Science.gov

Sample records for modellering af naturlig

  1. AfsR recruits RNA polymerase to the afsS promoter: a model for transcriptional activation by SARPs.

    PubMed

    Tanaka, Akiko; Takano, Yuji; Ohnishi, Yasuo; Horinouchi, Sueharu

    2007-06-01

    AfsR, a protein belonging to the Streptomyces antibiotic regulatory protein (SARP) family, is a global regulator of secondary metabolism in Streptomyces coelicolor A3(2). AfsR consists of three major functional domains: an N-terminal SARP domain, a central ATPase domain, and a C-terminal tetratrico peptide repeat (TPR) domain. Two truncated AfsR proteins, AfsRDeltaTPR containing the SARP and ATPase domains and AfsRDeltaC containing only the SARP domain, exhibited the same DNA-binding specificity as that of full-length AfsR. Two monomers bound cooperatively to a direct repeat located eight nucleotides 5' to the -10 element of the afsS promoter. Both truncated AfsR proteins, as well as full-length AfsR, were able to form ternary complexes with the afsS promoter and RNA polymerase (RNAP), although RNAP alone could not bind to the DNA. The DNA-(AfsRDeltaC)(2)-RNAP complex was capable of initiating afsS transcription in vitro, indicating that the ATPase and TPR domains are dispensable for the basic function of AfsR as a transcriptional activator. However, the ATPase domain was required to fully compensate for the defect in actinorhodin production in an afsR-disrupted mutant, suggesting that the ATPase domain exerts a regulatory function on the basic SARP domain. Deletion or addition of even a single nucleotide between the AfsR-binding site and the -10 element of the afsS promoter abolished afsS transcription both in vitro and in vivo, indicating that the recruitment of RNAP by AfsR to the correct location relative to the -10 element is critical for transcriptional activation. Since SARP-binding sites with similar direct repeats are located at the same position relative to the -10 element of their target promoters as is the afsS binding site, the SARP family members presumably activate transcription of their targets by recruiting RNAP to the promoter, where a ternary DNA-SARP-RNAP complex competent for transcriptional initiation is formed.

  2. Modeling spall in HY100, HY130, and AF1410 steels

    NASA Astrophysics Data System (ADS)

    Garrett, R. K.; Rajendran, A. M.; Last, H. R.

    1996-05-01

    A comparison spall analysis between three matensitic steels: HY100, HY130, and AF1410 is presented Metallurgical observations on the fracture surfaces of uniaxial tensile specimens as well as the spalled target plates confirmed the nucleation, growth, and coalescence of microvoids in these steels. The threshold stress for void nucleation in these steels were determined from the spall analysis using the EPIC finite element code. According to the model, the spall nucleation occurred at higher stress levels in AF1410 compared to HY100 and HY130. A complete set of material model constants has been determined for these three steels.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model.

    PubMed

    Liu, Qiang; Chen, Longgui; Atkinson, Jennifer M; Claxton, David F; Wang, Hong-Gang

    2016-01-01

    Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation pathway that is hypothesized to be important for the maintenance of AML as well as contribute to chemotherapy response. Here we employ a mouse model of AML expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion, a key autophagy protein, on the malignant transformation and progression of AML. Consistent with a transient decrease in colony-forming potential in vitro, the in vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary transplantation prolonged the survival of recipient mice, suggesting that autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion of Atg5 in malignant AML cells during secondary transplantation did not influence the survival or chemotherapeutic response of leukemic mice. Interestingly, autophagy was found to be involved in the survival of differentiated myeloid cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that Atg5-dependent autophagy may contribute to the development but not chemotherapy sensitivity of murine AML induced by MLL-AF9. PMID:27607576

  8. Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model

    PubMed Central

    Liu, Qiang; Chen, Longgui; Atkinson, Jennifer M; Claxton, David F; Wang, Hong-Gang

    2016-01-01

    Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation pathway that is hypothesized to be important for the maintenance of AML as well as contribute to chemotherapy response. Here we employ a mouse model of AML expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion, a key autophagy protein, on the malignant transformation and progression of AML. Consistent with a transient decrease in colony-forming potential in vitro, the in vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary transplantation prolonged the survival of recipient mice, suggesting that autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion of Atg5 in malignant AML cells during secondary transplantation did not influence the survival or chemotherapeutic response of leukemic mice. Interestingly, autophagy was found to be involved in the survival of differentiated myeloid cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that Atg5-dependent autophagy may contribute to the development but not chemotherapy sensitivity of murine AML induced by MLL-AF9. PMID:27607576

  9. 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.

  10. 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. PMID:16930681

  11. 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.

  12. An Immunocompetent Mouse Model for MLL/AF9 Leukemia Reveals the Potential of Spontaneous Cytotoxic T-Cell Response to an Antigen Expressed in Leukemia Cells

    PubMed Central

    Hasegawa, Kana; Tanaka, Satomi; Fujiki, Fumihiro; Morimoto, Soyoko; Nakajima, Hiroko; Tatsumi, Naoya; Nakata, Jun; Takashima, Satoshi; Nishida, Sumiyuki; Tsuboi, Akihiro; Oka, Yoshihiro; Oji, Yusuke; Kumanogoh, Atsushi; Sugiyama, Haruo; Hosen, Naoki

    2015-01-01

    Leukemia differs substantially with respect to stromal milieu from tumors that progress locally as solid masses, and the physiological importance of immunosurveillance in leukemia remains unclear. However, currently available mouse leukemia models have critical limitations in the context of analyzing immunological regulation of leukemia development. In this study, we transferred mouse MLL/AF9 leukemia-initiating cells into immunocompetent recipient mice without any pre-conditioning such as irradiation, and then analyzed the spontaneous T cell response to an immunogenic antigen expressed in leukemia cells. When the minimum numbers of leukemia-initiating cells for engraftment were transferred, leukemia cells were eradicated by the adaptive immune response in most, if not all, wild-type mice, but not in Rag2-/- recipient mice, which lack adaptive immunity. By contrast, mice transplanted with larger numbers of leukemia cells always developed leukemia. In mice with advanced leukemia, antigen-specific CTLs were also expanded, but were unresponsive to antigen stimulation and expressed high levels of PD-1 and LAG-3. These results provide the first clear demonstration that the spontaneous CTL response to a tumor-cell antigen has the potential to eradicate leukemia, whereas antigen-specific CTLs are exhausted in animals with advanced leukemia. This immunocompetent mouse leukemia model provides a useful platform for developing effective immunotherapies against leukemia. PMID:26658107

  13. 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

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

    PubMed

    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

  15. 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.

  16. Tuning the Music: Acoustic Force Spectroscopy (AFS) 2.0.

    PubMed

    Kamsma, Douwe; Creyghton, Ramon; Sitters, Gerrit; Wuite, Gijs J L; Peterman, Erwin J G

    2016-08-01

    AFS is a recently introduced high-throughput single-molecule technique that allows studying structural and mechanochemical properties of many biomolecules in parallel. To further improve the method, we developed a modelling tool to optimize the layer thicknesses, and a calibration method to experimentally validate the modelled force profiles. After optimization, we are able to apply 350pN on 4.5μm polystyrene beads, without the use of an amplifier, at the coverslip side of the AFS chip. Furthermore, we present the use of a transparent piezo to generate the acoustic force and we show that AFS can be combined with high-NA oil or water-immersion objectives. With this set of developments AFS will be applicable to a broad range of single-molecule experiments. PMID:27163865

  17. The AFS Impact Study: Final Report. AFS Research Report 33.

    ERIC Educational Resources Information Center

    Hansel, Bettina

    The AFS Impact Study, initiated in 1977, is an attempt to document changes in learning and personal development associated with an intercultural "homestay" program. Completed in 1985, the study identifies several areas in which students show greater learning and educational growth than that shown by a group of students who had expressed interest…

  18. AF64A-induced brain damage and its relation to dementia.

    PubMed

    Hörtnagl, H

    1994-01-01

    Several data obtained in the AF64A-model are of particular relevance for our understanding of the pathogenesis and progression of Alzheimer's disease. The AF64A-induced withdrawal of cholinergic function in the rat hippocampus was associated with reversible functional changes in other neurotransmitters, including noradrenaline, serotonin, somatostatin and glutamate, thereby mimicking changes in Alzheimer's disease. Identical changes in markers for synaptic vesicles were found in Alzheimer's disease and AF64A-model. A study on the role of gender revealed a higher susceptibility to the neurotoxic action of AF64A in female rats. The cholinergic deficit was also responsible for a disinhibition of the negative feedback regulation of glucocorticoids. Increased exposure to glucocorticoids, however, enhanced the vulnerability of hippocampal cholinergic neurons to AF64A. These data indicate that the AF64A-induced cholinergic deficit in the rat brain represents a reliable tool to study several mechanisms possibly involved in Alzheimer's disease.

  19. 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.

  20. Effects of a novel cholinergic M1 agonist, AF102B, on ambulation and water drinking behavior in rats.

    PubMed

    Togashi, H; Matsumoto, M; Yoshioka, M; Saito, Y; Saito, H

    1991-01-01

    Effects of a novel M1 agonist, AF102B (cis-2-methylspiro(1,3-oxathiolane-5,3')quinuclidine HCl), on ambulation and water drinking behavior were examined using an Ambulo-Drinkometer. AF64A-treated rats, an animal model for senile dementia of the Alzheimer type (SDAT), and non-treated control rats were used. AF102B was administered orally via tap water at a concentration of 0.01% and 0.1% for an experimental therapeutic dose and a supramaximal dose, respectively. Four-week administration of 0.01% AF102B did not affect either ambulatory activity or water drinking activity in non-treated rats. Successive 0.1% AF102B administration for 4 weeks produced a significant decrease in drinking activity as compared with non-treated control rats. In AF64A-treated rats, AF102B did not change the cholinotoxin AF64A-induced high activity in ambulation. However, a decrease in water drinking activity was observed after 0.1% AF102B administration, as in non-treated rats. These results suggest that therapeutic dose of AF102B do not produce any changes in the spontaneous moter activity and water drinking behavior in normal rats or the animal model for SDAT. Several investigators reported that AF102B (FSK-508; cis-2-methylspiro (1,3-oxathiolane-5,3') quinuclidine HCl) had the property of a relatively specific muscarinic agonist of the M1-type This novel M1 agonist, AF102B, also exerted and ameliorating effect on experimental amnesia; in a T-maze, radial-arm maze task and passive avoidance tasks. AF102B improves the cognitive impairment in various animal models for memory disorders including senile dementia of the Alzheimer type (SDAT). Based on these observations, AF102B has been proposed for the treatment of SDAT.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Eaton AF5000+Genesis Communication Driver

    1995-05-25

    Communication driver allows the Genesis Control Series software to interact with Eaton AF5000+ frequency drives via RS-232 communications. All Eaton AF5000+ parameters that support communications are supported by the Genesis driver. Multidrop addressing to multiple units is available with the Genesis communication driver.

  2. 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

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

    MedlinePlus

    ... af Soomaali (Somali) Bilingual PDF Health Information Translations Tornadoes Sirens and Telephone Alerts - English Firimbiyada iyo Digniinaha telefonka - af Soomaali (Somali) PDF Healthy Roads Media Tornadoes - English Dabayl xoog badan (Ufo) - af Soomaali (Somali) ...

  4. 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.

  5. Concluding Report of Free-Spinning, Tumbling, and Recovery Characteristics of a 1/18-Scale Model of the Ryan X-13 Airplane, Coord. No. AF-199

    NASA Technical Reports Server (NTRS)

    Bowman, James S., Jr.

    1957-01-01

    An investigation has been completed in the Langley 20-foot free-spinning tunnel on a l/18-scale model of the Ryan X-13 airplane to determine its spin, recovery, and tumbling characteristics, and to determine the minimum altitude from which a belly landing could be made in case of power failure in hovering flight. Model spin tests were conducted with and without simulated engine rotation. Tests without simulated engine rotation indicated two types of spins: one, a slightly oscillatory flat spin; and the other, a violently oscillatory spin. Tests with simulated engine rotation indicated that spins to the left were fast rotating and steep and those to the right were slow rotating and flat. The optimum technique for recovery is reversal of the rudder to against the spin and simultaneous movement of the ailerons to full with the spin followed by movement of the elevators to neutral after the spin rotation ceases. Tumbling tests made on the model indicated that although the Ryan X-13 airplane will not tumble in the ordinary sense (end-over-end pitching motion), it may instead tend to enter a wild gyrating'motion. Tests made to simulate power failure in hovering flight by dropping the model indicated that the model entered what appeared to be a right spin. An attempt should be made to stop this motion immediately by moving the rudder to oppose the rotation (left pedal), moving the ailerons to with the spin (stick right), and moving the stick forward after the spin rotation ceases to obtain flying speed for pullout. The minimum altitude required for a belly landing in case of power failure in hovering flight was indicated to be about 4,200 feet.

  6. Critical behavior of a triangular lattice Ising AF/FM bilayer

    NASA Astrophysics Data System (ADS)

    Žukovič, M.; Bobák, A.

    2016-03-01

    We study a bilayer Ising spin system consisting of antiferromagnetic (AF) and ferromagnetic (FM) triangular planes, coupled by ferromagnetic exchange interaction, by standard Monte Carlo and parallel tempering methods. The AF/FM bilayer is found to display the critical behavior completely different from both the single FM and AF constituents as well as the FM/FM and AF/AF bilayers. Namely, by finite-size scaling (FSS) analysis we identify at the same temperature a standard Ising transition from the paramagnetic to FM state in the FM plane that induces a ferrimagnetic state with a finite net magnetic moment in the AF plane. At lower temperatures there is another phase transition, that takes place only in the AF plane, to different ferrimagnetic state with spins on two sublattices pointing parallel and on one sublattice antiparallel to the spins on the FM plane. FSS indicates that the corresponding critical exponents are close to the two-dimensional three-state ferromagnetic Potts model values.

  7. The equilibrium properties and folding kinetics of an all-atom Go xAF model of the Trp-cage

    NASA Astrophysics Data System (ADS)

    Linhananta, Apichart; Boer, Jesse; MacKay, Ian

    2005-03-01

    The ultrafast-folding 20-residue Trp-cage protein is quickly becoming a new benchmark for molecular dynamics studies. Already several all-atom simulations have probed its equilibrium and kinetic properties. In this work an all-atom Go ¯ model is used to accurately represent the side-chain packing and native atomic contacts of the Trp-cage. The model reproduces the hallmark thermodynamics cooperativity of small proteins. Folding simulations observe that in the fast-folding dominant pathway, partial α-helical structure forms before hydrophobic core collapse. In the slow-folding secondary pathway, partial core collapse occurs before helical structure. The slow-folding rate of the secondary pathway is attributed to the loss of side-chain rotational freedom, due to the early core collapse, which impedes the helix formation. A major finding is the observation of a low-temperature kinetic intermediate stabilized by a salt bridge between residues Asp-9 and Arg-16. Similar observations [R. Zhou, Proc. Natl. Acad. Sci. U.S.A. 100, 13280 (2003)] were reported in a recent study using an all-atom model of the Trp-cage in explicit water, in which the salt-bridge stabilized intermediate was hypothesized to be the origin of the ultrafast-folding mechanism. A theoretical mutation that eliminates the Asp-9-Arg-16 salt bridge, but leaves the residues intact, is performed. Folding simulations of the mutant Trp-cage observe a two-state free-energy landscape with no kinetic intermediate and a significant decrease in the folding rate, in support of the hypothesis.

  8. 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

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26079538

  10. 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

  11. 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.

  12. The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;NrasG12D acute myeloid leukemia

    PubMed Central

    Shi, Junwei; Wang, Eric; Zuber, Johannes; Rappaport, Amy; Taylor, Meredith; Johns, Christopher

    2014-01-01

    The Trithorax and Polycomb groups of chromatin regulators are critical for cell-lineage specification during normal development; functions that often become deregulated during tumorigenesis. As an example, oncogenic fusions of the Trithorax-related protein MLL can initiate aggressive leukemias by altering the transcriptional circuitry governing hematopoietic cell differentiation, a process that is known to require additional epigenetic pathways to implement. Here we used shRNA screening to identify chromatin regulators uniquely required in a mouse model of MLL-fusion acute myeloid leukemia, which revealed a role for the Polycomb Repressive Complex 2 (PRC2) in maintenance of this disease. shRNA-mediated suppression of PRC2 subunits Eed, Suz12, or Ezh1/Ezh2 led to proliferation-arrest and differentiation of leukemia cells, with a minimal impact on growth of several non-transformed hematopoietic cell lines. The requirement for PRC2 in leukemia is partly due to its role in direct transcriptional repression of genes that limit the self-renewal potential of hematopoietic cells, including Cdkn2a. In addition to implicating a role for PRC2 in the pathogenesis of MLL-fusion leukemia, our results suggest, more generally, that Trithorax and Polycomb group proteins can cooperate with one another to maintain aberrant lineage programs in cancer. PMID:22469984

  13. Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success

    PubMed Central

    Choi, Eue-Keun; Park, Jae Hyung; Lee, Ji-Young; Nam, Chung Mo; Hwang, Min Ki; Uhm, Jae-Sun; Joung, Boyoung; Ko, Young-Guk; Lee, Moon-Hyoung; Lubitz, Steven A; Ellinor, Patrick T; Pak, Hui-Nam

    2015-01-01

    Background Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF. Methods and Results We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10−16; PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10−11; ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10−14; KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation. Conclusions SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation. PMID:26272656

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. [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.

