbearing age remained uninfected and were therefore susceptible to primary infection. HCMV-IgG seroprevalence was associated with being female (p = 0.001), increasing age (p = 0.002) and crowding index (p = 0.003) and also with lower levels of both education (p < 0.001) and income (p = 0.008). Seroprevalence also differed significantly by marital status (p = 0.008) and sampling location (p < 0.001). A logistic regression model for HCMV-IgG seroprevalence showed associations with being female (OR = 1.89; 95 % CI: 1.10-3.25), increasing age (OR = 3.95; 95 % CI: 1.79-8.71) and decreasing income (OR = 0.72; 95 % CI: 0.54-0.96). A strong association was observed between increased seroprevalence of HCMV-IgM and decreasing household size (p = 0.008). Seroprevalence of HCMV is very high in Pakistan, although 6 % of women of childbearing age remain at risk of primary infection. The IgM seropositivity observed in some individuals

  17. Detecting voids in a 0.6 m coal seam, 7 m deep, using seismic reflection

    USGS Publications Warehouse

    Miller, R.D.; Steeples, D.W.

    1991-01-01

    Surface collapse over abandoned subsurface coal mines is a problem in many parts of the world. High-resolution P-wave reflection seismology was successfully used to evaluate the risk of an active sinkhole to a main north-south railroad line in an undermined area of southeastern Kansas, USA. Water-filled cavities responsible for sinkholes in this area are in a 0.6 m thick coal seam, 7 m deep. Dominant reflection frequencies in excess of 200 Hz enabled reflections from the coal seam to be discerned from the direct wave, refractions, air wave, and ground roll on unprocessed field files. Repetitive void sequences within competent coal on three seismic profiles are consistent with the "room and pillar" mining technique practiced in this area near the turn of the century. The seismic survey showed that the apparent active sinkhole was not the result of reactivated subsidence but probably erosion. ?? 1991.

  18. Electron Acoustic Waves in Pure Ion Plasmas

    NASA Astrophysics Data System (ADS)

    Anderegg, F.; Driscoll, C. F.; Dubin, D. H. E.; O'Neil, T. M.

    2009-11-01

    Electron Acoustic Waves (EAW) are the low frequency branch of electrostatic plasma waves. These waves exist in neutralized plasmas, pure electron plasmas and in pure ion plasmasfootnotetextF. Anderegg et al., PRL 102, 095001 (2009) and PoP 16, 055705 (2009). (where the name is deceptive). Here, we observe standing mθ= 0 mz= 1 EAWs in a pure ion plasma column. At small amplitude, the EAWs have a phase velocity vph ˜1.4 v, and the frequencies are in close agreement with theory. At moderate amplitudes, waves can be excited over a broad range of frequencies, with observed phase velocities in the range of 1.4 v <=vph <=2.1 v. This frequency variability comes from the plasma adjusting its velocity distribution so as to make the EAW resonant with the drive frequency. Our wave-coherent laser-induced fluorescence diagnostic shows that particles slower than vph oscillate in phase with the wave, while particles moving faster than vph oscillate 180^o out of phase with the wave. From a fluid perspective, this gives an unusual negative dynamical compressibility. That is, the wave pressure oscillations are 180^o out of phase from the density oscillations, almost fully canceling the electrostatic restoring force, giving the low and malleable frequency.

  19. M.S.A.D. 11 Adult Education for the Handicapped.

    ERIC Educational Resources Information Center

    Dulac, G. Paul; McCarthy, William F.

    Intended as a guide for implementation of an educational program for handicapped adults, this manual discusses essential components for an educational developmental disabilities program using an adult education delivery system. Materials are based on efforts of the MSAD (Maine School Administrative District) #11 to offer educational programming to…

  20. Diagnosing pure-electron plasmas with internal particle flux probes.

    PubMed

    Kremer, J P; Pedersen, T Sunn; Marksteiner, Q; Lefrancois, R G; Hahn, M

    2007-01-01

    Techniques for measuring local plasma potential, density, and temperature of pure-electron plasmas using emissive and Langmuir probes are described. The plasma potential is measured as the least negative potential at which a hot tungsten filament emits electrons. Temperature is measured, as is commonly done in quasineutral plasmas, through the interpretation of a Langmuir probe current-voltage characteristic. Due to the lack of ion-saturation current, the density must also be measured through the interpretation of this characteristic thereby greatly complicating the measurement. Measurements are further complicated by low densities, low cross field transport rates, and large flows typical of pure-electron plasmas. This article describes the use of these techniques on pure-electron plasmas in the Columbia Non-neutral Torus (CNT) stellarator. Measured values for present baseline experimental parameters in CNT are phi(p)=-200+/-2 V, T(e)=4+/-1 eV, and n(e) on the order of 10(12) m(-3) in the interior.

  1. Mixtures of maximally entangled pure states

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Flores, M.M., E-mail: mflores@nip.up.edu.ph; Galapon, E.A., E-mail: eric.galapon@gmail.com

    We study the conditions when mixtures of maximally entangled pure states remain entangled. We found that the resulting mixed state remains entangled when the number of entangled pure states to be mixed is less than or equal to the dimension of the pure states. For the latter case of mixing a number of pure states equal to their dimension, we found that the mixed state is entangled provided that the entangled pure states to be mixed are not equally weighted. We also found that one can restrict the set of pure states that one can mix from in order tomore » ensure that the resulting mixed state is genuinely entangled. Also, we demonstrate how these results could be applied as a way to detect entanglement in mixtures of the entangled pure states with noise.« less

  2. A complex mTOR response in habituation paradigms for a social signal in adult songbirds.

    PubMed

    Ahmadiantehrani, Somayeh; Gores, Elisa O; London, Sarah E

    2018-06-01

    Nonassociative learning is considered simple because it depends on presentation of a single stimulus, but it likely reflects complex molecular signaling. To advance understanding of the molecular mechanisms of one form of nonassociative learning, habituation, for ethologically relevant signals we examined song recognition learning in adult zebra finches. These colonial songbirds learn the unique song of individuals, which helps establish and maintain mate and other social bonds, and informs appropriate behavioral interactions with specific birds. We leveraged prior work demonstrating behavioral habituation for individual songs, and extended the molecular framework correlated with this behavior by investigating the mechanistic Target of Rapamycin (mTOR) signaling cascade. We hypothesized that mTOR may contribute to habituation because it integrates a variety of upstream signals and enhances associative learning, and it crosstalks with another cascade previously associated with habituation, ERK/ZENK. To begin probing for a possible role for mTOR in song recognition learning, we used a combination of song playback paradigms and bidirectional dysregulation of mTORC1 activation. We found that mTOR demonstrates the molecular signatures of a habituation mechanism, and that its manipulation reveals the complexity of processes that may be invoked during nonassociative learning. These results thus expand the molecular targets for habituation studies and raise new questions about neural processing of complex natural signals. © 2018 Ahmadiantehrani et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Postnatal Day 2 to 11 Constitutes a 5-HT-Sensitive Period Impacting Adult mPFC Function

    PubMed Central

    Rebello, Tahilia J.; Yu, Qinghui; Goodfellow, Nathalie M.; Caffrey Cagliostro, Martha K.; Teissier, Anne; Morelli, Emanuela; Demireva, Elena Y.; Chemiakine, Alexei; Rosoklija, Gorazd B.; Dwork, Andrew J.; Lambe, Evelyn K.; Ansorge, Mark S.

    2014-01-01

    Early-life serotonin [5-hydroxytryptamine (5-HT)] signaling modulates brain development, which impacts adult behavior, but 5-HT-sensitive periods, neural substrates, and behavioral consequences remain poorly understood. Here we identify the period ranging from postnatal day 2 (P2) to P11 as 5-HT sensitive, with 5-HT transporter (5-HTT) blockade increasing anxiety- and depression-like behavior, and impairing fear extinction learning and memory in adult mice. Concomitantly, P2–P11 5-HTT blockade causes dendritic hypotrophy and reduced excitability of infralimbic (IL) cortex pyramidal neurons that normally promote fear extinction. By contrast, the neighboring prelimbic (PL) pyramidal neurons, which normally inhibit fear extinction, become more excitable. Excitotoxic IL but not PL lesions in adult control mice reproduce the anxiety-related phenotypes. These findings suggest that increased 5-HT signaling during P2–P11 alters adult mPFC function to increase anxiety and impair fear extinction, and imply a differential role for IL and PL neurons in regulating affective behaviors. Together, our results support a developmental mechanism for the etiology and pathophysiology of affective disorders and fear-related behaviors. PMID:25209278

  4. Prevalence of Thalassemia and Glucose-6-Phosphate Dehydrogenase Deficiency in Newborns and Adults at the Ramathibodi Hospital, Bangkok, Thailand.

    PubMed

    Banyatsuppasin, Wansa; Jindadamrongwech, Sumalee; Limrungsikul, Anchalee; Butthep, Punnee

    Thalassemias and glucose-6-phosphate dehydrogenase (G6PD) deficiency are the most common inherited blood disorders. They are distributed among populations living in malaria endemic regions resulting in survival advantage from severe malaria disease. The aims of this study were to analyze the prevalence of thalassemias and G6PD deficiency at the Ramathibodi Hospital, Bangkok, Thailand. A total of 616 adult and 174 cord blood samples were collected and analyzed for red blood cell (RBC) parameters, hemoglobin (Hb) typing and DNA analysis for G6PD mutations and α-thalassemia (α-thal). The two most prominent types of thalassemia were heterozygous Hb E (HBB: c.79G>A), (19.5% in newborns and 35.6% in adults) followed by heterozygous α-thal-2 [-α 3.7 (rightward) deletion] at 18.7% in newborns and 19.5% in adults. After performing G6PD genotyping using multiplex amplification refractory mutation system-polymerase chain reaction (multiplex ARMS-PCR) for 10 G6PD mutations, the prevalence of G6PD mutation was found in 12.0% of newborns and 11.7% of adults. The G6PD Viangchan [871 (G>A)] is the most common G6PD mutation in newborns (42.9%) and adults (52.8%). In addition, coinheritance of various types of thalassemia with G6PD deficiency were found. The results indicated that heterozygous Hb E and G6PD Viangchan are predominant both in newborns and adults in this study.

  5. A randomised controlled trial of face to face versus pure online self-help cognitive behavioural treatment for perfectionism.

    PubMed

    Egan, Sarah J; van Noort, Emily; Chee, Abby; Kane, Robert T; Hoiles, Kimberley J; Shafran, Roz; Wade, Tracey D

    2014-12-01

    Previous research has shown cognitive-behavioural treatment (CBT) to be effective in reducing perfectionism. The present study investigated the efficacy of two formats of CBT for perfectionism (CBT-P), face-to-face and pure online self-help, in reducing perfectionism and associated psychological symptoms. Participants were randomly allocated to face-to-face CBT-P (n = 18), pure online self-help CBT-P (n = 16), or a waitlist control period (n = 18). There was no significant change for the waitlist group on any of the outcome measures at the end of treatment. Both the face-to-face and pure online self-help groups reported significant reductions at the end of treatment for the perfectionism variables which were maintained at the 6-month follow-up. The face-to-face group also reported significant reductions over this time in depression, anxiety, and stress, and a significant pre-post increase in self-esteem, all of which were maintained at the 6-month follow-up. In contrast, the pure online self-help group showed no significant changes on these outcomes. The face-to-face group was statistically superior to the pure online self-help group at follow-up on the perfectionism measures, concern over mistakes and personal standards. The results show promising evidence for CBT for perfectionism, especially when offered face to face, where sustained benefit across a broad range of outcomes can be expected. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  6. Use of pure glycerol in fattening heavy pigs.

    PubMed

    Della Casa, G; Bochicchio, D; Faeti, V; Marchetto, G; Poletti, E; Rossi, A; Garavaldi, A; Panciroli, A; Brogna, N

    2009-01-01

    Eighty Italian Duroc×Italian Large White pigs (BW 42.6±3.37kg) were used to determine the effects of pure glycerol on growth performance and meat quality of heavy pigs. Pigs were divided into five groups receiving 0% (control), 5% or 10% during the growing and finishing phases (42.6-160kg BW) (G+F5,G+F10) or 5% or 10% during the finishing period (100-160kg BW) (FIN5,FIN10) of pure glycerol in substitution for maize meal (on a dry matter basis). The pigs were slaughtered at approximately 160kg BW. The growth performance of pigs fed 5% glycerol did not differ from controls regardless of feeding duration, whereas those fed 10% glycerol showed reduced growth and poorer feed:gain ratio. Fat quality and meat suitability for raw ham curing were not affected by dietary treatment. Differences were not consistent enough to draw any conclusion about the effects of feeding glycerol on sensory characteristics.

  7. Creation of Optically Pure Crystals from a Meso-Type Gold(I) Metalloligand with d- and l-Amino Acids: A Coordination Trick.

    PubMed

    Itai, Takuma; Kojima, Tatsuhiro; Kuwamura, Naoto; Konno, Takumi

    2017-11-21

    A unique example of a coordination system that creates optically pure crystals from a meso compound with d- and l-amino acids is reported. The 1:1 reaction of a newly prepared meso digold(I) complex, [Au 2 (dcpe)(d-Hpen)(l-Hpen)] ([H 2 1]), with Co(OAc) 2 under aerobic conditions yielded a cationic Au I 2 Co III trinuclear complex, [Au 2 Co(dcpe)(d-pen)(l-pen)] + [2] + , in which [1] 2- acts as a hexadentate-N 2 ,O 2 ,S 2 metalloligand to a Co III center. Similar reactions with M(OAc) 2 (M=Ni and Zn) produced analogous but neutral Au I 2 M II complexes, [Au 2 M(dcpe)(d-pen)(l-pen)] ([3 M ]). Complexes [2] + and [3 M ] are chiral (C vs. A) at the octahedral Co III and M II centers due to the arrangement of the N 2 ,O 2 ,S 2 donor set. In addition, through spontaneous resolution, [3 M ] gave optically pure C-[3 M ] and A-[3 M ] crystals, showing the creation of homochirality from meso-[1] 2- and achiral M 2+ through crystallization. Such a phenomenon was not observed for [2] + , which gave a racemic compound containing both C-[2] + and A-[2] + . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Pure Air`s Bailly scrubber: A four-year retrospective

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Manavi, G.B.; Vymazal, D.C.; Sarkus, T.A.

    1997-12-31

    Pure Air`s Advanced Flue Gas Desulfurization (AFGD) Clean Coal Project has completed four highly successful years of operation at NIPSCO`s Bailly Station. As part of their program, Pure Air has concluded a six-part study of system performance. This paper summarizes the results of the demonstration program, including AFGD performance on coals ranging from 2.0--2.4% sulfur. The paper highlights novel aspects of the Bailly facility, including pulverized limestone injection, air rotary sparger for oxidation, wastewater evaporation system and the production of PowerChip{reg_sign} gypsum. Operations and maintenance which have led to the facility`s notable 99.47% availability record are also discussed. A projectmore » company, Pure Air on the Lake Limited Partnership, owns the AFGD facility. Pure Air was the turn key contractor and Air Products and Chemicals, Inc. is the operator of the AFGD system.« less

  9. Altered soleus responses to magnetic stimulation in pure cerebellar ataxia.

    PubMed

    Kurokawa-Kuroda, Tomomi; Ogata, Katsuya; Suga, Rie; Goto, Yoshinobu; Taniwaki, Takayuki; Kira, Jun-Ichi; Tobimatsu, Shozo

    2007-06-01

    Transcranial magnetic stimulation (TMS) over the leg motor area elicits a soleus primary response (SPR) and a soleus late response (SLR). We evaluated the influence of the cerebellofugal pathway on the SPR and SLR in patients with 'pure' cerebellar ataxia. SPRs and SLRs were recorded from 11 healthy subjects and 9 patients with 'pure' cerebellar cortical degeneration; 5 with spinocerebellar ataxia type 6 (SCA6), and 4 with late cortical cerebellar ataxia (LCCA). In addition, three patients with localized cerebellar lesions were tested. The SPR latency was significantly longer in patients than in controls, but primary responses in the tibialis anterior muscle were normal. The frequency of abnormal SLR was 38.9% in the supine position and 83.3% in the standing position. Two out of three patients with localized cerebellar lesions also showed abnormal SLR. Altered SPRs in patients may result from a dysfunction of the primary motor cortex caused by crossed cerebello-cerebral diaschisis. In addition, our results suggest that 'pure' cerebellar degeneration involves the mechanism responsible for evoking SLR which is related to the control of posture. SLR can be a useful neurophysiological parameter for evaluating cerebellofugal function.

  10. m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.

    PubMed

    Liu, Jiqin; Ren, Dangli; Du, Zhenhua; Wang, Hekong; Zhang, Hua; Jin, Ying

    2018-08-25

    N 6 -Methyladenosine (m 6 A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m 6 A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m 6 A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m 6 A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m 6 A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m 6 A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Phosphorylation of FMRP and alterations of FMRP complex underlie enhanced mLTD in adult rats triggered by early life seizures.

    PubMed

    Bernard, Paul B; Castano, Anna M; O'Leary, Heather; Simpson, Kameron; Browning, Michael D; Benke, Tim A

    2013-11-01

    Outside of Fragile X syndrome (FXS), the role of Fragile-X Mental Retardation Protein (FMRP) in mediating neuropsychological abnormalities is not clear. FMRP, p70-S6 kinase (S6K) and protein phosphatase 2A (PP2A) are thought to cooperate as a dynamic signaling complex. In our prior work, adult rats have enhanced CA1 hippocampal long-term depression (LTD) following an early life seizure (ELS). We now show that mGluR-mediated LTD (mLTD) is specifically enhanced following ELS, similar to FMRP knock-outs. Total FMRP expression is unchanged but S6K is hyperphosphorylated, consistent with S6K overactivation. We postulated that either disruption of the FMRP-S6K-PP2A complex and/or removal of this complex from synapses could explain our findings. Using subcellular fractionation, we were surprised to find that concentrations of FMRP and PP2A were undisturbed in the synaptosomal compartment but reduced in parallel in the cytosolic compartment. Following ELS FMRP phosphorylation was reduced in the cytosolic compartment and increased in the synaptic compartment, in parallel with the compartmentalization of S6K activation. Furthermore, FMRP and PP2A remain bound following ELS. In contrast, the interaction of S6K with FMRP is reduced by ELS. Blockade of PP2A results in enhanced mLTD; this is occluded by ELS. This suggests a critical role for the location and function of the FMRP-S6K-PP2A signaling complex in limiting the amount of mLTD. Specifically, non-synaptic targeting and the function of the complex may influence the "set-point" for regulating mLTD. Consistent with this, striatal-enriched protein tyrosine phosphatase (STEP), an FMRP "target" which regulates mLTD expression, is specifically increased in the synaptosomal compartment following ELS. Further, we provide behavioral data to suggest that FMRP complex dysfunction may underlie altered socialization, a symptom associated and observed in other rodent models of autism, including FXS. © 2013.

  12. Polarized spectral properties and 1.5-1.6 μm laser operation of Er:Sr3Yb2(BO3)4 crystal

    NASA Astrophysics Data System (ADS)

    Lin, F. L.; Huang, J. H.; Chen, Y. J.; Gong, X. H.; Lin, Y. F.; Luo, Z. D.; Huang, Y. D.

    2013-10-01

    Undoped and Er3+-doped Sr3Yb2(BO3)4 crystals were grown by the Czochralski method. Room temperature polarized spectral properties of the Er:Sr3Yb2(BO3)4 crystal were investigated. The efficiency of the energy transfer from Yb3+ to Er3+ ions in this crystal was calculated to be about 95%. End-pumped by a diode laser at 970 nm in a hemispherical cavity, a 0.75 W quasi-CW laser at 1.5-1.6 μm with a slope efficiency of 7% and an absorbed pump threshold of 3.8 W was achieved in a 0.5-mm-thick Z-cut crystal glued on a 5-mm-thick pure YAG crystal with UV-curable adhesive.

  13. Multiple lipopolysaccharide (LPS) injections alter interleukin 6 (IL-6), IL-7, IL-10 and IL-6 and IL-7 receptor mRNA in CNS and spleen.

    PubMed

    Szot, Patricia; Franklin, Allyn; Figlewicz, Dianne P; Beuca, Timothy Petru; Bullock, Kristin; Hansen, Kim; Banks, William A; Raskind, Murray A; Peskind, Elaine R

    2017-07-04

    Neuroinflammation is proposed to be an important component in the development of several central nervous system (CNS) disorders including depression, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, exactly how neuroinflammation leads to, or contributes to, these central disorders is unclear. The objective of the study was to examine and compare the expression of mRNAs for interleukin-6 (IL-6), IL-7, IL-10 and the receptors for IL-6 (IL-6R) and IL-7 (IL-7R) using in situ hybridization in discrete brain regions and in the spleen after multiple injections of 3mg/kg lipopolysaccharide (LPS), a model of neuroinflammation. In the spleen, LPS significantly elevated IL-6 mRNA expression, then IL-10 mRNA, with no effect on IL-7 or IL-7R mRNA, while significantly decreasing IL-6R mRNA expression. In the CNS, LPS administration had the greatest effect on IL-6 and IL-6R mRNA. LPS increased IL-6 mRNA expression only in non-neuronal cells throughout the brain, but significantly elevated IL-6R mRNA in neuronal populations, where observed, except the cerebellum. LPS resulted in variable effects on IL-10 mRNA, and had no effect on IL-7 or IL-7R mRNA expression. These studies indicate that LPS-induced neuroinflammation has substantial but variable effects on the regional and cellular patterns of CNS IL-6, IL-7 and IL-10, and for IL-6R and IL-7R mRNA expression. It is apparent that administration of LPS can affect non-neuronal and neuronal cells in the brain. Further research is required to determine how CNS inflammatory changes associated with IL-6, IL-10 and IL-6R could in turn contribute to the development of CNS neurological disorders. Published by Elsevier Ltd.

  14. On the Search for Mid-IR and Pure Rotational H3+ Emission in Jupiter's Northern Aurora

    NASA Astrophysics Data System (ADS)

    Trafton, Laurence M.; Miller, Steve; Lacy, John H.; Greathouse, Thomas K.

