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Sample records for modellering af naturlig

  1. Modeling and Analysis of AF Depot Business Practices for Supply

    DTIC Science & Technology

    2012-03-22

    operations, the Bill of Materials ( BOM ) to process an aircraft through PDM is generated after I-Dock in the ‘Generate PDM BOM ’ section of the model...of five docks and takes between 15 and 17 days to complete. The inspections that take place here form the basis for the negotiated bill of materials ...between the maintenance wing and program office. Each aircraft has a pre existing bill of materials for the planned PDM work, but during I-Dock

  2. Multiple-image-depth modeling for hotspot and AF printing detections

    NASA Astrophysics Data System (ADS)

    Tang, Y. P.; Chou, C. S.; Huang, W. C.; Liu, R. G.; Gau, T. S.

    2012-03-01

    Typical OPC models focus on predicting wafer contour or CD; therefore, the modeling approach emphasizes careful determination of feature and edge locations in the photo-resist (PR) as well as the exposure threshold, so that the 'cut' model image matches the wafer SEM contours or cut-line CDs most closely. This is an exquisite approach with regard to the contour-based OPC, for the model is calibrated directly from wafer CDs. However, for other applications such as hotspot detection or assist feature (AF) printing prediction that might occur at the top or the bottom of the PR, the typical OPC model approach may not be accurate enough. Usually, these kinds of phenomenon can only be properly described by rigorous simulation, which is very time-consuming and hence not suitable for OPC. In this paper, the approach of building the OPC model with multiple image depths will be discussed. This approach references the images at the bottom and/or the top of the PR. This way, the behavior of the images which are not shown at the normal image depth can be predicted more accurately without distorting the optical model. This compromised OPC modeling approach is beneficial for runtime reduction compared to the rigorous simulation, and for better accuracy compared to conventional model. The applications for AF printing and hotspot predictions using the multiple image depth approach will be demonstrated.

  3. Common data model for natural language processing based on two existing standard information models: CDA+GrAF.

    PubMed

    Meystre, Stéphane M; Lee, Sanghoon; Jung, Chai Young; Chevrier, Raphaël D

    2012-08-01

    An increasing need for collaboration and resources sharing in the Natural Language Processing (NLP) research and development community motivates efforts to create and share a common data model and a common terminology for all information annotated and extracted from clinical text. We have combined two existing standards: the HL7 Clinical Document Architecture (CDA), and the ISO Graph Annotation Format (GrAF; in development), to develop such a data model entitled "CDA+GrAF". We experimented with several methods to combine these existing standards, and eventually selected a method wrapping separate CDA and GrAF parts in a common standoff annotation (i.e., separate from the annotated text) XML document. Two use cases, clinical document sections, and the 2010 i2b2/VA NLP Challenge (i.e., problems, tests, and treatments, with their assertions and relations), were used to create examples of such standoff annotation documents, and were successfully validated with the XML schemata provided with both standards. We developed a tool to automatically translate annotation documents from the 2010 i2b2/VA NLP Challenge format to GrAF, and automatically generated 50 annotation documents using this tool, all successfully validated. Finally, we adapted the XSL stylesheet provided with HL7 CDA to allow viewing annotation XML documents in a web browser, and plan to adapt existing tools for translating annotation documents between CDA+GrAF and the UIMA and GATE frameworks. This common data model may ease directly comparing NLP tools and applications, combining their output, transforming and "translating" annotations between different NLP applications, and eventually "plug-and-play" of different modules in NLP applications.

  4. AF printability check with a full-chip 3D resist profile model

    NASA Astrophysics Data System (ADS)

    Wu, Cheng-En R.; Chang, Jason; Song, Hua; Shiely, James

    2013-09-01

    A single compact resist model capable of predicting 3D resist profile is strongly demanded for the advanced technology nodes to avoid the potential hotspots due to imperfect resist pattern shape and its lack of resistance in the subsequent etch process. In this work, we propose a resist 3D (R3D) compact model that takes acidz-diffusion effect into account. The chemical reaction between acid and base along z-direction is treated as second order effect that is absorbed into the anisotropic diffusion length as a fitting parameter. Meanwhile, the resist model in the x-y wafer plane is still kept in general by applying the compact solution of 2D reaction-diffusion equation. In order to have the 2D contour predictability at arbitrary resist height, calibration from entire 3D data (CDs at several heights) areconducted simultaneously witha single cost function so that the R3D compact model is described by a common set of resist free parameters and threshold for all resist heights. With the low energy approximation, the acid z-diffusion effect is equivalent to a z-diffused TCC that takes the form of linear combination of pure optical TCCs sampled at discrete image-depth which can be pre-calculated. With this benefit, the R3D compact model offers a more physical approach but adds no runtime concern on the OPC and verification applications. The predicted resist cross-section profiles from our test patterns are compared those computed with rigorous lithography simulator SLITHO and show very good matching results between them. The demonstration of the AF printability check from the predicted cross-section profile at AF indicates the success of our R3D compact model.

  5. Comparison of the ferromagnetic Blume-Emery-Griffiths model and the AF spin-1 longitudinal Ising model at low temperature

    NASA Astrophysics Data System (ADS)

    Thomaz, M. T.; Corrêa Silva, E. V.

    2016-03-01

    We derive the exact Helmholtz free energy (HFE) of the standard and staggered one-dimensional Blume-Emery-Griffiths (BEG) model in the presence of an external longitudinal magnetic field. We discuss in detail the thermodynamic behavior of the ferromagnetic version of the model, which exhibits magnetic field-dependent plateaux in the z-component of its magnetization at low temperatures. We also study the behavior of its specific heat and entropy, both per site, at finite temperature. The degeneracy of the ground state, at T=0, along the lines that separate distinct phases in the phase diagram of the ferromagnetic BEG model is calculated, extending the study of the phase diagram of the spin-1 antiferromagnetic (AF) Ising model in S.M. de Souza and M.T. Thomaz, J. Magn. and Magn. Mater. 354 (2014) 205 [5]. We explore the implications of the equality of phase diagrams, at T=0, of the ferromagnetic BEG model with K/|J| = - 2 and of the spin-1 AF Ising model for D/|J| > 1/2.

  6. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s disease

    PubMed Central

    Fisher, Abraham; Bezprozvanny, Ilya; Wu, Lili; Ryskamp, Daniel A.; Bar-Ner, Nira; Natan, Niva; Brandeis, Rachel; Elkon, Hanoch; Nahum, Victoria; Gershonov, Eitan; LaFerla, Frank M.; Medeiros, Rodrigo

    2015-01-01

    We previously developed orthosteric M1 muscarinic agonists (e.g., AF102B, AF267B, and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (phopho-ERK1/2, phospho-CREB). AF710B (1–30 µg/kg, po) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its anti-amnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice AF710B (10 µg/kg, ip/daily/2 months) – i) mitigated cognitive impairments in Morris water maze; ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ40, Aβ42, plaques and tau pathologies. AF710B differs from conventional σ1, M1 muscarinic (orthosteric, allosteric or bi-topic) or σ1/muscarinic agonists. These results highlight AF710B as a potential treatment for AD (e.g., improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies. PMID:26606130

  7. Comparison of the exact thermodynamics of the AF Blume-Emery-Grifiths and of the spin-1 ferromagnetic Ising models

    NASA Astrophysics Data System (ADS)

    Corrêa Silva, E. V.; Thomaz, M. T.

    2016-11-01

    We study in detail the thermodynamics of the anti-ferromagnetic Blume-Emery-Griffiths (AF BEG) model in the presence of a longitudinal magnetic field. Its thermodynamics is derived from the exact Helmholtz free energy (HFE) of the model, valid for T > 0. Numerical simulations of this model on a periodic space chain with 10 sites (N=10) yield the energy spectra of the model at K/J = 2 for D/J = 1 and D/J = 2, thus helping us compare, for a broad range of temperature, how some (per site) thermodynamic functions with the same value of K/J but distinct values of D/J behave, namely: the z-component of the magnetization, the specific heat and the entropy. These thermodynamic functions of the AF BEG model at K/|J| = 2 are compared to those of the spin-1 ferromagnetic Ising model with D/|J| > 1.5, for which the T=0 phase diagrams of both models are identical. This comparison is done in a large interval of temperature.

  8. Linear quadratic game and non-cooperative predictive methods for potential application to modelling driver-AFS interactive steering control

    NASA Astrophysics Data System (ADS)

    Na, Xiaoxiang; Cole, David J.

    2013-02-01

    This paper is concerned with the modelling of strategic interactions between the human driver and the vehicle active front steering (AFS) controller in a path-following task where the two controllers hold different target paths. The work is aimed at extending the use of mathematical models in representing driver steering behaviour in complicated driving situations. Two game theoretic approaches, namely linear quadratic game and non-cooperative model predictive control (non-cooperative MPC), are used for developing the driver-AFS interactive steering control model. For each approach, the open-loop Nash steering control solution is derived; the influences of the path-following weights, preview and control horizons, driver time delay and arm neuromuscular system (NMS) dynamics are investigated, and the CPU time consumed is recorded. It is found that the two approaches give identical time histories as well as control gains, while the non-cooperative MPC method uses much less CPU time. Specifically, it is observed that the introduction of weight on the integral of vehicle lateral displacement error helps to eliminate the steady-state path-following error; the increase in preview horizon and NMS natural frequency and the decline in time delay and NMS damping ratio improve the path-following accuracy.

  9. A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification.

    PubMed

    Bueno, Clara; Montes, Rosa; Melen, Gustavo J; Ramos-Mejia, Verónica; Real, Pedro J; Ayllón, Verónica; Sanchez, Laura; Ligero, Gertrudis; Gutierrez-Aranda, Iván; Fernández, Agustín F; Fraga, Mario F; Moreno-Gimeno, Inmaculada; Burks, Deborah; Plaza-Calonge, María del Carmen; Rodríguez-Manzaneque, Juan C; Menendez, Pablo

    2012-06-01

    The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs but strongly impairs further hematopoietic commitment in favor of an endothelial cell fate. MLL-AF4 hESCs are transcriptionally primed to differentiate towards hemogenic precursors prone to endothelial maturation, as reflected by the marked upregulation of master genes associated to vascular-endothelial functions and early hematopoiesis. Furthermore, we report that MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells. This work illustrates how hESCs may provide unique insights into human development and further our understanding of how leukemic fusion genes, known to arise prenatally, regulate human embryonic hematopoietic specification.

  10. A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification

    PubMed Central

    Bueno, Clara; Montes, Rosa; Melen, Gustavo J; Ramos-Mejia, Verónica; Real, Pedro J; Ayllón, Verónica; Sanchez, Laura; Ligero, Gertrudis; Gutierrez-Aranda, Iván; Fernández, Agustín F; Fraga, Mario F; Moreno-Gimeno, Inmaculada; Burks, Deborah; del Carmen Plaza-Calonge, María; Rodríguez-Manzaneque, Juan C; Menendez, Pablo

    2012-01-01

    The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs but strongly impairs further hematopoietic commitment in favor of an endothelial cell fate. MLL-AF4 hESCs are transcriptionally primed to differentiate towards hemogenic precursors prone to endothelial maturation, as reflected by the marked upregulation of master genes associated to vascular-endothelial functions and early hematopoiesis. Furthermore, we report that MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells. This work illustrates how hESCs may provide unique insights into human development and further our understanding of how leukemic fusion genes, known to arise prenatally, regulate human embryonic hematopoietic specification. PMID:22212479

  11. Neuroprotective and Anti-Inflammatory Effects of the Flavonoid-Enriched Fraction AF4 in a Mouse Model of Hypoxic-Ischemic Brain Injury

    PubMed Central

    Keddy, Paul G. W.; Dunlop, Kate; Warford, Jordan; Samson, Michel L.; Jones, Quinton R. D.; Rupasinghe, H. P. Vasantha; Robertson, George S.

    2012-01-01

    We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4) in a mouse of model of hypoxic-ischemic (HI) brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days) prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days) produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o.) prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days) in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml), but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling. PMID:23251498

  12. Neuroprotective and anti-inflammatory effects of the flavonoid-enriched fraction AF4 in a mouse model of hypoxic-ischemic brain injury.

    PubMed

    Keddy, Paul G W; Dunlop, Kate; Warford, Jordan; Samson, Michel L; Jones, Quinton R D; Rupasinghe, H P Vasantha; Robertson, George S

    2012-01-01

    We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4) in a mouse of model of hypoxic-ischemic (HI) brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days) prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days) produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o.) prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days) in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml), but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling.

  13. Modeling and Prediction of Corrosion-Fatigue Failures in AF1410 Steel Test Specimens

    DTIC Science & Technology

    2009-01-12

    the curve was modeled using the Coffin- Manson equation (references 9 and 10); with the equation coefficients derived from a log-log regression of the...fatigue test data were modeled using a bilinear log-log fit of the Coffin- Manson relation described previously. The elastic portion of the Coffin... Manson curve was assumed fixed. The slope (B) and intercept (A) errors of the plastic strain regression curve are Student-t distributed when transformed

  14. A silk peptide fraction restores cognitive function in AF64A-induced Alzheimer disease model rats by increasing expression of choline acetyltransferase gene.

    PubMed

    Cha, Yeseul; Lee, Sang Hoon; Jang, Su Kil; Guo, Haiyu; Ban, Young-Hwan; Park, Dongsun; Jang, Gwi Yeong; Yeon, Sungho; Lee, Jeong-Yong; Choi, Ehn-Kyoung; Joo, Seong Soo; Jeong, Heon-Sang; Kim, Yun-Bae

    2017-01-01

    This study investigated the effects of a silk peptide fraction obtained by incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive dysfunction of Alzheimer disease model rats. In order to elucidate underlying mechanisms, the effect of SP-NN on the expression of choline acetyltransferase (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma cells; active amino acid sequence was identified using HPLC-MS. The expression of ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by treatment with SP-NN fraction. The active peptide in SP-NN was identified as tyrosine-glycine with 238.1 of molecular weight. Male rats were orally administered with SP-NN (50 or 300mg/kg) and challenged with a cholinotoxin AF64A. As a result of brain injury and decreased brain acetylcholine level, AF64A induced astrocytic activation, resulting in impairment of learning and memory function. Treatment with SP-NN exerted recovering activities on acetylcholine depletion and brain injury, as well as cognitive deficit induced by AF64A. The results indicate that, in addition to a neuroprotective activity, the SP-NN preparation restores cognitive function of Alzheimer disease model rats by increasing the release of acetylcholine.

  15. AF fixer: new incremental OPC method for optimizing assist feature

    NASA Astrophysics Data System (ADS)

    Jung, Sung-Gon; Kim, Sang-Wook; Suh, Sung-Soo; Kim, Young-Chang; Lee, Suk-Joo; Choi, Sung-Woon; Han, Woo-Sung; Moon, Joo-Tae; Barnes, Levi D.; Li, Xiaohai; Lugg, Robert M.; Lee, Sooryong; Koo, Kyoil; Do, Munhoe; Amoroso, Frank P.; Painter, Benjamin

    2008-05-01

    Due to shrinking design nodes and to some limitations of scanners, extreme off-axis illumination (OAI) required and its use and implementation of assist features (AF) to solve depth of focus (DOF) problems for isolated features and specific pitch regions is essential. But unfortunately, the strong periodic character of OAI illumination makes AF's print more easily. Present OPC flows generate AFs before OPC, which is also causes some AF printing problems. At present, mask manufacturers must downsize AF's below 30nm to solve this problem. This is challenging and increases mask cost. We report on an AF-fixer tool which is able to check AF printability and correct weak points with minimal cost in terms of DOF after OPC. We have devised an effective algorithm that removes printing AF's. It can not only search for the best non-printing AF condition to meet the DOF spec, but also reports uncorrectable spots, which could be marked as design errors. To limit correction times and to maximize DOF in full-chip correction, a process window (PW) model and incremental OPC method are applied. This AF fixer, which suggests optimum AF in only weak point region, solves AF printing problems economically and accurately.

  16. Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome.

    PubMed

    Marechal, Damien; Lopes Pereira, Patricia; Duchon, Arnaud; Herault, Yann

    2015-01-01

    Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features.

  17. Dosage of the Abcg1-U2af1 Region Modifies Locomotor and Cognitive Deficits Observed in the Tc1 Mouse Model of Down Syndrome

    PubMed Central

    Marechal, Damien; Pereira, Patricia Lopes; Duchon, Arnaud; Herault, Yann

    2015-01-01

    Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects. The transchromosomic Tc1 mouse model carrying an extra freely-segregating copy of human chromosome 21 was developed to better characterize the relation between genotype and phenotype in DS. The Tc1 mouse exhibits several locomotor and cognitive deficits related to DS. In this report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the Ms2Yah model carrying a deletion of the corresponding interval in the mouse genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how the different behavioral phenotypes are affected. We detected subtle changes with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah compound mutants performed better in the rotarod than the Tc1 mice. This data support the impact of genes from the Abcg1-U2af1 region as modifiers of Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex interactions between triplicated genes inducing DS features. PMID:25706610

  18. Application of a GIS-AF/RF model to assess the risk of herbicide leaching in a citrus-growing area of the Valencia Community, Spain.

    PubMed

    de Paz, José M; Rubio, José L

    2006-12-01

    We integrated an index-based attenuation factor/retardation factor (AF/RF) model into a GIS to evaluate the risk of leaching of the most frequently applied herbicides (glyphosate, diuron, diquat, bromacil, simazine, linuron, terbuthylazine, and terbumeton) used in citrus orchards of the Valencia Community, Spain. The GIS-model system was applied to a region of 33,800 ha located near Valencia City. The soil and climate data required by the model were stored in an Arc/Info GIS in which the model algorithms were integrated using the AML programming language. A graphical user interface was developed to facilitate the use of the GIS-model system. The resulting simulation maps indicate that terbumeton, bromacil, and simazine herbicides have the highest risk of leaching because of their high mobility and low K(oc) (32-158 mg l(-1)). The remaining herbicides are strongly adsorbed by clay particles and organic matter, thus minimising the risk of leaching through the soil profile and into groundwater. The obtained ranking of the leaching potential of analysed herbicides is as follows, from highest to lowest risk: terbumeton>bromacil>simazine>terbuthylazine>diuron>linuron>glyphosate>diquat.

  19. DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex

    PubMed Central

    Mück, Fabian; Bracharz, Silvia; Marschalek, Rolf

    2016-01-01

    AF4/AFF1 and AF5/AFF4 are both backbones for the assembly of “super elongation complexes” (SECs) that exert 2 distinct functions after the recruitment of P-TEFb from the 7SK snRNP: (1) initiation and elongation of RNA polymerase II gene transcription, and (2) modification of transcribed gene regions by distinct histone methylation patterns. In this study we aimed to investigate one of the initial steps, namely how P-TEFb is transferred from 7SK snRNPs to the SECs. In particular, we were interested in the role of DDX6 that we have recently identified as part of the AF4 complex. DDX6 is an evolutionarily conserved member of the DEAD-box RNA helicase family that is known to control miRNA and mRNA biology (translation, storage and degradation). Overexpressed DDX6 is associated with different cancer types and with c-Myc protein overexpression. We could demonstrate that DDX6 binds to 7SK snRNA and causes the release and transfer of P-TEFb to the AF4/AF4N SEC. DDX6 also binds stably to AF4 and AF4N as demonstrated by GST pull-down and co-immunoprecipitation experiments. As a consequence, overexpression of either AF4/AF4N or DDX6 resulted in a strong increase of mRNA production (5-6 fold), while their simultaneous expression increased the cellular mRNA production by 11-fold. Conversely, the corresponding knockdown of DDX6 decreased mRNA production by 70%. In conclusion, AF4/AF4N and DDX6 represent key molecules for the elongation process of gene transcription and a model will be proposed for the hand-over process of P-TEFb to SECs. PMID:27679741

  20. Chronotropic Modulation of the Source-Sink Relationship of Sinoatrial-Atrial Impulse Conduction and Its Significance to Initiation of AF: A One-Dimensional Model Study

    PubMed Central

    Cacciani, Francesca; Zaniboni, Massimiliano

    2015-01-01

    Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulation GKr, which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in ICaL. Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies. PMID:26229960

  1. The leukemogenic CALM/AF10 fusion protein alters the subcellular localization of the lymphoid regulator Ikaros.

    PubMed

    Greif, P A; Tizazu, B; Krause, A; Kremmer, E; Bohlander, S K

    2008-05-01

    The t(10;11)(p13;q14) translocation leads to the fusion of the CALM and AF10 genes. This translocation can be found as the sole cytogenetic abnormality in acute lymphoblastic leukemia, acute myeloid leukemia and in malignant lymphomas. The expression of CALM/AF10 in primary murine bone marrow cells results in the development of an aggressive leukemia in a murine bone marrow transplantation model. Using a yeast two-hybrid screen, we identified the lymphoid regulator Ikaros as an AF10 interacting protein. Interestingly, Ikaros is required for normal development of lymphocytes, and aberrant expression of Ikaros has been found in leukemia. In a murine model, the expression of a dominant negative isoform of Ikaros causes leukemias and lymphomas. The Ikaros interaction domain of AF10 was mapped to the leucine zipper domain of AF10, which is required for malignant transformation both by the CALM/AF10 and the MLL/AF10 fusion proteins. The interaction between AF10 and Ikaros was confirmed by GST pull down and co-immunoprecipitation. Coexpression of CALM/AF10 but not of AF10 alters the subcellular localization of Ikaros in murine fibroblasts. The transcriptional repressor activity of Ikaros is reduced by AF10. These results suggest that CALM/AF10 might interfere with normal Ikaros function, and thereby block lymphoid differentiation in CALM/AF10 positive leukemias.

  2. A new AF gravitational instanton

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Teo, Edward

    2011-09-01

    It has long been conjectured that the Euclidean Schwarzschild and Euclidean Kerr instantons are the only non-trivial asymptotically flat (AF) gravitational instantons. In this Letter, we show that this conjecture is false by explicitly constructing a new two-parameter AF gravitational instanton with a U (1) × U (1) isometry group, using the inverse-scattering method. It has Euler number χ = 3 and Hirzebruch signature τ = 1, and its global topology is CP2 with a circle S1 removed appropriately. Various other properties of this gravitational instanton are also discussed.

  3. AF-GEOSpace Version 2.5: Space Environment Software

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Hall, T.; Roth, C.; Ling, A.; Ginet, G. P.; Madden, D.

    2010-12-01

    AF-GEOSpace is a graphics-intensive software program with space environment models and applications developed by the Space Weather Center of Excellence at AFRL. The software addresses a wide range of physical domains, e.g., solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. AF-GEOSpace has become a platform for developing and prototyping space weather visualization products. The new AF-GEOSpace Version 2.5 (release scheduled for 2010) expands on the content of Version 2.1 by including modules addressing the following new topics: (1) energetic proton maps for the South Atlantic Anomaly (from Ginet et al. [2007]), (2) GPS scintillation outage simulation tools, (3) magnetopause location determination (Shue et al. [1998]), (4) a plasmasphere model (Global Core Plasma Model, 2009 version based on Gallagher et al. [2000]), (5) a standard ionospheric model (International Reference Ionosphere 2007), (6) the CAMMICE/MICS model of inner magnetosphere plasma population (based on Roeder et al. [2005]), (7) magnetic field models (e.g., Tsyganenko and Sitnov [2005]), and (8) loading and displaying externally-produced 3D gridded data sets within AF-GEOSpace. Improvements to existing Version 2.1 capabilities include: (1) a 2005 update to the geomagnetic cutoff rigidity model of Smart and Shea [2003], (2) a 2005 update to the ionospheric scintillation Wide-Band Model (WBMOD) of Secan and Bussey [1994], and (3) improved magnetic field flux mapping options for the existing set of AF-GEOSpace radiation belt models. A basic review of these new AF-GEOSpace capabilities will be provided. To obtain a copy of the software, please contact the first author.

  4. Installation Restoration Program. Phase 1 - Records Search AAC-Northern Region, Galena AFS, Campion AFS, Cape Lisburne AFS, Fort Yukon AFS, Indian Mountain AFS, Kotzebue AFS, Murphy Dome AFS, and Tin City AFS

    DTIC Science & Technology

    1985-09-01

    registered with Defense Technical Information Center should direct requests for copies of this report to: Defense Technical Information Center Cameron Station ...Information Center should direct requests for copies of this report to: Defense Technical Information Center Cameron Station Alexandria, Virginia 22314 U’ B...Contract No. F08637 84 C0070. The locations of these installations are shown in Figure 1. INSTALLATION DESCRIPTION Galena AFS * Galena Air Force Station

  5. GPIM AF-M315E Propulsion System

    NASA Technical Reports Server (NTRS)

    Spores, Ronald A.; Masse, Robert; Kimbrel, Scott; McLean, Chris

    2014-01-01

    The NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) will demonstrate an operational AF-M315E green propellant propulsion system. Aerojet-Rocketdyne is responsible for the development of the propulsion system payload. This paper statuses the propulsion system module development, including thruster design and system design; Initial test results for the 1N engineering model thruster are presented. The culmination of this program will be high-performance, green AF-M315E propulsion system technology at TRL 7+, with components demonstrated to TRL 9, ready for direct infusion to a wide range of applications for the space user community.

  6. The Aspergillus fumigatus transcriptional regulator AfYap1 represents the major regulator for defense against reactive oxygen intermediates but is dispensable for pathogenicity in an intranasal mouse infection model.

    PubMed

    Lessing, Franziska; Kniemeyer, Olaf; Wozniok, Iwona; Loeffler, Juergen; Kurzai, Oliver; Haertl, Albert; Brakhage, Axel A

    2007-12-01

    Macrophages and neutrophils kill the airborne fungal pathogen Aspergillus fumigatus. The dependency of this killing process on reactive oxygen intermediates (ROI) has been strongly suggested. Therefore, we investigated the enzymatic ROI detoxifying system by proteome analysis of A. fumigatus challenged by H(2)O(2). Since many of the identified proteins and genes are apparently regulated by a putative Saccharomyces cerevisiae Yap1 homolog, the corresponding gene of A. fumigatus was identified and designated Afyap1. Nuclear localization of a functional AfYap1-eGFP fusion was stress dependent. Deletion of the Afyap1 gene led to drastically increased sensitivity of the deletion mutant against H(2)O(2) and menadione, but not against diamide and NO radicals. Proteome analysis of the DeltaAfyap1 mutant strain challenged with 2 mM H(2)O(2) indicated that 29 proteins are controlled directly or indirectly by AfYap1, including catalase 2. Despite its importance for defense against reactive agents, the Afyap1 deletion mutant did not show attenuated virulence in a murine model of Aspergillus infection. These data challenge the hypothesis that ROI such as superoxide anions and peroxides play a direct role in killing of A. fumigatus in an immunocompromised host. This conclusion was further supported by the finding that killing of A. fumigatus wild-type and DeltaAfyap1 mutant germlings by human neutrophilic granulocytes worked equally well irrespective of whether the ROI scavenger glutathione or an NADPH-oxidase inhibitor was added to the cells.

  7. Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo

    PubMed Central

    Shirai, Cara Lunn; Ley, James N.; White, Brian S.; Kim, Sanghyun; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Wadugu, Brian; Duncavage, Eric J.; Okeyo-Owuor, Theresa; Liu, Tuoen; Griffith, Malachi; McGrath, Sean; Magrini, Vincent; Fulton, Robert S.; Fronick, Catrina; O’Laughlin, Michelle; Graubert, Timothy A.; Walter, Matthew J.

    2015-01-01

    SUMMARY Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ~11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease. We examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F) display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic progenitor cells by whole transcriptome analysis (RNA-seq). Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently-mutated MDS and acute myeloid leukemia-associated genes. These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in MDS patients. PMID:25965570

  8. A Conditional Role of U2AF in Splicing of Introns with Unconventional Polypyrimidine Tracts▿ †

    PubMed Central

    Sridharan, Vinod; Singh, Ravinder

    2007-01-01

    Recognition of polypyrimidine (Py) tracts typically present between the branch point and the 3′ splice site by the large subunit of the essential splicing factor U2AF is a key early step in pre-mRNA splicing. Diverse intronic sequence arrangements exist, however, including 3′ splice sites lacking recognizable Py tracts, which raises the question of how general the requirement for U2AF is for various intron architectures. Our analysis of fission yeast introns in vivo has unexpectedly revealed that whereas introns lacking Py tracts altogether remain dependent on both subunits of U2AF, introns with long Py tracts, unconventionally positioned upstream of branch points, are unaffected by U2AF inactivation. Nevertheless, mutation of these Py tracts causes strong dependence on the large subunit U2AF59. We also find that Py tract diversity influences the requirement for the conserved C-terminal domain of U2AF59 (RNA recognition motif 3), which has been implicated in protein-protein interactions with other splicing factors. Together, these results suggest that in addition to Py tract binding by U2AF, supplementary mechanisms of U2AF recruitment and 3′ splice site identification exist to accommodate diverse intron architectures, which have gone unappreciated in biochemical studies of model pre-mRNAs. PMID:17709389

  9. Health Information in Somali (af Soomaali): MedlinePlus

    MedlinePlus

    ... af Soomaali (Somali) Bilingual PDF Health Information Translations Wildfires Wildfires - English Dabka duurka - af Soomaali (Somali) Multimedia Healthy Roads Media Wildfires - English Dabka duurka - af Soomaali (Somali) PDF Healthy ...

  10. Investigation of Incipient Spin Characteristics of a 1/35-Scale Model of the Convair F-102A Airplane, Coord. No. AF-AM-79

    NASA Technical Reports Server (NTRS)

    Healy, Frederick M.

    1958-01-01

    Incipient spin characteristics have been investigated on a l/35-scale dynamic model of the Convair F-10% airplane. The model was launched by a catapult apparatus into free flight with various control settings, and the motions obtained were photographed. The model was ballasted for the combat loading. All tests were made with the speed brakes and landing gear retracted, and engine effects were not simulated. The results of the investigation indicated that the model would enter motions apparently simulating entry phases of spins when the elevators were deflected full up. Deflecting the rudder had little effect on the direction of the motion obtained, but when ailerons were deflected the model always rotated in a direction opposite to the aileron setting (that is, the model entered a right spin with the stick to the left). The ailerons were very influential in initiating spin entry, and the pilot should avoid, as far as possible, the use of ailerons in low-speed flight.

  11. STBC AF relay for unmanned aircraft system

    NASA Astrophysics Data System (ADS)

    Adachi, Fumiyuki; Miyazaki, Hiroyuki; Endo, Chikara

    2015-01-01

    If a large scale disaster similar to the Great East Japan Earthquake 2011 happens, some areas may be isolated from the communications network. Recently, unmanned aircraft system (UAS) based wireless relay communication has been attracting much attention since it is able to quickly re-establish the connection between isolated areas and the network. However, the channel between ground station (GS) and unmanned aircraft (UA) is unreliable due to UA's swing motion and as consequence, the relay communication quality degrades. In this paper, we introduce space-time block coded (STBC) amplify-and-forward (AF) relay for UAS based wireless relay communication to improve relay communication quality. A group of UAs forms single frequency network (SFN) to perform STBC-AF cooperative relay. In STBC-AF relay, only conjugate operation, block exchange and amplifying are required at UAs. Therefore, STBC-AF relay improves the relay communication quality while alleviating the complexity problem at UAs. It is shown by computer simulation that STBC-AF relay can achieve better throughput performance than conventional AF relay.

  12. Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

    PubMed Central

    Washington, Erica J.; Mukhtar, M. Shahid; Finkel, Omri M.; Wan, Li; Kieber, Joseph J.; Dangl, Jeffery L.

    2016-01-01

    HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis. We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogen-associated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site-specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts. PMID:27274076

  13. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

    PubMed

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

    2015-08-21

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties.

  14. Hospitalizations in patients with atrial fibrillation: an analysis from ROCKET AF

    PubMed Central

    DeVore, Adam D.; Hellkamp, Anne S.; Becker, Richard C.; Berkowitz, Scott D.; Breithardt, Guenter; Hacke, Werner; Halperin, Jonathan L.; Hankey, Graeme J.; Mahaffey, Kenneth W.; Nessel, Christopher C.; Singer, Daniel E.; Fox, Keith A. A.; Patel, Manesh R.; Piccini, Jonathan P.

    2016-01-01

    Aims The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. Methods and results The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29–1.66], diabetes [1.22, (1.11–1.34)], prior MI [1.27, (1.13–1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04–1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. Conclusion Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization. PMID:27174904

  15. Gymnasterkoreaynes A-F, cytotoxic polyacetylenes from Gymnaster koraiensis.

    PubMed

    Jung, Hyun-Ju; Min, Byung-Sun; Park, Jin-Young; Kim, Young-Ho; Lee, Hyeong-Kyu; Bae, Ki-Hwan

    2002-06-01

    Six new polyacetylenes, gymnasterkoreaynes A-F (1-6), were isolated from the roots of Gymnaster koraiensis, together with 2,9,16-heptadecatrien-4,6-diyn-8-ol (7) and 1,9,16-heptadecatriene-4,6-diyn-3,8-diol (8), by bioassay-guided fractionation using the L1210 tumor cell line as a model for cytotoxicity. The structures of compounds 1-6 were established spectroscopically, which included 2D NMR experiments. Gymnasterkoreaynes A-F (1-6) are linear diacetylenes and are structurally related to falcarinol, panaxynol, panaxydiol, and panaxytriol. Of the compounds isolated, gymnasterkoreaynes B (2), C (3), F (6), and 1,9,16-heptadecatrien-4,6-diyn-3,8-diol (8) exhibited significant cytotoxicity against L1210 tumor cells with ED(50) values of 0.12-3.3 microg/mL.

  16. Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)

    PubMed Central

    Steinberg, Benjamin A; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C; Gersh, Bernard J; Holmqvist, Fredrik; Hylek, Elaine; Kowey, Peter R; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Chang, Paul; Peterson, Eric D; Piccini, Jonathan P

    2015-01-01

    Background Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF. Methods and Results We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Conclusions Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. Clinical Trial Registration URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710. PMID:26370445

  17. An Implicit LU/AF FDTD Method

    NASA Technical Reports Server (NTRS)

    Beggs, John H.; Briley, W. Roger

    2001-01-01

    There has been some recent work to develop two and three-dimensional alternating direction implicit (ADI) FDTD schemes. These ADI schemes are based upon the original ADI concept developed by Peaceman and Rachford and Douglas and Gunn, which is a popular solution method in Computational Fluid Dynamics (CFD). These ADI schemes work well and they require solution of a tridiagonal system of equations. A new approach proposed in this paper applies a LU/AF approximate factorization technique from CFD to Maxwell s equations in flux conservative form for one space dimension. The result is a scheme that will retain its unconditional stability in three space dimensions, but does not require the solution of tridiagonal systems. The theory for this new algorithm is outlined in a one-dimensional context for clarity. An extension to two and threedimensional cases is discussed. Results of Fourier analysis are discussed for both stability and dispersion/damping properties of the algorithm. Results are presented for a one-dimensional model problem, and the explicit FDTD algorithm is chosen as a convenient reference for comparison.

  18. The Advancing State of AF-M315E Technology

    NASA Technical Reports Server (NTRS)

    Masse, Robert; Spores, Ronald A.; McLean, Chris

    2014-01-01

    The culmination of twenty years of applied research in hydroxyl ammonium nitrate (HAN)-based monopropellants, the NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) will achieve the first on-orbit demonstration of an operational AF-M315E green propellant propulsion system by the end of 2015. Following an contextual overview of the completed flight design of the GPIM propellant storage and feed system, results of first operation of a flight-representative heavyweight 20-N engineering model thruster (to be conducted in mid-2014) are presented with performance comparisons to prior lab model (heavyweight) test articles.

  19. Degradation of AF1Q by chaperone-mediated autophagy

    SciTech Connect

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  20. AFS Estuaries Section - A Successful Partnership

    EPA Science Inventory

    The Estuaries Section of the American Fisheries Society offers travel awards to students in support of their attendance and presentations at the AFS meeting. Since 2007, the Southern Association of Marine Laboratories has partnered with the Estuaries Section to sponsor two stude...

  1. Topological ferrimagnetic behaviours of coordination polymers containing manganese(II) chains with mixed azide and carboxylate bridges and alternating F/AF/AF'/AF'/AF interactions.

    PubMed

    Wang, Yan-Qin; Liu, Hou-Ting; Qi, Yan; Gao, En-Qing

    2014-08-21

    Two Mn(ii) complexes with azide and a new zwitterionic tetracarboxylate ligand 1,2,4,5-tetrakis(4-carboxylatopyridinium-1-methylene)benzene (L(1)), {[Mn5(L(1))2(N3)8(OH)2]·12H2O}n () and {[Mn5(L(1))2(N3)8(H2O)2](ClO4)2·6H2O}n (), have been synthesized and characterized crystallographically and magnetically. and contain similar alternating chains constructed by azide and carboxylate bridges. The independent sets of bridges alternate in an ABCCB sequence between adjacent Mn(ii) ions: (EO-N3)2 double bridges (EO = end-on) (denoted as A), [(EO-N3)(OCO)2] triple bridges (denoted as B) and [(EO-N3)(OCO)] double bridges (denoted as C). The alternating chains are interlinked into 2D coordination networks by the tetrapyridinium spacers. Magnetic studies demonstrate that the magnetic coupling through the double EO azide bridges is ferromagnetic and that through mixed azide/carboxylate bridges is antiferromagnetic. The unprecedented F/AF/AF'/AF'/AF coupling sequence along the chain dictates an uncompensated ground spin state (S = 5/2 per Mn5 unit) and leads to one-dimensional topological ferrimagnetism, which features a minimum in the χT versus T plot.

  2. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    NASA Technical Reports Server (NTRS)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  3. [AF + BAF for treating effluent in the sewage plant of the resin and chemical industry park].

    PubMed

    Tu, Yong; Liu, Wei-Jing; Zhang, Yao-Hui; Xu, Jun; Tang, Min; Chen, Yong; Bai, Yong-Gang

    2014-06-01

    The anaerobic filter (AF) and biological aerated filter (BAF) were employed to treat the effluent in a sewage plant of the resin and chemical industry park. The ceramsite was used in BAF. In this study, the influent COD was 200-300 mg x L(-1) and the pilot model scale was 2-4 L x d(-1). According to the results, the AF-BAF treatment had a good effect on organic wastewater. When the AF HRT was 24 h and BAF was 12 h, the removal of COD reached 73.4%, and that of NH4(+)-N reached 93.8%. From gas chromatography-mass spectrometry (GC-MS) and three-dimensional fluorescence analysis, it was found that small organic molecules and microbial metabolites could be removed effectively. However, there was no obviously effect on the removal of saturated alkane and nitrogenous heterocyclic compounds. From the denature gradient gel electrophoresis (DGGE) spectra analysis, it was shown that there were more kinds of microorganism in the sludge of the AF than in the up-flow anaerobic sludge bed (UASB), which indicates that the AF-BAF system is more effective on treating effluent in a sewage plant of the resin and chemical industry park.

  4. Evaluation of the Sustainability and Clinical Outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) in a Child Protection Center

    ERIC Educational Resources Information Center

    Kolko, David J.; Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for…

  5. Coaxially electrospun PVDF-Teflon AF and Teflon AF-PVDF core-sheath nanofiber mats with superhydrophobic properties.

    PubMed

    Muthiah, Palanikkumaran; Hsu, Shu-Hau; Sigmund, Wolfgang

    2010-08-03

    This work reports the coaxial electrospinning of poly(vinylidene fluoride) (PVDF)-Teflon amorphous fluoropolymer (AF) and Teflon AF-PVDF core-sheath nanofiber mats yielding superhydrophobic properties. The coaxial electrospinning configuration allows for the electrospinning of Teflon AF, a nonelectrospinnable polymer, with the help of an electrospinnable PVDF polymer. PVDF-Teflon AF and Teflon AF-PVDF core-sheath fibers have been found to a have mean fiber diameter ranging from 400 nm to less than 100 nm. TEM micrographs exhibit a typical core-sheath fiber structure for these fibers, where the sheath fiber coats the core fiber almost thoroughly. Water contact angle measurements by sessile drop method on these core-sheath nanofiber mats exhibited superhydrophobic characteristics with contact angles close to or higher than 150 degrees. Surprisingly, PVDF-Teflon AF and Teflon AF-PVDF nanofiber mat surface properties were dominated by the fiber dimensions and less influenced by the type of sheath polymer. This suggests that highly fluorinated polymer Teflon AF does not advance the hydrophobicity beyond what surface physics and slightly fluorinated polymer PVDF can achieve. It is concluded that PVDF-Teflon AF and Teflon AF-PVDF core-sheath electrospun nanofiber mats may be used in lithium (Li)-air batteries.

  6. Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

    PubMed

    Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

    2016-01-01

    A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts.

  7. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 14 2013-01-01 2013-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  8. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 14 2012-01-01 2012-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  9. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 14 2014-01-01 2014-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  10. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  11. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  12. Part III: AFS - A Secure Distributed File System

    SciTech Connect

    Wachsmann, A.; /SLAC

    2005-06-29

    AFS is a secure distributed global file system providing location independence, scalability and transparent migration capabilities for data. AFS works across a multitude of Unix and non-Unix operating systems and is used at many large sites in production for many years. AFS still provides unique features that are not available with other distributed file systems even though AFS is almost 20 years old. This age might make it less appealing to some but with IBM making AFS available as open-source in 2000, new interest in use and development was sparked. When talking about AFS, people often mention other file systems as potential alternatives. Coda (http://www.coda.cs.cmu.edu/) with its disconnected mode will always be a research project and never have production quality. Intermezzo (http://www.inter-mezzo.org/) is now in the Linux kernel but not available for any other operating systems. NFSv4 (http://www.nfsv4.org/) which picked up many ideas from AFS and Coda is not mature enough yet to be used in serious production mode. This article presents the rich features of AFS and invites readers to play with it.

  13. Compliance Testing of the Clear AFS Power Plant, Coal-Fired Boiler 1 Clear AFS, Alaska

    DTIC Science & Technology

    1989-10-01

    Background On 3 February 1987 Clear AFS requested a permit modification to allow limited burning of waste oil for their power plant shown in Figure 1...The Alaska DEC rescindel Permit to Operate No. 8331-AA003 and issued Permit No. 8731-AA004 (Appendix B) allowing the burning of waste oil. As a...below. 1. Visible Emissions (18 AAC 50.050(a)) Visible emissions, excluding condensed water vapor from an industrial process or fuel burning

  14. Expression of MLL-AF4 or AF4-MLL fusions does not impact the efficiency of DNA damage repair.

    PubMed

    Castaño, Julio; Herrero, Ana B; Bursen, Aldeheid; González, Federico; Marschalek, Rolf; Gutiérrez, Norma C; Menendez, Pablo

    2016-05-24

    The most frequent rearrangement of the human MLL gene fuses MLL to AF4 resulting in high-risk infant B-cell acute lymphoblastic leukemia (B-ALL). MLL fusions are also hallmark oncogenic events in secondary acute myeloid leukemia. They are a direct consequence of mis-repaired DNA double strand breaks (DNA-DSBs) due to defects in the DNA damage response associated with exposure to topoisomerase-II poisons such as etoposide. It has been suggested that MLL fusions render cells susceptible to additional chromosomal damage upon exposure to etoposide. Conversely, the genome-wide mutational landscape in MLL-rearranged infant B-ALL has been reported silent. Thus, whether MLL fusions compromise the recognition and/or repair of DNA damage remains unanswered. Here, the fusion proteins MLL-AF4 (MA4) and AF4-MLL (A4M) were CRISPR/Cas9-genome edited in the AAVS1 locus of HEK293 cells as a model to study MLL fusion-mediated DNA-DSB formation/repair. Repair kinetics of etoposide- and ionizing radiation-induced DSBs was identical in WT, MA4- and A4M-expressing cells, as revealed by flow cytometry, by immunoblot for γH2AX and by comet assay. Accordingly, no differences were observed between WT, MA4- and A4M-expressing cells in the presence of master proteins involved in non-homologous end-joining (NHEJ; i.e.KU86, KU70), alternative-NHEJ (Alt-NHEJ; i.e.LigIIIa, WRN and PARP1), and homologous recombination (HR, i.e.RAD51). Moreover, functional assays revealed identical NHEJ and HR efficiency irrespective of the genotype. Treatment with etoposide consistently induced cell cycle arrest in S/G2/M independent of MA4/A4M expression, revealing a proper activation of the DNA damage checkpoints. Collectively, expression of MA4 or A4M does neither influence DNA signaling nor DNA-DSB repair.

  15. Antisecretory Factor Peptide AF-16 Inhibits the Secreted Autotransporter Toxin-Stimulated Transcellular and Paracellular Passages of Fluid in Cultured Human Enterocyte-Like Cells

    PubMed Central

    Nicolas, Valérie

    2014-01-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of d-[1-14C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-β-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  16. Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non-valvular atrial fibrillation: results from ROCKET AF.

    PubMed

    Girgis, I G; Patel, M R; Peters, G R; Moore, K T; Mahaffey, K W; Nessel, C C; Halperin, J L; Califf, R M; Fox, K A A; Becker, R C

    2014-08-01

    Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF.

  17. Tin City AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-04-01

    GL&bAL CLIMATOLOGY 9 RA14CH T AC NG VERSUS Vi’SIBILITY A .FAT"E S[ PfIC /mAC I .17 TI CITY AFS AK 73-74,77-81 T 1b. 3 19.5 17.S 19.5 19.5...2. GOVT ACCESSION NO. 3 RECIPIENT’S CATALOG NUMBER USAFETAC/DS 83017 4. TITLE (d SubtII-)Reised Uniform Summary of Surface 5 TYPE OF REPORT & PERIOD...WINDS PART 0 CEILING VERSUS VISIBILITY PART F STATION PRESSURE SKYCOVER SEA LEVEL PRESSURE STANDARD 3 -HOUR GROUPS All su-nseri- requiring diurnal

  18. Indian Mountain AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-06-01

    31 8... . 1B b w., B. 0- r] N I o N.. Ob.. M.., N.. .1 N.-. it% To’p.Wo.- R. .1.__-___ 0 F 322 F *67 F *73 F 60S F *93 F To. 4 .. P , PSYCHROMETRIC...Psychrometrl- summary Surfoc, Worlds Extreme temperature Ceiling versus vis:boloi-; Helative Humidity -Climatological data (over) 20 ABSTRACT ’C- P ,, -1...uSAFETAC A2 4EATR SERVICE/MAC WEATHER CONDITIONS 70173C INDIAN MOUNTAIN AFS AK 73-8? P PEOCENTAGE FREQUENCY OF OCCURRENCE OF WEATHER CONDITIONS FROP HOURLY

  19. Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis.

    PubMed

    Valerio, Daria G; Xu, Haiming; Chen, Chun-Wei; Hoshii, Takayuki; Eisold, Meghan E; Delaney, Christopher; Cusan, Monica; Deshpande, Aniruddha J; Huang, Chun-Hao; Lujambio, Amaia; Zheng, YuJun George; Zuber, Johannes; Pandita, Tej K; Lowe, Scott W; Armstrong, Scott A

    2017-02-15

    Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof-deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small-molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore, Mof inactivation suppressed leukemia development in an NUP98-HOXA9-driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL-rearranged leukemias. Cancer Res; 77(7); 1-10. ©2017 AACR.

  20. Cape Newenham AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-04-01

    OBSERVATIONS) L P- 14 H~N A A-F S .~ 73-F2 ____ JA&,. ALL WI- LAt E -- .. - - 6 7 0 11 16 17 21 22 27 28- 33 34 *0 41 A7 48 5 .7 * . .3 .4 .4 . 1 . i E...PERCENTAGE FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 4LL . LAT -E- - 10 1 1 i 7 23 22 ’ 2 3 3 A 40 A 3 5 A7 A • ’ .. 5 .t",5...SCOTT A. APR 03 UNCLASSIFIED USAFETAC/DS-83/019 SBI-AD-EB50 397 F/6 4/2 NL SU 2. lii .0 EM *,*,- Ica L- 11111 1.25 s~w ,r- 1 . 11.6 I MiCRQ OPY

  1. Sabiperones A-F, new diterpenoids from Juniperus sabina.

    PubMed

    Janar, Jenis; Nugroho, Alfarius Eko; Wong, Chin Piow; Hirasawa, Yusuke; Kaneda, Toshio; Shirota, Osamu; Morita, Hiroshi

    2012-01-01

    Six new diterpenoids, sabiperones A-F (1-6) have been isolated from the aerial part of Juniperus sabina. Their structures were elucidated by spectroscopic methods including 2D NMR techniques. Sabiperone F showed moderate cell growth inhibitory activities against five human cancer cell lines.

  2. Action of AF64A on rat brain muscarinic receptors

    SciTech Connect

    Eva, C.; Costa, E.

    1986-03-01

    ICV administration of compound AF64A (ethylcholine mustard aziridium ion) induces a long-term selective cholinergic hypofunction; however, it does not modify the characteristics of muscarinic receptors. In brain muscarinic receptor activation can either stimulate phosphoinositide turnover or inhibit adenylate cyclase. ICV infusion of AF64A (5 nmol/side/2.5 ..mu..l) reduced the hippocampal ACh content 10 or 30 days after the treatment to 75% of the control values. Under these conditions neither in the striatum nor in the frontal cortex ACh levels were decreased. The carbachol dose-dependent stimulation in hippocampal slices differed from that observed in control rats. The carbachol efficacy was increased but its potency was unchanged by AF64A. In contrast, ICV administration of AF64A failed to alter the oxotremorine efficacy or potency in inhibiting the forskolin stimulated adenylate cyclase in rat hippocampal membranes. These results suggest the two transducer systems coupled to muscarinic receptors may be differentially regulatable by cholinergic input.

  3. An Empirical Test of Oklahoma's A-F School Grades

    ERIC Educational Resources Information Center

    Adams, Curt M.; Forsyth, Patrick B.; Ware, Jordan; Mwavita, Mwarumba; Barnes, Laura L.; Khojasteb, Jam

    2016-01-01

    Oklahoma is one of 16 states electing to use an A-F letter grade as an indicator of school quality. On the surface, letter grades are an attractive policy instrument for school improvement; they are seemingly clear, simple, and easy to interpret. Evidence, however, on the use of letter grades as an instrument to rank and improve schools is scant…

  4. Transonic-Wind-Tunnel Tests of the Aerodynamic Characteristics of a 0.15-Scale Model of the North American Aviation 255-Inch Fin-Stabilized External Store, Coord No. AF-AM-4

    NASA Technical Reports Server (NTRS)

    Fischetti, Thomas L.

    1958-01-01

    An investigation has been made in the Langley 8-foot transonic tunnels on the aerodynamic characteristics of a 0.15-scale model of the North American Aviation 255-inch fin-stabilized external store over a maximum Mach number range of 0.60 to 1.2 and on the effects of mounting lugs, of fin orientation, of fin aspect ratio, and of fixed-transition. The Reynolds number (based on a body length of 37.50 inches) varied from 9.8 x 10(exp 6) to 13.1 x 10(exp 6). The results indicate that the static margin of the finned store at low lift coefficients was only 9 percent of body length at subsonic Mach numbers and was reduced to zero at a Mach number of 1.0, Increasing the fin aspect ratio from 1.82 to 2.41 increased the subsonic static margin to 18 percent and provided a minimum margin of 9 percent near a Mach number of l.O. Store mounting lugs or fin orientation had only small effects on the aerodynamic characteristics of the basic store.

  5. Extracting Uranium from Seawater: Promising AF Series Adsorbents

    SciTech Connect

    Das, S.; Oyola, Y.; Mayes, Richard T.; Janke, Chris J.; Kuo, L. -J.; Gill, G.; Wood, J. R.; Dai, S.

    2016-04-20

    A new family of high-surface-area polyethylene fiber adsorbents named the AF series was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series adsorbents were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/comonomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154-354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44 M KOH at 80 °C followed by screening at ORNL with sodium-based synthetic aqueous solution, spiked with 8 ppm uranium. The uranium adsorption capacity in simulated seawater screening ranged from 170 to 200 g-U/kg-ads irrespective of %DOG. A monomer/comonomer molar ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through column experiments to determine uranium loading capacity with varying KOH conditioning times at 80 °C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1 and 3 h of KOH conditioning at 80 °C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 1 to 3 h at 80 °C resulted in a 22-27% decrease in uranium adsorption capacity in seawater.

  6. Extracting uranium from seawater: Promising AF series adsorbents

    SciTech Connect

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; Janke, Christopher James; Kuo, Li-Jung; Gill, Gary; Wood, Jordana; Dai, Sheng

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8 ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.

  7. Extracting uranium from seawater: Promising AF series adsorbents

    DOE PAGES

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; ...

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8more » ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.« less

  8. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Aspergillus flavus AF36; exemption... FOOD Exemptions From Tolerances § 180.1206 Aspergillus flavus AF36; exemption from the requirement of a... pesticide Aspergillus flavus AF36 in or on cotton, gin byproducts; cotton, hulls; cotton, meal;...

  9. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  10. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  11. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  12. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  13. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  14. Evaluation of the sustainability and clinical outcome of alternatives for families: A cognitive-behavioral therapy (AF-CBT) in a child protection center

    PubMed Central

    Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for child physical abuse and family aggression/conflict that was included in the National Child Traumatic Stress Network’s initial EBT dissemination efforts in 2002. Seven practitioners participated in a year-long Learning Collaborative in AF-CBT and in similar training programs for 4 other EBTs. The agency’s routine data collection system was used to document the clinical and adjustment outcomes of 52 families presenting with a physically abused child who received their services between 2 and 5 years after the AF-CBT training had ended. Measures of the use of all 5 EBTs documented their frequency, internal consistency, and intercorrelations. Controlling for the unique content of the other four EBTs, the amount of AF-CBT Abuse-specific content delivered was related to improvements on standardized parent rating scales (i.e., child externalizing behavior, anger, anxiety, social competence) and both parent and clinician ratings of the child’s adjustment at discharge (i.e., child more safe, less scared/sad, more appropriate with peers). The amount of AF-CBT General content was related to a few discharge ratings (better child prognosis, helpfulness to parents). These novel data provide suggestive evidence for the sustainability and clinical benefits of AF-CBT in an existing community clinic serving physically abused children and their families, and are discussed in the context of key developments in the treatment model and dissemination literature. PMID:21354619

  15. Embossed Teflon AF Laminate Membrane Microfluidic Diaphragm Valves

    NASA Technical Reports Server (NTRS)

    Willis, Peter; Hunt, Brian; White,Victor; Grunthaner, Frank

    2008-01-01

    A microfluidic system has been designed to survive spaceflight and to function autonomously on the Martian surface. It manipulates microscopic quantities of liquid water and performs chemical analyses on these samples to assay for the presence of molecules associated with past or present living processes. This technology lies at the core of the Urey Instrument, which is scheduled for inclusion on the Pasteur Payload of the ESA ExoMars rover mission in 2013. Fabrication processes have been developed to make the microfabricated Teflon-AF microfluidic diaphragm pumps capable of surviving extreme temperature excursions before and after exposure to liquid water. Two glass wafers are etched with features and a continuous Teflon membrane is sandwiched between them (see figure). Single valves are constructed using this geometry. The microfabricated devices are then post processed by heating the assembled device while applying pneumatic pressure to force the Teflon diaphragm against the valve seat while it is softened. After cooling the device, the embossed membrane retains this new shape. This solves previous problems with bubble introduction into the fluid flow where deformations of the membrane at the valve seat occurred during device bonding at elevated temperatures (100-150 C). The use of laminated membranes containing commercial Teflon AF 2400 sheet sandwiched between spun Teflon AF 1600 layers performed best, and were less gas permeable than Teflon AF 1600 membranes on their own. Spinning Teflon AF 1600 solution (6 percent in FLOURINERT(Registered TradeMark) FC40 solvent, 3M Company) at 500 rpm for 1.5 seconds, followed by 1,000 rpm for 3 seconds onto Borofloat glass wafers, results in a 10-micron-thick film of extremely smooth Teflon AF. This spinning process is repeated several times on flat, blank, glass wafers in order to gradually build a thick, smooth membrane. After running this process at least five times, the wafer and Teflon coating are heated under vacuum

  16. Interaction between Subunits of Heterodimeric Splicing Factor U2AF Is Essential In Vivo

    PubMed Central

    Rudner, David Z.; Kanaar, Roland; Breger, Kevin S.; Rio, Donald C.

    1998-01-01

    The heterodimeric pre-mRNA splicing factor, U2AF (U2 snRNP auxiliary factor), plays a critical role in 3′ splice site selection. Although the U2AF subunits associate in a tight complex, biochemical experiments designed to address the requirement for both subunits in splicing have yielded conflicting results. We have taken a genetic approach to assess the requirement for the Drosophila U2AF heterodimer in vivo. We developed a novel Escherichia coli copurification assay to map the domain on the Drosophila U2AF large subunit (dU2AF50) that interacts with the Drosophila small subunit (dU2AF38). A 28-amino-acid fragment on dU2AF50 that is both necessary and sufficient for interaction with dU2AF38 was identified. Using the copurification assay, we scanned this 28-amino-acid interaction domain for mutations that abrogate heterodimer formation. A collection of these dU2AF50 point mutants was then tested in vivo for genetic complementation of a recessive lethal dU2AF50 allele. A mutation that completely abolished interaction with dU2AF38 was incapable of complementation, whereas dU2AF50 mutations that did not effect heterodimer formation rescued the recessive lethal dU2AF50 allele. Analysis of heterodimer formation in embryo extracts derived from these interaction mutant lines revealed a perfect correlation between the efficiency of subunit association and the ability to complement the dU2AF50 recessive lethal allele. These data indicate that Drosophila U2AF heterodimer formation is essential for viability in vivo, consistent with a requirement for both subunits in splicing in vitro. PMID:9528748

  17. The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

    DTIC Science & Technology

    2015-10-01

    to U2AF1(WT). We validated several homologous dysregulated junctions (i.e., across species) in MDS patient bone marrow samples that have mutant ...U2AF1(S34F) versus U2AF1(WT). Together, these results suggest that mutant U2AF1 expression contributes to the altered hematopoiesis and pre-mRNA...whether the U2AF1(S34F) mutation alters hematopoiesis in vivo. We will inducibly express wild-type and S34F mutant (resulting from the most common

  18. Characterization of physically vapor deposited AF2400 thin films

    SciTech Connect

    Chow, R.; Spragge, M.K.; Loomis, G.E.; Rainer, F.; Ward, R.; Thomas, I.M.; Kozlowski, M.R.

    1993-11-01

    Anti-reflective coatings made with Teflon AF2400 had the highest damage thresholds recorded for physical vapor deposited coatings at the Lawrence Livermore National Laboratory damage facility. Physical vapor deposited layers of Teflon AF2400, a perfluorinated amorphous polymer, maintained the bulk optical properties of a high transmittance from 200 nm to 1600 nm, and a low refractive index. In addition, the refractive index can be intentionally reduced by control of two common deposition parameters, deposition rate and substrate temperature. Scanning electron microscopy and nuclear magnetic resonance observations indicated that morphological changes caused the variations in the refractive index rather than compositional changes. The coatings adhered to fused silica and silicon wafers under normal laboratory handling conditions.

  19. Intranasal Administration of the Antisecretory Peptide AF-16 Reduces Edema and Improves Cognitive Function Following Diffuse Traumatic Brain Injury in the Rat

    PubMed Central

    Clausen, Fredrik; Hansson, Hans-Arne; Raud, Johan; Marklund, Niklas

    2017-01-01

    A synthetic peptide with antisecretory activity, antisecretory factor (AF)-16, improves injury-related deficits in water and ion transport and decreases intracranial pressure after experimental cold lesion injury and encephalitis although its role in traumatic brain injury (TBI) is unknown. AF-16 or an inactive reference peptide was administrated intranasally 30 min following midline fluid percussion injury (mFPI; n = 52), a model of diffuse mild-moderate TBI in rats. Sham-injured (n = 14) or naïve (n = 24) animals were used as controls. The rats survived for either 48 h or 15 days post-injury. At 48 h, the animals were tested in the Morris water maze (MWM) for memory function and their brains analyzed for cerebral edema. Here, mFPI-induced brain edema compared to sham or naïve controls that was significantly reduced by AF-16 treatment (p < 0.05) although MWM performance was not altered. In the 15-day survival groups, the MWM learning and memory abilities as well as histological changes were analyzed. AF-16-treated brain-injured animals shortened both MWM latency and swim path in the learning trials (p < 0.05) and improved probe trial performance compared to brain-injured controls treated with the inactive reference peptide. A modest decrease by AF-16 on TBI-induced changes in hippocampal glial acidic fibrillary protein (GFAP) staining (p = 0.11) was observed. AF-16 treatment did not alter any other immunohistochemical analyses (degenerating neurons, beta-amyloid precursor protein (β-APP), and Olig2). In conclusion, intranasal AF-16-attenuated brain edema and enhanced visuospatial learning and memory following diffuse TBI in the rat. Intranasal administration early post-injury of a promising neuroprotective substance offers a novel treatment approach for TBI. PMID:28261150

  20. Improved AF Squadron Command Structure for Leadership, Accountability, and Efficiency

    DTIC Science & Technology

    2011-04-20

    of Defense respectively focus on span of control. The concept of span of control was developed in 1922 by Sir Ian Hamilton based on the assumption...For the AF, this means squadrons must be organized across a wing to minimize inconsistency within units as well as across them. A study by Dewar ... Dewar , Robert D., and Simet, Donald P. “A Level Specific Prediction of Spans of Control Examining the Effects of Size, Technology, and

  1. Adiabatic Compression Sensitivity of AF-M315E

    DTIC Science & Technology

    2015-07-01

    the development of green rocket propellants . The Air Force Research Laboratory’s (AFRL) monopropellant, AF-M315E, has been selected for...art rocket fuels and propellants . A known quantity of liquid propellant is placed in a metal U-tube and held isothermally in a preheated mixture of... Propellant Infusion Mission (GPIM) program. As the propulsion system developed by Aerojet- Rocketdyne for this propellant advances in maturity, studies

  2. Installation Restoration Program. Records Search, Newark AFS, Ohio

    DTIC Science & Technology

    1985-04-01

    plants. In this assignment and all that follow, a part of each was spent in conducting health and environment compliance inspections and audits at mili...OH 434&33 EiLO)( 2 bJATEP SYSTE-M, KTTC𔃻EN TAP, ’DATE: 76-P6-16*’.TI- E: 1304.1, APPEA0AfJCE OF SbmPLE CLEAR, TEA;:, 72 I PFE -ULTS OF ANALYS15 C T

  3. Genomic functions of U2AF in constitutive and regulated splicing.

    PubMed

    Wu, Tongbin; Fu, Xiang-Dong

    2015-01-01

    The U2AF heterodimer is generally accepted to play a vital role in defining functional 3' splice sites in pre-mRNA splicing. Given prevalent mutations in U2AF, particularly in the U2AF1 gene (which encodes for the U2AF35 subunit) in blood disorders and other human cancers, there are renewed interests in these classic splicing factors to further understand their regulatory functions in RNA metabolism in both physiological and disease settings. We recently reported that U2AF has a maximal capacity to directly bind ˜88% of functional 3' splice sites in the human genome and that numerous U2AF binding events also occur in various exonic and intronic locations, thus providing additional mechanisms for the regulation of alternative splicing besides their traditional role in titrating weak splice sites in the cell. These findings, coupled with the existence of multiple related proteins to both U2AF65 and U2AF35, beg a series of questions on the universal role of U2AF in functional 3' splice site definition, their binding specificities in vivo, potential mechanisms to bypass their requirement for certain intron removal events, contribution of splicing-independent functions of U2AF to important cellular functions, and the mechanism for U2AF mutations to invoke specific diseases in humans.