  20. MLL-AF6 fusion oncogene sequesters AF6 into the nucleus to trigger RAS activation in myeloid leukemia.

    PubMed

    Manara, Elena; Baron, Emma; Tregnago, Claudia; Aveic, Sanja; Bisio, Valeria; Bresolin, Silvia; Masetti, Riccardo; Locatelli, Franco; Basso, Giuseppe; Pigazzi, Martina

    2014-07-10

    A rare location, t(6;11)(q27;q23) (MLL-AF6), is associated with poor outcome in childhood acute myeloid leukemia (AML). The described mechanism by which MLL-AF6, through constitutive self-association and in cooperation with DOT-1L, activates aberrant gene expression does not explain the biological differences existing between t(6;11)-rearranged and other MLL-positive patients nor their different clinical outcome. Here, we show that AF6 is expressed in the cytoplasm of healthy bone marrow cells and controls rat sarcoma viral oncogene (RAS)-guanosine triphosphate (GTP) levels. By contrast, in MLL-AF6-rearranged cells, AF6 is found localized in the nucleus, leading to aberrant activation of RAS and of its downstream targets. Silencing MLL-AF6, we restored AF6 localization in the cytoplasm, thus mediating significant reduction of RAS-GTP levels and of cell clonogenic potential. The rescue of RAS-GTP levels after MLL-AF6 and AF6 co-silencing confirmed that MLL-AF6 oncoprotein potentiates the activity of the RAS pathway through retention of AF6 within the nucleus. Exposure of MLL-AF6-rearranged AML blasts to tipifarnib, a RAS inhibitor, leads to cell autophagy and apoptosis, thus supporting RAS targeting as a novel potential therapeutic strategy in patients carrying t(6;11). Altogether, these data point to a novel role of the MLL-AF6 chimera and show that its gene partner, AF6, is crucial in AML development.

  1. 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…

  2. 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. PMID:26589820

  3. 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.

  4. [Progress in Teflon AF LWCC/LCW applications].

    PubMed

    Sun, Zhao-Hua; Zhou, Wen; Xu, Zhan-Tang; Ye, Hai-Bin; Yang, Chao-Yu; Lin, Jun-Fang; Hu, Shui-Bo; Yang, Yue-Zhong; Li, Cai; Cao, Wen-Xi

    2011-11-01

    Teflon AF is chemically very inert, quite physically and optically stable, a highly vapor-permeable polymer with optical transparency through much of the UV-Vis region and with an RI lower than that of water, so Teflon AF LWCC/LCW (Long path-length liquid waveguide capillary cell/liquid core waveguides) has been used with a range of different detection techniques, including absorbance spectroscopy, fluorescence spectroscopy, Raman spectroscopy, and gas sensor. The present article describes the properties and the aspects of Teflon AF LWCC/LCW instrumentation and applications. And finally,the future prospect and outlook of Teflon AF LWCC/LCW is also discussed.

  5. AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions

    PubMed Central

    Scholz, Bastian; Kowarz, Eric; Rössler, Tanja; Ahmad, Khalil; Steinhilber, Dieter; Marschalek, Rolf

    2015-01-01

    AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble “super-elongation complexes” (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes. PMID:26171280

  6. AF-MSCs fate can be regulated by culture conditions

    PubMed Central

    Zagoura, D S; Trohatou, O; Bitsika, V; Makridakis, M; Pappa, K I; Vlahou, A; Roubelakis, M G; Anagnou, N P

    2013-01-01

    Human mesenchymal stem cells (hMSCs) represent a population of multipotent adherent cells able to differentiate into many lineages. In our previous studies, we isolated and expanded fetal MSCs from second-trimester amniotic fluid (AF) and characterized them based on their phenotype, pluripotency and proteomic profile. In the present study, we investigated the plasticity of these cells based on their differentiation, dedifferentiation and transdifferentiation potential in vitro. To this end, adipocyte-like cells (AL cells) derived from AF-MSCs can regain, under certain culture conditions, a more primitive phenotype through the process of dedifferentiation. Dedifferentiated AL cells derived from AF-MSCs (DAF-MSCs), gradually lost the expression of adipogenic markers and obtained similar morphology and differentiation potential to AF-MSCs, together with regaining the pluripotency marker expression. Moreover, a comparative proteomic analysis of AF-MSCs, AL cells and DAF-MSCs revealed 31 differentially expressed proteins among the three cell populations. Proteins, such as vimentin, galectin-1 and prohibitin that have a significant role in stem cell regulatory mechanisms, were expressed in higher levels in AF-MSCs and DAF-MSCs compared with AL cells. We next investigated whether AL cells could transdifferentiate into hepatocyte-like cells (HL cells) directly or through a dedifferentiation step. AL cells were cultured in hepatogenic medium and 4 days later they obtained a phenotype similar to AF-MSCs, and were termed as transdifferentiated AF-MSCs (TRAF-MSCs). This finding, together with the increase in pluripotency marker expression, indicated the adaption of a more primitive phenotype before transdifferentiation. Additionally, we observed that AF-, DAF- and TRAF-MSCs displayed similar clonogenic potential, secretome and proteome profile. Considering the easy access to this fetal cell source, the plasticity of AF-MSCs and their potential to dedifferentiate and

  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, 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...

  9. 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...

  10. 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...

  11. 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...

  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. Embedding Assessment for Learning (AfL) into Science

    ERIC Educational Resources Information Center

    Crossland, John

    2012-01-01

    Although the National Strategies for improving English schools no longer exist, the "Pedagogy and Practice" pack provides a valuable resource for producing an Assessment for Learning (AfL) framework that describes a hierarchy of skills for AfL. Based on the hierarchy, training took place in three North Yorkshire schools. To focus attention on the…

  14. Toward a petabyte-scale AFS service at CERN

    NASA Astrophysics Data System (ADS)

    van der Ster, Daniel; Moscicki, Jakub T.; Wiebalck, Arne

    2014-06-01

    AFS is a mature and reliable storage service at CERN, having worked for more than 20 years as the provider of Unix home directories and project areas. Recently, the AFS service has grown at unprecedented rates (200% in the past year); this growth was unlocked thanks to innovations in both the hardware and software components of our file servers. This work presents how AFS is used at CERN and how the service offering is evolving with the increasing storage needs of its local and remote user communities. In particular, we demonstrate the usage patterns for home directories, workspaces and project spaces, as well as show the daily work which is required to rebalance data and maintaining stability and performance. Finally, we highlight some recent changes and optimisations made to the AFS Service, thereby revealing how AFS can possibly operate at all while being subjected to frequent-almost DDOS-like-attacks from its users.

  15. Modeling the Interaction of Binary and Ternary Mixtures of Estradiol with Bisphenol A and Bisphenol AF in an In Vitro Estrogen-Mediated Transcriptional Activation Assay (T47D-KBluc)

    PubMed Central

    Bermudez, Dieldrich S.; Gray, Leon E.; Wilson, Vickie S.

    2010-01-01

    Exposure to xenoestrogens occurs against a backdrop to physiological levels of endogenous estrogens. Endogenous estrogen levels vary from low levels in early childhood to high levels during pregnancy and in young women. However, few studies have addressed how xenoestrogens interact with endogenous estrogens. The current study was designed to characterize the individual dose-response curves of estradiol-17β (E2), bisphenol A (BPA), tetrabromo-bisphenol A (TBBPA), and bisphenol AF (BPAF, 4,4'-hexafluoroisopropylidene diphenol) on estrogen-dependent luciferase expression in T47D-KBluc cells and to determine how binary (8 × 8 factorial) and ternary (4 × 4 × 4 factorial) mixtures of an endogenous estrogen (E2) interact with BPA and/or BPAF. Log EC50 and hillslope values with SEs, respectively, for individual compounds were as follows: E2, −12.10M ± 0.06071, 0.7702 ± 0.1739; BPA, −6.679M ± 0.08505, 1.194 ± 0.2137; and BPAF, −7.648M ± 0.05527, 1.273 ± 0.1739. TBBPA was not evaluated in mixture studies because of its minimally estrogenic response at 3 ×10−5M and elicited cytotoxicity at higher concentrations. Both the binary mixtures of E2 with BPA and BPAF and the ternary mixture of E2, BPA, and BPAF behaved in an additive manner. For binary mixtures, as E2 concentration increased, higher concentrations of BPA and BPAF were necessary to induce a significant increase in the estrogenic response. Understanding the behavior of mixture interactions of xenoestrogens, like BPA and BPAF, with endogenous estrogens will allow a better assessment of the potential risk associated with exposure to these chemicals, individually or as mixtures. PMID:20498000

  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. Complex Transcriptional Control of the Antibiotic Regulator afsS in Streptomyces: PhoP and AfsR Are Overlapping, Competitive Activators▿

    PubMed Central

    Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F.

    2011-01-01

    The afsS gene of several Streptomyces species encodes a small sigma factor-like protein that acts as an activator of several pathway-specific regulatory genes (e.g., actII-ORF4 and redD in Streptomyces coelicolor). The two pleiotropic regulators AfsR and PhoP bind to overlapping sequences in the −35 region of the afsS promoter and control its expression. Using mutated afsS promoters containing specific point mutations in the AfsR and PhoP binding sequences, we proved that the overlapping recognition sequences for AfsR and PhoP are displaced by 1 nucleotide. Different nucleotide positions are important for binding of AfsR or PhoP, as shown by electrophoretic mobility shift assays and by reporter studies using the luxAB gene coupled to the different promoters. Mutant promoter M5 (with a nucleotide change at position 5 of the consensus box) binds AfsR but not PhoP with high affinity (named “superAfsR”). Expression of the afsS gene from this promoter led to overproduction of actinorhodin. Mutant promoter M16 binds PhoP with extremely high affinity (“superPhoP”). Studies with ΔafsR and ΔphoP mutants (lacking AfsR and PhoP, respectively) showed that both global regulators are competitive transcriptional activators of afsS. AfsR has greater influence on expression of afsS than PhoP, as shown by reverse transcriptase PCR (RT-PCR) and promoter reporter (luciferase) studies. These two high-level regulators appear to integrate different nutritional signals (particularly phosphate limitation sensed by PhoR), S-adenosylmethionine, and other still unknown environmental signals (leading to AfsR phosphorylation) for the AfsS-mediated control of biosynthesis of secondary metabolites. PMID:21378195

  18. Complex transcriptional control of the antibiotic regulator afsS in Streptomyces: PhoP and AfsR are overlapping, competitive activators.

    PubMed

    Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F

    2011-05-01

    The afsS gene of several Streptomyces species encodes a small sigma factor-like protein that acts as an activator of several pathway-specific regulatory genes (e.g., actII-ORF4 and redD in Streptomyces coelicolor). The two pleiotropic regulators AfsR and PhoP bind to overlapping sequences in the -35 region of the afsS promoter and control its expression. Using mutated afsS promoters containing specific point mutations in the AfsR and PhoP binding sequences, we proved that the overlapping recognition sequences for AfsR and PhoP are displaced by 1 nucleotide. Different nucleotide positions are important for binding of AfsR or PhoP, as shown by electrophoretic mobility shift assays and by reporter studies using the luxAB gene coupled to the different promoters. Mutant promoter M5 (with a nucleotide change at position 5 of the consensus box) binds AfsR but not PhoP with high affinity (named "superAfsR"). Expression of the afsS gene from this promoter led to overproduction of actinorhodin. Mutant promoter M16 binds PhoP with extremely high affinity ("superPhoP"). Studies with ΔafsR and ΔphoP mutants (lacking AfsR and PhoP, respectively) showed that both global regulators are competitive transcriptional activators of afsS. AfsR has greater influence on expression of afsS than PhoP, as shown by reverse transcriptase PCR (RT-PCR) and promoter reporter (luciferase) studies. These two high-level regulators appear to integrate different nutritional signals (particularly phosphate limitation sensed by PhoR), S-adenosylmethionine, and other still unknown environmental signals (leading to AfsR phosphorylation) for the AfsS-mediated control of biosynthesis of secondary metabolites.

  19. Escherichia coli Strain RDEC-1 AF/R1 Endogenous Fimbrial Glycoconjugate Receptor Molecules in Rabbit Small Intestine

    PubMed Central

    Ryu, Hyoik; Kim, Young S.; Grange, Philippe A.; Cassels, Frederick J.

    2001-01-01

    Escherichia coli strain RDEC-1 causes a diarrheagenic infection in rabbits with AF/R1 fimbriae, which have been identified as an important colonization factor in RDEC-1 adherence leading to disease. The AF/R1-mediated RDEC-1 adherence model has been used as a model systems for E. coli diarrheal diseases. In this study, RDEC-1 adhered specifically to small intestinal brush borders, with both sialic acid and β-galactosyl residues apparently involved. The AF/R1-mediated adherence activity of [14C]-labeled RDEC-1 was analyzed quantitatively by using 24-well plates coated with purified brush borders and purified microvilli. Two microvillus membrane proteins (130 and 140 kDa) were individually isolated, and chicken antibody raised to each protein inhibited bacterial adherence. These same two proteins, previously shown to be recognized by AF/R1, were individually digested with trypsin, and the amino acid sequences of peptides were determined by reversed-phase capillary liquid chromatography-mass spectrometry tandem mass spectrometry (LC-MS). This LC-MS analysis indicated that these proteins are subunits of the rabbit sucrase-isomaltase protein (SI) complex. Guinea pig serum raised to purified rabbit SI complex inhibited bacterial adherence to microvilli. Additionally, as determined by high-performance thin-layer chromatography and autoradiography, RDEC-1 adhered selectively, via AF/R1 fimbriae, to a glycolipid tentatively identified as galactosylceramide (Galβ1-1Cer) in the lipid extract of rabbit small intestinal brush borders. RDEC-1 adherence to Galβ1-1Cer was partially inhibited in the presence of galactose. These combined results indicate that the endogenous receptor molecule for AF/R1 fimbriae of RDEC-1 is each individual component of the SI complex, although binding to glycolipid may be responsible for an additional adherence mechanism. PMID:11159950

  20. Effects of iron depletion on CALM-AF10 leukemias.

    PubMed

    Heath, Jessica L; Weiss, Joshua M; Lavau, Catherine P; Wechsler, Daniel S

    2014-12-01

    Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis. The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by clathrin-mediated endocytosis. CALM-AF10 leukemias harbor a single copy of the normal CALM gene and therefore may be more sensitive to the growth-inhibitory effect of iron restriction compared with normal hematopoietic cells. We found that CALM heterozygous (CALM(HET)) murine fibroblasts exhibit signs of iron deficiency, with increased surface transferrin receptor levels and reduced growth rates. CALM(HET) hematopoietic cells are more sensitive in vitro to iron chelators than their wild type counterparts. Iron chelation also displayed toxicity toward cultured CALM(HET)CALM-AF10 leukemia cells, and this effect was additive to that of chemotherapy. In mice transplanted with CALM(HET)CALM-AF10 leukemia, we found that dietary iron restriction reduced tumor burden in the spleen. However, dietary iron restriction, used alone or in conjunction with chemotherapy, did not increase survival of mice with CALM(HET)CALM-AF10 leukemia. In summary, although CALM heterozygosity results in iron deficiency and increased sensitivity to iron chelation in vitro, our data in mice do not suggest that iron depletion strategies would be beneficial for the therapy of CALM-AF10 leukemia patients.

  1. afsS is a target of AfsR, a transcriptional factor with ATPase activity that globally controls secondary metabolism in Streptomyces coelicolor A3(2).

    PubMed

    Lee, Ping-Chin; Umeyama, Takashi; Horinouchi, Sueharu

    2002-03-01

    AfsR is a pleiotropic, global regulator that controls the production of actinorhodin, undecylprodigiosin and calcium-dependent antibiotic in Streptomyces coelicolor A3(2). AfsR, with 993 amino acids, is phosphorylated on serine and threonine residues by a protein serine/threonine kinase AfsK and contains an OmpR-like DNA-binding fold at its N-terminal portion and A- and B-type nucleotide-binding motifs in the middle of the protein. The DNA-binding domain, in-dependently of the nucleotide-binding domain, contributed the binding of AfsR to the upstream region of afsS that locates immediately 3' to afsR and encodes a 63-amino-acid protein. No transcription of afsS in the DeltaafsR background and restoration of afsS transcription by afsR on a plasmid in the same genetic background indicated that afsR served as a transcriptional activator for afsS. Interestingly, the AfsR binding site overlapped the promoter of afsS, as determined by DNase I protection assay and high-resolution S1 nuclease mapping. The nucleotide-binding domain contributed distinct ATPase and GTPase activity. The phosphorylation of AfsR by AfsK greatly enhanced the DNA-binding activity and modulated the ATPase activity. The DNA-binding ability of AfsR was independent of the ATPase activity. However, the ATPase activity was essential for transcriptional activation of afsS, probably because the energy available from ATP hydrolysis is required for the isomerization of the closed complex between AfsR and RNA polymerase to a transcriptionally competent open complex. Thus, AfsR turns out to be a unique transcriptional factor, in that it is modular, in which DNA-binding and ATPase activities are physically separable, and the two functions are modulated by phosphorylation on serine and threonine residues.

  2. Implementation of AF-CBT by community practitioners serving child welfare and mental health: a randomized trial.

    PubMed

    Kolko, David J; Baumann, Barbara L; Herschell, Amy D; Hart, Jonathan A; Holden, Elizabeth A; Wisniewski, Stephen R

    2012-02-01

    The Partnerships for Families project is a randomized clinical trial designed to evaluate the implementation of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT), an evidence-based treatment for family conflict, coercion, and aggression, including child physical abuse. To evaluate the effectiveness of a training program in this model, 182 community practitioners from 10 agencies were randomized to receive AF-CBT training (n = 90) using a learning community model (workshops, consultation visits) or Training as Usual (TAU; n = 92) which provided trainings per agency routine. Practitioners completed self-report measures at four time points (0, 6, 12, and 18 months following baseline). Of those assigned to AF-CBT, 89% participated in at least one training activity and 68% met a "training completion" definition. A total of 80 (44%) practitioners were still active clinicians in the study by 18-month assessment in that they had not met our staff turnover or study withdrawal criteria. Using an intent-to-train design, hierarchical linear modeling analyses revealed significantly greater initial improvements for those in the AF-CBT training condition (vs. TAU condition) in CBT-related knowledge and use of AF-CBT teaching processes, abuse-specific skills, and general psychological skills. In addition, practitioners in both groups reported significantly more negative perceptions of organizational climate through the intervention phase. These significant, albeit modest, findings are discussed in the context of treatment training, research, and work force issues as they relate to the diverse backgrounds, settings, and populations served by community practitioners.

  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. Ornicorrugatin, a new siderophore from Pseudomonas fluorescens AF76.

    PubMed

    Matthijs, Sandra; Budzikiewicz, Herbert; Schäfer, Mathias; Wathelet, Bernard; Cornelis, Pierre

    2008-01-01

    From a pyoverdin-negative mutant of Pseudomonas fluorescens AF76 a new lipopeptidic siderophore (ornicorrugatin) could be isolated. It is structurally related to the siderophore of Pseudomonas corrugata differing in the replacement of one Dab unit by Orn. PMID:18386480

  5. 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.