    2017-06-01

    The first identification of astronomical spectral emission from the H3+ ion was made in Jupiter’s southern auroral region in the first overtone band near 2 μm (Drossart et al. 1989; Nature 340, 539). Trafton et al. (1989; ApJ 343, L73) also detected H3+ emission from this band near each of Jupiter’s auroral poles, but without identifying it. Shortly thereafter, Maillard et al (1990; ApJ 363, L37) detected the fundamental band emission near 4 μm. In order to determine the non-LTE column abundance of H3+, which is Jupiter’s primary ionospheric coolant, we searched in 2001-2002, initially above 10 μm, for emission lines from the H3+ pure rotational and ν1 -> ν2 difference band. This was done near the northern auroral “hot spot” at System III longitude 180 deg based on predicted theoretical frequencies. The results were reported by Trafton et al. (2009; Icarus 203, 189). No pure rotational lines were detected but there were marginal detections of two metastable difference band lines. The IR-inactive ν1 levels are populated in thermal equilibrium so these difference band lines are proxies for the pure rotational lines in establishing the total H3+ column. These marginal results are consistent with a vibrational relaxation of the ν2 level by a factor of ~6, consistent with the non-LTE calculation of Melin et al. (2005; Icarus 178, 97).We report here results from subsequent observations of Jupiter’s H3+ hot spot spectrum below 10 μm, where better detectivity was expected from the lower thermal background. However, this was offset by the reduced availability of emission from known hydrocarbons, leading to acquisition and guiding difficulty, which was resolved by offsetting from a Galilean satellite. The observations were made with the TEXES high-resolution mid-IR spectrograph at the IRTF telescope on Oct 1, 6, and 8 of 2012. Of the 18 lines predicted for this wavelength regime, half avoided blending with lines apparent in Jupiter’s auroral spectrum or

  15. Role of a Modulator in the Synthesis of Phase-Pure NU-1000.

    PubMed

    Webber, Thomas E; Liu, Wei-Guang; Desai, Sai Puneet; Lu, Connie C; Truhlar, Donald G; Penn, R Lee

    2017-11-15

    NU-1000 is a robust, mesoporous metal-organic framework (MOF) with hexazirconium nodes ([Zr 6 O 16 H 16 ] 8+ , referred to as oxo-Zr 6 nodes) that can be synthesized by combining a solution of ZrOCl 2 ·8H 2 O and a benzoic acid modulator in N,N-dimethylformamide with a solution of linker (1,3,6,8-tetrakis(p-benzoic acid)pyrene, referred to as H 4 TBAPy) and by aging at an elevated temperature. Typically, the resulting crystals are primarily composed of NU-1000 domains that crystallize with a more dense phase that shares structural similarity with NU-901, which is an MOF composed of the same linker molecules and nodes. Density differences between the two polymorphs arise from the differences in the node orientation: in NU-1000, the oxo-Zr 6 nodes rotate 120° from node to node, whereas in NU-901, all nodes are aligned in parallel. Considering this structural difference leads to the hypothesis that changing the modulator from benzoic acid to a larger and more rigid biphenyl-4-carboxylic acid might lead to a stronger steric interaction between the modulator coordinating on the oxo-Zr 6 node and misaligned nodes or linkers in the large pore and inhibit the growth of the more dense NU-901-like material, resulting in phase-pure NU-1000. Side-by-side reactions comparing the products of synthesis using benzoic acid or biphenyl-4-carboxylic acid as a modulator produce structurally heterogeneous crystals and phase-pure NU-1000 crystals. It can be concluded that the larger and more rigid biphenyl-4-carboxylate inhibits the incorporation of nodes with an alignment parallel to the neighboring nodes already residing in the crystal.

  16. Determination the active compounds of herbal preparation by UHPLC-MS/MS and its application on the preclinical pharmacokinetics of pure ephedrine, single herbal extract of Ephedra, and a multiple herbal preparation in rats.

    PubMed

    Wang, Ju-Wen; Chiang, Meng-Hsuan; Lu, Chia-Ming; Tsai, Tung-Hu

    2016-07-15

    The herbal preparation Ma-Xing-Gan-Shi-Tang (MXGST) is a popular traditional Chinese formulation that has been used for the treatment of coughs and fevers. The potential active components of MXGST are ephedrine, amygdalin, and glycyrrhizic acid. The aim of this study was to develop a validated analytical method to measure these analytes in the herbal preparation MXGST using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Multiple reaction monitoring (MRM) was used to monitor m/z 166.1→148.1 for ephedrine ([M+H](+)), 475.2→163.0 for amygdalin ([M+NH4](+)), and 840.6→453.3 ([M+NH4](+)) for glycyrrhizic acid. The analytes were separated by a reverse phase C18 column (100×2.1mm, 2.6μm). The mobile phase consisted of 5mM ammonium acetate (0.1% formic acid) and 100% methanol (0.1% formic acid) with a linear gradient elution. Five brands of commercial pharmaceutical herbal products and a laboratory extract of MXGST were analyzed. Moreover, the modified UHPLC-MS/MS method was applied to the comparative pharmacokinetics of ephedrine in rats from the following three sources: (1) pure ephedrine, (2) an herbal extract of Ephedra, and (3) an herbal preparation of MXGST. Plasma samples from rats were prepared by protein precipitation, evaporation and reconstitution. The pharmacokinetic data showed that pure ephedrine was absorbed significantly faster than ephedrine of the Ephedra extract or the MXGST herbal preparation. However, the elimination half-life of ephedrine administered as the pure compound was 93.9±8.07min, but for ephedrine from the Ephedra extract and the MXGST, the half-lives were 133±17 and 247±57.6min, respectively. The area under the concentration curves (AUC) did not show significant differences among the three groups. These data suggest that the rest of the herbal ingredients in the Ephedra extract and the MXGST may provide a compensation effect that reduces the peak concentration of ephedrine and prolongs the

  17. CCS mRNA transcripts and serum CCS protein as copper marker in adults suffering inflammatory processes.

    PubMed

    Araya, Magdalena; Gutiérrez, Ricardo; Arredondo, Miguel

    2014-08-01

    The chaperone to Zn-Cu superoxide dismutase (CCS) has been postulated as a candidate copper indicator, changing in a consistent manner in induced and recovered copper deficiency, in experimental cell and animal models. In real life people have various conditions that may modify molecules acting as acute phase proteins, such as serum ceruloplasmin and copper concentration and could alter CCS responses. With the hypothesis that CCS mRNA transcripts and protein would be different in individuals suffering inflammatory processes in comparison to healthy individuals, we assessed adult individuals who, although not ill had conditions known to induce variable degrees of inflammation. Screening of 600 adults resulted in two study groups, formed on the basis of their clinical history and levels of serum C reactive protein (CRP): Group 1 (n = 61, mean (range) CRP = 0.9 (0.3-2.0 mg/dL) and Group 2 (n = 150, mean (range) CRP = 6.1 (4.3-8.7 mg/dL). Results showed that mRNA transcripts relative abundance was not different for CCS, MTIIA, TNF-alpha and Cu-Zn-SOD by group (p > 0.05, one way Anova), nor between sexes (p > 0.05, one way Anova). Distribution of CCS mRNA transcripts and CCS protein in serum did not show any differences or trends. Results disproved our hypothesis that CCS abundance of transcripts and CCS protein would be different in individuals suffering inflammatory processes, adding further support to the idea that CCS may be a copper marker.

  18. Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension).

    PubMed

    Terauchi, Y; Koyama, M; Cheng, X; Sumi, M; Riddle, M C; Bolli, G B; Hirose, T

    2017-10-01

    To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months. EDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed. The 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA 1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤3.9mmol/L [≤70mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00-05:59h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments. Over 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Newly Identified TLR9 Stimulant, M6-395 Is a Potent Polyclonal Activator for Murine B Cells.

    PubMed

    Park, Mi-Hee; Jung, Yu-Jin; Kim, Pyeung-Hyeun

    2012-02-01

    Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-β1-induced germ line transcript α (GLTα) and IL-4-induced GLTγ1 as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.

  20. THE MAGNETIC SYSTEMS TRIGGERING THE M6.6 CLASS SOLAR FLARE IN NOAA ACTIVE REGION 11158

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Toriumi, Shin; Iida, Yusuke; Bamba, Yumi

    2013-08-20

    We report a detailed event analysis of the M6.6 class flare in the active region (AR) NOAA 11158 on 2011 February 13. AR 11158, which consisted of two major emerging bipoles, showed prominent activity including one X- and several M-class flares. In order to investigate the magnetic structures related to the M6.6 event, particularly the formation process of a flare-triggering magnetic region, we analyzed multiple spacecraft observations and numerical results of a flare simulation. We observed that, in the center of this quadrupolar AR, a highly sheared polarity inversion line (PIL) was formed through proper motions of the major magneticmore » elements, which built a sheared coronal arcade lying over the PIL. The observations lend support to the interpretation that the target flare was triggered by a localized magnetic region that had an intrusive structure, namely, a positive polarity penetrating into a negative counterpart. The geometrical relationship between the sheared coronal arcade and the triggering region is consistent with the theoretical flare model based on the previous numerical study. We found that the formation of the trigger region was due to the continuous accumulation of small-scale magnetic patches. A few hours before the flare occurred, the series of emerged/advected patches reconnected with a pre-existing field. Finally, the abrupt flare eruption of the M6.6 event started around 17:30 UT. Our analysis suggests that in the process of triggering flare activity, all magnetic systems on multiple scales are included, not only the entire AR evolution but also the fine magnetic elements.« less

  1. High-performance thermoelectric minerals: Colusites Cu26V2M6S32 (M = Ge, Sn)

    NASA Astrophysics Data System (ADS)

    Suekuni, Koichiro; Kim, Fiseong S.; Nishiate, Hirotaka; Ohta, Michihiro; Tanaka, Hiromi I.; Takabatake, Toshiro

    2014-09-01

    We report thermoelectric (TE) properties of dense samples of colusites Cu26V2M6S32 (M = Ge, Sn), most of which are composed of earth-abundant elements; Cu and S. The combination of p-type metallic conduction and large thermopowers greater than 200 μV/K leads to high TE power factors of 0.61 and 0.48 mW/K2 m at 663 K for M = Ge and Sn samples, respectively. Furthermore, the lattice thermal conductivity is smaller than 0.6 W/Km over the temperature range from 350 K to 663 K due to the structural complexity. As a consequence, the values of dimensionless TE figure of merit ZT for M = Ge and Sn reach 0.73 and 0.56 at 663 K, respectively. Thus, the colusites are promising candidates for environmental friendly TE materials usable in the range of 500-700 K.

  2. c-Raf/MEK/ERK pathway controls protein kinase C-mediated p70S6K activation in adult cardiac muscle cells.

    PubMed

    Iijima, Yoshihiro; Laser, Martin; Shiraishi, Hirokazu; Willey, Christopher D; Sundaravadivel, Balasubramanian; Xu, Lin; McDermott, Paul J; Kuppuswamy, Dhandapani

    2002-06-21

    p70S6 kinase (S6K1) plays a pivotal role in hypertrophic cardiac growth via ribosomal biogenesis. In pressure-overloaded myocardium, we show S6K1 activation accompanied by activation of protein kinase C (PKC), c-Raf, and mitogen-activated protein kinases (MAPKs). To explore the importance of the c-Raf/MAPK kinase (MEK)/MAPK pathway, we stimulated adult feline cardiomyocytes with 12-O-tetradecanoylphorbol-13-acetate (TPA), insulin, or forskolin to activate PKC, phosphatidylinositol-3-OH kinase, or protein kinase A (PKA), respectively. These treatments resulted in S6K1 activation with Thr-389 phosphorylation as well as mammalian target of rapamycin (mTOR) and S6 protein phosphorylation. Thr-421/Ser-424 phosphorylation of S6K1 was observed predominantly in TPA-treated cells. Dominant negative c-Raf expression or a MEK1/2 inhibitor (U0126) treatment showed a profound blocking effect only on the TPA-stimulated phosphorylation of S6K1 and mTOR. Whereas p38 MAPK inhibitors exhibited only partial effect, MAPK-phosphatase-3 expression significantly blocked the TPA-stimulated S6K1 and mTOR phosphorylation. Inhibition of mTOR with rapamycin blocked the Thr-389 but not the Thr-421/Ser-424 phosphorylation of S6K1. Therefore, during PKC activation, the c-Raf/MEK/extracellular signal-regulated kinase-1/2 (ERK1/2) pathway mediates both the Thr-421/Ser-424 and the Thr-389 phosphorylation in an mTOR-independent and -dependent manner, respectively. Together, our in vivo and in vitro studies indicate that the PKC/c-Raf/MEK/ERK pathway plays a major role in the S6K1 activation in hypertrophic cardiac growth.

  3. Rrp6p controls mRNA polyA tail length and its decoration with polyA binding proteins

    PubMed Central

    Schmid, Manfred; Poulsen, Mathias Bach; Olszewski, Pawel; Pelechano, Vicent; Saguez, Cyril; Gupta, Ishaan; Steinmetz, Lars M.; Moore, Claire; Jensen, Torben Heick

    2012-01-01

    PolyA (pA) tail binding proteins (PABPs) control mRNA polyadenylation, stability and translation. In a purified system, S. cerevisiae PABPs, Pab1p and Nab2p, are individually sufficient to provide normal pA tail length. However, it is unknown how this occurs in more complex environments. Here we find that the nuclear exosome subunit Rrp6p counteracts the in vitro and in vivo extension of mature pA tails by the non-canonical pA polymerase Trf4p. Moreover, PABP loading onto nascent pA tails is controlled by Rrp6p; while Pab1p is the major PABP, Nab2p only associates in the absence of Rrp6p. This is because Rrp6p can interact with Nab2p and displace it from pA tails, potentially leading to RNA turnover as evidenced for certain pre-mRNAs. We suggest that a nuclear mRNP surveillance step involves targeting of Rrp6p by Nab2p-bound pA-tailed RNPs and that pre-mRNA abundance is regulated at this level. PMID:22683267

  4. The association between sleep duration and weight gain in adults: a 6-year prospective study from the Quebec Family Study.

    PubMed

    Chaput, Jean-Philippe; Després, Jean-Pierre; Bouchard, Claude; Tremblay, Angelo

    2008-04-01

    To investigate the relationship between sleep duration and subsequent body weight and fat gain. Six-year longitudinal study. Community setting. Two hundred seventy-six adults aged 21 to 64 years from the Quebec Family Study. More than half of the sample is drawn from families with at least 1 parent and 1 offspring with a body mass index of 32 kg/m2 or higher. Body composition measurements and self-reported sleep duration were determined. Changes in adiposity indices were compared between short- (5-6 hours), average- (7-8 hours), and long- (9-10 hours) duration sleeper groups. After adjustment for age, sex, and baseline body mass index, short-duration sleepers gained 1.98 kg (95% confidence interval: 1.16-2.82) more and long-duration sleepers gained 1.58 kg (95% CI: 1.02-2.56) more than did average-duration sleepers over 6 years. Short- and long-duration sleepers were 35% and 25% more likely to experience a 5-kg weight gain, respectively, as compared with average-duration sleepers over 6 years. The risk of developing obesity was elevated for short- and long-duration sleepers as compared with average-duration sleepers, with 27% and 21% increases in risk, respectively. These associations remained significant after inclusion of important covariates and were not affected by adjustment for energy intake and physical activity participation. This study provides evidence that both short and long sleeping times predict an increased risk of future body weight and fat gain in adults. Hence, these results emphasize the need to add sleep duration to the panel of determinants that contribute to weight gain and obesity.

  5. Beyond Sex Education: How Adults Relate to Children's Sensuality.

    ERIC Educational Resources Information Center

    Fogel, Alan

    Current cultural attitudes toward children's sexuality resemble attitudes toward adults' sexuality; there is an emphasis on purely genital and orgasmic pleasure. Adults and children need warmth, physical contact, and a sense of belonging for which genital stimulation may be unnecessary or inappropriate. Children's sexual advances to adults, as…

  6. CTX-M ESBL-producing Enterobacteriaceae: estimated prevalence in adults in England in 2014

    PubMed Central

    McNulty, Cliodna A M; Lecky, Donna M; Xu-McCrae, Li; Nakiboneka-Ssenabulya, Deborah; Chung, Keun-Taik; Nichols, Tom; Thomas, Helen Lucy; Thomas, Mike; Alvarez-Buylla, Adela; Turner, Kim; Shabir, Sahida; Manzoor, Susan; Smith, Stephen; Crocker, Linda; Hawkey, Peter M

    2018-01-01

    Abstract Background ESBL-producing Enterobacteriaceae (ESBLPE) are increasing in prevalence worldwide and are more difficult to treat than non-ESBLPE. Their prevalence in the UK general population is unknown, as the only previous UK ESBLPE faecal colonization study involved patients with diarrhoea. Objectives To estimate the prevalence of CTX-M ESBLPE faecal colonization in the general adult population of England in 2014, and investigate risk factors. Methods A stratified random sample of 58 337 registered patients from 16 general practices within four areas of England were invited to participate by returning faeces specimens and self-completed questionnaires. Specimens were tested for ESBLPE and carbapenemase-producing Enterobacteriaceae (CPE). Results 2430 individuals participated (4% of those invited). The estimated prevalence of colonization with CTX-M ESBLPE in England was 7.3% (95% CI 5.6%–9.4%) (Shropshire 774 participants, 4.9% colonization; Southampton City 740 participants, 9.2%; Newham 612 participants, 12.7%; Heart of Birmingham 234 individuals, 16.0%) and was particularly high in: those born in Afghanistan (10 participants, 60.0% colonization, 95% CI 29.7%–84.2%); those born on the Indian subcontinent (India, Pakistan, Bangladesh or Sri Lanka) (259 participants, 25.0% colonization, 95% CI 18.5%–32.9%); travellers to South Asia (India, Pakistan, Bangladesh, Sri Lanka or Nepal) in the last year (140 participants, 38.5% colonization, 95% CI 27.8%–50.5%); and healthcare domestics (8 participants, unweighted 37.5% colonization, 95% CI 8.5%–75.5%). Risk factors identified included: being born in the Indian subcontinent (aOR 5.4, 95% CI 3.0–9.7); travel to South Asia (aOR 2.9, 95% CI 1.8–4.8) or to Africa, China, South or Central America, South East or Pacific Asia or Afghanistan (aOR 2.6, 95% CI 1.7–4.1) in the last year; and working as a healthcare domestic (aOR 6.2, 95% CI 1.3–31). None of the 48 participants who took co-amoxiclav in

  7. Generalized pure Lovelock gravity

    NASA Astrophysics Data System (ADS)

    Concha, Patrick; Rodríguez, Evelyn

    2017-11-01

    We present a generalization of the n-dimensional (pure) Lovelock Gravity theory based on an enlarged Lorentz symmetry. In particular, we propose an alternative way to introduce a cosmological term. Interestingly, we show that the usual pure Lovelock gravity is recovered in a matter-free configuration. The five and six-dimensional cases are explicitly studied.

  8. Low-Temperature Blanching as a Tool to Modulate the Structure of Pectin in Blueberry Purees.

    PubMed

    Chevalier, Laura M; Rioux, Laurie-Eve; Angers, Paul; Turgeon, Sylvie L

    2017-09-01

    Blueberry composition was characterized for 6 cultivars. It contains a good amount of dietary fiber (10% to 20%) and pectin (4% to 7%) whose degree of methylation (DM) is sensitive to food processing. A low temperature blanching (LTB: 60 °C/1 h) was applied on blueberry purees to decrease pectin DM, in order to modulate puree properties and functionalities (that is, viscosity and stability), and to enhance pectin affinity toward other components within food matrices. Fiber content, viscosity, pectin solubility, DM, and monosaccharide composition were determined for both pasteurized, and LTB+pasteurized blueberry purees. The results showed that neither the amount of fiber, nor the viscosity were affected by LTB, indicating that this treatment did not result in any significant pectin depolymerization and degradation. LTB caused a decrease both in pectin DM from 58-67% to 45-47% and in the amount of water-soluble pectin fraction, the latter remaining the major fraction of total pectin at 52% to 57%. A LTB is a simple and mild process to produce blueberry purees with mostly soluble and low-methylated pectin in order to extend functionality and opportunities for interactions with other food ingredients. © 2017 Institute of Food Technologists®.

  9. Pure akinesia: a kinematic analysis in a case responsive to rotigotine

    PubMed Central

    Di Fabio, Roberto; Serrao, Mariano; Pierelli, Francesco; Fragiotta, Gaia; Sandrini, Giorgio

    2013-01-01

    Summary A patient with pure akinesia is described. This rare gait disorder, poorly responsive to therapy, is characterized by gait impairment which may be associated with handwriting and speech difficulties, in the absence of further signs of extrapyramidal involvement. Here, we report the improvement in a patient suffering from pure akinesia after low doses of rotigotine, a non-ergolinic dopamine agonist, detailing the kinematic analysis before and after the treatment. After therapy, an improvement in all of the gait parameters, particularly gait speed, was observed with a trend toward normalization. Our case report suggests that rotigotine may be a therapeutic option in cases of pure akinesia. PMID:24125564

  10. Low risk of attrition among adults on antiretroviral therapy in the Rwandan national program: a retrospective cohort analysis of 6, 12, and 18 month outcomes.