  4. Durable Superhydrophobic Surfaces via Spontaneous Wrinkling of Teflon AF.

    PubMed

    Scarratt, Liam R J; Hoatson, Ben S; Wood, Elliot S; Hawkett, Brian S; Neto, Chiara

    2016-03-01

    We report the fabrication of both single-scale and hierarchical superhydrophobic surfaces, created by exploiting the spontaneous wrinkling of a rigid Teflon AF film on two types of shrinkable plastic substrates. Sub-100 nm to micrometric wrinkles were reproducibly generated by this simple process, with remarkable control over the size and hierarchy. Hierarchical Teflon AF wrinkled surfaces showed extremely high water repellence (contact angle 172°) and very low contact angle hysteresis (2°), resulting in droplets rolling off the surface at tilt angles lower than 5°. The wrinkling process intimately binds the Teflon AF layer with its substrate, making these surfaces mechanically robust, as revealed by macroscale and nanoscale wear tests: hardness values were close to that of commercial optical lenses and aluminum films, resistance to scratch was comparable to commercial hydrophobic coatings, and damage by extensive sonication did not significantly affect water repellence. By this fabrication method the size of the wrinkles can be reproducibly tuned from the nanoscale to the microscale, across the whole surface in one step; the fabrication procedure is extremely rapid, requiring only 2 min of thermal annealing to produce the desired topography, and uses inexpensive materials. The very low roll-off angles achieved in the hierarchical surfaces offer a potentially up-scalable alternative as self-cleaning and drag-reducing coatings.

  5. Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival

    PubMed Central

    Fei, Dennis Liang; Motowski, Hayley; Chatrikhi, Rakesh; Gao, Shaojian; Kielkopf, Clara L.; Varmus, Harold

    2016-01-01

    We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry the U2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele. PMID:27776121

  6. Alternative splicing of U2AF1 reveals a shared repression mechanism for duplicated exons

    PubMed Central

    Kralovicova, Jana; Vorechovsky, Igor

    2017-01-01

    The auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF) facilitates branch point (BP) recognition and formation of lariat introns. The gene for the 35-kD subunit of U2AF gives rise to two protein isoforms (termed U2AF35a and U2AF35b) that are encoded by alternatively spliced exons 3 and Ab, respectively. The splicing recognition sequences of exon 3 are less favorable than exon Ab, yet U2AF35a expression is higher than U2AF35b across tissues. We show that U2AF35b repression is facilitated by weak, closely spaced BPs next to a long polypyrimidine tract of exon Ab. Each BP lacked canonical uridines at position -2 relative to the BP adenines, with efficient U2 base-pairing interactions predicted only for shifted registers reminiscent of programmed ribosomal frameshifting. The BP cluster was compensated by interactions involving unpaired cytosines in an upstream, EvoFold-predicted stem loop (termed ESL) that binds FUBP1/2. Exon Ab inclusion correlated with predicted free energies of mutant ESLs, suggesting that the ESL operates as a conserved rheostat between long inverted repeats upstream of each exon. The isoform-specific U2AF35 expression was U2AF65-dependent, required interactions between the U2AF-homology motif (UHM) and the α6 helix of U2AF35, and was fine-tuned by exon Ab/3 variants. Finally, we identify tandem homologous exons regulated by U2AF and show that their preferential responses to U2AF65-related proteins and SRSF3 are associated with unpaired pre-mRNA segments upstream of U2AF-repressed 3′ss. These results provide new insights into tissue-specific subfunctionalization of duplicated exons in vertebrate evolution and expand the repertoire of exon repression mechanisms that control alternative splicing. PMID:27566151

  7. Loss of Dnmt3b accelerates MLL-AF9 leukemia progression.

    PubMed

    Zheng, Y; Zhang, H; Wang, Y; Li, X; Lu, P; Dong, F; Pang, Y; Ma, S; Cheng, H; Hao, S; Tang, F; Yuan, W; Zhang, X; Cheng, T

    2016-12-01

    Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder with a poor prognosis. Abnormal DNA methylation is involved in the initiation and progression of AML. The de novo methyltransferases Dnmt3a and Dnmt3b are responsible for the generation of genomic methylation patterns. While DNMT3A is frequently mutated in hematological malignancies, DNMT3B is rarely mutated. Although it has been previously reported that Dnmt3b functions as a tumor suppressor in a mouse model of Myc-induced lymphomagenesis, its function in AML is yet to be determined. In this study, we demonstrated that deletion of Dnmt3b accelerated the progression of MLL-AF9 leukemia by increasing stemness and enhancing cell cycle progression. Gene profiling analysis revealed upregulation of the oncogenic gene set and downregulation of the cell differentiation gene set. Furthermore, loss of Dnmt3b was able to synergize with Dnmt3a deficiency in leukemia development. Taken together, these results demonstrate that Dnmt3b plays a tumor suppressive role in MLL-AF9 AML progression, thereby providing new insights into the roles of DNA methylation in leukemia development.

  8. Intracardiac impedance response during acute AF internal cardioversion using novel rectilinear and capacitor-discharge waveforms.

    PubMed

    Rababah, A S; Walsh, S J; Manoharan, G; Walsh, P R; Escalona, O J

    2016-07-01

    Intracardiac impedance (ICI) is a major determinant of success during internal cardioversion of atrial fibrillation (AF). However, there have been few studies that have examined the dynamic behaviour of atrial impedance during internal cardioversion in relation to clinical outcome. In this study, voltage and current waveforms captured during internal cardioversion of acute AF in ovine models using novel radiofrequency (RF) generated low-tilt rectilinear and conventional capacitor-discharge based shock waveforms were retrospectively analysed using a digital signal processing algorithm to investigate the dynamic behaviour of atrial impedance during cardioversion. The algorithm was specifically designed to facilitate the simultaneous analysis of multiple impedance parameters, including: mean intracardiac impedance (Z M), intracardiac impedance variance (ICIV) and impedance amplitude spectrum area (IAMSA) for each cardioversion event. A significant reduction in ICI was observed when comparing two successive shocks of increasing energy where cardioversion outcome was successful. In addition, ICIV and IAMSA variables were found to inversely correlate to the magnitude of energy delivered; with a stronger correlation found to the former parameter. In conclusion, ICIV and IAMSA have been evidenced as two key dynamic intracardiac impedance variables that may prove useful in better understanding of the cardioversion process and that could potentially act as prognostic markers with respect to clinical outcome.

  9. AFS dynamics in a short-lived active region

    NASA Astrophysics Data System (ADS)

    Zuccarello, F.; Battiato, V.; Contarino, L.; Romano, P.; Spadaro, D.; Vlahos, L.

    2005-11-01

    In the framework of the study on active region emergence, we report the results obtained from the analysis of the short-lived (7 days) active region NOAA 10407. The data used were acquired during an observational campaign carried out with the THEMIS telescope in IPM mode in July 2003, coordinated with other ground- and space-based instruments (INAF-OACT, DOT, BBSO, MDI/SOHO, EIT/SOHO, TRACE). We determined the morphological and magnetic evolution of NOAA 10407, as well as the velocity fields associated with its magnetic structures. Within the limits imposed by the spatial and temporal resolution of the images analyzed, the first evidence of the active region formation is initially observed in the transition region and lower corona, and later on (i.e. after about 7 h) in the inner layers, as found in a previous analysis concerning a long-lived, recurrent active region. The results also indicate that the AFS formed in the active region shows typical upward motion at the AFS's tops and downward motion at the footpoints. The velocity values relevant to the upward motions decrease over the evolution of the region, similarly to the case of the recurrent active region, while we notice an increasing trend in the downflow velocity during the early phases of the time interval analyzed by THEMIS. On the other hand, the AFS preceding legs show a higher downflow than the following ones, a result in contrast with that found in the long-lived active region. The chromospheric area overhanging the sunspot umbra shows an upward motion of ˜ 2 km s-1, while that above the pores shows a downward motion of ~4 km s-1.

  10. RX-26-AY/AF rifle bullet tests

    SciTech Connect

    Sharp, D.D.

    1980-11-01

    A series of rifle bullet tests was performed on two explosives, RX-26-AY and RX-26-AF, using the Pantex version of the Picatinny Arsenal Test (PA-2). With the exception of one test, both explosives displayed a relatively low sensitivity to bullet impact. However, a marked difference was noted in the average burn time duration between the two types of explosives being tested. A minor modification was made on the rifle barrel used at the test site in order to improve the sighting procedure.

  11. NMR study of the AF-SC-SC-AF phased transition in a pnictide superconductor LaFeAsO1-xHx

    NASA Astrophysics Data System (ADS)

    Fujiwara, Naoki; Sakurai, Ryosuke; Iimura, Soushi; Matsuishi, Satoru; Hosono, Hideo; Yamakawa, Youichi; Kontani, Hiroshi

    2014-03-01

    We have performed 75As and 1H NMR measurements in LaFeAsO1xHx, an isomorphic compound of LaFeAsO1xFx. LaFeAsO1xHx is an electron doped system, and O2- can be replaced with H- up to x = 0.5. LaFeAsO1xHx is known for having double superconducting (SC) domes on H doping. Recently, we discovered that a new antiferromagnetic (AF) phase follows the double SC domes on further H doping, forming a symmetric AF-SC-SC-AF phase alignment in the electronic phase diagram Unlike the AF ordering in the lightly H-doped regime, the AF ordering in the highly H-doped regime is attributed to the nesting between electron pockets. In the conference, we will show the data of both NMR spectra and the relaxation rate 1/T1 in the whole doping region. We will discuss the difference of electronic states between the lightly H-doped AF-SC phases and highly H-doped SC-AF phases. This work is supported by a Grant-in-Aid (Grant No. KAKENHI 23340101) from the Ministry of Education, Science, and Culture, Japan.

  12. Self-assembly of amphiphilic peptide (AF)6H5K15 derivatives: roles of hydrophilic and hydrophobic residues.

    PubMed

    Thota, Naresh; Jiang, Jianwen

    2014-03-13

    A molecular dynamics simulation study is reported to investigate the roles of hydrophilic and hydrophobic residues in the self-assembly of (AF)6H5K15 peptide derivatives. The peptide, as well as water and counterions, are represented by the MARTINI coarse-grained model. The assembly is observed to follow a three-step process: formation of small clusters, large clusters, and micelles. With increasing length of hydrophilic Lys residues in (AF)6H5Kn (n = 10, 15, 20, and 25), assembly capability is found to be reduced with the formation of smaller micelles or the presence of individual peptide chains. Upon replacing Ala by more hydrophobic Phe in AmFnH5K15 (m + n = 12), larger micelles are formed. With increasing length of hydrophobic Phe residues in FnH5K15 (n = 4, 8, 12, and 16), micelle size increases and the morphology shifts from spherical to fiber-like. The simulation study provides mechanistic insight into the crucial roles of hydrophilicity and hydrophobicity in the assembly of (AF)6H5K15 derivatives; it reveals that assembly capability is reduced by increasing hydrophilicity, whereas increasing hydrophobicity leads to morphology transition.

  13. AFS men and women differ most in their lifestyle choices

    USGS Publications Warehouse

    Connelly, N.A.; Brown, T.L.; Hardiman, J.M.

    2006-01-01

    The American Fisheries Society sponsored a survey to examine the career development choices of men and women and how they might differ by gender. A random sample of 700 men and 700 women was selected from the AFS membership database. The survey was mailed out in October 2004 and 991 questionnaires were returned for an adjusted response rate of 71%. Some differences exist between men and women in the areas of interest development, education, and employment, but the substantive differences occur in lifestyle choices. Women with a fisheries career are less likely to be married than men, even when age is controlled for, and women who are married are more likely to have dual-career considerations than their male counterparts. Among respondents without dependents in their home during their professional career, twice as many women as men think having children will adversely affect their career. For those with dependents, more than twice as many women as men said they had to put their career "on hold" because of their dependents. While AFS members do not represent all members of the fisheries profession, their experiences shed substantial light on the lifestyle choices likely faced by most members of the profession.

  14. Fluorous Polymeric Membranes for Ionophore-Based Ion-Selective Potentiometry: How Inert is Teflon AF?

    PubMed Central

    Lai, Chun-Ze; Koseoglu, Secil S.; Lugert, Elizabeth C.; Boswell, Paul G.; Rábai, József; Lodge, Timothy P.; Bühlmann, Philippe

    2011-01-01

    Fluorous media are the least polar and polarizable condensed phases known. Their use as membrane materials considerably increases the selectivity and robustness of ion-selective electrodes (ISEs). In this research, a fluorous amorphous perfluoropolymer was used for the first time as a matrix for an ISE membrane. Electrodes for pH measurements with membranes composed of poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole]-co-poly(tetrafluoroethylene) (87% dioxole monomer content; known as Teflon AF2400) as polymer matrix, a linear perfluorooligoether as plasticizer, sodium tetrakis[3,5-bis(perfluorohexyl)phenyl]borate providing for ionic sites, and bis[(perfluorooctyl)propyl]-2,2,2-trifluoroethylamine as H+-ionophore were investigated. All electrodes had excellent potentiometric selectivities, showed Nernstian responses to H+ over a wide pH range, exhibited enhanced mechanical stability and maintained their selectivity over at least four weeks. For membranes of low ionophore concentration, the polymer affected the sensor selectivity noticeably at polymer concentrations exceeding 15%. Also, the membrane resistance increased quite strongly at high polymer concentrations, which cannot be explained by the Mackie–Meares obstruction model. The selectivities and resistances depend on the polymer concentration because of a functional group associated with Teflon AF2400, with a concentration of one functional group per 854 monomer units of the polymer. In the fluorous environment of these membranes, this functional group binds to Na+, K+, Ca2+, and the unprotonated ionophore with binding constants of 103.5, 101.8, 106.8 and 104.4 M−1, respectively. Potentiometric and spectroscopic evidence indicates that these functional groups are COOH groups formed by the hydrolysis of carboxylic acid fluoride (COF) groups originally present in Teflon AF2400. The use of higher ionophore concentrations removes the undesirable effect of these COOH groups almost completely

  15. Evaluation of the atoxigenic Aspergillus flavus strain AF36 in pistachio orchards

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The atoxigenic strain Aspergillus flavus AF36, which has been extensively used as a biocontrol agent in commercial corn and cotton fields to reduce aflatoxin contamination, was applied in research pistachio orchards from 2002 to 2005 and in commercial pistachio orchards from 2008 to 2011. AF36 was a...

  16. Seladoeflavones A-F, six novel flavonoids from Selaginella doederleinii.

    PubMed

    Zou, ZhenXing; Xu, KangPing; Xu, PingSheng; Li, XiaoMin; Cheng, Fei; Li, Jing; Yu, Xia; Cao, DongSheng; Li, Dan; Zeng, Wei; Zhang, GuoGang; Tan, GuiShan

    2017-01-01

    Six new flavonoids, seladoeflavones A-F (1-6), were isolated from the whole herbs of Selaginella doederleinii, together with one known flavonoid (7). Their structures including absolute configuration were characterized on the basis of extensive spectroscopic methods including NMR, HRMS, and electronic circular dichroism (ECD). All compounds consist of an aryl substituent at the C-3' position of naringenin or apigenin skeletons, and compounds 1 and 6 were identified as R configurations, which are uncommonly encountered in nature. A possible biosynthetic pathway was postulated. In addition, bioassay of the isolates revealed that 5-7 exhibited moderate cytotoxicity against three human cancer cell lines NCI-H460, A549, and K562 in vitro with IC50 values ranging from 8.17 to 18.66μM.

  17. Optimised secure transmission through untrusted AF relays using link adaptation

    NASA Astrophysics Data System (ADS)

    Taki, Mehrdad; Sadeghi, Mohammad

    2016-05-01

    A new transmission scheme is presented for a two-hop relay network including two AF relays, considering physical layer security where relays are not able to detect signal with an acceptable bit error rate (BER) but the combined received signal is detected with an acceptable BER at the final receiver. It is assumed that there is no direct path between the transmitter and the receiver (relay network without diversity). Adaptive modulation and coding is utilised at the transmitter and transmission powers of the transmitter and of the relays are continuously adapted provisioning individual average power constraint for each node. Numerical evaluations show that an acceptable performance degradation is seen by the proposed secure relaying scheme compared to the optimum relay selection scheme without security constraint.

  18. Automation under suspicion--case flight AF-447 Air France.

    PubMed

    Martins, Edgard; Soares, Marcelo

    2012-01-01

    The probes allow the pilot to control the aircraft speed was essential to the balance of the flight. Opinions of experts who claim that "the design of the plane would have exercised a not inconsiderable role in the occurrence of a disaster." These messages revealed a series of important operating errors in a zone of turbulence, "making the plane uncontrollable, leading to a rapid depressurization device, according to these reports. A lawsuit in Toulouse and in Brazil aims to recognition of the liability of Air France and Airbus not insignificant role in the design and operation of the aircraft in the event of catastrophe. Opinions are taken from senior pilots that no commercial aviation training for certain situations abnormal flight that, if realized, could have influenced the pilots of the AF-447 to remove the plane's fatal dive show what experiments performed in simulators for military pilots, who are permanently subject to critical flight situations.

  19. The ultraviolet-bright, slowly declining transient PS1-11af as a partial tidal disruption event

    SciTech Connect

    Chornock, R.; Berger, E.; Zauderer, B. A.; Kamble, A.; Soderberg, A. M.; Czekala, I.; Dittmann, J.; Drout, M.; Foley, R. J.; Fong, W.; Kirshner, R. P.; Lunnan, R.; Marion, G. H.; Narayan, G.; Gezari, S.; Rest, A.; Riess, A. G.; Chomiuk, L.; Huber, M. E.; Lawrence, A.; and others

    2014-01-01

    We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of known types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only ∼0.002 M {sub ☉}, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.

  20. Letter to the Editor: H-1, C-13 and N-15 Assignments for the Archaeglobus fulgidis Protein AF2095.

    SciTech Connect

    Powers, Robert; Acton, Thomas; Chiang, Yiwen; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Ma, LiChung; Rost, Burkhard; Montelione, Gaetano

    2004-09-01

    The Human genome project promises to provide an unprecedented wealth of information on cell biology, development, evolution and physiology. Translating this immense increase in genomic information into advances in medicine and human health requires a concerted effort to explore and investigate the structure and molecular activity for the vast amount of proteins in the Human proteome that lack any such explicit experimental information. Structural genomics is providing a means to determine the molecular and cellular function of these proteins by characterizing the complete range of protein folds (Montelione, 2001). By annotating sequence information with a protein structure, it is sometimes possible to decipher the biochemical activity of hypothetical proteins from structural similarity and the conservation of spatial arrangement of active site residues. Homology can often be inferred by structural similarity even in the absence of recognizable sequence similarity, and can sometimes be used to identify functional relationships between distantly related proteins. Determining an experimental structure for each protein in a proteome is currently impractical because of the significant time commitment and resources required by X-ray and NMR. Therefore, the current paradigm of structural genomics is to determine a representative structure for each cluster of homologous protein domain sequences that lack similarity to a protein domain with a known structure. In this manner, comparative modeling using a single experimental structure can provide approximate but useful 3D structural information for an entire protein domain family. The Northeast Structural Genomics Consortium (NESG; www.nesg.org) is a pilot project funded by the National Institutes of Health Protein Structure Initiative, focusing on proteins from eukaryotic model organisms including humans. The thermophillic archaea Archaeglobus fulgidis AF2095 protein is an example of a protein of unknown biological function

  1. The identification of GPR3 inverse agonist AF64394; the first small molecule inhibitor of GPR3 receptor function.

    PubMed

    Jensen, Thomas; Elster, Lisbeth; Nielsen, Søren Møller; Poda, Suresh Babu; Loechel, Frosty; Volbracht, Christiane; Klewe, Ib Vestergaard; David, Laurent; Watson, Stephen P

    2014-11-15

    The identification of the novel and selective GPR3 inverse agonist AF64394, the first small molecule inhibitor of GPR3 receptor function, is described. Structure activity relationships and syntheses based around AF64394 are reported.

  2. ROK AFS, Kwandae-ri, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1968-04-15

    KlmANCAF RI KCREA/kC, AFS K-6 1-54 AL L STATION STATION NAME YEARS MONTH PERCEfNT G ’F C., YS , 1Th VPR IC Lc AT CSP-F PIC P H-C F FRCf. CAILY C4SV...DS 301 iq WTIONS Op THIS pOrn AM OIomr ATA PRrCESSIN;G C[ S!CN ETAC, LSAF SURFACE WINDS AS#-EVILLE9 N. C. 28E01 PERCENTAGE FREQUENCY OF WIND...NNW VAREIL F -3.4 7.4 5.4 .7 _ 1.0 TOTAL NUMBER OF OISERVATIONS 146 1210 WS j 0--S (0. SO) SSIeo.. KDSTIO,. oP TIN PORN AN O.S.OC. I [~. [ATA

  3. The Inhibition of Inflammasome by Brazilian Propolis (EPP-AF)

    PubMed Central

    Hori, Juliana I.; Zamboni, Dario S.; Carrão, Daniel B.; Goldman, Gustavo Henrique; Berretta, Andresa A.

    2013-01-01

    Propolis extracts have gained the attention of consumers and researchers due to their unique chemical compositions and functional properties such as its anti-inflammatory activity. Recently, it was described a complex that is also important in inflammatory processes, named inflammasome. The inflammasomes are a large molecular platform formed in the cell cytosol in response to stress signals, toxins, and microbial infections. Once activated, the inflammasome induces caspase-1, which in turn induces the processing of inflammatory cytokines such as IL-1β and IL-18. So, to understand inflammasomes regulation becomes crucial to treat several disorders including autoinflammatory diseases. Since green propolis extracts are able to regulate inflammatory pathways, this work purpose was to investigate if this extract could also act on inflammasomes regulation. First, the extract was characterized and it demonstrated the presence of important compounds, especially Artepillin C. This extract was effective in reducing the IL-1β secretion in mouse macrophages and this reduction was correlated with a decrease in activation of the protease caspase-1. Furthermore, we found that the extract at a concentration of 30 μg/mL was not toxic to the cells even after a 18-hour treatment. Altogether, these data indicate that Brazilian green propolis (EPP-AF) extract has a role in regulating the inflammasomes. PMID:23690844

  4. Flacourtosides A-F, phenolic glycosides isolated from Flacourtia ramontchi.

    PubMed

    Bourjot, Mélanie; Leyssen, Pieter; Eydoux, Cécilia; Guillemot, Jean-Claude; Canard, Bruno; Rasoanaivo, Philippe; Guéritte, Françoise; Litaudon, Marc

    2012-04-27

    In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts of madagascan plants was performed in a virus-cell-based assay for CHIKV, and a DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark of Flacourtia ramontchi was selected for its significant activity in both assays. Six new phenolic glycosides, named flacourtosides A-F (1-6), phenolic glycosides itoside H, xylosmin, scolochinenoside D, and poliothrysoside, and betulinic acid 3β-caffeate were obtained using the bioassay-guided isolation process. Their structures were elucidated by comprehensive analyses of NMR spectroscopic and mass spectrometric data. Even though several extracts and fractions showed significant selective antiviral activity in the CHIKV virus-cell-based assay, none of the purified compounds did. However, in the DENV RNA polymerase assay, significant inhibition was observed with betulinic acid 3β-caffeate (IC(50) = 0.85 ± 0.1 μM) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC(50) values ~10 μM).

  5. Catalytic soman scavenging by Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes

    PubMed Central

    Kovarik, Zrinka; Hrvat, Nikolina Maček; Katalinić, Maja; Sit, Rakesh K.; Paradyse, Alexander; Žunec, Suzana; Musilek, Kamil; Fokin, Valery V.; Taylor, Palmer; Radić, Zoran

    2016-01-01

    Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman. HI-6 was previously shown in vitro to efficiently reactivate this mutant upon soman, as well as VX, cyclosarin, sarin and paraoxon inhibition. We here demonstrate that ex vivo, in whole human blood, 1 μM soman was detoxified within 30 minutes when supplemented with 0.5 μM Y337A/F338A AChE and 100 μM HI-6. This combination was further tested in vivo. Catalytic scavenging of soman in mice improved the therapeutic outcome and resulted in the delayed onset of toxicity symptoms. Furthermore, in a preliminary in vitro screen we identified an even more efficacious oxime than HI-6, in a series of forty-two pyridinium aldoximes, and five imidazole 2-aldoxime N-propyl pyridinium derivatives. One of the later imidazole aldoximes, RS-170B, was a 2–3 –fold more effective reactivator of Y337A/F338A AChE than HI-6 due to the smaller imidazole ring, as indicated by computational molecular models, that affords a more productive angle of nucleophilic attack. PMID:25835984

  6. High-resolution micropatterned Teflon AF substrates for biocompatible nanofluidic devices.

    PubMed

    Czolkos, Ilja; Hakonen, Bodil; Orwar, Owe; Jesorka, Aldo

    2012-02-14

    We describe a general photolithography-based process for the microfabrication of surface-supported Teflon AF structures. Teflon AF patterns primarily benefit from superior optical properties such as very low autofluorescence and a low refractive index. The process ensures that the Teflon AF patterns remain strongly hydrophobic in order to allow rapid lipid monolayer spreading and generates a characteristic edge morphology which assists directed cell growth along the structured surfaces. We provide application examples, demonstrating the well-controlled mixing of lipid films on Teflon AF structures and showing how the patterned surfaces can be used as biocompatible growth-directing substrates for cell culture. Chinese hamster ovary (CHO) cells develop in a guided fashion along the sides of the microstructures, selectively avoiding to grow over the patterned areas.

  7. Adiabatic Compression Sensitivity of AF-M315E (Briefing Charts)

    DTIC Science & Technology

    2015-07-27

    dynamic response • Waterhammer effect Distribution A: Approved for public release; distribution unlimited Hydroxyethylhydrazinium Nitrate ...Hydroxylammonium Nitrate (HEHN) (HAN) [ ]-NO3 + [ ]HOCH2CH2N2H4 [ ]-+[ ]NH3OH NO3 AF-M315E

  8. Air Sampling of Polychlorinated Dibenzodioxins, Polychlorinated Dibenzofurans, and Polychlorinated Biphenyls Arnold AFS, Tennessee.

    DTIC Science & Technology

    1987-01-01

    DIBENZOFURANS, AND POLYCHLORINATED BIPHENYLS ARNOLD AFS TN ISAAC ATKINS, JR., CAPTAIN, USAF, BSC January 1987 D I ~ELECTE FINAL REPORT 0Wfl D LU...NO 11. TITLE (Include Security ClassificatiOtl) Air Sampling of Polychlorinated Dibenzodioxins, Polychlorinated Dibenzofurans, and Polychlorinated ... Biphenyls at Arnold AFS TN (U) 12. PERSONAL AUTHOR(S) Captaiq Isaac Atkins, Jr. 13a. TYP OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year, Month

  9. Services Officer Utilization Field (AFS 62XX and Equivalent-Grade Civilians).

    DTIC Science & Technology

    1986-06-01

    CHART le~ -- Sq ,.. O. pt’*. q UNITED STATES AIR FORCE cv, Lfl o D SERVICES OFFICER UTILIZATION FIELD (AFS 62XX AND EQUIVALENT-GRADE CIVILLANS) AFPT 90...Administration From January through Ma’ch 1985, job inventories were administered to all elicible AFSC 62XX nfficer: in the continental United States ... PUBLIC RELEASE: DISTRIBUTION UNLIMITED t, , . . . .. .. . . . . , . . . . . . , . _". ... , I! . . $ IJSTRIBIJTION FOR AFS( u-)XX OSR AND SUPPORTING

  10. AF-M315E Propulsion System Advances and Improvements

    NASA Technical Reports Server (NTRS)

    Masse, Robert K.; Allen, May; Driscoll, Elizabeth; Spores, Ronald A.; Arrington, Lynn A.; Schneider, Steven J.; Vasek, Thomas E.

    2016-01-01

    Even as for the GR-1 awaits its first on-orbit demonstration on the planned 2017 launch of NASA's Green Propulsion Infusion Mission (GPIM) program, ongoing efforts continue to advance the technical state-of-the-art through improvements in the performance, life capability, and affordability of both Aerojet Rocketdyne's 1-N-class GR-1 and 20-N-class GR-22 green monopropellant thrusters. Hot-fire testing of a design upgrade of the GR-22 thruster successfully demonstrated resolution of a life-limiting thermo-structural issue encountered during prototype testing on the GPIM program, yielding both an approximately 2x increase in demonstrating life capability, as well as fundamental insights relating to how ionic liquid thrusters operate, thruster scaling, and operational factors affecting catalyst bed life. Further, a number of producibility improvements, related to both materials and processes and promising up to 50% unit cost reduction, have been identified through a comprehensive Design for Manufacturing and Assembly (DFMA) assessment activity recently completed at Aerojet Rocketdyne. Focused specifically on the GR-1 but applicable to the common-core architecture of both thrusters, ongoing laboratory (heavyweight) thruster testing being conducted under a Space Act Agreement at NASA Glenn Research Center has already validated a number of these proposed manufacturability upgrades, additionally achieving a greater than 40% increase in thruster life. In parallel with technical advancements relevant to conventional large spacecraft, a joint effort between NASA and Aerojet Rocketdyne is underway to prepare 1-U CubeSat AF-M315E propulsion module for first flight demonstration in 2018.

  11. Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome

    PubMed Central

    Shirai, Cara Lunn; White, Brian S.; Tripathi, Manorama; Tapia, Roberto; Ley, James N.; Ndonwi, Matthew; Kim, Sanghyun; Shao, Jin; Carver, Alexa; Saez, Borja; Fulton, Robert S.; Fronick, Catrina; O'Laughlin, Michelle; Lagisetti, Chandraiah; Webb, Thomas R.; Graubert, Timothy A.; Walter, Matthew J.

    2017-01-01

    Somatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing. We find that haematopoietic cells expressing mutant U2AF1(S34F), including primary patient cells, have an increased sensitivity to in vitro sudemycin treatment relative to controls. In vivo sudemycin treatment of U2AF1(S34F) transgenic mice alters splicing and reverts haematopoietic progenitor cell expansion induced by mutant U2AF1 expression. The splicing effects of sudemycin and U2AF1(S34F) can be cumulative in cells exposed to both perturbations—drug and mutation—compared with cells exposed to either alone. These cumulative effects may result in downstream phenotypic consequences in sudemycin-treated mutant cells. Taken together, these data suggest a potential for treating haematological cancers harbouring U2AF1 mutations with pre-mRNA splicing modulators like sudemycins. PMID:28067246

  12. Nicotine improves AF64A-induced spatial memory deficits in Morris water maze in rats.

    PubMed

    Yamada, Kazuo; Furukawa, Satoshi; Iwasaki, Tsuneo; Ichitani, Yukio

    2010-01-18

    Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxic derivative of choline that produces not only long-term presynaptic cholinergic deficits, but also various memory deficits in rats similar to some characteristics observed in Alzheimer's disease patients. This study investigated whether nicotine (NCT) administration attenuated spatial learning deficits induced by intracerebroventricular AF64A treatment. AF64A (6 nmol/6 microl)-or saline (SAL)-treated rats were trained in Morris water maze task. NCT (0.025-0.25mg/kg) was subcutaneously injected 5 min before the training every day. The results showed that moderate dose (0.10mg/kg) of NCT attenuated AF64A-induced prolongation of escape latency. Furthermore, NCT dose-dependently recovered the AF64A-induced decrease of time spent in the target quadrant in the probe test. These results suggest that NCT improves AF64A-induced spatial memory deficits, and thus it is a potential therapeutic agent for the treatment of memory deficits in dementia.

  13. Oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system.

    PubMed

    Meng, Yao; Jost, Carsten; Mumme, Jan; Wang, Kaijun; Linke, Bernd

    2016-07-01

    In order to investigate the oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system, the effect of microaeration on thermophilic anaerobic digestion of maize straw was investigated under batch conditions and in the UASS with AF system. Aeration intensities of 0-431mL O2/gvs were conducted as pretreatment under batch conditions. Aeration pretreatment obviously enhanced anaerobic digestion and an aeration intensity of 431mL O2/gvs increased the methane yield by 82.2%. Aeration intensities of 0-355mL O2/gvs were conducted in the process liquor circulation of the UASS with AF system. Dissolved oxygen (DO) of UASS and AF reactors kept around 1.39±0.27 and 0.99±0.38mg/L, respectively. pH was relatively stable around 7.11±0.04. Volatile fatty acids and soluble chemical oxygen demand concentration in UASS reactor were higher than those in AF reactor. Methane yield of the whole system was almost stable at 85±7mL/gvs as aeration intensity increased step by step. The UASS with AF system showed good oxygen tolerance capacity.

  14. Estimating the Prevalence of Atrial Fibrillation from A Three-Class Mixture Model for Repeated Diagnoses

    PubMed Central

    Li, Liang; Mao, Huzhang; Ishwaran, Hemant; Rajeswaran, Jeevanantham; Ehrlinger, John; Blackstone, Eugene H.

    2016-01-01

    Atrial fibrillation (AF) is an abnormal heart rhythm characterized by rapid and irregular heart beat, with or without perceivable symptoms. In clinical practice, the electrocardiogram (ECG) is often used for diagnosis of AF. Since the AF often arrives as recurrent episodes of varying frequency and duration and only the episodes that occur at the time of ECG can be detected, the AF is often underdiagnosed when a limited number of repeated ECGs are used. In studies evaluating the efficacy of AF ablation surgery, each patient undergo multiple ECGs and the AF status at the time of ECG is recorded. The objective of this paper is to estimate the marginal proportions of patients with or without AF in a population, which are important measures of the efficacy of the treatment. The underdiagnosis problem is addressed by a three-class mixture regression model in which a patient’s probability of having no AF, paroxysmal AF, and permanent AF is modeled by auxiliary baseline covariates in a nested logistic regression. A binomial regression model is specified conditional on a subject being in the paroxysmal AF group. The model parameters are estimated by the EM algorithm. These parameters are themselves nuisance parameters for the purpose of this research, but the estimators of the marginal proportions of interest can be expressed as functions of the data and these nuisance parameters and their variances can be estimated by the sandwich method. We examine the performance of the proposed methodology in simulations and two real data applications. PMID:27983754

  15. The PDZ Protein Canoe/AF-6 Links Ras-MAPK, Notch and Wingless/Wnt Signaling Pathways by Directly Interacting with Ras, Notch and Dishevelled

    PubMed Central

    Carmena, Ana; Speicher, Stephan; Baylies, Mary

    2006-01-01

    Over the past few years, it has become increasingly apparent that signal transduction pathways are not merely linear cascades; they are organized into complex signaling networks that require high levels of regulation to generate precise and unique cell responses. However, the underlying regulatory mechanisms by which signaling pathways cross-communicate remain poorly understood. Here we show that the Ras-binding protein Canoe (Cno)/AF-6, a PDZ protein normally associated with cellular junctions, is a key modulator of Wingless (Wg)/Wnt, Ras-Mitogen Activated Protein Kinase (MAPK) and Notch (N) signaling pathways cross-communication. Our data show a repressive effect of Cno/AF-6 on these three signaling pathways through physical interactions with Ras, N and the cytoplasmic protein Dishevelled (Dsh), a key Wg effector. We propose a model in which Cno, through those interactions, actively coordinates, at the membrane level, Ras-MAPK, N and Wg signaling pathways during progenitor specification. PMID:17183697

  16. Recognition of the 3' splice site RNA by the U2AF heterodimer involves a dynamic population shift.

    PubMed

    Voith von Voithenberg, Lena; Sánchez-Rico, Carolina; Kang, Hyun-Seo; Madl, Tobias; Zanier, Katia; Barth, Anders; Warner, Lisa R; Sattler, Michael; Lamb, Don C

    2016-11-15

    An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3' splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3' splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein-RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3' splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants.

  17. Perturbative magnetoresistance technique used to investigate FM/AF coupled bilayers

    NASA Astrophysics Data System (ADS)

    Oliveira, Alexandre; da Costa, Ricardo; Melo, Abner; Chesman, Carlos

    2014-03-01

    In this study we introduced modifications to a collinear four probe magnetoresistance set-up in order to measure magnetic properties that can only be sensed by techniques based on magnetization perturbation. In addition to the applied DC magnetic field (Hdc) , in magnetoresistance experiments, a small and quasi-static alternating magnetic field (hac, less than 10 Oe and around 800 Hz) is applied perpendicularly, both parallel to the sample plane. Due to Zeeman interaction, hac drives sample magnetization to oscillate slightly around its equilibrium position. Although we apply only DC current (few mA), the detected voltage carries DC and AC components. The DC voltage component provides information on magnetoresistance (MR) and the AC component is called perturbative magnetoresistance (PMR). We successfully demonstrated that the PMR signal is proportional to the first derivative of resistance with respect to hac. Using this technique and a phenomenological model that takes into account the relevant free energy terms of FM/AF coupled bilayers, we were able to study reversible and irreversible magnetization rotation processes in these magnetic systems. With respect to magnetic anisotropy, we investigated rotatable anisotropy, proposed by McMichael et al and Geshev et al. Financial support: CNPq, FAPERN and CAPES (Brazilian agencies).

  18. Chemically peculiar A/F stars in open clusters of the Milky Way

    NASA Astrophysics Data System (ADS)

    Gebran, M.; Monier, R.

    2010-12-01

    Abundance anomalies have been determined at the surface of many field and open cluster A and F dwarfs. These abundance anomalies are most likely caused by microscopic diffusion at work within the stable envelopes of A stars. However diffusion can be counteracted by several other mixing processes such as convection, rotational mixing and mass loss. We present a short review of the surface abundance patterns of A/F stars in the Pleiades (100 Myr), Coma Berenices (450 Myr) and Hyades (650 Myr) open clusters. Real star-to-star variations of the abundances were found for several chemical elements in the A dwarfs in these clusters. The derived abundances are then compared to evolutionary models from the Montreal group. These comparisons strongly suggest the occurence of hydrodynamical processes at play within the radiative zones of these stars and hindering the effects of microscopic diffusion (mixing processes/mass loss). In the frame of Gaia mission, simulations are presented that predict the number of A stars and open clusters that Gaia will observe in the Galaxy.

  19. Extra-nuclear effects of estrogen on cortical bone in males require ERαAF-1

    PubMed Central

    Wu, J; Gustafsson, K L; Windahl, S H; Kim, S H; Katzenellenbogen, J A; Ohlsson, C; Lagerquist, M K

    2017-01-01

    Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERαAF-1-inactivated (ERαAF-10) mice were orchidectomized and treated with equimolar doses of 17β-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERαAF-10 males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERαAF-10 mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERαAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis. PMID:28057769

  20. Extra-nuclear effects of estrogen on cortical bone in males require ERαAF-1.

    PubMed

    Farman, H H; Wu, J; Gustafsson, K L; Windahl, S H; Kim, S H; Katzenellenbogen, J A; Ohlsson, C; Lagerquist, M K

    2017-02-01

    Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERαAF-1-inactivated (ERαAF-1(0)) mice were orchidectomized and treated with equimolar doses of 17β-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERαAF-1(0) males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERαAF-1(0) mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERαAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis.

  1. The binding of (3H)AF-DX 384 to rat ileal smooth muscle muscarinic receptors

    SciTech Connect

    Entzeroth, M.; Mayer, N. )

    1991-01-01

    The tritiated cardioselective muscarinic antagonist AF-DX 384 (5,11-dihydro-11-(2-(-(8-dipropylamino)methyl)-1-piperidinyl-ethyl-amino-carbonyl)-6H-pyrido (2,3-b) (1,4)benzodiazepin-6-one) was used to label muscarinic receptors in the rat ileum. Saturation binding to membrane suspensions revealed a high affinity binding site with a Kd of 9.2 nM. The maximal number of binding sites labeled in this tissue (Bmax) is 237 fmol/mg protein. The association and dissociation kinetics were well represented by single exponential reactions, and the dissociation constant obtained from the ratio of rate constants was in agreement with that derived from saturation experiments. Specific binding was inhibited by muscarinic antagonists with a rank order of potencies of atropine (pKi: 8.80) greater than 4-DAMP (pKi: 8.23) = AF-DX 384 (pKi: 8.20) greater than AF-DX 116 (pKi: 7.09) = hexahydro-sila-difenidol (pKi: 6.97) greater than pirenzepine (pKi: 6.49) and is consistent with the interaction of (3H)AF-DX 384 with muscarinic receptors of the M2 subtype. It can be concluded that (3H)AF-DX 384 can be used to selectively label M2 muscarinic receptors in heterogeneous receptor populations.

  2. A simple web-based tool to compare freshwater fish data collected using AFS standard methods

    USGS Publications Warehouse

    Bonar, Scott A.; Mercado-Silva, Norman; Rahr, Matt; Torrey, Yuta T.; Cate, Averill

    2016-01-01

    The American Fisheries Society (AFS) recently published Standard Methods for Sampling North American Freshwater Fishes. Enlisting the expertise of 284 scientists from 107 organizations throughout Canada, Mexico, and the United States, this text was developed to facilitate comparisons of fish data across regions or time. Here we describe a user-friendly web tool that automates among-sample comparisons in individual fish condition, population length-frequency distributions, and catch per unit effort (CPUE) data collected using AFS standard methods. Currently, the web tool (1) provides instantaneous summaries of almost 4,000 data sets of condition, length frequency, and CPUE of common freshwater fishes collected using standard gears in 43 states and provinces; (2) is easily appended with new standardized field data to update subsequent queries and summaries; (3) compares fish data from a particular water body with continent, ecoregion, and state data summaries; and (4) provides additional information about AFS standard fish sampling including benefits, ongoing validation studies, and opportunities to comment on specific methods. The web tool—programmed in a PHP-based Drupal framework—was supported by several AFS Sections, agencies, and universities and is freely available from the AFS website and fisheriesstandardsampling.org. With widespread use, the online tool could become an important resource for fisheries biologists.

  3. Low strain, long life creep fatigue of AF2-1DA and INCO 718

    NASA Technical Reports Server (NTRS)

    Thakker, A. B.; Cowles, B. A.

    1983-01-01

    Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

  4. GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

    PubMed

    Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

  5. Prenylation inhibitors stimulate both estrogen receptor α transcriptional activity through AF-1 and AF-2 and estrogen receptor β transcriptional activity

    PubMed Central

    Cestac, Philippe; Sarrabayrouse, Guillaume; Médale-Giamarchi, Claire; Rochaix, Philippe; Balaguer, Patrick; Favre, Gilles; Faye, Jean-Charles; Doisneau-Sixou, Sophie

    2005-01-01

    Introduction We showed in a previous study that prenylated proteins play a role in estradiol stimulation of proliferation. However, these proteins antagonize the ability of estrogen receptor (ER) α to stimulate estrogen response element (ERE)-dependent transcriptional activity, potentially through the formation of a co-regulator complex. The present study investigates, in further detail, how prenylated proteins modulate the transcriptional activities mediated by ERα and by ERβ. Methods The ERE-β-globin-Luc-SV-Neo plasmid was either stably transfected into MCF-7 cells or HeLa cells (MELN cells and HELN cells, respectively) or transiently transfected into MCF-7 cells using polyethylenimine. Cells deprived of estradiol were analyzed for ERE-dependent luciferase activity 16 hours after estradiol stimulation and treatment with FTI-277 (a farnesyltransferase inhibitor) or with GGTI-298 (a geranylgeranyltransferase I inhibitor). In HELN cells, the effect of prenyltransferase inhibitors on luciferase activity was compared after transient transfection of plasmids coding either the full-length ERα, the full-length ERβ, the AF-1-deleted ERα or the AF-2-deleted ERα. The presence of ERα was then detected by immunocytochemistry in either the nuclei or the cytoplasms of MCF-7 cells. Finally, Clostridium botulinum C3 exoenzyme treatment was used to determine the involvement of Rho proteins in ERE-dependent luciferase activity. Results FTI-277 and GGTI-298 only stimulate ERE-dependent luciferase activity in stably transfected MCF-7 cells. They stimulate both ERα-mediated and ERβ-mediated ERE-dependent luciferase activity in HELN cells, in the presence of and in the absence of estradiol. The roles of both AF-1 and AF-2 are significant in this effect. Nuclear ERα is decreased in the presence of prenyltransferase inhibitors in MCF-7 cells, again in the presence of and in the absence of estradiol. By contrast, cytoplasmic ERα is mainly decreased after treatment with FTI

  6. Structure-guided U2AF65 variant improves recognition and splicing of a defective pre-mRNA

    PubMed Central

    Agrawal, Anant A.; McLaughlin, Krystle J.; Jenkins, Jermaine L.; Kielkopf, Clara L.

    2014-01-01

    Purine interruptions of polypyrimidine (Py) tract splice site signals contribute to human genetic diseases. The essential splicing factor U2AF65 normally recognizes a Py tract consensus sequence preceding the major class of 3′ splice sites. We found that neurofibromatosis- or retinitis pigmentosa-causing mutations in the 5′ regions of Py tracts severely reduce U2AF65 affinity. Conversely, we identified a preferred binding site of U2AF65 for purine substitutions in the 3′ regions of Py tracts. Based on a comparison of new U2AF65 structures bound to either A- or G-containing Py tracts with previously identified pyrimidine-containing structures, we expected to find that a D231V amino acid change in U2AF65 would specify U over other nucleotides. We found that the crystal structure of the U2AF65-D231V variant confirms favorable packing between the engineered valine and a target uracil base. The D231V amino acid change restores U2AF65 affinity for two mutated splice sites that cause human genetic diseases and successfully promotes splicing of a defective retinitis pigmentosa-causing transcript. We conclude that reduced U2AF65 binding is a molecular consequence of disease-relevant mutations, and that a structure-guided U2AF65 variant is capable of manipulating gene expression in eukaryotic cells. PMID:25422459

  7. An Evaluation of the Impacts of AF-M315E Propulsion Systems for Varied Mission Applications

    NASA Technical Reports Server (NTRS)

    Deans, Matthew C.; Oleson, Steven R.; Fittje, James; Colozza, Anthony; Packard, Tom; Gyekenyesi, John; McLean, Christopher H.; Spores, Ronald A.

    2015-01-01

    The purpose of the AF-M315E COMPASS study is to identify near-term (3-5 years) and long term (5 years +) opportunities for infusion, specifically the thruster and associated component technologies being developed as part of the GPIM project. Develop design reference missions which show the advantages of the AF-M315E green propulsion system. Utilize a combination of past COMPASS designs and selected new designs to demonstrate AF-M315E advantages. Use the COMPASS process to show the puts and takes of using AF-M315E at the integrated system level.

  8. The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.

    PubMed

    Whisenant, Thomas C; Peralta, Eigen R; Aarreberg, Lauren D; Gao, Nina J; Head, Steven R; Ordoukhanian, Phillip; Williamson, Jamie R; Salomon, Daniel R

    2015-01-01

    Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as "central" interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, "peripheral" interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA

  9. The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells

    PubMed Central

    Aarreberg, Lauren D.; Gao, Nina J.; Head, Steven R.; Ordoukhanian, Phillip; Williamson, Jamie R.; Salomon, Daniel R.

    2015-01-01

    Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as “central” interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, “peripheral” interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly

  10. 27. "SITE PLAN." Specifications No. OC15775, Drawing No. AF600915, sheet ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. "SITE PLAN." Specifications No. OC1-57-75, Drawing No. AF-60-09-15, sheet 1 of 96, D.O. Series No. AF 1394/20, Rev. B. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract no. 5296 Rev. B, Date: 11/17/59. Site plan of 20,000-foot track, including construction phasing notes. - Edwards Air Force Base, South Base Sled Track, Edwards Air Force Base, North of Avenue B, between 100th & 140th Streets East, Lancaster, Los Angeles County, CA

  11. The splicing factor U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis

    SciTech Connect

    Kim, Jeonghee; Chung, In Kwon

    2014-01-17

    Highlights: •Identification of U2AF65 as a novel TRF1-interacting protein. •U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. •U2AF65 interferes with the interaction between TRF1 and Fbx4. •U2AF65 represents a new route for modulating TRF1 function at telomeres. -- Abstract: The human telomeric protein TRF1 is a component of the six-subunit protein complex shelterin, which provides telomere protection by organizing the telomere into a high-order structure. TRF1 functions as a negative regulator of telomere length by controlling the access of telomerase to telomeres. Thus, the cellular abundance of TRF1 at telomeres should be maintained and tightly regulated to ensure proper telomere function. Here, we identify U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 (U2AF65), an essential pre-mRNA splicing factor, as a novel TRF1-interacting protein. U2AF65 interacts with TRF1 in vitro and in vivo and is capable of stabilizing TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. We also found that U2AF65 interferes with the interaction between TRF1 and Fbx4, an E3 ubiquitin ligase for TRF1. Depletion of endogenous U2AF65 expression by short interfering RNA (siRNA) reduced the stability of endogenous TRF1 whereas overexpression of U2AF65 significantly extended the half-life of TRF1. These findings demonstrate that U2AF65 plays a critical role in regulating the level of TRF1 through physical interaction and ubiquitin-mediated proteolysis. Hence, U2AF65 represents a new route for modulating TRF1 function at telomeres.

  12. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea

    PubMed Central

    dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues

    2015-01-01

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1. PMID:26634755

  13. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea.

    PubMed

    Dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues; Goldman, Gustavo H; Riaño-Pachón, Diego M

    2015-12-03

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1.

  14. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  15. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  16. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  17. Flow ozonolysis using a semipermeable Teflon AF-2400 membrane to effect gas-liquid contact.

    PubMed

    O'Brien, Matthew; Baxendale, Ian R; Ley, Steven V

    2010-04-02

    A flow-through chemistry apparatus has been developed which allows gases and liquids to contact via a semipermeable Teflon AF-2400 membrane. In this preliminary investigation, the concept was proven by application to the ozonolysis of a series of alkenes.

  18. Utilizing an Experiential Approach to Teacher Learning about AfL: A Consciousness Raising Opportunity

    ERIC Educational Resources Information Center

    Dixon, Helen; Hawe, Eleanor

    2016-01-01

    In this article we focus on how an experiential based approach to teacher learning about assessment for learning (AfL) provided opportunities for teachers to examine: their deep-seated beliefs about effective learning (and teaching); how these beliefs permeated their day-to-day actions and interactions with students, and the consequence of these…

  19. Fracture Mechanics Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, J. W.; Martinez, J.; McLean, C.

    2016-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant on orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent processing flaws will not cause failure during the design life of the tank. Material property inputs for this analysis require testing to determine the stress intensity factor for environment-assisted cracking (KEAC) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched, or SE(B), specimens representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to AF-M315E at 50 C for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor for environment-assisted cracking of the Ti 6Al-4V forged tank material was found to be at least 22 ksivin and at least 31 ksivin for the weld material when exposed to AF-M315E monopropellant.

  20. First report of an infant botulism case due to Clostridium botulinum type Af.

    PubMed

    de Jong, Laura I T; Fernández, Rafael A; Pareja, Virtudes; Giaroli, Gabriel; Guidarelli, Sergio R; Dykes, Janet K; Lúquez, Carolina

    2015-02-01

    Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely, Clostridium botulinum strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to C. botulinum type Af worldwide.

  1. Genome Sequence of the Native Apiculate Wine Yeast Hanseniaspora vineae T02/19AF

    PubMed Central

    Giorello, Facundo M.; Berná, Luisa; Greif, Gonzalo; Camesasca, Laura; Salzman, Valentina; Medina, Karina; Robello, Carlos; Gaggero, Carina; Aguilar, Pablo S.

    2014-01-01

    The use of novel yeast strains for winemaking improves quality and provides variety including subtle characteristic differences in fine wines. Here we report the first genome of a yeast strain native to Uruguay, Hanseniaspora vineae T02/19AF, which has been shown to positively contribute to aroma and wine quality. PMID:24874663

  2. 28. Site Plan: AF Station P67, Fort Custer, Michigan, Plot ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. Site Plan: AF Station P-67, Fort Custer, Michigan, Plot Plan (to accompany FY 1956 project planning report), USACOE, 22 July 1954. - Fort Custer Military Reservation, P-67 Radar Station, .25 mile north of Dickman Road, east of Clark Road, Battle Creek, Calhoun County, MI

  3. Mylar and Teflon-AF as cell culture substrates for studying endothelial cell adhesion.

    PubMed

    Anamelechi, Charles C; Truskey, George A; Reichert, W Monty

    2005-12-01

    The textured and opaque nature of Dacron and ePTFE has prevented the use of these fabrics in conventional cell culture techniques normally employed to optimize cell attachment and retention. This lack of optimization has led, in part, to the poor performance of endothelialization strategies for improving vascular graft patency. Here we show that thin, transparent films of Mylar and Teflon-AF are viable in vitro cell culture mimics of Dacron and ePTFE vascular graft materials, particularly for the study of protein mediated endothelial cell (EC) attachment, spreading and adhesion. Glass substrates were used as controls. X-ray photoelectron spectroscopy (XPS) and contact angle analysis showed that Mylar and Teflon-AF have surface chemistries that closely match Dacron and ePTFE. (125)I radiolabeling was used to quantify fibronectin (FN) adsorption, and FN and biotinylated-BSA "dual ligand" co-adsorption onto glass, Mylar and Teflon-AF substrates. Native human umbilical vein endothelial cells (HUVEC) and streptavidin-incubated biotinylated-HUVEC (SA-b-HUVEC) spreading was measured using phase contrast microscopy. Cell retention and adhesion was determined using phase contrast microscopy under laminar flow. All surfaces lacking protein pre-treatment, regardless of surface type, showed the lowest degree of cell spreading and retention. Dual ligand treated Mylar films showed significantly greater SA-b-HUVEC spreading up to 2 h, but were similar to HUVEC on FN treated Mylar at longer times; whereas SA-b-HUVEC spreading on dual ligand treated Teflon-AF was never significantly different from HUVEC on FN treated Teflon-AF at any time point. SA-b-HUVEC retention was significantly greater on dual ligand treated Mylar compared to HUVEC on FN treated Mylar over the entire range of shear stresses tested (3.54-28.3 dynes/cm(2)); whereas SA-b-HUVEC retention to dual ligand and HUVEC retention to FN treated Teflon-AF gave similar results at each shear stress, with only the mid

  4. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.

  5. Low incidence of left atrial delayed enhancement with MRI in patients with AF: a single-centre experience

    PubMed Central

    Bois, John P; Glockner, James; Young, Phillip M; Foley, Thomas A; Sheldon, Seth; Newman, Darrell B; Lin, Grace; Packer, Douglas L; Brady, Peter A

    2017-01-01

    Background Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. One potential target for ablation is left atrial (LA) scar (LAS) regions that may be the substrate for re-entry within the atria, thereby sustaining AF. Identification of LAS through LA delayed gadolinium enhancement (LADE) with MRI has been proposed. Objectives We sought to evaluate LADE in patients referred for catheter ablation of AF. Methods Prospective analysis was conducted of consecutive patients who underwent pulmonary vein antrum isolation (PVAI) ablation for AF at a single institution. Patients underwent LADE with MRI to determine LAS regions before ablation. MRI data were analysed independently in accordance with prespecified institutional protocol by two staff cardiac radiologists to whom patient outcomes were masked, and reports of LADE were documented. Where no initial consensus occurred regarding delayed enhancement (DE), a third staff cardiac radiologist independently reviewed the case and had the deciding vote. Results Of the 149 consecutive patients (mean (SD) age, 59 (9) years), AF was persistent in 64 (43%) and paroxysmal in 85 (57%); 45 (30%) had prior ablation. Only five patients (3%) had identifiable DE in LA walls (persistent AF, n=1; paroxysmal AF, n=4). LADE was present in two (4%) of the 45 patients with previous left PVAI. The presence of LADE was not associated with a higher recurrence rate of AF. Conclusions In contrast to previous studies, the finding of DE within LA walls was uncommon and, when present, did not correlate with AF type or risk of AF recurrence. It therefore is of unclear clinical significance. PMID:28123766

  6. Equalization characteristics of an upflow sludge blanket-aerated biofilter (USB-AF) system.

    PubMed

    Jun, H B; Park, S M; Park, J K; Lee, S H

    2005-01-01

    Equalization characteristics of the upflow sludge blanket-aerated bio-filter (USB-AF) were investigated with the fluctuated raw domestic sewage. Recycle of nitrified effluent from AF to USB triggered the equalization characteristics of the sludge blanket on both soluble and particulate organic matter. Increment of EPS in sludge blanket by nitrate recycle was detected and removal of turbidity and particulates increased at higher recycle ratios by bio-flocculation. Increased TCOD removal in the USB was due to both denitrification of recycled nitrate and entrapment of the particulate organic matter in sludge blanket. Capture of both soluble and particulate organic matter increased sludge blanket layer in the USB, which improved the reactor performances and reduced the organic load on the subsequent AF. Overall TCOD and SS removal efficiencies were about 98% and 96%, respectively in the USB-AF system. Turbidity in the USB effluent was about 44, 20 and 5.5 NTU, at recycle ratios of 0, 100 and 200%, respectively. Particle counts in the range 2-4 microm in the USB effluent were higher than those in influent without nitrate recycle, while particle counts in the range of 0.5-15 microm in the USB effluent decreased 70% at recycle ratio of 200%. The major constituent of EPS extracted from anaerobic sludge was protein and total EPS increased from 109.1 to 165.7 mg/g-VSS with nitrate recycle of 100%. Removal efficiency and concentration of T-N in the UBS-AF effluent was over 70% and below 16 mg/L, respectively.

  7. Properties and transport behavior of perfluorotripentylamine (FC-70)-doped amorphous teflon AF 2400 films.

    PubMed

    Zhang, Hong; Hussam, Abul; Weber, Stephen G

    2010-12-22

    Teflon AF 2400 films are known to imbibe solvents, making films in the presence of solvents less fluorous than they might otherwise be. Herein, we demonstrate that doping films with perfluorotripentylamine (Fluorinert FC-70) maintains the fluorous nature of Teflon AF 2400 and improves transport selectivity for fluorine-containing organic compounds. Density measurements on the FC-70-doped films reveal that free volume decreases dramatically as the dopant concentration increases (0-12 wt %) and then increases to approach that of pure FC-70. Remarkably, films from 0 to 12 wt % FC-70 have the same w/v concentration of Teflon AF 2400, indicating that FC-70 fills the free volume of Teflon AF 2400. This is consistent with the observed increased storage modulus and significant decrease (compared to undoped films) of solute diffusion coefficients in the same range of FC-70 concentrations. In contrast, FC-70 at concentrations greater than 12 wt % dilutes Teflon AF 2400, leading to a decrease of storage modulus and dramatic increase in solute diffusion coefficients. Sorption of chloroform decreases from 11.8 g of chloroform/100 g of film (pure Teflon film) to 3.8 g of chloroform/100 g of film (27 wt % FC-70-doped Teflon film), less than the solubility of chloroform in pure FC-70 (4.06 g of chloroform/100 g of FC-70). Solute partition coefficients from chloroform to FC-70-doped films generally decrease with increased dopant concentration. However, within a series of toluenes and nitrobenzenes, selectivity for F-containing solutes over analogous H-containing solutes increases as dopant concentration increases if the substitution is on the aromatic ring but not if it is on the methyl group (toluene). Transport (partitioning × diffusion) rates, as they involve both thermodynamic and kinetic factors, are not simply related to composition.

  8. TYPE AF CERTIFICATE FOR TRANSPORTATION OF LOW ENRICHED URANIUM OXIDE (LEUO) FOR DISPOSAL

    SciTech Connect

    Opperman, E; Kenneth Yates, K

    2007-10-19

    Washington Savannah River Company (WSRC) operates the Savannah River Site (SRS) in Aiken, SC under contract with the U.S. Department of Energy (DOE). SRS had the need to ship 227 drums of low enriched uranium oxide (LEUO) to a disposal site. The LEUO had been packaged nearly 25 years ago in U.S. Department of Transportation (DOT) 17C 55-gallon drums and stored in a warehouse. Since the 235U enrichment was just above 1 percent by weight (wt%) the material did not qualify for the fissile material exceptions in 49 CFR 173.453, and therefore was categorized as 'fissile material' for shipping purposes. WSRC evaluated all existing Type AF packages and did not identify any feasible packaging. Applying for a new Type AF certificate of compliance was considered too costly for a one-time/one-way shipment for disposal. Down-blending the material with depleted uranium (to reduce enrichment below 1 wt% and enable shipment as low specific activity (LSA) radioactive material) was considered, but appropriate blending facilities do not exist at SRS. After reviewing all options, WSRC concluded that seeking a DOT Special Permit was the best option to enable shipment of the material for permanent disposal. WSRC submitted the Special Permit application to the DOT, and after one request-for-additional-information (RAI) the permit was considered acceptable. However, in an interesting development that resulted from the DOT Special Permit application process, it was determined that it was more appropriate for the DOE to issue a Type AF certificate [Ref. 1] for this shipping campaign. This paper will outline the DOT Special Permit application and Type AF considerations, and will discuss the issuance of the new DOE Type AF certificate of compliance.

  9. A Specific Antibody to Neuropeptide AF1 (KNEFIRFamide) Recognizes a Small Subset of Neurons in Ascaris suum: Differences from Caenorhabditis elegans

    PubMed Central

    Sithigorngul, Paisarn; Jarecki, Jessica L.; Stretton, Antony O.W.

    2016-01-01

    A monoclonal antibody, AF1-003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C-terminal FIR-Famide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide-like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two-step HPLC, the only fractions recognized by AF1-003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1-003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or -B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp-8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540– 550); the URX neurons express AF1 in both species, but, in C. elegans, flp-8 expression was not detected in RIP, PQR, and PDA or -B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. PMID:21452223

  10. Characterization of plasma-enhanced teflon AF for sensing benzene, toluene, and xylenes in water with near-IR surface plasmon resonance.

    PubMed

    Erickson, Tim A; Nijjar, Rajvir; Kipper, Matt J; Lear, Kevin L

    2014-02-01

    Near-IR surface plasmon resonance is used to characterize Teflon AF films for refractive index-based detection of the aromatic hydrocarbon contaminants benzene, toluene, and xylenes in water. The technique requires no sample preparation, and film sensitivity is found to be enhanced by oxygen plasma etching. A diffusion equation model is used to extract the diffusion and partition coefficients, which indicate film enrichment factors exceeding two orders of magnitude, permitting a limit of detection of 183, 105 and 55 ppb for benzene, toluene, and xylenes, respectively. The effect of other potential interfering contaminants is quantified.

  11. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Accellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2015-09-01

    Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Li, Zhongyu CONTRACTING ORGANIZATION: Wake Forest...Gap Peripheral Nerve Injuries Using 5a. CONTRACT NUMBER Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). 5b. GRANT NUMBER...Major accomplishments this year include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up

  12. An Observational, Prospective Survey Assessing the Control of Atrial Fibrillation in Asia Pacific: Rationale and Design of the RecordAF-AP Registry

    PubMed Central

    Amerena, John; Chen, Shih-Ann; Sriratanasathavorn, Charn; Cho, Jeong-Gwan; Dejia, Huang; Omar, Razali; Fat, Tse Hung; King, Anthony

    2011-01-01

    Background: The literature suggests that the prevalence of atrial fibrillation (AF) may be lower in Asian countries than in Western countries. Nevertheless, AF remains a significant public health problem in the region. The burden of AF, the experiences of previous trials and the lack of data on AF and its management in Asia Pacific highlight the need for a comprehensive prospective study of AF management. Methods: The REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation Asia Pacific (RecordAF-AP) is a prospective, observational survey of the management of recently diagnosed AF patients with 1-year follow-up in 8 countries across Asia Pacific. Eligible patients presenting with AF, treated or not, will be included in the registry and data will be recorded prospectively during follow-up visits at 6 and 12 months. Results: RecordAF-AP will recruit more than 3000 patients. Study recruitment commenced in April 2009 and the final results anticipated at the end of 2011. Conclusions: RecordAF-AP will assess the real-life management of AF patients in Asia Pacific, including a comparison of clinical outcomes in rhythm versus rate control strategies, providing much needed insight into the costs, treatment choices and clinical outcomes of AF patients in this region. PMID:21344019

  13. Identification and functional characterization of an afsR homolog regulatory gene from Streptomyces venezuelae ATCC 15439.