  6. Extracting uranium from seawater: Promising AF series adsorbents

    DOE PAGES

    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 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

  7. 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.

  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. Evaluation of the sustainability and clinical outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) in a child protection center.

    PubMed

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

    2011-02-01

    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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Identification and functional characterization of grass carp IL-17A/F1: An evaluation of the immunoregulatory role of teleost IL-17A/F1.

    PubMed

    Du, Linyong; Feng, Shiyu; Yin, Licheng; Wang, Xinyan; Zhang, Anying; Yang, Kun; Zhou, Hong

    2015-07-01

    In mammals, IL-17A and IL-17F are hallmark cytokines of Th17 cells which act significant roles in eradicating extracellular pathogens. IL-17A and IL-17F homologs nominated as IL-17A/F1-3 have been revealed in fish and their functions remain largely undefined. Here we identified and characterized grass carp IL-17A/F1 (gcIL-17A/F1) in fish immune system. In this regard, both tissue distribution and inductive expression of gcIL-17A/F1 indicated its possible involvement in immune response. Moreover, recombinant gcIL-17A/F1 (rgcIL-17A/F1) was prepared and displayed an ability to enhance pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) mRNA expression in head kidney leukocytes. It is suggestive of that gcIL-17A/F1 may act as a proinflammatory cytokine in fish immunity. Besides, rgcIL-17A/F1 induced gene expression and protein release of grass carp chemokine CXCL-8 (gcCXCL-8) in head kidney cells (HKCs), probably via NF-κB, p38 and Erk1/2 pathways. In particular, culture medium from the HKCs treated by rgcIL-17A/F1 could stimulate peripheral blood leukocytes migration and immunoneutralization of endogenous gcCXCL-8 could partially attenuate this stimulation, suggesting that rgcIL-17A/F1 could recruit immune cells through producing gcCXCL-8 as mammalian IL-17 A and F. Taken together, we not only identified the pro-inflammatory role of gcIL-17A/F1 in host defense, but also provided the basis for clarifying Th17 cells in teleost. PMID:25847875

  15. Improvement and biological applications of fluorescent probes for zinc, ZnAFs.

    PubMed

    Hirano, Tomoya; Kikuchi, Kazuya; Urano, Yasuteru; Nagano, Tetsuo

    2002-06-12

    The development and cellular applications of novel fluorescent probes for Zn2+, ZnAF-1F, and ZnAF-2F are described. Fluorescein is used as a fluorophore of ZnAFs, because its excitation and emission wavelengths are in the visible range, which minimizes cell damage and autofluorescence by excitation light. N,N-Bis(2-pyridylmethyl)ethylenediamine, used as an acceptor for Zn2+, is attached directly to the benzoic acid moiety of fluorescein, resulting in very low quantum yields of 0.004 for ZnAF-1F and 0.006 for ZnAF-2F under physiological conditions (pH 7.4) due to the photoinduced electron-transfer mechanism. Upon the addition of Zn2+, the fluorescence intensity is quickly increased up to 69-fold for ZnAF-1F and 60-fold for ZnAF-2F. Apparent dissociation constants (K(d)) are in the nanomolar range, which affords sufficient sensitivity for biological applications. ZnAFs do not fluoresce in the presence of other biologically important cations such as Ca2+ and Mg2+, and are insensitive to change of pH. The complexes with Zn2+ of previously developed ZnAFs, ZnAF-1, and ZnAF-2 decrease in fluorescence intensity below pH 7.0 owing to protonation of the phenolic hydroxyl group of fluorescein, whose pKa value is 6.2. On the other hand, the Zn2+ complexes of ZnAF-1F and ZnAF-2F emit stable fluorescence around neutral and slightly acidic conditions because the pKa values are shifted to 4.9 by substitution of electron-withdrawing fluorine at the ortho position of the phenolic hydroxyl group. For application to living cells, the diacetyl derivative of ZnAF-2F, ZnAF-2F DA, was synthesized. ZnAF-2F DA can permeate through the cell membrane, and is hydrolyzed by esterase in the cytosol to yield ZnAF-2F, which is retained in the cells. Using ZnAF-2F DA, we could measure the changes of intracellular Zn2+ in cultured cells and hippocampal slices.

  16. AF-GEOSpace Version 2.0: Space Environment Software Products for 2002

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Tautz, M.

    2002-05-01

    AF-GEOSpace Version 2.0 (release 2002 on WindowsNT/2000/XP) is a graphics-intensive software program developed by AFRL with space environment models and applications. It has grown steadily to become a development tool for automated space weather visualization products and helps with a variety of tasks: orbit specification for radiation hazard avoidance; satellite design assessment and post-event analysis; solar disturbance effects forecasting; frequency and antenna management for radar and HF communications; determination of link outage regions for active ionospheric conditions; and physics research and education. The object-oriented C++ code is divided into five module classes. Science Modules control science models to give output data on user-specified grids. Application Modules manipulate these data and provide orbit generation and magnetic field line tracing capabilities. Data Modules read and assist with the analysis of user-generated data sets. Graphics Modules enable the display of features such as plane slices, magnetic field lines, line plots, axes, the Earth, stars, and satellites. Worksheet Modules provide commonly requested coordinate transformations and calendar conversion tools. Common input data archive sets, application modules, and 1-, 2-, and 3-D visualization tools are provided to all models. The code documentation includes detailed examples with click-by-click instructions for investigating phenomena that have well known effects on communications and spacecraft systems. AF-GEOSpace Version 2.0 builds on the success of its predecessors. The first release (Version 1.21, 1996/IRIX on SGI) contained radiation belt particle flux and dose models derived from CRRES satellite data, an aurora model, an ionosphere model, and ionospheric HF ray tracing capabilities. Next (Version 1.4, 1999/IRIX on SGI) science modules were added related to cosmic rays and solar protons, low-Earth orbit radiation dosages, single event effects probability maps, ionospheric

  17. Binding sites for two novel phosphoproteins, 3AF5 and 3AF3, are required for rbcS-3A expression.

    PubMed Central

    Sarokin, L P; Chua, N H

    1992-01-01

    Previous studies of boxes II (-151 to -138) and III (-125 to -114), binding sites for the nuclear factor GT-1 within the -166 deleted promoter of the ribulose-1,5-bisphosphate carboxylase-3A (rbcS-3A) gene, suggested that GT-1 might act in concert with an additional protein to confer light-responsive rbcS-3A expression. In this work, S1 analysis of RNA isolated from transgenic tobacco plants carrying mutant rbcS-3A constructs led to the identification of two short sequences located at the 5' and 3' ends of box III that are required for expression. These two sequences serve as binding sites for two novel proteins, 3AF5 and 3AF3. Gel shift studies using tetramerized binding sites for both 3AF5 and 3AF3 showed that complexes with faster mobilities were formed using nuclear extracts prepared from dark-adapted plants compared with those from light-grown tobacco plants. Phosphatase treatment of extracts from light-grown plants resulted in the formation of complexes with faster mobility. Although the binding of 3AF3 to its target site is dependent upon phosphorylation, the binding of 3AF5 does not appear to be affected by its phosphorylation state. These results suggest that the phosphorylated forms of both 3AF5 and 3AF3 are required for -166 rbcS-3A expression but that the mechanisms differ by which phosphorylation regulates the activities of 3AF5 and 3AF3. PMID:1498605

  18. 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. PMID:27328164

  19. Characterization of Soil Organic Matter from African Dark Earth (AfDE) Soils

    NASA Astrophysics Data System (ADS)

    Plante, A. F.; Fujiu, M.; Ohno, T.; Solomon, D.; Lehmann, J.; Fraser, J. A.; Leach, M.; Fairhead, J.

    2014-12-01

    Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. While tropical soils are typically characterized by low soil organic matter (SOM) concentrations, African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils formed through an extant but ancient soil management system. The objective of this study was to characterize the organic matter accumulated in AfDE and contrast it with non-AfDE soils. Characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) resulted in substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant, but the fertility gains in AfDE are generated by labile, more rapidly cycling pools of SOM. As a result, we characterized hot water- and pyrophosphate-extractable pools of SOM using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FT-ICR-MS). EEM/PARAFAC data suggests that AfDE samples had a greater fraction of their DOM that was more humic-like than the paired non-AfDE samples. Similarly, FT-ICR-MS analyses of extracts suggest that differences among the sites analyzed were larger than between the paired AfDE and non-AfDE extracts. Overall, in spite of substantial differences in the composition of bulk SOM, the extractable fractions appear to be relatively similar between the AfDE and non-AfDE soils.

  20. MicroRNA-205 downregulates mixed-lineage-AF4 oncogene expression in acute lymphoblastic leukemia

    PubMed Central

    Dou, Liping; Li, Jingxin; Zheng, Dehua; Li, Yonghui; Gao, Xiaoning; Xu, Chengwang; Gao, Li; Wang, Lili; Yu, Li

    2013-01-01

    Myeloid/lymphoid or mixed-lineage AF4 acute lymphoblastic leukemia (MLL-AF4 ALL) is a pediatric leukemia that occurs rarely in adults. MLL-AF4 ALL is typically characterized by the presence of chromosomal translocation (t(4;1l)(q21;q23)), leading to expression of MLL-AF4 fusion protein. Although MLL-AF4 fusion protein triggers a molecular pathogenesis and hematological presentations that are unique to leukemias, the precise role of this oncogene in leukemogenesis remains unclear. Previous studies have indicated that microRNAs (miRs) might modulate the expression of MLL-AF4 ALL fusion protein, thereby suggesting the involvement of miR in progression or suppression of MLL-AF4 ALL. We have previously demonstrated that miR-205 negatively regulates transcription of an MLL-AF4 luciferase reporter. Here, we report that exogenous expression of miR-205 in MLL-AF4 human cell lines (RS4;11 and MV4-11) inversely regulates the expression of MLL-AF4 at both messenger RNA (mRNA) and protein level. Furthermore, miR-205 significantly induced apoptosis in MLL-AF4 cells as evidenced by Annex in V staining using fluorescence-activated cell sorting (FACS) analysis. The proliferative capacity of leukemic cells was suppressed by miR-205. The addition of an miR-205 inhibitor was able to restore the observed effects. In conclusion, these findings demonstrate that miR-205 may have potential value as a novel therapeutic agent in the treatment of MLL-AF4 ALL. PMID:24009426

  1. Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

    PubMed

    Konno, K; Hisada, M; Naoki, H; Itagaki, Y; Kawai, N; Miwa, A; Yasuhara, T; Morimoto, Y; Nakata, Y

    2000-11-01

    A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

  2. 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.

  3. Identification and characterization of the afsR homologue regulatory gene from Streptomyces peucetius ATCC 27952.

    PubMed

    Parajuli, Niranjan; Viet, Hung Trinh; Ishida, Kenji; Tong, Hang Thi; Lee, Hei Chan; Liou, Kwangkyoung; Sohng, Jae Kyung

    2005-01-01

    We have isolated an afsR homologue, called afsR-p, through genome analysis of Streptomyces peucetius ATCC 27952. AfsR-p shares 60% sequence identity with AfsR from Streptomyces coelicolor A3 (2). afsR-p was expressed under the control of the ermE* promoter in its hosts S. peucetius, Streptomyces lividans TK 24, Streptomyces clavuligerus and Streptomyces griseus. We observed overproduction of doxorubicin (4-fold) in S. peucetius, gamma-actinorhodin (2.6-fold) in S. lividans, clavulanic acid (1.5-fold) in S. clavuligerus and streptomycin (slight) in S. griseus. Overproduction was due to expression of the gene in these strains as compared to the wild-type strains harboring the vector only. Comparative study of the expression of afsR-p revealed that regulatory networking in Streptomyces is not uniform. We speculate that phosphorylated AfsR-p becomes bound to the promoter region of afsS. The latter activates other regulatory genes, including pathway regulatory genes, and induces the production of secondary metabolites including antibiotics. We identified specific conserved amino acids and exploited them for the isolation of the partial sequence of the afsR homologue from S. clavuligerus and Streptomyces achromogens (rubradirin producer). Such findings provide additional evidence for the presence of a serine/threonine and tyrosine kinase-dependent global regulatory network in Streptomyces.

  4. Identification and characterization of the afsR homologue regulatory gene from Streptomyces peucetius ATCC 27952.

    PubMed

    Parajuli, Niranjan; Viet, Hung Trinh; Ishida, Kenji; Tong, Hang Thi; Lee, Hei Chan; Liou, Kwangkyoung; Sohng, Jae Kyung

    2005-01-01

    We have isolated an afsR homologue, called afsR-p, through genome analysis of Streptomyces peucetius ATCC 27952. AfsR-p shares 60% sequence identity with AfsR from Streptomyces coelicolor A3 (2). afsR-p was expressed under the control of the ermE* promoter in its hosts S. peucetius, Streptomyces lividans TK 24, Streptomyces clavuligerus and Streptomyces griseus. We observed overproduction of doxorubicin (4-fold) in S. peucetius, gamma-actinorhodin (2.6-fold) in S. lividans, clavulanic acid (1.5-fold) in S. clavuligerus and streptomycin (slight) in S. griseus. Overproduction was due to expression of the gene in these strains as compared to the wild-type strains harboring the vector only. Comparative study of the expression of afsR-p revealed that regulatory networking in Streptomyces is not uniform. We speculate that phosphorylated AfsR-p becomes bound to the promoter region of afsS. The latter activates other regulatory genes, including pathway regulatory genes, and induces the production of secondary metabolites including antibiotics. We identified specific conserved amino acids and exploited them for the isolation of the partial sequence of the afsR homologue from S. clavuligerus and Streptomyces achromogens (rubradirin producer). Such findings provide additional evidence for the presence of a serine/threonine and tyrosine kinase-dependent global regulatory network in Streptomyces. PMID:15921897

  5. 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.

  6. A Stochastic Individual-Based Model of the Progression of Atrial Fibrillation in Individuals and Populations

    PubMed Central

    Galla, Tobias; Clayton, Richard H.

    2016-01-01

    Models that represent the mechanisms that initiate and sustain atrial fibrillation (AF) in the heart are computationally expensive to simulate and therefore only capture short time scales of a few heart beats. It is therefore difficult to embed biophysical mechanisms into both policy-level disease models, which consider populations of patients over multiple decades, and guidelines that recommend treatment strategies for patients. The aim of this study is to link these modelling paradigms using a stylised population-level model that both represents AF progression over a long time-scale and retains a description of biophysical mechanisms. We develop a non-Markovian binary switching model incorporating three different aspects of AF progression: genetic disposition, disease/age related remodelling, and AF-related remodelling. This approach allows us to simulate individual AF episodes as well as the natural progression of AF in patients over a period of decades. Model parameters are derived, where possible, from the literature, and the model development has highlighted a need for quantitative data that describe the progression of AF in population of patients. The model produces time series data of AF episodes over the lifetimes of simulated patients. These are analysed to quantitatively describe progression of AF in terms of several underlying parameters. Overall, the model has potential to link mechanisms of AF to progression, and to be used as a tool to study clinical markers of AF or as training data for AF classification algorithms. PMID:27070920

  7. In vitro and in vivo characterisation of Lu AF64280, a novel, brain penetrant phosphodiesterase (PDE) 2A inhibitor: potential relevance to cognitive deficits in schizophrenia.

    PubMed

    Redrobe, John P; Jørgensen, Morten; Christoffersen, Claus T; Montezinho, Liliana P; Bastlund, Jesper F; Carnerup, Martin; Bundgaard, Christoffer; Lerdrup, Linda; Plath, Niels

    2014-08-01

    Here, we present the pharmacological characterisation of Lu AF64280, a novel, selective, brain penetrant phosphodiesterase (PDE) 2A inhibitor, in in vitro/in vivo assays indicative of PDE2A inhibition, and in vivo models/assays relevant to cognitive processing or antipsychotic-like activity. The in vitro selectivity of Lu AF64280 was determined against a panel of PDE enzymes and 3',5'-cyclic guanosine monophosphate (cGMP) levels in the hippocampus were determined using in vivo microdialysis. Lu AF64280 potently inhibited hPDE2A (Ki = 20 nM), 50-fold above moderate inhibition of both hPDE9A (Ki = 1,000 nM) and hPDE10A (Ki = 1,800 nM), and displayed a >250-fold selectivity over all other full-length human recombinant PDE family members (Ki above 5,000 nM). Lu AF64280 (20 mg/kg) significantly increased cGMP levels in the hippocampus (p < 0.01 versus vehicle-treated mice), attenuated sub-chronic phencyclidine-induced deficits in novel object exploration in rats (10 mg/kg, p < 0.001 versus vehicle-treated), blocked early postnatal phencyclidine-induced deficits in the intradimensional/extradimensional shift task in rats (1 and 10 mg/kg, p < 0.001 versus vehicle-treated) and attenuated spontaneous P20-N40 auditory gating deficits in DBA/2 mice (20 mg/kg, p < 0.05 versus vehicle-treated). In contrast, Lu AF64280 failed to attenuate phencyclidine-induced hyperactivity in mice, and was devoid of antipsychotic-like activity in the conditioned avoidance response paradigm in rats, at any dose tested. Lu AF64280 represents a novel tool compound for selective PDE2A inhibition that substantiates a critical role of this enzyme in cognitive processes under normal and pathological conditions.

  8. Characterisation of Lu AF33241: A novel, brain-penetrant, dual inhibitor of phosphodiesterase (PDE) 2A and PDE10A.

    PubMed

    Redrobe, John P; Rasmussen, Lars K; Christoffersen, Claus T; Bundgaard, Christoffer; Jørgensen, Morten

    2015-08-15

    Here, we present a preliminary pharmacological characterisation of Lu AF33241, a novel, brain penetrant phosphodiesterase inhibitor of (PDE) 2A and 10A tool compound, in in vitro/in vivo assays indicative of PDE2A and/or PDE10A inhibition, and in vivo models/assays relevant to cognitive processing and antipsychotic-like activity. An assay was also included to investigate potential effects on motor activity. The in vitro selectivity of Lu AF33241 was determined against a panel of PDE enzymes. Lu AF33241 potently inhibited both full-length recombinant hPDE2A (Ki=4.2nM) and hPDE10A (Ki=42nM). The compound moderately inhibited both hPDE1C (Ki=1200nM), hPDE7B (Ki=890nM), and hPDE11A (Ki=1800nM). Lu AF33241 displayed a Ki above 5000nM against all other tested members of the PDE family. Albeit within a narrow dose range, Lu AF33241 attenuated sub-chronic phencyclidine-induced deficits in novel object recognition (3 and 10mg/kg), displayed antipsychotic-like activity in the conditioned avoidance response paradigm (10mg/kg), and did not induce catalepsy within a dose-range of 2-6mg/kg. Further catalepsy studies are needed to investigate a predictive safety window. Lu AF33241 represents a novel PDE2A/PDE10A inhibitor tool compound that may serve to further the understanding of the roles played by these enzymes in various CNS disorders.