    PubMed

    Nuwagaba-Biribonwoha, Harriet; Jakubowski, Aleksandra; Mugisha, Veronicah; Basinga, Paulin; Asiimwe, Anita; Nash, Denis; Elul, Batya

    2014-08-29

    We report levels and determinants of attrition in Rwanda, one of the few African countries with universal ART access. We analyzed data abstracted from health facility records of a nationally representative sample of adults [≥ 18 years] who initiated ART 6, 12, and 18 months prior to data collection; and collected facility characteristics with a health facility assessment questionnaire. Weighted proportions and rates of attrition [loss to follow-up or death] were calculated, and patient- and health facility-level factors associated with attrition examined using Cox proportional hazard models. 1678 adults initiated ART 6, 12 and 18 months prior to data collection, with 1508 person-years [PY] on ART. Attrition was 6.8% [95% confidence interval [CI] 6.0-7.8]: 2.9% [2.4-3.5] recorded deaths and 3.9% [3.4-4.5] lost to follow-up. Population attrition rate was 7.5/100 PY [6.1-9.3]. Adjusted hazard ratio [aHR] for attrition was 4.2 [3.0-5.7] among adults enrolled from in-patient wards [vs 2.2 [1.6-3.0] from PMTCT, ref: VCT]. Compared to adults who initiated ART 18 months earlier, aHR for adults who initiated ART 12 and 6 months earlier was 1.8 [1.3-2.5] and 1.3 [0.9-1.9] respectively. Male aHR was 1.4 [1.0-1.8]. AHR of adults enrolled at urban health facilities was 1.4 [1.1-1.8, ref: rural health facilities]. AHR for adults with CD4+ ≥ 200 cells/μL vs <200 cells/μL was 0.8 [0.6-1.0]; and adults attending facilities with performance-based financing since 2004-2006 [vs. 2007-2008] had aHR 0.8 [0.6-0.9]. Attrition was low in the Rwandan national program. The above patient and facility correlates of attrition can be the focus of interventions to sustain high retention.

  11. Decryption of pure-position permutation algorithms.

    PubMed

    Zhao, Xiao-Yu; Chen, Gang; Zhang, Dan; Wang, Xiao-Hong; Dong, Guang-Chang

    2004-07-01

    Pure position permutation image encryption algorithms, commonly used as image encryption investigated in this work are unfortunately frail under known-text attack. In view of the weakness of pure position permutation algorithm, we put forward an effective decryption algorithm for all pure-position permutation algorithms. First, a summary of the pure position permutation image encryption algorithms is given by introducing the concept of ergodic matrices. Then, by using probability theory and algebraic principles, the decryption probability of pure-position permutation algorithms is verified theoretically; and then, by defining the operation system of fuzzy ergodic matrices, we improve a specific decryption algorithm. Finally, some simulation results are shown.

  12. Newly Identified TLR9 Stimulant, M6-395 Is a Potent Polyclonal Activator for Murine B Cells

    PubMed Central

    Park, Mi-Hee; Jung, Yu-Jin

    2012-01-01

    Background Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. Methods In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. Results First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-β1-induced germ line transcript α (GLTα) and IL-4-induced GLTγ1 as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. Conclusion Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching. PMID:22536167

  13. Perspectives on the Pure-Tone Audiogram.

    PubMed

    Musiek, Frank E; Shinn, Jennifer; Chermak, Gail D; Bamiou, Doris-Eva

    The pure-tone audiogram, though fundamental to audiology, presents limitations, especially in the case of central auditory involvement. Advances in auditory neuroscience underscore the considerably larger role of the central auditory nervous system (CANS) in hearing and related disorders. Given the availability of behavioral audiological tests and electrophysiological procedures that can provide better insights as to the function of the various components of the auditory system, this perspective piece reviews the limitations of the pure-tone audiogram and notes some of the advantages of other tests and procedures used in tandem with the pure-tone threshold measurement. To review and synthesize the literature regarding the utility and limitations of the pure-tone audiogram in determining dysfunction of peripheral sensory and neural systems, as well as the CANS, and to identify other tests and procedures that can supplement pure-tone thresholds and provide enhanced diagnostic insight, especially regarding problems of the central auditory system. A systematic review and synthesis of the literature. The authors independently searched and reviewed literature (journal articles, book chapters) pertaining to the limitations of the pure-tone audiogram. The pure-tone audiogram provides information as to hearing sensitivity across a selected frequency range. Normal or near-normal pure-tone thresholds sometimes are observed despite cochlear damage. There are a surprising number of patients with acoustic neuromas who have essentially normal pure-tone thresholds. In cases of central deafness, depressed pure-tone thresholds may not accurately reflect the status of the peripheral auditory system. Listening difficulties are seen in the presence of normal pure-tone thresholds. Suprathreshold procedures and a variety of other tests can provide information regarding other and often more central functions of the auditory system. The audiogram is a primary tool for determining type

  14. Factors affecting sensitivity to frequency change in school-age children and adults.

    PubMed

    Buss, Emily; Taylor, Crystal N; Leibold, Lori J

    2014-10-01

    The factors affecting frequency discrimination in school-age children are poorly understood. The goal of the present study was to evaluate developmental effects related to memory for pitch and the utilization of temporal fine structure. Listeners were 5.1- to 13.6-year-olds and adults, all with normal hearing. A subgroup of children had musical training. The task was a 3-alternative forced choice in which listeners identified the interval with the higher frequency tone or the tone characterized by frequency modulation (FM). The standard was 500 or 5000 Hz, and the FM rate was either 2 or 20 Hz. Thresholds tended to be higher for younger children than for older children and adults for all conditions, although this age effect was smaller for FM detection than for pure-tone frequency discrimination. Neither standard frequency nor modulation rate affected the child/adult difference FM thresholds. Children with musical training performed better than their peers on pure-tone frequency discrimination at 500 Hz. Testing frequency discrimination using a low-rate FM detection task may minimize effects related to cognitive factors like memory for pitch or training effects. Maturation of frequency discrimination does not appear to differ across conditions in which listeners are hypothesized to rely on temporal cues and place cues.

  15. Normative Data for the Words-in-Noise Test for 6- to 12-Year-Old Children

    ERIC Educational Resources Information Center

    Wilson, Richard H.; Farmer, Nicole M.; Gandhi, Avni; Shelburne, Emily; Weaver, Jamie

    2010-01-01

    Purpose: To establish normative data for children on the Words-in-Noise Test (WIN; R. H. Wilson, 2003; R. H. Wilson & R. McArdle, 2007). Method: Forty-two children in each of 7 age groups, ranging in age from 6 to 12 years (n = 294), and 24 young adults (age range: 18-27 years) with normal hearing for pure tones participated. All listeners…

  16. The First Comparative Study of the Perioperative Outcomes Between Pure Laparoscopic Donor Hepatectomy and Laparoscopy-Assisted Donor Hepatectomy in a Single Institution.

    PubMed

    Takahara, Takeshi; Wakabayashi, Go; Nitta, Hiroyuki; Hasegawa, Yasushi; Katagiri, Hirokatsu; Umemura, Akira; Takeda, Daiki; Makabe, Kenji; Otsuka, Koki; Koeda, Keisuke; Sasaki, Akira

    2017-07-01

    In a statement from the second International Consensus Conference for Laparoscopic Liver Resection, adult-to-adult laparoscopic donor surgery was the earliest phase of development. It was recommended that the procedure be performed under institutional ethical approval and a reporting registry. At our institute, we started laparoscopy-assisted donor hepatectomy (LADH) in 2007 and changed to pure laparoscopic donor hepatectomy (PLDH) in 2012. This study included 40 living donors who underwent LADH and 14 live donors who underwent PLDH. We describe the technical aspects and outcomes of our donor hepatectomy from assist to pure and examine the liver allograft outcomes of the recipients after LADH and PLDH. There was significantly less blood loss in the PLDH group (81.07 ± 52.78 g) than that in the LADH group (238.50 ± 177.05 g), although the operative time was significantly longer in the PLDH group (454.93 ± 85.60 minutes) than in the LADH group (380.40 ± 44.08 minutes). And there were no significant differences in postoperative complication rate in the 2 groups. The liver allograft outcomes were acceptable and comparable with open living donor hepatectomy. By changing our routine approach from assist to pure, PLDH can be performed safely, with better exposure due to magnification, and with less blood loss under pneumoperitoneal pressure. PLDH, which has become our promising donor procedure, results in less blood loss, better cosmesis, and the donor's complete rehabilitation without deterioration in donor safety.

  17. The Relationship Between Balance Measured With a Modified Bathroom Scale and Falls and Disability in Older Adults: A 6-Month Follow-Up Study

    PubMed Central

    2015-01-01

    Background There are indications that older adults who suffer from poor balance have an increased risk for adverse health outcomes, such as falls and disability. Monitoring the development of balance over time enables early detection of balance decline, which can identify older adults who could benefit from interventions aimed at prevention of these adverse outcomes. An innovative and easy-to-use device that can be used by older adults for home-based monitoring of balance is a modified bathroom scale. Objective The objective of this paper is to study the relationship between balance scores obtained with a modified bathroom scale and falls and disability in a sample of older adults. Methods For this 6-month follow-up study, participants were recruited via physiotherapists working in a nursing home, geriatricians, exercise classes, and at an event about health for older adults. Inclusion criteria were being aged 65 years or older, being able to stand on a bathroom scale independently, and able to provide informed consent. A total of 41 nursing home patients and 139 community-dwelling older adults stepped onto the modified bathroom scale three consecutive times at baseline to measure their balance. Their mean balance scores on a scale from 0 to 16 were calculated—higher scores indicated better balance. Questionnaires were used to study falls and disability at baseline and after 6 months of follow-up. The cross-sectional relationship between balance and falls and disability at baseline was studied using t tests and Spearman rank correlations. Univariate and multivariate logistic regression analyses were conducted to study the relationship between balance measured at baseline and falls and disability development after 6 months of follow-up. Results A total of 128 participants with complete datasets—25.8% (33/128) male—and a mean age of 75.33 years (SD 6.26) were included in the analyses of this study. Balance scores of participants who reported at baseline that

  18. 17-N-Allylamino-17-Demethoxygeldanamycin and Bortezomib in Treating Patients With Relapsed or Refractory Hematologic Cancer

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  19. Pure laparoscopic radical resection for type IIIa hilar cholangiocarcinoma.

    PubMed

    Zhang, Cheng-Wu; Liu, Jie; Hong, De-Fei; Wang, Zhi-Fei; Hu, Zhi-Ming; Huang, Dong-Shen; Shang, Min-Jie; Yao, Wei-Feng

    2018-03-01

    Pure laparoscopic radical resection of hilar cholangiocarcinoma is still a challenging procedure, in which laparoscopic lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy were included [1-4]. Relative report is rare in the world up to now. Hilar cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis or vessel invasion [5, 6]. We recently had a patient who underwent a pure laparoscopic extended right hepatectomy and lymph node dissection and hepaticojejunostomy for a type IIIa hilar cholangiocarcinoma. The tumor was 20 × 15 × 12 mm in diameter and located in the right bile duct and common hepatic duct. Radiological examination showed that hepatic artery and portal vein was not invaded. After the division and mutilation of the right hepatic artery and the right portal vein, short hepatic veins were divided and cut off with clip and ultrasound knife from the anterior face of the vena cava. Mobilization was performed after the devascularization of the right liver, followed by the transection of liver parenchymal with CUSA and ultrasound knife. Finally, left hepatic bile duct jejunum Roux-en-Y reconstruction was performed. This patient underwent successfully with a totally laparoscopic procedure. An extended right hepatectomy (right hemihepatectomy combined with caudate lobectomy) and complete lymph node dissection and hepaticojejunostomy were performed in this operation. The operation time was nearly 590 min, and the intraoperative blood loss was about 300 ml. No obvious complication was observed and the postoperative hospital stay was 11 days. The final diagnosis of the hilar cholangiocarcinoma with no lymph node metastasis was pT2bN0M0 stage II (American Joint Committee on Cancer, AJCC). Pure laparoscopic resection for hilar cholangiocarcinoma was proved safe and feasible, which enabled the patient to recover early and have an opportunity to receive chemotherapy as soon as possible. We

  20. The m6A methyltransferase Ime4 epitranscriptionally regulates triacylglycerol metabolism and vacuolar morphology in haploid yeast cells.

    PubMed

    Yadav, Pradeep Kumar; Rajasekharan, Ram

    2017-08-18

    N 6 -Methyladenosine (m 6 A) is among the most common modifications in eukaryotic mRNA. The role of yeast m 6 A methyltransferase, Ime4, in meiosis and sporulation in diploid strains is very well studied, but its role in haploid strains has remained unknown. Here, with the help of an immunoblotting strategy and Ime4-GFP protein localization studies, we establish the physiological role of Ime4 in haploid cells. Our data showed that Ime4 epitranscriptionally regulates triacylglycerol metabolism and vacuolar morphology through the long-chain fatty acyl-CoA synthetase Faa1, independently of the RNA methylation complex (MIS complex). The MIS complex consists of the Ime4, Mum2, and Slz1 proteins. Our affinity enrichment strategy (methylated RNA immunoprecipitation assays) using m 6 A polyclonal antibodies coupled with mRNA isolation, quantitative real-time PCR, and standard PCR analyses confirmed the presence of m 6 A-modified FAA1 transcripts in haploid yeast cells. The term "epitranscriptional regulation" encompasses the RNA modification-mediated regulation of genes. Moreover, we demonstrate that the Aft2 transcription factor up-regulates FAA1 expression. Because the m 6 A methylation machinery is fundamentally conserved throughout eukaryotes, our findings will help advance the rapidly emerging field of RNA epitranscriptomics. The metabolic link identified here between m 6 A methylation and triacylglycerol metabolism via the Ime4 protein provides new insights into lipid metabolism and the pathophysiology of lipid-related metabolic disorders, such as obesity. Because the yeast vacuole is an analogue of the mammalian lysosome, our findings pave the way to better understand the role of m 6 A methylation in lysosome-related functions and diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. The mTOR Substrate S6 Kinase 1 (S6K1) Is a Negative Regulator of Axon Regeneration and a Potential Drug Target for Central Nervous System Injury

    PubMed Central

    Ding, Ying; Slepak, Tatiana; Sun, Yan; Martinez, Yania; Xu, Xiao-Ming

    2017-01-01

    The mammalian target of rapamycin (mTOR) positively regulates axon growth in the mammalian central nervous system (CNS). Although axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a negative regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR's positive effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by twofold to threefold. Biochemical analysis revealed that an mTOR-dependent induction of PI3K signaling is involved in mediating this effect of S6K1 inhibition. Importantly, treating female mice in vivo with PF-4708671, a selective S6K1 inhibitor, stimulated corticospinal tract regeneration across a dorsal spinal hemisection between the cervical 5 and 6 cord segments (C5/C6), increasing axon counts for at least 3 mm beyond the injury site at 8 weeks after injury. Concomitantly, treatment with PF-4708671 produced significant locomotor recovery. Pharmacological targeting of S6K1 may therefore constitute an attractive strategy for promoting axon regeneration following CNS injury, especially given that S6K1 inhibitors are being assessed in clinical trials for nononcological indications. SIGNIFICANCE STATEMENT Despite mTOR's well-established function in promoting axon regeneration, the role of its downstream target, S6 kinase 1 (S6K1), has been unclear. We used cellular assays with primary neurons to demonstrate that S6K1 is a negative regulator of neurite outgrowth, and a spinal cord injury model to show that it is a viable pharmacological target for inducing axon regeneration. We provide mechanistic evidence that S6K1's negative feedback to PI3K signaling is involved in axon growth inhibition, and show that phosphorylation of S6K1 is a more

  2. Role of temperament in early adolescent pure and co-occurring internalizing and externalizing problems using a bifactor model: Moderation by parenting and gender.

    PubMed

    Wang, Frances L; Eisenberg, Nancy; Valiente, Carlos; Spinrad, Tracy L

    2016-11-01

    We contribute to the literature on the relations of temperament to externalizing and internalizing problems by considering parental emotional expressivity and child gender as moderators of such relations and examining prediction of pure and co-occurring problem behaviors during early to middle adolescence using bifactor models (which provide unique and continuous factors for pure and co-occurring internalizing and externalizing problems). Parents and teachers reported on children's (4.5- to 8-year-olds; N = 214) and early adolescents' (6 years later; N = 168) effortful control, impulsivity, anger, sadness, and problem behaviors. Parental emotional expressivity was measured observationally and with parents' self-reports. Early-adolescents' pure externalizing and co-occurring problems shared childhood and/or early-adolescent risk factors of low effortful control, high impulsivity, and high anger. Lower childhood and early-adolescent impulsivity and higher early-adolescent sadness predicted early-adolescents' pure internalizing. Childhood positive parental emotional expressivity more consistently related to early-adolescents' lower pure externalizing compared to co-occurring problems and pure internalizing. Lower effortful control predicted changes in externalizing (pure and co-occurring) over 6 years, but only when parental positive expressivity was low. Higher impulsivity predicted co-occurring problems only for boys. Findings highlight the probable complex developmental pathways to adolescent pure and co-occurring externalizing and internalizing problems.

  3. Metastatic Urothelial Carcinoma with Glandular Differentiation That Confirmed the Response by Autopsy Specimen to Second-Line mFOLFOX6 (Fluorouracil, Oxaliplatin, and Leucovorin) plus Bevacizumab Chemotherapy

    PubMed Central

    Naiki, Taku; Etani, Toshiki; Naiki-Ito, Aya; Fujii, Kana; Ando, Ryosuke; Iida, Keitaro; Nagai, Takashi; Sugiyama, Yosuke; Nakagawa, Motoo; Kawai, Noriyasu; Yasui, Takahiro

    2017-01-01

    The prognostic significance of glandular differentiation in urothelial carcinoma (UC) is controversial, and thus far there is no established treatment strategy against metastasis of glandular component. We describe here a case of metastatic UC with glandular differentiation that had histological disappearance of adenocarcinoma components at autopsy after sequential chemotherapy with S-1 and cisplatin (CDDP) and with mFOLFOX6 (fluorouracil, oxaliplatin, and leucovorin) plus bevacizumab (mFOLFOX6+Bev). A 62-year-old Asian male was diagnosed with invasive UC with glandular differentiation (T2N0M0) by radical cystectomy and ileal conduit, and careful follow-up observation was made. Eight years after radical operation, peritoneal metastases occurred, and a biopsy specimen using colon fiber revealed high-grade adenocarcinomas with an immunohistochemical profile that included positivity for cytokeratin 7 (CK7) and negativity for cytokeratin 20 (CK20) and uroplakin, which was identical to the radical cystectomy specimen. Thus, he received combination chemotherapy consisting of S-1 and CDDP; however, the peritoneal metastasis worsened after 2 cycles. Therefore, second-line mFOLFOX6+Bev chemotherapy was performed for a total of 5 courses. In spite of this, the patient died, and the final diagnosis by autopsy was multiple metastases of infiltrating pure UC to the lung, bone, and peritoneum. Interestingly, there were no pathological findings of adenocarcinoma, and the immunohistochemical profile of the metastatic lesions was identical to that of the previous specimens from the bladder and colon. This suggests that sequential chemotherapy of S-1 and CDDP and second-line mFOLFOX6+Bev might be a feasible option in metastatic UC with glandular differentiation. PMID:29515396

  4. Diagnostic pure-tone audiometry in schools: mobile testing without a sound-treated environment.

    PubMed

    Swanepoel, De Wet; Maclennan-Smith, Felicity; Hall, James W

    2013-01-01

    To validate diagnostic pure-tone audiometry in schools without a sound-treated environment using an audiometer that incorporates insert earphones covered by circumaural earcups and real-time environmental noise monitoring. A within-subject repeated measures design was employed to compare air (250 to 8000 Hz) and bone (250 to 4000 Hz) conduction pure-tone thresholds measured in natural school environments with thresholds measured in a sound-treated booth. 149 children (54% female) with an average age of 6.9 yr (SD = 0.6; range = 5-8). Average difference between the booth and natural environment thresholds was 0.0 dB (SD = 3.6) for air conduction and 0.1 dB (SD = 3.1) for bone conduction. Average absolute difference between the booth and natural environment was 2.1 dB (SD = 2.9) for air conduction and 1.6 dB (SD = 2.7) for bone conduction. Almost all air- (96%) and bone-conduction (97%) threshold comparisons between the natural and booth test environments were within 0 to 5 dB. No statistically significant differences between thresholds recorded in the natural and booth environments for air- and bone-conduction audiometry were found (p > 0.01). Diagnostic air- and bone-conduction audiometry in schools, without a sound-treated room, is possible with sufficient earphone attenuation and real-time monitoring of environmental noise. Audiological diagnosis on-site for school screening may address concerns of false-positive referrals and poor follow-up compliance and allow for direct referral to audiological and/or medical intervention. American Academy of Audiology.

  5. Involvement of T6 pili in biofilm formation by serotype M6 Streptococcus pyogenes.

    PubMed

    Kimura, Keiji Richard; Nakata, Masanobu; Sumitomo, Tomoko; Kreikemeyer, Bernd; Podbielski, Andreas; Terao, Yutaka; Kawabata, Shigetada

    2012-02-01

    The group A streptococcus (GAS) Streptococcus pyogenes is known to cause self-limiting purulent infections in humans. The role of GAS pili in host cell adhesion and biofilm formation is likely fundamental in early colonization. Pilus genes are found in the FCT (fibronectin-binding protein, collagen-binding protein, and trypsin-resistant antigen) genomic region, which has been classified into nine subtypes based on the diversity of gene content and nucleotide sequence. Several epidemiological studies have indicated that FCT type 1 strains, including serotype M6, produce large amounts of monospecies biofilm in vitro. We examined the direct involvement of pili in biofilm formation by serotype M6 clinical isolates. In the majority of tested strains, deletion of the tee6 gene encoding pilus shaft protein T6 compromised the ability to form biofilm on an abiotic surface. Deletion of the fctX and srtB genes, which encode pilus ancillary protein and class C pilus-associated sortase, respectively, also decreased biofilm formation by a representative strain. Unexpectedly, these mutant strains showed increased bacterial aggregation compared with that of the wild-type strain. When the entire FCT type 1 pilus region was ectopically expressed in serotype M1 strain SF370, biofilm formation was promoted and autoaggregation was inhibited. These findings indicate that assembled FCT type 1 pili contribute to biofilm formation and also function as attenuators of bacterial aggregation. Taken together, our results show the potential role of FCT type 1 pili in the pathogenesis of GAS infections.