    PubMed

    Maharjan, Sushila; Oh, Tae-Jin; Lee, Hei Chan; Sohng, Jae Kyung

    2009-02-01

    Sequencing analysis of a 5-kb DNA fragment from Streptomyces venezuelae ATCC 15439 revealed the presence of one 3.1-kb open reading frame (ORF), designated afsRsv. The deduced product of afsR-sv (1,056 aa) was found to have high homology with the global regulatory protein AfsR. Homology-based analysis showed that afsR-sv represents a transcriptional activator belonging to the Streptomyces antibiotic regulatory protein (SARP) family that includes an Nterminal SARP domain containing a bacterial transcriptional activation domain (BTAD), an NB-ARC domain, and a Cterminal tetratricopeptide repeat domain. Gene expression analysis by reverse transcriptase PCR (RT-PCR) demonstrated the activation of transcription of genes belonging to pikromycin production, when afsR-sv was overexpressed in S. venezuelae. Heterologous expression of the afsR-sv in different Streptomyces strains resulted in increased production of the respective antibiotics, suggesting that afsR-sv is a positive regulator of antibiotics biosynthesis.

  14. Hot Isostatic Pressing/Heat Treatment of Cast Superalloy AF2-1DA, Radial Turbine Wheels.

    DTIC Science & Technology

    1980-06-01

    showing typical 19 shrinkage porosity Mag: 400X Etch: Electrolytic oxalic acid 10 Microstructure of HIPped AF2-1DA alloy 29 Mag: 400X Etch...Electrolytic oxalic acid 11 Microstructure of HIPped AF2-1DA alloy note 30 void formations form incipient melting after 2250OF hip Mag: 400X Etch: Electrolytic... oxalic acid V a.w LIST OF ILLUSTRATIONS (Continued) Figure Title Page 12 Microstructure of HIPped AF2-1DA showing effects 31 of solution heat

  15. King Salmon, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-08-10

    1 .2 - i 121 1b 15 o -- 9 2.4 z 2 22 2 2 2fi 2 13 1ee (X) I me. O.. N.. o Nof " . Tom .eet W .. I T 0 F s 32P IN 67 P 3 FNP -93 P T...I w e Or ulb t...CLIMATOLOGY BRANCHT 2 AkETAHRSRVC/A PSYCHROMETRIC SUMMARY2 I ETE EVC /A 7 3260_ KING SALMON AFS AK 73-82 JAN STAT.Oft STATION NWAI villOAN *PAGE ? 1890...T,,.) .. ." " " , . - . . 1 i. . , ’. . ; : ; .-. A f;: ’ ,- ;. * GLr rA E LMTL~ T AC? PSYCHROMETRIC SUMMARYT2 FAH- EVC /A 7 3267 XING SALM4ON AFS

  16. Nanopatterning of mobile lipid monolayers on electron-beam-sculpted Teflon AF surfaces.

    PubMed

    Shaali, Mehrnaz; Lara-Avila, Samuel; Dommersnes, Paul; Ainla, Alar; Kubatkin, Sergey; Jesorka, Aldo

    2015-02-24

    Direct electron-beam lithography is used to fabricate nanostructured Teflon AF surfaces, which are utilized to pattern surface-supported monolayer phospholipid films with 50 nm lateral feature size. In comparison with unexposed Teflon AF coatings, e-beam-irradiated areas show reduced surface tension and surface potential. For phospholipid monolayer spreading experiments, these areas can be designed to function as barriers that enclose unexposed areas of nanometer dimensions and confine the lipid film within. We show that the effectiveness of the barrier is defined by pattern geometry and radiation dose. This surface preparation technique represents an efficient, yet simple, nanopatterning strategy supporting studies of lipid monolayer behavior in ultraconfined spaces. The generated structures are useful for imaging studies of biomimetic membranes and other specialized surface applications requiring spatially controlled formation of self-assembled, molecularly thin films on optically transparent patterned polymer surfaces with very low autofluorescence.

  17. Unciflavones A-F, six novel flavonoids from Selaginella uncinata (Desv.) Spring.

    PubMed

    Zou, Hui; Xu, Kang-Ping; Li, Fu-Shuang; Zou, Zhen-Xing; Liu, Rui; Liu, Rui-Huan; Li, Jing; Tan, Lei-Hong; Tan, Gui-Shan

    2014-12-01

    Six new flavonoids, unciflavones A-F (1-6), have been isolated from medicinal plant Selaginella uncinata (Desv.) Spring. Their structures were established on the basis of extensive NMR analysis including 1D NMR ((1)H, (13)C and DEPT) and 2D NMR (COSY, HSQC, HMBC) experiments as well as HRESIMS analysis. All compounds possess exceptional structural features with an aryl substituent at the C-8 position, which are uncommonly encountered in natural resources and firstly reported in genus Selaginella.

  18. Installation Restoration Program. Technical Support Document for Record of Decision, Cape Newenham, AFS.

    DTIC Science & Technology

    1988-01-18

    observed at any site. o No threatened or endangered species are known to use or exist on the installation. 0 No economically or commercially important ...which have the potential to exist in the environment at Cape Newenham AFS include many substances commonly used at LRRS installations. The most important ...Once adsorbed, PCBs 2-20 73/5/21 do not readily desorb. The implication is that PCBs will not leach or diffuse in soils; transport into the hydrosphere

  19. Oxytrofalcatins A-F, N-benzoylindole analogues from the roots of Oxytropis falcata (Leguminosae).

    PubMed

    Chen, Wen-Hao; Wu, Quan-Xiang; Wang, Rui; Shi, Yan-Ping

    2010-06-01

    Indole alkaloids, oxytrofalcatins A-F (1-6), together with five other known alkaloids (7-11), were isolated from the roots of Oxytropis falcata. Their structures were elucidated by comprehensive spectroscopic analyses, including using 1D and 2D NMR spectroscopy and mass spectrometry. This is the first report of N-benzoylindoles from a natural source. Compounds 1-6 lacked significant cytotoxicity against SGC-7901 and HL-60 tumor cell lines.

  20. Evolution of iron speciation during hydration of C{sub 4}AF

    SciTech Connect

    Rose, J.; El Mrabet, S.; Masion, A.; Moulin, I.; Briois, V.; Olivi, L.; Bottero, J.-Y.

    2006-07-01

    It is now well accepted and demonstrated that calcium silicate, calcium aluminate and calcium sulfo aluminate (ettringite, AFm) phases exhibit a good capability to fix metals and metalloids. Unfortunately the role of minor phases and especially calcium-ferric aluminate phase, shorthand C{sub 4}AF is not well defined. In other systems like in soils or sediments iron phases play a key role in the fixation of pollutant. In cement sorption isotherms, indicated that various metals can be retained by the C{sub 4}AF hydrated products. Therefore the capabilities of those phase to retain heavy metal should not be neglected. Previous investigations have shown that the minerals formed during the hydration of C{sub 4}AF are similar to those formed from C3A (pure tri-calcium aluminate) under comparable conditions. Nevertheless no investigation was conducted at the molecular level and there is still a controversy whether Fe substitutes for Al in the hydrated minerals in whole or in part, or if it forms FeOOH clusters scattered throughout the matrix. In this context we have conducted XAS experiments using synchrotron radiation. It was found that the hydration of C{sub 4}AF forms C{sub 3}AH{sub 6} (hydrogarnet) in which Fe randomly substitutes for Al as well as an amorphous FeOOH phase. Intermediate products like AFm (i.e., an ill organized lamellar phase) are also formed but rapidly evolve to C{sub 3}AH{sub 6}; iron does not seem to be incorporated in the AFm structure.

  1. AF-TRUST, Air Force Team for Research in Ubiquitous Secure Technology

    DTIC Science & Technology

    2010-07-26

    Live Streaming Systems. PhD. June 2008 • Jeffrey Hartline. Incremental Optimization, PhD, January 2008 AF-TRUST Final Performance Report...Against Intrusion in a Live Streaming Multicast System. Maya Haridasan, Robbert van Renesse. In Proceedings of the 6th IEEE International Conference...Walker White. In Proceedings of SIGMOD 2007 2008 Enforcing Fairness in a Live - Streaming System. Maya Haridasan, Ingrid Jansch-Porto, Kenneth Birman

  2. Updated Reference Genome Sequence and Annotation of Mycobacterium bovis AF2122/97

    PubMed Central

    Farrell, Damien; Stuber, Tod P.; Schubert, Olga T.; Aebersold, Ruedi; Robbe-Austerman, Suelee

    2017-01-01

    ABSTRACT We report here an update to the reference genome sequence of the bovine tuberculosis bacillus Mycobacterium bovis AF2122/97, generated using an integrative multiomics approach. The update includes 42 new coding sequences (CDSs), 14 modified annotations, 26 single-nucleotide polymorphism (SNP) corrections, and disclosure that the RD900 locus, previously described as absent from the genome, is in fact present. PMID:28385856

  3. Air Traffic Control Radar Specialty AFS 303X1. Volume II.

    DTIC Science & Technology

    1981-05-01

    Surveillance Radars, and AN/ MPN -14H Mobile RAPCONs. Typical tasks performed by these incumbents when maintaining these radar systems include: perform PMIs on...document forms (AF Form 264) issue job control numbers maintain status boards, graphs, or charts maintain equipment status reports document equipment...related matters determine work priorities plan work assignments maintain training records, charts , or graphs These incumbents are the most senior of all

  4. ROCKET AF adds more concerns about Digoxin safety in patients with atrial fibrillation.

    PubMed

    ElMaghawry, Mohamed

    2015-01-01

    In a recent article in the Journal, we have reviewed the adverse cardiovascular outcomes observed with digoxin use in the PALLAS study.(1) The PALLAS study was designed to determine if dronedarone would reduce major vascular events in patients with permanent atrial fibrillation (AF).(2) However the study was stopped early because of safety reasons, as a significant number of patients on the dronedarone arm reached the co-primary end point composite of stroke, myocardial infarction, systemic embolism, or cardiovascular death. Data sub-analyses suggested that digoxin-dronedarone interaction was responsible for the higher arrhythmic death rate observed in the trial. These observations are consistent with several other studies that demonstrate the potential hazard of the use of digoxin in heart failure and/or atrial fibrillation. A more recent article published in the Lancet studied the use and outcomes of digoxin in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism in Atrial Fibrillation (ROCKET AF) trial.(3) The investigators concluded that digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF.

  5. Fracture Growth Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, Jeffrey W.; Martinez, Jonathan; McLean, Christopher

    2015-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant in orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent flaws will not cause failure during the design life. Material property inputs for this analysis require testing to determine the stress intensity factor for environmentally-assisted cracking (K (sub EAC)) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched specimens SE(B) representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to the monopropellant at 50 degrees Centigrade for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor of the Ti 6Al-4V forged tank material when exposed to AF-M315E monopropellant was found to be at least 22.0 kilopounds per square inch. The stress intensity factor of the weld material was at least 31.3 kilopounds per square inch.

  6. [Improvement of natamycin production in an industrial strain by heterologous expression of the afsRS(cla) global regulatory genes].

    PubMed

    Tao, Zhengsheng; Wang, Yemin; Zheng, Hualiang; Tao, Meifeng

    2015-05-01

    The afsRS(cla) global regulatory genes from Streptomyces clavuligerus activate the production of two antibiotics in Streptomyces lividans. In this study, we gained an increase of 38% in the production of natamycin (3.56 g/L) in an industrial strain Streptomyces gilvosporeus TZ1401 through the integration of pHL851 that bears the afsRS(cla) global regulatory genes into its genome. We discovered by quantitive real-time reverse transcription PCR (qRT-PCR) that the expression of 6 genes of the natamycin biosynthetic gene cluster were improved from 1.9 to 2.7 times. This suggests that afsRS(cla) improve the production of natamycin through increased transcription. This study provides a good example for applying afsRS(cla) in high yield breeding of industrial antibiotic producers.

  7. Meeting in Florida: Using Asymmetric Flow Field-Flow Fractionation (AF4) to Determine C60 Colloidal Size Distributions

    EPA Science Inventory

    The study of nanomaterials in environmental systems requires robust and specific analytical methods. Analytical methods which discriminate based on particle size and molecular composition are not widely available. Asymmetric Flow Field-Flow Fractionation (AF4) is a separation...

  8. Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

    PubMed

    Potpara, Tatjana S; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S; Polovina, Marija M; Petranov, Stanislav L; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y H

    2016-02-12

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.

  9. UHM–ULM interactions in the RBM39–U2AF65 splicing-factor complex

    SciTech Connect

    Stepanyuk, Galina A.; Serrano, Pedro; Peralta, Eigen; Farr, Carol L.; Axelrod, Herbert L.; Geralt, Michael; Das, Debanu; Chiu, Hsiu-Ju; Jaroszewski, Lukasz; Deacon, Ashley M.; Lesley, Scott A.; Elsliger, Marc-André; Godzik, Adam; Wilson, Ian A.; Wüthrich, Kurt; Salomon, Daniel R.; Williamson, James R.

    2016-03-24

    RNA-binding protein 39 (RBM39) is a splicing factor and a transcriptional co-activator of estrogen receptors and Jun/AP-1, and its function has been associated with malignant progression in a number of cancers. The C-terminal RRM domain of RBM39 belongs to the U2AF homology motif family (UHM), which mediate protein–protein interactions through a short tryptophan-containing peptide known as the UHM-ligand motif (ULM). Here, crystal and solution NMR structures of the RBM39-UHM domain, and the crystal structure of its complex with U2AF65-ULM, are reported. The RBM39–U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, by isothermal titration calorimetry and by NMR chemical shift perturbation experiments with the purified proteins. When compared with related complexes, such as U2AF35–U2AF65 and RBM39–SF3b155, the RBM39-UHM–U2AF65-ULM complex reveals both common and discriminating recognition elements in the UHM–ULM binding interface, providing a rationale for the known specificity of UHM–ULM interactions. This study therefore establishes a structural basis for specific UHM–ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells.

  10. Enhanced removal of bisphenol-AF onto chitosan-modified zeolite by sodium cholate in aqueous solutions.

    PubMed

    Peng, Sha; Hao, Kunyan; Han, Feng; Tang, Zheng; Niu, Beibei; Zhang, Xu; Wang, Zhen; Hong, Song

    2015-10-05

    The removal of bisphenol-AF (BPAF) from aqueous solutions onto chitosan-modified zeolite (Ch-Z) in the absence and presence of sodium cholate (NaC) was investigated. It was found that NaC significantly increased the adsorption capacity of Ch-Z for BPAF. At an initial concentration of 100 μmol/L, the removal of BPAF by adsorption onto Ch-Z with NaC was more than ninefold higher than without NaC, and the maximum removal was achieved at a Ch-Z dosage of 1g/L with a NaC concentration of 1.68 mmol/L. Besides, batch studies were performed to evaluate the effects of various experimental parameters on the removal of BPAF. Kinetic studies and adsorption isotherms indicated that the adsorption process of BPAF onto Ch-Z with NaC could be expressed by a pseudo second-order model and the Freundlich isotherm model, respectively. For the enhanced removal, an interaction mechanism was proposed involving the co-effect of BPAF and NaC adsorbed onto Ch-Z.

  11. Microstructural basis for the effect of chromium on the strength and toughness of AF1410-based high performance steels

    NASA Astrophysics Data System (ADS)

    Ayer, Raghavan; Machmeier, P. M.

    1996-09-01

    The variation in strength and Charpy impact toughness as a function of tempering temperature in the range of 200 ‡C to 650 ‡C was investigated in AF 1410 and AF 1410 + 1 pct Cr steels produced in a laboratory-scale, and a commercially produced AerMet 100 steel. The tensile test results showed that AF 1410 + 1 pct Cr had lower strength compared to AF 1410, while AerMet 100 had the highest strength of the three steels examined. Transmission electron microscopy (TEM) studies demonstrated that the strength variations among the steels can be attributed to differences in the matrix/carbide coherency strain and the volume fraction of the strengthening M2C carbides. The toughness values of the three steels were comparable when tempered up to 424 ‡C. Tempering at and above 454 ‡C resulted in a relative enhancement of toughness in AF 1410 + 1 pct Cr steel compared to AF 1410. This toughening was attributed to the destabilization of cementite at lath and prior austenite boundaries and the formation of reverted austenite.

  12. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    PubMed

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-02-27

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata.

  13. Structural Basis for Polypyrimidine Tract Recognition by the Essential Pre-mRNA Splicing Factor U2AF65

    SciTech Connect

    Sickmier,E.; Frato, K.; Shen, H.; Paranawithana, S.; Green, M.; Kielkopf, C.

    2006-01-01

    The essential pre-mRNA splicing factor, U2AF{sup 65}, guides the early stages of splice site choice by recognizing a polypyrimidine (Py)-tract consensus sequence near the 3'-splice site. Since Py-tracts are relatively poorly conserved in higher eukaryotes, U2AF{sup 65} is faced with the problem of specifying uridine-rich sequences, yet tolerating a variety of nucleotide substitutions found in natural Py-tracts. To better understand these apparently contradictory RNA binding characteristics, the X-ray structure of the U2AF{sup 65} RNA binding domain bound to a Py-tract composed of seven uridines has been determined at 2.5Angstroms resolution. Specific hydrogen bonds between U2AF{sup 65} and the uracil bases provide an explanation for polyuridine recognition. Flexible sidechains and bound water molecules form the majority of the base contacts, and potentially could rearrange when the U2AF{sup 65} structure adapts to different Py-tract sequences. The energetic importance of conserved residues for Py-tract binding is established by analysis of site-directed mutant U2AF{sup 65} proteins using surface plasmon resonance.

  14. [Biomechanics of AF new 3-d pedical screw system and treatment of 31 patients with unstable thoracolumbar fracture].

    PubMed

    Zou, D; Hai, Y; Ma, H

    1995-04-01

    For anatomic reduction of the spinal frectures, the 3 dimensional multiple correction forces were needed. Several pedical screw systems were designed for reducion and fixation of the spinal fractures as the AO universal joint system and the RF angle screw system. Because of the contradiction of the universal joint and the fixed angle, a new generation of RF was designed and named AF (atlas fixator) system. This is a new concept of 3-D reduction, without complex structure as universal joint, but has truly 3-D adjustment that allowed to reduce the intra-canal compromise. It also provided rigid fixation to maintain the reduction. Comparison with CD, AO, Steffee, and RF, the AF was truly 3-D reduction in XTZ axis. It provided strong symmetric transmitter orthotic force to correct the deformity. 31 patients with unstable thoracolumbar fractures were treated with the new AF system. 17 had partial (15) or complete (2) neurologic deficits. The AF system provided accurate angle to restore the normal thoracic-lumbar lordosis and to maintain it. All patients had a anatomic reduction by AF system. The spinal canal area increased over 33% by CT scan (P < 0.01). All cases were followed up over 8 months. No one deteriorated neurologically after AF fixation.

  15. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  16. Responsiveness of AF6, a new, short, validated, atrial fibrillation-specific questionnaire—symptomatic benefit of direct current cardioversion

    PubMed Central

    Härdén, Marie; Nyström, Britta; Bengtson, Ann; Medin, Jennie; Frison, Lars

    2010-01-01

    Objectives To measure the effects on symptoms of electrical cardioversion (DC) in patients with atrial fibrillation (AF) by means of a new, short, validated, AF-specific questionnaire, the AF6. Methods One hundred eleven patients (67 ± 12 years, 89 men) were screened before and 12 ± 3 days after DC using AF6, covering ‘breathing difficulties at rest’, ‘breathing difficulties on exertion’, ‘limitations in day-to-day life due to atrial fibrillation’, ‘feeling of discomfort due to atrial fibrillation’, ‘tiredness due to atrial fibrillation’, and ‘worry/anxiety due to atrial fibrillation’. A single global score was calculated. The Toronto AF Symptoms and Severity Check List (AFSS) and the generic SF-36 were also administered. Patients in sinus rhythm at 12 ± 3 days (n = 56) were defined as responders and patients in AF (n = 55) as non-responders. Results The mean single global score decreased in all patients (18 ± 12.4 to 13 ± 11.6, p < 0.0001) and in responders (22 ± 14 vs. 12 ± 12, p < 0.01) but not in non-responders (14 ± 9 vs. 14 ± 11, N.S). The AFSS frequency scores decreased from 14.5 ± 7.7 to 9.5 ± 7.8 in responders, p = 0.001, but not in non-responders. There was a strong correlation between changes in the AF6 and the SF-36 regarding four of the six items. Effect sizes of AF6 ranged from 0 to 0.52 in all patients, in responders from 0.10 to 0.85 and in non-responders from −0.23 to 0.34, the highest figures consistently referring to ‘tiredness due to atrial fibrillation’. Conclusions The symptom scores measured by AF6 decreased significantly, especially in responders. AF6 demonstrated adequate responsiveness to change, and effect sizes were mostly moderate, in responders moderate to high. PMID:20461545

  17. Differential modulation of plant immune responses by diverse members of the Pseudomonas savastanoi pv. savastanoi HopAF type III effector family.

    PubMed

    Castañeda-Ojeda, M Pilar; López-Solanilla, Emilia; Ramos, Cayo

    2016-04-26

    The Pseudomonas savastanoi pv. savastanoi NCPPB 3335 type III secretion system (T3SS) effector repertoire includes 33 candidates, seven of which translocate into host cells and interfere with plant defences. The present study was performed to investigate the co-existence of both plasmid- and chromosomal-encoded members of the HopAF effector family, HopAF1-1 and HopAF1-2, respectively, in the genome of NCPPB 3335. Here, we show that the HopAF1 paralogues are widely distributed in the Pseudomonas syringae complex, where HopAF1-1 is most similar to the homologues encoded by other P. syringae pathovars infecting woody hosts that belong to phylogroups 1 and 3. We show that the expression of both HopAF1-1 and HopAF-2 is transcriptionally dependent on HrpL and demonstrate their delivery into Nicotiana tabacum leaves. Although the heterologous delivery of either HopAF1-1 or HopAF1-2 significantly suppressed the production of defence-associated reactive oxygen species levels, only HopAF1-2 reduced the levels of callose deposition. Moreover, the expression of HopAF1-2 by functionally effectorless P. syringae pv. tomato DC3000D28E completely inhibited the hypersensitive response in tobacco and significantly increased the competitiveness of the strain in Nicotiana benthamiana. Despite their functional differences, subcellular localization studies reveal that green fluorescent protein (GFP) fusions to either HopAF1-1 or HopAF1-2 are targeted to the plasma membrane when they are expressed in plant cells, a process that is completely dependent on the integrity of their N-myristoylation motif. Our results further support the notion that highly similar T3SS effectors might differentially interact with diverse plant targets, even when they co-localize in the same cell compartment.

  18. Monitoring of individual human exposure to aflatoxins (AF) and N-nitrosamines (NNO) by immunoassays

    SciTech Connect

    Wild, C.P.; Umbenhauer, D.; Chapot, B.; Montesano, R.

    1986-01-01

    Highly sensitive immunoassays have been used to quantitate aflatoxins (AF) and N-nitrosamines (NNO) in human body fluids and tissues, respectively. This approach was taken in order to quantitate environmental exposure to these agents at an individual level to facilitate the investigation of their role in the etiology of human cancer. In order to analyse AF in human urine, an immunopurification step has been developed by using AF-specific antibody bound to AH-Sepharose 4B gel in a small (4-ml gel volume) affinity column prior to enzyme-linked immunosorbent assay (ELISA). The ELISA can be used to quantitate aflatoxin B1 (AFB1) over the range 0.01 ng/ml to 10 ng/ml and the assay system has been validated by using human urine samples spiked with AFB1 over this concentration range. In addition, 29 urine samples from the Philippines have been analyzed and found to contain a range of levels from zero to 4.25 ng/ml AFB1 equivalent with a mean of 0.875 ng/ml. This compared with a mean of 0.066 ng/ml AFB1 equivalent in samples from France. Radioimmunoassay of O6-methyldeoxyguanosine (O6-medG) has been performed on human esophageal and cardiac stomach mucosal DNA from tissue samples obtained during surgery in Linxian County, People's Republic of China, an area of high risk for both esophageal and stomach cancer. Using the methodology described and having 1 mg of hydrolyzed DNA allows the detection of approximately 25 fmol O6medG per mg DNA.

  19. Involvenflavones A-F, six new flavonoids with 3'-aryl substituent from Selaginella involven.

    PubMed

    Long, Hong-Ping; Zou, Hui; Li, Fu-Shuang; Li, Jing; Luo, Ping; Zou, Zhen-Xing; Hu, Chang-Ping; Xu, Kang-Ping; Tan, Gui-Shan

    2015-09-01

    Six new flavonoids, involvenflavones A-F (1-6), were isolated from Selaginella involven. Their structures were elucidated based on UV, IR, 1D and 2D NMR as well as HR-ESI-MS techniques. All compounds belong to apigenin derivatives with 3'-aryl substituent. This is the first report of the apigenin derivatives with 3'-aryl substituent from nature resources. These compounds also exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro.

  20. Fulda AAF, Germany. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1972-02-08

    SPEED (FROM HOURLY OBSERVATIONS) 355 Fi,&DA GERMiN ~IY 4AF b-~-Z______ STATON STATION MAN9 ICA.$ O.N ALL EATnE., 3" ,-.5 cuss NOUAS (L s 1 SPEEDN MEAN...30,1 33,1 3346 33,3 33 O 33, 34.7 1600 0 30,4 319,2 33,3 33,3 337. 239, 11000 1 4, 2 7,2 279 213 29,9 30.1 3,4 33.1 33.4 33,3 36 3,6 ’,>_20oo2. Zola

  1. Candenatenins A-F, phenolic compounds from the heartwood of Dalbergia candenatensis.

    PubMed

    Cheenpracha, Sarot; Karalai, Chatchanok; Ponglimanont, Chanita; Kanjana-Opas, Akkharawit

    2009-08-01

    Chemical investigation of the CH2Cl2 extract of the heartwood of Dalbergia candenatensis affored six new phenolic compounds, designated candenatenins A-F (1-6), as well as four known compounds, (2R,3R)-3,5-dihydroxy-7-methoxyflavanone (7), 4-hydroxy-3-methoxy-8,9-methylenedioxypterocarpan (8), nutiducol (9), and sophoraflavanone A (10). The structures of the new compounds were determined by 1D- and 2D-NMR spectroscopic studies as well as by MS analysis. The cytotoxic activities of the isolated compounds are also reported.

  2. Dover AFB Delaware. Revised Uniform Summary of Surface Weather Observations. Parts A-F

    DTIC Science & Technology

    1974-08-07

    SNOW X OF SMOKE DUST X OF OSS TOTALMONTH T. STORMS AD/OR RAIN &/fOR AND/OR HAIL IObs WITH FOG AND/ORt BOWIG AND/ORt WITH ORST NO. OF( ST )DRIZZLE DRIZZLE...OBSERVATIONS) 13707 DUVEF AF8 DELAWARE 4 Ago4 f!,SL 55 AR STATION STATION RA50 01055 MONTH ALL WEATHER ALL CLASS NOVAS ( ST .) ( CONDITION SPE MEAN (NT...DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 1.3707 )0VEIc AFB 0ELAwAIRE 43-46251-72 JAN4 ALL WEATHEV, 0600-0800 Cuss x05o5 ILL ST .) SIPEED i MEAN (KNTS

  3. A novel clinical multimodal multiphoton tomograph for AF, SHG, CARS imaging, and FLIM

    NASA Astrophysics Data System (ADS)

    Weinigel, Martin; Breunig, Hans Georg; König, Karsten

    2014-02-01

    We report on a flexible nonlinear medical tomograph with multiple miniaturized detectors for simultaneous acquisition of two-photon autofluorescence (AF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) images. The simultaneous visualization of the distribution of endogenous fluorophores NAD(P)H, melanin and elastin, SHG-active collagen and as well as non-fluorescent lipids within human skin in vivo is possible. Furthermore, fluorescence lifetime images (FLIM) can be generated using time-correlated single photon counting.

  4. miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221.

    PubMed

    Kotani, Ai; Ha, Daon; Hsieh, James; Rao, Prakash K; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2009-11-05

    MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

  5. Acceleration of Regeneration of Large Gap-Peripheral Nerve Injuries Using Acellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2015-10-01

    amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Thomas L. Smith, PhD CONTRACTING ORGANIZATION: Wake Forest University Health Sciences...Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). 5a. CONTRACT NUMBER W81XWH-13-1-0309 5b. GRANT NUMBER OR120157 5c...year include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up to 72 hours after seeding. The

  6. Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference 'research perspectives in AF'.

    PubMed

    Kirchhof, Paulus; Bax, Jeroen; Blomstrom-Lundquist, Carina; Calkins, Hugh; Camm, A John; Cappato, Ricardo; Cosio, Francisco; Crijns, Harry; Diener, Hans-Christian; Goette, Andreas; Israel, Carsten W; Kuck, Karl-Heinz; Lip, Gregory Y H; Nattel, Stanley; Page, Richard L; Ravens, Ursula; Schotten, Ulrich; Steinbeck, Gerhard; Vardas, Panos; Waldo, Albert; Wegscheider, Karl; Willems, Stephan; Breithardt, Günter

    2009-12-01

    Atrial fibrillation (AF) causes important mortality and morbidity on a population-level. So far, we do not have the means to prevent AF or AF-related complications adequately. Therefore, over 70 experts on atrial fibrillation convened for the 2nd AFNET/EHRA consensus conference to suggest directions for research to improve management of AF patients (Appendix 1). The group defined three main areas in need for research in AF: 1. better understanding of the mechanisms of AF; 2. Improving rhythm control monitoring and management; and 3. comprehensive cardiovascular risk management in AF patients. The group put forward the hypothesis that successful therapy of AF and its associated complications will require comprehensive therapy. This applies e.g. to the "old" debate of "rate versus rhythm control", since rhythm control is generally added to underlying (continued) rate control therapy, but also to the emerging debate of "antiarrhythmic drugs versus catheter ablation", of which both may be needed in most patients to maintain sinus rhythm, but also to therapy of conditions that predispose to AF and contribute to cardiovascular complications such as stroke, cognitive decline, heart failure, and acute coronary syndromes. We call for research initiatives aiming at a better understanding of the different causes of AF and its complications, and at development and validation of mechanism-based therapies. The future of AF therapy may require a combination of management of underlying and concomitant conditions, early and comprehensive rhythm control therapy, adequate control of ventricular rate and cardiac function, and continuous therapy to prevent AF-associated complications (e.g. antithrombotic therapy). The reasons for these suggestions are detailed in this paper.

  7. The splicing factor U2AF65 is functionally conserved in the thermotolerant deep-sea worm Alvinella pompejana.

    PubMed

    Henscheid, Kristy L; Shin, David S; Cary, S Craig; Berglund, J Andrew

    2005-03-10

    Due to their inherent stability, thermophilic bacteria and archaea serve as important resources for biochemical and biophysical analyses of many biological processes. Unfortunately, scientists characterizing eukaryote-specific processes, such as nuclear pre-mRNA splicing, are unable to take advantage of these sources of thermostable proteins. To identify and provide a source of thermostable eukaryotic proteins, we are characterizing splicing factors in the thermotolerant deep-sea vent polychaete, Alvinella pompejana. This worm, also known as the Pompeii worm, is found in the extreme environment of deep-sea hydrothermal vents, and is one of the most thermotolerant eukaryotic organisms known. We report on detailed analyses of U2AF65, the large subunit of the U2 small nuclear ribonucleoprotein auxiliary factor, an essential splicing factor important for intron definition and alternative splicing. The cloning and characterization of Pompeii U2AF65 show it is highly similar to human U2AF65 in sequence and function and is more thermostable than the human protein when bound to RNA in vitro. Notably, Pompeii U2AF65 can restore splicing in a human extract depleted of human U2AF. We also determine that the general splicing mechanisms and signal sequences are conserved in the Pompeii worm, an annelid which has previously been uncharacterized in terms of splicing factors and signals.

  8. Air Force Systems Engineering Assessment Model (AF SEAM) Management Guide, Version 2

    DTIC Science & Technology

    2010-09-21

    Document ( OBD ) during operational use with stakeholder coordination. Develop mechanisms to ensure conformity to the OBD (i.e., health monitoring and...among related products. Typical Work Products: □ Surveillance test plan □ Weapon Systems Evaluation Program □ OBD Reference Material: AFI 63

  9. Substrate specificity and gene expression of two Penicillium chrysogenum α-L-arabinofuranosidases (AFQ1 and AFS1) belonging to glycoside hydrolase families 51 and 54.

    PubMed

    Sakamoto, Tatsuji; Inui, Misako; Yasui, Kana; Hosokawa, Sachiko; Ihara, Hideshi

    2013-02-01

    We previously isolated two α-L-arabinofuranosidases (ABFs), termed AFQ1 and AFS1, from the culture filtrate of Penicillium chrysogenum 31B. afq1 and afs1 complementary DNAs encoding AFQ1 and AFS1 were isolated by in vitro cloning. The deduced amino acid sequences of AFQ1 and AFS1 are highly similar to those of Penicillium purpurogenum ABF 2 and ABF 1, respectively, which belong to glycoside hydrolase (GH) families 51 and 54, respectively. Pfam analysis revealed an "Alpha-L-AF_C" domain in AFQ1 and "ArabFuran-catal" and "AbfB" domains in AFS1. Semi-quantitative RT-PCR analysis indicated that the afq1 gene was constitutively expressed in P. chrysogenum 31B at a low level, although the expression was slightly induced with arabinose, arabinitol, arabinan, and arabinoxylan. In contrast, expression of the afs1 gene was strongly expressed by the above four carbohydrates and less strongly induced by galactan. Recombinant enzymes (rAFQ1 and rAFS1) expressed in Escherichia coli were active against both p-nitrophenyl α-L-arabinofuranoside and polysaccharides with different specificities. (1)H-NMR analysis revealed that rAFS1 degraded arabinofuranosyl side chains that were both singly and doubly linked to the backbones of arabinoxylan and L-arabinan. On the other hand, rAFQ1 preferentially released arabinose linked to C-3 of single-substituted xylose or arabinose residues in the two polysaccharides.

  10. Molecular genetic analysis of the heterodimeric splicing factor U2AF: the RS domain on either the large or small Drosophila subunit is dispensable in vivo

    PubMed Central

    Rudner, David Z.; Breger, Kevin S.; Rio, Donald C.

    1998-01-01

    The pre-mRNA splicing factor U2AF (U2 snRNP auxiliary factor) has an essential role in 3′ splice site selection. U2AF binds the intron pyrimidine tract between the branchpoint and the 3′ splice site and recruits U2 snRNP to the branch site at an early step in spliceosome assembly. Human U2AF is a heterodimer composed of large (hU2AF65) and small (hU2AF35) subunits. Both subunits contain a domain enriched in arginine–serine dipeptide repeats termed an RS domain. The two U2AF RS domains have been assigned essential and independent roles in spliceosome assembly in vitro—the hU2AF65 RS domain is required to target U2 snRNP to the branch site and the hU2AF35 RS domain is necessary for protein–protein interactions with constitutive and alternative splicing factors. We have investigated the functional requirements for the RS domains on the Drosophila U2AF homolog in vivo. In sharp contrast to its essential role in U2 snRNP recruitment in vitro, the RS domain on the Drosophila large subunit homolog (dU2AF50) was completely dispensable in vivo. Prompted by this unexpected result, we analyzed the RS domain on the Drosophila small subunit homolog (dU2AF38). Despite its requirement for enhancer-dependent splicing activity in vitro, the dU2AF38 RS domain was also inessential in vivo. Finally, we have tested whether the Drosophila U2AF heterodimer requires any RS domain. Flies mutant for both the small and large subunits could not be rescued by dU2AF50ΔRS and dU2AF38ΔRS transgenes. Therefore, in contrast to the separate roles assigned to the U2AF RS domains in vitro, our genetic data suggest that they may have redundant functions in vivo. PMID:9531538

  11. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection.

    PubMed

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-07-17

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes' status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors' detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability.

  12. Smyd2 is a Myc-regulated gene critical for MLL-AF9 induced leukemogenesis

    PubMed Central

    Bagislar, Sevgi; Sabò, Arianna; Kress, Theresia R.; Doni, Mirko; Nicoli, Paola; Campaner, Stefano; Amati, Bruno

    2016-01-01

    The Smyd2 protein (Set- and Mynd domain containing protein 2) is a methyl-transferase that can modify both histones and cytoplasmic proteins. Smyd2 is over-expressed in several cancer types and was shown to be limiting for tumor development in the pancreas. However, genetic evidence for a role of Smyd2 in other cancers or in mouse development was missing to date. Using germ line-deleted mouse strains, we now show that Smyd2 and the related protein Smyd3 are dispensable for normal development. Ablation of Smyd2 did not affect hematopoiesis, but retarded the development of leukemia promoted by MLL-AF9, a fusion oncogene associated with acute myeloid leukemia (AML) in humans. Smyd2-deleted leukemic cells showed a competitive disadvantage relative to wild-type cells, either in vitro or in vivo. The Smyd2 gene was directly activated by the oncogenic transcription factor Myc in either MLL9-AF9-induced leukemias, Myc-induced lymphomas, or fibroblasts. However, unlike leukemias, the development of lymphomas was not dependent upon Smyd2. Our data indicate that Smyd2 has a critical role downstream of Myc in AML. PMID:27655694

  13. Advanced Compatibility Characterization Of AF-M315E With Spacecraft Propulsion System Materials Project

    NASA Technical Reports Server (NTRS)

    McClure, Mark B.; Greene, Benjamin

    2014-01-01

    All spacecraft require propulsion systems for thrust and maneuvering. Propulsion systems can be chemical, nuclear, electrical, cold gas or combinations thereof. Chemical propulsion has proven to be the most reliable technology since the deployment of launch vehicles. Performance, storability, and handling are three important aspects of liquid chemical propulsion. Bipropellant systems require a fuel and an oxidizer for propulsion, but monopropellants only require a fuel and a catalyst for propulsion and are therefore simpler and lighter. Hydrazine is the state of the art propellant for monopropellant systems, but has drawbacks because it is highly hazardous to human health, which requires extensive care in handling, complex ground ops due to safety and environmental considerations, and lengthy turnaround times for reusable spacecraft. All users of hydrazine monopropellant must contend with these issues and their associated costs. The development of a new monopropellant, intended to replace hydrazine, has been in progress for years. This project will apply advanced techniques to characterize the engineering properties of materials used in AF-M315E propulsion systems after propellant exposure. AF-M315E monopropellant has been selected HQ's Green Propellant Infusion Mission (GPIM) to replace toxic hydrazine for improved performance and reduce safety and health issues that will shorten reusable spacecraft turn-around time. In addition, this project will fundamentally strengthen JSC's core competency to evaluate, use and infuse liquid propellant systems.

  14. Development of FDR-AF (Frictional Drag Reduction Anti-Fouling) Marine Coating

    NASA Astrophysics Data System (ADS)

    Lee, Inwon; Park, Hyun; Chun, Ho Hwan; GCRC-SOP Team

    2013-11-01

    In this study, a novel skin-friction reducing marine paint has been developed by mixing fine powder of PEO(PolyEthyleneOxide) with SPC (Self-Polishing Copolymer) AF (Anti-Fouling) paint. The PEO is well known as one of drag reducing agent to exhibit Toms effect, the attenuation of turbulent flows by long chain polymer molecules in the near wall region. The frictional drag reduction has been implemented by injecting such polymer solutions to liquid flows. However, the injection holes have been a significant obstacle to marine application. The present PEO-containing marine paint is proposed as an alternative to realize Toms effect without any hole on the ship surface. The erosion mechanism of SPC paint resin and the subsequent dissolution of PEO enable the controlled release of PEO solution from the coating. Various tests such as towing tank drag measurement of flat plate and turbulence measurement in circulating water tunnel demonstrated over 10% frictional drag reduction compared with conventional AF paint. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) through GCRC-SOP(No. 2011-0030013).

  15. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection

    PubMed Central

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-01-01

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes’ status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors’ detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability. PMID:26193280

  16. The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9

    SciTech Connect

    Haribaskar, Ramachandran; Puetz, Michael; Schupp, Birte; Skouloudaki, Kassiani; Bietenbeck, Andreas; Walz, Gerd; Schaefer, Tobias

    2009-09-11

    The planar cell polarity (PCP) pathway, a {beta}-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks {beta}-catenin-dependent and promotes {beta}-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.

  17. A novel poly(3-hydroxybutyrate)-degrading Streptoverticillium kashmirense AF1 isolated from soil and purification of PHB-depolymerase.

    PubMed

    Shah, A A; Hasan, Fariha; Hameed, A; Ahmed, Safia

    2008-12-01

    A new bacterial strain, capable of degrading poly(3-hydroxybutyrate) (PHB) was isolated from soil. This organism, identified as Streptoverticillium kashmirense AF1, secreted PHB depolymerases both on solid as well as in liquid mineral salt medium containing poly(3-hydroxybutyrate) as sole carbon source. The optimum production of PHB depolymerase was observed at pH 8 and 7, at 45 degrees C, 1% substrate concentration and in the presence of lactose as an additional carbon source. The extracellular PHB depolymerase was purified by gel permeation chromatography using Sephadex G-75. The Streptoverticillium kashmirense AF1 produced two types of PHB depolymerases having molecular weights of about 37 and 45 kDa as determined by SDS-PAGE. The difference in dry cell mass and amount of CO2 evolved in the test and control calculated gravimetrically through Sturm test indicated the degradative capabilities of Streptoverticillium kashmirense AF1.

  18. Impact of tissue geometry on simulated cholinergic atrial fibrillation: A modeling study

    NASA Astrophysics Data System (ADS)

    Comtois, Philippe; Nattel, Stanley

    2011-03-01

    Atrial fibrillation (AF), arising in the cardiac atria, is a common cardiac rhythm disorder that is incompletely understood. Numerous characteristics of the atrial tissue are thought to play a role in the maintenance of AF. Most traditional theoretical models of AF have considered the atrium to be a flat two-dimensional sheet. Here, we analyzed the relationship between atrial geometry, substrate size, and AF persistence, in a mathematical model involving heterogeneity. Spatially periodic properties were created by variations in times required for reactivation due to periodic acetylcholine concentration [ACh] distribution. The differences in AF maintenance between the sheet and the cylinder geometry are found for intermediate gradients of inexcitable time (intermediate [ACh]). The maximum difference in AF maintenance between geometry decreases with increasing tissue size, down to zero for a substrate of dimensions 20 × 10 cm. Generators have the tendency to be anchored to the regions of longer inexcitable period (low [ACh]). The differences in AF maintenance between geometries correlate with situations of moderate anchoring for which rotor-core drifts between low-[ACh] regions occur, favoring generator disappearance. The drift of generators increases their probability of disappearance at the tissue borders, resulting in a decreased maintenance rate in the sheet due to the higher number of no-flux boundaries. These interactions between biological variables and the role of geometry must be considered when selecting an appropriate model for AF in intact hearts.

  19. Development of a transgenic goat model wih cardiac-specific overexpression of transforming growth factor - {beta} 1 to study the relationship between atrial fibrosis and atrial fibrillation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies on patients, large animal models and transgenic mouse models have shown a strong association of atrial fibrosis with atrial fibrillation (AF). However, it is unclear whether there is a causal relationship between atrial fibrosis and AF or whether these events appear as a result of independen...

  20. Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement

    PubMed Central

    Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.

    2016-01-01

    Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193

  1. A Comparison of Atrial Fibrillation Monitoring Strategies After Cryptogenic Stroke (from the Cryptogenic Stroke and Underlying AF Trial).

    PubMed

    Choe, William C; Passman, Rod S; Brachmann, Johannes; Morillo, Carlos A; Sanna, Tommaso; Bernstein, Richard A; Di Lazzaro, Vincenzo; Diener, Hans-Christoph; Rymer, Marilyn M; Beckers, Frank; Koehler, Jodi; Ziegler, Paul D

    2015-09-15

    Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p <0.001). Long-term continuous electrocardiographic monitoring with ICMs is significantly more effective than any of the simulated intermittent monitoring strategies for identifying AF in patients with previous cryptogenic stroke.

  2. USAF Bioenvironmental Noise Data Handbook. Volume 166. AF/M32T-1 Tester, Pressurized Cabin Leakage, Aircraft,

    DTIC Science & Technology

    1982-07-01

    OPERATOR NOISE MEASUREMENTS AF/M32T-1 Tester, Pressurized Cabin Leakage, Aircraft Tyndall AFB, 19 June 1980 NSN 4920-00- 347 -9455, Field * J108...a- a a o a af .4a a0 1 P ,? o4 o1 01 ao aD Nh s 1AA a ~ ~ a naaa .4 a aif CL O va I am wEj r .M PO -ODM.a)a D aa CDo NW)N 4 % ma a a. . 9 w ao N~ a I

  3. Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms.

    PubMed

    Brace, Robert A; Anderson, Debra F; Cheung, Cecilia Y

    2014-11-15

    Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport.

  4. Activation of Wnt signaling pathway by AF1q enriches stem-like population and enhance mammosphere formation of breast cells.

    PubMed

    Tse, Charlotte Olivia; Kim, Soojin; Park, Jino

    2017-03-18

    Wnt signaling pathway is believed to be responsible for control over various types of stem cells and may act as a niche factor to maintain stem cells in a self-renewing state. Moreover, dysregulated Wnt signaling pathway is strongly associated with several diseases including cancer. Previously, we have shown that AF1q associates with a poor prognosis in leukemia, myelodysplastic syndromes, multiple myeloid, ovarian cancer, and breast cancer. Also, AF1q plays a pivotal role as an oncogene and metastasis enhancer in breast cancer via activation of Wnt signaling pathway. AF1q is highly expressed in stem cells, and this expression is diminished by differentiation. To understand the role of AF1q in stem-like population, we examined stem-like cells derived from breast cells which dysregulated Wnt signaling pathway by alteration of AF1q expression. The effect of Wnt signaling pathway by AF1q on EMT marker expression, stem cell marker expression, and sphere formation was determined. Activated Wnt signaling pathway by AF1q enriched stem-like population showed enhanced sphere formation ability. Interestingly, Wnt signaling pathway inhibitor, Quercetin, decreased the sphere formation in these cells. These results suggest that AF1q would have a role as an enhancer in generation of stem-like population through activation of Wnt signaling pathway.

  5. 75 FR 9596 - Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-03

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food... residues of the antifungal ] agent, Aspergillus flavus AF36, in or on corn food and feed commodities....

  6. Clone-derived human AF-amniotic fluid stem cells are capable of skeletal myogenic differentiation in vitro and in vivo.

    PubMed

    Ma, Xiaorong; Zhang, Shengli; Zhou, Junmei; Chen, Baisong; Shang, Yafeng; Gao, Tongbing; Wang, Xue; Xie, Hua; Chen, Fang

    2012-08-01

    Stem cell-based therapy may be the most promising method to cure skeletal muscle degenerative diseases such as Duchenne muscular dystrophy (DMD) and trauma in the future. Human amniotic fluid is enriched with early-stage stem cells from developing fetuses and these cells have cardiomyogenic potential both in vitro and in vivo. In the present study, we investigated the characteristics of human amniotic fluid-derived AF-type stem (HAF-AFS) cells by flow cytometry, immunofluorescence staining, reverse-transcription polymerase chain reaction, and osteogenic and adipogenic differentiation analysis. After confirming the stemness of HAF-AFS cells, we tested whether HAF-AFS cells could differentiate into skeletal myogenic cells in vitro and incorporate into regenerating skeletal muscle in vivo. By temporary exposure to the DNA demethylation agent 5-aza-2'-deoxycytidine (5-Aza dC) or co-cultured with C2C12 myoblasts, HAF-AFS cells differentiated into skeletal myogenic cells, expressing skeletal myogenic cell-specific markers such as Desmin, Troponin I (Tn I) and α-Actinin. Four weeks after transplantation into cardiotoxin-injured and X-ray-irradiated tibialis anterior (TA) muscles of NOD/SCID mice, HAF-AFS cells survived, differentiated into myogenic precursor cells and fused with host myofibres. The findings that HAF-AFS cells differentiate into myogenic cells in vitro and incorporate in skeletal muscle regeneration in vivo hold the promise of HAF-AFS cell-based therapy for skeletal muscle degenerative diseases.

  7. Slurry sampling in serum blood for mercury determination by CV-AFS.

    PubMed

    Aranda, Pedro R; Gil, Raúl A; Moyano, Susana; De Vito, Irma; Martinez, Luis D

    2009-01-30

    The heavy metal mercury (Hg) is a neurotoxin known to have a serious health impact even at relatively low concentrations. A slurry method was developed for the sensitive and precise determination of mercury in human serum blood samples by cold vapor generation coupled to atomic fluorescence spectrometry (CV-AFS). All variables related to the slurry formation were studied. The optimal hydrochloric concentration and tin(II) chloride concentration for CV generation were evaluated. Calibration within the range 0.1-10 microg L(-1) Hg was performed with the standard addition method, and compared with an external calibration. Additionally, the reliability of the results obtained was evaluated by analyzing mercury in the same samples, but submitted to microwave-assisted digestion method. The limit of detection was calculated as 25 ng L(-1) and the relative standard deviation was 3.9% at levels around of 0.4 microg L(-1)Hg.

  8. Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

    PubMed

    Zhou, Wen-Bing; Zeng, Guang-Zhi; Xu, Hui-Min; He, Wen-Jun; Zhang, Yu-Mei; Tan, Ning-Hua

    2014-03-01

    Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 μM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 μM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 μM.

  9. Adak NAS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-08-24

    operated by the U. S. Ser- vices aoi some foreig;n stations .silim, similar reporting prscticei. UiJesu otlherwise noted the Co ~luwilof suianries are...34 TRNSITERVEoRE .iF Oct 3.94 Longviev hAl Weather Sot available NA N/ N/A statin (Jo~Unit hAP & Navy) 2. 2 2/31/13 Ad~k(Joint’Unit) AF & Not available N/A I/A N/A...641214.15 2.18 cO 4 18.1 7.2 17. 9 .1.4421 FES 5 . 18.1 5.4 17.2 1 .5 19.1 17.4 L. 4 2.1 .1 76.Z IIG2 4 .7 _9.57) 1.97 MAN 5 5.5 19.5 13.3 1I.3 12. 9

  10. RAF Lakenheath, United Kingdom. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1988-02-01

    3: 1 ... . 2 . . jb -3VI SO I 7.27b 6 . ( 5.764 5.103 4.571 4.47 1 4.367 .47 5.244 b.712 7.717 7.3< 7 5.4.7 1333 osJ 915 a37 91 ’ɘ 911 645 0. 92’ 1...LA II WE17,rY uSAFLTAC fqL" LUlLy CFS[kVATO.V AIR .LA IHfP SERVICC/MAC STATIO, NUMPER: 75 3- STAIIOf, NAME : R AF LAKtNI-ATH L91[EU KINGf0CM L CIEC

  11. Hill AFB, Utah Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1984-09-01

    GLCqAL CLIMATOLOGY QRANCN b AX EAT,.C PSYCHROMETRIC SUMMARY AIP WE THER+ SEPICE /CPNIAC ?9 𔃿’ HILL AF- uT 14-81 ST" e~- STA?1010 1M1 VIA STN PAGE2 yeP...1 *, * 1-,* . 1 1 . I ! I i !9 -./ ., 1. 4 ,; ? , j : .. 7, dc L_ 1 I_ ’ I a AA I 6 if / "i - IT 𔃾 _ _"_ __. i ./ 2 . , 2 ., 921 ,- ’ 7 3 7.3...SEP. OCT NOV. DC ANNUAL MEAN ’’’ 7 *L 𔃾.3 23. .8 7.7 𔃽.3 4C.8 34.8 79.3 23.4 14.9 9.s SO 5D *143 7 4 7.128 7 . 94 6 .8g4 7.2;5 7 9 ;3 9.2 42 8 .632

  12. Palhicerines A-F, Lycopodium alkaloids from the club moss Palhinhaea cernua.

    PubMed

    Tang, Yu; Xiong, Juan; Zou, Yike; Zhang, Hai-Yan; Hu, Jin-Feng

    2016-11-01

    Four fawcettimine-type (palhicerines A-D, resp.) and two lycopodine-type (palhicerines E and F) Lycopodium alkaloids together with twenty known ones were isolated from the whole plant of Palhinhaea cernua. The structures and absolute configurations of the palhicerines A-F were determined by extensive spectroscopic methods, single-crystal X-ray diffraction analyses, chemical transformation, and electronic circular dichroism (ECD) calculations or induced electronic circular dichroism (IECD) spectra. Among the isolates, the new C/D-ring of the palhicerines A-C (trans-fused fawcettimine-type alkaloids) are rare, and each possesses a β-oriented C-16 methyl group and a distinctive tertiary methoxy group at C-13. Chemotaxonomy for differentiating species in the genus Palhinhaea is briefly discussed.

  13. Holloman AFB, New Mexico. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1982-04-12

    Information is provided: a. The min body of the sumary comslste of a bivariate percentage frequency distribution of wet-bulb depression in 17 classes...SERVICE/MAC C. 747320 HOLLOMAN AFS NM 68-70.7S-81 MAR STATION STATION WA&C VYZWS WONT" C PAGE 1 0 -MO. Temp. WET OUL11 TEMPEIATUIDE DEPRESSION (F) TOTAL...Tep. WET SUL& TEMPERATURE DEPRESSION (P) TOTAL TOTAL (F) 0 1-2 3-4 5-6 7-1 9.10 11-1213-14 15-16 17.18 19. 21.n23-24 25-262.029.20 -31 .L’W. S Ib Wt

  14. Extrasolar planets and brown dwarfs around AF-type stars. IX. The HARPS southern sample

    NASA Astrophysics Data System (ADS)

    Borgniet, S.; Lagrange, A.-M.; Meunier, N.; Galland, F.

    2017-03-01

    Context. Massive, main-sequence (MS) AF-type stars have so far remained unexplored in past radial velocities (RV) surveys due to their small number of spectral lines and high rotational velocities that prevent the classic RV computation method. Aims: Our aim is to search for giant planets (GPs) around AF MS stars, to get primary statistical information on their occurrence rate and to compare the results with evolved stars and lower-mass MS stars. Methods: We used the HARPS spectrograph located on the 3.6 m telescope at ESO La Silla Observatory to observe 108 AF MS stars with B-V in the range -0.04 to 0.58 and masses in the range 1.1 to 3.6 M⊙. We used our SAFIR software developed to compute the RV and other spectroscopic observables of these early-type stars. We characterized the detected companions as well as the intrinsic stellar variability. We computed the detection limits and used them as well as the detected companions to derive the first estimates of the close-in brown dwarf (BD) and GP frequencies around AF stars. Results: We report the detection of a mpsini = 4.51MJup planetary companion with an 826-day period to the F6V dwarf HD 111998. We also present new data on the two-planet system around the F6IV-V dwarf HD 60532. We also report the detections of 14 binaries with long-term RV trends and/or high-amplitude RV variations combined to a flat RV-bisector span diagram. We constrain the minimal masses and semi-major axes of these companions and check that these constraints are compatible with the stellar companions previously detected by direct imaging or astrometry for six of these targets. We get detection limits deep into the planetary domain with 70% of our targets showing detection limits between 0.1 and 10 MJup at all orbital periods in the 1- to 103-day range. We derive BD (13 ≤mpsini ≤ 80 MJup) occurrence rates in the 1- to 103-day period range of 2-2+5% and 2.6-2.6+6.7% for stars with M⋆ in the ranges 1.1 to 1.5 and 1.5 to 3 M

  15. Pope AFB, North Carolina Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1985-03-01

    OL.A IRE.IOA$ E0.T10S 01.S T 04. RtU ASP OOtE)U 6 *L’-AL .LI"!ATCL)GY i %A %Cm 2_T SURFACE WINDS .AT-Fd 1.RV1CL’?1AC PERCENTAGE FREQUENCY OF WIND...DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 72V~ -JP AF-!_~ _________ 7-L_________ tot ST A-T 0 k.I IsA .;T. A .L .LAT" E-’ •_ _-_ SPEED MEAN KNTS 1...0 , T ._ . _ * ,... . K . --- .. j , ,.. ’ . .. , m E¢ 800 1 ,00 2! 6100 9 . t 1200- ___? .. ..00 . . . : 100 2! goo EXAMPLE # 1 lHead ceiling

  16. RNA structure replaces the need for U2AF2 in splicing

    PubMed Central

    Lin, Chien-Ling; Taggart, Allison J.; Lim, Kian Huat; Cygan, Kamil J.; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G.

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes. PMID:26566657

  17. RNA structure replaces the need for U2AF2 in splicing.

    PubMed

    Lin, Chien-Ling; Taggart, Allison J; Lim, Kian Huat; Cygan, Kamil J; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes.

  18. Taipei IAP, Taiwan. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1973-09-07

    t5LLA TwP r <,AT okES DFC F fk’ *J.Y SFRkv A C.. 4 66 T ’ " lrA.IPtl JAP TYA1xA 54-7, ’ AN FEB AR APR ~ A’ Wl -. A’ Af N NNC.A 5EA. 51-o1 5,4 58,9 64 77...C AC7-RESS Z2 REPORT ZA-E US~ t ~ ~ 7 Sep, 73 Air Weather Service (MAC) N~BR2 A Scott AFB IL 62225 4 M041TORINS A CN’.Y N AME 3 AUCAE3S,f :ie- floll t ...over) ’ T & report is sx-pat t sti~ calsmmr of surface weather observations for h,,jei IAP, Taiwan It contains the following parts: (A) Weather

  19. Hot-Fire Testing of a 1N AF-M315E Thruster

    NASA Technical Reports Server (NTRS)

    Burnside, Christopher G.; Pedersen, Kevin; Pierce, Charles W.

    2015-01-01

    This hot-fire test continues NASA investigation of green propellant technologies for future missions. To show the potential for green propellants to replace some hydrazine systems in future spacecraft, NASA Marshall Space Flight Center (MSFC) is continuing to embark on hot-fire test campaigns with various green propellant blends. NASA completed a hot-fire test of a 1N AF-M315E monopropellant thruster at the Marshall Space Flight Center in the small altitude test stand located in building 4205. The thruster is a ground test article used for basic performance determination and catalyst studies. The purpose of the hot-fire testing was for performance determination of a 1N size thruster and form a baseline from which to study catalyst performance and life with follow-on testing to be conducted at a later date. The thruster performed as expected. The result of the hot-fire testing are presented in this paper and presentation.

  20. Study of the Antiferromagnetic Blume-Capel Model on kagomé Lattice

    NASA Astrophysics Data System (ADS)

    Hwang, Chi-Ok; Park, Sojeong; Kwak, Wooseop

    2016-09-01

    We study the anti-ferromagnetic (AF) Ising model and the AF Blume-Capel (BC) model on the kagomé lattice. Using the Wang-Landau sampling method, we estimate the joint density functions for both models on the lattice, and we obtain the exact critical magnetic fields at zero temperature by using the micro-canonical analysis. We also show the patterns of critical lines for the models from micro-canonical analysis.

  1. Hawaii Gravity Model

    SciTech Connect

    Nicole Lautze

    2015-12-15

    Gravity model for the state of Hawaii. Data is from the following source: Flinders, A.F., Ito, G., Garcia, M.O., Sinton, J.M., Kauahikaua, J.P., and Taylor, B., 2013, Intrusive dike complexes, cumulate cores, and the extrusive growth of Hawaiian volcanoes: Geophysical Research Letters, v. 40, p. 3367–3373, doi:10.1002/grl.50633.

  2. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF

    PubMed Central

    Bassand, Jean-Pierre; Accetta, Gabriele; Camm, Alan John; Cools, Frank; Fitzmaurice, David A.; Fox, Keith A.A.; Goldhaber, Samuel Z.; Goto, Shinya; Haas, Sylvia; Hacke, Werner; Kayani, Gloria; Mantovani, Lorenzo G.; Misselwitz, Frank; ten Cate, Hugo; Turpie, Alexander G.G.; Verheugt, Freek W.A.; Kakkar, Ajay K.

    2016-01-01

    Aims The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. Methods and results GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. Conclusion The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. Clinical Trial Registration http://www.clinicaltrials.gov. Unique identifier: NCT01090362. PMID:27357359

  3. Reworking Practice through an AfL Project: An Analysis of Teachers' Collaborative Engagement with New Assessment Guidelines

    ERIC Educational Resources Information Center

    Hermansen, Hege; Nerland, Monika

    2014-01-01

    In recent years, the concept of Assessment for Learning (AfL) has travelled across countries, giving rise to a range of educational policy initiatives and school development projects. While researchers have focused on issues such as how formative assessment can support student learning and lead to more efficient classroom practices, less attention…

  4. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

    PubMed

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

    2016-10-04

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

  5. Distribution of muscarinic receptor subtypes in rat brain as determined in binding studies with AF-DX 116 and pirenzepine

    SciTech Connect

    Giraldo, E.; Hammer, R.; Ladinsky, H.

    1987-03-02

    In vitro competition binding experiments with the selective muscarinic antagonists AF-DX 116 and pirenzepine (PZ) vs /sup 3/H-N-methylscopolamine as radioligand revealed a characteristic distribution of muscarinic receptor subtypes in different regions of rat brain. Based on nonlinear least squares analysis, the binding data were compatible with the presence of three different subtypes: the M/sub 1/ receptor (high affinity for PZ), the cardiac M/sub 2/ receptor (high affinity for AF-DX 116) and the glandular M/sub 2/ receptor (low affinity for PZ and AF-DX 116). The highest proportion of M/sub 1/ receptors was found in the hippocampus, while the cerebellum and the hypothalamus were the regions with the largest fraction of the cardiac M/sub 2/ and glandular M/sub 2/ receptors, respectively. In certain brain areas, depending on the relative proportions of the subtypes, flat binding curves were seen for AF-DX 116 and PZ. Based on these data, an approximate distribution pattern of the subtypes in the various brain regions is presented. 19 references, 1 figure, 2 tables.

  6. Rhein-Main Apt, Germany/Franfurt. Revised Uniform Summary of Surface Weather Observations. Parts A-F

    DTIC Science & Technology

    1977-08-01

    DATA PROCESSING BRANCH usAF E’ C CEILING, VERSUS VISIBILITY AIR WEATHER SERVICE/MAC 0 RHEINMAIN APT GERMANY/FRAtKFURT...SERVICE/MAC RHEINMAIN APT GENMANY/FRANKFURT 67-7o OEZ U. PERCENTAGE FREQUENCY OF OCCURRENCE 0000-.)200 , (FROM HOURLY OBSERVATIONS) o , - VISIBILITY

  7. Determining Aqueous Fullerene Particle Size Distributions by Asymmetric Flow Field-Flow Fractionation (AF4) without Surfactants

    EPA Science Inventory

    To determine the behavior of nanoparticles in environmental systems, methods must be developed to measure nanoparticle size. Asymmetric Flow Field Flow Fractionation (AF4) is an aqueous compatible size separation technique which is able to separate particles from 1 nm to 10 µm in...

  8. The Implementation of Collaborative Learning Using AfL through Giving Feedback Strategy for Improving Students’ Attention to Mathematics Lesson

    NASA Astrophysics Data System (ADS)

    Kurniasih, R.; Sujadi, I.; Pramesti, G.