  9. Fluorous polymeric membranes for ionophore-based ion-selective potentiometry: how inert is Teflon AF?

    PubMed

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

    2009-02-01

    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 4 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 10(3.5), 10(1.8), 10(6.8), and 10(4.4) 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

  10. 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.

  11. Installation-restoration program. Records search, Newark AFS, Ohio

    SciTech Connect

    Not Available

    1985-04-01

    Since 1962, many hazardous and potentially hazardous wastes have been generated by industrial operations in Building 4 at Newark AFS. Dirty freon is recycled through a recovery still inside the building and reused. A beryllium dust collection system is located on the east side of Building 4. The collected dust is encapsulated in cement and sent off-station for disposal. Twelve hazardous materials storage or staging areas were identified. During interviews, it was determined that large quantities of dirty freon had been dumped along the entire perimeter fence line and in particular two specific locations. An additional spill site was located in the area at the north-east corner of Building 4 near the location of the virgin freon tanks. An unknown amount of spent battery acid and spent solvents were spilled in this area between 1962 and 1964.

  12. [HG-AFS determination of selenium in Moringa oleifera].

    PubMed

    Huang, Guo-qing; Xiao, Zi-jun

    2007-02-01

    The Se content in Moringa oleifera was studied by hydride generation atom fluorescence spectrometry (HG-AFS) with wet digestion. The effects of the way of digestion, the work condition of apparatus, the reaction medium and acidity, and the reducing agent and masking agent on the determination of Se were investigated. And the operating condition of apparatus was optimized. The results showed that the detection limit of Se in this method was 0.42 ng x mL(-1) in the linear ranger of 0-120 ng x mL(-1), the relative standard deviation was 3.53% (n = 11), and the recovery of the method was 95.2%-104.6%. It was showed that the method was very sensitive, simple, rapid and accurate.

  13. 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.

  14. 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...

  15. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2014-07-01 2014-07-01 false AF Form 813, Request for Environmental...

  16. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2013-07-01 2013-07-01 false AF Form 813, Request for Environmental...

  17. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental...

  18. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2012-07-01 2012-07-01 false AF Form 813, Request for Environmental...

  19. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2011-07-01 2011-07-01 false AF Form 813, Request for Environmental...

  20. AF Therapy Now and in the Future: Drugs, Biologicals, and Ablation

    PubMed Central

    Woods, Christopher E.; Olgin, Jeffrey

    2014-01-01

    Rationale Atrial fibrillation (AF) is a complex disease with multiple interrelating causes culminating in rapid, seemingly disorganized atrial activation. Therapy targeting AF is rapidly changing and improving. Objective The purpose of this review is to summarize current state-of-the-art diagnostic and therapeutic modalities for treatment of atrial fibrillation. The review focuses on reviewing treatment as it relates to the pathophysiological basis of disease and reviews pre-clinical and clinical evidence for potential new diagnostic and therapeutic modalities, including imaging, biomarkers, pharmacologic therapy as well as ablative strategies for AF. Conclusions Current ablation and drug therapy approaches to treating AF are largely based on treating the arrhythmia once the substrate occurs and is more effective in paroxysmal AF rather than persistent or permanent AF. However, there is much research aimed at prevention strategies, targeting AF substrate—so called upstream therapy. Improved diagnostics, using imaging, genetics and biomarkers are needed to better identify sub-types of AF based on underlying substrate/mechanism to allow more directed therapeutic approaches. In addition, novel anti-arrhythmics with more atrial specific effects may reduce limiting pro-arrhythmic side-effects. Advances in ablation therapy are aimed at improving technology to reduce procedure time and in mechanism targeted approaches. PMID:24763469

  1. Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer.

    PubMed

    Sun, Ting Ting; Wang, Yan; Cheng, Hong; Xiao, Hu Zhang; Xiang, Juan Juan; Zhang, Jie Ting; Yu, Siu Bun Sydney; Martin, Tracey Amanda; Ye, Lin; Tsang, Lai Ling; Jiang, Wen Guo; Xiaohua, Jiang; Chan, Hsiao Chang

    2014-03-01

    How mutations or dysfunction of CFTR may increase the risk of malignancies in various tissues remains an open question. Here we report the interaction between CFTR and an adherens junction molecule, AF-6/afadin, and its involvement in the development of colon cancer. We have found that CFTR and AF-6/afadin are co-localized at the cell-cell contacts and physically interact with each other in colon cancer cell lines. Knockdown of CFTR results in reduced epithelial tightness and enhanced malignancies, with increased degradation and reduced stability of AF-6/afadin protein. The enhanced invasive phenotype of CFTR-knockdown cells can be completely reversed by either AF-6/afadin over-expression or ERK inhibitor, indicating the involvement of AF-6/MAPK pathway. More interestingly, the expression levels of CFTR and AF-6/afadin are significantly downregulated in human colon cancer tissues and lower expression of CFTR and/or AF-6/afadin is correlated with poor prognosis of colon cancer patients. The present study has revealed a previously unrecognized interaction between CFTR and AF-6/afadin that is involved in the pathogenesis of colon cancer and indicated the potential of the two as novel markers of metastasis and prognostic predictors for human colon cancer.

  2. B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

    PubMed Central

    Sinner, Moritz F.; Stepas, Katherine A.; Moser, Carlee B.; Krijthe, Bouwe P.; Aspelund, Thor; Sotoodehnia, Nona; Fontes, João D.; Janssens, A. Cecile J.W.; Kronmal, Richard A.; Magnani, Jared W.; Witteman, Jacqueline C.; Chamberlain, Alanna M.; Lubitz, Steven A.; Schnabel, Renate B.; Vasan, Ramachandran S.; Wang, Thomas J.; Agarwal, Sunil K.; McManus, David D.; Franco, Oscar H.; Yin, Xiaoyan; Larson, Martin G.; Burke, Gregory L.; Launer, Lenore J.; Hofman, Albert; Levy, Daniel; Gottdiener, John S.; Kääb, Stefan; Couper, David; Harris, Tamara B.; Astor, Brad C.; Ballantyne, Christie M.; Hoogeveen, Ron C.; Arai, Andrew E.; Soliman, Elsayed Z.; Ellinor, Patrick T.; Stricker, Bruno H.C.; Gudnason, Vilmundur; Heckbert, Susan R.; Pencina, Michael J.; Benjamin, Emelia J.; Alonso, Alvaro

    2014-01-01

    Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56–1.76], P < 0.0001 and 1.18 (95% CI, 1.11–1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022–0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322–0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. PMID:25037055

  3. 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.

  4. The Ultraviolet-bright, Slowly Declining Transient PS1-11af as a Partial Tidal Disruption Event

    NASA Astrophysics Data System (ADS)

    Chornock, R.; Berger, E.; Gezari, S.; Zauderer, B. A.; Rest, A.; Chomiuk, L.; Kamble, A.; Soderberg, A. M.; Czekala, I.; Dittmann, J.; Drout, M.; Foley, R. J.; Fong, W.; Huber, M. E.; Kirshner, R. P.; Lawrence, A.; Lunnan, R.; Marion, G. H.; Narayan, G.; Riess, A. G.; Roth, K. C.; Sanders, N. E.; Scolnic, D.; Smartt, S. J.; Smith, K.; Stubbs, C. W.; Tonry, J. L.; Burgett, W. S.; Chambers, K. C.; Flewelling, H.; Hodapp, K. W.; Kaiser, N.; Magnier, E. A.; Martin, D. C.; Neill, J. D.; Price, P. A.; Wainscoat, R.

    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 ⊙, 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.

  5. 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

  6. 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.

  7. Effect of long-term dietary arginyl-fructose (AF) on hyperglycemia and HbA1c in diabetic db/db mice.

    PubMed

    Lee, Kwang-Hyoung; Ha, Kyoung-Soo; Jo, Sung-Hoon; Lee, Chong M; Kim, Young-Cheul; Chung, Kwang-Hoe; Kwon, Young-In

    2014-05-12

    We have previously reported that Amadori compounds exert anti-diabetic effects by lowering sucrose-induced hyperglycemia in normal Sprague-Dawley rats. In the present study we extended our recent findings to evaluate whether α-glucosidase inhibitor arginyl-fructose (AF) lowers blood glucose level in diabetic db/db mice, a genetic model for type 2 diabetes. The db/db mice were randomly assigned to high-carbohydrate diets (66.1% corn starch) with and without AF (4% in the diet) for 6 weeks. Changes in body weight, blood glucose level, and food intake were measured daily for 42 days. Dietary supplementation of AF resulted in a significant decrease of blood glucose level (p < 0.001) and body weight (p < 0.001). The level of HbA1c, a better indicator of plasma glucose concentration over prolonged periods of time, was also significantly decreased for 6-week period (p < 0.001). Dietary treatment of acarbose® (0.04% in diet), a positive control, also significantly alleviated the level of blood glucose, HbA1c, and body weight. These results indicate that AF Maillard reaction product improves postprandial hyperglycemia by suppressing glucose absorption as well as decreasing HbA1c level.

  8. Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia.

    PubMed

    Mizukawa, Benjamin; Wei, Junping; Shrestha, Mahesh; Wunderlich, Mark; Chou, Fu-Sheng; Griesinger, Andrea; Harris, Chad E; Kumar, Ashish R; Zheng, Yi; Williams, David A; Mulloy, James C

    2011-11-10

    The Rac family of small Rho GTPases coordinates diverse cellular functions in hematopoietic cells including adhesion, migration, cytoskeleton rearrangements, gene transcription, proliferation, and survival. The integrity of Rac signaling has also been found to critically regulate cellular functions in the initiation and maintenance of hematopoietic malignancies. Using an in vivo gene targeting approach, we demonstrate that Rac2, but not Rac1, is critical to the initiation of acute myeloid leukemia in a retroviral expression model of MLL-AF9 leukemogenesis. However, loss of either Rac1 or Rac2 is sufficient to impair survival and growth of the transformed MLL-AF9 leukemia. Rac2 is known to positively regulate expression of Bcl-2 family proteins toward a prosurvival balance. We demonstrate that disruption of downstream survival signaling through antiapoptotic Bcl-2 proteins is implicated in mediating the effects of Rac2 deficiency in MLL-AF9 leukemia. Indeed, overexpression of Bcl-xL is able to rescue the effects of Rac2 deficiency and MLL-AF9 cells are exquisitely sensitive to direct inhibition of Bcl-2 family proteins by the BH3-mimetic, ABT-737. Furthermore, concurrent exposure to NSC23766, a small-molecule inhibitor of Rac activation, increases the apoptotic effect of ABT-737, indicating the Rac/Bcl-2 survival pathway may be targeted synergistically.

  9. Professional Development of Teachers--A Prerequisite for AfL to Be Successfully Implemented in the Classroom

    ERIC Educational Resources Information Center

    Smith, Kari

    2011-01-01

    A prerequisite for AfL to be successfully implemented in the classroom is the teachers' assessment practice. In many contexts, including the Norwegian, AfL has not been successfully dealt with during initial teacher education, and there is a need for qualified teachers to engage in professional development in AfL. This article first discusses…

  10. Patterns of missplicing due to somatic U2AF1 mutations in myeloid neoplasms

    PubMed Central

    Przychodzen, Bartlomiej; Jerez, Andres; Guinta, Kathryn; Sekeres, Mikkael A.; Padgett, Richard; Maciejewski, Jaroslaw P.

    2013-01-01

    Recently, recurrent mutations of spliceosomal genes were frequently identified in myeloid malignancies, as well as other types of cancers. One of these spliceosomal genes, U2AF1, was affected by canonical somatic mutations in aggressive type of myeloid malignancies. We hypothesized that U2AF1 mutations causes defects of splicing (missplicing) in specific genes and that such misspliced genes might be important in leukemogenesis. We analyzed RNA deep sequencing to compare splicing patterns of 201 837 exons between the cases with U2AF1 mutations (n = 6) and wild type (n = 14). We identified different alternative splicing patterns in 35 genes comparing cells with mutant and wild-type U2AF1. U2AF1 mutations are associated with abnormal splicing of genes involved in functionally important pathways, such as cell cycle progression and RNA processing. In addition, many of these genes are somatically mutated or deleted in various cancers. Of note is that the alternative splicing patterns associated with U2AF1 mutations were associated with specific sequence signals at the affected splice sites. These novel observations support the hypothesis that U2AF1 mutations play a significant role in myeloid leukemogenesis due to selective missplicing of tumor-associated genes. PMID:23775717

  11. 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

  12. 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). PMID:22439591

  13. Cross-talk between two global regulators in Streptomyces: PhoP and AfsR interact in the control of afsS, pstS and phoRP transcription.

    PubMed

    Santos-Beneit, Fernando; Rodríguez-García, Antonio; Sola-Landa, Alberto; Martín, Juan F

    2009-04-01

    The regulatory proteins AfsR and PhoP control expression of the biosynthesis of actinorhodin and undecylprodigiosin in Streptomyces coelicolor. Electrophoretic mobility shift assays showed that PhoP(DBD) does not bind directly to the actII-ORF4, redD and atrA promoters, but it binds to the afsS promoter, in a region overlapping with the AfsR operator. DNase I footprinting studies revealed a PhoP protected region of 26 nt (PHO box; two direct repeats of 11 nt) that overlaps with the AfsR binding sequence. Binding experiments indicated a competition between AfsR and PhoP; increasing concentrations of PhoP(DBD) resulted in the disappearance of the AfsR-DNA complex. Expression studies using the reporter luxAB gene coupled to afsS promoter showed that PhoP downregulates afsS expression probably by a competition with the AfsR activator. Interestingly, AfsR binds to other PhoP-regulated promoters including those of pstS (a component of the phosphate transport system) and phoRP (encoding the two component system itself). Analysis of the AfsR-protected sequences in each of these promoters allowed us to distinguish the AfsR binding sequence from the overlapping PHO box. The reciprocal regulation of the phoRP promoter by AfsR and of afsS by PhoP suggests a fine interplay of these regulators on the control of secondary metabolism.

  14. Phosphorylation of AfsR by multiple serine/threonine kinases in Streptomyces coelicolor A3(2).

    PubMed

    Sawai, Reiko; Suzuki, Ayano; Takano, Yuji; Lee, Ping-Chin; Horinouchi, Sueharu

    2004-06-01

    AfsK, a protein serine/threonine kinase, autophosphorylates on serine and threonine residues and phosphorylates serine and threonine residues of AfsR, a transcriptional activator for afsS involved in secondary metabolism in Streptomyces coelicolor A3(2). pkaG encoding a 592-amino-acid protein and SCD10.09 (named afsL) encoding a 580-amino-acid protein, both of which encode an AfsK-like protein, were transcribed throughout growth. PkaG with a histidine-tag and the kinase catalytic domain of PkaG, produced in Escherichia coli, autophosphorylated dominantly on threonine and slightly on serine residues. In addition, these proteins phosphorylated AfsR on threonine and serine residues. The catalytic domain of AfsL also autophosphorylated and phosphorylated AfsR, on threonine and serine residues in both cases. AfsR was thus found to be phosphorylated by multiple kinases. Disruption of the chromosomal pkaG gene resulted in slightly reduced production of the pigmented antibiotic actinorhodin. These findings, together with the presence of about 40 AfsK homologues and at least five AfsR homologues in S. coelicolor A3(2), suggest that the regulatory networks via eukaryotic-type protein phosphorylation are more diverse and versatile than we have expected.

  15. Photometric Properties for Selected Algol-type Binaries. VIII. The Triple Systems DI Peg and AF Gem Revisited

    NASA Astrophysics Data System (ADS)

    Yang, Yuan-Gui; Yang, Ying; Li, Shu-Zheng

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are fp = 78.2(± 0.4)% for DI Peg, and fp = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O-C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P 3 = 54.6(± 0.5) yr and P 4 = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M in = 0.095 M ⊙ and M out = 0.170 M ⊙, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  16. Photometric properties for selected algol-type binaries. VIII. The triple systems DI Peg and AF Gem revisited

    SciTech Connect

    Yang, Yuan-Gui; Li, Shu-Zheng; Yang, Ying E-mail: yangyg@chnu.edu.cn

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are f{sub p} = 78.2(± 0.4)% for DI Peg, and f{sub p} = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O–C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P {sub 3} = 54.6(± 0.5) yr and P {sub 4} = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M {sub in} = 0.095 M {sub ☉} and M {sub out} = 0.170 M {sub ☉}, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  17. 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

  18. Totally thorascopic surgical ablation of persistent AF and long-standing persistent atrial fibrillation using the "Dallas" lesion set.

    PubMed

    Edgerton, James R; Jackman, Warren M; Mahoney, Cecile; Mack, Michael J

    2009-12-01

    Minimally invasive surgery consisting of bipolar radiofrequency pulmonary vein (PV) isolation and limited ganglionated plexus ablation is effective in eliminating atrial fibrillation (AF) in patients with paroxysmal AF but is less effective in those with persistent AF or long-standing persistent AF. The purpose of this study was examine the results of minimally invasive surgery incorporating an additional set of radiofrequency ablation lines replicating a left-sided Cox maze III procedure. Thirty patients with persistent AF (n = 10) or long-standing persistent AF (n = 20) underwent minimally invasive surgery with an extended lesion set and PV isolation for a minimum follow-up of 6 months. Linear lesions were created at the roof line, at the anterior line, and between the roof line and the left atrial appendage. All patients underwent limited ganglionated plexus ablation and left atrial appendage excision as well as PV isolation verification. Block across the roof and anterior lines was confirmed in 29 (96.6%) of the 30 patients. Follow-up included 2-week event monitoring with auto-trigger in 21 patients, pacemaker interrogation in 8, and ECG in 1 who was in AF and refused longer-term monitoring. No operative mortality or major morbidity occurred. At 6 months, 24 (80%) of the 30 patients were free of AF: 15 (75%) with long-standing persistent AF and 9 (90%) with persistent AF. Among the six failures, burden of AF was low: one had 1 episode >15 seconds, two had 4 episodes, one had 6 episodes, one had >50 episodes, and one had AF on ECG and refused further monitoring. Early results of minimally invasive surgery with a new extended linear lesion set suggest increased efficacy over PV isolation and limited ganglionated plexus ablation in patients with persistent AF or long-standing persistent AF. PMID:19959146

  19. Lack of Concordance between Empirical Scores and Physician Assessments of Stroke and Bleeding Risk in Atrial Fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry

    PubMed Central

    Steinberg, Benjamin A.; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C.; Hylek, Elaine; Ansell, Jack; Go, Alan S.; Chang, Paul; Kowey, Peter; Gersh, Bernard J.; Mahaffey, Kenneth W.; Singer, Daniel E; Piccini, Jonathan P.; Peterson, Eric D.