  6. Involvement of T6 Pili in Biofilm Formation by Serotype M6 Streptococcus pyogenes

    PubMed Central

    Kimura, Keiji Richard; Nakata, Masanobu; Sumitomo, Tomoko; Kreikemeyer, Bernd; Podbielski, Andreas; Terao, Yutaka

    2012-01-01

    The group A streptococcus (GAS) Streptococcus pyogenes is known to cause self-limiting purulent infections in humans. The role of GAS pili in host cell adhesion and biofilm formation is likely fundamental in early colonization. Pilus genes are found in the FCT (fibronectin-binding protein, collagen-binding protein, and trypsin-resistant antigen) genomic region, which has been classified into nine subtypes based on the diversity of gene content and nucleotide sequence. Several epidemiological studies have indicated that FCT type 1 strains, including serotype M6, produce large amounts of monospecies biofilm in vitro. We examined the direct involvement of pili in biofilm formation by serotype M6 clinical isolates. In the majority of tested strains, deletion of the tee6 gene encoding pilus shaft protein T6 compromised the ability to form biofilm on an abiotic surface. Deletion of the fctX and srtB genes, which encode pilus ancillary protein and class C pilus-associated sortase, respectively, also decreased biofilm formation by a representative strain. Unexpectedly, these mutant strains showed increased bacterial aggregation compared with that of the wild-type strain. When the entire FCT type 1 pilus region was ectopically expressed in serotype M1 strain SF370, biofilm formation was promoted and autoaggregation was inhibited. These findings indicate that assembled FCT type 1 pili contribute to biofilm formation and also function as attenuators of bacterial aggregation. Taken together, our results show the potential role of FCT type 1 pili in the pathogenesis of GAS infections. PMID:22155780

  7. High heat flux properties of pure tungsten and plasma sprayed tungsten coatings

    NASA Astrophysics Data System (ADS)

    Liu, X.; Tamura, S.; Tokunaga, K.; Yoshida, N.; Noda, N.; Yang, L.; Xu, Z.

    2004-08-01

    High heat flux properties of pure tungsten and plasma sprayed tungsten coatings on carbon substrates have been studied by annealing and cyclic heat loading. The recrystallization temperature and an activation energy QR=126 kJ/mol for grain growth of tungsten coating by vacuum plasma spray (VPS) were estimated, and the microstructural changes of multi-layer tungsten and rhenium interface pre-deposited by physical vapor deposition (PVD) with anneal temperature were investigated. Cyclic load tests indicated that pure tungsten and VPS-tungsten coating could withstand 1000 cycles at 33-35 MW/m 2 heat flux and 3 s pulse duration, and inert gas plasma spray (IPS)-tungsten coating showed local cracks by 300 cycles but did not induce failure by further cycles. However, the failure of pure tungsten and VPS-tungsten coating by fatigue cracking was observed under higher heat load (55-60 MW/m 2) for 420 and 230 cycles, respectively.

  8. pureS2HAT: S 2HAT-based Pure E/B Harmonic Transforms

    NASA Astrophysics Data System (ADS)

    Grain, J.; Stompor, R.; Tristram, M.

    2011-10-01

    The pS2HAT routines allow efficient, parallel calculation of the so-called 'pure' polarized multipoles. The computed multipole coefficients are equal to the standard pseudo-multipoles calculated for the apodized sky maps of the Stokes parameters Q and U subsequently corrected by so-called counterterms. If the applied apodizations fullfill certain boundary conditions, these multipoles correspond to the pure multipoles. Pure multipoles of one type, i.e., either E or B, are ensured not to contain contributions from the other one, at least to within numerical artifacts. They can be therefore further used in the estimation of the sky power spectra via the pseudo power spectrum technique, which has to however correctly account for the applied apodization on the one hand, and the presence of the counterterms, on the other. In addition, the package contains the routines permitting calculation of the spin-weighted apodizations, given an input scalar, i.e., spin-0 window. The former are needed to compute the counterterms. It also provides routines for maps and window manipulations. The routines are written in C and based on the S2HAT library, which is used to perform all required spherical harmonic transforms as well as all inter-processor communication. They are therefore parallelized using MPI and follow the distributed-memory computational model. The data distribution patterns, pixelization choices, conventions etc are all as those assumed/allowed by the S2HAT library.

  9. Proteomic analysis of Mortierella isabellina M6-22 during cold stress.

    PubMed

    Hu, Binbin; Luo, Minzhou; Ji, Xiuling; Lin, Lianbing; Wei, Yunlin; Zhang, Qi

    2016-11-01

    We aimed to gain a better understanding of cold adaption in Mortierella isabellina M6-22 by using proteomics approaches. The temperature range and optimal temperature for M6-22 growth were investigated, and composition changes in fatty acids were analyzed. Accompanied with the 2-D gel electrophoresis, MALDI-TOF/TOF-MS analysis was conducted to characterize alterations in protein profiling in M6-22 cultured at 30 °C for 24 h and 15 °C for another 24 h when compared with those cultured at 30 °C for 48 h. Gene Ontology (GO) cluster analysis was finally conducted for successfully identified proteins. M6-22 cells could grow well at temperatures ranging from 15 to 30 °C. As temperature decreased from 30 to 15 °C, LA and GLA significantly increased from 11.63 to 17.85 % and from 9.12 to 13.19 %, respectively, while oleic acid significantly decreased from 47.25 to 36.53 %. Proteomics analyses revealed 111 differentially expressed protein spots, among which 5 unique proteins (A38, A40, A47, A49 and A58), 29 up-regulated proteins and 10 down-regulated proteins were identified by MALDI-TOF/TOF-MS. GO enrichment analysis demonstrated that these proteins mainly involved in glycolytic pathway (A34 and A50), electron transport (A28), ATP production (A35 and B39) and protein modification (A38). A total of 44 differentially expressed proteins have been successfully identified in M. isabellina M6-22 cultured at 15 °C. These proteins may play important roles in cold adaption via regulation of ATP synthesis, activation of cold-adaptive proteins, degradation of needless protein, accumulation of PUFAs, etc.

  10. RGD-containing peptides activate S6K1 through beta3 integrin in adult cardiac muscle cells.

    PubMed

    Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

    2003-10-24

    The enzyme p70S6 kinase (S6K1) is critical for cell growth, and we have reported its activation during cardiac hypertrophy. Because cardiac hypertrophy also involves integrin activation, we analyzed whether integrins could contribute to S6K1 activation. Using adult feline cardiomyocytes, here we report that integrin-interacting Arg-Gly-Asp (RGD) peptides activate S6K1 as observed by band shifting, kinase activity and phosphorylation at Thr-389 and Thr-421/Ser-424 of S6K1, and S6 protein phosphorylation. Perturbation of specific integrin function with blocking antibodies and by overexpressing the beta1A cytoplasmic tail revealed that beta3 but not beta1 integrin mediates the RGD-induced S6K1 activation. This activation is focal adhesion complex-independent and is accompanied by the activation of extracellular signal-regulated kinases 1/2 (ERK) and mammalian target of rapamycin (mTOR). Studies using specific inhibitors and dominant negative c-Raf expression in cardiomyocytes indicate that the S6K1 activation involves mTOR, MEK/ERK, and phosphatidylinositol 3-kinase pathways and is independent of protein kinase C and c-Raf. Finally, addition of fluorescent-labeled RGD peptide to cardiomyocytes exhibits its internalization and localization to the endocytic vesicles, and pretreatment of cardiomyocytes with endocytic inhibitors reduced the S6K1 activation. These data suggest that RGD interaction with beta3 integrin and its subsequent endocytosis trigger specific signaling pathway(s) for S6K1 activation in cardiomyocytes and that this process may contribute to hypertrophic growth and remodeling of myocardium.

  11. A novel mutation m.8561C>G in MT-ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism.

    PubMed

    Kytövuori, Laura; Lipponen, Joonas; Rusanen, Harri; Komulainen, Tuomas; Martikainen, Mika H; Majamaa, Kari

    2016-11-01

    Defects in the respiratory chain or mitochondrial ATP synthase (complex V) result in mitochondrial dysfunction that is an important cause of inherited neurological disease. Two of the subunits of complex V are encoded by MT-ATP6 and MT-ATP8 in the mitochondrial genome. Pathogenic mutations in MT-ATP6 are associated with the Leigh syndrome, the syndrome of neuropathy, ataxia, and retinitis pigmentosa (NARP), as well as with non-classical phenotypes, while MT-ATP8 is less frequently mutated in patients with mitochondrial disease. We investigated two adult siblings presenting with features of cerebellar ataxia, peripheral neuropathy, diabetes mellitus, sensorineural hearing impairment, and hypergonadotropic hypogonadism. As the phenotype was suggestive of mitochondrial disease, mitochondrial DNA was sequenced and a novel heteroplasmic mutation m.8561C>G in the overlapping region of the MT-ATP6 and MT-ATP8 was found. The mutation changed amino acids in both subunits. Mutation heteroplasmy correlated with the disease phenotype in five family members. An additional assembly intermediate of complex V and increased amount of subcomplex F 1 were observed in myoblasts of the two patients, but the total amount of complex V was unaffected. Furthermore, intracellular ATP concentration was lower in patient myoblasts indicating defective energy production. We suggest that the m.8561C>G mutation in MT-ATP6/8 is pathogenic, leads biochemically to impaired assembly and decreased ATP production of complex V, and results clinically in a phenotype with the core features of cerebellar ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism.

  12. Nonfatal and fatal intoxications with pure caffeine - report of three different cases.

    PubMed

    Magdalan, Jan; Zawadzki, Marcin; Skowronek, Rafał; Czuba, Magdalena; Porębska, Barbara; Sozański, Tomasz; Szpot, Paweł

    2017-09-01

    Caffeine is not usually perceived as a drug by most people because it is found in many foods and drinks, including caffeinated energy drinks, as well as in over the counter analgesics and cold preparations. Recently in Poland it has become increasingly common to take pure caffeine, bought through online stores, as a psychoanaleptic. This creates a much higher risk of severe and even fatal poisoning in comparison with the risk associated with the abuse of food products and non-prescription medicines containing low doses of caffeine. This paper presents three different cases of poisoning that occurred when pure caffeine was taken as psychostimulant; in cases 1 and 2 poisoning was the result of a single overdose, while in the case 3 poisoning resulted from a cumulative overdose. In the case 1 there was a severe intoxication (persistent vomiting, hypotension, tremor), and the concentration of caffeine in the blood was found to be 80.16 μg/mL. The patient was treated using hemodialysis, which caused a rapid decrease in blood levels of caffeine and relief of the clinical symptoms of poisoning. Cases 2 and 3 were fatal poisonings, and recorded levels of caffeine in post mortem blood samples were 140.64 μg/mL and 613.0 μg/mL. In case 2 the patient died 10 min after admission to hospital as a result of sudden cardiac arrest, which was preceded by an attack of convulsions, and in case 3 death occurred in home and was also sudden in nature. Taking pure caffeine as a stimulant is associated with a high risk of overdose and the development of serious and even fatal poisoning, and those using pure caffeine are generally completely unaware of these risks. In such cases, death is usually sudden due to functional mechanisms.

  13. Cost-effectiveness analysis of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer.

    PubMed

    Graham, Christopher N; Hechmati, Guy; Hjelmgren, Jonas; de Liège, Frédérique; Lanier, Julie; Knox, Hediyyih; Barber, Beth

    2014-11-01

    To investigate the cost-effectiveness of panitumumab plus mFOLFOX6 (oxaliplatin, 5-fluorouracil and leucovorin) compared with bevacizumab plus mFOLFOX6 in first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC). A semi-Markov model was constructed from a French health collective perspective, with health states related to first-line treatment (progression-free), disease progression with and without subsequent active treatment, resection of metastases, disease-free after successful resection and death. Parametric survival analyses of patient-level progression-free and overall survival data from the only head-to-head clinical trial of panitumumab and bevacizumab (PEAK) were performed to estimate transitions to disease progression and death. Additional data from PEAK informed the amount of each drug consumed, duration of therapy, subsequent therapy use, and toxicities related to mCRC treatment. Literature and French public data sources were used to estimate unit costs associated with treatment and duration of subsequent active therapies. Utility weights were calculated from patient-level data from panitumumab trials in the first-, second- and third-line settings. A life-time perspective was applied. Scenario, one-way, and probabilistic sensitivity analyses were performed. Based on a head-to-head clinical trial that demonstrates better efficacy outcomes for patients with wild-type RAS mCRC who receive panitumumab plus mFOLFOX6 versus bevacizumab plus mFOLFOX6, the incremental cost per life-year gained was estimated to be €26,918, and the incremental cost per quality-adjusted life year (QALY) gained was estimated to be €36,577. Sensitivity analyses indicate the model is robust to alternative parameters and assumptions. The incremental cost per QALY gained indicates that panitumumab plus mFOLFOX6 represents good value for money in comparison to bevacizumab plus mFOLFOX6 and, with a willingness-to-pay ranging from €40,000 to €60

  14. Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in relation to CYP2B6*6 polymorphism.

    PubMed

    Pan, Wei; Bae, Soo-Kyung; Shim, Eon-Jeong; Park, Sung-Eun; Lee, Sang-Seop; Park, Soo-Jin; Yeo, Chang-Woo; Zhou, Hong-Hao; Shon, Ji-Hong; Shin, Jae-Gook

    2013-02-01

    Plasma concentrations of sibutramine and its two active metabolites after single oral dose of sibutramine were determined in Korean healthy male subjects with different CYP2B6 genotypes (CYP2B6*1/*1, *1/*6 and *6/*6), either alone or after four-day pretreatment with clopidogrel or clarithromycin. The pretreatment with clopidogrel and clarithromycin raised the mean area under the concentration-time curve (AUC) of sibutramine by 163% and 255%, respectively. Co-administration of clarithromycin, combined with CYP2B6*6/*6 genotype, led to highest concentration of sibutramine. The molar sum AUC (M1 + M2) was raised by 35% in the clopidogrel phase but not significantly affected by clarithromycin or CYP2B6 genotype. The CYP2B6*6/*6 subjects in the clopidogrel phase showed the highest molar AUC (M1 + M2) among three genotype groups throughout the three phases. The exposure of sibutramine and its metabolites seemed to be associated with the CYP2B6 genotype. The treatment of clopidogrel significantly altered the disposition of active metabolites as well as sibutramine, but clarithromycin only affects the disposition of sibutramine. These results suggest that the perturbation of CYP2B6 activity may contribute to the inter-individual variation of sibutramine drug responses although the clinical relevance is remained to be established.

  15. Stabilization of the H,K-ATPase M5M6 membrane hairpin by K+ ions. Mechanistic significance for p2-type atpases.

    PubMed

    Gatto, C; Lutsenko, S; Shin, J M; Sachs, G; Kaplan, J H

    1999-05-14

    The integral membrane protein, the gastric H,K-ATPase, is an alpha-beta heterodimer, with 10 putative transmembrane segments in the alpha-subunit and one such segment in the beta-subunit. All transmembrane segments remain within the membrane domain following trypsinization of the intact gastric H,K-ATPase in the presence of K+ ions, identified as M1M2, M3M4, M5M6, and M7, M8, M9, and M10. Removal of K+ ions from this digested preparation results in the selective loss of the M5M6 hairpin from the membrane. The release of the M5M6 fragment is directed to the extracellular phase as evidenced by the accumulation of the released M5M6 hairpin inside the sealed inside out vesicles. The stabilization of the M5M6 hairpin in the membrane phase by the transported cation as well as loss to the aqueous phase in the absence of the transported cation has been previously observed for another P2-type ATPase, the Na, K-ATPase (Lutsenko, S., Anderko, R., and Kaplan, J. H. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 7936-7940). Thus, the effects of the counter-transported cation on retention of the M5M6 segment in the membrane as compared with the other membrane pairs may be a general feature of P2-ATPase ion pumps, reflecting a flexibility of this region that relates to the mechanism of transport.

  16. [Inhibition of Bacillus coagulans growth in laboratory media and in fruit purees].

    PubMed

    Cerrutti, P; Alzamora, S M; de Huergo, M S

    2000-01-01

    The growth of two strains of B. coagulans was inhibited in laboratory media at pH < or = 4.5, and at water activity (aw) levels of 0.96 for B. coagulans NRS 609 and 0.95 for B. coagulans ATCC 803. The growth of both strains was also inhibited in apple and strawberry purees (pH = 3.5) stored at 37 degrees C for over two months. B. coagulans was able to grow in banana puree (pH approximately equal to 5.0) but acidification of the puree at pH = 3.5 was enough to prevent growth. The addition of up to 3,000 ppm vainillin ("natural" preservative) or 1,000 ppm potassium sorbate (traditional preservative) at pH higher than the inhibitory level previously determined could not prevent growth of B. coagulans in laboratory or in fruits, but 100 ppm lysozyme retarded growth in laboratory media at different pH levels (from 4.5 to 6.7) and in banana puree. As lysozyme showed to be effective at pH < or = 6.7, it might be used to prevent growth of B. coagulans at an eventual increment of pH during storage.

  17. Transcriptional profiling of pure fibrolamellar hepatocellular carcinoma reveals an endocrine signature.

    PubMed

    Malouf, Gabriel G; Job, Sylvie; Paradis, Valérie; Fabre, Monique; Brugières, Laurence; Saintigny, Pierre; Vescovo, Laure; Belghiti, Jacques; Branchereau, Sophie; Faivre, Sandrine; de Reyniès, Aurélien; Raymond, Eric

    2014-06-01

    Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of liver cancer occurring mostly in children and young adults. We have shown that FLC comprises two separate entities: pure (p-FLC) and mixed-FLC (m-FLC), differing in clinical presentation and course. We show that p-FLCs have a distinct gene expression signature different from that of m-FLCs, which have a signature similar to that of classical hepatocellular carcinomas. We found p-FLC profiles to be unique among 263 profiles related to diverse tumoral and nontumoral liver samples. We identified two distinct molecular subgroups of p-FLCs with different outcomes. Pathway analysis of p-FLCs revealed ERBB2 overexpression and an up-regulation of glycolysis, possibly leading to compensatory mitochondrial hyperplasia and oncocytic differentiation. Four of the sixteen genes most significantly overexpressed in p-FLCs were neuroendocrine genes: prohormone convertase 1 (PCSK1); neurotensin; delta/notch-like EGF repeat containing; and calcitonin. PCSK1 overexpression was validated by immunohistochemistry, yielding specific, diffuse staining of the protein throughout the cytoplasm, possibly corresponding to a functional form of this convertase. p-FLCs have a unique transcriptomic signature characterized by the strong expression of specific neuroendocrine genes, suggesting that these tumors may have a cellular origin different from that of HCC. Our data have implications for the use of genomic profiling for diagnosis and selection of targeted therapies in patients with p-FLC. © 2014 by the American Association for the Study of Liver Diseases.

  18. A determination of the external forces required to move the benchmark active controls testing model in pure plunge and pure pitch

    NASA Technical Reports Server (NTRS)

    Dcruz, Jonathan

    1993-01-01

    In view of the strong need for a well-documented set of experimental data which is suitable for the validation and/or calibration of modern Computational Fluid Dynamics codes, the Benchmark Models Program was initiated by the Structural Dynamics Division of the NASA Langley Research Center. One of the models in the program, the Benchmark Active Controls Testing Model, consists of a rigid wing of rectangular planform with a NACA 0012 profile and three control surfaces (a trailing-edge control surface, a lower-surface spoiler, and an upper-surface spoiler). The model is affixed to a flexible mount system which allows only plunging and/or pitching motion. An approximate analytical determination of the forces required to move this model, with its control surfaces fixed, in pure plunge and pure pitch at a number of test conditions is included. This provides a good indication of the type of actuator system required to generate the aerodynamic data resulting from pure plunging and pure pitching motion, in which much interest was expressed. The analysis makes use of previously obtained numerical results.

  19. Self-esteem in pure bullies and bully/victims: a longitudinal analysis.

    PubMed

    Pollastri, Alisha R; Cardemil, Esteban V; O'Donnell, Ellen H

    2010-08-01

    Past research on the self-esteem of bullies has produced equivocal results. Recent studies have suggested that the inconsistent findings may be due, in part, to the failure to account for bully/victims: those children who both bully and are victims of bullying. In this longitudinal study, we examined the distinctions among pure bullies, pure victims, bully/victims, and noninvolved children in a sample of 307 middle school students. Analyses of cross-sectional and longitudinal results supported the importance of distinguishing between pure bullies and bully/victims. In addition, results revealed some interesting sex differences: girls in the pure bully and bully/victim groups reported significant increases in self-esteem over time, with girls in the pure bully group reporting the greatest increase, whereas boys in these groups reported no significant changes in self-esteem over time.

  20. chemf: A purely functional chemistry toolkit.

    PubMed

    Höck, Stefan; Riedl, Rainer

    2012-12-20

    Although programming in a type-safe and referentially transparent style offers several advantages over working with mutable data structures and side effects, this style of programming has not seen much use in chemistry-related software. Since functional programming languages were designed with referential transparency in mind, these languages offer a lot of support when writing immutable data structures and side-effects free code. We therefore started implementing our own toolkit based on the above programming paradigms in a modern, versatile programming language. We present our initial results with functional programming in chemistry by first describing an immutable data structure for molecular graphs together with a couple of simple algorithms to calculate basic molecular properties before writing a complete SMILES parser in accordance with the OpenSMILES specification. Along the way we show how to deal with input validation, error handling, bulk operations, and parallelization in a purely functional way. At the end we also analyze and improve our algorithms and data structures in terms of performance and compare it to existing toolkits both object-oriented and purely functional. All code was written in Scala, a modern multi-paradigm programming language with a strong support for functional programming and a highly sophisticated type system. We have successfully made the first important steps towards a purely functional chemistry toolkit. The data structures and algorithms presented in this article perform well while at the same time they can be safely used in parallelized applications, such as computer aided drug design experiments, without further adjustments. This stands in contrast to existing object-oriented toolkits where thread safety of data structures and algorithms is a deliberate design decision that can be hard to implement. Finally, the level of type-safety achieved by Scala highly increased the reliability of our code as well as the productivity of

  1. A Signature of Self-Organized Criticality in the HT-6M Edge Plasma Turbulence

    NASA Astrophysics Data System (ADS)

    Wang, Wen-Hao; Yu, Chang-Xuan; Wen, Yi-Zhi; Xu, Yu-Hong; Ling, Bi-Li; Gong, Xian-Zu; Liu, Bao-Hua; Wan, Bao-Nian

    2001-03-01

    Power spectra of electron density and floating potential fluctuations in the velocity shear layer of the HT-6M edge region have been measured and analysed. All the spectra have three distinct frequency regions with the spectral decay indices typical of self-organized criticality systems (0, -1 and -4) when Doppler shift effects induced by the plasma E×B flow velocity have been taken into account. These results are consistent with the predictions of the self-organized criticality models, which may be an indication of edge plasma turbulence in the HT-6M tokamak evolving into a critical state independent of local plasma parameters.