    2016-02-01

    This research aims to describe the process of implementation collaborative learning with AfL through giving feedback strategy for improving students’ attention to mathematics lesson. Data which is collected in this research are students’ attention towards learning and students’ achievement. The result of this research showed that the learning steps by using collaborative learning with AfL through giving feedback strategy which can improve students’ attention are: 1) pre activity: the teacher delivers the purpose of the learning, successful criteria, apperception, and motivation. 2) main activity: the teacher gives the background of learning activity, explains learning materials at a glance, divides students discuss, the teacher observes and guides students to the problem solving, present their discussion result, gives feedback, the students do AfL problem and the answer is collected and result will be given before next meeting. 3) post activity: the teacher with students concludes the material. Test result, the percentage of students who complete the examination in the second cycle is 77.27%. Based on those results can be concluded that the implementation of collaborative learning using AfL through giving feedback can improve students’ attention towards learning and students’ achievement of XI IPA Students MA Al-Islam Jamsaren Surakarta academic year 2013/2014.

  9. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis

    PubMed Central

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy te; Basso, Giuseppe

    2016-01-01

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations. PMID:27698462

  10. Ultrasound body composition traits response to an endotoxin challenge in Brahman heifers supplemented with Omnigen-AF

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the body composition traits response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183 ± 5 kg) from the Texas AgriLife Research Center in Overton, TX, were separat...

  11. OmniGen-AF supplementation modulated the physiological and acute phase responses of Brahman heifers to an endotoxin challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the physiological and acute phase responses (APR) of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton...

  12. Modulation of the metabolic response to an endotoxin challenge in Brahman heifers through OmniGen-AF supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the metabolic response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton, TX, were separated into 2...

  13. Complementary DNA cloning, sequence analysis, and tissue transcription profile of a novel U2AF2 gene from the Chinese Banna mini-pig inbred line.

    PubMed

    Wang, S Y; Huo, J L; Miao, Y W; Cheng, W M; Zeng, Y Z

    2013-04-02

    U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an important gene for pre-messenger RNA splicing in higher eukaryotes. In this study, the Banna mini-pig inbred line (BMI) U2AF2 coding sequence (CDS) was cloned, sequenced, and characterized. The U2AF2 complete CDS was amplified using the reverse transcription-polymerase chain reaction (RT-PCR) technique based on the conserved sequence information of cattle and known highly homologous swine expressed sequence tags. This novel gene was deposited into the National Center for Biotechnology Information database (Accession No. JQ839267). Sequence analysis revealed that the BMI U2AF2 coding sequence consisted of 1416 bp and encoded 471 amino acids with a molecular weight of 53.12 kDa. The protein sequence has high sequence homology with U2AF65 of 6 species - Homo sapiens (100%), Equus caballus (100%), Canis lupus (100%), Macaca mulatta (99.8%), Bos taurus (74.4%), and Mus musculus (74.4%). The phylogenetic tree analysis revealed that BMI U2AF65 has a closer genetic relationship with B. taurus U2AF65 than with U2AF65 of E. caballus, C. lupus, M. mulatta, H. sapiens, and M. musculus. RT-PCR analysis showed that BMI U2AF2 was most highly expressed in the brain; moderately expressed in the spleen, lung, muscle, and skin; and weakly expressed in the liver, kidney, and ovary. Its expression was nearly silent in the spinal cord, nerve fiber, heart, stomach, pancreas, and intestine. Three microRNA target sites were predicted in the CDS of BMI U2AF2 messenger RNA. Our results establish a foundation for further insight into this swine gene.

  14. Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

    PubMed Central

    Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

    2014-01-01

    Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

  15. The Elongation Complex Components BRD4 and MLLT3/AF9 Are Transcriptional Coactivators of Nuclear Retinoid Receptors

    PubMed Central

    Flajollet, Sébastien; Rachez, Christophe; Ploton, Maheul; Schulz, Céline; Gallais, Rozenn; Métivier, Raphaël; Pawlak, Michal; Leray, Aymeric; Issulahi, Al Amine; Héliot, Laurent; Staels, Bart; Salbert, Gilles; Lefebvre, Philippe

    2013-01-01

    Nuclear all-trans retinoic acid receptors (RARs) initiate early transcriptional events which engage pluripotent cells to differentiate into specific lineages. RAR-controlled transactivation depends mostly on agonist-induced structural transitions in RAR C-terminus (AF-2), thus bridging coactivators or corepressors to chromatin, hence controlling preinitiation complex assembly. However, the contribution of other domains of RAR to its overall transcriptional activity remains poorly defined. A proteomic characterization of nuclear proteins interacting with RAR regions distinct from the AF-2 revealed unsuspected functional properties of the RAR N-terminus. Indeed, mass spectrometry fingerprinting identified the Bromodomain-containing protein 4 (BRD4) and ALL1-fused gene from chromosome 9 (AF9/MLLT3), known to associate with and regulates the activity of Positive Transcription Elongation Factor b (P-TEFb), as novel RAR coactivators. In addition to promoter sequences, RAR binds to genomic, transcribed regions of retinoid-regulated genes, in association with RNA polymerase II and as a function of P-TEFb activity. Knockdown of either AF9 or BRD4 expression affected differentially the neural differentiation of stem cell-like P19 cells. Clusters of retinoid-regulated genes were selectively dependent on BRD4 and/or AF9 expression, which correlated with RAR association to transcribed regions. Thus RAR establishes physical and functional links with components of the elongation complex, enabling the rapid retinoid-induced induction of genes required for neuronal differentiation. Our data thereby extends the previously known RAR interactome from classical transcriptional modulators to components of the elongation machinery, and unravel a functional role of RAR in transcriptional elongation. PMID:23762261

  16. Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4–MLL Fusion Protein

    PubMed Central

    Sabiani, Samaneh; Geppert, Tim; Engelbrecht, Christian; Kowarz, Eric; Schneider, Gisbert; Marschalek, Rolf

    2015-01-01

    We have recently demonstrated that Taspase1-mediated cleavage of the AF4–MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (αββα). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4–MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4–MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4–MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4–MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed. PMID:26137584

  17. Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hepatitis C

    PubMed Central

    Sabry, Dina; Elamir, Azza; Mahmoud, Rania Hosny; Abdelaziz, Ahmed Ali; Fathy, Wael

    2017-01-01

    Background The current study aimed at testing the effect of corticosteroid therapy on serum levels of interleukin-10 (IL-10) and IL-17 as well as lncRNA-AF085935 in patients of rheumatoid arthritis (RA) associated with hepatitis C virus (HCV) and evaluating the usefulness of using these parameters to predict the therapeutic efficacy of steroids in these patients. Methods Thirty healthy control subjects and 65 chronic HCV patients with RA were included in our study. Patients were subjected to clinical examination, abdominal ultrasound, and liver biopsy and received 6-methyl-prednisolone (PDN) 16 mg/day for 48 weeks. Blood samples were collected from all subjects and serum was separated to assess IL-10 and IL-17 by ELISA and HCV RNA and lncRNA-AF085935 by qRT-PCR. Results Our study revealed that there were significant increases in serum levels of IL-10, IL-17 and lncRNA-AF085935 in RA patients associated with HCV compared with healthy control subjects. Also there were significant increases in serum levels of IL-10 and HCV RNA and a significant decrease in serum level of IL-17 in patients after corticosteroid therapy, while lncRNA-AF085935 is not significantly changed. Conclusion LncRNA-AF085935 might be a useful candidate biomarker for the early detection of RA associated with HCV, providing potential new strategies for early screening and therapy of these patients. IL-17 is a non-invasive prognostic marker to predict the efficacy of corticosteroid therapy in RA patients associated with chronic hepatitis C. PMID:28392862

  18. Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers: insights from mathematical models and experimental correlates.

    PubMed

    Comtois, Philippe; Sakabe, Masao; Vigmond, Edward J; Munoz, Mauricio; Texier, Anne; Shiroshita-Takeshita, Akiko; Nattel, Stanley

    2008-10-01

    Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is a problem of growing proportions. Recent studies have increased interest in fast-unbinding Na(+) channel blockers like vernakalant (RSD1235) and ranolazine for AF therapy, but the mechanism of efficacy is poorly understood. To study how fast-unbinding I(Na) blockers affect AF, we developed realistic mathematical models of state-dependent Na(+) channel block, using a lidocaine model as a prototype, and studied the effects on simulated cholinergic AF in two- and three-dimensional atrial substrates. We then compared the results with in vivo effects of lidocaine on vagotonic AF in dogs. Lidocaine action was modeled with the Hondeghem-Katzung modulated-receptor theory and maximum affinity for activated Na(+) channels. Lidocaine produced frequency-dependent Na(+) channel blocking and conduction slowing effects and terminated AF in both two- and three-dimensional models with concentration-dependent efficacy (maximum approximately 89% at 60 microM). AF termination was not related to increases in wavelength, which tended to decrease with the drug, but rather to decreased source Na(+) current in the face of large ACh-sensitive K(+) current-related sinks, leading to the destabilization of primary generator rotors and a great reduction in wavebreak, which caused primary rotor annihilations in the absence of secondary rotors to resume generator activity. Lidocaine also reduced the variability and maximum values of the dominant frequency distribution during AF. Qualitatively similar results were obtained in vivo for lidocaine effects on vagal AF in dogs, with an efficacy of 86% at 2 mg/kg iv, as well as with simulations using the guarded-receptor model of lidocaine action. These results provide new insights into the mechanisms by which rapidly unbinding class I antiarrhythmic agents, a class including several novel compounds of considerable promise, terminate AF.

  19. U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs

    PubMed Central

    Jenkins, Jermaine L.; Agrawal, Anant A.; Gupta, Ankit; Green, Michael R.; Kielkopf, Clara L.

    2013-01-01

    Degenerate splice site sequences mark the intron boundaries of pre-mRNA transcripts in multicellular eukaryotes. The essential pre-mRNA splicing factor U2AF65 is faced with the paradoxical tasks of accurately targeting polypyrimidine (Py) tracts preceding 3′ splice sites while adapting to both cytidine and uridine nucleotides with nearly equivalent frequencies. To understand how U2AF65 recognizes degenerate Py tracts, we determined six crystal structures of human U2AF65 bound to cytidine-containing Py tracts. As deoxy-ribose backbones were required for co-crystallization with these Py tracts, we also determined two baseline structures of U2AF65 bound to the deoxy-uridine counterparts and compared the original, RNA-bound structure. Local structural changes suggest that the N-terminal RNA recognition motif 1 (RRM1) is more promiscuous for cytosine-containing Py tracts than the C-terminal RRM2. These structural differences between the RRMs were reinforced by the specificities of wild-type and site-directed mutant U2AF65 for region-dependent cytosine- and uracil-containing RNA sites. Small-angle X-ray scattering analyses further demonstrated that Py tract variations select distinct inter-RRM spacings from a pre-existing ensemble of U2AF65 conformations. Our results highlight both local and global conformational selection as a means for universal 3′ splice site recognition by U2AF65. PMID:23376934

  20. Flavonoid-enriched apple fraction AF4 induces cell cycle arrest, DNA topoisomerase II inhibition, and apoptosis in human liver cancer HepG2 cells.

    PubMed

    Sudan, Sudhanshu; Rupasinghe, H P Vasantha

    2014-01-01

    Apples are a major source of dietary phytochemicals such as flavonoids in the Western diet. Here we report anticancer properties and possible mechanism of action of apple flavonoid-enriched fraction (AF4) isolated from the peels of Northern Spy apples in human hepatocellular carcinoma cells, HepG2. Treatment with AF4 induced cell growth inhibition in HepG2 cells in time- and dose-dependent manner. Concentration of 50 μg/ml (50 μg total monomeric polyphenols/ml) AF4 was sufficient to induce a significant reduction in cell viability within 6 h of treatment (92%, P < 0.05) but had very low toxicity (minimum 4% to maximum 16%) on primary liver and lung cells, which was significantly lower than currently prescribed chemotherapy drug Sorafenib (minimum 29% to maximum 49%, P < 0.05). AF4 induced apoptosis in HepG2 cells within 6 h of treatment via activation of caspase-3. Cell cycle analysis via flow-cytometer showed that AF4 induced G2/M phase arrest. Further, results showed that AF4 acts as a strong DNA topoisomerase II catalytic inhibitor, which may be a plausible reason to drive the cells to apoptosis. Overall, our data suggests that AF4 possesses a significantly stronger antiproliferative and specific action than Sorafenib in vitro and is a potential natural chemotherapy agent for treatment of liver cancer.

  1. Photon and electron absorbed fractions calculated from a new tomographic rat model

    NASA Astrophysics Data System (ADS)

    Peixoto, P. H. R.; Vieira, J. W.; Yoriyaz, H.; Lima, F. R. A.

    2008-10-01

    This paper describes the development of a tomographic model of a rat developed using CT images of an adult male Wistar rat for radiation transport studies. It also presents calculations of absorbed fractions (AFs) under internal photon and electron sources using this rat model and the Monte Carlo code MCNP. All data related to the developed phantom were made available for the scientific community as well as the MCNP inputs prepared for AF calculations in that phantom and also all estimated AF values, which could be used to obtain absorbed dose estimates—following the MIRD methodology—in rats similar in size to the presently developed model. Comparison between the rat model developed in this study and that published by Stabin et al (2006 J. Nucl. Med. 47 655) for a 248 g Sprague-Dawley rat, as well as between the estimated AF values for both models, has been presented.

  2. Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

    PubMed

    Lowres, Nicole; Neubeck, Lis; Salkeld, Glenn; Krass, Ines; McLachlan, Andrew J; Redfern, Julie; Bennett, Alexandra A; Briffa, Tom; Bauman, Adrian; Martinez, Carlos; Wallenhorst, Christopher; Lau, Jerrett K; Brieger, David B; Sy, Raymond W; Freedman, S Ben

    2014-06-01

    Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.

  3. Insecticidal activity of Vip3Aa, Vip3Ad, Vip3Ae, and Vip3Af from Bacillus thuringiensis against lepidopteran corn pests.

    PubMed

    Hernández-Martínez, Patricia; Hernández-Rodríguez, Carmen Sara; Rie, Jeroen Van; Escriche, Baltasar; Ferré, Juan

    2013-05-01

    Vip3Aa, Vip3Ad, Vip3Ae, and Vip3Af proteins from Bacillus thuringiensis were tested for their toxicity against Spodoptera frugiperda and Agrotis ipsilon. Vip3Ad was non-toxic to the two species. Vip3Ae and Vip3Af were significantly more toxic than Vip3Aa against S. frugiperda, both as protoxins and as toxins. Against A. ipsilon, Vip3Ae protoxin was more toxic than Vip3Aa and Vip3Af protoxins. Purification by metal-chelate affinity chromatography significantly affected Vip3Ae toxicity against the two insect species.

  4. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity.

    PubMed Central

    Durand, B; Saunders, M; Gaudon, C; Roy, B; Losson, R; Chambon, P

    1994-01-01

    A motif essential for the transcriptional activation function 2 (AF-2) present in the E region of retinoic acid receptor (RAR) alpha and 9-cis retinoic acid receptor (RXR) alpha has been characterized as an amphipathic alpha-helix whose main features are conserved between transcriptionally active members of the nuclear receptor superfamily. This conserved motif, which can activate autonomously in the absence of ligand in animal and yeast cells, can be swapped between nuclear receptors without affecting the ligand dependency for activation of transcription, thus indicating that a ligand-dependent conformational change is necessary to reveal the AF-2 activation potential within the E region of the nuclear receptor. Interestingly, we show that the precise nature of the direct repeat response element to which RAR/RXR heterodimers are bound can affect the activity of the AF-2s of the heterodimeric partners, as well as the relative efficiency with which all-trans and 9-cis retinoic acids activate the RAR partner. Images PMID:7957103

  5. Performance Analysis of Beamforming in Fixed-gain AF Relay Networks with Asymmetric Correlated Fading Channels

    NASA Astrophysics Data System (ADS)

    Li, Min

    2014-07-01

    In this paper, the performance of beamforming (BF) for a dual-hop amplify-and-forward (AF) relay network, where the source and destination are each equipped with multiple antennas, is investigated. It is assumed that the source-relay and relay-destination channels experience mixed fading distributions, namely, correlated Nakagami-m/Rician and correlated Rician/Nakagami-m, respectively. By considering fixed-gain relaying, analytical expressions for outage probability (OP) and average symbol error rate (ASER) are derived in closed-form. Numerical results are presented to demonstrate the efficacy of our performance analysis, also illustrate the impact of channel correlation, fading severity, Rician factor and antenna configuration on the performance of the system. It is shown that the correlated Nakagami-m/Rician fading channel can achieve better performance than the correlated Rician/Nakagami-m fading channel with the increase of fading severity parameter, and the correlated Rician/Nakagami-m fading channel may outperform the correlated Nakagami-m/Rician fading channel by enlarging the Rician factor.

  6. Search for A-F Spectral type pulsating components in Algol-type eclipsing binary systems

    NASA Astrophysics Data System (ADS)

    Kim, S.-L.; Lee, J. W.; Kwon, S.-G.; Youn, J.-H.; Mkrtichian, D. E.; Kim, C.

    2003-07-01

    We present the results of a systematic search for pulsating components in Algol-type eclipsing binary systems. A total number of 14 eclipsing binaries with A-F spectral type primary components were observed for 22 nights. We confirmed small-amplitude oscillating features of a recently detected pulsator TW Dra, which has a pulsating period of 0.053 day and a semi-amplitude of about 5 mmag in B-passband. We discovered new pulsating components in two eclipsing binaries of RX Hya and AB Per. The primary component of RX Hya is pulsating with a dominant period of 0.052 day and a semi-amplitude of about 7 mmag. AB Per has also a pulsating component with a period of 0.196 day and a semi-amplitude of about 10 mmag in B-passband. We suggest that these two new pulsators are members of the newly introduced group of mass-accreting pulsating stars in semi-detached Algol-type eclipsing binary systems. Table 4 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/405/231

  7. INTERPRETATION OF AT-LINE SPECTRA FROM AFS-2 BATCH #3 FERROUS SULFAMATE TREATMENT

    SciTech Connect

    Kyser, E.; O'Rourke, P.

    2013-12-10

    Spectra from the “at-line” spectrometer were obtained during the ferrous sulfamate (FS) valence adjustment step of AFS-2 Batch #3 on 9/18/2013. These spectra were analyzed by mathematical principal component regression (PCR) techniques to evaluate the effectiveness of this treatment. Despite the complications from Pu(IV), we conclude that all Pu(VI) was consumed during the FS treatment, and that by the end of the treatment, about 85% was as Pu(IV) and about 15% was as Pu(III). Due to the concerns about the “odd” shape of the Pu(IV) peak and the possibility of this behavior being observed in the future, a follow-up sample was sent to SRNL to investigate this further. Analysis of this sample confirmed the previous results and concluded that it “odd” shape was due to an intermediate acid concentration. Since the spectral evidence shows complete reduction of Pu(VI) we conclude that it is appropriate to proceed with processing of this the batch of feed solution for HB-Line including the complexation of the fluoride with aluminum nitrate.

  8. Joint Source-Relay Design for Full-Duplex MIMO AF Relay Systems

    NASA Astrophysics Data System (ADS)

    Shi, Qingjiang; Hong, Mingyi; Gao, Xiqi; Song, Enbin; Cai, Yunlong; Xu, Weiqiang

    2016-12-01

    The performance of full-duplex (FD) relay systems can be greatly impacted by the self-interference (SI) at relays. By exploiting multi-antenna in FD relay systems, the spectral efficiency of FD relay systems can be enhanced through spatial SI mitigation. This paper studies joint source transmit beamforming and relay processing to achieve rate maximization for FD MIMO amplify-and-forward (AF) relay systems with consideration of relay processing delay. The problem is difficult to solve due mainly to the SI constraint induced by the relay processing delay. In this paper, we first present a sufficient condition under which the relay amplification matrix has rank one structure. Then, for the case of rank one amplification matrix, the rate maximization problem is equivalently simplified into an unconstrained problem which can be locally solved using gradient ascent method. Next, we propose a penalty-based algorithmic framework, called P-BSUM, for a class of constrained optimization problems which have difficult equality constraints in addition to some convex constraints. By rewriting the rate maximization problem with a set of auxiliary variables, we apply the P-BSUM algorithm to the rate maximization problem in the general case. Finally, numerical results validate the efficiency of the proposed algorithms and show that the joint source-relay design approach under the rank one assumption could be strictly suboptimal as compared to the P-BSUM-based joint source-relay design approach.

  9. Dover AFB, Delaware Revised Uniform Summary of Surface Weather Observations (RUSSWO) Parts A-F.

    DTIC Science & Technology

    1981-10-16

    90. 92. 93.8 94.4 94 7 9497 94o8 94.9 95.0 95.0 95.0 95.1 95.* >oo 11. 75.1 86, 91.2 93.6 94* 95.3 95.6 95.6 95.7 95.8 95.9 95.9 95.9 95, 9 95.9...BRANCH uI AUFTAC PSYCHROMETRIC SUMMARY ! A. EATHCR SERVICE/MAC 1 7 7 LOVER AF3 Or 70,73-81 FEE STATION STATION NAkE Ytms MONTe PAGE I nb ~iJ-CS( ~OtAS 4L...30 31(IN.H;) B AR OMET R I C P RE S S URE ( NB ) 100 150 600 650 900 950 1000 1050 (O1) II -I’ g 5 1 I I F P R E S 5 U R E A L T I T U D E (10 0 O’S FT

  10. High temperature dielectric properties of Apical, Kapton, Peek, Teflon AF, and Upilex polymers

    NASA Technical Reports Server (NTRS)

    Hammoud, A. N.; Baumann, E. D.; Overton, E.; Myers, I. T.; Suthar, J. L.; Khachen, W.; Laghari, J. R.

    1992-01-01

    Reliable lightweight systems capable of providing electrical power at the magawatt level are a requirement for future manned space exploration missions. This can be achieved by the development of high temperature insulating materials which are not only capable of surviving the hostile space environment but can contribute to reducing the mass and weight of the heat rejection system. In this work, Apical, Upilex, Kapton, Teflon AF, and Peek polymers are characterized for AC and DC dielectric breakdown in air and in silicone oil at temperatures up to 250 C. The materials are also tested in terms of their dielectric constant and dissipation factor at high temperatures with an electrical stress of 60 Hz, 200 V/mil present. The effects of thermal aging on the properties of the films are determined after 15 hours of exposure to 200 and 250 C, each. The results obtained are discussed and conclusions are made concerning the suitability of these dielectrics for use in capacitors and cable insulations in high temperature environments.

  11. AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription

    PubMed Central

    Okuda, Hiroshi; Kanai, Akinori; Ito, Shinji; Matsui, Hirotaka; Yokoyama, Akihiko

    2015-01-01

    Gene rearrangements generate MLL fusion genes, which can lead to aggressive leukemia. In most cases, MLL fuses with a gene encoding a component of the AEP (AF4 family/ENL family/P-TEFb) coactivator complex. MLL–AEP fusion proteins constitutively activate their target genes to immortalize haematopoietic progenitors. Here we show that AEP and MLL–AEP fusion proteins activate transcription through selectivity factor 1 (SL1), a core component of the pre-initiation complex (PIC) of RNA polymerase I (RNAP1). The pSER domain of AF4 family proteins associates with SL1 on chromatin and loads TATA-binding protein (TBP) onto the promoter to initiate RNA polymerase II (RNAP2)-dependent transcription. These results reveal a previously unknown transcription initiation mechanism involving AEP and a role for SL1 as a TBP-loading factor in RNAP2-dependent gene activation. PMID:26593443

  12. Tinian Island Nas, Mariana Islands. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1973-05-25

    unlimited distribution of this report to the public at large, or by DDC to the National Technical Information Service (NTIS). a technical report has be...OBSOLETE DATA PROCESSING RRANCH ETAC/USAF SURFACE WINDS 2 AIR WEATER SERVICE /MAC PERCENTAGE FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY... Service ( MAC ) REVISED UNIFORM SUMMARY OF SURF6CE WEATHER OBSERVATION5 TINIAN NAS MARIANA IS WBAN #41413 N 150 0 E 145 38 ELEV 250 FT WMO# PARTS A-F

  13. An Updated Version of the U.S. Air Force Multi-Attribute Task Battery (AF-MATB)

    DTIC Science & Technology

    2014-08-01

    assessing human performance in a controlled multitask environment. The most recent release of AF-MATB contains numerous improvements and additions...Strategic Behavior, MATB, Multitasking , Task Battery, Simulator, Multi-Attribute Task Battery, Automation 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...performance and multitasking strategy. As a result, a specific Information Throughput (IT) Mode was designed to customize the task to fit the Human

  14. Dianthosaponins A-F, triterpene saponins, flavonoid glycoside, aromatic amide glucoside and γ-pyrone glucoside from Dianthus japonicus.

    PubMed

    Nakano, Takahiro; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2011-01-01

    From aerial parts of Dianthus japonicus, six new and seven known oleanane-type triterpene saponins were isolated. The structures of the new saponins, named dianthosaponins A-F, were elucidated by means of high resolution mass spectrometry, and extensive inspection of one- and two-dimensional NMR spectroscopic data. A new C-glycosyl flavone, a glycosidic derivative of anthranilic acid amide and a maltol glucoside were also isolated.

  15. Environmental Assessment for Clear AFS Grid Tie-in and Heat Plant, Clear Air Force Station, Alaska

    DTIC Science & Technology

    2013-07-01

    Alaska Administrative Code AAAQS Alaska ambient air quality standards ACM asbestos -containing material ADEC Alaska Department of Environmental...maintenance activities. While asbestos or lead based paint may be encountered during the expansion of the existing mechanical rooms and within the...AFS July 2013 13 products. All work would be done in compliance with Federal and State regulations as well as the OSHA Asbestos Standard (29 CFR

  16. A spent SRB used on STS-87 is lifted in a hoisting slip in Hangar AF at CCAS

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is lifted in a hoisting slip in the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  17. The SRB recovery ship Liberty Star reenters the Hangar AF area at CCAS with a spent SRB used on STS-

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Seen carrying a spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is the solid rocket booster recovery ship Liberty Star as it reenters the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  18. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists.

    PubMed

    Fitzmaurice, David A; Accetta, Gabriele; Haas, Sylvia; Kayani, Gloria; Lucas Luciardi, Hector; Misselwitz, Frank; Pieper, Karen; Ten Cate, Hugo; Turpie, Alexander G G; Kakkar, Ajay K

    2016-08-01

    Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably.

  19. Stroke prevention in atrial fibrillation and ‘real world’ adherence to guidelines in the Balkan Region: The BALKAN-AF Survey

    PubMed Central

    Potpara, Tatjana S.; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S.; Polovina, Marija M.; Petranov, Stanislav L.; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y. H.; Potpara, Tatjana S.; Polovina, Marija; Milanov, Srdjan; Pavlovic, Marija; Petrovic, Marijana; Simovic, Stefan; Mitic, Gorana; Milanov, Marko; Savic, Jelena; Gnip, Sanja; Radovic, Pavica; Markovic, Snezana; Koncarevic, Ivana; Gavrilovic, Jelena; Acimovic, Tijana; Djikic, Dijana; Malic, Semir; Hodzic, Jusuf; Stojanovic, Milovan; Ilic, Marina Deljanin; Zlatar, Milan; Matic, Dragan; Lazic, Snezana; Peric, Vladan; Markovic, Sanja; Kovacevic, Snezana; Arandjelovic, Aleksandra; Asanin, Milika; Zdravkovic, Marija; Dan, Gheorghe-Andrei; Breha, Anca; Dan, Anca Rodica; Musetescu, Rodica; Popescu, Mircea Ioachim; Badila, Elisabeta; Georgescu, Catalina Arsenescu; Pop, Sorina; Popescu, Raluca; Neamtu, Simina; Oancea, Floriana; Trendafilova, Elina; Dimitrova, Elena; Goshev, Evgenii; Velichkova, Anna; Petranov, Stanislav; Kamenova, Delyana; Kamenova, Penka; Elefterova, Svetoslava; Shterev, Valentin; Zekova, Maria; Diukiandzhieva, Stela; Dimitrov, Boiko; Sotirov, Tihomir; Simeonova, Valentina; Drianovska, Dimitrina; Boiadzhieva, Liliya Ivanova Vasileva; Buchukova, Darina; Goda, Artan; Paparisto, Vilma; Gjergo, Hortensia; Mijo, Alma; Shirka, Ervina; Gjini, Viktor; Ekmekciu, Uliks; Refatllari, Ina; Kusljugic, Zumreta; Loncar, Daniela; Mrsic, Denis; Tulumovic, Hazim; Pojskic, Belma; Sijamija, Alma; Bijedic, Amira; Karamujic, Indira; Bijedic, Irma; Halilovic, Sanela; Sokolovic, Sekib; Manola, Sime; Zeljkovic, Ivan; Pavlovic, Nikola; Radeljic, Vjekoslav; Brusich, Sandro; Anic, Ante; Jeric, Melita; Pekic, Petar; Milas, Kresimir; Music, Ljilja; Bulatovic, Nebojsa; Nenezic, Ana; Asanovic, Dijana

    2016-01-01

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary ‘real-world’ AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the ‘truly low-risk’ patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region. PMID:26869284

  20. SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice

    PubMed Central

    Börjesson, Anna E.; Farman, Helen H.; Movérare-Skrtic, Sofia; Engdahl, Cecilia; Antal, Maria Cristina; Koskela, Antti; Tuukkanen, Juha; Carlsten, Hans; Krust, Andrée; Chambon, Pierre; Sjögren, Klara; Lagerquist, Marie K.; Windahl, Sara H.

    2016-01-01

    The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-10) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-10 mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis. PMID:27048997

  1. Predictors for Stroke and Death in Non-Anticoagulated Asian Patients with Atrial Fibrillation: The Fushimi AF Registry

    PubMed Central

    Hamatani, Yasuhiro; Yamashita, Yugo; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru

    2015-01-01

    Background Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in ‘real-world’ AF patients are limited, especially from large prospective Asian cohorts. Methods The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for ‘death, stroke, and systemic embolism (SE)’ during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline. Results The mean age was 73.1 ± 12.5 years, and 673 (44%) patients were female. The mean CHADS2 and CHA2DS2-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24–2.29), underweight (body mass index <18.5 kg/m2) (HR: 1.71, 95% CI: 1.25–2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25–2.30), heart failure (HR: 1.59, 95% CI: 1.17–2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16–2.02), and anemia (HR: 2.41, 95% CI: 1.78–3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry. Conclusions Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients. PMID:26540107

  2. Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

    PubMed Central

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-01-01

    Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. PMID:26501309

  3. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR).

    PubMed

    Weber, Axel; Taube, Sylvia; Zur Stadt, Udo; Horstmann, Martin; Krohn, Knut; Bradtke, Jutta; Teigler-Schlegel, Andrea; Leiblein, Sabine; Christiansen, Holger

    2012-11-09

    The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available.

  4. U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-mRNA 3' End Formation.

    PubMed

    Park, Sung Mi; Ou, Jianhong; Chamberlain, Lynn; Simone, Tessa M; Yang, Huan; Virbasius, Ching-Man; Ali, Abdullah M; Zhu, Lihua Julie; Mukherjee, Siddhartha; Raza, Azra; Green, Michael R

    2016-05-19

    Recurrent mutations in the splicing factor U2AF35 are found in several cancers and myelodysplastic syndrome (MDS). How oncogenic U2AF35 mutants promote transformation remains to be determined. Here we derive cell lines transformed by the oncogenic U2AF35(S34F) mutant and identify aberrantly processed pre-mRNAs by deep sequencing. We find that in U2AF35(S34F)-transformed cells the autophagy-related factor 7 (Atg7) pre-mRNA is abnormally processed, which unexpectedly is not due to altered splicing but rather selection of a distal cleavage and polyadenylation (CP) site. This longer Atg7 mRNA is translated inefficiently, leading to decreased ATG7 levels and an autophagy defect that predisposes cells to secondary mutations, resulting in transformation. MDS and acute myeloid leukemia patient samples harboring U2AF35(S34F) have a similar increased use of the ATG7 distal CP site, and previous studies have shown that mice with hematopoietic cells lacking Atg7 develop an MDS-like syndrome. Collectively, our results reveal a basis for U2AF35(S34F) oncogenic activity.

  5. Computational fluid dynamics modelling of left valvular heart diseases during atrial fibrillation

    PubMed Central

    Saglietto, Andrea; Gaita, Fiorenzo; Ridolfi, Luca; Anselmino, Matteo

    2016-01-01

    Background: Although atrial fibrillation (AF), a common arrhythmia, frequently presents in patients with underlying valvular disease, its hemodynamic contributions are not fully understood. The present work aimed to computationally study how physical conditions imposed by pathologic valvular anatomy act on AF hemodynamics. Methods: We simulated AF with different severity grades of left-sided valvular diseases and compared the cardiovascular effects that they exert during AF, compared to lone AF. The fluid dynamics model used here has been recently validated for lone AF and relies on a lumped parameterization of the four heart chambers, together with the systemic and pulmonary circulation. The AF modelling involves: (i) irregular, uncorrelated and faster heart rate; (ii) atrial contractility dysfunction. Three different grades of severity (mild, moderate, severe) were analyzed for each of the four valvulopathies (AS, aortic stenosis, MS, mitral stenosis, AR, aortic regurgitation, MR, mitral regurgitation), by varying–through the valve opening angle–the valve area. Results: Regurgitation was hemodynamically more relevant than stenosis, as the latter led to inefficient cardiac flow, while the former introduced more drastic fluid dynamics variation. Moreover, mitral valvulopathies were more significant than aortic ones. In case of aortic valve diseases, proper mitral functioning damps out changes at atrial and pulmonary levels. In the case of mitral valvulopathy, the mitral valve lost its regulating capability, thus hemodynamic variations almost equally affected regions upstream and downstream of the valve. In particular, the present study revealed that both mitral and aortic regurgitation strongly affect hemodynamics, followed by mitral stenosis, while aortic stenosis has the least impact among the analyzed valvular diseases. Discussion: The proposed approach can provide new mechanistic insights as to which valvular pathologies merit more aggressive treatment of

  6. Mechanisms of stochastic onset and termination of atrial fibrillation studied with a cellular automaton model

    PubMed Central

    2017-01-01

    Mathematical models of cardiac electrical excitation are increasingly complex, with multiscale models seeking to represent and bridge physiological behaviours across temporal and spatial scales. The increasing complexity of these models makes it computationally expensive to both evaluate long term (more than 60 s) behaviour and determine sensitivity of model outputs to inputs. This is particularly relevant in models of atrial fibrillation (AF), where individual episodes last from seconds to days, and interepisode waiting times can be minutes to months. Potential mechanisms of transition between sinus rhythm and AF have been identified but are not well understood, and it is difficult to simulate AF for long periods of time using state-of-the-art models. In this study, we implemented a Moe-type cellular automaton on a novel, topologically equivalent surface geometry of the left atrium. We used the model to simulate stochastic initiation and spontaneous termination of AF, arising from bursts of spontaneous activation near pulmonary veins. The simplified representation of atrial electrical activity reduced computational cost, and so permitted us to investigate AF mechanisms in a probabilistic setting. We computed large numbers (approx. 105) of sample paths of the model, to infer stochastic initiation and termination rates of AF episodes using different model parameters. By generating statistical distributions of model outputs, we demonstrated how to propagate uncertainties of inputs within our microscopic level model up to a macroscopic level. Lastly, we investigated spontaneous termination in the model and found a complex dependence on its past AF trajectory, the mechanism of which merits future investigation. PMID:28356539

  7. Second-Hand Smoke Increases Bronchial Hyperreactivity and Eosinophilia in a Murine Model of Allergic Aspergillosis

    PubMed Central

    Seymour, Brian W. P.; Schelegle, Edward S.; Pinkerton, Kent E.; Friebertshauser, Kathleen E.; Peake, Janice L.; Kurup, Viswanath P.; Coffman, Robert L.; Gershwin, Laurel J.

    2003-01-01

    Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af) cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS) on a murine model of allergic bronchopulmonary aspergillosis (ABPA). BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-γ indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia. PMID:14575156

  8. Second-hand smoke increases bronchial hyperreactivity and eosinophilia in a murine model of allergic aspergillosis.

    PubMed

    Seymour, Brian W P; Schelegle, Edward S; Pinkerton, Kent E; Friebertshauser, Kathleen E; Peake, Janice L; Kurup, Viswanath P; Coffman, Robert L; Gershwin, Laurel J

    2003-03-01

    Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af) cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS) on a murine model of allergic bronchopulmonary aspergillosis (ABPA). BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-gamma indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia.

  9. Morphometric evaluation of the Afşin-Elbistan lignite basin using kernel density estimation and Getis-Ord's statistics of DEM derived indices, SE Turkey

    NASA Astrophysics Data System (ADS)

    Sarp, Gulcan; Duzgun, Sebnem

    2015-11-01

    A morphometric analysis of river network, basins and relief using geomorphic indices and geostatistical analyses of Digital Elevation Model (DEM) are useful tools for discussing the morphometric evolution of the basin area. In this study, three different indices including valley floor width to height ratio (Vf), stream gradient (SL), and stream sinuosity were applied to Afşin-Elbistan lignite basin to test the imprints of tectonic activity. Perturbations of these indices are usually indicative of differences in the resistance of outcropping lithological units to erosion and active faulting. To map the clusters of high and low indices values, the Kernel density estimation (K) and the Getis-Ord Gi∗ statistics were applied to the DEM-derived indices. The K method and Gi∗ statistic highlighting hot spots and cold spots of the SL index, the stream sinuosity and the Vf index values helped to identify the relative tectonic activity of the basin area. The results indicated that the estimation by the K and Gi∗ including three conceptualization of spatial relationships (CSR) for hot spots (percent volume contours 50 and 95 categorized as high and low respectively) yielded almost similar results in regions of high tectonic activity and low tectonic activity. According to the K and Getis-Ord Gi∗ statistics, the northern, northwestern and southern parts of the basin indicates a high tectonic activity. On the other hand, low elevation plain in the central part of the basin area shows a relatively low tectonic activity.

  10. [Psychometric analysis of the AF5 multidimensional scale of self-concept in a sample of adolescents and adults in Catalonia].

    PubMed

    Malo Cerrato, Sara; Bataller Sallent, Sílvia; Casas Aznar, Ferran; Gras Pérez, Ma Eugenia; González Carrasco, Mònica

    2011-11-01

    The aim of this study is to carry out a psychometric study of the AF5 scale in a sample of 4.825 Catalan subjects from 11 to 63 years-old. They are students from secondary compulsory education (ESO), from high school, middle-level vocational training (CFGM) and from the university. Using a principal component analysis (PCA) the theoretical validity of the components is established and the reliability of the instrument is also analyzed. Differential analyses are performed by gender and normative group using a 2 x 6 factorial design. The normative group variable includes the different levels classified into 6 sub-groups: university, post-compulsory secondary education (high school and CFGM), 4th of ESO, 3rd of ESO, 2nd of ESO and 1st of ESO. The results indicate that the reliability of the Catalan version of the scale is similar to the original scale. The factorial structure also fits with the original model established beforehand. Significant differences by normative group in the four components of self-concept explored (social, family, academic/occupational and physical) are observed. By gender, significant differences appear in the component of physical self-concept, academic and social but not in the family component.

  11. Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

    PubMed

    Spencer, Ryan J; Amerena, John V

    2015-12-01

    Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

  12. Adsorption/desorption phenomena on pure and Teflon AF-coated titania surfaces studied by dynamic contact angle analysis.

    PubMed

    Rupp, F; Axmann, D; Ziegler, C; Geis-Gerstorfer, J

    2002-12-15

    As a result of inflammatory processes, plaque formation on dental titanium implants often leads to clinically pathogenic situations. This special biofilm formation on (bio)materials in contact with saliva is initiated by ionic and protein interactions. In this interfacial process, albumin becomes a main constituent of dental pellicle. Interfacial reactions change the surface characteristics. They determine the following steps of macromolecular adsorption and bacterial adhesion. This work focuses on the dynamic contact angle analysis (DCA), which is a tool for online measurements of dynamic changes of wettability without disturbing the interface during detection. Repeatability of the DCA method has been assessed according to the Bland and Altman method. The kinetics and equilibrium data of shifts in the wetting tension hysteresis indicate ionic influences at the titanium/bovine serum albumin (BSA) interface: the Ca-mediated increase of the BSA adsorption on titanium and the adsorption maximum at the isoelectric point (IEP) of BSA. Ti was surface modified by Teflon AF polymeric coatings. The result of the assessment gives reason to consider Teflon AF as a reference material for DCA repeatability studies. This surface modification caused drastic changes in the dynamic interfacial reactions. Shifts in the wetting tensions during DCA adsorption-desorption experiments clearly demonstrated the partially irreversible adsorption of BSA on Teflon AF. In contrast, reversible adsorption behavior was detected on pure Ti surfaces. These findings strengthen the hypothesis that the analysis of dynamic changes in wetting tension and wetting tension hysteresis is a sensitive analytical method for the detection of dynamic interfacial changes at biomaterial/biosystem interfaces during the initial steps of biofilm formation.

  13. Single-unit activity during natural vision: diversity, consistency, and spatial sensitivity among AF face patch neurons.

    PubMed

    McMahon, David B T; Russ, Brian E; Elnaiem, Heba D; Kurnikova, Anastasia I; Leopold, David A

    2015-04-08

    Several visual areas within the STS of the macaque brain respond strongly to faces and other biological stimuli. Determining the principles that govern neural responses in this region has proven challenging, due in part to the inherently complex stimulus domain of dynamic biological stimuli that are not captured by an easily parameterized stimulus set. Here we investigated neural responses in one fMRI-defined face patch in the anterior fundus (AF) of the STS while macaques freely view complex videos rich with natural social content. Longitudinal single-unit recordings allowed for the accumulation of each neuron's responses to repeated video presentations across sessions. We found that individual neurons, while diverse in their response patterns, were consistently and deterministically driven by the video content. We used principal component analysis to compute a family of eigenneurons, which summarized 24% of the shared population activity in the first two components. We found that the most prominent component of AF activity reflected an interaction between visible body region and scene layout. Close-up shots of faces elicited the strongest neural responses, whereas far away shots of faces or close-up shots of hindquarters elicited weak or inhibitory responses. Sensitivity to the apparent proximity of faces was also observed in gamma band local field potential. This category-selective sensitivity to spatial scale, together with the known exchange of anatomical projections of this area with regions involved in visuospatial analysis, suggests that the AF face patch may be specialized in aspects of face perception that pertain to the layout of a social scene.

  14. Progress Report on Activities in Support of Composite Repair Engineering Development Program Tasks AF, AH and AI

    DTIC Science & Technology

    2006-11-01

    Task AF Designation Aluminium Alloy Surface Preparation GBSP 7075T76UC Bare 7075-T76 Scotchbrite abrade, solvent clean, grit-blast, 1% aqueous epoxy...silane, BR-127 prime GBSNP 7075T76UC Bare 7075-T76 Scotchbrite abrade, solvent clean, grit-blast, 1% aqueous epoxy silane GBSP 7075T6C Clad 7075-T76...Cohesive Failure (%) Specimen 1 2 3 4 5 Average GBSP 7075T76UC 100 85 90 90 95 92.0 GBSNP 7075T76UC 94 94 98 100 100 97.2 GBSP 7075T6C 30 40 50 35 20 35

  15. U-Tapao RTNAS, Thailand. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1973-10-26

    to unlimited distribution of this report to the public at large, or by DTIC to the National Technical Information Service (NTIS). This technical...Force Environmental Technical App1. Center Scott AFB IL 62225 ,bs~yfR ffoFFICE NAME AND ADDRESS 12. REPORT DATE Air Weather Service (MAC) 3. 26 OCT... Service (MAC ) " REVISED NIFORM SUMMARY OF SURFACE WEA1HER OBSERVATIONS U-TAPAO RTNAS THAILAND WBAN* 41028 N 12 41 E 101 01 ELEV 69 FT VTLU WMO# PARTS A-F

  16. Volk FLD. Camp Douglas, Wisconsin. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1970-08-03

    REVISED’UNIFORWSUMMARY OF SURFACE WEATHER, OBSERVATION4S CAMP DOUGLAS WISCONSIN/VOLK FLO WSAN# 94930 N 43 56 W 90󈧔, ELEVi 925 FT. KVOK Wt ~O#I t PARTS A-F’ POR...Observations (RUSSW0)- Volk FLD,’ Camp Douglas , Wisconsin b PERORMINc ORG REPORT NUW ER 7. AUTHOR(o) CNTRACT OR GRANT HUMBER() 9, PERFORMING ORGANIZATION NAME...STATIONIFTI) KBAAOMEICR OAI 1 Volk Fld/Camp Douglas Wsconsin A Jur ,. Sep 66 N 43 56 W 90 16 925 Ancrold 13to19 1 No Change A Oct V Oct 68 No Change No

  17. Short Interspersed Nuclear Element (SINE) Sequences in the Genome of the Human Pathogenic Fungus Aspergillus fumigatus Af293

    PubMed Central

    Kanhayuwa, Lakkhana; Coutts, Robert H. A.

    2016-01-01

    Novel families of short interspersed nuclear element (SINE) sequences in the human pathogenic fungus Aspergillus fumigatus, clinical isolate Af293, were identified and categorised into tRNA-related and 5S rRNA-related SINEs. Eight predicted tRNA-related SINE families originating from different tRNAs, and nominated as AfuSINE2 sequences, contained target site duplications of short direct repeat sequences (4–14 bp) flanking the elements, an extended tRNA-unrelated region and typical features of RNA polymerase III promoter sequences. The elements ranged in size from 140–493 bp and were present in low copy number in the genome and five out of eight were actively transcribed. One putative tRNAArg-derived sequence, AfuSINE2-1a possessed a unique feature of repeated trinucleotide ACT residues at its 3’-terminus. This element was similar in sequence to the I-4_AO element found in A. oryzae and an I-1_AF long nuclear interspersed element-like sequence identified in A. fumigatus Af293. Families of 5S rRNA-related SINE sequences, nominated as AfuSINE3, were also identified and their 5'-5S rRNA-related regions show 50–65% and 60–75% similarity to respectively A. fumigatus 5S rRNAs and SINE3-1_AO found in A. oryzae. A. fumigatus Af293 contains five copies of AfuSINE3 sequences ranging in size from 259–343 bp and two out of five AfuSINE3 sequences were actively transcribed. Investigations on AfuSINE distribution in the fungal genome revealed that the elements are enriched in pericentromeric and subtelomeric regions and inserted within gene-rich regions. We also demonstrated that some, but not all, AfuSINE sequences are targeted by host RNA silencing mechanisms. Finally, we demonstrated that infection of the fungus with mycoviruses had no apparent effects on SINE activity. PMID:27736869

  18. AFS-2 FLOWSHEET MODIFICATIONS TO ADDRESS THE INGROWTH OF PU(VI) DURING METAL DISSOLUTION

    SciTech Connect

    Crapse, K.; Rudisill, T.; O'Rourke, P.; Kyser, E.

    2014-07-02

    In support of the Alternate Feed Stock Two (AFS-2) PuO{sub 2} production campaign, Savannah River National Laboratory (SRNL) conducted a series of experiments concluding that dissolving Pu metal at 95°C using a 6–10 M HNO{sub 3} solution containing 0.05–0.2 M KF and 0–2 g/L B could reduce the oxidation of Pu(IV) to Pu(VI) as compared to dissolving Pu metal under the same conditions but at or near the boiling temperature. This flowsheet was demonstrated by conducting Pu metal dissolutions at 95°C to ensure that PuO{sub 2} solids were not formed during the dissolution. These dissolution parameters can be used for dissolving both Aqueous Polishing (AP) and MOX Process (MP) specification materials. Preceding the studies reported herein, two batches of Pu metal were dissolved in the H-Canyon 6.1D dissolver to prepare feed solution for the AFS-2 PuO{sub 2} production campaign. While in storage, UV-visible spectra obtained from an at-line spectrophotometer indicated the presence of Pu(VI). Analysis of the solutions also showed the presence of Fe, Ni, and Cr. Oxidation of Pu(IV) produced during metal dissolution to Pu(VI) is a concern for anion exchange purification. Anion exchange requires Pu in the +4 oxidation state for formation of the anionic plutonium(IV) hexanitrato complex which absorbs onto the resin. The presence of Pu(VI) in the anion feed solution would require a valence adjustment step to prevent losses. In addition, the presence of Cr(VI) would result in absorption of chromate ion onto the resin and could limit the purification of Pu from Cr which may challenge the purity specification of the final PuO{sub 2} product. Initial experiments were performed to quantify the rate of oxidation of Pu(IV) to Pu(VI) (presumed to be facilitated by Cr(VI)) as functions of the HNO{sub 3} concentration and temperature in simulated dissolution solutions containing Cr, Fe, and Ni. In these simulated Pu dissolutions studies, lowering the temperature from near boiling

  19. Heterotopic Ossification Following Extremity Blast Amputation: An Animal Model in the Sprague Dawley Rat

    DTIC Science & Technology

    2012-10-01

    Joint Surg Am. 1985;67:400-3. 4 10. Brooker AF, Bowerman JW, Robinson RA, Riley LH Jr. Ectopic ossification following total 5 hip replacement ...progressiva (FOP). J Bone Miner Res. 2008;23:305-13. 3. Brooker AF, Bowerman JW, Robinson RA, Riley LH Jr. Ectopic ossification following total hip ...Optimal timing of preoperative radiation for prophylaxis against heterotopic ossification: a rabbit hip model. J Bone Joint Surg Am. 2005;87:366-73

  20. A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation

    PubMed Central

    Rosenberg, Michael A.; Das, Saumya; Pinzon, Pablo Quintero; Knight, Ashley C.; Sosnovik, David E.; Ellinor, Patrick T.; Rosenzweig, Anthony

    2012-01-01

    Cardiac hypertrophy is a major risk factor for the development of atrial fibrillation (AF). However, there are few animal models of AF associated with cardiac hypertrophy. In this study, we describe the in vivo electrophysiological characteristics and histopathology of a mouse model of cardiac hypertrophy that develops AF. Myostatin is a well-known negative regulator of skeletal muscle growth that was recently found to additionally regulate cardiac muscle growth. Using cardiac-specific expression of the inhibitory myostatin pro-peptide, we generated transgenic (TG) mice with dominant-negative regulation of MSTN (DN-MSTN). One line (DN-MSTN TG13) displayed ventricular hypertrophy, as well as spontaneous AF on the surface electrocardiogram (ECG), and was further evaluated. DN-MSTN TG13 had normal systolic function, but displayed atrial enlargement on cardiac MRI, as well as atrial fibrosis histologically. Baseline ECG revealed an increased P wave duration and QRS interval compared with wild-type littermate (WT) mice. Seven of 19 DN-MSTN TG13 mice had spontaneous or inducible AF, while none of the WT mice had atrial arrhythmias (p<0.05). Connexin40 (Cx40) was decreased in DN-MSTN TG13 mice, even in the absence of AF or significant atrial fibrosis, raising the possibility that MSTN signaling may play a role in Cx40 down-regulation and the development of AF in this mouse model. In conclusion, DN-MSTN TG13 mice represent a novel model of AF, in which molecular changes including an initial loss of Cx40 are noted prior to fibrosis and the development of atrial arrhythmias. PMID:23243484

  1. Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2)

    PubMed Central

    Lian, Wei; Jayapal, Karthik P; Charaniya, Salim; Mehra, Sarika; Glod, Frank; Kyung, Yun-Seung; Sherman, David H; Hu, Wei-Shou

    2008-01-01

    Background A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in Streptomyces coelicolor. Overexpression of afsS in S. coelicolor and certain related species causes antibiotic stimulatory effects in the host organism. Although recent studies have uncovered some of the upstream events activating this gene, the mechanisms through which this signal is relayed downstream leading to the eventual induction of antibiotic pathways remain unclear. Results In this study, we employed whole-genome DNA microarrays and quantitative PCRs to examine the transcriptome of an afsS disruption mutant that is completely deficient in the production of actinorhodin, a major S. coelicolor antibiotic. The production of undecylprodigiosin, another prominent antibiotic, was, however, perturbed only marginally in the mutant. Principal component analysis of temporal gene expression profiles identified two major gene classes each exhibiting a distinct coordinate differential expression pattern. Surprisingly, nearly 70% of the >117 differentially expressed genes were conspicuously associated with nutrient starvation response, particularly those of phosphate, nitrogen and sulfate. Furthermore, expression profiles of some transcriptional regulators including at least two sigma factors were perturbed in the mutant. In almost every case, the effect of afsS disruption was not observed until the onset of stationary phase. Conclusion Our data suggests a comprehensive role for S. coelicolor AfsS as a master regulator of both antibiotic synthesis and nutritional stress response, reminiscent of alternative sigma factors found in several bacteria. PMID:18230178

  2. Models of Defeat

    DTIC Science & Technology

    2002-04-01

    soldier, or a political entity. Every blob has a small set of primitive actions it can perform: PRIMITIVE- MOVE , APPLY-FORCE (push), and CHANGE- SHAPE. All...some distance from their center. The ball and spring model means that blobs are amoeba -like: they can assume almost any two dimensional shape without...tuning AFS, we have used it to simulate billiard balls, robots moving from room to room, rats scurrying about on a network of streets, and military

  3. Inhibitory and Apoptosis-Inducing Effects of Newcastle Disease Virus Strain AF2240 on Mammary Carcinoma Cell Line

    PubMed Central

    Keong, Yong Yoke; Othman, Fauziah

    2015-01-01

    Breast cancer is the malignant tumour that developed from cells of the breast and is the first leading cause of cancer death among women worldwide. Surgery, radiotherapy, and chemotherapy are the available treatments for breast cancer, but these were reported to have side effects. Newcastle disease virus (NDV) known as Avian paramyxovirus type-1 (APMV1) belongs to the genus Avulavirus in a family Paramyxoviridae. NDV is shown to be a promising anticancer agent, killing tumour cells while sparing normal cells unharmed. In this study, the oncolytic and cytotoxic activities of NDV AF2240 strain were evaluated on MDA-MB-231, human mammary carcinoma cell line, using MTT assay, and its inhibitory effects were further studied using proliferation and migration assays. Morphological and apoptotic-inducing effects of NDV on MD-MB-231 cells were observed using phase contrast and fluorescence microscopes. Detection of DNA fragmentation was done following terminal deoxyribonucleotide transferase-mediated Br-dUTP nick end labeling staining (TUNEL) assay, which confirmed that the mode of death was through apoptosis and was quantified by flow cytometry. Furthermore, analysis of cellular DNA content demonstrated that the virus caused an increase in the sub-G1 phase (apoptotic peak) of the cell cycle. It appears that NDV AF2240 strain is a potent anticancer agent that induced apoptosis in time-dependent manner. PMID:25821783

  4. Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

    PubMed Central

    Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

    2016-01-01

    Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are

  5. Optimization of In Vivo Confocal Autofluorescence Imaging of the Ocular Fundus in Mice and Its Application to Models of Human Retinal Degeneration

    PubMed Central

    Issa, Peter Charbel; Singh, Mandeep S.; Lipinski, Daniel M.; Chong, Ngaihang V.; Delori, François C.; Barnard, Alun R.; MacLaren, Robert E.

    2012-01-01

    Purpose. To investigate the feasibility and to identify sources of experimental variability of quantitative and qualitative fundus autofluorescence (AF) assessment in mice. Methods. Blue (488 nm) and near-infrared (790 nm) fundus AF imaging was performed in various mouse strains and disease models (129S2, C57Bl/6, Abca4−/−, C3H-Pde6brd1/rd1, Rho−/−, and BALB/c mice) using a commercially available scanning laser ophthalmoscope. Gray-level analysis was used to explore factors influencing fundus AF measurements. Results. A contact lens avoided cataract development and resulted in consistent fundus AF recordings. Fundus illumination and magnification were sensitive to changes of the camera position. Standardized adjustment of the recorded confocal plane and consideration of the pupil area allowed reproducible recording of fundus AF from the retinal pigment epithelium with an intersession coefficient of repeatability of ±22%. Photopigment bleaching occurred during the first 1.5 seconds of exposure to 488 nm blue light (∼10 mW/cm2), resulting in an increase of fundus AF. In addition, there was a slight decrease in fundus AF during prolonged blue light exposure. Fundus AF at 488 nm was low in animals with an absence of a normal visual cycle, and high in BALB/c and Abca4−/− mice. Degenerative alterations in Pde6brd1/rd1 and Rho−/− were reminiscent of findings in human retinal disease. Conclusions. Investigation of retinal phenotypes in mice is possible in vivo using standardized fundus AF imaging. Correlation with postmortem analysis is likely to lead to further understanding of human disease phenotypes and of retinal degenerations in general. Fundus AF imaging may be useful as an outcome measure in preclinical trials, such as for monitoring effects aimed at lowering lipofuscin accumulation in the retinal pigment epithelium. PMID:22169101

  6. Heterologous expression of metK1-sp and afsR-sp in Streptomyces venezuelae for the production of pikromycin.

    PubMed

    Maharjan, Sushila; Oh, Tae-Jin; Lee, Hei Chan; Sohng, Jae Kyung

    2008-09-01

    Two regulator genes, metK1-sp and afsR-sp, from Streptomyces peucetius ATCC 27952 were heterologously expressed in S. venezuelae ATCC 15439, to produce 14-membered pikromycin antibiotics. The production of pikromycin was increased by 1.6-fold and 2.6-fold by the expression of metK1-sp and afsR-sp, respectively. The overexpression of metK1-sp and afsR-sp in S. venezuelae stimulated the expression of the pathway-specific regulatory genes, pikD and ketosynthase, as demonstrated by RT-PCR. The elevated transcripts of the pikD and ketosynthase genes were consistent with the enhanced production of pikromycin.

  7. Methods for the development and assessment of atrial fibrillation and heart failure dog models

    PubMed Central

    Urban, Jon F; Gerhart, Renee L; Krzeszak, Jason R; Leet, Corey R; Lentz, Linnea R; McClay, Carolyn B

    2011-01-01

    Objective To report Medtronic experiences with the development of animal models for atrial fibrillation (AF) and chronic heart failure (CHF) using high-rate pacing for AF and microemboli for CHF. Methods For the AF model, an atrial lead was attached to a Medtronic Synergy™ neurostimulator, which was programmed to stimulate at 50 Hz in an on-off duty cycle. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and N-terminal pro brain natriuretic peptide (NT-proBNP) were assayed at select time points. For CHF model, a serial injection of 90 µm polystyrene microspheres at 62,400 beads/mL (Polybead, Polysciences, Inc.) was performed to induce global ischemia, either with weekly monitoring and embolization schedule (group 1, n = 25) or with biweekly monitoring and emboliation schedule (group 2, n = 36 ). Echocardiograms were used along with ventriculograms and magnetic resonance imaging scans weekly to assess cardiac function and ANP, BNP and NT-proBNP were monitored. Results For the AF model, the days to sustained AF for four animals following surgery were 7, 25, 21 and 19, respectively; For the CHF model, the days to meet CHF endpoints were 116 in group 1 and 89 in group 2. For both AF and CHF models, NT-proBNP correlated well with the development of disease states. Conclusion Our experience for the development and assessment of AF and CHF dog models may help researchers who are in search for animal model for assessing the safety and efficacy of a device-based therapy. PMID:22783299

  8. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.

    PubMed Central

    vom Baur, E; Zechel, C; Heery, D; Heine, M J; Garnier, J M; Vivat, V; Le Douarin, B; Gronemeyer, H; Chambon, P; Losson, R

    1996-01-01

    Using a yeast two-hybrid system we report the isolation of a novel mouse protein, mSUG1, that interacts with retinoic acid receptor alpha (RAR alpha) both in yeast cells and in vitro in a ligand- and AF-2 activating domain (AF-2 AD)-dependent manner and show that it is a structural and functional homologue of the essential yeast protein SUG1. mSUG1 also efficiently interacts with other nuclear receptors, including oestrogen (ER), thyroid hormone (TR), Vitamin D3 (VDR) and retinoid X (RXR) receptors. By comparing the interaction properties of these receptors with mSUG1 and TIF1, we demonstrate that: (i) RXR alpha efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER efficiently interact with mSUG1 and TIF1; (ii) the amphipathic alpha-helix core of the AF-2 AD is differentially involved in interactions of RAR alpha with mSUG1 and TIF1; (iii) the AF-2 AD cores of RAR alpha and ER are similarly involved in their interaction with TIF1, but not with mSUG1. Thus, the interaction interfaces between the different receptors and either mSUG1 or TIF1 may vary depending on the nature of the receptor and the putative mediator of its AF-2 function. We discuss the possibility that mSUG1 and TIF1 may mediate the transcriptional activity of the AF-2 of nuclear receptors through different mechanisms. Images PMID:8598193

  9. Effect of aerosols and NO2 concentration on ultraviolet actinic flux near Mexico City during MILAGRO: measurements and model calculations

    NASA Astrophysics Data System (ADS)

    Palancar, G. G.; Lefer, B. L.; Hall, S. R.; Shaw, W. J.; Corr, C. A.; Herndon, S. C.; Slusser, J. R.; Madronich, S.

    2012-08-01

    Urban air pollution absorbs and scatters solar ultraviolet (UV) radiation, and thus has a potentially large effect on tropospheric photochemical rates. We present the first detailed comparison between UV actinic fluxes (AF) measured in highly polluted conditions and simulated with the Tropospheric Ultraviolet-Visible (TUV) model. Measurements were made during the MILAGRO campaign near Mexico City in March 2006, at a ground-based station near Mexico City (the T1 supersite) and from the NSF/NCAR C-130 aircraft. At the surface, measured AF values are typically smaller than the model by up to 25% in the morning, 10% at noon, and 40% in the afternoon, for pollution-free and cloud-free conditions. When measurements of PBL height, NO2 concentration and aerosols optical properties are included in the model, the agreement improves to within ±10% in the morning and afternoon, and ±3% at noon. Based on daily averages, aerosols account for 67% and NO2 for 25% of AF reductions observed at the surface. Several overpasses from the C-130 aircraft provided the opportunity to examine the AF perturbations aloft, and also show better agreement with the model when aerosol and NO2 effects are included above and below the flight altitude. TUV model simulations show that the vertical structure of the actinic flux is sensitive to the choice of the aerosol single scattering albedo (SSA) at UV wavelengths. Typically, aerosols enhance AF above the PBL and reduce AF near the surface. However, for highly scattering aerosols (SSA > 0.95), enhancements can penetrate well into the PBL, while for strongly absorbing aerosols (SSA < 0.6) reductions in AF are computed in the free troposphere as well as in the PBL. Additional measurements of the SSA at these wavelengths are needed to better constrain the effect of aerosols on the vertical structure of the AF.

  10. Effect of aerosols and NO2 concentration on ultraviolet actinic flux near Mexico City during MILAGRO: measurements and model calculations

    NASA Astrophysics Data System (ADS)

    Palancar, G. G.; Lefer, B. L.; Hall, S. R.; Shaw, W. J.; Corr, C. A.; Herndon, S. C.; Slusser, J. R.; Madronich, S.

    2013-01-01

    Urban air pollution absorbs and scatters solar ultraviolet (UV) radiation, and thus has a potentially large effect on tropospheric photochemical rates. We present the first detailed comparison between actinic fluxes (AF) in the wavelength range 330-420 nm measured in highly polluted conditions and simulated with the Tropospheric Ultraviolet-Visible (TUV) model. Measurements were made during the MILAGRO campaign near Mexico City in March 2006, at a ground-based station near Mexico City (the T1 supersite) and from the NSF/NCAR C-130 aircraft. At the surface, measured AF values are typically smaller than the model by up to 25% in the morning, 10% at noon, and 40% in the afternoon, for pollution-free and cloud-free conditions. When measurements of PBL height, NO2 concentration and aerosols optical properties are included in the model, the agreement improves to within ±10% in the morning and afternoon, and ±3% at noon. Based on daily averages, aerosols account for 68% and NO2 for 25% of AF reductions observed at the surface. Several overpasses from the C-130 aircraft provided the opportunity to examine the AF perturbations aloft, and also show better agreement with the model when aerosol and NO2 effects are included above and below the flight altitude. TUV model simulations show that the vertical structure of the actinic flux is sensitive to the choice of the aerosol single scattering albedo (SSA) at UV wavelengths. Typically, aerosols enhance AF above the PBL and reduce AF near the surface. However, for highly scattering aerosols (SSA > 0.95), enhancements can penetrate well into the PBL, while for strongly absorbing aerosols (SSA < 0.6) reductions in AF are computed in the free troposphere as well as in the PBL. Additional measurements of the SSA at these wavelengths are needed to better constrain the effect of aerosols on the vertical structure of the AF.