    2014-01-01

    Background Physicians treating patients with atrial fibrillation (AF) must weigh the benefits of anticoagulation in preventing stroke versus the risk of bleeding. While empirical models have been developed to predict such risks, the degree to which these coincide with clinicians’ estimates is unclear. Methods and Results We examined 10,094 AF patients enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) registry between June, 2010 and August, 2011. Empirical stroke and bleeding risks were assessed using the CHADS2 and ATRIA scores, respectively. Separately, physicians were asked to categorize their patients’ stroke and bleeding risks: low- (<3%); intermediate- (3-6%); and high-risk (>6%). Overall, 72% (n=7251) in ORBIT-AF had high-risk CHADS2 scores (≥2). However, only 16% were assessed as high stroke risk by physicians. While 17% (n=1749) had high ATRIA bleeding risk (score ≥5), only 7% (n=719) were considered so by physicians. The associations between empirical and physician-estimated stroke and bleeding risks were low (weighted Kappa 0.1 and 0.11, respectively). Physicians weighed hypertension, heart failure, and diabetes less significantly than empirical models in estimating stroke risk; physicians weighted anemia and dialysis less significantly than empirical models when estimating bleeding risks. Anticoagulation use was highest among patients with high stroke risk, assessed by either empirical model or physician estimates. In contrast, physician and empirical estimates of bleeding had limited impact on treatment choice. Conclusions There is little agreement between provider-assessed risk and empirical scores in AF. These differences may explain, in part, current divergence of anticoagulation treatment decisions from guideline recommendations. PMID:24682387

  20. Facilitation of memory storage by the acetylcholine M2 muscarinic receptor antagonist AF-DX 116.

    PubMed

    Baratti, C M; Opezzo, J W; Kopf, S R

    1993-07-01

    Post-training administration of the acetylcholine muscarinic M2 presynaptic receptor antagonist AF-DX 116 (0.1-10.0 mg/kg, ip), facilitated 48 h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. AF-DX 116 did not increase the retention latencies of mice that had not received a footshock during training. The influence of AF-DX 116 (1 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by AF-DX 116 (1 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to AF-DX 116 treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training AF-DX 116 on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and AF-DX 116 (0.1 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of AF-DX 116 (0.1 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the activation of a muscarinic cholinergic presynaptic inhibitory mechanism, probably by increasing brain acetylcholine release, may modulate the activity of post-training processes involved in memory storage. PMID:8216161

  1. Facilitation of memory storage by the acetylcholine M2 muscarinic receptor antagonist AF-DX 116.

    PubMed

    Baratti, C M; Opezzo, J W; Kopf, S R

    1993-07-01

    Post-training administration of the acetylcholine muscarinic M2 presynaptic receptor antagonist AF-DX 116 (0.1-10.0 mg/kg, ip), facilitated 48 h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. AF-DX 116 did not increase the retention latencies of mice that had not received a footshock during training. The influence of AF-DX 116 (1 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by AF-DX 116 (1 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to AF-DX 116 treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training AF-DX 116 on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and AF-DX 116 (0.1 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of AF-DX 116 (0.1 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the activation of a muscarinic cholinergic presynaptic inhibitory mechanism, probably by increasing brain acetylcholine release, may modulate the activity of post-training processes involved in memory storage.

  2. 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.

  3. 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. PMID:27372134

  4. AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson's disease

    PubMed Central

    Haskin, Joseph; Szargel, Raymonde; Shani, Vered; Mekies, Lucy N.; Rott, Ruth; Lim, Grace G. Y.; Lim, Kah-Leong; Bandopadhyay, Rina; Wolosker, Herman; Engelender, Simone

    2013-01-01

    Parkin E3 ubiquitin-ligase activity and its role in mitochondria homeostasis are thought to play a role in Parkinson's disease (PD). We now report that AF-6 is a novel parkin interacting protein that modulates parkin ubiquitin-ligase activity and mitochondrial roles. Parkin interacts with the AF-6 PDZ region through its C-terminus. This leads to ubiquitination of cytosolic AF-6 and its degradation by the proteasome. On the other hand, endogenous AF-6 robustly increases parkin translocation and ubiquitin-ligase activity at the mitochondria. Mitochondrial AF-6 is not a parkin substrate, but rather co-localizes with parkin and enhances mitochondria degradation through PINK1/parkin-mediated mitophagy. On the other hand, several parkin and PINK1 juvenile disease-mutants are insensitive to AF-6 effects. AF-6 is present in Lewy bodies and its soluble levels are strikingly decreased in the caudate/putamen and substantia nigra of sporadic PD patients, suggesting that decreased AF-6 levels may contribute to the accumulation of dysfunctional mitochondria in the disease. The identification of AF-6 as a positive modulator of parkin translocation to the mitochondria sheds light on the mechanisms involved in PD and underscores AF-6 as a novel target for future therapeutics. PMID:23393160

  5. 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

  6. MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.

    PubMed

    Stavropoulou, Vaia; Kaspar, Susanne; Brault, Laurent; Sanders, Mathijs A; Juge, Sabine; Morettini, Stefano; Tzankov, Alexandar; Iacovino, Michelina; Lau, I-Jun; Milne, Thomas A; Royo, Hélène; Kyba, Michael; Valk, Peter J M; Peters, Antoine H F M; Schwaller, Juerg

    2016-07-11

    To address the impact of cellular origin on acute myeloid leukemia (AML), we generated an inducible transgenic mouse model for MLL-AF9-driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion. In vivo, 20% LT-HSC-derived AML were particularly aggressive with extensive tissue infiltration, chemoresistance, and expressed genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulator ZEB1 significantly reduced leukemic blast invasion. By classifying mouse and human leukemias according to Evi1/EVI1 and Erg/ERG expression, reflecting aggressiveness and cell of origin, and performing comparative transcriptomics, we identified several EMT-related genes that were significantly associated with poor overall survival of AML patients. PMID:27344946

  7. 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).

  8. Statin Therapy for the Prevention of Atrial Fibrillation Trial (SToP AF trial)

    PubMed Central

    Negi, Smita; Shukrullah, Irfan; Veledar, Emir; Bloom, Heather L.; Jones, Dean P.; Dudley, Samuel C.

    2010-01-01

    Background Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation. (NCT00252967) Methods and Results In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n=33) or placebo (n=31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers [ high sensitivity C- reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α (TNFα)] were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (p=0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, p=0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median (IR): 29 (2-145) days vs. 22 (7-70) days, p=0.9). While no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, p= 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, p=0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (p=0.03). Conclusions High dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress. PMID:20946227

  9. [Study and investigation of mechanism of atrial fibrillation--(II). Atrial fibrillation animal model and data analysis method].

    PubMed

    Zhang, Cuiying; Zhang, Shangjun

    2007-10-01

    The first thorny problem in the study of atrial fibrillation (AF) is the establishment of reliable animal models. This paper presents how to create a canine sterile pericarditis model. A new data analysis method, Fast Fourier Transform is introduced. The data from canine sterile pericarditis model was analyzed using FFT. The results demonstrate that canine sterile pericarditis model is a reliable animal model for studying AF and that FFT is a rapid and effective method for analyzing AF data. PMID:18027692

  10. 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.

  11. 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.

  12. 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.

  13. 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. PMID:24551202

  14. Neuronal and microvascular alterations induced by the cholinergic toxin AF64A in the rat retina.

    PubMed

    Gómez-Ramos, P; Galea, E; Estrada, C

    1990-06-18

    The choline analogue ethylcholine mustard aziridinium ion (AF64A) produces both neuronal and non-neuronal alterations in the rat retina. The possible involvement of the retinal capillaries in the origin of the apparently non-specific lesions has been investigated. Two hours after a single intraocular injection of 5 nmol AF64A, ultrastructural alterations were observed in neurons of the inner nuclear layer and the ganglion cell layer, where cholinergic cells are located. One week later, the number of cholinergic neurons, identified by choline acetyltransferase immunohistochemistry, was decreased to 65% of control, the neurons located in the inner nuclear layer being more sensitive than those in the ganglion cell layer. The same dose of AF64A also induced ultrastructural changes in retinal capillaries, which showed a significant increase in the number of pinocytotic vesicles and microvilli in the endothelial cells, 2-5 h after the toxin administration. One day later, arterioles and capillaries presented contracted profiles and the lumen was occasionally lost. The sensitivity of endothelial cells to the toxic effects of AF64A may be explained by the presence in the cerebral endothelium of a choline transport mechanism with an affinity close to that of cerebral synaptosomes. In vitro, both neuronal and endothelial choline uptake systems were equally sensitive to the toxin inhibitory effect. The early and severe vascular alterations induced in the retinal microvessels by AF64A may produce changes in blood perfusion and capillary permeability that could account for the apparently non-specific histological damage.

  15. Detection of human tumor cells by amplicon fusion site polymerase chain reaction (AFS-PCR)

    PubMed Central

    Weber, Axel; Taube, Sylvia; Starke, Sven; Bergmann, Eckhard; Christiansen, Nina Merete; Christiansen, Holger

    2011-01-01

    Reliable diagnostic strategies for individuals with cancer demand practical methods for highly sensitive and specific detection of tumor cells. Amplification of genomic regions that include putative oncogenes is common in tumor cells of various types. Genomic array platforms offer the opportunity to identify and precisely map amplified genomic regions (ampGRs). The stable existence of these tumor cell–specific genomic aberrations during and after therapy, in theory, make ampGRs optimal targets for cancer diagnostics. In this study, we mapped ampGRs around the proto-oncogene MYCN of human neuroblastomas using a high-resolution tiling array (HR-TA). Based on the HR-TA data, we were able to precisely describe the telomeric and centromeric borders of the ampGRs and deduce virtual fusion sites of the joined ampGRs (amplicon fusion sites [AFSs]). These AFSs served as blueprints for the subsequent design of AFS bridging PCR assays (AFS-PCRs). Strikingly, these assays were absolutely tumor cell specific and capable of detecting 1 tumor cell in 1 × 106 to 8 × 106 control cells. We successfully proved the in vivo practicability of AFS-PCR by detecting and quantifying the specific AFS DNA of human MYCN-amplified neuroblastomas in the patients’ corresponding peripheral blood and bone marrow samples. Thus, we believe AFS-PCR could become a powerful and nevertheless feasible personalized diagnostic tool applicable to a large number of cancer patients, including children with MYCN-amplified neuroblastomas. PMID:21293059

  16. Detection of human tumor cells by amplicon fusion site polymerase chain reaction (AFS-PCR).

    PubMed

    Weber, Axel; Taube, Sylvia; Starke, Sven; Bergmann, Eckhard; Christiansen, Nina Merete; Christiansen, Holger

    2011-02-01

    Reliable diagnostic strategies for individuals with cancer demand practical methods for highly sensitive and specific detection of tumor cells. Amplification of genomic regions that include putative oncogenes is common in tumor cells of various types. Genomic array platforms offer the opportunity to identify and precisely map amplified genomic regions (ampGRs). The stable existence of these tumor cell–specific genomic aberrations during and after therapy, in theory, make ampGRs optimal targets for cancer diagnostics. In this study, we mapped ampGRs around the proto-oncogene MYCN of human neuroblastomas using a high-resolution tiling array (HR-TA). Based on the HR-TA data, we were able to precisely describe the telomeric and centromeric borders of the ampGRs and deduce virtual fusion sites of the joined ampGRs (amplicon fusion sites [AFSs]). These AFSs served as blueprints for the subsequent design of AFS bridging PCR assays (AFS-PCRs). Strikingly, these assays were absolutely tumor cell specific and capable of detecting 1 tumor cell in 1 × 10(6) to 8 × 10(6) control cells. We successfully proved the in vivo practicability of AFS-PCR by detecting and quantifying the specific AFS DNA of human MYCN-amplified neuroblastomas in the patients’ corresponding peripheral blood and bone marrow samples. Thus, we believe AFS-PCR could become a powerful and nevertheless feasible personalized diagnostic tool applicable to a large number of cancer patients, including children with MYCN-amplified neuroblastomas.

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

    SciTech Connect

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

    1983-04-01

    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.

  18. 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.

  19. MLL-AF9– and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C

    PubMed Central

    Zhu, Nan; Chen, Mo; Eng, Rowena; DeJong, Joshua; Sinha, Amit U.; Rahnamay, Noushin F.; Koche, Richard; Al-Shahrour, Fatima; Minehart, Janna C.; Chen, Chun-Wei; Deshpande, Aniruddha J.; Xu, Haiming; Chu, S. Haihua; Ebert, Benjamin L.; Roeder, Robert G.; Armstrong, Scott A.

    2016-01-01

    Self-renewal is a hallmark of both hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs); therefore, the identification of mechanisms that are required for LSC, but not HSC, function could provide therapeutic opportunities that are more effective and less toxic than current treatments. Here, we employed an in vivo shRNA screen and identified jumonji domain–containing protein JMJD1C as an important driver of MLL-AF9 leukemia. Using a conditional mouse model, we showed that loss of JMJD1C substantially decreased LSC frequency and caused differentiation of MLL-AF9– and homeobox A9–driven (HOXA9-driven) leukemias. We determined that JMJD1C directly interacts with HOXA9 and modulates a HOXA9-controlled gene-expression program. In contrast, loss of JMJD1C led to only minor defects in blood homeostasis and modest effects on HSC self-renewal. Together, these data establish JMJD1C as an important mediator of MLL-AF9– and HOXA9-driven LSC function that is largely dispensable for HSC function. PMID:26878175

  20. Cloning and characterization of two duplicated interleukin-17A/F2 genes in common carp (Cyprinus carpio L.): Transcripts expression and bioactivity of recombinant IL-17A/F2.

    PubMed

    Li, Hongxia; Yu, Juhua; Li, Jianlin; Tang, Yongkai; Yu, Fan; Zhou, Jie; Yu, Wenjuan

    2016-04-01

    Interleukin-17 (IL-17) plays an important role in inflammation and host defense in mammals. In this study, we identified two duplicated IL-17A/F2 genes in the common carp (Cyprinus carpio) (ccIL-17A/F2a and ccIL-17A/F2b), putative encoded proteins contain 140 amino acids (aa) with conserved IL-17 family motifs. Expression analysis revealed high constitutive expression of ccIL-17A/F2s in mucosal tissues, including gill, skin and intestine, their expression could be induced by Aeromonas hydrophila, suggesting a potential role in mucosal immunity. Recombinant ccIL-17A/F2a protein (rccIL-17A/F2a) produced in Escherichia coli could induce the expression of proinflammatory cytokines (IL-1β) and the antimicrobial peptides S100A1, S100A10a and S100A10b in the primary kidney in a dose- and time-dependent manner. Above findings suggest that ccIL-17A/F2 plays an important role in both proinflammatory and innate immunity. Two duplicated ccIL-17A/F2s showed different expression level with ccIL-17A/F2a higher than b, comparison of two 5' regulatory regions indicated the length from anticipated promoter to transcriptional start site (TSS) and putative transcription factor binding site (TFBS) were different. Promoter activity of ccIL-17A/F2a was 2.5 times of ccIL-17A/F2b which consistent with expression results of two genes. These suggest mutations in 5'regulatory region contributed to the differentiation of duplicated genes. To our knowledge, this is the first report to analyze 5'regulatory region of piscine IL-17 family genes. PMID:26921542

  1. 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

  2. Plate description of active deformation in the Africa (AF)-Arabia (AR)-Eurasia (EU) zone of plate interaction

    NASA Astrophysics Data System (ADS)

    Vernant, P.; McClusky, S.; Reilinger, R.

    2006-12-01

    We present the results of 17 years of GPS monitoring in this zone of plate interaction and show that to the resolution of our observations (i.e., ~1-2 mm/yr; ~ ±10 % of relative plate motions), deformation is consistent with plate-block models with relative motion between adjacent plates/blocks accommodated by elastic strain accumulation. Relative plate motions are consistent with geologically recent (~ 3 Ma) plate motions where geologic estimates of relative plate motion have been determined (AR- Nubia: Red Sea; AR-Somalia: Gulf of Aden; AF-EU; AR-EU). Furthermore, fault slip rates derived from the GPS block motions are mostly equal to geologic slip rates determined for long enough time intervals to average out earthquake cycle effects. We conclude that a plate description (i.e., relative Euler vectors) is appropriate to describe the kinematics of continental deformation during the past few Myr in this zone of plate interaction.

  3. 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.

  4. 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

  5. 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

  6. (/sup 3/H)AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart

    SciTech Connect

    Wang, J.X.; Roeske, W.R.; Gulya, K.; Wang, W.; Yamamura, H.I.

    1987-10-05

    The in vitro binding properties of the novel muscarinic antagonist (/sup 3/H)AF-DX 116 were studied using a rapid filtration technique. Association and dissociation rates of (/sup 3/H)AF-DX 116 binding were rapid at 25/sup 0/C but 20-40 times slower at 0-4/sup 0/C. Kinetic dissociation constants (K/sub d/s) were estimated to be 31.8 nM and 30.9 nM at 25/sup 0/C; 23.1 nM and 22.9 nM at 0-4/sup 0/C for the cerebral cortex and heart, respectively. In saturation studies, (/sup 3/H)AF-DX 116 labeled 29% of the total (/sup 3/H)(-)QNB binding sites in the cerebral cortical membranes and 87% in the cardiac membranes, with K/sub d/ values of 28.9 nM and 17.9 nM, respectively. Muscarinic antagonists inhibited (/sup 3/H)AF-DX 116 binding in a rank order of potency of atropine > dexetimide > AF-DX 116 > PZ > levetimide in both tissues. Except for PZ/(/sup 3/H)AF-DX 116 and AF-DX 116/(/sup 3/H)AF-DX 116 in the cerebral cortex, all the antagonist competition curves had Hill coefficients close to one. 19 references, 2 figures, 4 tables.