  2. Role of temperament in early adolescent pure and co-occurring internalizing and externalizing problems using a bifactor model: Moderation by parenting and gender

    PubMed Central

    WANG, FRANCES L.; EISENBERG, NANCY; VALIENTE, CARLOS; SPINRAD, TRACY L.

    2015-01-01

    We contribute to the literature on the relations of temperament to externalizing and internalizing problems by considering parental emotional expressivity and child gender as moderators of such relations and examining prediction of pure and co-occurring problem behaviors during early to middle adolescence using bifactor models (which provide unique and continuous factors for pure and co-occurring internalizing and externalizing problems). Parents and teachers reported on children’s (4.5- to 8-year-olds; N = 214) and early adolescents’ (6 years later; N = 168) effortful control, impulsivity, anger, sadness, and problem behaviors. Parental emotional expressivity was measured observationally and with parents’ self-reports. Early-adolescents’ pure externalizing and co-occurring problems shared childhood and/or early-adolescent risk factors of low effortful control, high impulsivity, and high anger. Lower childhood and early-adolescent impulsivity and higher early-adolescent sadness predicted early-adolescents’ pure internalizing. Childhood positive parental emotional expressivity more consistently related to early-adolescents’ lower pure externalizing compared to co-occurring problems and pure internalizing. Lower effortful control predicted changes in externalizing (pure and co-occurring) over 6 years, but only when parental positive expressivity was low. Higher impulsivity predicted co-occurring problems only for boys. Findings highlight the probable complex developmental pathways to adolescent pure and co-occurring externalizing and internalizing problems. PMID:26646352

  3. Temperature-dependent Raman and ultraviolet photoelectron spectroscopy studies on phase transition behavior of VO{sub 2} films with M1 and M2 phases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Okimura, Kunio, E-mail: okifn@keyaki.cc.u-tokai.ac.jp; Hanis Azhan, Nurul; Hajiri, Tetsuya

    Structural and electronic phase transitions behavior of two polycrystalline VO{sub 2} films, one with pure M1 phase and the other with pure M2 phase at room temperature, were investigated by temperature-controlled Raman spectroscopy and ultraviolet photoelectron spectroscopy (UPS). We observed characteristic transient dynamics in which the Raman modes at 195 cm{sup −1} (V-V vibration) and 616 cm{sup −1} (V-O vibration) showed remarkable hardening along the temperature in M1 phase film, indicating the rearrangements of V-V pairs and VO{sub 6} octahedra. It was also shown that the M1 Raman mode frequency approached those of invariant M2 peaks before entering rutile phase. In UPSmore » spectra with high energy resolution of 0.03 eV for the M2 phase film, narrower V{sub 3d} band was observed together with smaller gap compared to those of M1 phase film, supporting the nature of Mott insulator of M2 phase even in the polycrystalline film. Cooperative behavior of lattice rearrangements and electronic phase transition was suggested for M1 phase film.« less

  4. Revealing the effect of 6-gingerol, 6-shogaol and curcumin on mPGES-1, GSK-3β and β-catenin pathway in A549 cell line.

    PubMed

    Eren, Demirpolat; Betul, Yerer Mukerrem

    2016-10-25

    In our study, anticancer effects of 6-gingerol, 6-shogaol from ginger and curcumin from turmeric were investigated and the results were compared with each other. We aimed to reveal their effects on microsomal prostaglandine E2 synthase 1 (mPGES-1) which is related with cancer progression and inflammation as well as β-catenin and glycogen synthase kinase 3β (GSK-3β) that are the main components of Wnt/GSK3 pathway. As it is known activation of GSK-3β and high levels of mPGES-1 pathway leads to cell proliferation and aggravates cancer progression. Therefore both of them are potential targets for cancer therapy. 6-shogaol and 6-gingerol' s effect on this pathway is not known very well up to now while curcumin that is known as an mPGES-1 inhibitor has anticancer properties via this pathway and many other pathways. Besides being in Zingiberaceae family, ginger's 6-gingerol and 6-shogaol have a molecular similarity with turmeric's curcumin. In our study we investigated their effects using a popular non small lung cancer cell line named A549 which expresses mPGES-1 and has active GSK3β pathway. IL-1β was used for inducing mPGES-1 and enabling the cancer characteristics such as cell proliferation. So compounds that inactivates or decreases the level of these components might be potential anticancer agents. A549 cells were incubated with interleukin 1β (IL-1β) for 24 h in order to maintain mPGES-1 enzyme induction. Experiments were performed both on IL-1β and non-IL-1β group. Real time cell analysis was performed to determine the cytotoxicity. Samples for western blotting and RT-PCR were collected after 24 h incubation with compounds to determine the amount of mPGES-1, GSK-3β, p-GSK-3β, β-catenin protein and mRNA. PGE2 which is the end product of mPGES-1 was measured by using ELISA kit. As a result of cell profile assay, cells exposed to IL-1β proliferate faster than non-IL-1β ones. This shows that induced mPGES-1 might play a role through GSK3β pathway

  5. Novel Nd 2WO 6-type Sm 2- xA xM 1- yB yO 6- δ (A = Ca, Sr; M = Mo, W; B = Ce, Ni) mixed conductors

    NASA Astrophysics Data System (ADS)

    Li, Qin; Thangadurai, Venkataraman

    In the present work, we have explored novel Nd 2WO 6-type structure Sm 2- xA xM 1- yB yO 6- δ (A = Ca, Sr; M = Mo, W; B = Ce, Ni) as precursor for the development of solid oxide fuel cells (SOFCs) anodes. The formation of single-phase monoclinic structure was confirmed by powder X-ray diffraction (PXRD) for the A- and B-doped Sm 2MO 6 (SMO). Samples after AC measurements under wet H 2 up to 850 °C changed from Nd 2WO 6-type structure into Sm 2MoO 5 due to the reduction of Mo VI that was confirmed by PXRD and is consistent with literature. The electrical conductivity was determined using 2-probe AC impedance and DC method and was compared with 4-probe DC method. The total electrical conductivity obtained from these two different techniques was found to vary within the experimental error over the investigated temperature of 350-650 °C. Ionic and electronic conductivity were studied using electron-blocking electrodes technique. Among the samples studied, Sm 1.8Ca 0.2MoO 6- δ exhibits total conductivity of 0.12 S cm -1 at 550 °C in wet H 2 with an activation energy of 0.06 eV. Ca-doped SMO appears to be chemically stable against reaction with YSZ electrolyte at 800 °C for 24 h in wet H 2. The ionic transference number (t i) of Sm 1.9Ca 0.1MoO 6- δ in wet H 2 at 550 °C (pO 2 = 10 -25.5 atm) was found to be about 0.012 after subtraction of electrical lead resistance from the 2-probe AC data and showed predominate electronic conductors.

  6. Transitioning to a narrow path: the impact of fear of falling in older adults.

    PubMed

    Dunlap, Pamela; Perera, Subashan; VanSwearingen, Jessie M; Wert, David; Brach, Jennifer S

    2012-01-01

    Everyday ambulation requires navigation of variable terrain, transitions from wide to narrow pathways, and avoiding obstacles. While the effect of age on the transition to a narrow path has been examined briefly, little is known about the impact of fear of falling on gait during the transition to a narrow path. The purpose was to examine the effect of age and fear of falling on gait during transition to a narrow path. In 31 young, mean age=25.3 years, and 30 older adults, mean age=79.6 years, step length, step time, step width and gait speed were examined during usual and transition to narrow pathway using an instrumented walkway. During the transition to narrow walk condition, fearful older adults compared to young had a wider step width (0.06 m vs 0.04 m) prior to the narrow path and took shorter steps (0.53 m vs 0.72 m; p<0.001). Compared to non-fearful older adults, fearful older adults walked slower and took shorter steps during narrow path walking (gait speed: 1.1m/s vs 0.82 m/s; p=0.01; step length: 0.60 m vs 0.47 m; p=0.03). In young and non-fearful older adults narrow path gait was similar to usual gait. Whereas older adults who were fearful, walked slower (0.82 m/s vs 0.91 m/s; p=0.001) and took shorter steps (0.44 m vs 0.53 m; p=0.004) during narrow path walking compared to usual walking. Changes in gait characteristics with transitioning to a narrow pathway were greater for fear of falling than for age. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group.

    PubMed

    Barnard, Dorothy R; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly; Woods, William G

    2007-07-01

    Myelodysplastic syndromes (MDS), acute erythroleukemia (FAB M6), and acute megakaryocytic leukemia (FAB M7) have overlapping features. Children without Down syndrome or acute promyelocytic leukemia who were newly diagnosed with primary myelodysplastic syndrome or acute myeloid leukemia (AML) M6 or M7 were compared to children with de novo AML M0-M5. All children were entered on the Children's Cancer Group therapeutic research study CCG 2891. The presentation and outcomes of the 132 children diagnosed with MDS (60 children), AML FAB M6 (19 children), or AML FAB M7 (53 children) were similar. Children with AML FAB M7 were diagnosed at a significantly younger age (P = 0.001). Children with MDS, M6, or M7 had significantly lower white blood cell (WBC) counts (P = 0.001), lower peripheral blast counts (P < 0.001), and an increased frequency of -7/7q- (P = 0.003) at presentation. All three groups had significantly inferior overall survival (OS) (P < 0.001) and event free survival (P < 0.001) compared with the 748 children diagnosed with AML FAB M0-M5 when assessed from entry on study. This poor survival was largely attributable to induction death and failure. However, when assessed from successful completion of induction therapy, the 5-year OS (P = 0.090)(49.1 vs. 56.9%) and disease-free survival (DFS) (P = 0.113)(38.0 vs. 46.3%) therapy were not significantly different from other children with AML. Childhood AML FAB M6 and AML M7 resemble MDS in presentation, poor induction success rates, and outcomes.

  8. Geometric characterization of separability and entanglement in pure Gaussian states by single-mode unitary operations

    NASA Astrophysics Data System (ADS)

    Adesso, Gerardo; Giampaolo, Salvatore M.; Illuminati, Fabrizio

    2007-10-01

    We present a geometric approach to the characterization of separability and entanglement in pure Gaussian states of an arbitrary number of modes. The analysis is performed adapting to continuous variables a formalism based on single subsystem unitary transformations that has been recently introduced to characterize separability and entanglement in pure states of qubits and qutrits [S. M. Giampaolo and F. Illuminati, Phys. Rev. A 76, 042301 (2007)]. In analogy with the finite-dimensional case, we demonstrate that the 1×M bipartite entanglement of a multimode pure Gaussian state can be quantified by the minimum squared Euclidean distance between the state itself and the set of states obtained by transforming it via suitable local symplectic (unitary) operations. This minimum distance, corresponding to a , uniquely determined, extremal local operation, defines an entanglement monotone equivalent to the entropy of entanglement, and amenable to direct experimental measurement with linear optical schemes.

  9. Assessment of underground gamma ray fluxes at a depth of 1230 m

    NASA Astrophysics Data System (ADS)

    Bakich, A. M.; Omori, M.; Peak, L. S.; Wearne, N. T.

    1984-10-01

    A sodium iodide crystal detector has been used to measure gamma ray spectra at a depth of 1230 m underground in a silver, lead and zinc mine. Both unshielded and shielded runs using blocks of lead and paraffin were taken. The results are considered in three different energy ranges, 0-3 MeV, 3-6 MeV and greater than 6 MeV. The low energy results are predictable in terms of the familiar isotopes to be expected in the ore body around the detector. The intermediate energy results indicate some residual alpha activity in the crystal assembly whilst the high energy results show a flux of gammas extending well past 10 MeV. Very pure shielding would be required to substantially reduce this flux.

  10. Verification of pure moment testing in a multi-degree of freedom spine testing apparatus.

    PubMed

    Fuller, Amy M; Chui, Jennifer M; Cook, Daniel J; Yeager, Matthew S; Gladowski, David A; Cheng, Boyle C

    2012-01-01

    Pure moment testing is a common method used in cadaveric spine testing. The fundamental basis for the widespread acceptance of applying a pure moment is uniform loading along the column of the spine. To our knowledge, this protocol has not been experimentally verified on a multi-degree of freedom testing apparatus. Given its ubiquitous use in spine biomechanics laboratories, confirmation of this comparative cadaveric test protocol is paramount. Group A specimens (n =13) were used to test the pure moment protocol, by use of 3 constructs that changed the number of involved vertebrae, orientation, and rigidity of the spine construct. Group B specimens (n = 6) were used to determine whether potting orientation, testing order, or degradation affected the range of motion (ROM) by use of 8 constructs. Each group was subjected to 3 cycles of flexion-extension, lateral bending, and axial torsion. The data from the third cycle were used to calculate the ROM for each method. Group A testing resulted in significant differences in ROM across the 3 constructs for lateral bending and axial torsion (P < .02) and trended toward a difference for flexion-extension (P = .055). Group B testing showed an increase in ROM across 8 constructs (P < .04) but no significant difference due to the orientation change. The increased ROM across constructs observed in both groups indicates that the cause is likely the testing order or degradation of the specimens, with orientation having no observed effect. The data do not invalidate pure moment testing, and its use should persist.

  11. Pure Motor Stroke Secondary to Cerebral Infarction of Recurrent Artery of Heubner after Mild Head Trauma: A Case Report.

    PubMed

    Yilmaz, Ali; Kizilay, Zahir; Ozkul, Ayca; Çirak, Bayram

    2016-03-15

    The recurrent Heubner's artery is the distal part of the medial striate artery. Occlusion of the recurrent artery of Heubner, classically contralateral hemiparesis with fasciobrachiocrural predominance, is attributed to the occlusion of the recurrent artery of Heubner and is widely known as a stroke syndrome in adults. However, isolated occlusion of the deep perforating arteries following mild head trauma also occurs extremely rarely in childhood. Here we report the case of an 11-year-old boy with pure motor stroke. The brain MRI showed an acute ischemia in the recurrent artery of Heubner supply area following mild head trauma. His fasciobrachial hemiparesis and dysarthria were thought to be secondary to the stretching of deep perforating arteries leading to occlusion of the recurrent artery of Heubner. Post-traumatic pure motor ischemic stroke can be secondary to stretching of the deep perforating arteries especially in childhood.

  12. Parenting Stress as a Mediator Between Childhood ADHD and Early Adult Female Outcomes.

    PubMed

    Gordon, Chanelle T; Hinshaw, Stephen P

    2017-01-01

    The purpose of this study is to examine the mediating role of parenting stress (both parental distress and stress due to dysfunctional interactions in the mother-daughter relationship [PSDI]) in the link between childhood attention-deficit/hyperactivity disorder (ADHD) status and several important young adult outcomes. The diverse sample comprised 140 girls with ADHD and 88 age- and ethnicity-matched comparisons, evaluated at ages 6-12 years and followed prospectively for five years (M age = 14.2) and 10 years (M age = 19.6). The PSDI experienced by a mother during her daughter's adolescence mediated the link between her daughter's childhood ADHD status and adult externalizing and internalizing symptoms. PSDI also mediated the link between ADHD status and young adult nonsuicidal self-injury and had an indirect effect in the relation between childhood ADHD and young adult depressive symptoms. The mediating role of PSDI with respect to internalizing symptoms and depressive symptoms remained in place even when covarying adolescent internalizing/depressive symptoms. Parenting stress, particularly related to maternal perceptions of dysfunctional interactions with adolescent daughters, serves as a key mediator in the association between childhood ADHD status and important domains of young adult functioning. Minimizing parenting stress and dysfunctional mother-daughter interactions during adolescence might reduce the risk of adverse adult outcomes for girls with ADHD.

  13. The TRPM6 Kinase Domain Determines the Mg·ATP Sensitivity of TRPM7/M6 Heteromeric Ion Channels*

    PubMed Central

    Zhang, Zheng; Yu, Haijie; Huang, Junhao; Faouzi, Malika; Schmitz, Carsten; Penner, Reinhold; Fleig, Andrea

    2014-01-01

    The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg2+) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg2+ and therefore unlikely to be active at physiological levels of [Mg2+]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex. PMID:24385424

  14. The TRPM6 kinase domain determines the Mg·ATP sensitivity of TRPM7/M6 heteromeric ion channels.

    PubMed

    Zhang, Zheng; Yu, Haijie; Huang, Junhao; Faouzi, Malika; Schmitz, Carsten; Penner, Reinhold; Fleig, Andrea

    2014-02-21

    The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg(2+)) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg(2+) and therefore unlikely to be active at physiological levels of [Mg(2+)]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex.

  15. Effect of Discharge Time on Plasma Electrolytic Borocarbonitriding of Pure Iron

    NASA Astrophysics Data System (ADS)

    Jin, Xiaoyue; Wu, Jie; Wang, Bin; Yang, Xuan; Chen, Lin; Qu, Yao; Xue, Wenbin

    The plasma electrolytic borocarbonitriding (PEB/C/N) process on pure iron was carried out in 25% borax solution with glycerine and carbamide additives under different discharge time at 360V. The morphology and structure of PEB/C/N hardened layers were analyzed by SEM and XRD. The hardness profiles of hardened layers were measured by microhardness test. Corrosion behavior of PEB/C/N layers was evaluated by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). Their wear performance was carried out using a pin-disc friction and wear tester under dry sliding test. The PEB/C/N samples mainly consisted of α-Fe, Fe2B, Fe3C, FeN, FeB, Fe2O3 and Fe4N phases, and the Fe2B phase was the dominant phase in the boride layer. It was found that the thickness of boride layer increased with the discharge time and reached 14μm after 60min treatment. The microhardness of the boride layer was up to 2100HV, which was much higher than that of the bare pure iron (about 150HV). After PEB/C/N treatment, the corrosion resistance of pure iron was slightly improved. The friction coefficient of PEB/C/N treated pure iron decreased to 0.129 from 0.556 of pure iron substrate. The wear rate of the PEB/C/N layer after 60min under dry sliding against ZrO2 ball was only 1/10 of that of the bare pure iron. The PEB/C/N treatment is an effective way to improve the wear behavior of pure iron.

  16. 155Gd Mössbauer Spectroscopic Study of GdM(CN)6 · 4H2O (M = CrIII, FeIII and CoIII) and KGdM(CN)6 · 3H2O (M = FeII and RuII)

    NASA Astrophysics Data System (ADS)

    Wang, Junhu; Abe, Junko; Kitazawa, Takafumi; Takahashi, Masashi; Takeda, Masuo

    2002-07-01

    155Gd Mössbauer spectroscopic studies of the title complexes have been performed. Although the 155Gd isomer shifts (d) varied scarcely, the quadrupole coupling constants (e2qQ) changed in the range 4.07-4.81 mm s-1. The e2qQ values of KGdM(CN)6 · 3H2O (M = FeII and RuII) are larger than those of GdM(CN)6 · 4H2O (M = CrIII, FeIII, and CoIII), these values increasing with increasing orthorhombic distortion of the crystal structures. A relationship between the e2qQ values and the ionic radii of the transition metal ions has also been recognized

  17. Factor Structure of the Kessler Psychological Distress Scale (K6) among Emerging Adults

    ERIC Educational Resources Information Center

    Bessaha, Melissa L.

    2017-01-01

    Objective: Confirmatory factor analysis was used to assess the factor structure of the 6-item version of the Kessler Psychological Distress Scale (K6). Methods: A subsample of emerging adults, aged 18-29 (n = 20,699), from the 2013 National Survey of Drug Use and Health were used in this study. Results: Each of the models (one-factor, two-factor…

  18. Cardiovascular Morbidity and Pure Red Cell Aplasia Associated With Epoetin Theta Therapy in Patients With Chronic Kidney Disease: A Prospective, Noninterventional, Multicenter Cohort Study.

    PubMed

    Lammerich, Andreas; Balcke, Peter; Bias, Peter; Mangold, Simone; Wiesholzer, Martin

    2016-02-01

    The European Medicines Agency recommends limiting the hemoglobin (Hb) concentration to 10 to 12 g/dL in adults with chronic kidney disease (CKD) receiving erythropoiesis-stimulating agents such as epoetin theta. This postauthorization study assessed the incidence and intensity of cardiovascular events, including ischemic stroke, in patients receiving epoetin theta for anemia associated with CKD. A secondary end point was adverse drug reactions, including pure red cell aplasia. In this prospective, noninterventional, multinational cohort study, consecutive patients with advanced or end-stage renal disease and receiving epoetin theta were followed up for 6 months. Data on reportable adverse events (RAEs) (cardiac disorders, cardiac failure, myocardial infarction, and ischemic stroke and respective subterms), epoetin theta dosage, and Hb concentrations were collected. A post hoc exploratory analysis assessed the incidences of RAEs according to tertiles for individual mean Hb concentration (≤10.7, >10.7-11.47, and >11.47 g/dL for low, intermediate, and high, respectively) and mean weekly epoetin theta dosage (≤62, >62-125, and >125 IU/kg/wk for low, intermediate, and high). Data from 1039 patients were included (577 men, 462 women; mean age, 68.7 years). A total of 101 RAEs were documented in 89 patients (8.6%), for an event rate of 0.1985/person-year. Sixty-four patients (6.1%) died; none of the deaths was considered related to epoetin theta use. The incidence of RAEs was lowest at intermediate Hb concentrations (6.2%) compared with low (11.3%) and high (7.8%) Hb concentrations. The incidence of ischemic stroke was 1.5% at high Hb concentrations versus 0.6% at both the low and intermediate Hb concentrations. The incidence of any RAE was greater in the high-dose group (10.1%) than in the intermediate-dose (8.0%) and low-dose (7.6%) groups. The risk for any cardiovascular RAE or ischemic stroke was greatest in the high-dose/high-Hb group (13.3%), followed by high

  19. Heterodyne detection of Arcturus at 10.6 $mu$m

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Batz, B.D.; Granes, P.; Gay, J.