  11. Variation of B1 gene and AF146527 repeat element copy numbers according to Toxoplasma gondii strains assessed using real-time quantitative PCR.

    PubMed

    Costa, Jean-Marc; Bretagne, Stéphane

    2012-04-01

    Using the multicopy B1 gene and AF146527 element for the amplification of Toxoplasma gondii DNA raises the issue of reliable quantification for clinical diagnosis. We applied relative quantification to reference strains using the single-copy P30 gene as a reference. According to the parasite type, the copy numbers for the B1 gene and AF146527 element were found to be 5 to 12 and 4 to 8 times lower than the previous estimations of 35 and 230 copies, respectively.

  12. Heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex demonstrated by the selective antagonist AF-DX 116

    SciTech Connect

    Bloom, J.W.; Halonen, M.; Seaver, N.A.; Yamamura, H.I.

    1987-07-27

    Recent studies have demonstrated that the majority of muscarinic receptors in rabbit peripheral lung homogenates bind pirenzepine with high affinity (putative M1 subtype). In experiments of AF-DX 116 inhibiting (TH)(-)quinuclidinyl benzilate or (TH)pirenzepine, the authors found similar inhibitory constants for AF-DX 116 binding in rat heart and rabbit peripheral lung that were 4-fold smaller (i.e. of higher affinity) than the inhibitory constant for rat cerebral cortex. This results demonstrates heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex. 20 references, 1 figure, 2 tables.

  13. Effects of Milk Yield, Feed Composition, and Feed Contamination with Aflatoxin B1 on the Aflatoxin M1 Concentration in Dairy Cows’ Milk Investigated Using Monte Carlo Simulation Modelling

    PubMed Central

    van der Fels-Klerx, H. J.; Camenzuli, Louise

    2016-01-01

    This study investigated the presence of aflatoxin M1 (AfM1) in dairy cows’ milk, given predefined scenarios for milk production, compound feed (CF) contamination with aflatoxin B1 (AfB1), and inclusion rates of ingredients, using Monte Carlo simulation modelling. The model simulated a typical dairy farm in the Netherlands. Six different scenarios were considered, based on two lactation and three CF composition scenarios. AfB1 contamination of the CF was based on results from the Dutch national monitoring programme for AfB1 in feed materials from 2000 until 2010. Monitoring data from feed materials used in CF production for dairy cattle in the Netherlands were used. Additionally, AfB1 contamination data from an incident in maize in 2013 were used. In each scenario, five different transfer equations of AfB1 from feed to AfM1 in the milk were used, and 1000 iterations were run for each scenario. The results showed that under these six scenarios, the weekly farm concentration of AfM1 in milk was above the EC threshold in less than 1% of the iterations, with all five transfer equations considered. However, this increased substantially in weeks when concentrations from the contaminated maize batch were included, and up to 28.5% of the iterations exceeded the EC threshold. It was also observed that an increase in the milk production had a minimal effect on the exceedance of the AfM1 threshold due to an apparent dilution effect. Feeding regimes, including the composition of CF and feeding roughages of dairy cows, should be carefully considered based on the potential AfM1 contamination of the farm’s milk. PMID:27735836

  14. Generalized internal model robust control for active front steering intervention

    NASA Astrophysics Data System (ADS)

    Wu, Jian; Zhao, Youqun; Ji, Xuewu; Liu, Yahui; Zhang, Lipeng

    2015-03-01

    Because of the tire nonlinearity and vehicle's parameters' uncertainties, robust control methods based on the worst cases, such as H ∞, µ synthesis, have been widely used in active front steering control, however, in order to guarantee the stability of active front steering system (AFS) controller, the robust control is at the cost of performance so that the robust controller is a little conservative and has low performance for AFS control. In this paper, a generalized internal model robust control (GIMC) that can overcome the contradiction between performance and stability is used in the AFS control. In GIMC, the Youla parameterization is used in an improved way. And GIMC controller includes two sections: a high performance controller designed for the nominal vehicle model and a robust controller compensating the vehicle parameters' uncertainties and some external disturbances. Simulations of double lane change (DLC) maneuver and that of braking on split- µ road are conducted to compare the performance and stability of the GIMC control, the nominal performance PID controller and the H ∞ controller. Simulation results show that the high nominal performance PID controller will be unstable under some extreme situations because of large vehicle's parameters variations, H ∞ controller is conservative so that the performance is a little low, and only the GIMC controller overcomes the contradiction between performance and robustness, which can both ensure the stability of the AFS controller and guarantee the high performance of the AFS controller. Therefore, the GIMC method proposed for AFS can overcome some disadvantages of control methods used by current AFS system, that is, can solve the instability of PID or LQP control methods and the low performance of the standard H ∞ controller.

  15. The Spatiotemporal Stability of Dominant Frequency Sites in In-Silico Modeling of 3-Dimensional Left Atrial Mapping of Atrial Fibrillation

    PubMed Central

    Hwang, Minki; Song, Jun-Seop; Lee, Young-Seon; Joung, Boyoung; Pak, Hui-Nam

    2016-01-01

    Background We previously reported that stable rotors were observed in in-silico human atrial fibrillation (AF) models, and were well represented by dominant frequency (DF). We explored the spatiotemporal stability of DF sites in 3D-AF models imported from patient CT images of the left atrium (LA). Methods We integrated 3-D CT images of the LA obtained from ten patients with persistent AF (male 80%, 61.8 ± 13.5 years old) into an in-silico AF model. After induction, we obtained 6 seconds of AF simulation data for DF analyses in 30 second intervals (T1–T9). The LA was divided into ten sections. Spatiotemporal changes and variations in the temporal consistency of DF were evaluated at each section of the LA. The high DF area was defined as the area with the highest 10% DF. Results 1. There was no spatial consistency in the high DF distribution at each LA section during T1–T9 except in one patient (p = 0.027). 2. Coefficients of variation for the high DF area were highly different among the ten LA sections (p < 0.001), and they were significantly higher in the four pulmonary vein (PV) areas, the LA appendage, and the peri-mitral area than in the other LA sections (p < 0.001). 3. When we conducted virtual ablation of 10%, 15%, and 20% of the highest DF areas (n = 270 cases), AF was changed to atrial tachycardia (AT) or terminated at a rate of 40%, 57%, and 76%, respectively. Conclusions Spatiotemporal consistency of the DF area was observed in 10% of AF patients, and high DF areas were temporally variable. Virtual ablation of DF is moderately effective in AF termination and AF changing into AT. PMID:27459377

  16. Autofluorescence discrimination of metabolic fingerprint in nutritional and genetic fatty liver models.

    PubMed

    Croce, Anna C; Ferrigno, Andrea; Di Pasqua, Laura G; Berardo, Clarissa; Piccolini, Valeria Maria; Bertone, Vittorio; Bottiroli, Giovanni; Vairetti, Mariapia

    2016-11-01

    Liver tissue autofluorescence (AF) has been characterized in two models with a different potential to undergo disease progression to steatohepatitis: Wistar rats, administered with a methionine, choline deficient diet (MCD), and Zucker (fa/fa) rats, homozygous for a spontaneous mutation of leptin receptor. AF spectra were recorded from liver tissue cryostatic sections by microspectrofluorometry, under 366nm excitation. Curve fitting analysis was used to estimate the contribution of different endogenous fluorophores (EFs) to the overall AF emission: i) fluorescing fatty acids, a fraction of liver lipids up to now poorly considered and complicated to detect by conventional procedures; ii) lipofuscin-like lipopigments, biomarkers of oxidizing events; iii) NAD(P)H and flavins, biomarkers of energy metabolism and tissue redox state. AF data and biochemical correlates of hepatocellular injury resulted to depend more on rat strain than on intratissue bulk lipid or ROS levels, reflecting a different metabolic ability of the two models to counteract potentially harmful agents. AF analysis can thus be proposed for extensive applications ranging from experimental hepatology to the clinics. AF based diagnostic procedures are expected to help both the prediction of the risk of fatty liver disease progression and the prescreening of marginal organs to be recruited as donors for transplantation. A support is also foreseen in the advancement and personalization of strategies to ameliorate the donor organ preservation outcome and the follow up of therapeutic interventions.

  17. Modifications on A-F hardening rule to assess ratcheting response of materials and its interaction with fatigue damage under uniaxial stress cycles

    NASA Astrophysics Data System (ADS)

    Ahmadzadehrishehri, Gholamreza

    Ratcheting deformation is accumulated progressively over three distinct stages in materials undergoing asymmetrical cyclic stresses. The present thesis evaluates the triphasic ratcheting response of materials from two stand points: (i) Mechanistic approach at which stages of ratcheting progress over stress cycles was related to mechanistic parameters such as stress level, lifespan, mechanical properties and the softening/hardening response of materials. Mechanistic approach formulated in this thesis was employed to assess ratcheting strain over triphasic stages in various steel and copper alloys under uniaxial stress cycles. Good agreements were achieved between the predicted ratcheting strain values based on the proposed formulation and those of experimentally reported. (ii) Kinematic hardening rule approach at which the hardening rule was characterized by the yield surface translation mechanism and the corresponding plastic modulus calculated based on the consistency condition. Various cyclic plasticity models were employed to assess ratcheting response of materials under different loading conditions. The Armstrong-Frederick (A-F) hardening rule was taken as the backbone of ratcheting analysis developed in this thesis mainly due to less complexity and number of coefficients in the hardening rule as compared with other earlier developed hardening rules in the literature. To predict triphasic ratcheting strain over stress cycles, the A-F hardening rule has been further developed by means of new strain rate coefficients gamma 2 and delta. These coefficients improved the hardening rule capability to calibrate and control the rate of ratcheting over its progressive stages. The modified hardening formulation holds the coefficients of the hardening rule to control stress-strain hysteresis loops generated over stress cycles during ratcheting process plus the ratcheting rates over stages I, II, and III. These coefficients were calibrated and defined based on the applied

  18. A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells.

    PubMed

    Kotani, Ai; Ha, Daon; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2010-03-15

    MLL-AF4 acute lymphocytic leukemia has a poor prognosis, and the mechanisms by which these leukemias develop are not understood despite intensive research based on well-known concepts and methods. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate expression of target mRNA transcripts. We recently reported that ectopic expression of miR-128b together with miR-221, two of the miRNAs downregulated in MLL-AF4 ALL, restores glucocorticoid resistance through downregulation of the MLL-AF4 chimeric fusion proteins MLL-AF4 and AF4-MLL that are generated by chromosomal translocation t(4;11). Here we report the identification of new mutations in miR-128b in RS4;11 cells, derived from MLL-AF4 ALL patient. One novel mutation significantly reduces the processing of miR-128b. Finally, this base change occurs in a primary MLL-AF4 ALL sample as an acquired mutation. These results demonstrate that the novel mutation in miR-128b in MLL-AF4 ALL alters the processing of miR-128b and that the resultant downregulation of mature miR-128b contributes to glucocorticoid resistance through the failure to downregulate the fusion oncogenes.

  19. Environmental Aging of Scotch-Weld(TradeMark) AF-555M Structural Adhesive in Composite to Composite Bonds

    NASA Technical Reports Server (NTRS)

    Hou, Tan-Hung; Miner, Gilda A.; Lowther, Sharon E.; Connell, John W.; Baughman, James M.

    2010-01-01

    Fiber reinforced resin matrix composites have found increased usage in recent years. Due to the lack of service history of these relatively new material systems, their long-term aging performance is not well established. In this study, adhesive bonds were prepared by the secondary bonding of Scotch-Weld(TradeMark) AF-555M between pre-cured adherends comprised of T800H/3900-2 uni-directional laminate. The adherends were co-cured with wet peel-ply for surface preparation. Each bond-line of single-lap-shear (SLS) specimen was measured to determine thickness and inspected visually for voids. A three-year environmental aging plan for the SLS specimens at 82 C and 85% relative humidity was initiated. SLS strengths were measured for both controls and aged specimens at room temperature and 82 C. The aging results of strength retention and failure modes to date are reported.

  20. Selenium species determination in selenium-enriched pumpkin (Cucurbita pepo L.) seeds by HPLC-UV-HG-AFS.

    PubMed

    Smrkolj, Polona; Stibilj, Vekoslava; Kreft, Ivan; Kapolna, Emese

    2005-12-01

    Pumpkins were treated by spraying the leaves in the flowering period with a water solution containing 1.5 mg Se per liter in the form of Na2SeO4. The average total selenium content of seeds was found to be 0.19 microg g(-1) in nontreated pumpkins and 1.1 microg g(-1) in exposed ones. For speciation analysis, enzymatic hydrolysis with different amounts of Protease XIV was carried out. Under optimal conditions of enzymatic hydrolysis, 90% of the total selenium was found in soluble forms. Separation of species was performed using HPLC on anion and cation exchange columns and for detection UVHG-AFS was applied. In enzymatic hydrolysis extracts, the main fraction of selenium was bound as selenomethionine (SeMet), representing on average of 81 +/- 8% of the total Se content in the sample.

  1. Rubusuaviins A-F, monomeric and oligomeric ellagitannins from Chinese sweet tea and their alpha-amylase inhibitory activity.

    PubMed

    Li, Haizhou; Tanaka, Takashi; Zhang, Ying-Jun; Yang, Chong-Ren; Kouno, Isao

    2007-09-01

    Six new ellagitannins herein, rubusuaviins A-F, were isolated from the aqueous acetone extract of Chinese sweet tea (Tien-cha, dried leaves of Rubus suavissimus S. LEE) together with seven known tannins. Rubusuaviin A was characterized as 1-O-galloyl-2,3-O-(S)-HHDP-4,6-O-(S)-sanguisorboyl-beta-D-glucopyranose. Rubusuaviins B, C, and E are dimeric, trimeric, and tetrameric ellagitannins, respectively, in which the sanguisorboyl groups were connected ellagitannin units. Rubusuaviins D and F were desgalloyl derivatives of rubusuaviins C and E, respectively. The inhibition of alpha-amylase activity by rubusuaviins and related ellagitannins was compared. Ellagitannins with beta-galloyl groups at the glucose C-1 positions showed stronger inhibition compared with the alpha-galloyl and desgalloyl compounds. The molecular weight of these compounds was not important for the inhibition of alpha-amylase activity.

  2. Overtreatment and undertreatment with anticoagulation in relation to cardioversion of atrial fibrillation (the RHYTHM-AF study).

    PubMed

    Lip, Gregory Y H; Gitt, Anselm K; Le Heuzey, Jean-Yves; Bash, Lori D; Morabito, Christopher J; Bernhardt, Alexandra A; Sisk, Christine McCrary; Chazelle, François; Crijns, Harry J

    2014-02-01

    Antithrombotic therapy is central to the management of atrial fibrillation. This analysis from the RHYTHM-atrial fibrillation (RHYTHM-AF) registry explored the appropriateness of antithrombotic therapy in relation to stroke risk and atrial fibrillation duration in patients with atrial fibrillation. RHYTHM-AF, a prospective multinational registry, enrolled consecutive adult patients with atrial fibrillation considered for cardioversion. We compared the type of antithrombotic therapy administered at the time of cardioversion and at discharge with stroke risk ("high stroke risk" defined by CHA2DS2-VASc >1) and duration of atrial fibrillation (≤48 vs >48 hours or unknown duration). Of 2,972 patients who were cardioverted (34.5% through pharmacologic cardioversion [PCV] and 65.5% through electrical cardioversion [ECV]), 65% were at high risk of stroke and 30% presented with atrial fibrillation of >48-hour or unknown duration. At the time of PCV and ECV, 36% (n = 242) and 84% (n = 1,075) of high-risk patients, respectively, were taking vitamin K antagonists or heparin. At discharge, these rates increased to 62% (n = 414) and 93% (n = 1,191), respectively. Of all low-stroke risk patients with short-duration atrial fibrillation undergoing PCV (n = 260) and ECV (n = 111), 7% (n = 17) and 30% (n = 33), respectively, were taking vitamin K antagonists or heparin at the time of cardioversion. At discharge, these rates increased to 19% (n = 50) and 40% (n = 44), respectively. In conclusion, ECV was frequently performed under appropriate antithrombotic therapy for most high-risk patients with atrial fibrillation, whereas PCV was frequently performed without appropriate antithrombotic therapy. To enhance pericardioversion stroke prevention, cardioversion algorithms should focus less on the type of conversion and more on stroke risk factors and atrial fibrillation duration.

  3. RHYTHM-AF: design of an international registry on cardioversion of atrial fibrillation and characteristics of participating centers

    PubMed Central

    2012-01-01

    Background Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. Methods/design RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (±10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. Discussion A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve

  4. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18.

    PubMed Central

    Le Douarin, B; Zechel, C; Garnier, J M; Lutz, Y; Tora, L; Pierrat, P; Heery, D; Gronemeyer, H; Chambon, P; Losson, R

    1995-01-01

    Nuclear receptors (NRs) bound to response elements mediate the effects of cognate ligands on gene expression. Their ligand-dependent activation function, AF-2, presumably acts on the basal transcription machinery through intermediary proteins/mediators. We have isolated a mouse nuclear protein, TIF1, which enhances RXR and RAR AF-2 in yeast and interacts in a ligand-dependent manner with several NRs in yeast and mammalian cells, as well as in vitro. Remarkably, these interactions require the amino acids constituting the AF-2 activating domain conserved in all active NRs. Moreover, the oestrogen receptor (ER) AF-2 antagonist hydroxytamoxifen cannot promote ER-TIF1 interaction. We propose that TIF1, which contains several conserved domains found in transcriptional regulatory proteins, is a mediator of ligand-dependent AF-2. Interestingly, the TIF1 N-terminal moiety is fused to B-raf in the mouse oncoprotein T18. Images PMID:7744009

  5. OmniGen-AF alters rectal temperature (RT) and leukocyte profiles in dairy cows exposed to heat stress (HS) following acute activation of the stress axis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in the response of OmniGen-AF (OG) supplemented dairy cows to a corticotropin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 162±1 days in milk)...

  6. Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal-Knorr pyrrole formation and gas concentration measurement by inline flow titration.

    PubMed

    Cranwell, Philippa B; O'Brien, Matthew; Browne, Duncan L; Koos, Peter; Polyzos, Anastasios; Peña-López, Miguel; Ley, Steven V

    2012-08-14

    Using a simple and accessible Teflon AF-2400 based tube-in-tube reactor, a series of pyrroles were synthesised in flow using the Paal-Knorr reaction of 1,4-diketones with gaseous ammonia. An inline flow titration technique allowed measurement of the ammonia concentration and its relationship to residence time and temperature.

  7. The Mouse Murr1 Gene Is Imprinted in the Adult Brain, Presumably Due to Transcriptional Interference by the Antisense-Oriented U2af1-rs1 Gene

    PubMed Central

    Wang, Youdong; Joh, Keiichiro; Masuko, Sadahiko; Yatsuki, Hitomi; Soejima, Hidenobu; Nabetani, Akira; Beechey, Colin V.; Okinami, Satoshi; Mukai, Tsunehiro

    2004-01-01

    The mouse Murr1 gene contains an imprinted gene, U2af1-rs1, in its first intron. U2af1-rs1 shows paternal allele-specific expression and is transcribed in the direction opposite to that of the Murr1 gene. In contrast to a previous report of biallelic expression of Murr1 in neonatal mice, we have found that the maternal allele is expressed predominantly in the adult brain and also preferentially in other adult tissues. This maternal-predominant expression is not observed in embryonic and neonatal brains. In situ hybridization experiments that used the adult brain indicated that Murr1 gene was maternally expressed in neuronal cells in all regions of the brain. We analyzed the developmental change in the expression levels of both Murr1 and U2af1-rs1 in the brain and liver, and we propose that the maternal-predominant expression of Murr1 results from transcriptional interference of the gene by U2af1-rs1 through the Murr1 promoter region. PMID:14673161

  8. 26 CFR 1.468A-8T - Special transfers to qualified funds pursuant to section 468A(f) (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) General rule—(1) In general. Under section 468A(f), a taxpayer maintaining a qualified nuclear decommissioning fund with respect to a nuclear power plant may transfer cash or property into the fund (a special... pre-2005 nonqualifying amount of nuclear decommissioning costs with respect to the nuclear power...

  9. Inactive allele-specific methylation and chromatin structure of the imprinted gene U2af1-rs1 on mouse chromosome 11

    SciTech Connect

    Shibata, Hideo; Yoshino, Kiyoshi; Kamiya, Mamoru

    1996-07-01

    The imprinted U2Af1-rs1 gene that maps to mouse chromosome 11 is predominately expressed from the paternal allele. We examined the methylation of genomic sequences in and around the U2af1-rs1 locus to establish the extent of sequence modifications that accompanied the silencing of the maternal allele. The analysis of HapII or HhaI sites showed that the silent maternal allele was hypermethylated in a block of CpG sequences that covered more than 10 kb. By comparison, the expressed paternal allele was unmethylated from a CpG island upstream of the transcribed region through 2 kb. An analysis of DNaseI hypersensitivity of a putative promoter of U2af1-rs1 showed an open chromatin conformation only on the unmethylated, expressed paternal allele. These results suggest that allele-specific hypermethylation covering the gene and its upstream CpG island plays a role in maternal allele repression of U2af1-rs1, which is reflected in altered chromatin conformation of DNaseI hypersensitive sites. 9 refs., 2 figs.

  10. BMSC paracrine activity attenuates interleukin-1β-induced inflammation and apoptosis in rat AF cells via inhibiting relative NF-κB signaling and the mitochondrial pathway

    PubMed Central

    Hu, Jinquan; Yan, Qiang; Shi, Changgui; Tian, Ye; Cao, Peng; Yuan, Wen

    2017-01-01

    We previously showed that bone mesenchymal stem cells (BMSCs) inhibit interleukin-1 beta (IL-1β) induced degenerative effects in NP cells by their paracrine activity, but the anti-inflammatory and anti-apoptotic effect of BMSC paracrine activity and the relative signaling pathway were not further investigated in annulus fibrosus (AF) cells. In this study, AF cells were exposed to IL-1β, which was applied to mimic intervertebral disc degeneration (IDD) in vitro. Indirect co-culture with BMSCs in a transwell co-culture system reduced the activity of nuclear factor-κB-p65 (NF-κB-p65) through the restoration of its inhibitor IκBa. Real time polymerase chain reaction (PT-PCR) and Western blotting revealed that the up-regulation of MMP-3 and MMP-13 induced by IL-1β were impeded by BMSC co-culture, and the decrease in aggrecan, collagen I and TIMP-1 were reversed. An ELISA showed that the increased inflammatory factors, such as nitrite, prostaglandin E-2 (PGE-2), IL-6 and cyclooxygenase-2 (COX-2), were decreased by the BMSC co-culture. Furthermore, the apoptosis rate of AF cells were detected by flow cytometry, and the apoptosis-related proteins, such as Bax, Bcl-2 and caspase-3, were analyzed by Western blotting and ELISA. The changes in mitochondrial membrane potentials were also detected by confocal microscopy. The results showed that IL-1β induced apoptosis of AF cells was attenuated by co-culturing, which suppressed the functions of the mitochondria function. We suggest that BMSC paracrine activity has an anti-inflammation effect and anti-apoptotic effect on IDD, and it is mediated, at least in part, via the relative NF-κF and mitochondrial apoptotic pathways in AF cells. PMID:28123635

  11. High-resolution endocardial and epicardial optical mapping in a sheep model of stretch-induced atrial fibrillation.

    PubMed

    Filgueiras-Rama, David; Martins, Raphael Pedro; Ennis, Steven R; Mironov, Sergey; Jiang, Jiang; Yamazaki, Masatoshi; Kalifa, Jérôme; Jalife, Josè; Berenfeld, Omer

    2011-07-29

    Atrial fibrillation (AF) is a complex cardiac arrhythmia with high morbidity and mortality.(1,2) It is the most common sustained cardiac rhythm disturbance seen in clinical practice and its prevalence is expected to increase in the coming years.(3) Increased intra-atrial pressure and dilatation have been long recognized to lead to AF,(1,4) which highlights the relevance of using animal models and stretch to study AF dynamics. Understanding the mechanisms underlying AF requires visualization of the cardiac electrical waves with high spatial and temporal resolution. While high-temporal resolution can be achieved by conventional electrical mapping traditionally used in human electrophysiological studies, the small number of intra-atrial electrodes that can be used simultaneously limits the spatial resolution and precludes any detailed tracking of the electrical waves during the arrhythmia. The introduction of optical mapping in the early 90's enabled wide-field characterization of fibrillatory activity together with sub-millimeter spatial resolution in animal models(5,6) and led to the identification of rapidly spinning electrical wave patterns (rotors) as the sources of the fibrillatory activity that may occur in the ventricles or the atria.(7-9) Using combined time- and frequency-domain analyses of optical mapping it is possible to demonstrate discrete sites of high frequency periodic activity during AF, along with frequency gradients between left and right atrium. The region with fastest rotors activates at the highest frequency and drives the overall arrhythmia.(10,11) The waves emanating from such rotor interact with either functional or anatomic obstacles in their path, resulting in the phenomenon of fibrillatory conduction.(12) Mapping the endocardial surface of the posterior left atrium (PLA) allows the tracking of AF wave dynamics in the region with the highest rotor frequency. Importantly, the PLA is the region where intracavitary catheter-based ablative

  12. Twenty-fourth Lunar and Planetary Science Conference. Part 1: A-F

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The topics covered include the following: petrology, petrography, meteoritic composition, planetary geology, atmospheric composition, astronomical spectroscopy, lunar geology, Mars (planet), Mars composition, Mars surface, volcanology, Mars volcanoes, Mars craters, lunar craters, mineralogy, mineral deposits, lithology, asteroids, impact melts, planetary composition, planetary atmospheres, planetary mapping, cosmic dust, photogeology, stratigraphy, lunar craters, lunar exploration, space exploration, geochronology, tectonics, atmospheric chemistry, astronomical models, and geochemistry.

  13. Twenty-fourth Lunar and Planetary Science Conference. Part 1: A-F

    SciTech Connect

    Not Available

    1993-01-01

    The topics covered include the following: petrology, petrography, meteoritic composition, planetary geology, atmospheric composition, astronomical spectroscopy, lunar geology, Mars (planet), Mars composition, Mars surface, volcanology, Mars volcanoes, Mars craters, lunar craters, mineralogy, mineral deposits, lithology, asteroids, impact melts, planetary composition, planetary atmospheres, planetary mapping, cosmic dust, photogeology, stratigraphy, lunar craters, lunar exploration, space exploration, geochronology, tectonics, atmospheric chemistry, astronomical models, and geochemistry. Separate abstracts have been prepared for articles from this report.

  14. Association of circulating factor seven activating protease (FSAP) and of oral Omega-3 fatty acids supplements with clinical outcome in patients with atrial fibrillation: the OMEGA-AF study.

    PubMed

    Parahuleva, Mariana S; Kanse, Sandip; Hölschermann, Hans; Zheleva, Kirila; Zandt, Daniel; Worsch, Michael; Parviz, Behnoush; Güttler, Norbert; Tillmanns, Harald; Böning, Andreas; Erdogan, Ali

    2014-04-01

    Factor VII Activating Protease (FSAP) activates factor VII (FVII) as well as pro-urokinase (uPA). Our goal was to evaluate the relation between plasma levels of FSAP and clinical instability in atrial fibrillation (AF) and possible effects of oral omega-3 fatty acids (FA) supplements. 101 patients with persistent AF were analyzed in the OMEGA-AF Study. Plasma FSAP levels were measured at baseline and after 12 weeks of treatment with omega-3 FA. The median FSAP antigen concentration, in contrast to FSAP activity, was higher in patients with persistent AF. The maintenance of SR after successful cardioversion (CV) did not lead to a normalization of FSAP concentration. Supplementation with omega-3 FA but not placebo significantly reduced elevated FSAP concentration. Furthermore, elevated FSAP levels did not indicate a significantly increased risk of recurrence of AF after electrical CV or cardiovascular clinical events during 1 year of follow-up. Plasma FSAP concentration was increased in patients with AF and may be involved in the pathogenesis of this condition. The possible effects of omega-3 FA on clinical AF potential could be linked with modulation of circulating FSAP levels.

  15. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells

    SciTech Connect

    Fujiki, Atsushi; Imamura, Toshihiko; Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya; Sugita, Kanji; Hosoi, Hajime

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein {alpha} (C/EBP{alpha}) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

  16. The distance to the Galactic center determined by A-F stars

    NASA Astrophysics Data System (ADS)

    Branham, Richard L.

    2015-10-01

    The distance from the sun to the center of the Galaxy R0 remains a fundamental parameter for Galactic structure. This study uses 36,061 A and F stars of all luminosity classes with position, parallax, and proper motion taken from the Hipparcos catalog and radial velocities from the Wilson and Strasbourg Data Center catalogs. The nonlinear kinematical equations of condition are solved by the Nelder-Mead simplex algorithm and give R0=7.68± 0.07 kpc. The randomness of the residuals, calculated by a runs test as 91.9 % probable, shows that the kinematical model yields satisfactory results.

  17. c b \\xAF spectrum and decay properties with coupled channel effects

    NASA Astrophysics Data System (ADS)

    Monteiro, Antony Prakash; Bhat, Manjunath; Kumar, K. B. Vijaya

    2017-03-01

    The mass spectrum of c b ¯ states has been obtained using the phenomenological relativistic quark model (RQM) with coupled channel effects. The Hamiltonian used in the investigation has confinement potential and confined one gluon exchange potential (COGEP). In the frame work of the RQM, a study of magnetic dipole and electric dipole transitions and radiative decays of c b ¯ states has been made. The weak decay widths in the spectator quark approximation have been estimated. An overall agreement is obtained with the experimental masses and decay widths.

  18. Magnetic order, Bose-Einstein condensation, and superfluidity in a bosonic t-J model of CP{sup 1} spinons and doped Higgs holons

    SciTech Connect

    Aoki, Koji; Ichinose, Ikuo; Sakakibara, Kazuhiko; Matsui, Tetsuo

    2009-10-01

    We study the three-dimensional U(1) lattice gauge theory of a CP{sup 1} spinon (Schwinger boson) field and a Higgs field. It is a bosonic t-J model in slave-particle representation, describing the antiferromagnetic (AF) Heisenberg spin model with doped bosonic holes expressed by the Higgs field. The spinon coupling term of the action favors AF long-range order, whereas the holon hopping term in the ferromagnetic channel favors Bose-Einstein condensation (BEC) of holons. We investigate the phase structure by means of Monte Carlo simulations and study an interplay of AF order and BEC of holes. We consider the two variations in the model; (i) the three-dimensional model at finite temperatures, and (ii) the two-dimensional model at vanishing temperature. In the model (i) we find that the AF order and BEC coexist at low temperatures and certain hole concentrations. In the model (ii), by varying the hole concentration and the stiffness of AF spin coupling, we find a phase diagram similar to the model (i). Implications of the results to systems of cold atoms and the fermionic t-J model of strongly correlated electrons are discussed.

  19. Stellar Kinematics and Metallicities in the Draco and Ursa Minor Dwarf Spheroidal Galaxies from WHT/AF2-WYFFOS

    NASA Astrophysics Data System (ADS)

    Jin, S.; Irwin, M.; Tolstoy, E.; Lewis, J.; Hartke, J.

    2016-10-01

    We present preliminary results from our chemo-dynamical survey of two Milky Way dwarf spheroidal (dSph) galaxies, Draco and Ursa Minor. The two galaxies have similar radial velocities and reside in close proximity in the outskirts of the Milky Way halo, yet exhibit noteworthy differences in their morphologies. We obtained spectroscopic data with AF2-WYFFOS on the WHT for several hundred red-giant-branch (RGB) candidates in each galaxy out to its tidal radius, from which we have identified approximately 100 velocity members in each system. Metallicities are determined for the individual RGB stars using the Ca II triplet lines. Whereas Ursa Minor shows an RGB population of well-mixed metallicities, a clear gradient is observed in Draco, in which the outer regions host stars of lower [Fe/H]. Such differences may be a reflection of their differing morphologies, with Ursa Minor having been tidally stirred to give rise to both its highly elongated shape and a more mixed [Fe/H] distribution.

  20. Grade-2 Teflon (AF1601) PCF for optical communication using 2D FDTD technique: a simplest design

    NASA Astrophysics Data System (ADS)

    Muduli, N.; Achary, J. S. N.; Padhy, Hemanta ku.

    2016-04-01

    A nonlinear ytterbium-doped rectangular proposed PCF structure of inner and outer cladding is used to analyze effective mode field area (Aeff), nonlinear coefficient (γ), dispersion (D), and confinement loss (CL) in a wide range of wavelength. The fabrication of PCF structure is due to different size doped air hole, pitch, and air hole diameter in a regular periodic geometrical array fashion. The various property of PCF structure such as mode field area, nonlinear coefficient, dispersion, and confinement loss are analyzed by implementing 2D FDTD technique. The above PCF property investigated using suitable parameters like Λ1, ?, ?, and ? in three different situations is discussed in simulation. The high nonlinear coefficient and dispersion property of PCF structure are tailored by setting the cladding parameter. However, highly nonlinear fibers with nonzero dispersion at the wavelength of 1.55 μm are very attractive for a range of optical communication application such as laser amplifier, pulse compression, wavelength conversion, all optical switching, and supercontinuum generation. So our newly proposed ytterbium-doped PCF seems to be most suitable exclusively for supercontinuum generation and nonlinear fiber optics. Finally, it is observed that ytterbium-doped Teflon (AF1601) PCF has more nonlinear coefficient (γ(λ) = 65.27 W-1 km-1) as compared to pure silica PCF (γ(λ) = 52 W-1 km-1) design to have same mode field area (Aeff) 1.7 μm2 at an operating wavelength of 1.55 μm.

  1. Determination of arsenic speciation in sulfidic waters by Ion Chromatography Hydride-Generation Atomic Fluorescence Spectrometry (IC-HG-AFS).

    PubMed

    Keller, Nicole S; Stefánsson, Andri; Sigfússon, Bergur

    2014-10-01

    A method for the analysis of arsenic species in aqueous sulfide samples is presented. The method uses an ion chromatography system connected with a Hydride-Generation Atomic Fluorescence Spectrometer (IC-HG-AFS). With this method inorganic As(III) and As(V) species in water samples can be analyzed, including arsenite (HnAs(III)O3(n-3)), thioarsenite (HnAs(III)S3(n-3)), arsenate (HnAs(V)O4(n-3)), monothioarsenate (HnAs(V)SO3(n-3)), dithioarsenate (HnAs(V)S2O2(n-3)), trithioarsenate (HnAs(V)S3O(n-3)) and tetrathioarsenate (HnAs(V)S4(n-3)). The peak identification and retention times were determined based on standard analysis of the various arsenic compounds. The analytical detection limit was ~1-3 µg L(-1) (LOD), depending on the quality of the baseline. This low detection limit makes this method also applicable to discriminate between waters meeting the drinking water standard of max. 10 µg L(-1) As, and waters that do not meet this standard. The new method was successfully applied for on-site determination of arsenic species in natural sulfidic waters, in which seven species were unambiguously identified.

  2. Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer.

    PubMed Central

    Moghal, N; Neel, B G

    1995-01-01

    Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo and in vitro. One of the earliest events following the exposure of bronchial epithelial cells to RA is the strong induction of RA receptor beta (RAR beta) mRNA. Previous work established that many lung cancer cell lines and primary tumors display abnormal RAR beta mRNA expression, most often absence or weak expression of the RAR beta 2 isoform, even after RA treatment. Restoration of RAR beta 2 into RAR beta-negative lung cancer cell lines has been reported to inhibit tumorigenicity. Since RAR beta 2 inactivation may contribute to lung cancer, we have investigated the molecular mechanism of defective RAR beta 2 expression. Nuclear run-on assays and transient transfections with RAR beta 2 promoter constructs indicate the presence of trans-acting transcriptional defects in most lung cancer cell lines, which map to the RA response element (RARE). These defects cannot be complemented by RAR-retinoid X receptor cotransfection and can be separated into two types: (i) one affecting transcription from direct repeat RAREs, but not palindromic RAREs, and (ii) another affecting transcription from both types of RARE. Studies using chimeras between RAR alpha, TR alpha, and other transcription factors suggest the existence of novel RAR-thyroid hormone receptor AF-2-specific cofactors, which are necessary for high levels of transcription. Furthermore, these factors may be frequently inactivated in human lung cancer. PMID:7791800

  3. Transition region fluxes in A-F Dwarfs: Basal fluxes and dynamo activity

    NASA Technical Reports Server (NTRS)

    Walter, Frederick M.; Schrijver, Carolus J.; Boyd, William

    1988-01-01

    The transition region spectra of 87 late A and early F dwarfs and subgiants were analyzed. The emission line fluxes are uniformly strong in the early F stars, and drop off rapidly among the late A stars. The basal flux level in the F stars is consistent with an extrapolation of that observed among the G stars, while the magnetic component displays the same flux-flux relations seen among solar-like stars. Despite the steep decrease in transition region emission flux for B-V less than 0.28, C II emission is detected in alpha Aql (B-V = 0.22). The dropoff in emission is inconsistent with models of the mechanically generated acoustic flux available. It is concluded that, although the nonmagnetic basal heating is an increasingly important source of atmospheric heating among the early F stars, magnetic heating occurs in any star which has a sufficiently thick convective zone to generate acoustic heating.

  4. Computer simulations for internal dosimetry using voxel models.

    PubMed

    Kinase, Sakae; Mohammadi, Akram; Takahashi, Masa; Saito, Kimiaki; Zankl, Maria; Kramer, Richard

    2011-07-01

    In the Japan Atomic Energy Agency, several studies have been conducted on the use of voxel models for internal dosimetry. Absorbed fractions (AFs) and S values have been evaluated for preclinical assessments of radiopharmaceuticals using human voxel models and a mouse voxel model. Computational calibration of in vivo measurement system has been also made using Japanese and Caucasian voxel models. In addition, for radiation protection of the environment, AFs have been evaluated using a frog voxel model. Each study was performed by using Monte Carlo simulations. Consequently, it was concluded that these data of Monte Carlo simulations and voxel models could adequately reproduce measurement results. Voxel models were found to be a significant tool for internal dosimetry since the models are anatomically realistic. This fact indicates that several studies on correction of the in vivo measurement efficiency for the variability of human subjects and interspecies scaling of organ doses will succeed.

  5. Asymmetric AB3 Miktoarm Star Polymers: Synthesis, Self-Assembly, and Study of Micelle Stability Using AF4 for Efficient Drug Delivery.

    PubMed

    Moquin, Alexandre; Sharma, Anjali; Cui, Yiming; Lau, Anthony; Maysinger, Dusica; Kakkar, Ashok

    2015-12-01

    A simple and versatile methodology, which employs a combination of ring-opening polymerization and alkyne-azide click chemistry to synthesize amphiphilic AB3 miktoarm stars, is reported. Their aqueous self-assembly behavior was studied using dynamic light scattering, fluorescence, and asymmetrical flow field-flow fractionation (AF4). AB3 miktoarm stars form micelles which incorporate curcumin with high efficiency, and significantly reduce the viability of glioblastoma cells in spheroids. We demonstrate that AF4 is an effective technique to determine the size distribution of self-assembled structures exposed to a biological medium. The ease, with which asymmetric AB3 miktoarm polymers are constructed, provides a platform that can be widely employed to deliver a variety of lipophilic drugs.

  6. Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12–15, 2009, Yaoundé, Cameroon

    PubMed Central

    Sirugo, Giorgio; Williams, Scott M.; Royal, Charmaine D. M.; Newport, Melanie J.; Hennig, Branwen J.; Mariani-Costantini, Renato; Buonaguro, Franco M.; Velez Edwards, Digna R.; Ibrahim, Muntaser; Soodyall, Himla; Wonkam, Ambroise; Ramesar, Raj; Rotimi, Charles N.

    2010-01-01

    The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural meeting in Accra, Ghana,1 has the stated missions of (1) disseminating information about human genetics research in Africa, (2) establishing a mentorship network providing educational resources, including the development of appropriate technology transfer, (3) providing advocacy for human genetic research in Africa, and (4) encouraging collaborative research. Despite its young age, the AfSHG has developed a strong cadre of active researchers, both within and outside of Africa, with more than 400 members (from 16 countries across Africa as well as 8 other countries), and has held six successful meetings, five in Africa and one in the United States. PMID:20682860

  7. An ultra-low-voltage electronic implementation of inertial neuron model with nonmonotonous Liao's activation function.

    PubMed

    Kant, Nasir Ali; Dar, Mohamad Rafiq; Khanday, Farooq Ahmad

    2015-01-01

    The output of every neuron in neural network is specified by the employed activation function (AF) and therefore forms the heart of neural networks. As far as the design of artificial neural networks (ANNs) is concerned, hardware approach is preferred over software one because it promises the full utilization of the application potential of ANNs. Therefore, besides some arithmetic blocks, designing AF in hardware is the most important for designing ANN. While attempting to design the AF in hardware, the designs should be compatible with the modern Very Large Scale Integration (VLSI) design techniques. In this regard, the implemented designs should: only be in Metal Oxide Semiconductor (MOS) technology in order to be compatible with the digital designs, provide electronic tunability feature, and be able to operate at ultra-low voltage. Companding is one of the promising circuit design techniques for achieving these goals. In this paper, 0.5 V design of Liao's AF using sinh-domain technique is introduced. Furthermore, the function is tested by implementing inertial neuron model. The performance of the AF and inertial neuron model have been evaluated through simulation results, using the PSPICE software with the MOS transistor models provided by the 0.18-μm Taiwan Semiconductor Manufacturer Complementary Metal Oxide Semiconductor (TSM CMOS) process.

  8. Zc(3900 ) as a resonance from the D DxAF* interaction

    NASA Astrophysics Data System (ADS)

    He, Jun

    2015-08-01

    In this paper it is proposed that the charged charmonium-like state Zc(3900 ) is a resonance above the threshold from the D D¯* interaction. The D D¯* interaction is described by the one-boson exchange model with light meson exchanges plus a short-range J /ψ exchange. The scattering amplitude is calculated within a Bethe-Salpeter equation approach, and the poles near the D D¯* threshold are searched. In the isoscalar sector, two poles found under the D D¯* threshold—i.e., bound states—have the quantum numbers IG(JPC)=0-(1+-) and 0+(1++). The latter can be related to the X (3872 ). In the isovector sector, a bound state with IG(JP)=1+(1+) is found with a large cutoff at about 3 GeV. If a cutoff at about 2 GeV is adopted with which a pole carrying the quantum number of the X (3872 ) is produced at an energy of about 3871 MeV, the pole for the bound state with 1+(1+) runs across the threshold to a second Riemann sheet and becomes a resonance above the D D¯* threshold, which can be identified with the Zc(3900 ). With such a cutoff, the D D¯* invariant mass spectrum is also investigated and the experimental results found by BESIII can be reproduced.

  9. Muscleblind-like 1 activates insulin receptor exon 11 inclusion by enhancing U2AF65 binding and splicing of the upstream intron.

    PubMed

    Echeverria, Gloria V; Cooper, Thomas A

    2014-02-01

    Alternative splicing regulates developmentally and tissue-specific gene expression programs, disruption of which have been implicated in numerous diseases. Muscleblind-like 1 (MBNL1) regulates splicing transitions, which are disrupted on loss of MBNL1 function in myotonic dystrophy type 1 (DM1). One such event is MBNL1-mediated activation of insulin receptor exon 11 inclusion, which requires an intronic enhancer element downstream of exon 11. The mechanism of MBNL1-mediated activation of exon inclusion is unknown. We developed an in vitro splicing assay, which robustly recapitulates MBNL1-mediated splicing activation of insulin receptor exon 11 and found that MBNL1 activates removal of the intron upstream of exon 11 upon binding its functional response element in the downstream intron. MBNL1 enhances early spliceosome assembly as evidenced by enhanced complex A formation and binding of U2 small nuclear ribonucleoprotein auxiliary factor 65 kDa subunit (U2AF65) on the upstream intron. We demonstrated that neither the 5' splice site nor exon 11 sequences are required for MBNL1-activated U2AF65 binding. Interestingly, the 5' splice site is required for MBNL1-mediated activation of upstream intron removal, although MBNL1 has no effect on U1 snRNA recruitment. These results suggest that MBNL1 directly activates binding of U2AF65 to enhance upstream intron removal to ultimately activate alternative exon inclusion.

  10. Role of the essential yeast protein PSU1 in p6anscriptional enhancement by the ligand-dependent activation function AF-2 of nuclear receptors.

    PubMed Central

    Gaudon, C; Chambon, P; Losson, R

    1999-01-01

    Nuclear receptors (NRs) can function as ligandinducible transregulators in both mammalian and yeast cells, indicating that important features of transcriptional control have been conserved throughout evolution. We report here the isolation and characterization of an essential yeast protein of unknown function, PSU1, which exhibits properties expected for a co-activator/mediator of the ligand-dependent activation function AF-2 present in the ligand-binding domain (LBD, region E) of NRs. PSU1 interacts in a ligand-dependent manner with the LBD of several NRs, including retinoic acid (RARalpha), retinoid X (RXRalpha), thyroid hormone (TRalpha), vitamin D3 (VDR) and oestrogen (ERalpha) receptors. Importantly, both in yeast and in vitro, these interactions require the integrity of the AF-2 activating domain. When tethered to a heterologous DNA-binding domain, PSU1 can activate transcription on its own. By using yeast reporter cells that express PSU1 conditionally, we show that PSU1 is required for transactivation by the AF-2 of ERalpha. Taken together these data suggest that in yeast, PSU1 is involved in ligand-dependent transactivation by NRs. Sequence analysis revealed that in addition to a highly conserved motif found in a family of MutT-related proteins, PSU1 contains several alpha-helical leucine-rich motifs sharing the consensus sequence LLxPhiL (x, any amino acid; Phi, hydrophobic amino acid) in regions that elicit either transactivation or NR-binding activity. PMID:10205176

  11. Amniotic fluid-derived mesenchymal stem cells prevent fibrosis and preserve renal function in a preclinical porcine model of kidney transplantation.

    PubMed

    Baulier, Edouard; Favreau, Frederic; Le Corf, Amélie; Jayle, Christophe; Schneider, Fabrice; Goujon, Jean-Michel; Feraud, Olivier; Bennaceur-Griscelli, Annelise; Hauet, Thierry; Turhan, Ali G

    2014-07-01

    It is well known that ischemia/reperfusion injuries strongly affect the success of human organ transplantation. Development of interstitial fibrosis and tubular atrophy is the main deleterious phenomenon involved. Stem cells are a promising therapeutic tool already validated in various ischemic diseases. Amniotic fluid-derived mesenchymal stem cells (af-MSCs), a subpopulation of multipotent cells identified in amniotic fluid, are known to secrete growth factors and anti-inflammatory cytokines. In addition, these cells are easy to collect, present higher proliferation and self-renewal rates compared with other adult stem cells (ASCs), and are suitable for banking. Consequently, af-MSCs represent a promising source of stem cells for regenerative therapies in humans. To determine the efficiency and the safety of af-MSC infusion in a preclinical porcine model of renal autotransplantation, we injected autologous af-MSCs in the renal artery 6 days after transplantation. The af-MSC injection improved glomerular and tubular functions, leading to full renal function recovery and abrogated fibrosis development at 3 months. The strong proof of concept generated by this translational porcine model is a first step toward evaluation of af-MSC-based therapies in human kidney transplantation.

  12. Crystallization and preliminary X-ray analysis of a U2AF{sup 65} variant in complex with a polypyrimidine-tract analogue by use of protein engineering

    SciTech Connect

    Sickmier, E. Allen; Frato, Katherine E.; Kielkopf, Clara L.

    2006-05-01

    A complex of the essential splicing factor U2AF{sup 65} and a deoxyuridine oligonucleotide has been crystallized by modification of an interdomain linker. The large subunit of the essential pre-mRNA splicing factor U2 auxiliary factor (U2AF{sup 65}) binds the polypyrimidine tract near the 3′ splice site of pre-mRNA introns and directs the association of the U2 small nuclear ribonucleoprotein particle (U2 snRNP) of the spliceosome with the pre-mRNA. Protein engineering, in which the flexible linker region connecting tandem RNA-recognition motifs (RRMs) within the U2AF{sup 65} RNA-binding domain was partially deleted, allowed successful crystallization of the protein–nucleic acid complex. Cocrystals of a U2AF{sup 65} variant with a deoxyuridine dodecamer diffract X-rays to 2.9 Å resolution and contain one complex per asymmetric unit.

  13. Simple Model for Identifying Critical Regions in Atrial Fibrillation

    PubMed Central

    Peters, Nicholas S.

    2015-01-01

    Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wave front propagation on an anisotropic structure mimicking the branching network of heart muscle cells. This integration of phenomenological dynamics and pertinent structure shows how AF emerges spontaneously when the transverse cell-to-cell coupling decreases, as occurs with age, beyond a threshold value. We identify critical regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia and express the threshold value of transversal cell-to-cell coupling as a function of the model parameters. This threshold value decreases with increasing refractory period by reducing the number of critical regions which can initiate and sustain microreentrant circuits. These biologically testable predictions might inform ablation therapies and arrhythmic risk assessment. PMID:25635565

  14. Simple Model for Identifying Critical Regions in Atrial Fibrillation

    NASA Astrophysics Data System (ADS)

    Christensen, Kim; Manani, Kishan A.; Peters, Nicholas S.

    2015-01-01

    Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wave front propagation on an anisotropic structure mimicking the branching network of heart muscle cells. This integration of phenomenological dynamics and pertinent structure shows how AF emerges spontaneously when the transverse cell-to-cell coupling decreases, as occurs with age, beyond a threshold value. We identify critical regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia and express the threshold value of transversal cell-to-cell coupling as a function of the model parameters. This threshold value decreases with increasing refractory period by reducing the number of critical regions which can initiate and sustain microreentrant circuits. These biologically testable predictions might inform ablation therapies and arrhythmic risk assessment.

  15. Role of inflammation in the initiation and maintenance of atrial fibrillation and the protective effect of atorvastatin in a goat model of aseptic pericarditis

    PubMed Central

    ZHANG, YE; WANG, YU-TANG; SHAN, ZHAO-LIANG; GUO, HONG-YANG; GUAN, YUAN; YUAN, HONG-TAO

    2015-01-01

    The present study was designed to determine the association between atrial fibrillation (AF) and inflammation in a goat sterile pericarditis model and to assess the effect of atorvastatin, a cholesterol-reducing drug, on AF. A total of 15 adult male goats were randomly divided into control, untreated pericarditis and atorvastatin-treated pericarditis groups. Pericarditis was induced via thoracotomy and atorvastatin was administered orally (60 mg/day) to the goats in the latter group for the duration of the study, commencing 1 week prior to surgery. The levels of high-sensitivity C-reactive protein (hs-CRP), interleukin(IL)-6 and tumor necrosis factor-α (TNF-α) were significantly elevated following surgery in the untreated pericarditis and atorvastatin groups compared with the control group (P<0.05). However, lower levels of hs-CRP, IL-6 and TNF-α were observed in the atorvastatin group compared with the untreated pericarditis group (P<0.05). Additionally, the animals in the atorvastatin-treated pericarditis group had a longer effective refractory period (ERP) and a higher rate adaptation of the ERP compared with those in the untreated pericarditis group (P<0.05). There was a significant negative correlation between the levels of ERP and hs-CRP in the untreated pericarditis group. The inducibility of AF in the left atrium and the duration of AF in the untreated pericarditis and atorvastatin-treated groups increased significantly following surgery (P<0.05). The pericarditis group, however, had a longer duration of AF compared with the atorvastatin group (P<0.05). Thus, inflammation may promote AF by shortening atrial ERP and by reducing the rate adaptation of ERP. These results suggested that atorvastatin can attenuate AF by inhibiting inflammation and may assist in preventing the occurrence and recurrence of AF following cardiac surgery. PMID:25524260

  16. In vivo diagnosis of colonic precancer and cancer using near-infrared autofluorescence spectroscopy and biochemical modeling

    NASA Astrophysics Data System (ADS)

    Shao, Xiaozhuo; Zheng, Wei; Huang, Zhiwei

    2011-06-01

    The aim of this study is to evaluate the biochemical foundation and clinical capability of an image-guided near-infrared (NIR) autofluorescence (AF) spectroscopy technique for in vivo diagnosis of colonic malignancies during clinical colonoscopy. A novel endoscopic fiber-optic AF system was utilized for in vivo NIR AF measurements at 785 nm excitation. A total of 263 in vivo NIR AF spectra of colonic tissues were measured from 100 patients, in which 164 spectra were from benign tissue (116 normal and 48 hyperplastic polyps), 34 spectra were from precancer (adenomatous polyps), and 65 spectra were from cancer. The non-negativity constrained least squares minimization biochemical modeling was explored to estimate the biochemical compositions of colonic tissue using nine basis reference spectra from the representative biochemicals (i.e., collagen I, elastin, β-nicotinamide adenine dinucleotide, flavin adenine dinucleotide, L-tryptophan, hematoporphyrin, 4-pyridoxic acid, pyridoxal 5'-phosphate, and water) associated with structural or cellular metabolic progression in colonic precancer and cancer. High-quality in vivo NIR AF spectra in the spectral range of 810 to 1000 nm were acquired from colonic benign, precancerous, and cancerous mucosa under white-light reflectance endoscopic imaging guidance. Partial least squares discriminant analysis, together with the leave-one tissue site-out, cross validation on in vivo NIR AF spectra yields diagnostic sensitivities of 85.4%, 76.5%, and 84.6%, and specificities of 89.9%, 93.4%, and 91.4%, respectively, for classification of benign, precancer, and cancer in the colon. This work demonstrates that image-guided NIR AF spectroscopy in conjunction with biochemical modeling has promising potential for improving in vivo detection and diagnosis of colonic precancer and cancer during clinical colonoscopic screening.

  17. Predictive model for the growth kinetics of Staphylococcus aureus in raw pork developed using Integrated Pathogen Modeling Program (IPMP) 2013.

    PubMed

    Lee, Yong Ju; Jung, Byeong Su; Kim, Kee-Tae; Paik, Hyun-Dong

    2015-09-01

    A predictive model was performed to describe the growth of Staphylococcus aureus in raw pork by using Integrated Pathogen Modeling Program 2013 and a polynomial model as a secondary predictive model. S. aureus requires approximately 180 h to reach 5-6 log CFU/g at 10 °C. At 15 °C and 25 °C, approximately 48 and 20 h, respectively, are required to cause food poisoning. Predicted data using the Gompertz model was the most accurate in this study. For lag time (LT) model, bias factor (Bf) and accuracy factor (Af) values were both 1.014, showing that the predictions were within a reliable range. For specific growth rate (SGR) model, Bf and Af were 1.188 and 1.190, respectively. Additionally, both Bf and Af values of the LT and SGR models were close to 1, indicating that IPMP Gompertz model is more adequate for predicting the growth of S. aureus on raw pork than other models.

  18. Ising t-J model close to half filling: a Monte Carlo study.

    PubMed

    Maśka, M M; Mierzejewski, M; Ferraz, A; Kochetov, E A

    2009-01-28

    Within the recently proposed doped-carrier representation of the projected lattice electron operators we derive a full Ising version of the t-J model. This model possesses the global discrete Z(2) symmetry as a maximal spin symmetry of the Hamiltonian at any values of the coupling constants, t and J. In contrast, in the spin anisotropic limit of the t-J model, usually referred to as the t-J(z) model, the global SU(2) invariance is fully restored at J(z) = 0, so that only the spin-spin interaction has in this model the true Ising form. We discuss a relationship between these two models and the standard isotropic t-J model. We show that the low-energy quasiparticles in all three models share qualitatively similar properties at low doping and small values of J/t. The main advantage of the proposed Ising t-J model over the t-J(z) one is that the former allows for the unbiased Monte Carlo calculations on large clusters of up to 10(3) sites. Within this model we discuss in detail the destruction of the antiferromagnetic (AF) order by doping as well as the interplay between the AF order and hole mobility. We also discuss the effect of the exchange interaction and that of the next-nearest-neighbour hoppings on the destruction of the AF order at finite doping. We show that the short-range AF order is observed in a wide range of temperatures and dopings, much beyond the boundaries of the AF phase. We explicitly demonstrate that the local no-double-occupancy constraint plays the dominant role in destroying the magnetic order at finite doping. Finally, a role of inhomogeneities is discussed.

  19. Clinical Characteristics, Management, and Control of Permanent vs. Nonpermanent Atrial Fibrillation: Insights from the RealiseAF Survey

    PubMed Central

    Murin, Jan; Naditch-Brûlé, Lisa; Brette, Sandrine; Chiang, Chern-En; O’Neill, James; Steg, P. Gabriel

    2014-01-01

    Background Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample. Methods and Results Data from RealiseAF, an international, observational, cross-sectional survey of 10,491 patients with atrial fibrillation, were used to characterize permanent atrial fibrillation (N = 4869) and nonpermanent atrial fibrillation (N = 5622) patients. Permanent atrial fibrillation patients were older, had a longer time since atrial fibrillation diagnosis, a higher symptom burden, and were more likely to be physically inactive. They also had a higher mean (SD) CHADS2 score (2.2 [1.3] vs. 1.7 [1.3], p<0.001), and a higher frequency of CHADS2 score ≥2 (67.3% vs. 53.0%, p<0.001) and comorbidities, most notably heart failure. Physicians indicated using a rate-control strategy in 84.2% of permanent atrial fibrillation patients (vs. 27.5% in nonpermanent atrial fibrillation). Only 50.2% (N = 2262/4508) of permanent atrial fibrillation patients were controlled. These patients had a longer time since atrial fibrillation diagnosis, a lower symptom burden, less obesity and physical inactivity, less severe heart failure, and fewer hospitalizations for acute heart failure than uncontrolled permanent atrial fibrillation patients, but with more arrhythmic events. The most frequent causes of hospitalization in the last 12 months were acute heart failure and stroke. Conclusion Permanent atrial fibrillation is a high-risk subset of atrial fibrillation, representing half of all atrial fibrillation patients, yet rate control is only achieved in around half. Since control is associated with lower symptom burden and heart

  20. The Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open Label, Clinical Trial (Substrate Modification with Aggressive Blood Pressure Control: SMAC- AF).

    PubMed

    Parkash, Ratika; Wells, George A; Sapp, John L; Healey, Jeffrey S; Tardif, Jean-Claude; Greiss, Isabelle; Rivard, Léna; Roux, Jean-Francois; Gula, Lorne; Nault, Isabelle; Novak, Paul G; Birnie, David H; Ha, Andrew C; Wilton, Stephen B; Mangat, Iqwal; Gray, Christopher J; Gardner, Martin J; Tang, Anthony S L

    2017-02-22

    Background -Radiofrequency catheter ablation for atrial fibrillation has become an important therapy for AF, however recurrence rates remain high. We proposed to determine whether aggressive blood pressure (BP) lowering prevents recurrent atrial fibrillation (AF) after catheter ablation in patients with AF and a high symptom burden. Methods -We randomly assigned 184 patients with AF and a BP greater than 130/80 mmHg to aggressive BP (target <120/80 mm Hg) or standard BP treatment (target <140/90 mmHg) prior to their scheduled AF catheter ablation. The primary outcome was symptomatic recurrence of AF/atrial tachycardia/atrial flutter lasting greater than 30 seconds, determined 3 months beyond catheter ablation by a blinded endpoint evaluation. Results -The median follow-up was 14 months. At six months, the mean systolic BP in the aggressive BP treatment group was 123.2±13.2 versus 135.4±15.7mm Hg (p<0.001) in the standard treatment group. The primary outcome occurred in 106 patients, 54 (61.4%) in the aggressive BP treatment group, compared to 52 (61.2%) in the standard treatment group, (Hazard Ratio 0.94, 95% Confidence Interval 0.65-1.38, p=0.763). In the prespecified subgroup analysis of the influence of age, patients aged ≥ 61 years had a lower primary outcome event rate with aggressive BP (Hazard Ratio 0.58, 95% Confidence Interval (0.34, 0.97), p=0.013). There was a higher rate of hypotension requiring medication adjustment in the aggressive BP group (26% versus 0%). Conclusions -In this study, this duration of aggressive BP treatment did not reduce atrial arrhythmia recurrence after catheter ablation for AF, but resulted in more hypotension. Clinical Trial Registration -Clinicaltrials.gov Identifier: NCT00438113.

  1. Study of atrial arrhythmias in a computer model based on magnetic resonance images of human atria

    NASA Astrophysics Data System (ADS)

    Virag, N.; Jacquemet, V.; Henriquez, C. S.; Zozor, S.; Blanc, O.; Vesin, J.-M.; Pruvot, E.; Kappenberger, L.

    2002-09-01

    The maintenance of multiple wavelets appears to be a consistent feature of atrial fibrillation (AF). In this paper, we investigate possible mechanisms of initiation and perpetuation of multiple wavelets in a computer model of AF. We developed a simplified model of human atria that uses an ionic-based membrane model and whose geometry is derived from a segmented magnetic resonance imaging data set. The three-dimensional surface has a realistic size and includes obstacles corresponding to the location of major vessels and valves, but it does not take into account anisotropy. The main advantage of this approach is its ability to simulate long duration arrhythmias (up to 40 s). Clinically relevant initiation protocols, such as single-site burst pacing, were used. The dynamics of simulated AF were investigated in models with different action potential durations and restitution properties, controlled by the conductance of the slow inward current in a modified Luo-Rudy model. The simulation studies show that (1) single-site burst pacing protocol can be used to induce wave breaks even in tissue with uniform membrane properties, (2) the restitution-based wave breaks in an atrial model with realistic size and conduction velocities are transient, and (3) a significant reduction in action potential duration (even with apparently flat restitution) increases the duration of AF.

  2. CDKN1A-mediated responsiveness of MLL-AF4-positive acute lymphoblastic leukemia to Aurora kinase-A inhibitors.

    PubMed

    Chen, Ya-Ping; Lin, Hui-Ju; Chen, Jiann-Shiuh; Tsai, Ming-Ying; Hsieh, Hsing-Pang; Chang, Jang-Yang; Chen, Nai-Feng; Chang, Kung-Chao; Huang, Wen-Tsung; Su, Wu-Chou; Yang, Shu-Ting; Chang, Wen-Chang; Hung, Liang-Yi; Chen, Tsai-Yun

    2014-08-01

    Overexpression of Aurora kinases is largely observed in many cancers, including hematologic malignancies. In this study, we investigated the effects and molecular mechanisms of Aurora kinase inhibitors in acute lymphoblastic leukemia (ALL). Western blot analysis showed that both Aurora-A and Aurora-B are overexpressed in ALL cell lines and primary ALL cells. Both VE-465 and VX-680 effectively inhibited Aurora kinase activities in nine ALL cell lines, which exhibited different susceptibilities to the inhibitors. Cells sensitive to Aurora kinase inhibitors underwent apoptosis at an IC50 of ∼10-30 nM and displayed a phenotype of Aurora-A inhibition, whereas cells resistant to Aurora kinase inhibitors (with an IC50 more than 10 μM) accumulated polyploidy, which may have resulted from Aurora-B inhibition. Drug susceptibility of ALL cell lines was not correlated with the expression level or activation status of Aurora kinases. Interestingly, RS4;11 and MV4;11 cells, which contain the MLL-AF4 gene, were both sensitive to Aurora kinase-A inhibitors treatment. Complementary DNA (cDNA) microarray analysis suggested that CDKN1A might govern the drug responsiveness of ALL cell lines in a TP53-independent manner. Most importantly, primary ALL cells with MLL-AF4 and CDKN1A expression were sensitive to Aurora kinase inhibitors. Our study suggests CDKN1A could be a potential biomarker in determining the drug responsiveness of Aurora kinase inhibitors in ALL, particularly in MLL-AF4-positive patients.