  7. 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.

  8. Identification and Characterization of an Antifungal Protein, AfAFPR9, Produced by Marine-Derived Aspergillus fumigatus R9.

    PubMed

    Rao, Qi; Guo, Wenbin; Chen, Xinhua

    2015-05-01

    A fungal strain, R9, was isolated from the South Atlantic sediment sample and identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 μg/disc, respectively. Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion and denaturant tolerance. The iodoacetamide assay showed that the disulfide bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity against C. gloeosporioides, T. viride, and A. longipes. These results reveal the antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus fumigatus and indicated its potential application in controlling plant pathogenic fungi. PMID:25394604

  9. Genome Sequence of Anoxybacillus thermarum AF/04T, Isolated from the Euganean Hot Springs in Abano Terme, Italy.

    PubMed

    Poli, Annarita; Nicolaus, Barbara; Chan, Kok-Gan; Kahar, Ummirul Mukminin; Chan, Chia Sing; Goh, Kian Mau

    2015-05-21

    Anoxybacillus thermarum AF/04(T) was isolated from the Euganean hot springs in Abano Terme, Italy. The present work reports a high-quality draft genome sequence of strain AF/04(T). This work also provides useful insights into glycoside hydrolases, glycoside transferases, and sugar transporters that may be involved in cellular carbohydrate metabolism.

  10. 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

  11. Innate immune cells express IL-17A/F in acute generalized exanthematous pustulosis and generalized pustular psoriasis.

    PubMed

    Kakeda, M; Schlapbach, Christoph; Danelon, G; Tang, M M; Cecchinato, V; Yawalkar, N; Uguccioni, M

    2014-12-01

    Acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) are rare pustular skin disorders with systemic involvement. IL-17A/F is a proinflammatory cytokine involved in various neutrophilic inflammatory disorders. Here we show that IL-17A/F is highly expressed by innate immune cells such as neutrophils and mast cells in both AGEP and GPP.

  12. AfsR as an integrator of signals that are sensed by multiple serine/threonine kinases in Streptomyces coelicolor A3(2).

    PubMed

    Horinouchi, Sueharu

    2003-08-01

    The genome sequence of Streptomyces coelicolor A3(2) has revealed the presence of about 40 protein serine/threonine or tyrosine kinases. AfsK, which is able to phosphorylate AfsR, a transcriptional activator with ATPase activity, represents the first instance in which a bacterial Hanks-type protein kinase phosphorylates a specific protein and exerts biologically important functions. The AfsK-AfsR system in S. coelicolor A3(2) globally controls secondary metabolism. The signal transduction pathway so far demonstrated or suggested is as follows: AfsK loosely attached to the membrane autophosphorylates threonine and serine residues, perhaps on sensing some external stimulus, and enhances its kinase activity. The kinase activity is modulated by KbpA, an AfsK-binding protein, by means of protein-protein interactions. The activated AfsK phosphorylates threonine and serine residues of AfsR in the cytoplasm, by which the DNA-binding activity of AfsR is greatly enhanced. In addition to AfsK, other kinases-including PkaG and AfsL-also phosphorylate AfsR, suggesting that AfsR serves as an integrator of multiple signals sensed by these kinases. The phosphorylated AfsR binds the promoter of afsS, which encodes a protein of 63 amino acids, and forms a closed complex with RNA polymerase. The closed complex is then converted to a transcriptionally active open complex by the energy available from ATP hydrolysis by AfsR. AfsS induced in this way activates transcription of pathway-specific transcriptional activators, such as actII-ORF4 for actinorhodin production and redD for undecylprodigiosin, in an as yet unknown manner.

  13. Unusual hydrogen bonding patterns in AF (aminofluorene) and AAF (acetylaminofluorene) modified DNA

    SciTech Connect

    Broyde, S.; Hingerty, B.E.; Shapiro, R.; Norman, D.

    1989-01-01

    New structures are presented for AF and AAF modified DNAs that place the carcinogen in the minor groove of a B-DNA helix. These structures employ non-Watson-Crick base pairing schemes with syn guanine at the modification site. 32 refs., 9 figs.

  14. 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.

  15. K-theory of the chair tiling via AF-algebras

    NASA Astrophysics Data System (ADS)

    Julien, Antoine; Savinien, Jean

    2016-08-01

    We compute the K-theory groups of the groupoid C∗-algebra of the chair tiling, using a new method. We use exact sequences of Putnam to compute these groups from the K-theory groups of the AF-algebras of the substitution and the induced lower dimensional substitutions on edges and vertices.

  16. 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,...

  17. 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,...

  18. 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,...

  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. Developing an Assessment for Learning (AfL) Culture in School: The Voice of the Principals

    ERIC Educational Resources Information Center

    Smith, Kari; Engelsen, Knut Steinar

    2013-01-01

    This study reflects the voice of school leaders (principals) in a Norwegian school development project focusing on assessment for learning (AfL). The central role of the principal in school improvement is well documented, however, less is written about how the principals themselves see their roles. The voices presented belong to two experienced…

  1. Acutangulosides A-F, monodesmosidic saponins from the bark of Barringtonia acutangula.

    PubMed

    Mills, Clive; Carroll, Anthony R; Quinn, Ronald J

    2005-03-01

    Nine triterpene saponins, acutangulosides A-F (2-7), and acutanguloside D-F methyl esters (5a-7a) and a single triterpene aglycone (1) were isolated from a water extract of the bark of Barringtonia acutangula. Their structures were assigned on the basis of spectroscopic data. PMID:15787427

  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. 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. PMID:26927796

  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. Atrial fibrillation in rats induced by rapid transesophageal atrial pacing during brief episodes of asphyxia: a new in vivo model.

    PubMed

    Haugan, Ketil; Lam, Henrik Rye; Knudsen, Carsten Boye; Petersen, Jørgen Søberg

    2004-07-01

    Non-pharmacological in vivo models of atrial fibrillation (AF) have been developed in large animals only. We aimed to develop and characterize a new small animal non-pharmacological in vivo model of AF. AF was induced by transesophageal atrial burst pacing during 35 seconds periods of asphyxia in anesthetized male Sprague-Dawley rats. AF was reproducibly induced in 81% of the rats. The presence of AF was associated with an increased heart rate, and a decreased blood pressure. Treatment with amiodarone, D,L-sotalol, flecainide, and propranolol all reduced duration of AF, whereas verapamil treatment was associated with a marked profibrillatory effect. Increasing gap junction intracellular communication using the antiarrhythmic peptide analogue AAP10 did not affect AF duration. Basal plasma level of epinephrine and norepinephrine were increased 5- to 20-fold relative to values reported by others, but unchanged following 35 seconds of asphyxia. The results from our study demonstrate that the rat model shares several clinical key characteristics with human AF: (1) hemodynamic response to AF; (2) increased autonomic tone; (3) antiarrhythmic effects of clinically used drugs; (4) profibrillatory effect of verapamil. Relative to existing models of AF in larger animals, this model offers rapid, predictive, and inexpensive testing of antiarrhythmic/profibrillatory effects of new drugs.

  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. 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.

  8. Jaspolides A-F, six new isomalabricane-type terpenoids from the sponge Jaspis sp.

    PubMed

    Tang, Shengan; Pei, Yuehu; Fu, Hongzheng; Deng, Zhiwei; Li, Jun; Proksch, Peter; Lin, Wenhan

    2006-01-01

    A chemical investigation of Jaspis sp., the marine sponge collected from the South China Sea led to the isolation of six new isomalabaricane-type compounds, jaspolides A-F (1-6). The structures of those compounds were elucidated by extensive spectroscopic methods. The structure-types of 1 to 6 could be classified into triterpenes (1, 2), sesterterpene (6), diterpenes (3, 4), and nortriterpene (5). The biogenetic transformation of the isolated compounds was also speculated.

  9. 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.

  10. 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.

  11. 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...

  12. Plastic flow and failure in HY100, HY130 and AF1410 alloy steels under high strain rate and impact loading conditions

    NASA Astrophysics Data System (ADS)

    Rajendran, A. M.; Last, H. R.; Garrett, R. K., Jr.

    1995-03-01

    This report presents the results from impact experiments, constitutive/failure modeling, and metallurgical failure analyses for three steels: HY100, HY130, and AF1410. The main objectives of this effort are: (1) to obtain fundamental engineering data in terms of stress-strain curves up to failure at different temperatures and strain rates, (2) to evaluate the observed differences in the macroscopic behaviors through microscopic metallurgical studies, and (3) to describe the flow and failure behaviors using already available material strength and spall models. The high strain rate and impact experiments considered are the split Hopkinson bar (SHB) and the planar plate impact tests, respectively. In addition, the baseline data include quasi-static (QS) tests at low strain rates. The QS and SHB data provide stress-strain curves at different strain rates and temperatures. The experimental data illustrate the effects of two important loading parameters (strain rate and temperature) on the flow and failure behaviors of HY100, HY130, and AF1410 steels.

  13. [3H]AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart.

    PubMed

    Wang, J X; Roeske, W R; Gulya, K; Wang, W; Yamamura, H I

    1987-10-01

    The in vitro binding properties of the novel muscarinic antagonist [3H]AF-DX 116 were studied using a rapid filtration technique. Association and dissociation rates of [3H]AF-DX 116 binding were rapid at 25 degrees C (2.74 and 2.70 X 10(7) min-1 M-1 for K+1; 0.87 and 0.93 min-1 for k-1) but 20-40 times slower at 0-4 degrees C (0.13 and 0.096 X 10(7) min-1 M-1 for k+1; 0.031 and 0.022 min-1 for k-1 in cerebral cortical and cardiac membranes, respectively). Kinetic dissociation constants (Kds) were estimated to be 31.8 nM and 30.9 nM at 25 degrees C; 23.1 nM and 0-4 degrees C for the cerebral cortex and heart, respectively. In saturation studies, [3H]AF-DX 116 labeled 29 percent of the total [3H](-)QNB binding sites in the cerebral cortical membranes and 87 percent in the cardiac membranes, with Kd values of 28.9 nM and 17.9 nM, respectively. Muscarinic antagonists inhibited [3H]AF-DX 116 binding in a rank order of potency of atropine greater than dexetimide greater than AF-DX 116 greater than PZ greater than levetimide in both tissues. Except for PZ/[3H]AF-DX 116 and AF-DX 116/[3H]AF-DX 116 in the cerebral cortex, all the antagonist competition curves had Hill coefficients close to one. Carbachol and oxotremorine produced shallow inhibition curves against [3H]AF-DX 116 binding in both tissues. Regional distribution studies with [3H](-)QNB, [3H]PZ and [3H]AF-DX 116 showed that most of the muscarinic receptors in the cerebral cortex, hippocampus, nucleus accumbens and corpus striatum are of the M1 subtype while those in the brainstem, cerebellum and other lower brain regions are of the M2 subtype. These results indicate that [3H]AF-DX 116 is a useful probe for the study of heterogeneity of muscarinic cholinergic receptors. PMID:3657382

  14. Molecular characterization of a rare MLL-AF4 (MLL-AFF1) fusion rearrangement in infant leukemia.

    PubMed

    Bizarro, Susana; Cerveira, Nuno; Correia, Cecília; Lisboa, Susana; Peixoto, Ana; Norton, Lucília; Teixeira, Manuel R

    2007-10-01

    The t(4;11)(q21;q23) involving the genes MLL and AF4 (alias for AFF1) is detected in 50-70% of infant leukemia. We characterize at both the DNA and RNA level a rare MLL-AF4 fusion transcript identified in a 15-month-old girl with acute lymphoblastic leukemia. Direct sequence analysis of the reverse transcriptase-polymerase chain reaction product showed an in-frame fusion between MLL exon 9 and AF4 exon 6. We further demonstrated that the genomic breakpoints were located 1,553 bp downstream of MLL exon 9 and 1,239 bp upstream of AF4 exon 6. Four Alu repeats were detected in MLL intron 9 and two Alu repeats and one LINE1 repetitive element were identified downstream of AF4 exon 5. Finally, a 9-bp polypurine (A) tract and an 8-bp polypyrimidine (T) tract were found flanking the translocation breakpoint. In summary, we have characterized at both the RNA and the DNA level a rare MLL-AF4 fusion variant that was presumably mediated by Alu repeats or polypurine and polypyrimidine tracts located in the vicinity of genomic breakpoints. PMID:17889710

  15. Potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK through a serine 118-independent pathway.

    PubMed

    Feng, W; Webb, P; Nguyen, P; Liu, X; Li, J; Karin, M; Kushner, P J

    2001-01-01

    Estrogen receptor (ER) is activated either by ligand or by signals from tyrosine kinase-linked cell surface receptors. We investigated whether the nonreceptor Src tyrosine kinase could affect ER activity. Expression of constitutively active Src or stimulation of the endogenous Src/JNK pathway enhances transcriptional activation by the estrogen-ER complex and strongly stimulates the otherwise weak activation by the unliganded ER and the tamoxifen-ER complex. Src affects ER activation function 1 (AF-1), and not ER AF-2, and does so through its tyrosine kinase activity. This effect of Src is mediated partly through a Raf/mitogen-activated ERK kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) signaling cascade and partly through a MEKK/JNKK/JNK cascade. Although, as previously shown, Src action through activated ERK stimulates AF-1 by phosphorylation at S118, Src action through activated JNK neither leads to phosphorylation of S118 nor requires S118 for its action. We therefore suggest that the Src/JNK pathway enhances AF-1 activity by modification of ER AF-1-associated proteins. Src potentiates activation functions in CREB-binding protein (CBP) and glucocorticoid receptor interacting protein 1 (GRIP1), and we discuss the possibility that the Src/JNK pathway enhances the activity of these coactivators, which are known to mediate AF-1 action. PMID:11145737

  16. 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

  17. 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

    2016-01-01

    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

  18. 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

  19. S-adenosyl-L-methionine activates actinorhodin biosynthesis by increasing autophosphorylation of the Ser/Thr protein kinase AfsK in Streptomyces coelicolor A3(2).

    PubMed

    Jin, Ying-Yu; Cheng, Jinhua; Yang, Seung Hwan; Meng, Lingzhu; Palaniyandi, Sasikumar Arunachalam; Zhao, Xin-Qing; Suh, Joo-Won

    2011-01-01

    S-Adenosyl-L-methionine (SAM) is one of the major methyl donors in all living organisms. The exogenous treatment with SAM leads to increased actinorhodin production in Streptomyces coelicolor A3(2). In this study, mutants from different stages of the AfsK-AfsR signal transduction cascade were used to test the possible target of SAM. SAM had no significant effect on actinorhodin production in afsK, afsR, afsS, or actII-open reading frame 4 (ORF4) mutant. This confirms that afsK plays a critical role in delivering the signal generated by exogenous SAM. The afsK-pHJL-KN mutant did not respond to SAM, suggesting the involvement of the C-terminal of AfsK in binding with SAM. SAM increased the in vitro autophosphorylation of kinase AfsK in a dose-dependent manner, and also abolished the effect of decreased actinorhodin production by a Ser/Thr kinase inhibitor, K252a. In sum, our results suggest that SAM activates actinorhodin biosynthesis in S. coelicolor M130 by increasing the phosphorylation of protein kinase AfsK.

  20. Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

    PubMed Central

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

    2015-01-01

    Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized 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 (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. PMID:25209598

  1. Studies on electrochemical oxidation of estrogenic disrupting compound bisphenol AF and its interaction with human serum albumin.

    PubMed

    Wang, Xin; Yang, Jichun; Wang, Yuejiao; Li, Yanhui; Wang, Fang; Zhang, Lei

    2014-07-15

    Bisphenol AF (BPAF) is an environmental pollutant to disrupt endocrine system or cause cancer, thus the detection of trace BPAF is very important. In this study, a simple and highly sensitive electroanalytical method for the determination of BPAF was developed. In pH 6.0 phosphate buffer solutions, carboxyl functionalized multi-walled carbon nanotubes (MWCNT-COOH) modified glassy carbon electrode exhibits an enhanced effectiveness for the oxidation of BPAF. This electrode exhibited two linear relationships with BPAF concentration range of 0.02μmolL(-1) to 8.0μmolL(-1) and a detection limit of 0.0077μmolL(-1) (S/N=3). The proposed method was successfully applied to determine BPAF in real samples and the results were satisfactory. The MWCNT-COOH/GCE electrode showed good reproducibility, stability and anti-interference. The electrochemistry and spectroscopy methods are also described for the evaluation of BPAF-HSA interaction. In the presence of HSA, the peak currents of BPAF decreased linearly due to the formation of a super-molecular complex. The binding constant between BPAF and HSA, obtained by differential pulse voltammetry (DPV), was consistent with the fluorescence analysis. The molecular modeling studies were carried out to clearly describe the interaction between BPAF and HSA.

  2. 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.