    1973-10-01

    It is stated that heterodyne detection of Arcturus was achieved at l0.6 mu m in April 1973 during observation at St. Michel Observatory, France. The experimental arrangement is described, and was based on the superimposition of coherent and incoherent beams achieved using a servomechanism working at 2.2 mu m. The local oscillator was a C0/sub 2/ laser working at 10.6 %mmm, and the detector was of the HgCdTe photovoltaic type. It is thought that atmospheric turbulence was responsible for some mismatching of the star and laser beams, causing a loss in the heterodyne signal, and this will be a handicapmore » in future exploitation of the method; the work described, however, is a first step in the direction of heterodyne aperture synthesis in the infrared. (UK)« less

  20. Analysis of pure maple syrup consumers

    Treesearch

    Paul E. Sendak

    1974-01-01

    Virtually all of the pure maple syrup productim in the United States is in the northern states of Maine, Massachusetts, Michigan, New Hampshire, New York, Ohio, Pennsylvania, Vermont, and Wisconsin. Pure maple syrup users living in the maple production area and users living in other areas of the United States were asked a series of questions about their use of pure...

  1. Does Pure Platelet-Rich Plasma Affect Postoperative Clinical Outcomes After Arthroscopic Rotator Cuff Repair? A Randomized Controlled Trial.

    PubMed

    Flury, Matthias; Rickenbacher, Dominik; Schwyzer, Hans-Kaspar; Jung, Christian; Schneider, Marco M; Stahnke, Katharina; Goldhahn, Jörg; Audigé, Laurent

    2016-08-01

    The exact role of platelet-rich plasma (PRP) in rotator cuff tendon reconstruction remains unclear. This study investigated whether an intraoperative pure PRP injection, compared with a local anesthetic injection, improves patient-reported outcomes at 3 and 6 months after arthroscopic rotator cuff repair. The hypothesis was that pure PRP improves patient-reported outcomes (Oxford Shoulder Score [OSS]) at 3 and 6 months after surgery and has the same pain-reducing effect compared with a postoperative subacromial local anesthetic (ropivacaine) injection. Randomized controlled trial; Level of evidence, 1. Between January 2011 and November 2012, a total of 120 patients who underwent arthroscopic double-row repair of a supraspinatus tendon rupture were randomized to receive either pure PRP by an injection at the footprint (PRP group; n = 60) or ropivacaine injected in the subacromial region (control group; n = 60). Seventy-eight percent of patients had other concomitant tears. All patients, surgeons, and follow-up investigators were blinded. Clinical parameters and various outcome scores (Constant-Murley shoulder score; OSS; patient American Shoulder and Elbow Surgeons score; quick Disabilities of the Arm, Shoulder and Hand score; EuroQol 5 dimensions) were documented preoperatively and at 3, 6, and 24 months postoperatively. The repair integrity was assessed by magnetic resonance imaging or ultrasound at 24 months. Furthermore, a pain diary was completed within the first 10 postoperative days, and adverse events were recorded. Group outcome differences were analyzed using t tests, Fisher exact tests, and mixed models. The final follow-up rate was 91%. An associated tear of the subscapularis tendon was diagnosed in 23% of PRP-treated patients and 36% of control patients. Three months after surgery, the mean (±SD) OSS was 32.9 ± 8.6 in PRP-treated patients and 30.7 ± 10.0 in control patients (P = .221). No significant differences were noted for other outcome

  2. A Multinomial Model for Identifying Significant Pure-Tone Threshold Shifts

    ERIC Educational Resources Information Center

    Schlauch, Robert S.; Carney, Edward

    2007-01-01

    Purpose: Significant threshold differences on retest for pure-tone audiometry are often evaluated by application of ad hoc rules, such as a shift in a pure-tone average or in 2 adjacent frequencies that exceeds a predefined amount. Rules that are so derived do not consider the probability of observing a particular audiogram. Methods: A general…

  3. Curcumin Attenuates Lipopolysaccharide-Induced Hepatic Lipid Metabolism Disorder by Modification of m6 A RNA Methylation in Piglets.

    PubMed

    Lu, Na; Li, Xingmei; Yu, Jiayao; Li, Yi; Wang, Chao; Zhang, Lili; Wang, Tian; Zhong, Xiang

    2018-01-01

    N 6 -methyladenosine (m 6 A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m 6 A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m 6 A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/kg dietary curcumin) groups (n = 8/group). The results showed that curcumin reduced the increase in relative liver weight as well as the concentrations of aspartate aminotransferase and lactate dehydrogenase induced by LPS injection in the plasma and liver of weaning piglets (p < 0.05). The amounts of total cholesterol and triacylglycerols were decreased by curcumin compared to that by the LPS injection (p < 0.05). Additionally, curcumin reduced the expression of Bcl-2 and Bax mRNA, whereas it increased the p53 mRNA level in the liver (p < 0.05). Curcumin inhibited the enhancement of SREBP-1c and SCD-1 mRNA levels induced by LPS in the liver. Notably, dietary curcumin affected the expression of METTL3, METTL14, ALKBH5, FTO, and YTHDF2 mRNA, and increased the abundance of m 6 A in the liver of piglets. In conclusion, the protective effect of curcumin in LPS-induced liver injury and hepatic lipid metabolism disruption might be due to the increase in m 6 A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases. © 2018 AOCS.

  4. Equivalence and test-retest reproducibility of conventional and extended-high-frequency audiometric thresholds obtained using pure-tone and narrow-band-noise stimuli.

    PubMed

    John, Andrew B; Kreisman, Brian M

    2017-09-01

    Extended high-frequency (EHF) audiometry is useful for evaluating ototoxic exposures and may relate to speech recognition, localisation and hearing aid benefit. There is a need to determine whether common clinical practice for EHF audiometry using tone and noise stimuli is reliable. We evaluated equivalence and compared test-retest (TRT) reproducibility for audiometric thresholds obtained using pure tones and narrowband noise (NBN) from 0.25 to 16 kHz. Thresholds and test-retest reproducibility for stimuli in the conventional (0.25-6 kHz) and EHF (8-16 kHz) frequency ranges were compared in a repeated-measures design. A total of 70 ears of adults with normal hearing. Thresholds obtained using NBN were significantly lower than thresholds obtained using pure tones from 0.5 to 16 kHz, but not 0.25 kHz. Good TRT reproducibility (within 2 dB) was observed for both stimuli at all frequencies. Responses at the lower limit of the presentation range for NBN centred at 14 and 16 kHz suggest unreliability for NBN as a threshold stimulus at these frequencies. Thresholds in the conventional and EHF ranges showed good test-retest reproducibility, but differed between stimulus types. Care should be taken when comparing pure-tone thresholds with NBN thresholds especially at these frequencies.

  5. Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC).

    PubMed

    Birmann, Brenda M; Andreotti, Gabriella; De Roos, Anneclaire J; Camp, Nicola J; Chiu, Brian C H; Spinelli, John J; Becker, Nikolaus; Benhaim-Luzon, Véronique; Bhatti, Parveen; Boffetta, Paolo; Brennan, Paul; Brown, Elizabeth E; Cocco, Pierluigi; Costas, Laura; Cozen, Wendy; de Sanjosé, Silvia; Foretová, Lenka; Giles, Graham G; Maynadié, Marc; Moysich, Kirsten; Nieters, Alexandra; Staines, Anthony; Tricot, Guido; Weisenburger, Dennis; Zhang, Yawei; Baris, Dalsu; Purdue, Mark P

    2017-06-01

    Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI. Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m 2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04-1.14; P = 0.007]. We observed significant heterogeneity by study design ( P = 0.04), noting the BMI-multiple myeloma association only for population-based studies ( P trend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m 2 ; OR, 1.2; 95% CI, 1.1-1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI ( P interaction <0.0001); we noted statistically significant associations with multiple myeloma for persons overweight (25-<30 kg/m 2 ) or obese (30+ kg/m 2 ) in both younger and usual adulthood (vs. individuals consistently <25 kg/m 2 ), but not for those overweight or obese at only one time period. Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood. Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Effect of surface contamination on adhesive bonding of cast pure titanium and Ti-6Al-4V alloy.

    PubMed

    Watanabe, I; Watanabe, E; Yoshida, K; Okabe, T

    1999-03-01

    There is little information regarding bond strengths of resin cements to cast titanium surfaces contaminated by investment material. This study examined the effect of surface contamination on the shear bond strength of resin cements to cast titanium and Ti-6Al-4V alloy. Two types of disks were cast from commercially pure titanium (CP-Ti) and Ti-6Al-4V alloy ingots using an argon-arc pressure casting unit and a phosphate-bonded Al2 O3 /LiAlSiO6 investment. After casting, disks were subjected to 3 surface treatments: (1) cast surface sandblasted (50 microm-sized Al2 O3 ) for 30 seconds; (2) metal surface sanded with silicon-carbide paper (600 grit) after grinding the contaminated cast surface (approximately 200 microm in thickness); and (3) metal surface sandblasted for 30 seconds after treatment 2. Surface structures were examined after each treatment with SEM and optical microscopy. Each type of disk was then bonded with 2 types of luting materials. Bonded specimens were subjected to thermocycling for up to 50,000 cycles, and shear bond strengths were determined after 0 (baseline) and 50,000 thermocycles. Results were statistically analyzed with 3-way ANOVA (P <.05). Microscopic observation of cast CP-Ti and Ti-6Al-4V exhibited noticeable structures on the cast surfaces apparently contaminated with investment material. However, there were no statistical differences (P >.05) in the bond strengths of both cements between contaminated (treatment 1) and uncontaminated surfaces (treatment 3) for both metals at baseline and after 50,000 thermocycles. The bond strength of specimens sanded with silicon-carbide paper (treatment 2) deteriorated dramatically after 50,000 thermocycles. Contamination of the cast metal surfaces by elements of the investment during casting did not affect bond strengths of the luting materials to CP-Ti and Ti-6Al-4V.

  7. Spectrophotometric determination of [2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid in pure form and in pharmaceuticals

    NASA Astrophysics Data System (ADS)

    Bazel, Yaroslav; Hunka, Iryna; Kormosh, Zholt; Andruch, Vasil

    2009-12-01

    A new sensitive and selective spectrophotometric method has been developed for the determination of [2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid in pharmaceuticals in the presence of nicotinic acid. The method is based on the reaction of [2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid with 1,3,3-trimethyl-5-phenyl-2-[3-(1,3,3-trimethyl-1,3-dihydro-indol-2-ylidene)-propenyl]-3 H-indolium chloride (PIC) followed by the extraction of the formed ion associate into toluene and spectrophotometric detection at 581 nm. Appropriate experimental conditions were found to be pH 7.8-9.8 and 3.6 × 10 -4 mol L -1 of PIC. The molar absorptivity is 5.0 × 10 -4 L mol -1 cm -1. The absorbance obeys Beer's law in the range 0.61-12.60 μg mL -1 of [2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid, and the detection limit calculated from a blank test was 0.20 μg mL -1.

  8. Noni puree (Morinda citrifolia) mixed in beef patties enhanced color stability.

    PubMed

    Tapp, W Nathan; Yancey, Janeal W S; Apple, Jason K; Dikeman, Michael E; Godbee, Richard G

    2012-06-01

    Ground beef, mixed with 0, 2, 4, and 6% Noni puree, was formed into 150-g patties, aerobically packaged, and displayed in retail for 5d. After 2 and 3d, patties with higher concentrations of Noni were perceived as redder and less discolored (P<0.05) by visual panelists. Noni patties were found to have greater (P<0.05) a* values than controls, even though all patties became less red during display. After 3 and 5d of retail display, patties with higher concentrations of Noni puree also had lower TBARS (were less oxidized; P<0.05). In fresh taste panels, panelists perceived the patties to have less beef flavor and greater incidence of off-flavors (P<0.05) as Noni puree concentration increased. The potential of Noni puree to improve the color stability and shelf life of fresh ground beef is very promising, but the flavors produced by the addition of Noni in ground beef may be detrimental to its use. Copyright © 2012. Published by Elsevier Ltd.

  9. Transport of Escherichia coli and F-RNA bacteriophages in a 5 m column of saturated pea gravel

    NASA Astrophysics Data System (ADS)

    Sinton, Lester W.; Mackenzie, Margaret L.; Karki, Naveena; Braithwaite, Robin R.; Hall, Carollyn H.; Flintoft, Mark J.

    2010-09-01

    The relative transport and attenuation of bacteria, bacteriophages, and bromide was determined in a 5 m long × 0.3 m diameter column of saturated pea gravel. The velocity ( V), longitudinal dispersivity ( αx) and total removal rate ( λ) were calculated from the breakthrough curves at 1 m, 3 m, and 5 m, at a flow rate of 32 L h - 1 . Inactivation ( μ) rates were determined in survival chambers. Two pure culture experiments with Escherichia coli J6-2 and F-RNA phage MS2 produced an overall V ranking of E. coli J6-2 > MS2 > bromide, consistent with velocity enhancement, whereby larger particles progressively move into faster, central streamlines of saturated pores. Removal rates were near zero for MS2, but were higher for E. coli J6-2. In two sewage experiments, E. coli and F-RNA phage Vs were similar (but > bromide). This was attributed to phage adsorption to colloids similar in size to E. coli cells. Sewage phage removal rates were higher than for the pure MS2 cultures. The application of filtration theory suggested that, whereas free phage were unaffected by settling, this was the primary removal mechanism for the colloid-associated phage. However, cultured and sewage E. coli removal rates were similar, suggesting the dominance of free E. coli cells in the sewage. When MS2 was attached to kaolin particles, it was transported faster than free MS2, but at similar rates to sewage phage. The μ values indicated little contribution of inactivation to removal of either cultured or sewage microorganisms. The results showed the importance of association with colloids in determining the relative transport of bacteria and viruses in gravels.

  10. Visibility in a pure model of golden spiral phyllotaxis.

    PubMed

    Herrmann, Burghard

    2018-07-01

    This paper considers the geometry of plants with golden spiral phyllotaxis, i.e. growing leaf by leaf on a spiral with golden divergence angle, via the simplest mathematical model, a cylinder with regular arrangement of points on its surface. As is well-known, Fibonacci numbers appear by means of the order of parastichies. This fact is shown to be a straightforward application of logical consequences to a particular model with respect to pure visibility. This notion is very similar to that of contact parastichies. The 3-D cylindrical model of golden spiral phyllotaxis abstracts from the form of leaves and identifies them with points. Pure visibility is specified in the 2-D representation so that common sense parastichies can be scrutinized. The main Theorem states that the orders of the purely most visible parastichies are Fibonacci numbers. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina

    PubMed Central

    Hickmott, Jack W; Chen, Chih-yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

    2016-01-01

    Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia. PMID:27556059

  12. PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina.

    PubMed

    Hickmott, Jack W; Chen, Chih-Yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

    2016-01-01

    Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

  13. Selective treatment of carious dentin using a mid-infrared tunable pulsed laser at 6 μm wavelength range

    NASA Astrophysics Data System (ADS)

    Saiki, Masayuki; Ishii, Katsunori; Yoshikawa, Kazushi; Yasuo, Kenzo; Yamamoto, Kazuyo; Awazu, Kunio

    2011-03-01

    Optical technologies have good potential for caries detection, prevention, excavation, and the realization of minimal intervention dentistry. This study aimed to develop a selective excavation technique of carious tissue using the specific absorption in 6 μm wavelength range. Bovine dentin demineralized with lactic acid solution was used as a carious dentin model. A mid-infrared tunable pulsed laser was obtained by difference-frequency generation technique. The wavelength was tuned to 6.02 and 6.42 μm which correspond to absorption bands called amide I and amide II, respectively. The laser delivers 5 ns pulse width at a repetition rate of 10 Hz. The morphological change after irradiation was observed with a scanning electron microscope, and the measurement of ablation depth was performed with a confocal laser microscope. At λ = 6.02 μm and the average power density of 15 W/cm2, demineralized dentin was removed selectively with less-invasive effect on sound dentin. The wavelength of 6.42 μm also showed the possibility of selective removal. High ablation efficiency and low thermal side effect were observed using the nanosecond pulsed laser with λ = 6.02 μm. In the near future, development of compact laser device will open the minimal invasive laser treatment to the dental clinic.

  14. Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue

    PubMed Central

    de Souza, M. Cristina P.; Deschênes, Marie-Eve; Laurencelle, Suzanne; Godet, Patrick; Roy, Claude C.; Djilali-Saiah, Idriss

    2016-01-01

    The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet. PMID:27446824

  15. Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue.

    PubMed

    de Souza, M Cristina P; Deschênes, Marie-Eve; Laurencelle, Suzanne; Godet, Patrick; Roy, Claude C; Djilali-Saiah, Idriss

    2016-01-01

    The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet.

  16. Theoretical study of the electron affinities of MF6 and MF - 6 (M=Cr, Mo, and W) using a model potential method

    NASA Astrophysics Data System (ADS)

    Sakai, Yoshiko; Miyoshi, Eisaku

    1987-09-01

    Electronic structures of MF6, MF-6, and MF2-6 (M=Cr, Mo, and W) were calculated using a model potential method in the Hartree-Fock-Roothaan scheme. Major relativistic effects were taken into account for the calculations on MoFq6 and WFq6 (q=0, -1, and -2). It is shown that the calculated electron affinities (EAs) are extremely high for all the MF6 molecules, and that the CrF-6 and MoF-6 anions also have positive EAs, whereas the WF-6 anion has a slightly negative EA. The behaviors of the EAs are interpreted with reference to the electronic structures of the MFq6 systems.

  17. Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d

    PubMed Central

    Knuckles, Philip; Lence, Tina; Haussmann, Irmgard U.; Jacob, Dominik; Kreim, Nastasja; Carl, Sarah H.; Masiello, Irene; Hares, Tina; Villaseñor, Rodrigo; Hess, Daniel; Andrade-Navarro, Miguel A.; Biggiogera, Marco; Helm, Mark; Soller, Matthias; Bühler, Marc; Roignant, Jean-Yves

    2018-01-01

    N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m6A is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of m6A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m6A levels and is involved in sex determination in Drosophila. We demonstrate that Flacc promotes m6A deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the m6A machinery. PMID:29535189

  18. Experience-Dependent Accumulation of N6-Methyladenosine in the Prefrontal Cortex Is Associated with Memory Processes in Mice.

    PubMed

    Widagdo, Jocelyn; Zhao, Qiong-Yi; Kempen, Marie-Jeanne; Tan, Men Chee; Ratnu, Vikram S; Wei, Wei; Leighton, Laura; Spadaro, Paola A; Edson, Janette; Anggono, Victor; Bredy, Timothy W

    2016-06-22

    The RNA modification N(6)-methyladenosine (m(6)A) influences mRNA stability and cell-type-specific developmental programming, and is highly abundant in the adult brain. However, it has not been determined whether m(6)A is dynamically regulated by experience. Based on transcriptome-wide profiling of m(6)A, we report that the level of m(6)A increases in the medial prefrontal cortex (mPFC) of mice in response to behavioral experience. The modulation was enriched near the stop codon of mRNAs, including genes related to neuronal plasticity. In primary cortical neurons, in vitro, modulation of m(6)A by the RNA demethylase FTO influenced the degradation profiles of a subset of transcripts with modulated sites. In vivo, the expression of Fto and the m(6)A methyltransferase, Mettl3 correlated with the observed increase in m(6)A levels post-training. Furthermore, targeted knockdown of FTO in the mPFC led to enhanced consolidation of cued fear memory. Thus, together with its role in early development, the dynamic regulation of m(6)A in the adult brain serves as an important epitranscriptomic mechanism associated with behavioral adaptation. N(6)-methyladenosine (m(6)A) is the most prevalent internal modification on RNA, however, its cellular dynamics in vivo remains elusive. Here we provide the first demonstration of m(6)A upregulation in the mouse medial prefrontal cortex (mPFC) following behavioral training. Knocking down the m(6)A demethylase FTO in the mPFC, which increases total m(6)A level, results in enhanced consolidation of fear memory. Our findings suggest that m(6)A is regulated in an activity-dependent manner in the adult brain, and may function to fine-tune mRNA turnover during memory-related processes. Copyright © 2016 the authors 0270-6474/16/366771-07$15.00/0.

  19. Assessment of semen quality in pure and crossbred Jersey bulls

    PubMed Central

    Kumar, Umesh; Gawande, Ajay P.; Sahatpure, Sunil K.; Patil, Manoj S.; Lakde, Chetan K.; Bonde, Sachin W.; Borkar, Pradnyankur L.; Poharkar, Ajay J.; Ramteke, Baldeo R.

    2015-01-01

    Aim: To compare the seminal attributes of neat, pre-freeze (at equilibration), and post-freeze (24 h after freezing) semen in pure and crossbred Jersey bulls. Materials and Methods: Total 36 ejaculates (3 ejaculates from each bull) were collected from 6 pure Jersey and 6 crossbred Jersey bulls and evaluated for various seminal attributes during neat, pre-freeze, and post-freeze semen. Results: The mean (±standard error [SE]) values of neat semen characteristics in pure and crossbred Jersey bulls were recorded such as volume (ml), color, consistency, mass activity (scale: 0-5), and sperm concentration (millions/ml). The extended semen was further investigated at pre-freeze and post-freeze stages and the mean (±SE) values recorded at neat, pre-freeze, and post-freeze semen were compared between pure and crossbred Jersey bulls; sperm motility (80.55±1.70%, 62.77±1.35%, 46.11±1.43% vs. 80.00±1.80%, 65.00±1.66%, 47.22±1.08%), live sperm count (83.63±1.08%, 71.72±1.09%, 58.67±1.02% vs. 80.00±1.08%, 67.91±1.20%, 51.63±0.97%), total abnormal sperm count (8.38±0.32%, 12.30±0.39%, 16.75±0.42% vs. 9.00±0.45%, 12.19±0.48%, 18.11±0.64%), hypo-osmotic swelling (HOS) reacted spermatozoa (71.88±0.77%, 62.05±0.80%, 47.27±1.05% vs. 72.77±1.02%, 62.11±0.89%, 45.94±1.33%), acrosome integrity (89.05±0.83%, 81.33±0.71%, 71.94±0.86% vs. 86.55±0.57%, 78.66±0.42%, 69.38±0.53%), and DNA integrity (99.88±0.07%, 100, 99.66±0.11% vs. 99.94±0.05%, 100, 99.44±0.18%,). The volume, color, consistency, sperm concentration, and initial motility in pure and crossbred Jersey bulls did not differ significantly (p>0.05). The mass activity was significantly (p<0.05) higher in pure Jersey as compare to crossbred Jersey bulls. Live sperm percentage and acrosome integrity was significantly (p<0.01) higher in pure Jersey bulls as compared to crossbred Jersey bulls. However, no statistical difference (p>0.05) was observed in abnormal sperm; HOS reacted spermatozoa and DNA

  20. Focal cerebral ischemic tolerance and change in blood-brain barrier permeability after repetitive pure oxygen exposure preconditioning in a rodent model.