  3. Quality of Vitamin K Antagonist Control and 1-Year Outcomes in Patients with Atrial Fibrillation: A Global Perspective from the GARFIELD-AF Registry

    PubMed Central

    Haas, Sylvia; ten Cate, Hugo; Accetta, Gabriele; Angchaisuksiri, Pantep; Bassand, Jean-Pierre; Camm, A. John; Corbalan, Ramon; Darius, Harald; Fitzmaurice, David A.; Goldhaber, Samuel Z.; Goto, Shinya; Jacobson, Barry; Kayani, Gloria; Mantovani, Lorenzo G.; Misselwitz, Frank; Pieper, Karen; Schellong, Sebastian M.; Stepinska, Janina; Turpie, Alexander G. G.; van Eickels, Martin; Kakkar, Ajay K.

    2016-01-01

    Aims Vitamin K antagonists (VKAs) need to be individually dosed. International guidelines recommend a target range of international normalised ratio (INR) of 2.0–3.0 for stroke prevention in atrial fibrillation (AF). We analysed the time in this therapeutic range (TTR) of VKA-treated patients with newly diagnosed AF in the ongoing, global, observational registry GARFIELD-AF. Taking TTR as a measure of the quality of patient management, we analysed its relationship with 1-year outcomes, including stroke/systemic embolism (SE), major bleeding, and all-cause mortality. Methods and Results TTR was calculated for 9934 patients using 136,082 INR measurements during 1-year follow-up. The mean TTR was 55.0%; values were similar for different VKAs. 5851 (58.9%) patients had TTR<65%; 4083 (41.1%) TTR≥65%. The proportion of patients with TTR≥65% varied from 16.7% in Asia to 49.4% in Europe. There was a 2.6-fold increase in the risk of stroke/SE, 1.5-fold increase in the risk of major bleeding, and 2.4-fold increase in the risk of all-cause mortality with TTR<65% versus ≥65% after adjusting for potential confounders. The population attributable fraction, i.e. the proportion of events attributable to suboptimal anticoagulation among VKA users, was 47.7% for stroke/SE, 16.7% for major bleeding, and 45.4% for all-cause mortality. In patients with TTR<65%, the risk of first stroke/SE was highest in the first 4 months and decreased thereafter (test for trend, p = 0.021). In these patients, the risk of first major bleed declined during follow-up (p = 0.005), whereas in patients with TTR≥65%, the risk increased over time (p = 0.027). Conclusion A large proportion of patients with AF had poor VKA control and these patients had higher risks of stroke/SE, major bleeding, and all-cause mortality. Our data suggest that there is room for improvement of VKA control in routine clinical practice and that this could substantially reduce adverse outcomes. Trial Registration Clinical

  4. Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation.

    PubMed

    Greiser, Maura; Neuberger, Hans-Ruprecht; Harks, Erik; El-Armouche, Ali; Boknik, Peter; de Haan, Sunniva; Verheyen, Fons; Verheule, Sander; Schmitz, Wilhelm; Ravens, Ursula; Nattel, Stanley; Allessie, Maurits A; Dobrev, Dobromir; Schotten, Ulrich

    2009-03-01

    Atrial dilatation is an independent risk factor for thromboembolism in patients with and without atrial fibrillation (AF). In many patients, atrial dilatation goes along with depressed contractile function of the dilated atria. While some mechanisms causing atrial contractile dysfunction in fibrillating atria have been addressed previously, the cellular and molecular mechanisms of atrial contractile remodeling in dilated atria are unknown. This study characterized in vivo atrial contractile function in a goat model of atrial dilatation and compared it to a goat model of AF. Differences in the underlying mechanisms were elucidated by studying contractile function, electrophysiology and sarcoplasmic reticulum (SR) Ca2+ load in atrial muscle bundles and by analyzing expression and phosphorylation levels of key Ca2+-handling proteins, myofilaments and the expression and activity of their upstream regulators. In 7 chronically instrumented, awake goats atrial contractile dysfunction was monitored during 3 weeks of progressive atrial dilatation after AV-node ablation (AV block goats (AVB)). In open chest experiments atrial work index (AWI) and refractoriness were measured (10 goats with AVB, 5 goats with ten days of AF induced by repetitive atrial burst pacing (AF), 10 controls). Isometric force of contraction (FC), transmembrane action potentials (APs) and rapid cooling contractures (RCC, a measure of SR Ca2+ load) were studied in right atrial muscle bundles. Total and phosphorylated Ca2+-handling and myofilament protein levels were quantified by Western blot. In AVB goats, atrial size increased by 18% (from 26.6+/-4.4 to 31.6+/-5.5 mm, n=7 p<0.01) while atrial fractional shortening (AFS) decreased (from 18.4+/-1.7 to 12.8+/-4.0% at 400 ms, n=7, p<0.01). In open chest experiments, AWI was reduced in AVB and in AF goats compared to controls (at 400 ms: 8.4+/-0.9, n=7, and 3.2+/-1.8, n=5, vs 18.9+/-5.3 mmxmmHg, n=7, respectively, p<0.05 vs control). FC of isolated right

  5. User’s Manual for Strategic Satellite System Terminal Segment Life Cycle Cost Model. Volume 1

    DTIC Science & Technology

    1981-03-01

    LE(NP) (AF) Operating Hours and Number of Missions: AMPM(NP,LO(NS)), APFH(NP,LO(NS)),TFAC(NP) (CN) Operating Labor Times: MMPD (NP,LO(NS)), MMPM(NP) (AF...Pata File 3 are MMPM(NP) and MMPD (NP,LO(NS)). These variables are not used in this version of the SSS LCC Model, but may be implemented at some future...date. Therefore, each of the values of MMPM(NP) and MMPD (NP,LO(NS)) must be set to zero. 6.4.5 Contractor Inputs to Data File 4 - Platform Terminal

  6. A Mathematical Model of Neonatal Rat Atrial Monolayers with Constitutively Active Acetylcholine-Mediated K+ Current

    PubMed Central

    Majumder, Rupamanjari; Jangsangthong, Wanchana; Feola, Iolanda; Ypey, Dirk L.; Pijnappels, Daniël A.; Panfilov, Alexander V.

    2016-01-01

    Atrial fibrillation (AF) is the most frequent form of arrhythmia occurring in the industrialized world. Because of its complex nature, each identified form of AF requires specialized treatment. Thus, an in-depth understanding of the bases of these arrhythmias is essential for therapeutic development. A variety of experimental studies aimed at understanding the mechanisms of AF are performed using primary cultures of neonatal rat atrial cardiomyocytes (NRAMs). Previously, we have shown that the distinct advantage of NRAM cultures is that they allow standardized, systematic, robust re-entry induction in the presence of a constitutively-active acetylcholine-mediated K+ current (IKACh-c). Experimental studies dedicated to mechanistic explorations of AF, using these cultures, often use computer models for detailed electrophysiological investigations. However, currently, no mathematical model for NRAMs is available. Therefore, in the present study we propose the first model for the action potential (AP) of a NRAM with constitutively-active acetylcholine-mediated K+ current (IKACh-c). The descriptions of the ionic currents were based on patch-clamp data obtained from neonatal rats. Our monolayer model closely mimics the action potential duration (APD) restitution and conduction velocity (CV) restitution curves presented in our previous in vitro studies. In addition, the model reproduces the experimentally observed dynamics of spiral wave rotation, in the absence and in the presence of drug interventions, and in the presence of localized myofibroblast heterogeneities. PMID:27332890

  7. The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3

    SciTech Connect

    Lalioti, M.D.; Rossier, C.; Antonarakis, S.E.

    1996-04-15

    We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF{sup 35} (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. contig, close to the cystathionine-{beta}-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3{prime} UTR and by FISH. As U2AF1 associated with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1. 24 refs., 1 fig.

  8. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors.

    PubMed Central

    Henttu, P M; Kalkhoven, E; Parker, M G

    1997-01-01

    Hormone-dependent transcriptional activation by nuclear receptors depends on the presence of a conserved C-terminal amphipathic alpha-helix (helix 12) in the ligand-binding domain. Here we show that a lysine residue, which is conserved in most nuclear receptors in the predicted helix 3, is also required for estrogen-dependent transactivation. The replacement of lysine 366 with alanine appreciably reduced activation function 2 (AF-2) activity without affecting steroid- or DNA-binding activity in the mouse estrogen receptor. The mutation dramatically reduced the ability of the receptor to bind steroid receptor coactivator 1 (SRC-1) but had no effect on receptor-interacting protein 140 (RIP-140) binding, indicating that while their sites of interaction overlap, they are not entirely consistent and in keeping with the proposal that the recruitment of coactivators, such as SRC-1, is required for AF-2 activity. Although the function of RIP-140 remains to be established, RIP-140 appears to be capable of recruiting the basal transcription machinery, since overexpression of the protein markedly increased the transcriptional activity of the mutant receptor. Since the lysine residue is conserved, we propose that it is required, together with residues in helix 12, to form the surface by which members of the nuclear receptor family interact with coactivators. PMID:9121431

  9. A novel Pseudomonas aeruginosa bacteriophage, Ab31, a chimera formed from temperate phage PAJU2 and P. putida lytic phage AF: characteristics and mechanism of bacterial resistance.

    PubMed

    Latino, Libera; Essoh, Christiane; Blouin, Yann; Vu Thien, Hoang; Pourcel, Christine

    2014-01-01

    A novel temperate bacteriophage of Pseudomonas aeruginosa, phage vB_PaeP_Tr60_Ab31 (alias Ab31) is described. Its genome is composed of structural genes related to those of lytic P. putida phage AF, and regulatory genes similar to those of temperate phage PAJU2. The virion structure resembles that of phage AF and other lytic Podoviridae (S. enterica Epsilon 15 and E. coli phiv10) with similar tail spikes. Ab31 was able to infect P. aeruginosa strain PA14 and two genetically related strains called Tr60 and Tr162, out of 35 diverse strains from cystic fibrosis patients. Analysis of resistant host variants revealed different phenotypes, including induction of pigment and alginate overproduction. Whole genome sequencing of resistant variants highlighted the existence of a large deletion of 234 kbp in two strains, encompassing a cluster of genes required for the production of CupA fimbriae. Stable lysogens formed by Ab31 in strain Tr60, permitted the identification of the insertion site. During colonization of the lung in cystic fibrosis patients, P. aeruginosa adapts by modifying its genome. We suggest that bacteriophages such as Ab31 may play an important role in this adaptation by selecting for bacterial characteristics that favor persistence of bacteria in the lung.

  10. TFG/TAF30/ANC1, a component of the yeast SWI/SNF complex that is similar to the leukemogenic proteins ENL and AF-9.

    PubMed Central

    Cairns, B R; Henry, N L; Kornberg, R D

    1996-01-01

    The SWI1/ADR6, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products are all required for proper transcriptional control of many genes in the yeast Saccharomyces cerevisiae. Genetic studies indicated that these gene products might form a multiprotein SWI/SNF complex important for chromatin transitions preceding transcription from RNA polymerase II promoters. Biochemical studies identified a SWI/SNF complex containing these and at least six additional polypeptides. Here we show that the 29-kDa component of the SWI/SNF complex is identical to TFG3/TAF30/ANC1. Thus, a component of the SWI/SNF complex is also a member of the TFIIF and TFIID transcription complexes. TFG3 interacted with the SNF5 component of the SWI/SNF complex in protein interaction blots. TFG3 is significantly similar to ENL and AF-9, two proteins implicated in human acute leukemia. These results suggest that ENL and AF-9 proteins interact with the SNF5 component of the human SWI/SNF complex and raise the possibility that the SWI/SNF complex is involved in acute leukemia. PMID:8668146

  11. Antimony speciation in soils: improving the detection limits using post-column pre-reduction hydride generation atomic fluorescence spectroscopy (HPLC/pre-reduction/HG-AFS).

    PubMed

    Quiroz, Waldo; Olivares, David; Bravo, Manuel; Feldmann, Jorg; Raab, Andrea

    2011-04-15

    HG-AFS is highly sensitive and low cost detection system and its use for antimony chemical speciation coupled to HPLC is gaining popularity. However speciation analysis in soils is strongly hampered because the most efficient extractant reported in the literature (oxalic acid) strongly inhibits the generation of SbH(3) by Sb(V), the major species in this kind of matrix, severely affecting its detection limits. The purpose of this research is to reduce the detection limit of Sb(V), by using a post column on-line reduction system with l-cysteine reagent (HPLC/pre-reduction/HG-AFS). The system was optimized by experimental design, optimum conditions found were 2% (w/v) and 10°C temperature coil. Detection limits of Sb(V) and Sb(III) in oxalic acid (0.25 mol L(-1)) were improved from 0.3 and 0.1 μg L(-1) to 0.07 and 0.07 μg L(-1), respectively. The methodology developed was applied to Chilean soils, where Sb(V) was the predominant species.

  12. Direct Competition between hnRNP C and U2AF65 Protects the Transcriptome from the Exonization of Alu Elements

    PubMed Central

    Zarnack, Kathi; König, Julian; Tajnik, Mojca; Martincorena, Iñigo; Eustermann, Sebastian; Stévant, Isabelle; Reyes, Alejandro; Anders, Simon; Luscombe, Nicholas M.; Ule, Jernej

    2013-01-01

    Summary There are ∼650,000 Alu elements in transcribed regions of the human genome. These elements contain cryptic splice sites, so they are in constant danger of aberrant incorporation into mature transcripts. Despite posing a major threat to transcriptome integrity, little is known about the molecular mechanisms preventing their inclusion. Here, we present a mechanism for protecting the human transcriptome from the aberrant exonization of transposable elements. Quantitative iCLIP data show that the RNA-binding protein hnRNP C competes with the splicing factor U2AF65 at many genuine and cryptic splice sites. Loss of hnRNP C leads to formation of previously suppressed Alu exons, which severely disrupt transcript function. Minigene experiments explain disease-associated mutations in Alu elements that hamper hnRNP C binding. Thus, by preventing U2AF65 binding to Alu elements, hnRNP C plays a critical role as a genome-wide sentinel protecting the transcriptome. The findings have important implications for human evolution and disease. PMID:23374342

  13. Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases.

    PubMed

    Antonucci, Ivana; Provenzano, Martina; Rodrigues, Melissa; Pantalone, Andrea; Salini, Vincenzo; Ballerini, Patrizia; Borlongan, Cesar V; Stuppia, Liborio

    2016-04-22

    In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS) for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS) represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers "in vitro". In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.

  14. Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases

    PubMed Central

    Antonucci, Ivana; Provenzano, Martina; Rodrigues, Melissa; Pantalone, Andrea; Salini, Vincenzo; Ballerini, Patrizia; Borlongan, Cesar V.; Stuppia, Liborio

    2016-01-01

    In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS) for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS) represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers “in vitro”. In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases. PMID:27110774

  15. Evaluation of a Prediction Model for the Development of Atrial Fibrillation in a Repository of Electronic Medical Records

    PubMed Central

    Kolek, Matthew J.; Graves, Amy J.; Xu, Meng; Bian, Aihua; Teixeira, Pedro Luis; Shoemaker, M. Benjamin; Parvez, Babar; Xu, Hua; Heckbert, Susan R.; Ellinor, Patrick T.; Benjamin, Emelia J.; Alonso, Alvaro; Denny, Joshua C.; Moons, Karel G.M.; Shintani, Ayumi K.; Harrell, Frank E.; Roden, Dan M.; Darbar, Dawood

    2017-01-01

    Importance Atrial fibrillation contributes to substantial morbidity, mortality, and healthcare expenditures. Accurate prediction of incident atrial fibrillation would enhance patient management and potentially improve outcomes. Objective We aimed to validate the atrial fibrillation risk prediction model originally developed by the CHARGE-AF investigators utilizing a large repository of electronic medical records. Design Using a database of de-identified medical records, we conducted a retrospective electronic medical record study of subjects without atrial fibrillation followed in Internal Medicine outpatient clinics at our institution. Individuals were followed for incident atrial fibrillation from 2005 until 2010. Adjusting for differences in baseline hazard, we applied the CHARGE-AF Cox proportional hazards model regression coefficients to our cohort. A simple version of the model, with no ECG variables was also evaluated. Setting Outpatient clinics at a large academic medical center. Participants 33,494 subjects of age ≥40 years, white or African American, and no previous history of atrial fibrillation. Predictors Predictors in the model included age, race, height, weight, systolic and diastolic blood pressure, treatment for hypertension, smoking status, diabetes, heart failure, history of myocardial infarction, left ventricular hypertrophy, and PR interval. Main outcome Incident atrial fibrillation. Results The median age was 57 years (25th to 75th percentile: 49 to 67), 57% of patients were women, 85.7% were white, 14.3% were African American. During the mean follow-up period of 4.8 ± 0.85 years, 2455 (7.3%) subjects developed atrial fibrillation. Both models had poor calibration in our cohort, with under-prediction of AF among low-risk subjects and over-prediction of AF among high-risk subjects. The full CHARGE-AF model had a C-index of 0.71 (95% confidence interval [CI]: 0.70 to 0.72) in our cohort. The simple model had similar discrimination (C-index: 0

  16. The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

    PubMed

    Ten Cate, V; Ten Cate, H; Verheugt, F W A

    2016-10-01

    There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.

  17. Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

    PubMed Central

    Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.

    2016-01-01

    Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063

  18. Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling

    PubMed Central

    Morgan, Ross; Colman, Michael A.; Chubb, Henry; Seemann, Gunnar; Aslanidi, Oleg V.

    2016-01-01

    Introduction: The genesis of atrial fibrillation (AF) and success of AF ablation therapy have been strongly linked with atrial fibrosis. Increasing evidence suggests that patient-specific distributions of fibrosis may determine the locations of electrical drivers (rotors) sustaining AF, but the underlying mechanisms are incompletely understood. This study aims to elucidate a missing mechanistic link between patient-specific fibrosis distributions and AF drivers. Methods: 3D atrial models integrated human atrial geometry, rule-based fiber orientation, region-specific electrophysiology, and AF-induced ionic remodeling. A novel detailed model for an atrial fibroblast was developed, and effects of myocyte-fibroblast (M-F) coupling were explored at single-cell, 1D tissue and 3D atria levels. Left atrial LGE MRI datasets from 3 chronic AF patients were segmented to provide the patient-specific distributions of fibrosis. The data was non-linearly registered and mapped to the 3D atria model. Six distinctive fibrosis levels (0–healthy tissue, 5–dense fibrosis) were identified based on LGE MRI intensity and modeled as progressively increasing M-F coupling and decreasing atrial tissue coupling. Uniform 3D atrial model with diffuse (level 2) fibrosis was considered for comparison. Results: In single cells and tissue, the largest effect of atrial M-F coupling was on the myocyte resting membrane potential, leading to partial inactivation of sodium current and reduction of conduction velocity (CV). In the 3D atria, further to the M-F coupling, effects of fibrosis on tissue coupling greatly reduce atrial CV. AF was initiated by fast pacing in each 3D model with either uniform or patient-specific fibrosis. High variation in fibrosis distributions between the models resulted in varying complexity of AF, with several drivers emerging. In the diffuse fibrosis models, waves randomly meandered through the atria, whereas in each the patient-specific models, rotors stabilized in

  19. Band-renormalization effect in coexistent state of d-wave superconducting and antiferromagnetic orders for Hubbard model

    NASA Astrophysics Data System (ADS)

    Sato, R.; Yokoyama, H.

    2016-11-01

    In view of cuprate superconductors, we apply a variational Monte Carlo method to a strongly correlated square-lattice Hubbard (t-t‧-U) model. As a one-body part in a trial wave function, we use a coexistent state of antiferromagnetic (AF) and d-wave superconducting (SC) orders for each of which band-renormalization effect (BRE) is considered independently. We focus on t‧/t and doping-rate (δ) dependence of properties of this state. It is found that the BRE for the AF order causes expansion of the AF area up to δ ∼ 0.2 for a large |t‧/t|. For t‧ / t = 0 (- 0.3), the AF and SC orders are coexistent (mutually exclusive), and the state is unstable toward (stable against) phase separation. This feature of coexistence or exclusion depends on the position of the Fermi surface in the underlying pure AF state, and indicates that antinodal Fermi surfaces are crucial for forming d-wave SC.

  20. Modelling progressive autonomic failure in MSA: where are we now?

    PubMed

    Stemberger, Sylvia; Wenning, Gregor K

    2011-05-01

    Multiple system atrophy (MSA) is a fatal late-onset α-synucleinopathy that presents with features of ataxia, Parkinsonism, and pyramidal dysfunction in any combination. Over the last decade, efforts have been made to develop preclinical MSA testbeds for novel interventional strategies. The main focus has been on murine analogues of MSA-linked motor features and their underlying brainstem, cerebellar and basal ganglia pathology. Although progressive autonomic failure (AF) is a prominent clinical feature of patients with MSA, reflecting a disruption of both central and peripheral autonomic networks controlling cardiovascular, respiratory, urogenital, gastrointestinal and sudomotor functions, attempts of modelling this aspect of the human disease have been limited. However, emerging evidence suggests that AF-like features may occur in transgenic MSA models reflecting α-synucleinopathy lesions in distributed autonomic networks. Further research is needed to fully characterize both autonomic and motor features in optimized preclinical MSA models.

  1. Pericellular Matrix Mechanics in the Anulus Fibrosus Predicted by a Three-Dimensional Finite Element Model and In Situ Morphology

    PubMed Central

    Cao, Li; Guilak, Farshid; Setton, Lori A.

    2009-01-01

    Anulus fibrosus (AF) cells have been demonstrated to exhibit dramatic differences in morphology and biologic responses to different types of mechanical stimuli. AF cells may reside as single cell, paired or multiple cells in a contiguous pericellular matrix (PCM), whose structure and properties are expected to have a significant influence on the mechanical stimuli that these cells may experience during physiologic loading of the spine, as well as in tissue degeneration and regeneration. In this study, a computational model was developed to predict the micromechanical stimuli, such as stress and strain, fluid pressure and flow, of cells and their surrounding PCM in the AF tissue using three-dimensional (3D) finite element models based on in situ morphology. 3D solid geometries of cell-PCM regions were registered from serial confocal images obtained from mature rat AF tissues by custom codes. Distinct cell-matrix units were modeled with a custom 3D biphasic finite element code (COMSOL Multiphysics), and simulated to experience uni-axial tensile strain along the local collagen fiber direction. AF cells were predicted to experience higher volumetric strain with a strain amplification ratio (relative to that in the extracellular matrix) of ~ 3.1 – 3.8 at equilibrium, as compared to the PCM domains (1.3 – 1.9). The strain concentrations were generally found at the cell/PCM interface and stress concentration at the PCM/ECM interface. Increased numbers of cells within a contiguous PCM was associated with an apparent increase of strain levels and decreased rate of fluid pressurization in the cell, with magnitudes dependent on the cell size, shape and relative position inside the PCM. These studies provide spatio-temporal information on micromechanics of AF cells in understanding the mechanotransduction in the intervertebral disc. PMID:19946619

  2. Spin glass behavior of the antiferromagnetic Heisenberg model on scale free network

    NASA Astrophysics Data System (ADS)

    Surungan, Tasrief; Zen, Freddy P.; Williams, Anthony G.

    2015-09-01

    Randomness and frustration are considered to be the key ingredients for the existence of spin glass (SG) phase. In a canonical system, these ingredients are realized by the random mixture of ferromagnetic (FM) and antiferromagnetic (AF) couplings. The study by Bartolozzi et al. [Phys. Rev. B73, 224419 (2006)] who observed the presence of SG phase on the AF Ising model on scale free network (SFN) is stimulating. It is a new type of SG system where randomness and frustration are not caused by the presence of FM and AF couplings. To further elaborate this type of system, here we study Heisenberg model on AF SFN and search for the SG phase. The canonical SG Heisenberg model is not observed in d-dimensional regular lattices for (d ≤ 3). We can make an analogy for the connectivity density (m) of SFN with the dimensionality of the regular lattice. It should be plausible to find the critical value of m for the existence of SG behaviour, analogous to the lower critical dimension (dl) for the canonical SG systems. Here we study system with m = 2, 3, 4 and 5. We used Replica Exchange algorithm of Monte Carlo Method and calculated the SG order parameter. We observed SG phase for each value of m and estimated its corersponding critical temperature.

  3. Brocazines A-F, Cytotoxic Bisthiodiketopiperazine Derivatives from Penicillium brocae MA-231, an Endophytic Fungus Derived from the Marine Mangrove Plant Avicennia marina.

    PubMed

    Meng, Ling-Hong; Li, Xiao-Ming; Lv, Cui-Ting; Huang, Cai-Guo; Wang, Bin-Gui

    2014-08-22

    Six new disulfide-bridged diketopiperazine derivatives, brocazines A-F (1-6), along with one known analogue (7), were isolated and identified from the cytotoxic extract of Penicillium brocae MA-231, a fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these compounds were established on the basis of detailed interpretation of NMR and mass spectroscopic data. X-ray crystallographic analysis confirmed the structure of 1 and established the structure and absolute configuration of 5, while the absolute configurations for compounds 1, 4, and 6 were deduced by comparison of the CD data with those of 5. Compounds 1, 2, 5, and 6 showed cytotoxic activities against several tumor cell lines.

  4. [Pehr af Bjerkén 1765-1818. Chief baber-surgeon at the Serafimer hospital. Physician to the king].

    PubMed

    Hallböök, Torgil

    2005-01-01

    Pehr af Bjerkén had his descent from a parish named Bjärka in western Sweden. His father was a medical doctor and assessor in Stockholm. At the age of sixteen Bjerkén began his studies in Uppsala. Later on he became a "chirurgiae studiosus" in Stockholm at the Serafimer hospital as a pupil of professor Olof Acrel. He defended a doctor's dissertation on "Febris puerperalis" in 1793. Thereafter Bjerkén went to London, where he spent three years. He was taken care of by mr Henry Cline and he met also John Hunter. After some time mr Cline made him a "House surgeon" at S:t Thomasis and Guys hospitals. He got good practice especially regarding the surgery of stones in the urinary bladder and in the surgery of the eye. During the stay he was appointed a member of the Medical Society of London. Back in Sweden Bjerkén practised the surgery with great success.and became physician in ordinary to the king. When in Februar 1808 the Russian tzar Alexander invaded Finland Bjerkén was appointed chief army surgeon in nothern Finland. During this war Bjerkén showed his courage on the battle fields operating and taking care of the wounded soldiers, also the enemies. Most wellknowned for us he became through a sentense in the poem "Döbeln at Juutas". In February 1809, when the Russian tzar had conquered all of Finland. Bjerkén resigned from the Finnish army. The first of June 1809 af Bjerkén was appointed to be head barber-surgeon (head surgeon) of the Serafimer hospital in Stockholm. He was then the most qualified surgeon in Sweden and was looked upon as the most important authority in surgery. Bjerkén was the first one to describe an operation and ligation of an aneurysm of the carotide artery. In 1812 he also published a ligation and resektion of a huge tongue reaching below the chin on a girl eleven years of age. Together with the description there was an engraving. This became the first illustrated publication in the proceedings of the Swedish Society of Medicine. He

  5. Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP.

    PubMed

    Tamura, Tomohide; Kiura, Katsuyuki; Seto, Takashi; Nakagawa, Kazuhiko; Maemondo, Makoto; Inoue, Akira; Hida, Toyoaki; Yoshioka, Hiroshige; Harada, Masao; Ohe, Yuichiro; Nogami, Naoyuki; Murakami, Haruyasu; Kuriki, Hiroshi; Shimada, Tadashi; Tanaka, Tomohiro; Takeuchi, Kengo; Nishio, Makoto

    2017-03-15

    Purpose Alectinib is an anaplastic lymphoma kinase (ALK) -specific kinase inhibitor that seems to be effective against non-small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor-naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.

  6. Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group.

    PubMed

    Tomizawa, Daisuke; Kato, Motohiro; Takahashi, Hiroyuki; Fujimura, Junya; Inukai, Takeshi; Fukushima, Takashi; Kiyokawa, Nobutaka; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira

    2015-11-01

    Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

  7. Lu AF21934, a positive allosteric modulator of mGlu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats.

    PubMed

    Ossowska, Krystyna; Wardas, Jadwiga; Berghauzen-Maciejewska, Klemencja; Głowacka, Urszula; Kuter, Katarzyna; Pilc, Andrzej; Zorn, Stevin H; Doller, Dario

    2014-08-01

    Harmaline induces tremor in animals resembling essential tremor which has been suggested to result from activation of the glutamatergic olivo-cerebellar projection. The aim of the present study was to examine the effects of systemic administration of Lu AF21934, a brain-penetrating positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu4), on the harmaline-induced tremor and other forms of motor activity in rats using fully automated Force Plate Actimeters. The influence of harmaline on the mGlu4 mRNA expression in the cerebellum and inferior olive was analysed by in situ hybridization. Harmaline at a dose of 15 mg/kg (ip) triggered tremor which was manifested by an increase in the power within 9-15 Hz band and in the tremor index (a difference in power between bands 9-15 Hz and 0-8 Hz). Harmaline induced a biphasic effect on mobility, initially inhibiting the exploratory locomotor activity of rats (0-30 min after administration), followed by an increase in their basic activity. Lu AF21934 (0.5-5 mg/kg sc) did not influence tremor but at doses of 0.5 and 2.5 mg/kg reversed harmaline-induced hyperactivity. MGlu4 mRNA expression was high in the cerebellar cortex and low in the inferior olive. Repeated harmaline (15 mg/kg ip once a day for 5 days] decreased mGlu4 mRNA in the cerebellum and inferior olive. The present study indicates that the mGlu4 stimulation counteracts hyperactivity induced by harmaline which suggests the involvement of cerebellar glutamatergic transmission in this process. In contrast, neuronal mechanisms involved in tremor seem to be insensitive to the stimulation of mGlu4.

  8. Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

  9. Helicobacter pylori infection related long noncoding RNA (lncRNA) AF147447 inhibits gastric cancer proliferation and invasion by targeting MUC2 and up-regulating miR-34c.

    PubMed

    Zhou, Xiaoying; Chen, Han; Zhu, Li; Hao, Bo; Zhang, Weifeng; Hua, Jie; Gu, Huiyuan; Jin, Wujuan; Zhang, Guoxin

    2016-12-13

    Long non-coding RNAs (lncRNAs) were shown to play critical roles in cancer biology. We investigated whether H. pylori infection could promote gastric cancer by regulating lncRNAs expression. Differentially expressed lncRNAs between H. pylori positive and negative tissues were identified by microarray and validated by qRT-PCR. Our results indicated that H. pylori positive tissues have a specific profile of lncRNAs. Cell biological assays with siRNA-mediated knockdown or lentivirus vector-mediated over-expression were performed to probe the functional relevance of the lncRNAs. We identified an lncRNA-AF147447 decreased expressed by H. pylori infection, which can inhibit GC proliferation and invasion in vitro and in vivo, act as a tumor suppressor in the development of H. pylori induced GC. LncRNA AF147447 could repress MUC2 expression by direct binding or increasing miR-34c expression. We also found that transcription factor E2F1 could be recruited to lncRNA AF147447 promoter by RNA immunoprecipatation and RNA pull down assays. These findings support a role of lncRNA AF147447 in tumor suppression. This discovery contributes to a better understanding of the importance of the deregulated lncRNAs by H. pylori infection and provides a rationale for the potential development of lncRNA-based targeted approaches for the treatment of H. pylori-related gastric cancer.

  10. 75 FR 6865 - Airworthiness Directives; The Boeing Company Model 737-700 (IGW) Series Airplanes Equipped With...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-12

    ... procedures for modifying the auxiliary fuel system (AFS). The modification of the auxiliary fuel cells of the... Model 737-700 (IGW) Series Airplanes Equipped With Auxiliary Fuel Tanks Installed in Accordance With... modification of PATS Aircraft, LLC, auxiliary fuel tanks. This proposed AD results from fuel system...

  11. Impact of gender on event rates at 1 year in patients with newly diagnosed non-valvular atrial fibrillation: contemporary perspective from the GARFIELD-AF registry

    PubMed Central

    Camm, A John; Accetta, Gabriele; Al Mahmeed, Wael; Ambrosio, Giuseppe; Goldhaber, Samuel Z; Haas, Sylvia; Jansky, Petr; Kayani, Gloria; Misselwitz, Frank; Oh, Seil; Oto, Ali; Raatikainen, Pekka; Steffel, Jan; van Eickels, Martin; Kakkar, Ajay K

    2017-01-01

    Objectives Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) explored the impact of gender, risk factors and anticoagulant (AC) treatment on 1-year outcomes in patients with non-valvular atrial fibrillation (NVAF). Design GARFIELD-AF is a prospective non-interventional registry. Setting Investigator sites (n=1048) are representative of the care settings/locations in each of the 35 countries. Participants Patients ≥18yrs with newly diagnosed (≤6 weeks' duration) NVAF and ≥1 investigator-determined stroke risk factors. Main outcome measures Event rates per 100 person-years were estimated from the Poisson model and HRs and 95% CIs calculated. Results Of 28 624 patients (women 44.4%; men 55.6%) enrolled, there were more elderly (≥75 years) women (46.9%) than men (30.4%). All-cause mortality rates per 100 person-years (95% CI) for women and men were 4.48 (4.12 to 4.87) and 4.04 (3.74 to 4.38), respectively, stroke/systemic embolism (SE) (1.62 (1.41 to 1.87) and 1.17 (1.01 to 1.36)) and major bleeding (0.93 (0.78 to 1.13) and 0.79 (0.66 to 0.95)). After adjustment for baseline risk factors in treated and untreated patients, HRs (95% CI) for women (relative to men) for stroke/SE rates were 1.3-fold higher in women (HR 1.30 (1.04 to 1.63)), and similar for major bleeding (1.13 (0.85 to 1.50)) and all-cause mortality (1.05 (0.92 to 1.19)). Antithrombotic treatment patterns in men and women were almost identical. 63.8% women and 62.9% men received AC± antiplatelets. Relative to no AC treatment, the reduction in stroke/SE rates with AC treatment was greater (p=0.01) in men (HR 0.45 (0.33 to 0.61)) than women 0.77 (0.57 to 1.03). All-cause mortality reduction with AC treatment was similar (women: 0.65 (0.54 to 0.77); men: 0.57 (0.48 to 0.68)). The risk of major bleeding when treated with AC versus no AC was 2.33 (1.41 to 3.84) in men and 1.86 (1.16 to 2.99) in women (p value=0.53). Conclusions Women have a higher risk of stroke/SE and

  12. The mechanism and kinetic model on the OH-initiated degradation of acetofenate in the atmosphere

    NASA Astrophysics Data System (ADS)

    Kang, Lingyan; Sun, Xiaomin; Zhang, Chenxi; Zhang, Xue; Chen, Jianmin

    2015-02-01

    As an analog of DDT, acetofenate (AF), one of the organochlorine pesticides, is widely used in agricultural and mosquito sprayings. In this paper, the main reaction mechanism of AF with the OH radical and ensuing reactions are researched, including the OH-initiated reaction, oxidation reaction in the presence of O2, bimolecular reaction of AF-OH-O2 with NO/H2O, bond cleavage of aromatic ring and C7-O bond, and dehydrogenation. Among all the reaction pathways, the main products are obtained via C2-C7/C7-O bond cleavage, C3-C4/C4-C5 bond cleavage of aromatic ring, and the generation of ketene and aldehyde. The kinetic model is constructed based on the rate constants of element reactions over a temperature range of 200-600 K, which are calculated with the transition state theory method and fitted with the Arrhenius formulas. According to the kinetic model, the atmospheric lifetime of AF, is 37 days, compared to OH radical.

  13. Magnetic order and Kondo effect in the Anderson-lattice model

    NASA Astrophysics Data System (ADS)

    Bernhard, B. H.; Aguiar, C.; Kogoutiouk, I.; Coqblin, B.

    The Anderson-lattice model has been extensively developed to account for the properties of many anomalous rare-earth compounds and in particular for the competition between the Kondo effect and an antiferromagnetic (AF) phase in a cubic lattice. Here we apply the higher-order decoupling of the equations of motion for the Green Functions (GF) introduced in [H.G. Luo, S.J. Wang, Phys. Rev. B 62 (2000) 1485]. We obtain an improved description of the phase diagram, where the AF phase subsists in a smaller range of the model parameters. As higher-order GF are included in the chain of equations, we are able to calculate directly the local spin-flip correlation function . As a further improvement to the previous approximation of [B.H. Bernhard, C. Aguiar, B. Coqblin, Physica B 378-380 (2006) 712], we obtain a reduced range of existence for the AF phase for the symmetric half-filled case and then we discuss the competition between the AF order and the Kondo effect as a function of the band filling.

  14. Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study

    PubMed Central

    Hwang, Minki; Lim, Byounghyun; Song, Jun-Seop; Yu, Hee Tae; Ryu, Ah-Jin; Lee, Young-Seon; Joung, Boyoung; Shim, Eun Bo; Pak, Hui-Nam

    2017-01-01

    Background The role of the autonomic nervous system (ANS) on atrial fibrillation (AF) is difficult to demonstrate in the intact human left atrium (LA) due to technical limitations of the current electrophysiological mapping technique. We examined the effects of the ANS on the initiation and maintenance of AF by employing a realistic in silico human left atrium (LA) model integrated with a model of ganglionated plexi (GPs). Methods We incorporated the morphology of the GP and parasympathetic nerves in a three-dimensional (3D) realistic LA model. For the model of ionic currents, we used a human atrial model. GPs were stimulated by increasing the IK[ACh], and sympathetic nerve stimulation was conducted through a homogeneous increase in the ICa-L. ANS-induced wave-dynamics changes were evaluated in a model that integrated a patient’s LA geometry, and we repeated simulation studies using LA geometries from 10 different patients. Results The two-dimensional model of pulmonary vein (PV) cells exhibited late phase 3 early afterdepolarization-like activity under 0.05μM acetylcholine (ACh) stimulation. In the 3D simulation model, PV tachycardia was induced, which degenerated to AF via GP (0.05μM ACh) and sympathetic (7.0×ICa-L) stimulations. Under sustained AF, local reentries were observed at the LA-PV junction. We also observed that GP stimulation reduced the complex fractionated atrial electrogram (CFAE)-cycle length (CL, p<0.01) and the life span of phase singularities (p<0.01). GP stimulation also increased the overlap area of the GP and CFAE areas (CFAE-CL≤120ms, p<0.01). When 3 patterns of virtual ablations were applied to the 3D AF models, circumferential PV isolation including the GP was the most effective in terminating AF. Conclusion Cardiac ANS stimulations demonstrated triggered activity, automaticity, and local reentries at the LA-PV junction, as well as co-localized GP and CFAE areas in the 3D in silico GP model of the LA. PMID:28245283

  15. Modelling Aspergillus flavus growth and aflatoxins production in pistachio nuts.

    PubMed

    Marín, Sonia; Ramos, Antonio J; Sanchis, V

    2012-12-01

    Aflatoxins (AFs) are the main contaminants in pistachio nuts. AFs production in pistachio has been attributed to Aspergillus flavus. The aim of this study was to apply existing models to predict growth and AFs production by an A. flavus isolated from pistachios as a function of moisture content and storage temperature of pistachios in order to test their usefulness and complementarities. A full factorial design was used: the moisture content levels assayed were 10, 15, 20, 25 and 30% and incubation temperatures were 10, 15, 20, 25, 30, 37 and 42 °C. Both kinetic and probability models were built to predict growth of the strain under the assayed conditions. Among the assayed models, cardinal ones gave a good quality fit for radial growth rate data. Moreover, the progressive approach, which was developed based on a reduced number of experimental points led to an improved prediction in the validation step. This is quite significant as may allow for improved experimental designs, less costly than full factorial ones. Probability model proved to be concordant in 91% of the calibration set observations. Even though the validation set included conditions around the growth/no-growth interface, there was a 100% agreement in the predictions from the data set (n = 16, cut off = 0.5) after 60 days. Similarly, the probability for AF presence was rightly predicted in 89% of the cases. According to our results EC maximum aflatoxin levels would be surpassed in a period as short as 1 month if pistachio nuts reach 20 °C, unless %mc is ≤10%.

  16. An Analysis of the Centaur Ground Processing System at the Kennedy Space Center/Cape Canaveral AFS.

    DTIC Science & Technology

    1985-12-01

    three TTF/four CISS model did even better with an output of 38 flights. This configuration was processing Centaur vehicles as fast as they arrived as...ACT,RLOGN(1.610,0.7782)*3; VENT SYS FUNCT CK FREE,CCLS,4; RELEASE CCLS E-4 ACT,, ,N51C; ACT,RLOGN(1.610,0.7782)*3,,N22AK; INSTL FORWORD BULKHEAD INSUL

  17. Benchmarking electrophysiological models of human atrial myocytes

    PubMed Central

    Wilhelms, Mathias; Hettmann, Hanne; Maleckar, Mary M.; Koivumäki, Jussi T.; Dössel, Olaf; Seemann, Gunnar

    2013-01-01

    Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation (AF). In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential (AP) alternans. To assess the models' ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation (cAF) was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate AP and restitution properties, as well as the initiation of reentrant circuits. PMID:23316167

  18. Mutations in the Caenorhabditis elegans U2AF Large Subunit UAF-1 Alter the Choice of a 3′ Splice Site In Vivo

    PubMed Central

    Ma, Long; Horvitz, H. Robert

    2009-01-01

    The removal of introns from eukaryotic RNA transcripts requires the activities of five multi-component ribonucleoprotein complexes and numerous associated proteins. The lack of mutations affecting splicing factors essential for animal survival has limited the study of the in vivo regulation of splicing. From a screen for suppressors of the Caenorhabditis elegans unc-93(e1500) rubberband Unc phenotype, we identified mutations in genes that encode the C. elegans orthologs of two splicing factors, the U2AF large subunit (UAF-1) and SF1/BBP (SFA-1). The uaf-1(n4588) mutation resulted in temperature-sensitive lethality and caused the unc-93 RNA transcript to be spliced using a cryptic 3′ splice site generated by the unc-93(e1500) missense mutation. The sfa-1(n4562) mutation did not cause the utilization of this cryptic 3′ splice site. We isolated four uaf-1(n4588) intragenic suppressors that restored the viability of uaf-1 mutants at 25°C. These suppressors differentially affected the recognition of the cryptic 3′ splice site and implicated a small region of UAF-1 between the U2AF small subunit-interaction domain and the first RNA recognition motif in affecting the choice of 3′ splice site. We constructed a reporter for unc-93 splicing and using site-directed mutagenesis found that the position of the cryptic splice site affects its recognition. We also identified nucleotides of the endogenous 3′ splice site important for recognition by wild-type UAF-1. Our genetic and molecular analyses suggested that the phenotypic suppression of the unc-93(e1500) Unc phenotype by uaf-1(n4588) and sfa-1(n4562) was likely caused by altered splicing of an unknown gene. Our observations provide in vivo evidence that UAF-1 can act in regulating 3′ splice-site choice and establish a system that can be used to investigate the in vivo regulation of RNA splicing in C. elegans. PMID:19893607

  19. Effect of Brazilian propolis (AF-08) on genotoxicity, cytotoxicity and clonogenic death of Chinese hamster ovary (CHO-K1) cells irradiated with (60)Co gamma-radiation.

    PubMed

    Santos, Geyza Spigoti; Tsutsumi, Shigetoshi; Vieira, Daniel Perez; Bartolini, Paolo; Okazaki, Kayo

    2014-03-01

    The present study was conducted in order to evaluate the effect of Brazilian propolis (AF-08; 5, 10, 15, 30, 50, 100, and 200μg/mL) in protecting CHO-K1 cells against genotoxic and cytotoxic damage and clonogenic death induced by (60)Co gamma-radiation (1.0, 2.0, 4.0, and 6.0Gy). For this purpose, three interlinked endpoints were analyzed: induction of DNA damage by use of the micronucleus (MN) test (genotoxic damage), cell viability by means of the MTS assay, and differential staining (cytotoxic damage) and clonogenic death via the colony-formation test (cytotoxic damage). The MN test revealed that propolis alone (5-100μg/mL) was not genotoxic up to 100μg/mL and that 30μg/mL of propolis reduced the radiation-induced DNA damage (∼56% reduction, p<0.05), exhibiting a radio-protective effect on irradiated CHO-K1 cells. On the other hand, analysis of cytotoxicity showed that a concentration of 50μg/mL presented a significant proliferative effect (p<0.001) when associated with radiation, decreasing the percentage of necrotic cells (p<0.01). No mediated cytotoxic effect was found, but the concentration of 200μg/mL was toxic when analyzed at 24 and 48h via the differential staining technique, but not at 72h after irradiation, analyzed with the MTS assay. Differential staining also showed that necrosis was the main death modality in irradiated cells and that apoptosis was induced only at the toxic concentration of propolis (200μg/mL). Concerning the clonogenic capacity, a concentration of 50μg/mL also exhibited a significant stimulating effect on cell proliferation (p<0.001), in agreement with the data from differential staining. Taken together, these data suggest that the use of propolis AF-08 for the prevention of the adverse effects of ionizing radiation is promising. Nevertheless, additional investigations are necessary for a better understanding of potential applications of propolis to improve human health.

  20. Binding of hnRNP H and U2AF65 to Respective G-codes and a Poly-Uridine Tract Collaborate in the N50-5'ss Selection of the REST N Exon in H69 Cells

    PubMed Central

    Ortuño-Pineda, Carlos; Galindo-Rosales, José Manuel; Calderón-Salinas, José Victor; Villegas-Sepúlveda, Nicolás; Saucedo-Cárdenas, Odila; De Nova-Ocampo, Mónica; Valdés, Jesús

    2012-01-01

    The splicing of the N exon in the pre-mRNA coding for the RE1-silencing transcription factor (REST) results in a truncated protein that modifies the expression pattern of some of its target genes. A weak 3'ss, three alternative 5'ss (N4-, N50-, and N62-5'ss) and a variety of putative target sites for splicing regulatory proteins are found around the N exon; two GGGG codes (G2-G3) and a poly-Uridine tract (N-PU) are found in front of the N50-5'ss. In this work we analyzed some of the regulatory factors and elements involved in the preferred selection of the N50-5'ss (N50 activation) in the small cell lung cancer cell line H69. Wild type and mutant N exon/β-globin minigenes recapitulated N50 exon splicing in H69 cells, and showed that the N-PU and the G2-G3 elements are required for N50 exon splicing. Biochemical and knockdown experiments identified these elements as U2AF65 and hnRNP H targets, respectively, and that they are also required for N50 exon activation. Compared to normal MRC5 cells, and in keeping with N50 exon activation, U2AF65, hnRNP H and other splicing factors were highly expressed in H69 cells. CLIP experiments revealed that hnRNP H RNA-binding occurs first and is a prerequisite for U2AF65 RNA binding, and EMSA and CLIP experiments suggest that U2AF65-RNA recognition displaces hnRNP H and helps to recruit other splicing factors (at least U1 70K) to the N50-5'ss. Our results evidenced novel hnRNP H and U2AF65 functions: respectively, U2AF65-recruiting to a 5'ss in humans and the hnRNP H-displacing function from two juxtaposed GGGG codes. PMID:22792276

  1. Mechanisms of arrhythmogenesis related to calcium-driven alternans in a model of human atrial fibrillation

    NASA Astrophysics Data System (ADS)

    Chang, Kelly C.; Trayanova, Natalia A.

    2016-11-01

    The occurrence of atrial fibrillation (AF) is associated with progressive changes in the calcium handling system of atrial myocytes. Calcium cycling instability has been implicated as an underlying mechanism of electrical alternans observed in patients who experience AF. However, the extent to which calcium-induced alternation of electrical activity in the atria contributes to arrhythmogenesis is unknown. In this study, we investigated the effects of calcium-driven alternans (CDA) on arrhythmia susceptibility in a biophysically detailed, 3D computer model of the human atria representing electrical and structural remodeling secondary to chronic AF. We found that elevated propensity to CDA rendered the atria vulnerable to ectopy-induced arrhythmia. It also increased the complexity and persistence of arrhythmias induced by fast pacing, with unstable scroll waves meandering and frequently breaking up to produce multiple wavelets. Our results suggest that calcium-induced electrical instability may increase arrhythmia vulnerability and promote increasing disorganization of arrhythmias in the chronic AF-remodeled atria, thus playing an important role in the progression of the disease.

  2. Mechanisms of arrhythmogenesis related to calcium-driven alternans in a model of human atrial fibrillation

    PubMed Central

    Chang, Kelly C.; Trayanova, Natalia A.

    2016-01-01

    The occurrence of atrial fibrillation (AF) is associated with progressive changes in the calcium handling system of atrial myocytes. Calcium cycling instability has been implicated as an underlying mechanism of electrical alternans observed in patients who experience AF. However, the extent to which calcium-induced alternation of electrical activity in the atria contributes to arrhythmogenesis is unknown. In this study, we investigated the effects of calcium-driven alternans (CDA) on arrhythmia susceptibility in a biophysically detailed, 3D computer model of the human atria representing electrical and structural remodeling secondary to chronic AF. We found that elevated propensity to CDA rendered the atria vulnerable to ectopy-induced arrhythmia. It also increased the complexity and persistence of arrhythmias induced by fast pacing, with unstable scroll waves meandering and frequently breaking up to produce multiple wavelets. Our results suggest that calcium-induced electrical instability may increase arrhythmia vulnerability and promote increasing disorganization of arrhythmias in the chronic AF-remodeled atria, thus playing an important role in the progression of the disease. PMID:27812021

  3. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation

    PubMed Central

    Bernardo, Bianca C.; Sapra, Geeta; Patterson, Natalie L.; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A.; McMullen, Julie R.

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions. PMID:26660322

  4. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

    PubMed

    Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

  5. Evaluation of the Squirrel Monkey (Saimiri sciureus) as an Experimental Animal Model for Dysbaric Osteonecrosis.

    DTIC Science & Technology

    1976-01-07

    Osteonecrosis , Squirrel monkeys, Dysbarism, Decompression AM STRACT (Coalftwo Af VOW0 df it 060006 Red AV Ihib 6 In an attempt to develop an animal model for...subclinical decomipression sickness was produced. No clinical, radiologic, or post-mortem evidence of osteonecrosis was discovered during either the 6...ANIMAL MODE[L FOR DYSBARIC OSTEONECROSIS Uwsimemnt Ctoilo Jamm L. Kuppwr, USAF VC Naval Medical Rearchh and Doevlwomfnt Commxw SM~~?000.OI .01 .7022 A

  6. Developing the aquatic-coupled reservoir model to simulate carbon dioxide emission from a young boreal hydroelectric reservoir

    NASA Astrophysics Data System (ADS)

    Kim, Y.; Roulet, N. T.; Strachan, I. B.; Tremblay, A.

    2013-12-01

    We developed a process-based biogeochemical reservoir model, called AF-DNDC (Aquatic-coupled Forest-DNDC), to project carbon (C) flux from water surface of a recently created hydro-electric reservoir that flooded a boreal landscape. The basis of the reservoir model is Forest-DNDC, a biogeochemical model for C and nitrogen cycling in forests and wetlands. AF-DNDC was developed by coupling a lake C model to a flooded version of Forest-DNDC. AF-DNDC includes the C cycling through the aquatic carbon pools, such as DIC (dissolved inorganic C), DOC (dissolved organic C), and planktonic community as well as C exchange between air, water, and sediment. AF-DNDC was used to examine the net change in carbon dioxide (CO2) exchange between the surface and the atmosphere over the first seven years post flooding of the Eastmain-1 reservoir in northern Quebec. With present day climate and environmental conditions, simulated daily CO2 emissions from the flooded forest averaged 1.69 g C m-2 d-1 (range 0 to 20.49), and from the flooded peatland averaged 0.87 g C m-2 d-1 (range 0 to 6.86). Simulated CO2 emissions decreased with the age of reservoir. They were larger than eddy-covariance measured CO2 fluxes from the water surface over flooded forests, but compared well to the eddy-covariance fluxes during the open-water period. The simulated emissions were significantly correlated with the measured fluxes from the flooded forest (r2 = 0.33; p < 0.01) and flooded peatland (r2 = 0.41; p < 0.01). The patterns over the year were similar. AF-DNDC is suitable for use to assess the major changes in CO2 exchange due to the creation of reservoirs in boreal regions.

  7. Measurement of the inclusive t t xAF production cross section in p p xAF collisions at √{s }=1.96 TeV and determination of the top quark pole mass

    NASA Astrophysics Data System (ADS)

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Agnew, J. P.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Askew, A.; Atkins, S.; Augsten, K.; Aushev, Y.; Avila, C.; Badaud, F.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bazterra, V.; Bean, A.; Begalli, M.; Bellantoni, L.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Blazey, G.; Blessing, S.; Bloom, K.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Borysova, M.; Brandt, A.; Brandt, O.; Brock, R.; Bross, A.; Brown, D.; Bu, X. B.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Buszello, C. P.; Camacho-Pérez, E.; Casey, B. C. K.; Castilla-Valdez, H.; Caughron, S.; Chakrabarti, S.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Cho, S. W.; Choi, S.; Choudhary, B.; Cihangir, S.; Claes, D.; Clutter, J.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M.-C.; Cuth, J.; Cutts, D.; Das, A.; Davies, G.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Deterre, C.; DeVaughan, K.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dominguez, A.; Dubey, A.; Dudko, L. V.; Duperrin, A.; Dutt, S.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Evans, H.; Evdokimov, A.; Evdokimov, V. N.; Fauré, A.; Feng, L.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Fortner, M.; Fox, H.; Franc, J.; Fuess, S.; Garbincius, P. H.; Garcia-Bellido, A.; García-González, J. A.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gershtein, Y.; Ginther, G.; Gogota, O.; Golovanov, G.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Gris, Ph.; Grivaz, J.-F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Gutierrez, G.; Gutierrez, P.; Haley, J.; Han, L.; Harder, K.; Harel, A.; Hauptman, J. M.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Holzbauer, J. L.; Howley, I.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jayasinghe, A.; Jeong, M. S.; Jesik, R.; Jiang, P.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Joshi, J.; Jung, A. W.; Juste, A.; Kajfasz, E.; Karmanov, D.; Katsanos, I.; Kaur, M.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kiselevich, I.; Kohli, J. M.; Kozelov, A. V.; Kraus, J.; Kumar, A.; Kupco, A.; Kurča, T.; Kuzmin, V. A.; Lammers, S.; Lebrun, P.; Lee, H. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, H.; Liu, Y.; Lobodenko, A.; Lokajicek, M.; Lopes de Sa, R.; Luna-Garcia, R.; Lyon, A. L.; Maciel, A. K. A.; Madar, R.; Magaña-Villalba, R.; Malik, S.; Malyshev, V. L.; Mansour, J.; Martínez-Ortega, J.; McCarthy, R.; McGivern, C. L.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Meyer, A.; Meyer, J.; Miconi, F.; Mondal, N. K.; Mulhearn, M.; Nagy, E.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nguyen, H. T.; Nunnemann, T.; Orduna, J.; Osman, N.; Osta, J.; Pal, A.; Parashar, N.; Parihar, V.; Park, S. K.; Partridge, R.; Parua, N.; Patwa, A.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Pleier, M.-A.; Podstavkov, V. M.; Popov, A. V.; Prewitt, M.; Price, D.; Prokopenko, N.; Qian, J.; Quadt, A.; Quinn, B.; Ratoff, P. N.; Razumov, I.; Ripp-Baudot, I.; Rizatdinova, F.; Rominsky, M.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Sánchez-Hernández, A.; Sanders, M. P.; Santos, A. S.; Savage, G.; Savitskyi, M.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schott, M.; Schwanenberger, C.; Schwienhorst, R.; Sekaric, J.; Severini, H.; Shabalina, E.; Shary, V.; Shaw, S.; Shchukin, A. A.; Simak, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Soustruznik, K.; Stark, J.; Stoyanova, D. A.; Strauss, M.; Suter, L.; Svoisky, P.; Titov, M.; Tokmenin, V. V.; Tsai, Y.-T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Verkheev, A. Y.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vilanova, D.; Vokac, P.; Wahl, H. D.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; Williams, M. R. J.; Wilson, G. W.; Wobisch, M.; Wood, D. R.; Wyatt, T. R.; Xie, Y.; Yamada, R.; Yang, S.; Yasuda, T.; Yatsunenko, Y. A.; Ye, W.; Ye, Z.; Yin, H.; Yip, K.; Youn, S. W.; Yu, J. M.; Zennamo, J.; Zhao, T. G.; Zhou, B.; Zhu, J.; Zielinski, M.; Zieminska, D.; Zivkovic, L.; D0 Collaboration

    2016-11-01

    The inclusive cross section of top quark-antiquark pairs produced in p p ¯ collisions at √{s }=1.96 TeV is measured in the lepton+jets and dilepton decay channels. The data sample corresponds to 9.7 fb-1 of integrated luminosity recorded with the D0 detector during Run II of the Fermilab Tevatron Collider. Employing multivariate analysis techniques we measure the cross section in the two decay channels and we perform a combined cross section measurement. For a top quark mass of 172.5 GeV, we measure a combined inclusive top quark-antiquark pair production cross section of σt t ¯=7.26 ±0.13 (stat )-0.50+0.57(syst ) pb which is consistent with standard model predictions. We also perform a likelihood fit to the measured and predicted top quark mass dependence of the inclusive cross section, which yields a measurement of the pole mass of the top quark. The extracted value is mt=172.8 ±1.1 (theo )-3.1+3.3(exp ) GeV .

  8. Tribological characteristics of bisphenol AF bis(diphenyl phosphate) as an antiwear additive in polyalkylene glycol and polyurea grease for significantly improved lubrication

    NASA Astrophysics Data System (ADS)

    Zhu, Lili; Wu, Xinhu; Zhao, Gaiqing; Wang, Xiaobo

    2016-02-01

    A new antiwear additive of Bisphenol AF bis(diphenyl phosphate) (BAFDP) was synthesized and characterized. The tribological behaviors of the additive for polyalkylene glycol (PAG) and polyurea grease (PG) application in steel/steel contacts were evaluated on an Optimol SRV-IV oscillating reciprocating friction and wear tester at elevated temperature. The results revealed that BAFDP could drastically reduce friction and wear of sliding pairs in both PAG and also in PG at 100 °C. The tribological properties of BAFDP are superior to the normally used zinc dialkyldithiophosphate-based additive package (ZDDP) in PAG and PG. Moreover, BAFDP as additive for PAG and PG displays relatively significant tribological properties in temperature-ramp tests by performing well at 50-300 °C, indicating the excellent high temperature friction reduction and anti-wear capacity of BAFDP. XPS results showed that boundary lubrication films composed of Fe(OH)O, Fe3O4, FePO4, FeF2, FeF3, compounds containing the Psbnd O bonds, nitrogen oxide, and so forth, were formed on the worn surface, which contributed to excellent friction reduction and antiwear performance.

  9. Analysis of β-glucan molar mass from barley malt and brewer's spent grain with asymmetric flow field-flow fractionation (AF4) and their association to proteins.

    PubMed

    Zielke, Claudia; Teixeira, Cristina; Ding, Huihuang; Cui, Steve; Nyman, Margareta; Nilsson, Lars

    2017-02-10

    β-Glucan benefits are related with its molar mass and it would be of interest to better understand how this parameter can be changed by processing and variety for design of food with specific health effects. For this purpose, extracts from barley malts and brewers' spent grain, processed at different conditions, were analysed regarding β-glucan content, molar mass, and protein content. Molar mass distribution was assessed using asymmetric flow field-flow fractionation (AF4) with multiangle light scattering (MALS), differential refractive index (dRI) and fluorescence (FL) detection. β-Glucan was detected in a wide molar mass range, <2000 to approximately 6.7×10(6)g/mol. Differences in molar masses were more noticeable between barley varieties and steeping malting conditions than by mashing of malt. Barley products processed to preserve β-glucan contained more β-glucan of high molar mass with potential to shift the fermentation site to the distal colon. Enzymatic degradation of proteins indicated presence of aggregates containing β-glucan and protein.

  10. Autophagy is dispensable for Kmt2a/Mll-Mllt3/Af9 AML maintenance and anti-leukemic effect of chloroquine.

    PubMed

    Chen, Xiaoyi; Clark, Jason; Wunderlich, Mark; Fan, Cuiqing; Davis, Ashley; Chen, Song; Guan, Jun-Lin; Mulloy, James C; Kumar, Ashish; Zheng, Yi

    2017-02-15

    Recently, macroautophagy/autophagy has emerged as a promising target in various types of solid tumor treatment. However, the impact of autophagy on acute myeloid leukemia (AML) maintenance and the validity of autophagy as a viable target in AML therapy remain unclear. Here we show that Kmt2a/Mll-Mllt3/Af9 AML (MA9-AML) cells have high autophagy flux compared with normal bone marrow cells, but autophagy-specific targeting, either through Rb1cc1-disruption to abolish autophagy initiation, or via Atg5-disruption to prevent phagophore (the autophagosome precursor) membrane elongation, does not affect the growth or survival of MA9-AML cells, either in vitro or in vivo. Mechanistically, neither Atg5 nor Rb1cc1 disruption impairs endolysosome formation or survival signaling pathways. The autophagy inhibitor chloroquine shows autophagy-independent anti-leukemic effects in vitro but has no efficacy in vivo likely due to limited achievable drug efficacy in blood. Further, vesicular exocytosis appears to mediate chloroquine resistance in AML cells, and exocytotic inhibition significantly enhances the anti-leukemic effect of chloroquine. Thus, chloroquine can induce leukemia cell death in vitro in an autophagy-independent manner but with inadequate efficacy in vivo, and vesicular exocytosis is a possible mechanism of chloroquine resistance in MA9-AML. This study also reveals that autophagy-specific targeting is unlikely to benefit MA9-AML therapy.

  11. The Effects of Temperature, Humidity and Aircraft Fluid Exposure on T800H/3900-2 Composites Bonded with AF-555M Adhesive

    NASA Technical Reports Server (NTRS)

    Miner, Gilda A.; Hou, Tan-Hung; Lowther, Sharon E.; Thibeault, Sheila A.; Connell, John W.; Blasini, Sheila Roman

    2010-01-01

    Fiber reinforced resin matrix composites and structural adhesives have found increased usage on commercial and military aircraft in recent years. Due to the lack of service history of these relatively new material systems, their long-term aging performance has not been well established. In this study, single lap shear specimens (SLS) were fabricated by secondary bonding of Scotch-Weld(TradeMark) AF-555M between pre-cured adherends comprised of T800H/3900-2 uni-directional laminates. The adherends were co-cured with wet peel-ply for surface preparation. Each bond-line of the SLS specimen was measured to determine thickness and inspected visually using an optical microscope for voids. A three-year environmental aging plan for the SLS specimens at 82 C (180 F) and 85% relative humidity was initiated. SLS strengths were measured for both controls and aged specimens at room temperature and 82 C. The effect of this exposure on lap shear strength and failure modes to date is reported. In addition, the effects of water, saline water, deicing fluid, JP-5 jet fuel and hydraulic fluid on both the composite material and the adhesive bonds were investigated. The up to date results on the effects of these exposures will be discussed.