  3. Quality control in boar semen production by use of the FACSCount AF system.

    PubMed

    Christensen, Preben; Knudsen, Dorte B; Wachmann, Henrik; Madsen, Mads T

    2004-10-01

    A simple and rapid flow cytometric method has recently been developed for simultaneous determination of sperm concentration and viability in semen from domestic animals. Use of SYBR-14 trade mark in combination with propidium iodide (PI) allows estimation of the proportion of live sperm (viability). An internal standard of fluorescent microspheres (beads) makes it possible to determine the sperm concentration during the same analysis. In the first experiment, the relationship between sperm viability and litter size was investigated. The second experiment explored whether a smaller variation in the number of motile sperm per insemination dose could be obtained using the FACSCount AF flow cytometer than using a spectrophotometer. Results in the first experiment show that sperm viability is closer related to litter size than is the traditionally used motility parameter. Although the flow cytometer is precise and objective, a limited effect on litter size should be anticipated if ejaculates are selected for insemination according to the percentage of viable sperm. However, the present trial used large insemination doses (2.3 x 10(9) motile sperm/dose) which partially compensate for the differences in motility and viability between boars and ejaculates. In the second experiment it was found that variation in the number of motile sperm per insemination dose could be reduced significantly if the FACSCount AF flow cytometer rather than the Corning 254 spectrophotometer was used for determination of sperm concentration in the raw semen. It is concluded that the FACSCount AF flow cytometer is a strong tool for improvement of the quality control in artificial insemination (AI) centres. PMID:15325548

  4. An improved AFS phase for AdS3 string integrability

    NASA Astrophysics Data System (ADS)

    Abbott, Michael C.; Aniceto, Inês

    2015-04-01

    We propose a number of modifications to the classical term in the dressing phase for integrable strings in AdS3 ×S3 ×S3 ×S1, and check these against existing perturbative calculations, crossing symmetry, and the semiclassical limit of the Bethe equations. The principal change is that the phase for different masses should start with a term Q1Q2, like the one-loop AdS3 dressing phase, rather than Q2Q3 as for the original AdS5 AFS phase.

  5. The strainrange partitioning behavior of an advanced gas turbine disk alloy, AF2-1DA

    NASA Technical Reports Server (NTRS)

    Halford, G. R.; Nachtigall, A. J.

    1979-01-01

    The low-cycle, creep-fatigue characteristics of the advanced gas turbine disk alloy, AF2-1DA have been determined at 1400 F and are presented in terms of the method of strainrange partitioning (SRP). The mean stresses which develop in the PC and CP type SRP cycles at the lowest inelastic strainrange were observed to influence the cyclic lives to a greater extent than the creep effects and hence interfered with a conventional interpretation of the results by SRP. A procedure is proposed for dealing with the mean stress effects on life which is compatible with SRP.

  6. 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.

  7. 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

    2009-11-01

    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.

  8. CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by mediating U2AF2 ubiquitination and degradation

    PubMed Central

    Fu, Ailing; Zhu, Huifeng; Ren, Qiao; Wang, Bochu; Xu, Xingran; Bai, Huiyuan; Dong, Cheng

    2016-01-01

    Melanoma is one of the most lethal forms of skin cancer due to its early metastatic spread. The variant form of CD44 (CD44v), a cell surface glycoprotein, is highly expressed on metastatic melanoma. The mechanisms of regulation of CD44 alternative splicing in melanoma and its pathogenic contributions are so far poorly understood. Here, we investigated the expression level of CD44 in a large set of melanocytic lesions at different stages. We found that the expression of CD44v8-10 and a splicing factor, U2AF2, is significantly increased during melanoma progression, while CD82/KAI1, a tetraspanin family of tumor suppressor, is reduced in metastatic melanoma. CD44v8-10 and U2AF2 expressions which are negatively correlated with CD82 levels are dramatically elevated in primary melanoma compared with dysplastic nevi and further increased in metastatic melanoma. We also showed that patients with higher CD44v8-10 and U2AF2 expression levels tended to have shorter survival. By using both in vivo and in vitro assays, we demonstrated that CD82 inhibits the production of CD44v8-10 on melanoma. Mechanistically, U2AF2 is a downstream target of CD82 and in malignant melanoma facilitates CD44v8-10 alternative splicing. U2AF2-mediated CD44 isoform switch is required for melanoma migration in vitro and lung and liver metastasis in vivo. Notably, overexpression of CD82 suppresses U2AF2 activity by inducing U2AF2 ubiquitination. In addition, our data suggested that enhancement of melanoma migration by U2AF2-dependent CD44v8-10 splicing is mediated by Src/FAK/RhoA activation and formation of stress fibers as well as CD44-E-selectin binding reinforcement. These findings uncovered a hitherto unappreciated function of CD82 in severing the linkage between U2AF2-mediated CD44 alternative splicing and cancer aggressiveness, with potential prognostic and therapeutic implications in melanoma. PMID:27041584

  9. A homogenization model of the annulus fibrosus.

    PubMed

    Yin, Luzhong; Elliott, Dawn M

    2005-08-01

    The objective of this study was to use a homogenization model of the anisotropic mechanical behavior of annulus fibrosus (AF) to address some of the issues raised in structural finite element and fiber-reinforced strain energy models. Homogenization theory describes the effect of microstructure on macroscopic material properties by assuming the material is composed of repeating representative volume elements. We first developed the general homogenization model and then specifically prescribed the model to in-plane single lamella and multi-lamellae AF properties. We compared model predictions to experimentally measured AF properties and performed parametric studies. The predicted tensile moduli (E theta and E z) and their dependence on fiber volume fraction and fiber angle were consistent with measured values. However, the model prediction for shear modulus (G thetaz) was two orders of magnitude larger than directly measured values. The values of E theta and E z were strongly dependent on the model input for matrix modulus, much more so than the fiber modulus. These parametric analyses demonstrated the contribution of the matrix in AF load support, which may play a role when protoeglycans are decreased in disc degeneration, and will also be an important design factor in tissue engineering. We next compared the homogenization model to a 3-D structural finite element model and fiber-reinforced energy models. Similarities between the three model types provided confidence in the ability of these models to predict AF tissue mechanics. This study provides a direct comparison between the several types of AF models and will be useful for interpreting previous studies and elucidating AF structure-function relationships in disc degeneration and for functional tissue engineering.

  10. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia.

    PubMed

    Sanjuan-Pla, Alejandra; Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W; Marschalek, Rolf; Menéndez, Pablo

    2015-12-17

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a "multiple-and-sequential-hit" model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one "big-hit" might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  11. Type I Interferon signaling constrains IL-17A/F secretion by γδ T cells during bacterial infections

    PubMed Central

    Henry, Thomas; Kirimanjeswara, Girish S.; Ruby, Thomas; Jones, Jonathan W.; Peng, Kaitian; Perret, Magali; Ho, Lena; Sauer, John-Demian; Iwakura, Yoichiro; Metzger, Dennis W.; Monack, Denise M.

    2010-01-01

    Recognition of intracellular bacteria by macrophages leads to secretion of type I Interferons. However, the role of type I IFN during bacterial infection is still poorly understood. Francisella tularensis, the causative agent of tularemia, is a pathogenic bacterium that replicates in the cytosol of macrophages leading to secretion of type I IFN. Here, we investigated the role of type I IFN in a mouse model of tularemia. Mice deficient for type I IFN receptor (IFNAR1−/−) are more resistant to intradermal infection with F. tularensis subspecies novicida (F. novicida). Increased resistance to infection was associated with a specific increase in IL-17A/F and a corresponding expansion of an IL-17A+ γδ T cell population, indicating that type I IFN negatively regulate the number of IL-17A+ γδ T cells during infection. Furthermore, IL-17A-deficient mice contained fewer neutrophils compared to WT mice upon infection, indicating that IL-17A contributes to neutrophil expansion during F. novicida infection. Accordingly, an increase in IL-17A in IFNAR1−/− mice correlated with an increase in splenic neutrophil numbers. Similar results were obtained in a mouse model of pneumonic tularemia using the highly virulent Francisella tularensis subspecies tularensis SchuS4 strain and in a mouse model of systemic Listeria monocytogenes infection. Our results indicate that the type I IFN-mediated negative regulation of IL-17A+ γδ T cell expansion is conserved during bacterial infections. We propose that this newly described activity of type I IFN signaling might participate in the resistance of the IFNAR1−/− mice to infection with F. novicida and other intracellular bacteria. PMID:20176744

  12. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia.

    PubMed

    Sanjuan-Pla, Alejandra; Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W; Marschalek, Rolf; Menéndez, Pablo

    2015-12-17

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a "multiple-and-sequential-hit" model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one "big-hit" might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models.

  13. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    PubMed Central

    Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W.; Marschalek, Rolf; Menéndez, Pablo

    2015-01-01

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a “multiple-and-sequential-hit” model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one “big-hit” might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  14. An extended U2AF65–RNA-binding domain recognizes the 3′ splice site signal

    PubMed Central

    Agrawal, Anant A.; Salsi, Enea; Chatrikhi, Rakesh; Henderson, Steven; Jenkins, Jermaine L.; Green, Michael R.; Ermolenko, Dmitri N.; Kielkopf, Clara L.

    2016-01-01

    How the essential pre-mRNA splicing factor U2AF65 recognizes the polypyrimidine (Py) signals of the major class of 3′ splice sites in human gene transcripts remains incompletely understood. We determined four structures of an extended U2AF65–RNA-binding domain bound to Py-tract oligonucleotides at resolutions between 2.0 and 1.5 Å. These structures together with RNA binding and splicing assays reveal unforeseen roles for U2AF65 inter-domain residues in recognizing a contiguous, nine-nucleotide Py tract. The U2AF65 linker residues between the dual RNA recognition motifs (RRMs) recognize the central nucleotide, whereas the N- and C-terminal RRM extensions recognize the 3′ terminus and third nucleotide. Single-molecule FRET experiments suggest that conformational selection and induced fit of the U2AF65 RRMs are complementary mechanisms for Py-tract association. Altogether, these results advance the mechanistic understanding of molecular recognition for a major class of splice site signals. PMID:26952537

  15. Response of Nitrosospira sp. Strain AF-Like Ammonia Oxidizers to Changes in Temperature, Soil Moisture Content, and Fertilizer Concentration▿

    PubMed Central

    Avrahami, Sharon; Bohannan, Brendan J. M.

    2007-01-01

    Very little is known regarding the ecology of Nitrosospira sp. strain AF-like bacteria, a unique group of ammonia oxidizers within the Betaproteobacteria. We studied the response of Nitrosospira sp. strain AF-like ammonia oxidizers to changing environmental conditions by applying molecular methods and physiological measurements to Californian grassland soil manipulated in the laboratory. This soil is naturally high in Nitrosospira sp. strain AF-like bacteria relative to the much-better-studied Nitrosospira multiformis-like ammonia-oxidizing bacteria. Increases in temperature, soil moisture, and fertilizer interacted to reduce the relative abundance of Nitrosospira sp. strain AF-like bacteria, although they remained numerically dominant. The overall abundance of ammonia-oxidizing bacteria increased with increasing soil moisture and decreased with increasing temperature. Potential nitrification activity was altered by interactions among temperature, soil moisture, and fertilizer, with activity tending to be higher when soil moisture and temperature were increased. The increase in potential nitrification activity with increased temperature was surprising, given that the overall abundance of ammonia-oxidizing bacteria decreased significantly under these conditions. This observation suggests that (i) Nitrosospira sp. strain AF-like bacteria may respond to increased temperature with an increase in activity, despite a decrease in abundance, or (ii) that potential nitrification activity in these soils may be due to organisms other than bacteria (e.g., archaeal ammonia oxidizers), at least under conditions of increased temperature. PMID:17158615

  16. Relationship between Af temperature and load changes in Ni-Ti orthodontic wire under different thermomechanical conditions.

    PubMed

    Kawashima, I; Ohno, H; Sachdeva, R

    1999-12-01

    Simple three point bending tests were performed on Ni-Ti wires with three different Af points (1 degree C, 13 degrees C and 34 degrees C) to clarify the relationship between Af temperature and load changes under constant deformation. Each wire was deformed at 37 degrees C and then thermal changes were imposed by temperatures of 2 degrees C or 60 degrees C. The load changes with thermal changes from 37 degrees C to 2 degrees C or 60 degrees C showed the same tendency on the wires with different Af points: In the loading stage, the load became lower than the initial level at 37 degrees C and in the unloading stage, the load became higher than the initial load. The largest load change in the unloading stage was measured with the 13 degrees C Af point wire. Care must be taken when handling Ni-Ti wire with an Af point of less than 1 degree C in order to prevent it from reaching the limit of critical stress of slip deformation when the temperature in the mouth rises to above 40 degrees C. PMID:10786161

  17. 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.

  18. Response of Nitrosospira sp. strain AF-like ammonia oxidizers to changes in temperature, soil moisture content, and fertilizer concentration.

    PubMed

    Avrahami, Sharon; Bohannan, Brendan J M

    2007-02-01

    Very little is known regarding the ecology of Nitrosospira sp. strain AF-like bacteria, a unique group of ammonia oxidizers within the Betaproteobacteria. We studied the response of Nitrosospira sp. strain AF-like ammonia oxidizers to changing environmental conditions by applying molecular methods and physiological measurements to Californian grassland soil manipulated in the laboratory. This soil is naturally high in Nitrosospira sp. strain AF-like bacteria relative to the much-better-studied Nitrosospira multiformis-like ammonia-oxidizing bacteria. Increases in temperature, soil moisture, and fertilizer interacted to reduce the relative abundance of Nitrosospira sp. strain AF-like bacteria, although they remained numerically dominant. The overall abundance of ammonia-oxidizing bacteria increased with increasing soil moisture and decreased with increasing temperature. Potential nitrification activity was altered by interactions among temperature, soil moisture, and fertilizer, with activity tending to be higher when soil moisture and temperature were increased. The increase in potential nitrification activity with increased temperature was surprising, given that the overall abundance of ammonia-oxidizing bacteria decreased significantly under these conditions. This observation suggests that (i) Nitrosospira sp. strain AF-like bacteria may respond to increased temperature with an increase in activity, despite a decrease in abundance, or (ii) that potential nitrification activity in these soils may be due to organisms other than bacteria (e.g., archaeal ammonia oxidizers), at least under conditions of increased temperature.

  19. 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

  20. 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).

  1. 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.

  2. 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.

  3. 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

  4. 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. PMID:26183793

  5. The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified

    PubMed Central

    Movérare-Skrtic, Sofia; Börjesson, Anna E.; Farman, Helen H.; Sjögren, Klara; Windahl, Sara H.; Lagerquist, Marie K.; Andersson, Annica; Stubelius, Alexandra; Carlsten, Hans; Gustafsson, Jan-Åke; Ohlsson, Claes

    2014-01-01

    The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-20) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-20 mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-20 mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. PMID:24395795

  6. 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.

  7. 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...

  8. Analyse de l'interface cuivre/Teflon AF1600 par spectroscopie des photoelectrons rayons x

    NASA Astrophysics Data System (ADS)

    Popovici, Dan

    The speed of electrical signals through the microelectronic multilevel interconnects depends of the delay time R x C. In order to improve the transmission speed of future microdevices, the microelectronics industry requires the use of metals having lower resistivities and insulators having lower permittivities. Copper and fluoropolymers are interesting candidates for the replacement of the presently used Al/polyimide technology. This thesis presents an X-ray photoelectron spectroscopy (XPS) analysis of the Cu/Teflon AF1600 interface, in order to have a better understanding of those interfacial interactions leading to improved adhesion. Several deposition methods, such as evaporation, sputtering and laser-induced chemical deposition were analyzed and compared. X-ray photoelectron spectroscopy (XPS) was used as the primary characterization technique of the different surfaces and interfaces. In the case of evaporation and sputtering, the loss of fluorine and oxygen atoms leads to graphitization and the crosslinking of carbon chains. The extent of damage caused by copper deposition is higher for sputter deposition because of the higher energies of the incidents atoms. This energy (two orders of magnitude higher than the energy involved in the evaporation) is also responsible for the total reaction of Cu with F and C. For the physical depositions (sputtering and evaporation), an angle-resolved XPS diffusion study showed the copper distribution as a function of depth. (i) For sputter deposition, this distribution is uniform. (ii) In the case of evaporation, we computed the concentration profile using the inverse Laplace transform. Several samples, annealed at different temperatures, were used to calculate the diffusion coefficients for the Cu/Teflon AF1600 interface. The study of interactions at the interface between Teflon AF1600 and copper deposited by different metallization techniques permitted us to elucidate some aspects related to the chemistry and structure of

  9. Structures, reactivities, and antibiotic properties of the marinopyrroles A-F.

    PubMed

    Hughes, Chambers C; Kauffman, Christopher A; Jensen, Paul R; Fenical, William

    2010-05-21

    Cultivation of actinomycete strain CNQ-418, retrieved from a deep ocean sediment sample off the coast of La Jolla, CA, has provided marinopyrroles A-F. Sharing just 98% 16S rRNA gene sequence identity with S. sannurensis, the strain likely represents a new Streptomyces species. The metabolites contain an unusual 1,3'-bipyrrole core decorated with several chlorine and bromine substituents and possess marked antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The congested N,C-biaryl bond establishes an axis of chirality that, for marinopyrroles A-E, is configurationally stable at room temperature. Moreover, the natural products are fashioned strictly in the M-configuration. The Paal-Knorr condensation was adapted for the synthesis of the 1,3'-bipyrrole core. Halogenation of this material with N-bromosuccinimide cleanly furnished the 4,4',5,5'-tetrahalogenated core that characterizes this class of marine-derived metabolites.

  10. 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

  11. 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.

  12. 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.

  13. Fatigue life estimation program for Part 23 airplanes, `AFS.FOR`

    SciTech Connect

    Kaul, S.K.

    1993-12-31

    The purpose of this paper is to introduce to the general aviation industry a computer program which estimates the safe fatigue life of any Federal Aviation Regulation (FAR) Part 23 airplane. The algorithm uses the methodology (Miner`s Linear Cumulative Damage Theory) and the various data presented in the Federal Aviation Administration (FAA) Report No. AFS-120-73-2, dated May 1973. The program is written in FORTRAN 77 language and is executable on a desk top personal computer. The program prompts the user for the input data needed and provides a variety of options for its intended use. The program is envisaged to be released through issuance of a FAA report, which will contain the appropriate comments, instructions, warnings and limitations.

  14. Verbesinosides A-F, 15,27-cyclooleanane saponins from the American native plant Verbesina virginica.

    PubMed

    Xu, Wen-Hui; Jacob, Melissa R; Agarwal, Ameeta K; Clark, Alice M; Liang, Zong-Suo; Li, Xing-Cong

    2009-06-01

    Verbesinosides A-F (1-6), six new 15,27-cyclooleanane-type triterpenoid saponins carrying different aromatic acyl moieties on the aglycon, were isolated from the leaves and flowers of Verbesina virginica. Their structures were established by interpretation of spectroscopic data and chemical methods. The representative major saponin, verbesinoside A (1), has the structure 21-trimethoxybenzoyl 15alpha,27-cycloolean-12-en-3beta,21beta-diol-28-oic acid 3-O-beta-D-xylopyranosyl(1-->4)-beta-D-xylopyranosyl(1-->2)-beta-D-glucopyranoside. This is the first report of triterpenoid saponins possessing the unique 15,27-cyclooleanane skeleton. The anisotropic effects of the aromatic acyl moieties on the triterpenoid skeleton are discussed.