    PubMed

    Wang, Xi; Kang, Kai; Wang, Shiquan; Yao, Jianhua; Zhang, Xijing

    2016-10-01

    OBJECTIVE The goal of this study was to demonstrate that repetitive pure oxygen exposure preconditioning (O 2 PC) for 8 hours per day for 3 or 7 days, a practicable preconditioning for clinical use, is able to induce cerebral ischemic tolerance (IT) and further clarify the accompanying changes in the blood-brain barrier (BBB) that may be involved. METHODS A total of 68 adult male Sprague-Dawley rats and eight 1-day-old rat pups were used in this study. The adult rats were exposed to pure O 2 (38 rats) 8 hours a day for 3 or 7 days or to room air (in an identical setup) for 8 hours a day for 7 days as controls (30 rats). Arterial O 2 tension (PaO 2 ) was measured in 6 rats exposed to O 2 and 3 controls. Focal cerebral ischemia was elicited by middle cerebral artery occlusion (MCAO) in 37 rats, of which 21 had been exposed to pure O 2 for 3 or 7 days and 16 to room air for 7 days as controls. Neurological behavior was scored with the Garcia score in 15 MCAO rats, of which 10 had been exposed to pure O 2 for 3 or 7 days and 5 to room air for 7 days as controls, and cerebral infarct volumes were assessed with TTC (2,3,5-triphenyltetrazolium chloride) staining in 10 rats (5 from each group) after 7 days of exposure. Formamide-extraction method was used to detect leakage of Evans blue (EB) dye in 7 rats exposed to pure O 2 for 7 days and 7 exposed to room air for 7 days. Fluorescence microscopy was used to analyze the leaked EB in the nonischemic areas of 4 rats exposed to pure O 2 for 7 days and 4 exposed to room air for 7 days before MCAO and the brain of the rats that had not been subjected to MCAO. Astrocyte changes associated with O 2 PC were evaluated by means of fluorescence microscopy and electron microscopy in 14 rats that were exposed to the same O 2 or control conditions as the MCAO rats but without MCAO. Astrocytes were also obtained from 8 rat pups and cultured; levels of AQP4 and VEGF were detected by Western blot and ELISA in cells with and without O 2

  1. Geometric characterization of separability and entanglement in pure Gaussian states by single-mode unitary operations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adesso, Gerardo; CNR-INFM Coherentia, Naples; CNISM, Unita di Salerno, Salerno

    2007-10-15

    We present a geometric approach to the characterization of separability and entanglement in pure Gaussian states of an arbitrary number of modes. The analysis is performed adapting to continuous variables a formalism based on single subsystem unitary transformations that has been recently introduced to characterize separability and entanglement in pure states of qubits and qutrits [S. M. Giampaolo and F. Illuminati, Phys. Rev. A 76, 042301 (2007)]. In analogy with the finite-dimensional case, we demonstrate that the 1xM bipartite entanglement of a multimode pure Gaussian state can be quantified by the minimum squared Euclidean distance between the state itself andmore » the set of states obtained by transforming it via suitable local symplectic (unitary) operations. This minimum distance, corresponding to a, uniquely determined, extremal local operation, defines an entanglement monotone equivalent to the entropy of entanglement, and amenable to direct experimental measurement with linear optical schemes.« less

  2. Physical Exercise with Multicomponent Cognitive Intervention for Older Adults with Alzheimer's Disease: A 6-Month Randomized Controlled Trial

    PubMed Central

    Kim, Min-Ji; Han, Chang-Wan; Min, Kyoung-Youn; Cho, Chae-Yoon; Lee, Chae-Won; Ogawa, Yoshiko; Mori, Etsuro; Kohzuki, Masahiro

    2016-01-01

    Aims This study aimed to investigate the effect of 6-month physical exercise with a multicomponent cognitive program (MCP) on the cognitive function of older adults with moderate to severe Alzheimer's disease (AD). Methods We included 33 participants with AD in a 6-month randomized controlled trial. The intervention group participated in physical exercise and received a MCP. The control group received only the MCP. Before and after the intervention, cognitive outcomes were assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Mini-Mental State Examination, and the Clock Drawing Test. Physical performance was evaluated by exercise time, the number of pedal rotation, total load, grip strength, and the Berg Balance Scale (BBS). Results In all cognitive measures, there were no significant improvements between the two groups after 6 months in the baseline value-adjusted primary analysis. However, the ADAS-cog score was significantly lower between the two groups in secondary analysis adjusted for baseline value, age, sex, and education years. All physical outcomes were significantly higher in the intervention group except for total load compared with baseline measurements. Conclusion This study indicates that it is possible to improve cognitive function in older adults with moderate to severe AD through 6-month physical exercise with a multicomponent cognitive intervention. PMID:27403134

  3. M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

    PubMed Central

    2013-01-01

    Background Microglia are the primary immune cells of the brain whose phenotype largely depends on their surrounding micro-environment. Microglia respond to a multitude of soluble molecules produced by a variety of brain cells. Macrophage colony-stimulating factor (M-CSF) is a cytokine found in the brain whose receptor is expressed by microglia. Previous studies suggest a critical role for M-CSF in brain development and normal functioning as well as in several disease processes involving neuroinflammation. Methods Using biopsy tissue from patients with intractable temporal epilepsy and autopsy tissue, we cultured primary adult human microglia to investigate their response to M-CSF. Mixed glial cultures were treated with 25 ng/ml M-CSF for 96 hours. Proliferation and phagocytosis assays, and high through-put immunocytochemistry, microscopy and image analysis were performed to investigate microglial phenotype and function. Results We found that the phenotype of primary adult human microglia was markedly changed following exposure to M-CSF. A greater number of microglia were present in the M-CSF- treated cultures as the percentage of proliferating (BrdU and Ki67-positive) microglia was greatly increased. A number of changes in protein expression occurred following M-CSF treatment, including increased transcription factors PU.1 and C/EBPβ, increased DAP12 adaptor protein, increased M-CSF receptor (CSF-1R) and IGF-1 receptor, and reduced HLA-DP, DQ, DR antigen presentation protein. Furthermore, a distinct morphological change was observed with elongation of microglial processes. These changes in phenotype were accompanied by a functional increase in phagocytosis of Aβ1-42 peptide. Conclusions We show here that the cytokine M-CSF dramatically influences the phenotype of adult human microglia. These results pave the way for future investigation of M-CSF-related targets for human therapeutic benefit. PMID:23866312

  4. X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations

    PubMed Central

    Shamim, Daniah; Alleyne, Karen

    2017-01-01

    Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10–13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease. PMID:29201369

  5. X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

    PubMed

    Shamim, Daniah; Alleyne, Karen

    2017-01-01

    Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

  6. Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum

    PubMed Central

    Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

    2014-01-01

    Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. J. Comp. Neurol. 522:3795–3816, 2014. © 2014 Wiley Periodicals, Inc. PMID:24782245

  7. Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum.

    PubMed

    Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

    2014-12-01

    Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. © 2014 Wiley Periodicals, Inc.

  8. Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain.

    PubMed

    Chang, Mengqi; Lv, Hongyi; Zhang, Weilong; Ma, Chunhui; He, Xue; Zhao, Shunli; Zhang, Zhi-Wei; Zeng, Yi-Xin; Song, Shuhui; Niu, Yamei; Tong, Wei-Min

    2017-09-01

    N 6 -methyladenosine (m 6 A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m 6 A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m 6 A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m 6 A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m 6 A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain. © 2017 The Authors.

  9. Pure laparoscopic hepatectomy with augmented reality-assisted indocyanine green fluorescence versus open hepatectomy for hepatocellular carcinoma with liver cirrhosis: A propensity analysis at a single center.

    PubMed

    Cheung, Tan To; Ma, Ka Wing; She, Wong Hoi; Dai, Wing Chiu; Tsang, Simon Hing Yin; Chan, Albert Chi Yan; Chok, Kenneth Siu Ho; Lo, Chung Mau

    2018-05-10

    Laparoscopic hepatectomy is considered an acceptable treatment of choice in selected patients with primary hepatocellular carcinoma (HCC). Whether indocyanine green (ICG) immunofluorescence, a new technology, may improve surgery outcomes has yet to be tested. The aim of the present study was to investigate and compare the effect of ICG fluorescence imaging on the outcomes of pure laparoscopic hepatectomy and open hepatectomy for primary HCC with background cirrhosis. From January 2015 to June 2016, 20 patients with HCC and liver cirrhosis underwent laparoscopic hepatectomy with ICG immunofluorescence. The outcomes of pure laparoscopic hepatectomy with ICG immunofluorescence were compared with those of open hepatectomy. To avoid selection bias, patients were propensity score matched in a ratio of 1 : 6, with 20 patients in the laparoscopic group and 120 in the open group. The laparoscopic group had 20 patients, and the open group had 120 patients. The laparoscopic group had less blood loss (125 vs 450 mL, P < 0.001), a shorter operation time (200 vs 250 min, P = 0.003), and a shorter hospital stay (5 vs 6 days, P < 0.001). The complication rate was 0% in the laparoscopic group compared to 15.0% in the open group (P = 0.135). All patients in the laparoscopic group had negative margin involvement. Four patients (3.3%) in the open resection group had positive margin involvement. Two patients in the ICG immunofluorescence group had additional lesions identified and resected during operation. Pure laparoscopic hepatectomy with ICG immunofluorescence for primary HCC can be carried out safely with favorable short-term outcomes even in cirrhotic patients. Better identification of the bile duct structure and better assessment of the tumor resection margin and perfusion are advantages of this new technique. © 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  10. Comparative in vitro biocompatibility of nickel-titanium, pure nickel, pure titanium, and stainless steel: genotoxicity and atomic absorption evaluation.

    PubMed

    Assad, M; Lemieux, N; Rivard, C H; Yahia, L H

    1999-01-01

    The genotoxicity level of nickel-titanium (NiTi) was compared to that of its pure constituents, pure nickel (Ni) and pure titanium (Ti) powders, and also to 316L stainless steel (316L SS) as clinical reference material. In order to do so, a dynamic in vitro semiphysiological extraction was performed with all metals using agitation and ISO requirements. Peripheral blood lymphocytes were then cultured in the presence of all material extracts, and their comparative genotoxicity levels were assessed using electron microscopy-in situ end-labeling (EM-ISEL) coupled to immunogold staining. Cellular chromatin exposition to pure Ni and 316L SS demonstrated a significantly stronger gold binding than exposition to NiTi, pure Ti, or the untreated control. In parallel, graphite furnace atomic absorption spectrophotometry (AAS) was also performed on all extraction media. The release of Ni atoms took the following decreasing distribution for the different resulting semiphysiological solutions: pure Ni, 316L SS, NiTi, Ti, and controls. Ti elements were detected after elution of pure titanium only. Both pure titanium and nickel-titanium specimens obtained a relative in vitro biocompatibility. Therefore, this quantitative in vitro study provides optimistic results for the eventual use of nickel-titanium alloys as surgical implant materials.

  11. Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

    PubMed Central

    Schmitt, Laura A.; Liu, Yi; Murphy, Patricia A.; Petrich, Jacob W.; Dixon, Philip M.; Birt, Diane F.

    2006-01-01

    Clinical evidence suggests that administration of Hypericum perforatum (Hp) extracts containing the photo-activated hypericin compounds may cause fewer skin photosensitization reactions than administration of pure hypericin. This study was conducted to determine whether the phototoxicity of hypericin in HaCaT keratinocytes could be attenuated by H. perforatum extracts and constituents. Two extracts, when supplemented with 20 μM hypericin: (1) an ethanol re-extraction of residue following a chloroform extraction (denoted ethanol(-chloroform)) (3.35 μM hypericin and 124.0 μM total flavonoids); and (2) a chloroform extract (hypericin and flavonoids not detected), showed 25% and 50% (p < 0.0001) less phototoxicity than 20 μM hypericin alone. Two H. perforatum constituents, when supplemented with 20 μM hypericin: (1) 10 μM chlorogenic acid; and (2) 0.25 μM pyropheophorbide, exhibited 24% (p < 0.05) and 40% (p < 0.05) less phototoxicity than 20 μM hypericin alone. The peroxidation of arachidonic acid was assessed as a measure of oxidative damage by photo-activated hypericin, but this parameter of lipid peroxidation was not influenced by the extracts or constituents. However α-tocopherol, a known antioxidant also did not influence the amount of lipid peroxidation induced in this system. These observations indicate that hypericin combined with H. perforatum extracts or constituents may exert less phototoxicity than pure hypericin, but possibly not through a reduction in arachidonic acid peroxidation. PMID:16859921

  12. Differential in vitro inhibition of M3G and M6G formation from morphine by (R)- and (S)-methadone and structurally related opioids

    PubMed Central

    Morrish, Glynn A; Foster, David J R; Somogyi, Andrew A

    2006-01-01

    Aims To determine the in vitro kinetics of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) formation and the inhibition potential by methadone enantiomers and structurally related opioids. Methods M3G and M6G formation kinetics from morphine were determined using microsomes from five human livers. Inhibition of glucuronide formation was investigated with eight inhibitors (100 µm) and the mechanism of inhibition determined for (R)- and (S)-methadone (70–500 µm) using three microsomal samples. Results Glucuronide formation displayed single enzyme kinetics. The M3G Vmax (mean ± SD) was 4.8-fold greater than M6G Vmax (555 ± 110 vs. 115 ± 19 nmol mg−1 protein h−1; P = 0.006, mean of difference 439; 95% confidence interval 313, 565 nmol mg−1 protein h−1). Km values for M3G and M6G formation were not significantly different (1.12 ± 0.37 vs. 1.11 ± 0.31 mm; P = 0.89, 0.02; −0.29, 0.32 mm). M3G and M6G formation was inhibited (P < 0.01) with a significant increase in the M3G/M6G ratio (P < 0.01) for all compounds tested. Detailed analysis with (R)- and (S)-methadone revealed noncompetitive inhibition with (R)-methadone Ki of 320 ± 42 µm and 192 ± 12 µm for M3G and M6G, respectively, and (S)-methadone Ki of 226 ± 30 µm and 152 ± 20 µm for M3G and M6G, respectively. Ki values for M3G inhibition were significantly greater than for M6G for (R)-methadone (P = 0.017, 128; 55, 202 µm) and (S)-methadone (P = 0.026, 75; 22, 128 µm). Conclusions Both methadone enantiomers noncompetitively inhibited the formation of morphine's primary metabolites, with greater inhibition of M6G formation compared with M3G. These findings indicate a mechanism for reduced morphine clearance in methadone-maintained patients and reduced relative formation of the opioid active M6G compared with M3G. PMID:16487227

  13. Spt6 Association with RNA Polymerase II Directs mRNA Turnover During Transcription.

    PubMed

    Dronamraju, Raghuvar; Hepperla, Austin J; Shibata, Yoichiro; Adams, Alexander T; Magnuson, Terry; Davis, Ian J; Strahl, Brian D

    2018-06-21

    Spt6 is an essential histone chaperone that mediates nucleosome reassembly during gene transcription. Spt6 also associates with RNA polymerase II (RNAPII) via a tandem Src2 homology domain. However, the significance of Spt6-RNAPII interaction is not well understood. Here, we show that Spt6 recruitment to genes and the nucleosome reassembly functions of Spt6 can still occur in the absence of its association with RNAPII. Surprisingly, we found that Spt6-RNAPII association is required for efficient recruitment of the Ccr4-Not de-adenylation complex to transcribed genes for essential degradation of a range of mRNAs, including mRNAs required for cell-cycle progression. These findings reveal an unexpected control mechanism for mRNA turnover during transcription facilitated by a histone chaperone. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. chemf: A purely functional chemistry toolkit

    PubMed Central

    2012-01-01

    Background Although programming in a type-safe and referentially transparent style offers several advantages over working with mutable data structures and side effects, this style of programming has not seen much use in chemistry-related software. Since functional programming languages were designed with referential transparency in mind, these languages offer a lot of support when writing immutable data structures and side-effects free code. We therefore started implementing our own toolkit based on the above programming paradigms in a modern, versatile programming language. Results We present our initial results with functional programming in chemistry by first describing an immutable data structure for molecular graphs together with a couple of simple algorithms to calculate basic molecular properties before writing a complete SMILES parser in accordance with the OpenSMILES specification. Along the way we show how to deal with input validation, error handling, bulk operations, and parallelization in a purely functional way. At the end we also analyze and improve our algorithms and data structures in terms of performance and compare it to existing toolkits both object-oriented and purely functional. All code was written in Scala, a modern multi-paradigm programming language with a strong support for functional programming and a highly sophisticated type system. Conclusions We have successfully made the first important steps towards a purely functional chemistry toolkit. The data structures and algorithms presented in this article perform well while at the same time they can be safely used in parallelized applications, such as computer aided drug design experiments, without further adjustments. This stands in contrast to existing object-oriented toolkits where thread safety of data structures and algorithms is a deliberate design decision that can be hard to implement. Finally, the level of type-safety achieved by Scala highly increased the reliability of our code

  15. Polarized ensembles of random pure states

    NASA Astrophysics Data System (ADS)

    Deelan Cunden, Fabio; Facchi, Paolo; Florio, Giuseppe

    2013-08-01

    A new family of polarized ensembles of random pure states is presented. These ensembles are obtained by linear superposition of two random pure states with suitable distributions, and are quite manageable. We will use the obtained results for two purposes: on the one hand we will be able to derive an efficient strategy for sampling states from isopurity manifolds. On the other, we will characterize the deviation of a pure quantum state from separability under the influence of noise.

  16. Microturbulence in HT-6M Tokamak

    NASA Astrophysics Data System (ADS)

    Zeng, Lei; Yu, Changxuan; Cao, Jinxiang; Zhu, Guoliang; Zhang, Daqing; Li, Youyi

    1993-08-01

    The small scale density fluctuations in the interior of HT-6M Ohmic plasma have been studied by CO2 laser collective scattering system in deuterium discharges covering a range of bar neqa (chord-average density times safety factor at the limiter) and energy confinement time. The relative density fluctuation level in the interior is inversely proportional to the toroidal magnetic field and average density, and the energy confinement time τE decreases with the fluctuation level increasing in the region where τE linearly increases with bar neqa and statisfies the Goldston scaling law. It is suggested that the microturbulence in the interior zone is responsible for anomalous transport in tokamaks.

  17. AdS6 solutions of type II supergravity

    NASA Astrophysics Data System (ADS)

    Apruzzi, Fabio; Fazzi, Marco; Passias, Achilleas; Rosa, Dario; Tomasiello, Alessandro

    2014-11-01

    Very few AdS6 × M 4 supersymmetric solutions are known: one in massive IIA, and two IIB solutions dual to it. The IIA solution is known to be unique; in this paper, we use the pure spinor approach to give a classification for IIB supergravity. We reduce the problem to two PDEs on a two-dimensional space Σ. M 4 is then a fibration of S 2 over Σ; the metric and fluxes are completely determined in terms of the solution to the PDEs. The results seem likely to accommodate near-horizon limits of ( p, q)-fivebrane webs studied in the literature as a source of CFT5's. We also show that there are no AdS6 solutions in eleven-dimensional supergravity.

  18. Aspergillus niger P6 and Rhodotorula mucilaginosa CH4 used for olive mill wastewater (OMW) biological treatment in single pure and successive cultures.

    PubMed

    Jarboui, Raja; Magdich, Salwa; Ayadi, Raja Jarboui; Gargouri, Ali; Gharsallah, Néji; Ammar, Emna

    2013-01-01

    The aim of this study was to investigate the Rhodotorula mucilaginosa CH4 and Aspergillus niger P6 abilities to purify olive mill wastewater (OMW) in single pure and mixed cultures during the treatment. Both fungi were molecularly identified. OMW was used at five dilutions from 5% to 30% with chemical oxygen demand (COD) ranging from 11,600 to 24,600 mg L(-1). Firstly, each fungus was used separately, then they were successively used to treat the OMW. In single pure culture, A. niger showed a better efficiency in OMW purification than R. mucilaginosa. Furthermore, when successively used, the two studied strains exhibited improvements in the decrease of COD, polyphenolic compounds concentration and effluent colour. COD removals were 95.68-56.71% by R. mucilaginosa and 98.02-69.51% by A. niger for OMW dilutions varying from 5% to 30%. Both strains showed an important polyphenolic compounds removal of 83-45% by R. mucilaginosa and 94-58% by A. niger, in accordance with the OMW COD initially used. The COD and phenolic compound removals fitted simple equation models, with high regression coefficients. The strains' growth kinetics decreased according to the OMW concentration, but, when successively used, fungal growth was improved, allowing efficient effluent treatment.

  19. Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia

    PubMed Central

    Rinaldi, Carlo; Schmidt, Thomas; Situ, Alan J.; Johnson, Janel O.; Lee, Philip R.; Chen, Ke-lian; Bott, Laura C.; Fadó, Rut; Harmison, George H.; Parodi, Sara; Grunseich, Christopher; Renvoisé, Benoît; Biesecker, Leslie G.; De Michele, Giuseppe; Santorelli, Filippo M.; Filla, Alessandro; Stevanin, Giovanni; Dürr, Alexandra; Brice, Alexis; Casals, Núria; Traynor, Bryan J.; Blackstone, Craig; Ulmer, Tobias S.; Fischbeck, Kenneth H.