  12. Multi-pair two-way massive MIMO AF relaying with ZFR/ZFT beamforming and imperfect CSI over ricean fading channels

    NASA Astrophysics Data System (ADS)

    Xu, Kui; Sun, Xiaoli; Zhang, Dongmei

    2016-10-01

    This paper investigates the spectral and energy efficiencies of a multi-pair two-way amplify-and-forward (AF) relay system over Ricean fading channels, where multiple user-pairs exchange information within pair through a relay with very large number of antennas, while each user equipped with a single antenna. Firstly, beamforming matrixe of zero-forcing reception/zero-forcing transmission (ZFR/ZFT) with imperfect channel state information (CSI) at the relay is given. Then, the unified asymptotic signal-to-interference-plus-noise ratio (SINR) expressions with imperfect CSI are obtained analytically. Finally, two power scaling schemes are proposed and the asymptotic spectral and energy efficiencies based on the proposed power scaling schemes are derived and verified by the Monte-Carlo simulations. Theoretical analyses and simulation results show that with imperfect CSI, if the number of relay antennas grows asymptotically large, we need cut down the transmit power of each user and relay to different proportion when the Ricean K-factor is non-zero and zero (Rayleigh fading) in order to maintain a desirable rate.

  13. General single phase wellbore flow model

    SciTech Connect

    Ouyang, Liang-Biao; Arbabi, S.; Aziz, K.

    1997-02-05

    A general wellbore flow model, which incorporates not only frictional, accelerational and gravitational pressure drops, but also the pressure drop caused by inflow, is presented in this report. The new wellbore model is readily applicable to any wellbore perforation patterns and well completions, and can be easily incorporated in reservoir simulators or analytical reservoir inflow models. Three dimensionless numbers, the accelerational to frictional pressure gradient ratio R{sub af}, the gravitational to frictional pressure gradient ratio R{sub gf}, and the inflow-directional to accelerational pressure gradient ratio R{sub da}, have been introduced to quantitatively describe the relative importance of different pressure gradient components. For fluid flow in a production well, it is expected that there may exist up to three different regions of the wellbore: the laminar flow region, the partially-developed turbulent flow region, and the fully-developed turbulent flow region. The laminar flow region is located near the well toe, the partially-turbulent flow region lies in the middle of the wellbore, while the fully-developed turbulent flow region is at the downstream end or the heel of the wellbore. Length of each region depends on fluid properties, wellbore geometry and flow rate. As the distance from the well toe increases, flow rate in the wellbore increases and the ratios R{sub af} and R{sub da} decrease. Consequently accelerational and inflow-directional pressure drops have the greatest impact in the toe region of the wellbore. Near the well heel the local wellbore flow rate becomes large and close to the total well production rate, here R{sub af} and R{sub da} are small, therefore, both the accelerational and inflow-directional pressure drops can be neglected.

  14. Evaluation of ultrasonic scattering in human cancellous bone by using a binary mixture model.

    PubMed

    Guo, Xiasheng; Zhang, Dong; Gong, Xiufen

    2007-01-07

    A weak scattering model based on small perturbations in a binary mixture is developed to estimate the ultrasonic scattering from human cancellous bone, which is modelled as a random isotropic continuum containing identical scatters. Ultrasonic scattering is determined by both velocity fluctuation and density fluctuation, when k(2)a(2) < 1 is satisfied. Two kinds of trabeculae thickness distributions, i.e. even distribution and Gauss distribution, are applied in the calculation of attenuation and backscattering. Frequency dependence of the backscatter coefficient is found to be Af(3.13) and Af(2.84) with the Gauss distribution and an even distribution, respectively. Both backscattering and attenuation change significantly against porosity for the case of high porosity. The predicted results are close to the measured ones from the literature. The errors of this theoretical model are also discussed in this paper.

  15. First Article Noise Survey of the A/F32T-9 Large Turbo Fan Engine Enclosed Noise Suppressor System, Far-Field Noise, McConnell AFB, Kansas.

    DTIC Science & Technology

    1987-05-01

    Continue on reverse if necessary and identify by block number) ’FIELD GROUP SUB-GROUP A/F32T-9 Jet Engine Noise Engine Test Cell Noise Suppressor Noise T-9...energy reflected off of the surrounding buildings and the spurious and transient nature of aircraft operations noise from the flight line . It is...interfering noise from highly active flight line operations. F-4s and KC-135 flyovers were routine, as were helicopters. Noise from ground support equipment

  16. First article noise survey of the A/F32T-9 large turbo fan engine enclosed noise suppressor system, far-field noise, McConnell AFB, Kansas

    NASA Astrophysics Data System (ADS)

    Fairman, Terry M.

    1987-05-01

    This report presents the results of noise measurements made on the A/F32T-9 Large Turbo Fan Engine, Enclosed Noise Suppressor System, during First Article Tests at McConnell AFB, Kansas. Noise measurements obtained at 100 meters distance are summarized for the following engines: the J57-59W, TF33-P3, TF30-P7, F100, TF41-A1, J85-5, F101-GE-102, and the F109-CF-100.

  17. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

    PubMed Central

    Dreyling, M H; Martinez-Climent, J A; Zheng, M; Mao, J; Rowley, J D; Bohlander, S K

    1996-01-01

    The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. Images Fig. 1 Fig. 3 PMID:8643484

  18. Prevalence of cry2-type genes in Bacillus thuringiensis isolates recovered from diverse habitats in India and isolation of a novel cry2Af2 gene toxic to Helicoverpa armigera (cotton boll worm).

    PubMed

    Katara, Jawahar Lal; Kaur, Sarvjeet; Kumari, Gouthami Krishna; Singh, Nagendra Kumar

    2016-12-01

    Insecticidal cry and vip genes from Bacillus thuringiensis (Bt) have been used for control of lepidopteran insects in transgenic crops. However, novel genes are required for gene pyramiding to delay evolution of resistance to the currently deployed genes. Two PCR-based techniques were employed for screening of cry2-type genes in 129 Bt isolates from diverse habitats in India and 27 known Bt strains. cry2Ab-type genes were more prevalent than cry2Aa- and cry2Ac-type genes. Correlation between source of isolates and abundance of cry2-type genes was not observed. Full-length cry2A-type genes were amplified by PCR from 9 Bt isolates and 4 Bt strains. The genes from Bt isolates SK-758 from Sorghum grain dust and SK-793 from Chilli seeds warehouse, Andhra Pradesh, were cloned and sequenced. The gene from SK-758 (NCBI GenBank accession No. GQ866915) was novel, while that from SK-793 (NCBI GenBank accession No. GQ866914) was identical to the cry2Ab1 gene. The Bacillus thuringiensis Nomenclature Committee ( http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/toxins2.html ) named these genes cry2Af2 and cry2Ab16, respectively. The cry2Af2 gene was expressed in Escherichia coli and found to be toxic towards Helicoverpa armigera. The cry2Af2 gene will be useful for pyramiding in transgenic crops.

  19. Clinical, Echocardiographic, and Electrocardiographic Predictors of Persistent Atrial Fibrillation after Dual-Chamber Pacemaker Implantation: An Integrated Scoring Model Approach

    PubMed Central

    Cho, Min Soo; Kim, Ju Hyeon; Kim, Minsu; Lee, Ji Hyun; Hwang, You Mi; Jo, Uk; Nam, Gi-Byoung; Choi, Kee-Joon; Kim, You-Ho

    2016-01-01

    Persistent atrial fibrillation (PeAF) predictors after dual-chamber pacemaker (PM) implantation remain unclear. We sought to determine these predictors and establish an integrated scoring model. Data were retrospectively reviewed for 649 patients (63.8 ± 12.3 years, 48.6% male, mean CHA2DS2–VASC score 2.7 ± 2.0) undergoing dual-chamber PM implantation. PeAF was defined as documented AF on two consecutive electrocardiograms acquired ≥7 days apart. During a 7.1-year median follow-up (interquartile range 4.5–10.1 years), 67 (10.3%) patients had PeAF. Multivariable analysis showed the following independent predictors of future PeAF: ischemic stroke or transient ischemic accident history (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.03–3.50, p = 0.040), atrial fibrillation/flutter history (HR 1.80, 95% CI 1.01–3.20, p = 0.046), sinus node disease (HR 2.24, 95% CI 1.16–4.35, p = 0.016), left atrial enlargement (>45 mm, HR 2.14, 95% CI 1.26–3.63, p = 0.005), and time in automatic mode switching >1% at first follow-up interrogation (HR 2.58, 95% CI 1.51–4.42, p < 0.001). An integrated scoring model combining these predictors showed good discrimination performance at the seven-year follow-up. (C-statistic 0.716, 95% CI 0.629–0.802, p < 0.001). Significantly greater seven-year PeAF incidences were seen in patients with higher scores (2–5) than in those with lower scores (0–1) (22.8% ± 3.8% vs. 5.3% ± 1.7%, p < 0.001). In conclusion, an integrated scoring model combining clinical, echocardiographic, and electrocardiographic characteristics is useful for predicting future PeAF in patients with a dual-chamber PM. PMID:27479069

  20. A Process Model of Organizational Commitment and Job Involvement.

    DTIC Science & Technology

    1982-09-01

    AD-A123 043 A PROCESS MODEL OF ORGANIZATIONAL COMMITMENT AND JOB I INVOLVEMENT(U) AIR FORCE INST OF TECH WR IGHT PATTERSON AFB OH SCHOL OF SYSTEMS...Appo @1 inu pubo 01004 Aocesston For NTIS CRA&I DTIC TAB Unannounced 0I Justfication - gI, Distr" ’ut ioi / Af t A PROCESS MODEL OF ORGANIZATIONAL...GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER LSSR 76-82 1,3b - 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED A PROCESS MODEL OF

  1. Effect of aerosols and NO2 concentration on ultraviolet actinic flux near Mexico City during MILAGRO: measurements and model calculations

    SciTech Connect

    Palancar, G. G.; Lefer, B. L.; Hall, S. R.; Shaw, W. J.; Corr, C. A.; Herndon, S. C.; Slusser, J. R.; Madronich, S.

    2013-01-24

    Ultraviolet (UV) actinic fluxes (AF) measured with three Scanning Actinic Flux Spectroradiometers (SAFS) are compared with the Tropospheric Ultraviolet-Visible (TUV) model v.5 in order to assess the effects of aerosols and NO2 concentrations on the radiation. Measurements were made during the MILAGRO campaign near Mexico City in March 2006, at a ground-based station near Mexico City (the T1 supersite) and from the NSF/NCAR C-130 aircraft. At the surface, measurements are typically smaller by up to 25 % in the morning, 10% at noon, and 40% in the afternoon, than actinic flux modeled for clean, cloud-free conditions. When measurements of PBL height, NO2 concentration and aerosols optical properties are included in the model, the agreement improves to within ±10% in the morning and afternoon, and ±3% at noon. Based on daily averages, aerosols account for 68%, NO2 for 25%, and residual uncertainties for 7% of these AF reductions observed at the surface. Several overpasses from the C-130 aircraft provided the opportunity to examine the actinic flux perturbations aloft, and also show better agreement with the model when aerosol and NO2 effects are included above and below the flight altitude. TUV model simulations show that the vertical structure of the actinic flux is sensitive to the choice of the aerosol single scattering albedo (SSA) at UV wavelengths. Typically, aerosols caused enhanced AF above the PBL and reduced AF near the surface. However, for highly scattering aerosols (SSA > 0.95), enhancements can penetrate well into the PBL, while for strongly absorbing aerosols (SSA<0.7) reductions in AF are computed in the free troposphere as well as in the PBL. Finally, additional measurements of the SSA at these wavelengths are needed to better constrain the effect of aerosols on the vertical structure of the actinic flux.

  2. Mathematical models and specific absorbed fractions of photon energy in the nonpregnant adult female and at the end of each trimester of pregnancy

    SciTech Connect

    Stabin, M.G.; Watson, E.E.; Cristy, M.; Ryman, J.C.; Eckerman, K.F.; Davis, J.L.; Marshall, D.; Gehlen, M.K.

    1995-05-08

    Mathematical phantoms representing the adult female at three, six, and nine months of gestation are described. They are modifications of the 15-year-old male/adult female phantom (15-AF phantom) of Cristy and Eckerman (1987). The model of uterine contents includes the fetus, fetal skeleton, and placenta. The model is suitable for dose calculations for the fetus as a whole; individual organs within the fetus (other than the skeleton) are not modeled. A new model for the nonpregnant adult female is also described, comprising (1) the 15-AF phantom; (2) an adjustment to specific absorbed fractions for organ self-dose from photons to better match Reference Woman masses; and (3) computation of specific absorbed fractions with Reference Woman masses from ICRP Publication 23 for both penetrating and nonpenetrating radiations. Specific absorbed fractions for photons emitted from various source regions are tabulated for the new non;pregnant adult female model and the three pregnancy models.

  3. Fluence-to-dose conversion coefficients based on the posture modification of Adult Male (AM) and Adult Female (AF) reference phantoms of ICRP 110

    NASA Astrophysics Data System (ADS)

    Galeano, D. C.; Santos, W. S.; Alves, M. C.; Souza, D. N.; Carvalho, A. B.

    2016-04-01

    The aim of this work was to modify the standing posture of the anthropomorphic reference phantoms of ICRP publication 110, AM (Adult Male) and AF (Adult Female), to the sitting posture. The change of posture was performed using the Visual Monte Carlo software (VMC) to rotate the thigh region of the phantoms and position it between the region of the leg and trunk. Scion Image software was used to reconstruct and smooth the knee and hip contours of the phantoms in a sitting posture. For 3D visualization of phantoms, the VolView software was used. In the change of postures, the organ and tissue masses were preserved. The MCNPX was used to calculate the equivalent and effective dose conversion coefficients (CCs) per fluence for photons for six irradiation geometries suggested by ICRP publication 110 (AP, PA, RLAT, LLAT, ROT and ISO) and energy range 0.010-10 MeV. The results were compared between the standing and sitting postures, for both sexes, in order to evaluate the differences of scattering and absorption of radiation for different postures. Significant differences in the CCs for equivalent dose were observed in the gonads, colon, prostate, urinary bladder and uterus, which are present in the pelvic region, and in organs distributed throughout the body, such as the lymphatic nodes, muscle, skeleton and skin, for the phantoms of both sexes. CCs for effective dose showed significant differences of up to 16% in the AP irradiation geometry, 27% in the PA irradiation geometry and 13% in the ROT irradiation geometry. These results demonstrate the importance of using phantoms in different postures in order to obtain more precise conversion coefficients for a given exposure scenario.

  4. Anteaglonialides A-F and Palmarumycins CE(1)-CE(3) from Anteaglonium sp. FL0768, a Fungal Endophyte of the Spikemoss Selaginella arenicola.

    PubMed

    Xu, Ya-ming; Mafezoli, Jair; Oliveira, Maria C F; U'Ren, Jana M; Arnold, A Elizabeth; Gunatilaka, A A Leslie

    2015-11-25

    Anteaglonialides A-F (1-6), bearing a spiro[6-(tetrahydro-7-furanyl)cyclohexane-1,2'-naphtho[1,8-de][1,3]-dioxin]-10-one skeleton, three new spirobisnaphthalenes, palmarumycins CE1-CE3 (7-9), nine known palmarumycin analogues, palmarumycins CP5 (10), CP4a (11), CP3 (12), CP17 (13), CP2 (14), and CP1 (15), CJ-12,371 (16), 4-O-methyl CJ-12,371 (17), and CP4 (18), together with a possible artifact, 4a(5)-anhydropalmarumycin CE2 (8a), and four known metabolites, O-methylherbarin (19), herbarin (20), herbaridine B (21), and hyalopyrone (22), were encountered in a cytotoxic extract of a potato dextrose agar culture of Anteaglonium sp. FL0768, an endophytic fungus of the sand spikemoss, Selaginella arenicola. The planar structures and relative configurations of the new metabolites 1-9 were elucidated by analysis of extensive spectroscopic data, and the absolute configuration of 1 was determined by the modified Mosher's ester method. Application of the modified Mosher's ester method combined with the NOESY data resulted in revision of the absolute configuration previously proposed for 10. Co-occurrence of 1-6 and 7-18 in this fungus led to the proposal that the anteagloniolides may be biogenetically derived from palmarumycins. Among the metabolites encountered, anteaglonialide F (6) and known palmarumycins CP3 (12) and CP1 (15) exhibited strong cytotoxic activity against the human Ewing's sarcoma cell line CHP-100, with IC50 values of 1.4, 0.5, and 1.6 μM, respectively.

  5. Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study)

    PubMed Central

    Takeuchi, K.; Togashi, Y.; Kamihara, Y.; Fukuyama, T.; Yoshioka, H.; Inoue, A.; Katsuki, H.; Kiura, K.; Nakagawa, K.; Seto, T.; Maemondo, M.; Hida, T.; Harada, M.; Ohe, Y.; Nogami, N.; Yamamoto, N.; Nishio, M.; Tamura, T.

    2016-01-01

    Background Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. Patients and methods In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. Result ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Conclusions Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. Registration number JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center). PMID:26487585

  6. Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension: a subgroup analysis of the J-ROCKET AF trial.

    PubMed

    Matsumoto, Masayasu; Hori, Masatsugu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-05-01

    The majority of the patients enrolled in the rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial had hypertension. In this subgroup analysis, we investigated differences in the safety and efficacy of rivaroxaban and warfarin in subjects with and without hypertension. The baseline blood pressure (BP) measurements of patients with hypertension in the rivaroxaban and warfarin groups were 130/77 mm Hg and 131/77 mm Hg, respectively, whereas those of patients without hypertension were 123/74 mm Hg and 124/73 mm Hg, respectively. The incidence rates of the principal safety outcomes in the rivaroxaban and warfarin groups were 18.39% per year and 16.81% per year, respectively, among patients with baseline hypertension (hazard ratio (HR): 1.10; 95% confidence interval (CI): 0.84-1.45) and 16.71% per year and 15.00% per year, respectively, among patients without hypertension at baseline (HR: 1.14; 95% CI: 0.66-1.97), indicating no significant interaction (P=0.933). The incidence rates of the primary efficacy endpoints in the rivaroxaban group and the warfarin group were 0.54% per year and 2.24% per year, respectively, in patients without baseline hypertension (HR: 0.25; 95% CI: 0.03-2.25), and 1.45% per year and 2.71% per year, respectively, in patients with baseline hypertension (HR: 0.54; 95% CI: 0.25-1.16), indicating no significant interaction (P=0.509). In conclusion, the safety and efficacy profile of rivaroxaban was similar to that of warfarin, independent of baseline hypertensive status.

  7. Development of a New Chemotherapy for Human African Trypanosomiasis by Using an Animal Model: Suramin with DL-Alpha-Difluoromethylornithine

    DTIC Science & Technology

    1989-09-14

    AD-A237 230_ DEVELOPMENT OF A NEW CHEMOTHERAPY FOR HUMAN AFRICAN TRYPANOSOMIASIS BY USING AN ANIMAL MODEL: SURAMIN WITH DL..DIFLUOROMETHYLORNITHINE... Chemotherapy for African trypanosomiasis by polyamine biosynthesis inhibition.) FINAL PROGRESS REPORT Allen B. Clarkson, Jr., Ph.D. September 14, 1989...AF 061 11. TITLE (include Security Classification) "Development of a New Chemotherapy for Human African Trypanosomiasis by Using an Animal Model

  8. Multi-decadal Variability of Indian Summer Monsoon in CMIP5 Models

    NASA Astrophysics Data System (ADS)

    Sandeep, S.; Ravindran, A.

    2013-12-01

    The multi-decadal variability of Indian Summer Monsoon (ISM) Rainfall in the fifth phase Coupled Model Inter-comparison Project (CMIP5) climate model simulations is analyzed. Recent studies, suggest a slight weakening of the Indian precipitation as assessed from CMIP3 simulations. The ISM rainfall simulated by CMIP5 runs with all historical forcing (AF) also suggest a strong multi-decadal weakening trend in ISM precipitation during 1901 - 2005. Further, the decadal scale variability in ISM land precipitation in multi model ensemble of AF simulations is fairly comparable with the observed variability. However, these simulations show patterns of regional variability and trends within the monsoon domain. The CMIP5 ensembles with natural variability alone and those with only Green House Gas (GHG) forcing could not reproduce the observed variability in ISM precipitation. This suggests strong influence of anthropogenic aerosols on multi-decadal variability in ISM precipitation, which is consistent with previous findings. Further investigation revealed that the weakening of zonal winds in AF simulations, possibly due to aerosol induced weakening in land-ocean thermal contrast, resulted in reduced moisture transport from ocean to the land. The trends and variability of ISM in multi model ensemble of CMIP5 simulations will be discussed in detail.

  9. The E-MS Algorithm: Model Selection with Incomplete Data.

    PubMed

    Jiang, Jiming; Nguyen, Thuan; Rao, J Sunil

    2015-04-04

    We propose a procedure associated with the idea of the E-M algorithm for model selection in the presence of missing data. The idea extends the concept of parameters to include both the model and the parameters under the model, and thus allows the model to be part of the E-M iterations. We develop the procedure, known as the E-MS algorithm, under the assumption that the class of candidate models is finite. Some special cases of the procedure are considered, including E-MS with the generalized information criteria (GIC), and E-MS with the adaptive fence (AF; Jiang et al. 2008). We prove numerical convergence of the E-MS algorithm as well as consistency in model selection of the limiting model of the E-MS convergence, for E-MS with GIC and E-MS with AF. We study the impact on model selection of different missing data mechanisms. Furthermore, we carry out extensive simulation studies on the finite-sample performance of the E-MS with comparisons to other procedures. The methodology is also illustrated on a real data analysis involving QTL mapping for an agricultural study on barley grains.

  10. Reentrant phase transitions of a coupled spin-electron model on doubly decorated planar lattices with two or three consecutive critical points

    NASA Astrophysics Data System (ADS)

    Čenčariková, Hana; Strečka, Jozef; Lyra, Marcelo L.

    2016-03-01

    The generalized decoration-iteration transformation is adapted for the exact study of a coupled spin-electron model on 2D lattices in which localized Ising spins reside on nodal lattice sites and mobile electrons are delocalized over pairs of decorating sites. The model takes into account a hopping term for mobile electrons, the Ising coupling between mobile electrons and localized spins as well as the Ising coupling between localized spins (J ‧). The ground state, spontaneous magnetization and specific heat are examined for both ferromagnetic (J ‧ > 0) as well as antiferromagnetic (J ‧ < 0) interaction between the localized spins. Several kinds of reentrant transitions between the paramagnetic (P), antiferromagnetic (AF) and ferromagnetic (F) phases have been found either with a single critical point, or with two consecutive critical points (P - AF / F - P) and three successive critical points AF / F - P - F / AF - P. Striking thermal variations of the spontaneous magnetization depict a strong reduction due to the interplay between annealed disorder and quantum fluctuations in addition to the aforementioned reentrance. It is shown that the specific heat displays diverse thermal dependencies including finite cusps at the critical temperatures.

  11. Atrial Fibrillation (AF or AFib)

    MedlinePlus

    ... Giving for Heart.org Media for Heart.org Arrhythmia About Arrhythmia Why Arrhythmia Matters Understand Your Risk for Arrhythmia Symptoms, Diagnosis & Monitoring of Arrhythmia Prevention & Treatment of ...

  12. AFS Orientation Handbook. Volume IV.

    ERIC Educational Resources Information Center

    Zaremba, Mary Ann; And Others

    This handbook is intended for use by all who design, plan, and lead orientation and cross-cultural training sessions for American Field Service students, natural and host families, and volunteers. It features orientation and training resources originating in Venezuela, France, Italy, Denmark, Canada, Argentina, Japan, Portugal, Germany, and the…

  13. A Model of Median Auroral Electron Flux Deduced from Hardy 2008 Model Probability Density Maps

    DTIC Science & Technology

    2013-11-01

    example of the precipitating electron energy flux map in the Northern hemisphere for Kp=3 produced by AF- Geospace software...AF- Geospace Software (Hilmer, 2010) illustrates the precipitating electron energy flux map in the Northern hemisphere for Kp = 3...precipitating electron energy flux map in the Northern hemisphere for Kp=3 produced by AF- Geospace software. The green line specifies the auroral oval

  14. Dissipative preparation of antiferromagnetic order in the Fermi-Hubbard model

    NASA Astrophysics Data System (ADS)

    Kaczmarczyk, J.; Weimer, H.; Lemeshko, M.

    2016-09-01

    The Fermi-Hubbard model is one of the key models of condensed matter physics, which holds a potential for explaining the mystery of high-temperature superconductivity. Recent progress in ultracold atoms in optical lattices has paved the way to studying the model’s phase diagram using the tools of quantum simulation, which emerged as a promising alternative to the numerical calculations plagued by the infamous sign problem. However, the temperatures achieved using elaborate laser cooling protocols so far have been too high to show the appearance of antiferromagnetic (AF) and superconducting quantum phases directly. In this work, we demonstrate that using the machinery of dissipative quantum state engineering, one can observe the emergence of the AF order in the Fermi-Hubbard model with fermions in optical lattices. The core of the approach is to add incoherent laser scattering in such a way that the AF state emerges as the dark state of the driven-dissipative dynamics. The proposed controlled dissipation channels described in this work are straightforward to add to already existing experimental setups.

  15. Renal Denervation Suppresses the Inducibility of Atrial Fibrillation in a Rabbit Model for Atrial Fibrosis

    PubMed Central

    Zhou, Genqing; Chen, Songwen; Ouyang, Ping; Liu, Shaowen

    2016-01-01

    Renal denervation (RD) was reported to reduce the susceptibility of atrial fibrillation (AF), but the underlying mechanism has not been well understood. This study was performed to investigate the effect of RD on the inducibility of AF in a rabbit model for atrial fibrosis and to explore the potential mechanisms. Thirty-five rabbits were randomly assigned into sham-operated group (n = 12), abdominal aortic constriction (AAC) group (n = 12) and AAC with RD (AAC-RD) group (n = 11). The incidence of AF induced by burst pacing in atriums was determined. Blood was collected to measure the levels of rennin, angiotensin II and aldosterone. Atrial samples were preserved to evaluate protein and gene expression of collagen, connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1). Our data suggested cardiac structure remodeling and atrial fibrosis were successfully induced by AAC. Compared with the AAC group, the AAC-RD rabbits had smaller ascending aortic diameter and left ventricular end-systolic diameter. For burst pacing at the left atrium (LA), AF was induced in two of the 12 rabbits in the sham-operated group, 10 of the 12 rabbits in the AAC group, and 2 of the 11 rabbits in the AAC-RD group, with great difference among the three groups (P = 0.001). The percentage of LA burst stimulations with induced AF achieved 47.2% in the AAC group, which was higher than those in both the AAC-RD (12.1%) and the Sham-operated (5.6%) groups. Significantly increasing intercellular space in the AAC group (P<0.001) compared with the sham-operated rabbits. RD clearly decreased the volume fraction of collagen in LA and right atrium compared with that of the AAC group (P< 0.01). AAC-induced elevation of collagen I, CTGF and TGF-β1 was suppressed by RD. In conclusion, RD suppressed the inducibility of AF in a rabbit model for pressure associated atrial fibrosis, potentially by modulating renin-angiotensin-aldosterone system and decreasing pro-fibrotic factors

  16. Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2015-01-01

    Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times

  17. Ostracoda (Crustacea) association and a new species (Dolerocypris anatolia nov. sp.) from the Pliocene-Pleistocene Afşin-Elbistan (Kahraman Maraş) Coal Basin of Turkey

    NASA Astrophysics Data System (ADS)

    Tunoǧlu, Cemal; Besbelli, Berk; Ertekin, İbrahim Kadri

    2012-04-01

    The Afşin-Elbistan Coal Basin, which is one of the largest and most important Pliocene-Pleistocene lignite basins of Turkey, is located in Eastern Anatolia. The basin was formed between two normal faults having NE-SW direction and these faults controlled both the sedimentation and the subsidence. The coal horizon of over 50 meters in thickness indicates the balance between the sedimentation and subsidence rates, and was preserved during peat deposition. Coals were generated in this extensive and shallow freshwater lake and evolved from the Pliocene to Pleistocene. Typical faunal and floral assemblages of this ancient Afşin-Elbistan freshwater lake are Ostracoda, Mollusca (Gastropoda and Pelecypoda), spore-pollen and Characeae (gyrogonites). Eleven Cypridoidea species were identified from the investigation area. Eight of them are already known (Candona neglecta Sars, Candona iliensis Mandelstam, Candona aff. candida (Müller), Pseudocandona compressa (Koch), Cyclocypris ovum (Jurine), Ilyocypris gibba (Ramdohr), Cypris pubera Müller, Heterocypris salina (Brady)), whereas three belong to open nomenclature — Candona sp. and Eucypris sp.; Dolerocypris anatolia nov. sp. is proposed as a new species. Dolerocypris Kaufmann is one of the largest genera among the freshwater Ostracoda. It has a very wide geographical distribution. Representatives of this genus are actively swimming species found in shallow zones of freshwater lakes and reported from small grassy water bodies with megascopic plants. Dolerocypris anatolia nov. sp. is recorded from core samples of the Pliocene-Pleistocene Afşin-Elbistan Coal Basin for the first time.

  18. Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings.

    PubMed

    Parra Lopez, Rafael; Nemes, Laszlo; Jimenez-Yuste, Victor; Rusen, Luminita; Cid, Ana R; Charnigo, Robert J; Baumann, James A; Smith, Lynne; Korth-Bradley, Joan M; Rendo, Pablo

    2015-10-01

    This prospective, open-label, postauthorisation safety surveillance study assessed clinically significant inhibitor development in patients with severe haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII) replacement products to reformulated moroctocog alfa (AF-CC). Males aged ≥ 12 years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs) to recombinant or plasma-derived FVIII products, and no detectable inhibitor at screening were enrolled. Primary end point was the incidence of clinically significant FVIII inhibitor development. Secondary end points included annualised bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII recovery. Patients were assigned to one of two cohorts based on whether they were transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146) or from another recombinant or plasma-derived FVIII product (cohort 2; n=62). Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor results, as determined by local laboratories, were reported in four patients; none were confirmed by a central laboratory, no inhibitor-related clinical manifestations were reported, and all anti-FVIII antibody assays were negative. Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on-demand and prophylactic regimens, respectively; 86.5% of bleeding episodes resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand and prophylaxis settings, respectively. FVIII recovery remained constant throughout the study. No new safety concerns were identified. This study found no increased risk of clinically significant FVIII inhibitor development in patients transitioning from moroctocog alfa or other FVIII replacement products to moroctocog alfa (AF-CC).

  19. Autofluorescence imaging device for real-time detection and tracking of pathogenic bacteria in a mouse skin wound model: preclinical feasibility studies

    NASA Astrophysics Data System (ADS)

    Wu, Yichao Charlie; Kulbatski, Iris; Medeiros, Philip J.; Maeda, Azusa; Bu, Jiachuan; Xu, Lizhen; Chen, Yonghong; DaCosta, Ralph S.

    2014-08-01

    Bacterial infection significantly impedes wound healing. Clinical diagnosis of wound infections is subjective and suboptimal, in part because bacteria are invisible to the naked eye during clinical examination. Moreover, bacterial infection can be present in asymptomatic patients, leading to missed opportunities for diagnosis and treatment. We developed a prototype handheld autofluorescence (AF) imaging device (Portable Real-time Optical Detection, Identification and Guidance for Intervention-PRODIGI) to noninvasively visualize and measure bacterial load in wounds in real time. We conducted preclinical pilot studies in an established nude mouse skin wound model inoculated with bioluminescent Staphylococcus aureus bacteria. We tested the feasibility of longitudinal AF imaging for in vivo visualization of bacterial load in skin wounds, validated by bioluminescence imaging. We showed that bacteria (S. aureus), occult to standard examination, can be visualized in wounds using PRODIGI. We also detected quantitative changes in wound bacterial load over time based on the antibiotic treatment and the correlation of bacterial AF intensity with bacterial load. AF imaging of wounds offers a safe, noninvasive method for visualizing the presence, location, and extent of bacteria as well as measuring relative changes in bacterial load in wounds in real time.

  20. Plume Characterization of a Laboratory Model 22 N GPIM Thruster via High-Frequency Raman Spectroscopy

    NASA Technical Reports Server (NTRS)

    Williams, George J.; Kojima, Jun J.; Arrington, Lynn A.; Deans, Matthew C.; Reed, Brian D.; Kinzbach, McKenzie I.; McLean, Christopher H.

    2015-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the capability of a green propulsion system, specifically, one using the monopropellant, AF-M315E. One of the risks identified for GPIM is potential contamination of sensitive areas of the spacecraft from the effluents in the plumes of AF-M315E thrusters. Plume characterization of a laboratory-model 22 N thruster via optical diagnostics was conducted at NASA GRC in a space-simulated environment. A high-frequency pulsed laser was coupled with an electron-multiplied ICCD camera to perform Raman spectroscopy in the near-field, low-pressure plume. The Raman data yielded plume constituents and temperatures over a range of thruster chamber pressures and as a function of thruster (catalyst) operating time. Schlieren images of the near-field plume enabled calculation of plume velocities and revealed general plume structure of the otherwise invisible plume. The measured velocities are compared to those predicted by a two-dimensional, kinetic model. Trends in data and numerical results are presented from catalyst mid-life to end-of-life. The results of this investigation were coupled with the Raman and Schlieren data to provide an anchor for plume impingement analysis presented in a companion paper. The results of both analyses will be used to improve understanding of the nature of AF-M315E plumes and their impacts to GPIM and other future missions.

  1. Tissue-Based Imaging Model of Human Trabecular Meshwork

    PubMed Central

    Chu, Edward R.; Gonzalez, Jose M.

    2014-01-01

    Abstract We have developed a tissue-based model of the human trabecular meshwork (TM) using viable postmortem corneoscleral donor tissue. Two-photon microscopy is used to optically section and image deep in the tissue to analyze cells and extracellular matrix (ECM) within the original three-dimensional (3D) environment of the TM. Multimodal techniques, including autofluorescence (AF), second harmonic generation (SHG), intravital dye fluorescence, and epifluorescence, are combined to provide unique views of the tissue at the cellular and subcellular level. SHG and AF imaging are non-invasive tissue imaging techniques with potential for clinical application, which can be modeled in the system. We describe the following in the tissue-based model: analysis of live cellularity to determine tissue viability; characteristics of live cells based on intravital labeling; features and composition of the TM's structural ECM; localization of specific ECM proteins to regions such as basement membrane; in situ induction and expression of tissue markers characteristic of cultured TM cells relevant to glaucoma; analysis of TM actin and pharmacological effects; in situ visualization of TM, inner wall endothelium, and Schlemm's canal; and application of 3D reconstruction, modeling, and quantitative analysis to the TM. The human model represents a cost-effective use of valuable and scarce yet available human tissue that allows unique cell biology, pharmacology, and translational studies of the TM. PMID:24517246

  2. Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

    DTIC Science & Technology

    2012-10-01

    DAPS AF constructs, fabricated complete DAPS comprised of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and designed and commencement of...of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and design and commencement of construction of a novel multi-axis bioreactor that will be... nanofiber AF and a hyaluronic acid hydrogel NP We have commenced fabrication and in vitro pre-culture of composite DAPS constructs. An AF region

  3. Preconcentration and speciation of ultra-trace Se (IV) and Se (VI) in environmental water samples with nano-sized TiO2 colloid and determination by HG-AFS.

    PubMed

    Fu, Jiaqi; Zhang, Xu; Qian, Shahua; Zhang, Lin

    2012-05-30

    A united method for speciation analysis of Se (IV) and Se (VI) in environmental water samples was developed using nano-sized TiO(2) colloid as adsorbent and hydride generation atomic fluorescence spectrometry (HG-AFS) as determination means. When the pH values of bulk solution were between 6.0 and 7.0, successful adsorption onto 1 mL nano-sized TiO(2) colloid (0.2%) was achieved for more than 97.0% of Se (IV) while Se (VI) barely got adsorbed. Therefore, the method made it possible to preconcentrate and determine Se (IV) and Se (VI) separately. The precipitated TiO(2) with concentrated selenium was directly converted to colloid without desorption. Selenium in the resulting colloid was then determined by HG-AFS. The detection limits (3σ) and relative standard deviations (R.S.D) of this method were 24 ng/L and 42 ng/L, 7.8% (n=6) and 7.0% (n=6) for Se (IV) and Se (VI), respectively. This simple, sensitive, and united method was successfully applied to the separation and speciation of ultra-trace Se (IV) and Se (VI) in environmental water samples.

  4. TEG-1 CD2BP2 regulates stem cell proliferation and sex determination in the C. elegans germ line and physically interacts with the UAF-1 U2AF65 splicing factor

    PubMed Central

    Wang, Chris; Wilson-Berry, Laura; Schedl, Tim; Hansen, Dave

    2012-01-01

    Background For a stem cell population to exist over an extended period, a balance must be maintained between self-renewing (proliferating) and differentiating daughter cells. Within the Caenorhabditis elegans germ line, this balance is controlled by a genetic regulatory pathway, which includes the canonical Notch signaling pathway. Results Genetic screens identified the gene teg-1 as being involved in regulating the proliferation vs. differentiation decision in the C. elegans germ line. Cloning of TEG-1 revealed that it is a homolog of mammalian CD2BP2, which has been implicated in a number of cellular processes, including in U4/U6.U5 tri-snRNP formation in the pre-mRNA splicing reaction. The position of teg-1 in the genetic pathway regulating the proliferation vs. differentiation decision, its single mutant phenotype, and its enrichment in nuclei, all suggest TEG-1 also functions as a splicing factor. TEG-1, as well as its human homolog, CD2BP2, directly bind to UAF-1 U2AF65, a component of the U2 auxiliary factor. Conclusions TEG-1 functions as a splicing factor and acts to regulate the proliferation vs. meiosis decision. The interaction of TEG-1 CD2BP2 with UAF-1 U2AF65, combined with its previously described function in U4/U6.U5 tri-snRNP, suggests that TEG-1 CD2BP2 functions in two distinct locations in the splicing cascade. PMID:22275078

  5. A comparative study on the effects of tumor necrosis factor-alpha (TNF-alpha), human angiogenic factor (h-AF) and basic fibroblast growth factor (bFGF) on the chorioallantoic membrane of the chick embryo.

    PubMed

    Olivo, M; Bhardwaj, R; Schulze-Osthoff, K; Sorg, C; Jacob, H J; Flamme, I

    1992-09-01

    The chorioallantoic membrane (CAM) assay is a widely used bioassay for testing angiogenic activities. In the present study we compared the gross and micromorphological effects of three angiogenic factors applied in Elvax carriers on the CAM: Tumor necrosis factor-alpha (TNF-alpha), human angiogenic factor (h-AF), and basic fibroblast growth factor (bFGF). Our question was whether the CAM responds to these factors which have very different actions with a stereotype or with a factor specific reaction. By microangiography and light microscopy, all positive reactions appeared as a spoke-wheel vascular pattern with a bundle of small capillary blood vessels in the center. These vessels were predominantly of a distended type in h-AF and TNF experiments, while narrower capillary vessels followed bFGF application. Chorioallantoic ectoderm and endoderm were thickened by cell accumulation and the mesenchymal stroma of the CAM was edematous and infiltrated with leucocytes in all three reactions. Additionally, bFGF experiments showed areas of densely arranged fibroblasts. Observations in vivo showed chorioallantoic tissue movements as a possible mechanism for the spokewheel vascular pattern. As compared with our results from studies of cytokinetics with bromodeoxyuridine, these current findings indicate that chemotaxis is responsible for the chorioallantoic angiogenic reaction rather than cellular proliferation.

  6. Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65 and modulates alternative pre-mRNA splicing in vivo

    PubMed Central

    Becerra, Soraya; Montes, Marta; Hernández-Munain, Cristina

    2015-01-01

    The first stable complex formed during the assembly of spliceosomes onto pre-mRNA substrates in mammals includes U1 snRNP, which recognizes the 5′ splice site, and the splicing factors SF1 and U2AF, which bind the branch point sequence, polypyrimidine tract, and 3′ splice site. The 5′ and 3′ splice site complexes are thought to be joined together by protein–protein interactions mediated by factors that ensure the fidelity of the initial splice site recognition. In this study, we identified and characterized PRPF40B, a putative mammalian ortholog of the U1 snRNP-associated yeast splicing factor Prp40. PRPF40B is highly enriched in speckles with a behavior similar to splicing factors. We demonstrated that PRPF40B interacts directly with SF1 and associates with U2AF65. Accordingly, PRPF40B colocalizes with these splicing factors in the cell nucleus. Splicing assays with reporter minigenes revealed that PRPF40B modulates alternative splice site selection. In the case of Fas regulation of alternative splicing, weak 5′ and 3′ splice sites and exonic sequences are required for PRPF40B function. Placing our data in a functional context, we also show that PRPF40B depletion increased Fas/CD95 receptor number and cell apoptosis, which suggests the ability of PRPF40B to alter the alternative splicing of key apoptotic genes to regulate cell survival. PMID:25605964

  7. Optimization of Catheter Ablation of Atrial Fibrillation: Insights Gained from Clinically-Derived Computer Models

    PubMed Central

    Zhao, Jichao; Kharche, Sanjay R.; Hansen, Brian J.; Csepe, Thomas A.; Wang, Yufeng; Stiles, Martin K.; Fedorov, Vadim V.

    2015-01-01

    Atrial fibrillation (AF) is the most common heart rhythm disturbance, and its treatment is an increasing economic burden on the health care system. Despite recent intense clinical, experimental and basic research activity, the treatment of AF with current antiarrhythmic drugs and catheter/surgical therapies remains limited. Radiofrequency catheter ablation (RFCA) is widely used to treat patients with AF. Current clinical ablation strategies are largely based on atrial anatomy and/or substrate detected using different approaches, and they vary from one clinical center to another. The nature of clinical ablation leads to ambiguity regarding the optimal patient personalization of the therapy partly due to the fact that each empirical configuration of ablation lines made in a patient is irreversible during one ablation procedure. To investigate optimized ablation lesion line sets, in silico experimentation is an ideal solution. 3D computer models give us a unique advantage to plan and assess the effectiveness of different ablation strategies before and during RFCA. Reliability of in silico assessment is ensured by inclusion of accurate 3D atrial geometry, realistic fiber orientation, accurate fibrosis distribution and cellular kinetics; however, most of this detailed information in the current computer models is extrapolated from animal models and not from the human heart. The predictive power of computer models will increase as they are validated with human experimental and clinical data. To make the most from a computer model, one needs to develop 3D computer models based on the same functionally and structurally mapped intact human atria with high spatial resolution. The purpose of this review paper is to summarize recent developments in clinically-derived computer models and the clinical insights they provide for catheter ablation. PMID:25984605

  8. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy

    PubMed Central

    Nedelsky, Natalia B.; Pennuto, Maria; Smith, Rebecca B.; Palazzolo, Isabella; Moore, Jennifer; Nie, Zhiping; Neale, Geoffrey; Taylor, J. Paul

    2012-01-01

    Summary Spinobulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by expansion of a polyglutamine tract in the androgen receptor (AR). This mutation confers toxic function to AR through unknown mechanisms. Mutant AR toxicity requires binding of its hormone ligand, suggesting that pathogenesis involves ligand-induced changes in AR. However, whether toxicity is mediated by native AR function or a novel AR function is unknown. We systematically investigated events downstream of ligand-dependent AR activation in a Drosophila model of SBMA. We show that nuclear translocation of AR is necessary but not sufficient for toxicity and that DNA binding by AR is necessary for toxicity. Mutagenesis studies demonstrated that a functional AF-2 domain is essential for toxicity, a finding corroborated by a genetic screen that identified AF-2 interactors as dominant modifiers of degeneration. These findings indicate that SBMA pathogenesis is mediated by misappropriation of native protein function, a mechanism that may apply broadly to polyglutamine diseases. PMID:20869592

  9. Neural Basis of Language: An Overview of An Evolving Model

    PubMed Central

    FUJII, Masazumi; MAESAWA, Satoshi; ISHIAI, Sumio; IWAMI, Kenichiro; FUTAMURA, Miyako; SAITO, Kiyoshi

    2016-01-01

    The neural basis of language had been considered as a simple model consisting of the Broca’s area, the Wernicke’s area, and the arcuate fasciculus (AF) connecting the above two cortical areas. However, it has grown to a larger and more complex model based upon recent advancements in neuroscience such as precise imaging studies of aphasic patients, diffusion tensor imaging studies, functional magnetic resonance imaging studies, and electrophysiological studies with cortical and subcortical stimulation during awake surgery. In the present model, language is considered to be processed through two distinct pathways, the dorsal stream and the ventral stream. The core of the dorsal stream is the superior longitudinal fasciculus/AF, which is mainly associated with phonological processing. On the other hand, semantic processing is done mainly with the ventral stream consisting of the inferior fronto-occipital fasciculus and the intratemporal networks. The frontal aslant tract has recently been named the deep frontal tract connecting the supplementary motor area and the Broca’s area and it plays an important role in driving and initiating speech. It is necessary for every neurosurgeon to have basic knowledge of the neural basis of language. This knowledge is essential to plan safer surgery and preserve the above neural structures during surgery. PMID:27087195

  10. Associations of Emotional Distress and Perceived Health in Persons With Atrial Fibrillation and Their Partners Using the Actor-Partner Interdependence Model.

    PubMed

    Dalteg, Tomas; Benzein, Eva; Sandgren, Anna; Malm, Dan; Årestedt, Kristofer

    2016-08-01

    Individual behavior affects and is affected by other people. The aim of this study was to examine if emotional distress in patients with atrial fibrillation (AF) and their spouses was associated with their own and their partner's perceived health. Participants included 91 dyads of patients and their spouses. Emotional distress was measured using the Hospital Anxiety and Depression Scale and perceived health was measured with the Short Form 36 Health Survey. The Actor-Partner Interdependence Model was used for dyad-level analyses of associations, using structural equation modeling. Higher levels of anxiety and depression were associated with lower levels of perceived health in patients and spouses. Higher levels of depression in patients were associated with lower levels of vitality in spouses and vice versa. As AF patients and their spouses influence each other, health-care interventions should consider the dyad to address dyadic dynamics. This may benefit the health of the individual patient and of the couple.

  11. Protective effects of epigallocatechin-3 gallate on atrial electrical and structural remodeling in a rabbit rapid atrial pacing model.

    PubMed

    Zhu, Jifa; Zhang, Xiao; Li, Ling; Su, Gang

    2015-03-01

    Epigallocatechin-3 gallate (EGCG) is the major catechin in green tea. The aim of this study is to investigate the effects of EGCG on atrial electrical and structural remodeling in a rabbit rapid atrial pacing (RAP) model. New Zealand white rabbits were subjected to RAP with or without EGCG treatment. The atrial electrophysiology was studied. ELISA, Western blots, and RT-PCR were performed to determine the level of the inflammation markers, oxidative stress, and fibrogenic agents. Atrial tissue was stained with Masson's trichrome stain for fibrosis detection. RAP rabbits showed a significantly shorter atrial effective refractory period than control rabbits. Higher AF inducibility and longer AF duration were seen in the RAP group. AERP of rabbits received high dose EGCG were prolonged compared to RAP rabbits, and AF inducibility and duration of rabbits received high dose EGCG were lower. RAP rabbits have higher inflammation markers, higher oxidative stress, and more significant fibrosis within atrium, while high dose intervention of EGCG can lower the inflammation, oxidative stress, and fibrosis induced by RAP. Results showed that EGCG have protective effects on atrial electrical and structural remodeling in a rabbit RAP model in terms of attenuating of inflammation and oxidative stress.

  12. Human amniotic fluid stem cells as a model for functional studies of genes involved in human genetic diseases or oncogenesis.

    PubMed

    Rosner, Margit; Dolznig, Helmut; Schipany, Katharina; Mikula, Mario; Brandau, Oliver; Hengstschläger, Markus

    2011-09-01

    functions in AFS cells was established. Since AFS cells are not tumorigenic, gene modulations not only allow to investigate the role of endogenous genes involved in human genetic diseases but also may help to reveal putative oncogenic gene functions in different biological models, both in vitro and in vivo. This concept is discussed and a "proof of principle", already obtained via modulating genes involved in the mammalian target of rapamycin (mTOR) pathway in AFS cells, is presented.

  13. Evaluation of absorbed doses in voxel-based and simplified models for small animals.

    PubMed

    Mohammadi, Akram; Kinase, Sakae; Saito, Kimiaki

    2012-07-01

    Internal dosimetry in non-human biota is desirable from the viewpoint of radiation protection of the environment. The International Commission on Radiological Protection (ICRP) proposed Reference Animals and Plants using simplified models, such as ellipsoids and spheres and calculated absorbed fractions (AFs) for whole bodies. In this study, photon and electron AFs in whole bodies of voxel-based rat and frog models have been calculated and compared with AFs in the reference models. It was found that the voxel-based and the reference frog (or rat) models can be consistent for the whole-body AFs within a discrepancy of 25%, as the source was uniformly distributed in the whole body. The specific absorbed fractions (SAFs) and S values were also evaluated in whole bodies and all organs of the voxel-based frog and rat models as the source was distributed in the whole body or skeleton. The results demonstrated that the whole-body SAFs reflect SAFs of all individual organs as the source was uniformly distributed per mass within the whole body by about 30% uncertainties with exceptions for body contour (up to -40%) for both electrons and photons due to enhanced radiation leakages, and for the skeleton for photons only (up to +185%) due to differences in the mass attenuation coefficients. For nuclides such as (90)Y and (90)Sr, which were concentrated in the skeleton, there were large differences between S values in the whole body and those in individual organs, however the whole-body S values for the reference models with the whole body as the source were remarkably similar to those for the voxel-based models with the skeleton as the source, within about 4 and 0.3%, respectively. It can be stated that whole-body SAFs or S values in simplified models without internal organs are not sufficient for accurate internal dosimetry because they do not reflect SAFs or S values of all individual organs as the source was not distributed uniformly in whole body. Thus, voxel-based models

  14. Understanding the effect of locked nucleic acid and 2'-O-methyl modification on the hybridization thermodynamics of a miRNA-mRNA pair in the presence and absence of AfPiwi protein.

    PubMed

    Kumar, Santosh; Mapa, Koyeli; Maiti, Souvik

    2014-03-18

    miRNAs are some of the key epigenetic regulators of gene expression. They act through hybridization with their target mRNA and modulate the level of respective proteins via different mechanisms. Various cancer conditions are known to be associated with up- and downregulation of the oncogenic and tumor suppressor miRNAs, respectively. The levels of aberrantly expressed oncogenic miRNAs can be downregulated in different ways. Similarly, restoration of tumor suppressor miRNAs to their normal levels can be achieved using miRNA mimics. However, the use of miRNA mimics is limited by their reduced biostability and function. We have studied the hybridization thermodynamics of the miRNA 26a (11-mer, including the seed sequence) guide strand with the mRNA (11-mer) target strand in the absence and presence of AfPiwi protein. We have also inserted locked nucleic acids (LNAs) and 2'-O-methyl-modified nucleotides into the guide strand, in a walk-through manner, to assess their effect on the binding efficiency between guide and target RNA. Insertion of LNA and 2'-O-methyl-modified nucleotides into the guide strand helped to strengthen the binding affinity irrespective of the position of insertion. However, in the presence of AfPiwi protein, these modifications reduced the binding affinity to different extents depending on the position of insertion. Insertion of a modification leads to an increase in the enthalpic contribution with an increased unfavorable entropic contribution, which negatively compensates for the higher favorable enthalpy.

  15. Designability and cooperative folding in a four-letter hydrophobic-polar model of proteins

    NASA Astrophysics Data System (ADS)

    Liu, Hai-Guang; Tang, Lei-Han

    2006-11-01

    The two-letter hydrophobic-polar (HP) model of Lau and Dill [Macromolecules 22, 3986 (1989)] has been widely used in theoretical studies of protein folding due to its conceptual and computational simplicity. Despite its success in elucidating various aspects of the sequence-structure relationship, thermodynamic behavior of the model is not in agreement with a sharp two-state folding transition of many single-domain proteins. To gain a better understanding of this discrepancy, we consider an extension of the HP model by including an “antiferromagnetic” (AF) interaction in the contact potential that favors amino acid residues with complementary attributes. With an enlarged four-letter alphabet, the density of states on the low energy side can be significantly decreased. Computational studies of the four-letter HP model are performed on 36-mer sequences on a square lattice. It is found that the designability of folded structures in the extended model exhibits strong correlation with that of the two-letter HP model, while the AF interaction alone selects a very different class of structures that resembles the Greek key motif for beta sheets. A procedure is introduced to select sequences which have the largest energy gap to the native state. Based on density of states and specific heat calculations in the full configuration space, we show that the optimized sequence is able to fold nearly as cooperatively as a corresponding Gō model.

  16. A Transportation Model for a Space Colonization and Manufacturing System: A Q-GERT Simulation.

    DTIC Science & Technology

    1982-12-01

    RAD-RI247685 A TRANSPORTATION MODEL OR A SPACE COLONIZATION AND1/ MANUFACTURING SYSTEM:..U) AIR FORCE INST OF TECH NRIGHT-PATTERSON AFB OH SCHOOL OF...it$ ""distribution is unlimitd- L CTF r DEPARTMENT OF THE AIR FORCE FEB 22 3 C.. AIR UNIVERSITY (ATC) • AIR FORCE INSTITUTE OF TECHNOLOG L&J Wright...Patterson Air Force Base, Ohio _ rig 2Z. 1" 7 AF IT/GSO/OS/82D-6 A TRANSPORTATION MODEL F AR SPACE . I a, cND MANUFACTURING SY-TEM: A 0--CtERT

  17. Growth and Modeling of Staphylococcus aureus in Flour Products under Isothermal and Nonisothermal Conditions.

    PubMed

    Cao, Hui; Wang, Tingting; Yuan, Min; Yu, Jingsong; Xu, Fei

    2017-03-01

    This study was conducted to investigate the growth of Staphylococcus aureus in traditional Chinese flour products under isothermal (10, 15, 20, 25, 30, and 37°C) and nonisothermal (10 to 20, 20 to 30, and 25 to 37°C) conditions. Then, models for the growth of S. aureus in flour products as a function of storage temperature, pH, and water activity (aw) were developed, and the goodness of fit of models was evaluated using the determination coefficient (R(2)), root mean square error (RMSE), bias factor (Bf), and accuracy factor (Af). Based on the above information, S. aureus growth in steamed bread under nonisothermal conditions was predicted from experiments performed under isothermal conditions. It was shown that different combinations of temperature and aw in flour products have a strong influence on the growth of S. aureus . The modified Gompertz model was found to be more suitable for describing the growth data of S. aureus in flour products, with an R(2) of >0.99 and an RMSE of <0.37. The newly developed secondary models were validated, and for the specific growth rate and the lag time, the R(2) values were 0.96 and 0.97, Af was 1.12 and 1.06, and Bf was 1.13 and 1.05, respectively. The predicted nonisothermal growth curves of S. aureus were in agreement with the reported experimental ones, with RMSE <0.29, Af value 1.02 to 1.09, and Bf value 0.92 to 0.99. These results indicated that the predictive models provided useful information for the establishment of safety standards and a risk assessment for S. aureus in flour products.

  18. An SF1 affinity model to identify branch point sequences in human introns

    PubMed Central

    Pastuszak, Alexander W.; Joachimiak, Marcin P.; Blanchette, Marco; Rio, Donald C.; Brenner, Steven E.; Frankel, Alan D.

    2011-01-01

    Splicing factor 1 (SF1) binds to the branch point sequence (BPS) of mammalian introns and is believed to be important for the splicing of some, but not all, introns. To help identify BPSs, particularly those that depend on SF1, we generated a BPS profile model in which SF1 binding affinity data, validated by branch point mapping, were iteratively incorporated into computational models. We searched a data set of 117 499 human introns for best matches to the SF1 Affinity Model above a threshold, and counted the number of matches at each intronic position. After subtracting a background value, we found that 87.9% of remaining high-scoring matches identified were located in a region upstream of 3′-splice sites where BPSs are typically found. Since U2AF65 recognizes the polypyrimidine tract (PPT) and forms a cooperative RNA complex with SF1, we combined the SF1 model with a PPT model computed from high affinity binding sequences for U2AF65. The combined model, together with binding site location constraints, accurately identified introns bound by SF1 that are candidates for SF1-dependent splicing. PMID:21071404

  19. Evaluation of the implementation and impact of an integrated prevention model on the academic progress of students with disabilities.

    PubMed

    Barlow, Alexandra; Humphrey, Neil; Lendrum, Ann; Wigelsworth, Michael; Squires, Garry

    2014-11-12

    In this paper we report on the implementation and impact of an integrated prevention model (Achievement for All - AfA) to improve the educational experiences and outcomes of students with disabilities. It comprises three inter-related strands: assessment, tracking and intervention; structured conversations with parents; and, developing provision for wider outcomes. Participants were 12,038 students with disabilities from 431 mainstream primary and secondary schools across 10 Local Authorities in England involved in the two-year AfA pilot. Pre- and post-test data on academic attainment in English and Maths were compared with national data on academic progress for students with and without disabilities over an equivalent period of time. School-level contextual and implementation data and student-level socio-demographic and psychosocial data were also collected. Four hypotheses were tested regarding the impact of AfA on academic attainment in English (H1) and Maths (H2); the influence of aspects of the implementation context and processes (H3); and individual differences between students (H4). Our findings are discussed in relation to the identification and validation of critical intervention components and standards for assessing the practical significance of attempts to improve outcomes for students.

  20. New grids of ATLAS9 atmospheres. II. Limb-darkening coefficients for the Strömgren photometric system for A-F stars

    NASA Astrophysics Data System (ADS)

    Barban, C.; Goupil, M. J.; Van't Veer-Menneret, C.; Garrido, R.; Kupka, F.; Heiter, U.

    2003-07-01

    Using up-to-date model atmospheres (Heiter et al. \\cite{Heiter02}) with the turbulent convection approach developed by Canuto et al. (\\cite{Canuto96}, CGM), quadratic, cubic and square root limb darkening coefficients (LDC) are calculated with a least square fit method for the Strömgren photometric system. This is done for a sample of solar metallicity models with effective temperatures between 6000 and 8500 K and with log g between 2.5 and 4.5. A comparison is made between these LDC and the ones computed from model atmospheres using the classical mixing length prescription with a mixing length parameter alpha =1.25 and alpha =0.5. For CGM model atmospheres, the law which reproduces better the model intensity is found to be the square root one for the u band and the cubic law for the v band. The results are more complex for the b and y bands depending on the temperature and gravity of the model. Similar conclusions are reached for MLT alpha =0.5 models. As expected much larger differences are found between CGM and MLT with alpha =1.25. In a second part, the weighted limb-darkening integrals, bl, and their derivatives with respect to temperature and gravity, are then computed using the best limb-darkening law. These integrals are known to be very important in the context of photometric mode identification of non-radial pulsating stars. The effect of convection treatment on these quantities is discussed and as expected differences in the bl coefficients and derivatives computed with CGM and MLT alpha =0.5 are much smaller than differences obtained between computations with CGM and MLT alpha =1.25. Table 1 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/405/1095

  1. Issues associated with the use of Yoshida nonlinear isotropic/kinematic hardening material model in Advanced High Strength Steels

    NASA Astrophysics Data System (ADS)

    Shi, Ming F.; Zhang, Li; Zhu, Xinhai

    2016-08-01

    The Yoshida nonlinear isotropic/kinematic hardening material model is often selected in forming simulations where an accurate springback prediction is required. Many successful application cases in the industrial scale automotive components using advanced high strength steels (AHSS) have been reported to give better springback predictions. Several issues have been raised recently in the use of the model for higher strength AHSS including the use of two C vs. one C material parameters in the Armstrong and Frederick model (AF model), the original Yoshida model vs. Original Yoshida model with modified hardening law, and constant Young's Modulus vs. decayed Young's Modulus as a function of plastic strain. In this paper, an industrial scale automotive component using 980 MPa strength materials is selected to study the effect of two C and one C material parameters in the AF model on both forming and springback prediction using the Yoshida model with and without the modified hardening law. The effect of decayed Young's Modulus on the springback prediction for AHSS is also evaluated. In addition, the limitations of the material parameters determined from tension and compression tests without multiple cycle tests are also discussed for components undergoing several bending and unbending deformations.

  2. Modeling the Determinants Influencing the Diffusion of Mobile Internet

    NASA Astrophysics Data System (ADS)

    Alwahaishi, Saleh; Snášel, Václav

    2013-04-01

    Understanding individual acceptance and use of Information and Communication Technology (ICT) is one of the most mature streams of information systems research. In Information Technology and Information System research, numerous theories are used to understand users' adoption of new technologies. Various models were developed including the Innovation Diffusion Theory, Theory of Reasoned Action, Theory of Planned Behavior, Technology Acceptance Model, and recently, the Unified Theory of Acceptance and Use of Technology. This research composes a new hybrid theoretical framework to identify the factors affecting the acceptance and use of Mobile Internet -as an ICT application- in a consumer context. The proposed model incorporates eight constructs: Performance Expectancy (PE), Effort Expectancy (EE), Facilitating Conditions (FC), Social Influences (SI), Perceived Value (PV), Perceived Playfulness (PP), Attention Focus (AF), and Behavioral intention (BI). Individual differences-namely, age, gender, education, income, and experience are moderating the effects of these constructs on behavioral intention and technology use.

  3. Characterization and expression pattern of KIFC1-like kinesin gene in the testis of the Macrobrachium nipponense with discussion of its relationship with structure lamellar complex (LCx) and acroframosome (AFS).

    PubMed

    Wang, Yan-Ting; Mao, Huan; Hou, Cong-Cong; Sun, Xiao; Wang, Da-Hui; Zhou, Hong; Yang, Wan-Xi

    2012-07-01

    Spermiogenesis is a developmental process undergoing continuous differentiation to drive a diploid spermatogonium towards a haploid sperm cell. This striking transformation from spermatogonium to spermatozoa is made possible by the stage-specific adaption of cytoskeleton and associated molecular motor proteins. KIFC1 is a C-terminal kinesin motor found to boast essential roles in acrosome biogenesis and nuclear reshaping during spermiogenesis in rat. To explore its functions during the same process in Macrobrachium nipponense, we have cloned and sequenced the cDNA of a mammalian KIFC1 homologue (termed mn-KIFC1) from the total RNA of the testis. The 2,296 bp mn-KIFC1 cDNA contained a 87 bp 5' untranslated region, a 211 bp 3' untranslated region and a 1,998 bp open reading frame. Protein alignment demonstrated that mn-KIFC1 had 37.7, 58.7, 38.4, 37.2, 38.9 and 37.8% identity with its homologues in Salmo salar, Eriocheir sinensis, Homo sapiens, Mus musculus, Danio rerio and Xenopus laevis respectively. The phylogenetic tree revealed that mn-KIFC1 is most related to E. Sinensis KIFC1 among the examined species. Tissue expression analysis showed the presence of mn-KIFC1 in the testis, hepatopancreas, gill, muscle and heart. In situ hybridization showed that the mn-KIFC1 mRNA was localized at the periphery of the nuclear membrane and in the proacrosomal vesicle in early and middle spermatids. In late spermatids and spermatozoa, mn-KIFC1 was expressed in the acrosome and in the spike. In situ hybridization also indicated that KIFC1 works together with lamellar complex (LCx) and acroframosome (AFS) to drive acrosome formation and cellular transformation. LCx and AFS have both been previously proved to have essential roles during spermiogenesis in M. nipponense. In conclusion, the expression of mn-kifc1 at specific stages of spermiogenesis suggests a role in cellular transformations in M. nipponense.

  4. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial

    PubMed Central

    Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D.; Hellkamp, Anne S.; Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Halperin, Jonathan L.; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2014-01-01

    Aims We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. Methods and results ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55–1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75–1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05–1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94–1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Conclusions Many patients with ‘non-valvular atrial fibrillation’ have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. PMID:25148838

  5. Voxel modeling of rabbits for use in radiological dose rate calculations.

    PubMed

    Caffrey, E A; Johansen, M P; Higley, K A

    2016-01-01

    Radiation dose to biota is generally calculated using Monte Carlo simulations of whole body ellipsoids with homogeneously distributed radioactivity throughout. More complex anatomical phantoms, termed voxel phantoms, have been developed to test the validity of these simplistic geometric models. In most voxel models created to date, human tissue composition and density values have been used in lieu of biologically accurate values for non-human biota. This has raised questions regarding variable tissue composition and density effects on the fraction of radioactive emission energy absorbed within tissues (e.g. the absorbed fraction - AF), along with implications for age-dependent dose rates as organisms mature. The results of this study on rabbits indicates that the variation in composition between two mammalian tissue types (e.g. human vs rabbit bones) made little difference in self-AF (SAF) values (within 5% over most energy ranges). However, variable tissue density (e.g. bone vs liver) can significantly impact SAF values. An examination of differences across life-stages revealed increasing SAF with testis and ovary size of over an order of magnitude for photons and several factors for electrons, indicating the potential for increasing dose rates to these sensitive organs as animals mature. AFs for electron energies of 0.1, 0.2, 0.4, 0.5, 0.7, 1.0, 1.5, 2.0, and 4.0 MeV and photon energies of 0.01, 0.015, 0.02, 0.03, 0.05, 0.1, 0.2, 0.5, 1.0, 1.5, 2.0, and 4.0 MeV are provided for eleven rabbit tissues. The data presented in this study can be used to calculate accurate organ dose rates for rabbits and other small rodents; to aide in extending dose results among different mammal species; and to validate the use of ellipsoidal models for regulatory purposes.

  6. Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

    DTIC Science & Technology

    2012-10-29

    PCL nanofiber AF and a hyaluronic acid hydrogel NP, and designed and commencement of construction of a multi-axis bioreactor that will be used to...of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and design and commencement of construction of a novel multi-axis bioreactor that will be... nanofiber AF and a hyaluronic acid hydrogel NP We have commenced fabrication and in vitro pre-culture of composite DAPS constructs. An AF region

  7. Cytogenetic Analysis of the South American Fruit Fly Anastrepha fraterculus (Diptera:Tephritidae) Species Complex: Construction of Detailed Photographic Polytene Chromosome Maps of the Argentinian Af. sp.1 Member

    PubMed Central

    Augustinos, Antonios A.; Drosopoulou, Elena; Lanzavecchia, Silvia B.; Cladera, Jorge L.; Caceres, Carlos; Bourtzis, Kostas; Mavragani-Tsipidou, Penelope; Zacharopoulou, Antigone

    2016-01-01

    Genetic and cytogenetic studies constitute a significant basis for understanding the biology of insect pests and the design and the construction of genetic tools for biological control strategies. Anastrepha fraterculus is an important pest of the Tephritidae family. It is distributed from southern Texas through eastern Mexico, Central America and South America causing significant crop damage and economic losses. Currently it is considered as a species complex; until now seven members have been described based on multidisciplinary approaches. Here we report the cytogenetic analysis of an Argentinian population characterized as Af. sp.1 member of the Anastrepha fraterculus species complex. The mitotic karyotype and the first detailed photographic maps of the salivary gland polytene chromosomes are presented. The mitotic metaphase complement consists of six (6) pairs of chromosomes, including one pair of heteromorphic sex chromosomes, with the male being the heterogametic sex. The analysis of the salivary gland polytene complement shows a total number of five long chromosomes that correspond to the five autosomes of the mitotic karyotype and a heterochromatic network corresponding to the sex chromosomes. Comparison of the polytene chromosome maps between this species and Anastrepha ludens shows significant similarity. The polytene maps presented here are suitable for cytogenetic studies that could shed light on the species limits within this species complex and support the development of genetic tools for sterile insect technique (SIT) applications. PMID:27362546

  8. A fast method for bisphenol A and six analogues (S, F, Z, P, AF, AP) determination in urine samples based on dispersive liquid-liquid microextraction and liquid chromatography-tandem mass spectrometry.

    PubMed

    Rocha, Bruno Alves; da Costa, Bruno Ruiz Brandão; de Albuquerque, Nayara Cristina Perez; de Oliveira, Anderson Rodrigo Moraes; Souza, Juliana Maria Oliveira; Al-Tameemi, Maha; Campiglia, Andres Dobal; Barbosa, Fernando

    2016-07-01

    In this study, a novel method combining dispersive liquid-liquid microextraction (DLLME) and fast liquid chromatography coupled to mass spectrometry (LC-MS/MS) was developed and validated for the extraction and determination of bisphenol A (BPA) and six bisphenol analogues, namely bisphenol S (BPS), bisphenol F (BPF), bisphenol P (BPP), bisphenol Z (BPZ), bisphenol AP (BPAP) and bisphenol AF (BPAF) in human urine samples. Type and volume of extraction and disperser solvents, pH sample, ionic strength, and agitation were evaluated. The matrix-matched calibration curves of all analytes were linear with correlation coefficients higher than 0.99 in the range level of 0.5-20.0ngmL(-1). The relative standard deviation (RSD), precision, at three concentrations (1.0, 8.0 and 15.0ngmL(-1)) was lower than 15% with accuracy ranging from 90 to 112%. The biomonitoring capability of the new method was confirmed with the analysis of 50 human urine samples randomly collected from Brazilians. BPA was detected in 92% of the analyzed samples at concentrations ranging

  9. Cytogenetic Analysis of the South American Fruit Fly Anastrepha fraterculus (Diptera:Tephritidae) Species Complex: Construction of Detailed Photographic Polytene Chromosome Maps of the Argentinian Af. sp.1 Member.

    PubMed

    Gariou-Papalexiou, Angeliki; Giardini, María Cecilia; Augustinos, Antonios A; Drosopoulou, Elena; Lanzavecchia, Silvia B; Cladera, Jorge L; Caceres, Carlos; Bourtzis, Kostas; Mavragani-Tsipidou, Penelope; Zacharopoulou, Antigone

    2016-01-01

    Genetic and cytogenetic studies constitute a significant basis for understanding the biology of insect pests and the design and the construction of genetic tools for biological control strategies. Anastrepha fraterculus is an important pest of the Tephritidae family. It is distributed from southern Texas through eastern Mexico, Central America and South America causing significant crop damage and economic losses. Currently it is considered as a species complex; until now seven members have been described based on multidisciplinary approaches. Here we report the cytogenetic analysis of an Argentinian population characterized as Af. sp.1 member of the Anastrepha fraterculus species complex. The mitotic karyotype and the first detailed photographic maps of the salivary gland polytene chromosomes are presented. The mitotic metaphase complement consists of six (6) pairs of chromosomes, including one pair of heteromorphic sex chromosomes, with the male being the heterogametic sex. The analysis of the salivary gland polytene complement shows a total number of five long chromosomes that correspond to the five autosomes of the mitotic karyotype and a heterochromatic network corresponding to the sex chromosomes. Comparison of the polytene chromosome maps between this species and Anastrepha ludens shows significant similarity. The polytene maps presented here are suitable for cytogenetic studies that could shed light on the species limits within this species complex and support the development of genetic tools for sterile insect technique (SIT) applications.

  10. Selective and sensitive determination of As(III) and tAs in Chinese herbal medicine samples using L-cysteine modified carbon paste electrode-based electrolytic hydride generation and AFS analysis.

    PubMed

    Lu, Xiao-Ping; Yang, Xin-An; Liu, Lin; Hu, Hui-Hui; Zhang, Wang-Bing

    2017-04-01

    A novel non-chromatographic speciation technique for ultra-trace arsenite [As(III)] and total arsenic (tAs) in Chinese herbal medicine (CHM) is developed and validated by electrolytic hydride generation (EHG) coupled with atomic fluorescence spectrometry (AFS). The studies show that As(III) can be converted efficiently to AsH3 on an L-cysteine modified carbon paste electrode (CMCPE), which has never been reported before. Significantly, other arsenic species such as arsenate [As(V)], monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) do not form any or only less volatile hydrides at low applied current mode (<1.0 A). The results also demonstrate that L-cysteine and graphite powder play different roles in the electrolytic generation of AsH3. Comparing with the traditional graphite electrode, CMCPE has better stability, sensitivity and interference tolerance. Under the optimal conditions, the limit of detection (LOD) of tAs and As(III) for this method are 0.087µgL(-1) and 0.095µgL(-1) respectively. The accuracy of the method is verified through the analysis of reference materials (CRM 08231 and SRM1568a), and the proposed method has been applied satisfactorily to the determination of As(III) and tAs in several CHM samples.

  11. A Model for On-Offshore Sediment Transport in the Surfzone.

    DTIC Science & Technology

    1982-12-01

    Association of Hydraulics Research, Lisbon, Portugal, 1957. Seymour, R. J., and D. B. King (1982). "Field comparisons of cross-shore transport models...I a I i I a I a 0 0 0 N (Aup.WI~W) ~aua uod~utji ~zoqsuo 48 DISTRIBUTION LIST AFB AF Tech Office (Mgt & Ops). Tyndall. FL; AULLSE 63-465. Maxwell AL...CESCH, Wright-Patterson; Stinfo Library. Offutt NE ARCTICSUBLAB Code 54, San Diego, CA ARMY BMDSC-RE (H. McClellan ) Huntsville AL; DAEN-MPE-D

  12. A Community Terrain-Following Ocean Modeling System (ROMS/TOMS)

    DTIC Science & Technology

    2011-09-30

    adjoint and variational data assimilation) at Scripps Institute of Oceanography, E. Di Lorenzo (Southern California predictability) at Georgia Institute...K.W. Bruland, E. Di Lorenzo , C.V.W Lewis, T.M. Powell, E. Curchitser, and K. Hedstrom, 2009: Modeling iron limitation of primary production in the...Di Lorenzo , K. Fennel, W.R. Geyer, A.J. Hermann, L. Lanerolle, J. Levin, J.C. McWilliams, A.J. Miller, A.M. Moore, T.M. Powell, A.F. Shchepetkin

  13. Behavior of a High Strength Concrete Model Subjected to Biaxial Compression.

    DTIC Science & Technology

    1982-12-01

    research project reported herein was to determine the stress-strain behavior, ultimate strength, and failure mechanism of high-strength concrete subjected to...Triaxial Stress," U.S. Bureau of Reclamation, Structural Research Lab. Report SP-23, October 1949, pp. 1-26. 7. Akroyd, T.N.W., " Concrete Under Triaxial...MODEL SUBJECTED TO BIAXIAL COMPRESSION 1-,4 BY [ JON C. HERRIN 𔃻 RAMON L. CARRASQUILLO 1DAVID W. FOWLER Ii RESEARCH REPORT AF- FOR UNITED STATES AIR

  14. A two-dimensional adsorption kinetic model for thermal hysteresis activity in antifreeze proteins

    NASA Astrophysics Data System (ADS)

    Li, Q. Z.; Yeh, Y.; Liu, J. J.; Feeney, R. E.; Krishnan, V. V.

    2006-05-01

    Antifreeze proteins (AFPs) and antifreeze glycoproteins (AFGPs), collectively abbreviated as AF(G)Ps, are synthesized by various organisms to enable their cells to survive in subzero environments. Although the AF(G)Ps are markedly diverse in structure, they all function by adsorbing to the surface of embryonic ice crystals to inhibit their growth. This adsorption results in a freezing temperature depression without an appreciable change in the melting temperature. The difference between the melting and freezing temperatures, termed thermal hysteresis (TH), is used to detect and quantify the antifreeze activity. Insights from crystallographic structures of a number of AFPs have led to a good understanding of the ice-protein interaction features. Computational studies have focused either on verifying a specific model of AFP-ice interaction or on understanding the protein-induced changes in the ice crystal morphology. In order to explain the origin of TH, we propose a novel two-dimensional adsorption kinetic model between AFPs and ice crystal surfaces. The validity of the model has been demonstrated by reproducing the TH curve on two different β-helical AFPs upon increasing the protein concentration. In particular, this model is able to accommodate the change in the TH behavior observed experimentally when the size of the AFPs is increased systematically. Our results suggest that in addition to the specificity of the AFPs for the ice, the coverage of the AFPs on the ice surface is an equally necessary condition for their TH activity.

  15. Construction of an E. Coli genome-scale atom mapping model for MFA calculations.

    PubMed

    Ravikirthi, Prabhasa; Suthers, Patrick F; Maranas, Costas D

    2011-06-01

    Metabolic flux analysis (MFA) has so far been restricted to lumped networks lacking many important pathways, partly due to the difficulty in automatically generating isotope mapping matrices for genome-scale metabolic networks. Here we introduce a procedure that uses a compound matching algorithm based on the graph theoretical concept of pattern recognition along with relevant reaction information to automatically generate genome-scale atom mappings which trace the path of atoms from reactants to products for every reaction. The procedure is applied to the iAF1260 metabolic reconstruction of Escherichia coli yielding the genome-scale isotope mapping model imPR90068. This model maps 90,068 non-hydrogen atoms that span all 2,077 reactions present in iAF1260 (previous largest mapping model included 238 reactions). The expanded scope of the isotope mapping model allows the complete tracking of labeled atoms through pathways such as cofactor and prosthetic group biosynthesis and histidine metabolism. An EMU representation of imPR90068 is also constructed and made available.

  16. Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI)

    NASA Astrophysics Data System (ADS)

    Rigaux, G.; Gheran, C. V.; Callewaert, M.; Cadiou, C.; Voicu, S. N.; Dinischiotu, A.; Andry, M. C.; Vander Elst, L.; Laurent, S.; Muller, R. N.; Berquand, A.; Molinari, M.; Huclier-Markai, S.; Chuburu, F.

    2017-02-01

    Chitosan CS—tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

  17. Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI).

    PubMed

    Rigaux, G; Gheran, C V; Callewaert, M; Cadiou, C; Voicu, S N; Dinischiotu, A; Andry, M C; Vander Elst, L; Laurent, S; Muller, R N; Berquand, A; Molinari, M; Huclier-Markai, S; Chuburu, F

    2017-02-03

    Chitosan CS-tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

  18. The CDK9 Inhibitor Dinaciclib Exerts Potent Apoptotic and Antitumor Effects in Preclinical Models of MLL-Rearranged Acute Myeloid Leukemia.

    PubMed

    Baker, Adele; Gregory, Gareth P; Verbrugge, Inge; Kats, Lev; Hilton, Joshua J; Vidacs, Eva; Lee, Erwin M; Lock, Richard B; Zuber, Johannes; Shortt, Jake; Johnstone, Ricky W

    2016-03-01

    Translocations of the mixed lineage leukemia (MLL) gene occur in 60% to 80% of all infant acute leukemias and are markers of poor prognosis. MLL-AF9 and other MLL fusion proteins aberrantly recruit epigenetic regulatory proteins, including histone deacetylases (HDAC), histone methyltransferases, bromodomain-containing proteins, and transcription elongation factors to mediate chromatin remodeling and regulate tumorigenic gene expression programs. We conducted a small-molecule inhibitor screen to test the ability of candidate pharmacologic agents targeting epigenetic and transcriptional regulatory proteins to induce apoptosis in leukemic cells derived from genetically engineered mouse models of MLL-AF9-driven acute myeloid leukemia (AML). We found that the CDK inhibitor dinaciclib and HDAC inhibitor panobinostat were the most potent inducers of apoptosis in short-term in vitro assays. Treatment of MLL-rearranged leukemic cells with dinaciclib resulted in rapidly decreased expression of the prosurvival protein Mcl-1, and accordingly, overexpression of Mcl-1 protected AML cells from dinaciclib-induced apoptosis. Administration of dinaciclib to mice bearing MLL-AF9-driven human and mouse leukemias elicited potent antitumor responses and significantly prolonged survival. Collectively, these studies highlight a new therapeutic approach to potentially overcome the resistance of MLL-rearranged AML to conventional chemotherapies and prompt further clinical evaluation of CDK inhibitors in AML patients harboring MLL fusion proteins.

  19. Effects of Persistent Atrial Fibrillation-Induced Electrical Remodeling on Atrial Electro-Mechanics – Insights from a 3D Model of the Human Atria

    PubMed Central

    Adeniran, Ismail; MacIver, David H.; Garratt, Clifford J.; Ye, Jianqiao; Hancox, Jules C.; Zhang, Henggui

    2015-01-01

    Aims Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. Methods and Results A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2–3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished. Conclusions This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients. PMID:26606047

  20. Dysconnectivity within the default mode in first-episode schizophrenia: a stochastic dynamic causal modeling study with functional magnetic resonance imaging.

    PubMed

    Bastos-Leite, António J; Ridgway, Gerard R; Silveira, Celeste; Norton, Andreia; Reis, Salomé; Friston, Karl J

    2015-01-01

    We report the first stochastic dynamic causal modeling (sDCM) study of effective connectivity within the default mode network (DMN) in schizophrenia. Thirty-three patients (9 women, mean age = 25.0 years, SD = 5) with a first episode of psychosis and diagnosis of schizophrenia--according to the Diagnostic and Statistic Manual of Mental Disorders, 4th edition, revised criteria--were studied. Fifteen healthy control subjects (4 women, mean age = 24.6 years, SD = 4) were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI) interspersed with 2 periods of continuous picture viewing. The anterior frontal (AF), posterior cingulate (PC), and the left and right parietal nodes of the DMN were localized in an unbiased fashion using data from 16 independent healthy volunteers (using an identical fMRI protocol). We used sDCM to estimate directed connections between and within nodes of the DMN, which were subsequently compared with t tests at the between subject level. The excitatory effect of the PC node on the AF node and the inhibitory self-connection of the AF node were significantly weaker in patients (mean values = 0.013 and -0.048 Hz, SD = 0.09 and 0.05, respectively) relative to healthy subjects (mean values = 0.084 and -0.088 Hz, SD = 0.15 and 0.77, respectively; P < .05). In summary, sDCM revealed reduced effective connectivity to the AF node of the DMN--reflecting a reduced postsynaptic efficacy of prefrontal afferents--in patients with first-episode schizophrenia.

  1. Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation.

    PubMed

    Ferrer, Ana; Sebastián, Rafael; Sánchez-Quintana, Damián; Rodríguez, José F; Godoy, Eduardo J; Martínez, Laura; Saiz, Javier

    2015-01-01

    Atrial arrhythmias, and specifically atrial fibrillation (AF), induce rapid and irregular activation patterns that appear on the torso surface as abnormal P-waves in electrocardiograms and body surface potential maps (BSPM). In recent years both P-waves and the BSPM have been used to identify the mechanisms underlying AF, such as localizing ectopic foci or high-frequency rotors. However, the relationship between the activation of the different areas of the atria and the characteristics of the BSPM and P-wave signals are still far from being completely understood. In this work we developed a multi-scale framework, which combines a highly-detailed 3D atrial model and a torso model to study the relationship between atrial activation and surface signals in sinus rhythm. Using this multi scale model, it was revealed that the best places for recording P-waves are the frontal upper right and the frontal and rear left quadrants of the torso. Our results also suggest that only nine regions (of the twenty-one structures in which the atrial surface was divided) make a significant contribution to the BSPM and determine the main P-wave characteristics.

  2. Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation

    PubMed Central

    Ferrer, Ana; Sebastián, Rafael; Sánchez-Quintana, Damián; Rodríguez, José F.; Godoy, Eduardo J.; Martínez, Laura; Saiz, Javier

    2015-01-01

    Atrial arrhythmias, and specifically atrial fibrillation (AF), induce rapid and irregular activation patterns that appear on the torso surface as abnormal P-waves in electrocardiograms and body surface potential maps (BSPM). In recent years both P-waves and the BSPM have been used to identify the mechanisms underlying AF, such as localizing ectopic foci or high-frequency rotors. However, the relationship between the activation of the different areas of the atria and the characteristics of the BSPM and P-wave signals are still far from being completely understood. In this work we developed a multi-scale framework, which combines a highly-detailed 3D atrial model and a torso model to study the relationship between atrial activation and surface signals in sinus rhythm. Using this multi scale model, it was revealed that the best places for recording P-waves are the frontal upper right and the frontal and rear left quadrants of the torso. Our results also suggest that only nine regions (of the twenty-one structures in which the atrial surface was divided) make a significant contribution to the BSPM and determine the main P-wave characteristics. PMID:26523732

  3. Chemical and Hydrodynamical Models of Cometary Comae

    NASA Technical Reports Server (NTRS)

    Charnley, Steven

    2012-01-01

    Multi-fluid modelling of the outflowing gases which sublimate from cometary nuclei as they approach the Sun is necessary for understanding the important physical and chemical processes occurring in this complex plasma. Coma chemistry models can be employed to interpret observational data and to ultimately determine chemical composition and structure of the nuclear ices and dust. We describe a combined chemical and hydrodynamical model [1] in which differential equations for the chemical abundances and the energy balance are solved as a function of distance from the cometary nucleus. The presence of negative ions (anions) in cometary comae is known from Giotto mass spectrometry of 1P/Halley. The anions O(-), OH(-), C(-), CH(-) and CN(-) have been detected, as well as unidentified anions with masses 22-65 and 85-110 amu [2]. Organic molecular anions such as C4H(-) and C6H(-) are known to have a significant impact on the charge balance of interstellar clouds and circumstellar envelopes and have been shown to act as catalysts for the gas-phase synthesis of larger hydrocarbon molecules in the ISM, but their importance in cometary comae has not yet been fully explored. We present details of new models for the chemistry of cometary comae that include atomic and molecular anions and calculate the impact of these anions on the coma physics and chemistry af the coma.

  4. IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS-AF randomised controlled trial

    PubMed Central

    Shantsila, Eduard; Haynes, Ronnie; Fisher, James; Kirchhof, Paulus; Gill, Paramjit S; Lip, Gregory Y H

    2016-01-01

    Introduction Patients with atrial fibrillation frequently suffer from heart failure with preserved ejection fraction. At present there is no proven therapy to improve physical capacity and quality of life in participants with permanent atrial fibrillation with preserved left ventricular contractility. Objective The single-centre IMproved exercise tolerance In heart failure With PReserved Ejection fraction by Spironolactone On myocardial fibrosiS In Atrial Fibrillation (IMPRESS-AF) trial aims to establish whether treatment with spironolactone as compared with placebo improves exercise tolerance (cardiopulmonary exercise testing), quality of life and diastolic function in patients with permanent atrial fibrillation. Methods and analysis A total of 250 patients have been randomised in this double-blinded trial for 2-year treatment with 25 mg daily dose of spironolactone or matched placebo. Included participants are 50 years old or older, have permanent atrial fibrillation and ejection fraction >55%. Exclusion criteria include contraindications to spironolactone, poorly controlled hypertension and presence of severe comorbidities with life expectancy <2 years. The primary outcome is improvement in exercise tolerance at 2 years and key secondary outcomes include quality of life (assessed using the EuroQol EQ-5D-5L (EQ-5D) and Minnesota Living with Heart Failure (MLWHF) questionnaires), diastolic function and all-cause hospitalisation. Ethics and dissemination The study has been approved by the National Research and Ethics Committee West Midlands—Coventry and Warwickshire (REC reference number 14/WM/1211). The results of the trial will be published in an international peer-reviewed journal. Trial registration numbers EudraCT2014-003702-33; NCT02673463; Pre-results. PMID:27707827

  5. The actin-binding protein Canoe/AF-6 forms a complex with Robo and is required for Slit-Robo signaling during axon pathfinding at the CNS midline.

    PubMed

    Slováková, Jana; Speicher, Stephan; Sánchez-Soriano, Natalia; Prokop, Andreas; Carmena, Ana

    2012-07-18

    Axon guidance is a key process during nervous system development and regeneration. One of the best established paradigms to study the mechanisms underlying this process is the axon decision of whether or not to cross the midline in the Drosophila CNS. An essential regulator of that decision is the well conserved Slit-Robo signaling pathway. Slit guidance cues act through Robo receptors to repel axons from the midline. Despite good progress in our knowledge about these proteins, the intracellular mechanisms associated with Robo function remain poorly defined. In this work, we found that the scaffolding protein Canoe (Cno), the Drosophila orthologue of AF-6/Afadin, is essential for Slit-Robo signaling. Cno is expressed along longitudinal axonal pioneer tracts, and longitudinal Robo/Fasciclin2-positive axons aberrantly cross the midline in cno mutant embryos. cno mutant primary neurons show a significant reduction of Robo localized in growth cone filopodia and Cno forms a complex with Robo in vivo. Moreover, the commissureless (comm) phenotype (i.e., lack of commissures due to constitutive surface presentation of Robo in all neurons) is suppressed in comm, cno double-mutant embryos. Specific genetic interactions between cno, slit, robo, and genes encoding other components of the Robo pathway, such as Neurexin-IV, Syndecan, and Rac GTPases, further confirm that Cno functionally interacts with the Slit-Robo pathway. Our data argue that Cno is a novel regulator of the Slit-Robo signaling pathway, crucial for regulating the subcellular localization of Robo and for transducing its signaling to the actin cytoskeleton during axon guidance at the midline.

  6. Control of growth, secondary metabolism and sporulation in Streptomyces venezuelae ISP5230 by jadW(1), a member of the afsA family of gamma-butyrolactone regulatory genes.

    PubMed

    Wang, Liru; Vining, Leo C

    2003-08-01

    Three new genes (jadW(1), jadW(2) and jadW(3)) were isolated from a region of the Streptomyces venezuelae ISP5230 chromosome at the left-hand end of the jad cluster for jadomycin B (JdB) biosynthesis. The deduced amino acid sequence of jadW(1) showed strong similarity to gene products associated in several streptomycetes with gamma-butyrolactone autoregulators controlling morphological differentiation and secondary metabolism. Examination of JadW(1) for conserved domains detected a repeat sequence characteristic of proteins in the AfsA regulatory family. Insertional inactivation of jadW(1) reduced the growth rate of S. venezuelae cultures in aerated liquid media containing complex nitrogen sources and altered growth morphology in minimal medium. It also affected sporulation on agar media. Cultures of jadW(1)-disrupted mutants grown under conditions supporting biosynthesis of JdB or chloramphenicol by the wild-type strain failed to produce either of the antibiotics. Complementing the disrupted strain by transformation with pJV435, containing a cloned copy of the gene, improved sporulation and restored antibiotic biosynthesis in transformants to titres close to those of the wild-type similarly transformed with pJV435 as a control. The results are consistent with a role for jadW(1) in regulating morphological and metabolic differentiation. Further sequence analysis of jadR(2), which functions with jadR(1) in stress-induced activation of JdB biosynthesis, indicated that this gene encodes a gamma-butyrolactone receptor homologue. The growth-rate-sensitive phenotype of the jadW(1)-disrupted mutant, and the proximity of jadW(1) to jadR(2) indicate that this region of the jad gene cluster contains a regulatory mechanism incorporating gamma-butyrolactone signalling and sensitivity to environmental stress.

  7. Modelling and predicting growth of psychrotolerant pseudomonads in milk and cottage cheese.

    PubMed

    Martinez-Rios, Veronica; Østergaard, Nina Bjerre; Gkogka, Elissavet; Rosshaug, Per Sand; Dalgaard, Paw

    2016-01-04

    Mathematical models were developed and evaluated for growth of psychrotolerant pseudomonads in chilled milk and in cottage cheese with cultured cream dressing. The mathematical models include the effect of temperature, pH, NaCl, lactic acid and sorbic acid. A simplified cardinal parameter growth rate model was developed based on growth in broth. Subsequently, the reference growth rate parameter μref25°C-broth of 1.031/h was calibrated by fitting the model to a total of 35 growth rates from cottage cheese with cultured cream dressing. This resulted in a μref25°C-cottage cheese value of 0.621/h. Predictions from both growth rate models were evaluated by comparison with literature and experimental data. Growth of psychrotolerant pseudomonads in heat-treated milk (n=33) resulted in a bias factor (Bf) of 1.08 and an accuracy factor (Af) of 1.32 (μref25°C-broth), whereas growth in cottage cheese with cultured cream dressing and in non-heated milk (n=26) resulted in Bf of 1.08 and Af of 1.43 (μref25°C-cottage cheese). Lag phase models were developed by using relative lag times and data from both the present study and from literature. The acceptable simulation zone method showed the developed models to successfully predict growth of psychrotolerant pseudomonads in milk and cottage cheese at both constant and dynamic temperature storage conditions. The developed models can be used to predict growth of psychrotolerant pseudomonads and shelf life of chilled cottage cheese and milk at constant and dynamic storage temperatures. The applied methodology and the developed models seem likely to be applicable for shelf life assessment of other types of products where psychrotolerant pseudomonads are important for spoilage.

  8. Atrial Model Development and Prototype Simulations: CRADA Final Report on Tasks 3 and 4

    SciTech Connect

    O'Hara, T.; Zhang, X.; Villongco, C.; Lightstone, F.; Richards, D.

    2016-10-28

    The goal of this CRADA was to develop essential tools needed to simulate human atrial electrophysiology in 3-dimensions using an anatomical image-based anatomy and physiologically detailed human cellular model. The atria were modeled as anisotropic, representing the preferentially longitudinal electrical coupling between myocytes. Across the entire anatomy, cellular electrophysiology was heterogeneous, with left and right atrial myocytes defined differently. Left and right cell types for the “control” case of sinus rhythm (SR) was compared with remodeled electrophysiology and calcium cycling characteristics of chronic atrial fibrillation (cAF). The effects of Isoproterenol (ISO), a beta-adrenergic agonist that represents the functional consequences of PKA phosphorylation of various ion channels and transporters, was also simulated in SR and cAF to represent atrial activity under physical or emotional stress. Results and findings from Tasks 3 & 4 are described. Tasks 3 and 4 are, respectively: Input parameters prepared for a Cardioid simulation; Report including recommendations for additional scenario development and post-processing analytic strategy.

  9. Abstracts of AF Materials Laboratory Reports

    DTIC Science & Technology

    1975-09-01

    NO: TITLE: AUTHOR(S): CONTRACT NO; CONTRACTOR: AFML-TR-73-307 200,397 IMPROVED AUTOMATED TAPE LAYING MACHINE M. Poullos, W. J. Murray, D.L...AUTOMATED IMPROVED AUTOMATED TAPE LAYING MACHINE AUTOMATION AUTOMATION OF COATING PROCESSES FOR GAS TURBINE DLADcS AND VANES 203222/111 203072...IMP90VE0 TAPE LAYING MACHINE IMPP)VED AUTOMATED TAPE LAYING MACHINE A STUDY O^ THE STRESS-STRAIN TEHAVIOR OF GRAPHITE

  10. FCRD Milestone Report: M21AF050901

    SciTech Connect

    Hoelzer, David T; Sokolov, Mikhail A; Byun, Thak Sang; Odette, George R.; Klingensmith, Doug; Gragg, David; Stergar, Eric; Fields, Kirk

    2011-09-01

    The objective of this study was to perform mechanical testing on large scale heats of the advanced ODS 14YWT alloy to investigate the effects of processing parameters on mechanical properties. Mechanical properties tests were conducted on two heats of the advanced ODS 14YWT ferritic alloy: the 14YWT-SM11 was produced by extrusion at ORNL and OW4 was produced by HIP at UCSB. The 14YWT-SM11 showed very high tensile strength compared to OW4, but showed less ductility as a result. The fracture toughness transition temperature of 14YWT-SM11 was determined in two orientations and showed T{sub 0} = 48 C in the favorably strong L-T direction while shifting by 63 C to T{sub 0} = 111 C in the weaker T-L direction. The fracture toughness transition temperature for OW4 was not determined but appeared to be within the range observed for 14YWT-SM11. The fracture toughness of 14YWT-SM11 at room temperature was 86.8 MPa{radical}m and 93.1 MPa{radical}m, which was much higher than that of OW4 (27.4 MPa{radical}m). The strain rate jump tests conducted on OW4 indicated that the creep properties were similar to MA957 at 750 C.

  11. Why Atrial Fibrillation (AF or AFib) Matters

    MedlinePlus

    ... Giving for Heart.org Media for Heart.org Arrhythmia About Arrhythmia Why Arrhythmia Matters Understand Your Risk for Arrhythmia Symptoms, Diagnosis & Monitoring of Arrhythmia Prevention & Treatment of ...

  12. Dental Assistant Specialty, AFS 981X0.

    DTIC Science & Technology

    1982-12-01

    GRP588, N=37) E. Prosthodontic Assistants (GRP453, N=35) F. Preventive Dentistry-Operative Assistants (GRP486, N=15) G. Orthodontic Assistants (GRP477, N...instruments Mix root canal fillings, cements, or materials Mix pulp capping or pulp insulating materials Mix zinc oxide and eugenol pastes Shield patients...matrices Mix temporary filling materials Mix composite resins Mix pulp capping or pulp insulating materials Though members of several other Dentists

  13. A SUB-GRID VOLUME-OF-FLUIDS (VOF) MODEL FOR MIXING IN RESOLVED SCALE AND IN UNRESOLVED SCALE COMPUTATIONS

    SciTech Connect

    VOLD, ERIK L.; SCANNAPIECO, TONY J.

    2007-10-16

    A sub-grid mix model based on a volume-of-fluids (VOF) representation is described for computational simulations of the transient mixing between reactive fluids, in which the atomically mixed components enter into the reactivity. The multi-fluid model allows each fluid species to have independent values for density, energy, pressure and temperature, as well as independent velocities and volume fractions. Fluid volume fractions are further divided into mix components to represent their 'mixedness' for more accurate prediction of reactivity. Time dependent conversion from unmixed volume fractions (denoted cf) to atomically mixed (af) fluids by diffusive processes is represented in resolved scale simulations with the volume fractions (cf, af mix). In unresolved scale simulations, the transition to atomically mixed materials begins with a conversion from unmixed material to a sub-grid volume fraction (pf). This fraction represents the unresolved small scales in the fluids, heterogeneously mixed by turbulent or multi-phase mixing processes, and this fraction then proceeds in a second step to the atomically mixed fraction by diffusion (cf, pf, af mix). Species velocities are evaluated with a species drift flux, {rho}{sub i}u{sub di} = {rho}{sub i}(u{sub i}-u), used to describe the fluid mixing sources in several closure options. A simple example of mixing fluids during 'interfacial deceleration mixing with a small amount of diffusion illustrates the generation of atomically mixed fluids in two cases, for resolved scale simulations and for unresolved scale simulations. Application to reactive mixing, including Inertial Confinement Fusion (ICF), is planned for future work.

  14. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation.

    PubMed

    Yue, L; Feng, J; Gaspo, R; Li, G R; Wang, Z; Nattel, S

    1997-10-01

    refractoriness associated with enhanced ability to maintain AF in the model.

  15. On line automated system for the determination of Sb(V), Sb(III), thrimethyl antimony(v) and total antimony in soil employing multisyringe flow injection analysis coupled to HG-AFS.

    PubMed

    Silva Junior, Mario M; Portugal, Lindomar A; Serra, Antonio M; Ferrer, Laura; Cerdà, Victor; Ferreira, Sergio L C

    2017-04-01

    This paper proposes the use of a multisyringe flow injection analysis (MSFIA) system for inorganic antimony speciation analysis, trimethyl antimony(V) and determination of total antimony in soil samples using hydride generation atomic fluorescence spectrometry (HG-AFS). Total antimony has been determined after reduction of antimony(V) to antimony(III) using potassium iodide and ascorbic acid. For determination of total inorganic antimony the sample is percolated in a mini-column containing the Dowex 50W-X8 resin for retention of the organic species of antimony. Antimony(III) is quantified in presence of 8-hydroxyquinoline as masking agent for antimony(V) after an extraction step of the organic antimony species using the also same mini-column. The trimethyl antimony(V) content is found by difference between total antimony and total inorganic antimony. By other hand, antimony(V) is quantified by difference between total inorganic antimony and antimony(III). The analytical determinations were performed using sodium tetrahydroborate as reducing agent. The optimization step was performed using two-level full factorial design and Doehlert matrix involving the factors: hydrochloric acid and sodium tetrahydroborate concentrations and sample flow rate. The optimized experimental conditions allow the antimony determination utilizing the external calibration technique with limits of detection and quantification of 0.9 and 3.1ngg(-1), respectively, and a precision expressed as relative standard deviation of 3.2% for an antimony solution of 5.0µgL(-1). The method accuracy was confirmed by analysis of the soil certified reference material furnished from Sigma-Aldrich RTC. Additionally, addition/recovery tests were performed employing synthetic solutions prepared using trimethyl antimony(V), antimony(III), antimony(V) and five soil samples. The antimony extraction step was performed in a closed system using hydrochloric acid, ultrasonic radiation and controlled temperature. The

  16. Searching for new mathematical growth model approaches for Listeria monocytogenes.

    PubMed

    Valero, A; Hervás, C; García-Gimeno, R M; Zurera, G

    2007-01-01

    Different secondary modeling approaches for the estimation of Listeria monocytogenes growth rate as a function of temperature (4 to 30 degrees C), citric acid (0% to 0.4% w/v), and ascorbic acid (0% to 0.4% w/v) are presented. Response surface (RS) and square-root (SR) models are proposed together with different artificial neural networks (ANN) based on product functions units (PU), sigmoidal functions units (SU), and a novel approach based on the use of hybrid functions units (PSU), which results from a combination of PU and SU. In this study, a significantly better goodness-of-fit was obtained in the case of the ANN models presented, reflected by the lower SEP values obtained (< 24.23 for both training and generalization datasets). Among these models, the SU model provided the best generalization capacity, displaying lower RMSE and SEP values, with fewer parameters compared to the PU and PSU models. The bias factor (B(f)) and accuracy factor (A(f)) of the mathematical validation dataset were above 1 in all cases, providing fail-safe predictions. The balance between generalization properties and the ease of use is the main consideration when applying secondary modeling approaches to achieve accurate predictions about the behavior of microorganisms.

  17. Nearest-neighbour antiferromagnetic interaction as a limiting factor for critical temperature in a model DMS system

    NASA Astrophysics Data System (ADS)

    Szałowski, Karol

    2011-07-01

    In numerous diluted magnetic semiconductor (DMS) systems, the competition takes place between the short-range antiferromagnetic (AF) superexchange interactions and the long-range Ruderman-Kittel-Kasuya-Yosida (RKKY) coupling mediated by the charge carriers. Such a situation strongly influences the critical temperature, the maximization of which constitutes a challenging task in DMS physics and technology. The aim of the paper is to discuss theoretically the limiting effect of AF interactions between nearest-neighbour magnetic ions on the stability of inhomogeneous ferromagnetic state in a model diluted magnetic system reflecting some crucial features of DMS. The modified molecular field-based model is constructed to account for the magnetic inhomogeneity. The behavior of the system is studied as a function of the ratio of superexchange integral to effective ferromagnetic coupling integral, including the possibility of clustering/anticlustering tendency for the magnetic ions. The ground state of the system is analysed. The critical temperature is found to change non-monotonically with the concentration of magnetic ions and decrease severely for larger concentrations. The behavior of the system significantly differs from the predictions of the usual homogeneous mean-field model. Brief comparison with selected experimental results for (Zn,Mn)Te is provided.

  18. Modelling the effect of lactic acid bacteria from starter- and aroma culture on growth of Listeria monocytogenes in cottage cheese.

    PubMed

    Østergaard, Nina Bjerre; Eklöw, Annelie; Dalgaard, Paw

    2014-10-01

    Four mathematical models were developed and validated for simultaneous growth of mesophilic lactic acid bacteria from added cultures and Listeria monocytogenes, during chilled storage of cottage cheese with fresh- or cultured cream dressing. The mathematical models include the effect of temperature, pH, NaCl, lactic- and sorbic acid and the interaction between these environmental factors. Growth models were developed by combining new and existing cardinal parameter values. Subsequently, the reference growth rate parameters (μref at 25°C) were fitted to a total of 52 growth rates from cottage cheese to improve model performance. The inhibiting effect of mesophilic lactic acid bacteria from added cultures on growth of L. monocytogenes was efficiently modelled using the Jameson approach. The new models appropriately predicted the maximum population density of L. monocytogenes in cottage cheese. The developed models were successfully validated by using 25 growth rates for L. monocytogenes, 17 growth rates for lactic acid bacteria and a total of 26 growth curves for simultaneous growth of L. monocytogenes and lactic acid bacteria in cottage cheese. These data were used in combination with bias- and accuracy factors and with the concept of acceptable simulation zone. Evaluation of predicted growth rates of L. monocytogenes in cottage cheese with fresh- or cultured cream dressing resulted in bias-factors (Bf) of 1.07-1.10 with corresponding accuracy factor (Af) values of 1.11 to 1.22. Lactic acid bacteria from added starter culture were on average predicted to grow 16% faster than observed (Bf of 1.16 and Af of 1.32) and growth of the diacetyl producing aroma culture was on average predicted 9% slower than observed (Bf of 0.91 and Af of 1.17). The acceptable simulation zone method showed the new models to successfully predict maximum population density of L. monocytogenes when growing together with lactic acid bacteria in cottage cheese. 11 of 13 simulations of L

  19. Rovibrational CO analysis in PDR models

    NASA Astrophysics Data System (ADS)

    Stancil, Phillip C.; Cumbee, Renata; Zhang, Ziwei; Walker, Kyle M.; Yang, Benhui; Ferland, Gary J.

    2016-01-01

    CO is one of the most important molecules in the interstellar medium and in photodissociation regions (PDRs). Most of the extragalactic non-stellar IR to submm CO emission originates in PDRs. (Hollenbach & Tielens 1999). Pure rotational CO lines have been previously used in PDR models to provide density, temperature, and other diagnostics. However, for environments exposed to intense UV radiation, CO vibrational levels become significantly populated. Given new calculations of rovibrational collisional rate coefficients for CO-H (Walker et al. 2015, Song et al. 2015) and CO-H2 (Yang et al. 2015), we explore their effects in standard Cloudy PDR (Ferland et al. 2013) and Radex (van der Tak et al. 2007) models. In particular, CO vibrational transitions due to H2 collisions are studied for the first time using reliable full-dimensional CO-H2 collisional data.Ferland, G. J., et al. 2013, Rev. Mex. Astron. y Astrof., 49, 137Hollenbach, D. J. & Tielens, A. G. G. M. 1999, RMP, 71, 173Song, L., et al. 2015, ApJ, in pressvan der Tak, F. F. S, et al. 2007, A&A, 468, 627Walker, K. M., et al. 2015, ApJ, 811, 27Yang, B., et al. 2015, Nature Comm., 6, 6629This work was supported in part by NASA grants NNX12AF42G and NNX15AI61G.

  20. Models and role models.

    PubMed

    ten Cate, Jacob M

    2015-01-01

    Developing experimental models to understand dental caries has been the theme in our research group. Our first, the pH-cycling model, was developed to investigate the chemical reactions in enamel or dentine, which lead to dental caries. It aimed to leverage our understanding of the fluoride mode of action and was also utilized for the formulation of oral care products. In addition, we made use of intra-oral (in situ) models to study other features of the oral environment that drive the de/remineralization balance in individual patients. This model addressed basic questions, such as how enamel and dentine are affected by challenges in the oral cavity, as well as practical issues related to fluoride toothpaste efficacy. The observation that perhaps fluoride is not sufficiently potent to reduce dental caries in the present-day society triggered us to expand our knowledge in the bacterial aetiology of dental caries. For this we developed the Amsterdam Active Attachment biofilm model. Different from studies on planktonic ('single') bacteria, this biofilm model captures bacteria in a habitat similar to dental plaque. With data from the combination of these models, it should be possible to study separate processes which together may lead to dental caries. Also products and novel agents could be evaluated that interfere with either of the processes. Having these separate models in place, a suggestion is made to design computer models to encompass the available information. Models but also role models are of the utmost importance in bringing and guiding research and researchers.

  1. Sublimating grains model of cometary coma.

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Tozzi, G. P.; Brucato, J. R.

    between organic and water icy grains by measuring their color and spectra. To understand solid cometary coma environment from observations it has been necessary to construct a theoretical model to connect each other the observational Sigma Af profiles with a theoretical profile achived from physical laws. In this talk we will present the architecture of the model and the results obtained from the comparison between theoretical Sigma Af profiles and observations of differents new Oort cloud comtes, in order to understand the nature of sublimating grains.

  2. Pairing symmetries in a Hubbard model on an anisotropic triangular lattice

    NASA Astrophysics Data System (ADS)

    Watanabe, Tsutomu; Yokoyama, Hisatoshi; Tanaka, Yukio; Inoue, Jun-ichiro

    2007-10-01

    To consider the paring symmetry formed in organic compounds κ-(BEDT-TTF)2X, we study the half-filled-band Hubbard model on an anisotropic triangular lattice (t in two bond directions and t‧ in the other), using an optimization VMC method. As trial states, we adopt a coexisting state of an antiferromagnetic (AF) order and the dx2-y2 -wave RVB gap, in addition to the d + id- and d + d-wave gap states. In these states, we take account of the effect of band (or Fermi surface) renormalization. Magnetic Mott transitions occur, and a regime of robust superconductivity could not be found, in contrast with our previous study. In the insulating regime, the coexisting state in which an AF order prevails is always the lowest-energy state up to remarkably large t‧/t (≲1.3), whereas a dxy-wave RVB state becomes predominant when t‧/t exceeds this value. In the insulating regime, the effective Fermi surface, determined by the renormalized value t˜‧ / t , is markedly renormalized into different directions according to t‧/t; for t‧/t ≲ 1.3, it approaches that of the square lattice (t˜‧ / t = 0) , whereas for t‧/t ≳ 1.3, it becomes almost one-dimensional (t˜‧ / t≫ 1) .

  3. Parameterization of Fire Injection Height in Large Scale Transport Model

    NASA Astrophysics Data System (ADS)

    Paugam, R.; Wooster, M.; Atherton, J.; Val Martin, M.; Freitas, S.; Kaiser, J. W.; Schultz, M. G.

    2012-12-01

    The parameterization of fire injection height in global chemistry transport model is currently a subject of debate in the atmospheric community. The approach usually proposed in the literature is based on relationships linking injection height and remote sensing products like the Fire Radiative Power (FRP) which can measure active fire properties. In this work we present an approach based on the Plume Rise Model (PRM) developed by Freitas et al (2007, 2010). This plume model is already used in different host models (e.g. WRF, BRAMS). In its original version, the fire is modeled by: a convective heat flux (CHF; pre-defined by the land cover and evaluated as a fixed part of the total heat released) and a plume radius (derived from the GOES Wildfire-ABBA product) which defines the fire extension where the CHF is homogeneously distributed. Here in our approach the Freitas model is modified, in particular we added (i) an equation for mass conservation, (ii) a scheme to parameterize horizontal entrainment/detrainment, and (iii) a new initialization module which estimates the sensible heat released by the fire on the basis of measured FRP rather than fuel cover type. FRP and Active Fire (AF) area necessary for the initialization of the model are directly derived from a modified version of the Dozier algorithm applied to the MOD14 product. An optimization (using the simulating annealing method) of this new version of the PRM is then proposed based on fire plume characteristics derived from the official MISR plume height project and atmospheric profiles extracted from the ECMWF analysis. The data set covers the main fire region (Africa, Siberia, Indonesia, and North and South America) and is set up to (i) retain fires where plume height and FRP can be easily linked (i.e. avoid large fire cluster where individual plume might interact), (ii) keep fire which show decrease of FRP and AF area after MISR overpass (i.e. to minimize effect of the time period needed for the plume to

  4. Developing High-resolution Soil Database for Regional Crop Modeling in East Africa

    NASA Astrophysics Data System (ADS)

    Han, E.; Ines, A. V. M.

    2014-12-01

    The most readily available soil data for regional crop modeling in Africa is the World Inventory of Soil Emission potentials (WISE) dataset, which has 1125 soil profiles for the world, but does not extensively cover countries Ethiopia, Kenya, Uganda and Tanzania in East Africa. Another dataset available is the HC27 (Harvest Choice by IFPRI) in a gridded format (10km) but composed of generic soil profiles based on only three criteria (texture, rooting depth, and organic carbon content). In this paper, we present a development and application of a high-resolution (1km), gridded soil database for regional crop modeling in East Africa. Basic soil information is extracted from Africa Soil Information Service (AfSIS), which provides essential soil properties (bulk density, soil organic carbon, soil PH and percentages of sand, silt and clay) for 6 different standardized soil layers (5, 15, 30, 60, 100 and 200 cm) in 1km resolution. Soil hydraulic properties (e.g., field capacity and wilting point) are derived from the AfSIS soil dataset using well-proven pedo-transfer functions and are customized for DSSAT-CSM soil data requirements. The crop model is used to evaluate crop yield forecasts using the new high resolution soil database and compared with WISE and HC27. In this paper we will present also the results of DSSAT loosely coupled with a hydrologic model (VIC) to assimilate root-zone soil moisture. Creating a grid-based soil database, which provides a consistent soil input for two different models (DSSAT and VIC) is a critical part of this work. The created soil database is expected to contribute to future applications of DSSAT crop simulation in East Africa where food security is highly vulnerable.

  5. Prediction of binding affinity and efficacy of thyroid hormone receptor ligands using QSAR and structure-based modeling methods

    SciTech Connect

    Politi, Regina; Rusyn, Ivan; Tropsha, Alexander

    2014-10-01

    The thyroid hormone receptor (THR) is an important member of the nuclear receptor family that can be activated by endocrine disrupting chemicals (EDC). Quantitative Structure–Activity Relationship (QSAR) models have been developed to facilitate the prioritization of THR-mediated EDC for the experimental validation. The largest database of binding affinities available at the time of the study for ligand binding domain (LBD) of THRβ was assembled to generate both continuous and classification QSAR models with an external accuracy of R{sup 2} = 0.55 and CCR = 0.76, respectively. In addition, for the first time a QSAR model was developed to predict binding affinities of antagonists inhibiting the interaction of coactivators with the AF-2 domain of THRβ (R{sup 2} = 0.70). Furthermore, molecular docking studies were performed for a set of THRβ ligands (57 agonists and 15 antagonists of LBD, 210 antagonists of the AF-2 domain, supplemented by putative decoys/non-binders) using several THRβ structures retrieved from the Protein Data Bank. We found that two agonist-bound THRβ conformations could effectively discriminate their corresponding ligands from presumed non-binders. Moreover, one of the agonist conformations could discriminate agonists from antagonists. Finally, we have conducted virtual screening of a chemical library compiled by the EPA as part of the Tox21 program to identify potential THRβ-mediated EDCs using both QSAR models and docking. We concluded that the library is unlikely to have any EDC that would bind to the THRβ. Models developed in this study can be employed either to identify environmental chemicals interacting with the THR or, conversely, to eliminate the THR-mediated mechanism of action for chemicals of concern. - Highlights: • This is the largest curated dataset for ligand binding domain (LBD) of the THRβ. • We report the first QSAR model for antagonists of AF-2 domain of THRβ. • A combination of QSAR and docking enables

  6. Models, Fiction, and Fictional Models

    NASA Astrophysics Data System (ADS)

    Liu, Chuang

    2014-03-01

    The following sections are included: * Introduction * Why Most Models in Science Are Not Fictional * Typically Fictional Models in Science * Modeling the Unobservable * Fictional Models for the Unobservable? * References

  7. Computation-Based Discovery of Related Transcriptional Regulatory Modules and Motifs Using an Experimentally Validated Combinatorial Model

    PubMed Central

    Halfon, Marc S.; Grad, Yonatan; Church, George M.; Michelson, Alan M.

    2002-01-01

    Gene expression is regulated by transcription factors that interact with cis-regulatory elements. Predicting these elements from sequence data has proven difficult. We describe here a successful computational search for elements that direct expression in a particular temporal-spatial pattern in the Drosophila embryo, based on a single well characterized enhancer model. The fly genome was searched to identify sequence elements containing the same combination of transcription factors as those found in the model. Experimental evaluation of the search results demonstrates that our method can correctly predict regulatory elements and highlights the importance of functional testing as a means of identifying false-positive results. We also show that the search results enable the identification of additional relevant sequence motifs whose functions can be empirically validated. This approach, combined with gene expression and phylogenetic sequence data, allows for genome-wide identification of related regulatory elements, an important step toward understanding the genetic regulatory networks involved in development. [Sequence data reported in this paper have been deposited in GenBank with accession nos. AF513981 (Eve MHE) and AF513982 (Hbr DME). Supplementary material is available online at http://www.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: R. Blackman] PMID:12097338

  8. Quantum dots as contrast agents for endoscopy: mathematical modeling and experimental validation of the optimal excitation wavelength

    NASA Astrophysics Data System (ADS)

    Roy, Mathieu; DaCosta, Ralph S.; Weersink, Robert; Netchev, George; Davidson, Sean R. H.; Chan, Warren; Wilson, Brian C.

    2007-02-01

    Our group is investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). Our studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. This work quantitatively evaluates the effect of the excitation wavelength on the SBR, using both experimental measurements and mathematical modeling. Experimental SBR measurements were done by imaging QD solutions placed onto (surface) or embedded in (sub-surface) ex vivo murine tissue samples (brain, kidney, liver, lung), using a polymethylmethacrylate (PMMA) microchannel phantom. The results suggest that the maximum contrast is reached when the excitation wavelength is set at 400+/-20 μm for the surface configuration. For the sub-surface configuration, the optimal excitation wavelength varies with the tissue type and QD emission wavelengths. Our mathematical model, based on an approximation to the diffusion equation, successfully predicts the optimal excitation wavelength for the surface configuration, but needs further modifications to be accurate in the sub-surface configuration.

  9. Inverse Modeling of Coastal Tides

    DTIC Science & Technology

    1999-09-30

    data in the tidal band. We have concluded that understanding this discrepancy and developing assimilation methods for baroclinic tides will require...Alexandre Kurapov to develop practical assimilation methods for coastal HF radar data. REFERENCES Bennett, A.F., B.S. Chua, and L.M. Leslie, Generalized

  10. Inverse Modeling of Coastal Tides

    DTIC Science & Technology

    1998-01-01

    produced. We are also working with Profs. J. Allen and R. Miller on developing practical assimilation methods for the coastal problem. REFERENCES...40, 81--108, 1997. Egbert, G.D. and A.F. Bennett, Data assimilation methods for ocean tides, in Modern approaches to data assimilation in ocean

  11. Regional approach to modeling the transport of floating plastic debris in the Adriatic Sea.

    PubMed

    Liubartseva, S; Coppini, G; Lecci, R; Creti, S

    2016-02-15

    Sea surface concentrations of plastics and their fluxes onto coastlines are simulated over 2009-2015. Calculations incorporate combinations of terrestrial and maritime litter inputs, the Lagrangian model MEDSLIK-II forced by AFS ocean current simulations, and ECMWF wind analyses. With a relatively short particle half-life of 43.7 days, the Adriatic Sea is defined as a highly dissipative basin where the shoreline is, by construction, the main sink of floating debris. Our model results show that the coastline of the Po Delta receives a plastic flux of approximately 70 kg(km day)(-1). The most polluted sea surface area (>10 g km(-2) floating debris) is represented by an elongated band shifted to the Italian coastline and narrowed from northwest to southeast. Evident seasonality is found in the calculated plastic concentration fields and the coastline fluxes. Complex source-receptor relationships among the basin's subregions are quantified in impact matrices.

  12. Animal model of Mycoplasma fermentans respiratory infection

    PubMed Central

    2013-01-01

    Background Mycoplasma fermentans has been associated with respiratory, genitourinary tract infections and rheumatoid diseases but its role as pathogen is controversial. The purpose of this study was to probe that Mycoplasma fermentans is able to produce respiratory tract infection and migrate to several organs on an experimental infection model in hamsters. One hundred and twenty six hamsters were divided in six groups (A-F) of 21 hamsters each. Animals of groups A, B, C were intratracheally injected with one of the mycoplasma strains: Mycoplasma fermentans P 140 (wild strain), Mycoplasma fermentans PG 18 (type strain) or Mycoplasma pneumoniae Eaton strain. Groups D, E, F were the negative, media, and sham controls. Fragments of trachea, lungs, kidney, heart, brain and spleen were cultured and used for the histopathological study. U frequency test was used to compare recovery of mycoplasmas from organs. Results Mycoplasmas were detected by culture and PCR. The three mycoplasma strains induced an interstitial pneumonia; they also migrated to several organs and persisted there for at least 50 days. Mycoplasma fermentans P 140 induced a more severe damage in lungs than Mycoplasma fermentans PG 18. Mycoplasma pneumoniae produced severe damage in lungs and renal damage. Conclusions Mycoplasma fermentans induced a respiratory tract infection and persisted in different organs for several weeks in hamsters. This finding may help to explain the ability of Mycoplasma fermentans to induce pneumonia and chronic infectious diseases in humans. PMID:23298636

  13. Mental Models, Conceptual Models, and Modelling.

    ERIC Educational Resources Information Center

    Greca, Ileana Maria; Moreira, Marco Antonio

    2000-01-01

    Reviews science education research into representations constructed by students in their interactions with the world, its phenomena, and artefacts. Features discussions of mental models, conceptual models, and the activity of modeling. (Contains 30 references.) (Author/WRM)

  14. Kondo effect of D\\xAFs and D\\xAFs* mesons in nuclear matter

    NASA Astrophysics Data System (ADS)

    Yasui, Shigehiro; Sudoh, Kazutaka

    2017-03-01

    We study the Kondo effect for D¯s and D¯s* mesons as impurity particles in nuclear matter. The spin-exchange interaction between the D¯s or D¯s* meson and the nucleon induces the enhancement of the effective coupling in the low-energy scattering in the infrared region, whose energy scale of singularity is given by the Kondo scale. We investigate the Kondo scale in the renormalization group equation at nucleon one-loop level. We furthermore study the ground state with the Kondo effect in the mean-field approach, and present that the Kondo scale is related to the mixing strength between the D¯s or D¯s* meson and the nucleon in nuclear matter. We show the spectral function of the impurity when the Kondo effect occurs.

  15. Cape Romanzof AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-03-01

    to unlimited distribution of this report to the public at large, or by DDC to the National Technical Information Service (NTIS). This techmical...m ,mm~ -- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - aI GLOBAL CLIMATOLOGY BRANCH UShCT AC AIR wEATER SERVICe /MAC WEATHER...CLIMATOLOGY BRANCH uSFCETAC SURFACE WINDS AIR WEATER SERVICE /MAC PERCENTAGE FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 71212c CAPE

  16. Tatalina AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-03-01

    at large, or by DDC to the National Technical Information Service (NTIS). This technical report has been revieed and is approved for publication...NUMSER F OSEtVATIONS 7 1 q IJSAFETAC M--5 0 L.A 1.VoltS (O,’,Q OF ’-S FOPS A4 CN f GL034L CLIMATOLOGY BRANCI4 2 USAFETAC SURFACE WINDS AI. WEATER SERVICE ...CiUSAPETAC �-5 (OL.A) PM"VCIJ lffloftl OF tI? Pos* An OSEO.I - - - f 6LOBAL CLINATOLO6Y BRANcHUSAFTAC SURFACE WINDS AI WEATER [l SERVICE /MAC PERCENTAGE

  17. Galena AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-07-28

    152 149 ft 24 5 Sane Sare Mar 79 Jul 83 Sare Same Sane Same 24 Ii I ia ; DATE SUFACI wis$ EINi[Mau INFOaR11Iie Of OF IPS f TrP p li Alcoa RtAfiS...ri sr .9 -I .,, i I _ 7 e" l .. ., III Ois Me,* fNw -l .ot R.I. 0 P 73 miP Imm IP mi93 Fn i ~ L :LlT12L3 y DA’% C42 7* T AC PSYCHROMETRIC SUMMARY 2 .AT

  18. Sparrevohn AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-03-01

    61.? 6.9 61.9 6i.f I.9 61. 61.9 b1. ’ 61.9 bl.Q 81 . , " bb . 6 S 6- .5 66 . ,o t b 6o 68.6 b8 .b 68.6 66.6 68.t 68.6 6.6 68 .6 5 6p . 72.1 74. 74,. 7S...8-.4 83 -.4’ 02.4 575 5.5 ,g. ’ 7 2.:7 74.o6 76.5 7% 7 8.6 a0.1 81 . 1 82 .?2 83.5 84. 8. 84.3 84. 61 4. 1 4 1 .6 7’o# 75.1 77. j 7A.TO 4 3. Al.a 2...1 15 6 4.4/ 43 .1 bi 2.2; 3.7- 2., .4 562 S62 414 61 _________,___,3J_1_____.SL_________ , -- . -. -.. - 82 5.6. b.-5, 2 5. ~.l41 li 1.41 3.5 b8 81 23

  19. Corepressive Action of CBP on Androgen Receptor Transactivation in Pericentric Heterochromatin in a Drosophila Experimental Model System▿ †

    PubMed Central

    Zhao, Yue; Takeyama, Ken-ichi; Sawatsubashi, Shun; Ito, Saya; Suzuki, Eriko; Yamagata, Kaoru; Tanabe, Masahiko; Kimura, Shuhei; Fujiyama, Sally; Ueda, Takashi; Murata, Takuya; Matsukawa, Hiroyuki; Shirode, Yuko; Kouzmenko, Alexander P.; Li, Feng; Tabata, Testuya; Kato, Shigeaki

    2009-01-01

    Ligand-bound nuclear receptors (NR) activate transcription of the target genes. This activation is coupled with histone modifications and chromatin remodeling through the function of various coregulators. However, the nature of the dependence of a NR coregulator action on the presence of the chromatin environment at the target genes is unclear. To address this issue, we have developed a modified position effect variegation experimental model system that includes an androgen-dependent reporter transgene inserted into either a pericentric heterochromatin region or a euchromatic region of Drosophila chromosome. Human androgen receptor (AR) and its constitutively active truncation mutant (AR AF-1) were transcriptionally functional in both chromosomal regions. Predictably, the level of AR-induced transactivation was lower in the pericentric heterochromatin. In genetic screening for AR AF-1 coregulators, Drosophila CREB binding protein (dCBP) was found to corepress AR transactivation at the pericentric region whereas it led to coactivation in the euchromatic area. Mutations of Sir2 acetylation sites or deletion of the CBP acetyltransferase domain abrogated dCBP corepressive action for AR at heterochromatic areas in vivo. Such a CBP corepressor function for AR was observed in the transcriptionally silent promoter of an AR target gene in cultured mammalian cells. Thus, our findings suggest that the action of NR coregulators may depend on the state of chromatin at the target loci. PMID:19075001

  20. Local inhibition of elastase reduces EMILIN1 cleavage reactivating lymphatic vessel function in a mouse lymphoedema model

    PubMed Central

    Pivetta, Eliana; Wassermann, Bruna; Belluz, Lisa Del Bel; Danussi, Carla; Modica, Teresa Maria Elisa; Maiorani, Orlando; Bosisio, Giulia; Boccardo, Francesco; Canzonieri, Vincenzo; Colombatti, Alfonso

    2016-01-01

    Lymphatic vasculature critically depends on the connections of lymphatic endothelial cells with the extracellular matrix (ECM), which are mediated by anchoring filaments (AFs). The ECM protein EMILIN1 is a component of AFs and is involved in the regulation of lymphatic vessel functions: accordingly, Emilin1−/− mice display lymphatic vascular morphological alterations, leading to functional defects such as mild lymphoedema, lymph leakage and compromised lymph drainage. In the present study, using a mouse post-surgical tail lymphoedema model, we show that the acute phase of acquired lymphoedema correlates with EMILIN1 degradation due to neutrophil elastase (NE) released by infiltrating neutrophils. As a consequence, the intercellular junctions of lymphatic endothelial cells are weakened and drainage to regional lymph nodes is severely affected. The local administration of sivelestat, a specific NE inhibitor, prevent