    2017-01-01

    IMPORTANCE The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability of next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients. OBJECTIVE To identify the genetic cause for a novel form of pure autosomal dominant HSP. DESIGN, SETTING, AND PARTICIPANTS We examined and followed up with a family presenting to a tertiary referral center for evaluation of HSP for a decade until August 2014. Whole-exome sequencing was performed in 4 patients from the same family and was integrated with linkage analysis. Sanger sequencing was used to confirm the presence of the candidate variant in the remaining affected and unaffected members of the family and screen the additional patients with HSP. Five affected and 6 unaffected participants from a 3-generation family with pure adult-onset autosomal dominant HSP of unknown genetic origin were included. Additionally, 163 unrelated participants with pure HSP of unknown genetic cause were screened. MAIN OUTCOME AND MEASURE Mutation in the neuronal isoform of carnitine palmitoyl-transferase (CPT1C) gene. RESULTS We identified the nucleotide substitution c.109C>T in exon 3 of CPT1C, which determined the base substitution of an evolutionarily conserved Cys residue for an Arg in the gene product. This variant strictly cosegregated with the disease phenotype and was absent in online single-nucleotide polymorphism databases and in 712 additional exomes of control participants. We showed that CPT1C, which localizes to the endoplasmic reticulum, is expressed in motor neurons and interacts with atlastin-1, an endoplasmic reticulum protein encoded by the ATL1 gene known to be mutated in pure HSPs. The mutation, as indicated by nuclear magnetic resonance spectroscopy studies, alters the protein conformation and reduces the mean (SD) number (213.0 [46.99] vs 81.9 [14.2]; P < .01) and size (0.29 [0.01] vs 0.26 [0

  20. Good Manufacturing Practices and Microbial Contamination Sources in Orange Fleshed Sweet Potato Puree Processing Plant in Kenya

    PubMed Central

    Abong', George Ooko

    2018-01-01

    Limited information exists on the status of hygiene and probable sources of microbial contamination in Orange Fleshed Sweet Potato (OFSP) puree processing. The current study is aimed at determining the level of compliance to Good Manufacturing Practices (GMPs), hygiene, and microbial quality in OFSP puree processing plant in Kenya. Intensive observation and interviews using a structured GMPs checklist, environmental sampling, and microbial analysis by standard microbiological methods were used in data collection. The results indicated low level of compliance to GMPs with an overall compliance score of 58%. Microbial counts on food equipment surfaces, installations, and personnel hands and in packaged OFSP puree were above the recommended microbial safety and quality legal limits. Steaming significantly (P < 0.05) reduced microbial load in OFSP cooked roots but the counts significantly (P < 0.05) increased in the puree due to postprocessing contamination. Total counts, yeasts and molds, Enterobacteriaceae, total coliforms, and E. coli and S. aureus counts in OFSP puree were 8.0, 4.0, 6.6, 5.8, 4.8, and 5.9 log10 cfu/g, respectively. In conclusion, equipment surfaces, personnel hands, and processing water were major sources of contamination in OFSP puree processing and handling. Plant hygiene inspection, environmental monitoring, and food safety trainings are recommended to improve hygiene, microbial quality, and safety of OFSP puree. PMID:29808161

  1. Good Manufacturing Practices and Microbial Contamination Sources in Orange Fleshed Sweet Potato Puree Processing Plant in Kenya.

    PubMed

    Malavi, Derick Nyabera; Muzhingi, Tawanda; Abong', George Ooko

    2018-01-01

    Limited information exists on the status of hygiene and probable sources of microbial contamination in Orange Fleshed Sweet Potato (OFSP) puree processing. The current study is aimed at determining the level of compliance to Good Manufacturing Practices (GMPs), hygiene, and microbial quality in OFSP puree processing plant in Kenya. Intensive observation and interviews using a structured GMPs checklist, environmental sampling, and microbial analysis by standard microbiological methods were used in data collection. The results indicated low level of compliance to GMPs with an overall compliance score of 58%. Microbial counts on food equipment surfaces, installations, and personnel hands and in packaged OFSP puree were above the recommended microbial safety and quality legal limits. Steaming significantly ( P < 0.05) reduced microbial load in OFSP cooked roots but the counts significantly ( P < 0.05) increased in the puree due to postprocessing contamination. Total counts, yeasts and molds, Enterobacteriaceae, total coliforms, and E. coli and S. aureus counts in OFSP puree were 8.0, 4.0, 6.6, 5.8, 4.8, and 5.9 log 10 cfu/g, respectively. In conclusion, equipment surfaces, personnel hands, and processing water were major sources of contamination in OFSP puree processing and handling. Plant hygiene inspection, environmental monitoring, and food safety trainings are recommended to improve hygiene, microbial quality, and safety of OFSP puree.

  2. A new nanospray drying method for the preparation of nicergoline pure nanoparticles

    NASA Astrophysics Data System (ADS)

    Martena, Valentina; Censi, Roberta; Hoti, Ela; Malaj, Ledjan; Di Martino, Piera

    2012-06-01

    Three different batches of pure nanoparticles (NPs) of nicergoline (NIC) were prepared by spray drying a water:ethanol solution by a new Nano Spray Dryer Büchi B-90. Spherical pure NPs were obtained, and several analytical techniques such as differential scanning calorimetry and X-ray powder diffractometry permitted to assess their amorphous character. A comparison of the solubility, intrinsic dissolution, and drug release of original particles and pure amorphous NPs were determined, revealing an interesting improvement of biopharmaceutical properties of amorphous NPs, due to both amorphous properties and nanosize dimensions. Since in a previous work, the high-thermodynamic stability of amorphous NIC was demonstrated, this study is addressed toward the formulation of NIC as pure amorphous NPs.

  3. Single crystal growth and characterization of pure and sodium-modified copper tartrate

    NASA Astrophysics Data System (ADS)

    Quasim, I.; Firdous, A.; Want, B.; Khosa, S. K.; Kotru, P. N.

    2008-12-01

    Single crystal growth of pure and modified copper tartrate crystals bearing composition (Cu) x(Na) yC 4H 4O 6· nH 2O (where x=1, 0.77, 0.65; y=0, 0.23, 0.35) is achieved using gel technique. The optimum conditions required for the growth of these crystals are worked out. The morphological development of these crystals is studied using optical and scanning electron microscopy. The dominant habit faces of the grown copper tartrate crystals are (0 0 1) and (1 1 1). Calculation of the cell parameters using CRYSFIRE software suggests that the pure copper tartrate crystal belongs to orthorhombic system with space group P2 1/c whereas the modified copper tartrate falls under tetragonal system with the space group P4 2/nbc. The external morphological development is shown to remain unaffected in the modified copper tartrate. The stoichiometric composition of the crystals is established by EDAX analysis, CH analysis, FTIR spectroscopy and thermoanalytical techniques. Thermal analysis of the grown crystals suggests that pure copper tartrate is thermally stable up to 42.84 °C whereas the modified copper tartrate crystals are stable only up to 33.11 and 25.11 °C. Calculation of the percentage weight loss from the thermogram supplemented by EDAX/CH analysis and FTIR spectroscopy suggest that the chemical formula of pure copper tartrate crystal is CuC 4H 4O 6·3H 2O whereas the chemical formula for the modified copper tartrate crystals is (Cu) 0.77(Na) 0.23C 4H 4O 6·3H 2O and (Cu) 0.65(Na) 0.35 C 4H 4O 6·H 2O.

  4. Ultra-pure, water-dispersed Au nanoparticles produced by femtosecond laser ablation and fragmentation

    PubMed Central

    Kubiliūtė, Reda; Maximova, Ksenia A; Lajevardipour, Alireza; Yong, Jiawey; Hartley, Jennifer S; Mohsin, Abu SM; Blandin, Pierre; Chon, James WM; Sentis, Marc; Stoddart, Paul R; Kabashin, Andrei; Rotomskis, Ričardas; Clayton, Andrew HA; Juodkazis, Saulius

    2013-01-01

    Aqueous solutions of ultra-pure gold nanoparticles have been prepared by methods of femtosecond laser ablation from a solid target and fragmentation from already formed colloids. Despite the absence of protecting ligands, the solutions could be (1) fairly stable and poly size-dispersed; or (2) very stable and monodispersed, for the two fabrication modalities, respectively. Fluorescence quenching behavior and its intricacies were revealed by fluorescence lifetime imaging microscopy in rhodamine 6G water solution. We show that surface-enhanced Raman scattering of rhodamine 6G on gold nanoparticles can be detected with high fidelity down to micromolar concentrations using the nanoparticles. Application potential of pure gold nanoparticles with polydispersed and nearly monodispersed size distributions are discussed. PMID:23888114

  5. O6-Methylguanine-DNA Methyltransferase (MGMT) mRNA Expression Predicts Outcome in Malignant Glioma Independent of MGMT Promoter Methylation

    PubMed Central

    Kreth, Simone; Thon, Niklas; Eigenbrod, Sabina; Lutz, Juergen; Ledderose, Carola; Egensperger, Rupert; Tonn, Joerg C.; Kretzschmar, Hans A.; Hinske, Ludwig C.; Kreth, Friedrich W.

    2011-01-01

    Background We analyzed prospectively whether MGMT (O6-methylguanine-DNA methyltransferase) mRNA expression gains prognostic/predictive impact independent of MGMT promoter methylation in malignant glioma patients undergoing radiotherapy with concomitant and adjuvant temozolomide or temozolomide alone. As DNA-methyltransferases (DNMTs) are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells, we analyzed further, whether MGMT promoter methylation is associated with upregulation of DNMT expression. Methodology/Principal Findings Adult patients with a histologically proven malignant astrocytoma (glioblastoma: N = 53, anaplastic astrocytoma: N = 10) were included. MGMT promoter methylation was determined by methylation-specific PCR (MSP) and sequencing analysis. Expression of MGMT and DNMTs mRNA were analysed by real-time qPCR. Prognostic factors were obtained from proportional hazards models. Correlation between MGMT mRNA expression and MGMT methylation status was validated using data from the Cancer Genome Atlas (TCGA) database (N = 229 glioblastomas). Low MGMT mRNA expression was strongly predictive for prolonged time to progression, treatment response, and length of survival in univariate and multivariate models (p<0.0001); the degree of MGMT mRNA expression was highly correlated with the MGMT promoter methylation status (p<0.0001); however, discordant findings were seen in 12 glioblastoma patients: Patients with methylated tumors with high MGMT mRNA expression (N = 6) did significantly worse than those with low transcriptional activity (p<0.01). Conversely, unmethylated tumors with low MGMT mRNA expression (N = 6) did better than their counterparts. A nearly identical frequency of concordant and discordant findings was obtained by analyzing the TCGA database (p<0.0001). Expression of DNMT1 and DNMT3b was strongly upregulated in tumor tissue, but not correlated with MGMT promoter methylation and MGMT

  6. Pure rotation of a prism on a ramp

    PubMed Central

    Zhao, Zhen; Liu, Caishan; Ma, Daolin

    2014-01-01

    In this work, we study a prism with a cross section in polygon rolling on a ramp inclined at a small angle. The prism under gravity rolls purely around each individual edge, intermittently interrupted by a sequence of face collisions between the side face of the prism and the ramp. By limiting the prism in a planar motion, we propose a mathematical model to deal with the events of the impacts. With a pair of laser-Doppler vibrometers, experiments are also conducted to measure the motions of various prisms made of different materials and with different edge number. Not only are good agreements achieved between our numerical and experimental results, but also an intriguing physical phenomenon is discovered: the purely rolling motion is nearly independent of the prism's materials, yet it is closely related to the prism's geometry. Imagine that an ideal circular section can be approximately equivalent to a polygon with a large enough edge number N, the finding presented in this paper may help discover the physical mechanism of rolling friction. PMID:25197242

  7. Pure rotation of a prism on a ramp.

    PubMed

    Zhao, Zhen; Liu, Caishan; Ma, Daolin

    2014-09-08

    In this work, we study a prism with a cross section in polygon rolling on a ramp inclined at a small angle. The prism under gravity rolls purely around each individual edge, intermittently interrupted by a sequence of face collisions between the side face of the prism and the ramp. By limiting the prism in a planar motion, we propose a mathematical model to deal with the events of the impacts. With a pair of laser-Doppler vibrometers, experiments are also conducted to measure the motions of various prisms made of different materials and with different edge number. Not only are good agreements achieved between our numerical and experimental results, but also an intriguing physical phenomenon is discovered: the purely rolling motion is nearly independent of the prism's materials, yet it is closely related to the prism's geometry. Imagine that an ideal circular section can be approximately equivalent to a polygon with a large enough edge number N , the finding presented in this paper may help discover the physical mechanism of rolling friction.

  8. 6. PHOTOCOPY OF MAP, G. M. HOPKINS COMPANY, ATLAS OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. PHOTOCOPY OF MAP, G. M. HOPKINS COMPANY, ATLAS OF HUDSON COUNTY, NEW JERSEY, VOL. 1. G. M. HOPKINS AND COMPANY, PHILADELPHIA, PENNSYLVANIA, 1908. - Lembeck & Betz Eagle Brewery, 164-190 Ninth Street, 515-519 Luis Munez Marin Boulevard, Jersey City, Hudson County, NJ

  9. Crystal-Site-Selective Spectrum of Fe3BO6 by Synchrotron Mössbauer Diffraction with Pure Nuclear Bragg Scattering

    NASA Astrophysics Data System (ADS)

    Nakamura, Shin; Mitsui, Takaya; Fujiwara, Kosuke; Ikeda, Naoshi; Kurokuzu, Masayuki; Shimomura, Susumu

    2017-08-01

    We have succeeded in obtaining the crystal-site-selective spectra of the collinear antiferromagnet Fe3BO6 using a synchrotron Mössbauer diffractometer with pure nuclear Bragg scattering at SPring-8 BL11XU. Well-resolved 300, 500, and 700 reflection spectra, having asymmetric line shapes owing to the higher-order interference effect between the nuclear energy levels, were quantitatively analyzed using a formula based on the dynamical theory of diffraction. Reasonable hyperfine parameters were obtained. The intensity ratio of Fe1 to Fe2 subspectra is in accordance with the nuclear structure factor. However, when the spectrum is measured at the peak position of the rocking curve (very near the Bragg position), the value of the center shift deviates from its intrinsic value. This is also due to the dynamical effect of γ-ray diffraction. To avoid this problem, it is necessary to use diffraction angles near the foot of the rocking curve, approximately 0.02° apart from the peak position.

  10. Laboratory generated M -6 earthquakes

    USGS Publications Warehouse

    McLaskey, Gregory C.; Kilgore, Brian D.; Lockner, David A.; Beeler, Nicholas M.

    2014-01-01

    We consider whether mm-scale earthquake-like seismic events generated in laboratory experiments are consistent with our understanding of the physics of larger earthquakes. This work focuses on a population of 48 very small shocks that are foreshocks and aftershocks of stick–slip events occurring on a 2.0 m by 0.4 m simulated strike-slip fault cut through a large granite sample. Unlike the larger stick–slip events that rupture the entirety of the simulated fault, the small foreshocks and aftershocks are contained events whose properties are controlled by the rigidity of the surrounding granite blocks rather than characteristics of the experimental apparatus. The large size of the experimental apparatus, high fidelity sensors, rigorous treatment of wave propagation effects, and in situ system calibration separates this study from traditional acoustic emission analyses and allows these sources to be studied with as much rigor as larger natural earthquakes. The tiny events have short (3–6 μs) rise times and are well modeled by simple double couple focal mechanisms that are consistent with left-lateral slip occurring on a mm-scale patch of the precut fault surface. The repeatability of the experiments indicates that they are the result of frictional processes on the simulated fault surface rather than grain crushing or fracture of fresh rock. Our waveform analysis shows no significant differences (other than size) between the M -7 to M -5.5 earthquakes reported here and larger natural earthquakes. Their source characteristics such as stress drop (1–10 MPa) appear to be entirely consistent with earthquake scaling laws derived for larger earthquakes.

  11. Correlation between grain boundary misorientation and M{sub 23}C{sub 6} precipitation behaviors in a wrought Ni-based superalloy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tang, Bin, E-mail: toby198489@163.com; Jiang, Li; Hu, Rui

    2013-04-15

    The correlation between the grain boundary misorientation and the precipitation behaviors of intergranular M{sub 23}C{sub 6} carbides in a wrought Ni–Cr–W superalloy was investigated by using the electron backscattered diffraction (EBSD) technique. It was observed that the grain boundaries with a misorientation angle less than 20°, as well as all coincidence site lattice (CSL) boundaries, are immune to precipitation of the M{sub 23}C{sub 6} carbides; in contrast, the random high-angle grain boundaries with a misorientation angle of 20°–40° provide preferential precipitation sites of the M{sub 23}C{sub 6} carbides at the random high-angle grain boundaries with a higher misorientation angle ofmore » 55°–60°/[2 2 3] turn to retard precipitation of M{sub 23}C{sub 6} carbides owing to their nature like the Σ3 grain boundaries and retard the precipitation of M{sub 23}C{sub 6} carbides. The low-angle and certain random grain boundary segments induced by twins were found to interrupt the precipitation of the M{sub 23}C{sub 6} carbides along the high-angle grain boundaries. - Highlights: ► The low angle grain boundaries and CSL boundaries are immune to precipitation. ► M23C6 precipitate preferentially at random grain boundaries within 20°–40°. ► Some certain random grain boundary segments interrupt M23C6 precipitation.« less

  12. A comparative study of the mechanical behaviour of thermally oxidised commercially pure titanium and zirconium.

    PubMed

    Alansari, A; Sun, Y

    2017-10-01

    The objective of this study is to compare the mechanical behaviour of thermally oxidised commercially pure titanium (CP-Ti) and commercially pure zirconium (CP-Zr). For this purpose, these two bio-metals were thermally oxidised under the same condition (650°C for 6h) and the oxidised specimens were characterised using various analytical and experimental techniques, including oxygen uptake analysis, layer thickness and hardness measurements, scratch tests, dry sliding friction and wear tests and tribocorrosion tests in Ringer's solution. The results show that under the present thermal oxidation condition, 4 times more oxygen is introduced into CP-Zr than into CP-Ti and the oxide layer produced on CP-Zr is nearly 6 times thicker than that on CP-Ti. Thermally oxidised CP-Zr possesses a higher hardness, a deeper hardening depth and better scratch resistance than thermally oxidised CP-Ti. Under dry sliding and tribocorrosion conditions, thermally oxidised CP-Zr also possesses much better resistance to material removal and a higher load bearing capacity than thermally oxidised CP-Ti. Thus, thermally oxidised Zr possesses much better mechanical behaviour than thermally oxidised Ti. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. mTOR Complex 2 mediates Akt Phosphorylation that Requires PKCε in Adult Cardiac Muscle Cells

    PubMed Central

    Moschella, Phillip C.; McKillop, John; Pleasant, Dorea L.; Harston, Rebecca K.; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

    2013-01-01

    Our earlier work showed that mammalian target of rapamycin (mTOR) is essential to the development of various hypertrophic responses, including cardiomyocyte survival. mTOR forms two independent complexes, mTORC1 and mTORC2, by associating with common and distinct cellular proteins. Both complexes are sensitive to a pharmacological inhibitor, torin1, although only mTORC1 is inhibited by rapamycin. Since mTORC2 is known to mediate the activation of a prosurvival kinase, Akt, we analyzed whether mTORC2 directly mediates Akt activation or whether it requires the participation of another prosurvival kinase, PKC ε (epsilon isoform of protein kinase-C). Our studies reveal that treatment of adult feline cardiomyocytes in vitro with insulin results in Akt phosphorylation at S473 for its activation which could be augmented with rapamycin but blocked by torin1. Silencing the expression of Rictor (rapamycin-insensitive companion of mTOR), an mTORC2 component, with a sh-RNA in cardiomyocytes lowers both insulin-stimulated Akt and PKC ε phosphorylation. Furthermore, phosphorylation of PKC ε and Akt at the critical S729 and S473 sites respectively was blocked by torin1 or Rictor knockdown but not by rapamycin, indicating that the phosphorylation at these specific sites occurs downstream of mTORC2. Additionally, expression of DN-PKC ε significantly lowered the insulin-stimulated Akt S473 phosphorylation, indicating an upstream role for PKC ε in the Akt activation. Biochemical analyses also revealed that PKC ε was part of Rictor but not Raptor (a binding partner and component of mTORC1). Together, these studies demonstrate that mTORC2 mediates prosurvival signaling in adult cardiomyocytes where PKC ε functions downstream of mTORC2 leading to Akt activation. PMID:23673367

  14. mTOR complex 2 mediates Akt phosphorylation that requires PKCε in adult cardiac muscle cells.

    PubMed

    Moschella, Phillip C; McKillop, John; Pleasant, Dorea L; Harston, Rebecca K; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

    2013-09-01

    Our earlier work showed that mammalian target of rapamycin (mTOR) is essential to the development of various hypertrophic responses, including cardiomyocyte survival. mTOR forms two independent complexes, mTORC1 and mTORC2, by associating with common and distinct cellular proteins. Both complexes are sensitive to a pharmacological inhibitor, torin1, although only mTORC1 is inhibited by rapamycin. Since mTORC2 is known to mediate the activation of a prosurvival kinase, Akt, we analyzed whether mTORC2 directly mediates Akt activation or whether it requires the participation of another prosurvival kinase, PKCε (epsilon isoform of protein kinase-C). Our studies reveal that treatment of adult feline cardiomyocytes in vitro with insulin results in Akt phosphorylation at S473 for its activation which could be augmented with rapamycin but blocked by torin1. Silencing the expression of Rictor (rapamycin-insensitive companion of mTOR), an mTORC2 component, with a sh-RNA in cardiomyocytes lowers both insulin-stimulated Akt and PKCε phosphorylation. Furthermore, phosphorylation of PKCε and Akt at the critical S729 and S473 sites respectively was blocked by torin1 or Rictor knockdown but not by rapamycin, indicating that the phosphorylation at these specific sites occurs downstream of mTORC2. Additionally, expression of DN-PKCε significantly lowered the insulin-stimulated Akt S473 phosphorylation, indicating an upstream role for PKCε in the Akt activation. Biochemical analyses also revealed that PKCε was part of Rictor but not Raptor (a binding partner and component of mTORC1). Together, these studies demonstrate that mTORC2 mediates prosurvival signaling in adult cardiomyocytes where PKCε functions downstream of mTORC2 leading to Akt activation. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

    PubMed

    Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

    2005-08-01

    The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

  16. Robotic assisted versus pure laparoscopic surgery of the adrenal glands: a case-control study comparing surgical techniques.

    PubMed