  15. 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.

  16. 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

  17. Characterization of extractable soil organic matter pools from African Dark Earths (AfDE): A case study in historical biochar and organic waste amendments

    NASA Astrophysics Data System (ADS)

    Fujiu, Manna; Plante, Alain; Ohno, Tsutomu; Solomon, Dawit; Lehmann, Johannes; Fraser, James; Leach, Melissa; Fairhead, James

    2014-05-01

    Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils that were formed from the original highly-weathered infertile yellowish to red Oxisols and Ultisols through an extant but hitherto overlooked climate-smart sustainable soil management system that has long been an important feature of the indigenous West African agricultural repertoire. Studies have demonstrated that ADE soils in general have significantly different organic matter properties compared to adjacent non-DE soils, largely attributable to the presence of high concentrations of ash-derived carbon. Quantification and characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) confirmed substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant or relatively stable, but the goal of the current study was to characterize the presumably labile, more rapidly cycling, pools of C in AfDEs through the characterization of hot water- and pyrophosphate-extractable fractions, referred to as HWEOC and PyroC respectively. Extracts were analyzed for carbon content, as well as composition using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FTICR-MS). The amount of extractable C as a proportion of total soil C was relatively low: less than ~0.8% for HWEOC and 2.8% for PyroC. The proportion of HWEOC did not differ (P = 0.18, paired t-test) between the AfDE and the non-AfDE soils, while the proportions of PyroC were significantly larger (P = 0.001) in the AfDE soils compared to the non-AfDE soils. Preliminary analysis of the EEM/PARAFAC data suggests that AfDE samples had

  18. 26 CFR 1.419A(f)(6)-1 - Exception for 10 or more employer plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... by the recipient. (c) Characteristics indicating a plan is not a 10 or more employer plan—(1) In general. The presence of any of the characteristics described in paragraphs (c)(2) through (c)(6) of this... requirements of section 419A(f)(6) and this section, a plan having any of the following characteristics is...

  19. 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...

  20. 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…

  1. 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

  2. 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.

  3. 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...

  4. Enhancement of the acute phase response to lipopolysaccharide in feedlot steers supplemented with OmniGen-AF

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the effect of supplementing feedlot steers with OmniGen-AF on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 270 ± 5 kilograms body weight) were separated into two treatment groups (n=9/treatment): one group was fed a standard ...

  5. 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...

  6. 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...

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

    PubMed Central

    Anderson, Debra F.; Cheung, Cecilia Y.

    2014-01-01

    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. PMID:25186112

  8. 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.

  9. afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2).

    PubMed

    Floriano, B; Bibb, M

    1996-07-01

    The N-terminal region of AfsR, a putative pleiotropic regulatory protein for antibiotic production in Streptomyces coelicolor A3(2), is homologous to RedD and Actil-ORF4, pathway-specific regulatory proteins required for the production of the antibiotics undecylprodigiosin (Red) and actinorhodin (Act), respectively. The recent identification of afsS, which lies immediately 3' of afsR and which stimulates antibiotic production when cloned at high copy number, questioned whether afsR was a pleiotropic regulatory gene. In this study we demonstrate that multiple copies of afsR can stimulate both Act and Red production and that, despite its homology, it cannot substitute for the pathway-specific regulatory genes. Moreover, an in-frame deletion that removed most of the afsR coding sequence resulted in loss of Act and Red production, and a marked reduction in the synthesis of the calcium-dependent antibiotic (CDA), but only under some (non-permissive) nutritional conditions. Although additional copies of afsR resulted in elevated levels of the actII-ORF4 and redD transcripts, transcription of the pathway-specific regulatory genes under non-permissive conditions was unaffected by deletion of afsR. While afsR may operate independently of the pathway-specific regulatory proteins to influence antibiotic production, the activity of ActII-ORF4 and of RedD under non-permissive conditions could depend on interaction with, or modification by, AfsR.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 46 CFR 160.047-2 - Model.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 6 2013-10-01 2013-10-01 false Model. 160.047-2 Section 160.047-2 Shipping COAST GUARD... § 160.047-2 Model. Each buoyant vest specified in this subpart is a: (a) Model AK-1, adult, kapok (for persons weighing more than 90 pounds); (b) Model AF-1, adult, fibrous glass (for persons weighing...

  15. 46 CFR 160.047-2 - Model.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 6 2014-10-01 2014-10-01 false Model. 160.047-2 Section 160.047-2 Shipping COAST GUARD... § 160.047-2 Model. Each buoyant vest specified in this subpart is a: (a) Model AK-1, adult, kapok (for persons weighing more than 90 pounds); (b) Model AF-1, adult, fibrous glass (for persons weighing...

  16. 46 CFR 160.047-2 - Model.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 6 2012-10-01 2012-10-01 false Model. 160.047-2 Section 160.047-2 Shipping COAST GUARD... § 160.047-2 Model. Each buoyant vest specified in this subpart is a: (a) Model AK-1, adult, kapok (for persons weighing more than 90 pounds); (b) Model AF-1, adult, fibrous glass (for persons weighing...

  17. 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. PMID:25256427

  18. Overlapping binding of PhoP and AfsR to the promoter region of glnR in Streptomyces coelicolor.

    PubMed

    Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F

    2012-10-12

    Growth of soil bacteria is often limited by the availability of essential nutrients such as carbon, nitrogen and phosphate. The reaction to a specific nutrient starvation triggers interconnected responses to equilibrate the metabolism. It is known that PhoP (response regulator involved in phosphate control) specifically binds to several promoters of genes involved in nitrogen metabolism which are also regulated by GlnR (regulator involved in nitrogen control). In this article we report a novel cross-talk between GlnR and the SARP-like regulator, AfsR. AfsR binds to some PhoP-regulated promoters including those of afsS (a small regulatory protein of secondary metabolism), pstS (a component of the phosphate transport system) and phoRP (encoding the two component system itself). We have characterized the regulation exerted upon the nitrogen regulator glnR gene by AfsR, using EMSA and DNase I footprinting assays as well as in vivo expression studies with ΔphoP, ΔafsR and ΔafsR-ΔphoP mutants. Both PhoP and AfsR proteins are able to bind to overlapping regions within the glnR promoter producing different effects. This work demonstrates a cross-talk of three different regulators of both primary and secondary metabolism.

  19. Estimates of Z' couplings within data on the AF B for Drell-Yan process at the LHC at √{s }=7 and 8 TeV

    NASA Astrophysics Data System (ADS)

    Pevzner, A.; Skalozub, V.

    2016-07-01

    A model-independent search for the Abelian Z' gauge boson in the Drell-Yan process at the LHC at √{s }=7 and 8 TeV is fulfilled. Estimations of the Z' axial-vector coupling af2 to the standard model fermions, the couplings of the axial vector to lepton vector currents afvl, and the couplings of the axial vector to quark vector currents afvq are derived within data on the forward-backward asymmetry presented by the CMS Collaboration. The analysis takes into consideration the behavior of the differential cross section, which exhibits itself if the derived already special relations between the couplings proper to the renormalizable theories are accounted for. In particular, they hold in all the models of Abelian Z' usually considered in the model-dependent analysis of the LHC data. The coupling values are estimated at ˜92 % confidence level by means of the maximum likelihood function. They weakly depend on the Z' mass in the investigated interval 1.2 TeV

  20. 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.

  1. 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. PMID:24687081

  2. Penarines A-F, (nor-)sesquiterpene carboxylic acids from Hygrophorus penarius (Basidiomycetes).

    PubMed

    Otto, Alexander; Porzel, Andrea; Schmidt, Jürgen; Wessjohann, Ludger; Arnold, Norbert

    2014-12-01

    Five sesquiterpene carboxylic acids (1-5) and one nor-sesquiterpene carboxylic acid (6) of the very rare ventricosane type, named penarines A-F, were isolated from fruiting bodies of the basidiomycete Hygrophorus penarius (Hygrophoraceae). This is the first report of (nor)-sesquiterpenes isolated from basidiocarps of the family Hygrophoraceae. Their structures were elucidated on the basis of extensive 1D ((1)H, (13)C) and 2D (HSQC, HMBC, COSY, ROESY) NMR spectroscopic analyses as well as high-resolution mass spectrometry studies. Additionally, the only known member of this rare type of sesquiterpenes, ventricos-7(13)-ene (7), could be identified via headspace GC-MS analysis in a fruiting body of H. penarius. Compounds 1-6 were devoid of remarkable antifungal activity against Cladosporium cucumerinum. Additionally, the cytotoxic activities of compounds 1 and 2 were evaluated against the human prostate cancer cell line PC-3 and the colon cancer cell line HT-29 showing no significant cytotoxic activity.

  3. The Detection of a Light Echo from Type Ia SN 2007af in NGC 5584

    NASA Astrophysics Data System (ADS)

    Drozdov, Dina; Leising, M. D.; Milne, P.; Riess, A. G.

    2013-06-01

    We report the discovery of a light echo (LE) at t ~1000 days past maximum from the normal Type Ia supernova (SNe Ia) SN 2007af in the spiral galaxy NGC 5584. The presence of a LE is supported by photometric data and analysis of the images acquired during the Cepheid campaign using the Hubble Space Telescope (HST) Wide Field Camera 3 (Riess et al. 2011). The F350 and F555 images show a distinct ring-like structure with an additional central source. The images, taken months apart, show an evolution of the ring structure, which is consistent with a growing light echo in time. We find an angular radius of the outer echo to be ~0.29'' - 0.36''. Using the Cepheid distance to NGC 5584 of 24 Mpc, we find the dust illuminated by the light echo to be at a distance ~800 pc from the supernova. This rare discovery adds to the select few light echoes found in Type Ia SNe: SN 1572, SN 1991T, SN 1995E, SN 1998bu, and SN 2006X. Light echoes are powerful tools that probe the environment around supernovae, determine dust properties and characteristics, and could provide constraints on the progenitors, which are not fully understood for SN Ia.

  4. 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.

  5. 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.

  6. Detection of a Light Echo from the Otherwise Normal SN 2007af

    NASA Astrophysics Data System (ADS)

    Drozdov, D.; Leising, M. D.; Milne, P. A.; Pearcy, J.; Riess, A. G.; Macri, L. M.; Bryngelson, G. L.; Garnavich, P. M.

    2015-05-01

    We present the discovery of a light echo from SN 2007af, a normal Type Ia supernova (SN Ia) in NGC 5584. Hubble Space Telescope images taken three years post explosion reveal two separate echoes: an outer echo and an extended central region, which we propose to be an inner echo for which details are unresolved. Multiple images were obtained in the F160W, F350LP, F555W, and F814W using the Wide Field Camera 3. If the outer echo is produced by an interstellar dust sheet perpendicular to the line of sight, it is located ∼800 pc in front of the SN. The dust for the inner echo is 0.45 pc \\lt d\\lt 90 pc away from the SN. The inner echo color is consistent with typical interstellar dust wavelength-dependent scattering cross-sections, while the outer echo is redder than predicted. Both dust sheets, if in the foreground, are optically thin for scattering, and the outer echo sheet thickness is consistent with the inferred extinction from peak brightness. Whether the inner echo is from interstellar or circumstellar dust is ambiguous. Overall, the echo characteristics are quite similar to previously observed SN Ia echoes.

  7. 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

  8. Purification, crystallization and preliminary crystallographic analysis of the non-Pfam protein AF1514 from Archeoglobus fulgidus DSM 4304

    SciTech Connect

    Bahti, Pazilat; Chen, Shunmei; Li, Yang; Shaw, Neil; Zhang, Xuejun; Zhang, Min; Cheng, Chongyun; Song, Gaojie; Yin, Jie; Zhang, Hua; Che, Dongsheng; Abbas, Abdulla; Xu, Hao; Wang, Bi-Cheng; Liu, Zhi-Jie

    2008-02-01

    A non-Pfam protein, AF1514, from A. fulgidus has been crystallized. A 10.5 kDa non-Pfam hypothetical protein, AF1514, from the hyperthermophilic archaeon Archeoglobus fulgidus has been overexpressed in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. The crystals diffracted X-rays to 2.09 Å resolution and a data set was collected at 100 K using Cu Kα radiation from a rotating-anode X-ray source. The crystals belong to space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 49.27, c = 106.61 Å. The calculated Matthews coefficient was 3.16 Å{sup 3} Da{sup −1}, suggesting the presence of one molecule in the asymmetric unit.

  9. Human PSENEN and U2AF1L4 genes are concertedly regulated by a genuine bidirectional promoter.

    PubMed

    Didych, D A; Shamsutdinov, M F; Smirnov, N A; Akopov, S B; Monastyrskaya, G S; Uspenskaya, N Y; Nikolaev, L G; Sverdlov, E D

    2013-02-15

    Head-to-head genes with a short distance between their transcription start sites may constitute up to 10% of all genes in the genomes of various species. It was hypothesized that this intergenic space may represent bidirectional promoters which are able to initiate transcription of both genes, but the true bidirectionality was proved only for a few of them. We present experimental evidence that, according to several criteria, a 269 bp region located between the PSENEN and U2AF1L4 human genes is a genuine bidirectional promoter regulating a concerted divergent transcription of these genes. Concerted transcription of PSENEN and U2AF1L4 can be necessary for regulation of T-cell activity. PMID:23246698

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

    PubMed

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

    2015-11-23

    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.

  11. 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.

  12. Rac1 signaling protects monocytic AML cells expressing the MLL-AF9 oncogene from caspase-mediated apoptotic death.

    PubMed

    Hinterleitner, C; Huelsenbeck, J; Henninger, C; Wartlick, F; Schorr, A; Kaina, B; Fritz, G

    2013-08-01

    We investigated the relevance of signaling mechanisms regulated by the Ras-homologous GTPase Rac1 for survival of acute myeloid leukemia (AML) cells harbouring the MLL-AF9 oncogene due to t(9;11)(p21;q23) translocation. Monocytic MLL-AF9 expressing cells (MM6, THP-1) were hypersensitive to both small-molecule inhibitors targeting Rac1 (EHT 1864, NSC 23766) (IC50EHT ~12.5 μM) and lipid lowering drugs (lovastatin, atorvastatin) (IC50Lova ~7.5 μM) as compared to acute myelocytic leukemia (NOMO-1, HL60) and T cell leukemia (Jurkat) cells (IC50EHT >30 μM; IC50Lova >25 μM). Hypersensitivity of monocytic cells following Rac1 inhibition resulted from caspase-driven apoptosis as shown by profound activation of caspase-8,-9,-7,-3 and substantial (~90 %) decrease in protein expression of pro-survival factors (survivin, XIAP, p-Akt). Apoptotic death was preceded by S139-posphorylation of histone H2AX (γH2AX), a prototypical surrogate marker of DNA double-strand breaks (DSBs). Taken together, abrogation of Rac1 signaling causes DSBs in acute monocytic leukemia cells harbouring the MLL-AF9 oncogene, which, together with downregulation of survivin, XIAP and p-Akt, results in massive induction of caspase-driven apoptotic death. Apparently, Rac1 signaling is required for maintaining genetic stability and maintaining survival in specific subtypes of AML. Hence, targeting of Rac1 is considered a promising novel strategy to induce lethality in MLL-AF9 expressing AML. PMID:23624644

  13. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    PubMed Central

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

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  14. 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. PMID:27071942

  15. 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.

  16. The M2 selective antagonist AF-DX 116 shows high affinity for muscarine receptors in bovine tracheal membranes.

    PubMed

    Roffel, A F; in't Hout, W G; de Zeeuw, R A; Zaagsma, J

    1987-05-01

    We have characterized the muscarine receptors in bovine tracheal and left ventricular membranes using 3H-dexetimide/pirenzepine and 3H-dexetimide/AF-DX 116 competition studies. Pirenzepine exhibited low (M2) affinity binding to both preparations; Kd was 590 nM in left ventricle and 463 nM in trachea. AF-DX 116 exhibited high (M2) affinity binding to left ventricle (Kd = 95.6 nM); in tracheal membranes it bound with high (M2) affinity (Kd = 40.7 nM) to 74% of the receptors and with low (M3) affinity (Kd = 2.26 microM) to 26% of the receptors. It is concluded that bovine tracheal muscle membranes contain a heterogeneous population of muscarine binding sites, the majority having M2 (heart) subtype characteristics and being located on the smooth muscle membranes; a minority having M3 (exocrine gland) subtype characteristics and presumed to be located in submucosal glands. This is the first report of high affinity binding of AF-DX 116 to non-cardiac peripheral muscarine receptors. PMID:3614390

  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. 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.

  19. Identification of a recurrent frameshift mutation at the LDLR exon 14 (c.2027delG, p.(G676Afs*33)) causing familial hypercholesterolemia in Saudi Arab homozygous children.

    PubMed

    Al-Allaf, Faisal A; Alashwal, Abdullah; Abduljaleel, Zainularifeen; Taher, Mohiuddin M; Siddiqui, Shahid S; Bouazzaoui, Abdellatif; Abalkhail, Hala; Aun, Rakan; Al-Allaf, Ahmad F; AbuMansour, Iman; Azhar, Zohor; Ba-Hammam, Faisal A; Khan, Wajahatullah; Athar, Mohammad

    2016-01-01

    Familial hypercholesterolemia (FH) is an autosomal dominant disease, predominantly caused by variants in the low-density lipoprotein (LDL) receptor gene (LDLR). Herein, we describe genetic analysis of severely affected homozygous FH patients who were mostly resistant to statin therapy and were managed on an apheresis program. We identified a recurrent frameshift mutation p.(G676Afs*33) in exon 14 of the LDLR gene in 9 probands and their relatives in an apparently unrelated Saudi families. We also describe a three dimensional homology model of the LDL receptor protein (LDLR) structure and examine the consequence of the frameshift mutation p.(G676Afs*33), as this could affect the LDLR structure in a region involved in dimer formation, and protein stability. This finding of a recurrent mutation causing FH in the Saudi population could serve to develop a rapid genetic screening procedure for FH, and the 3D-structure analysis of the mutant LDLR, may provide tools to develop a mechanistic model of the LDLR function.

  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. 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

  2. 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

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

    PubMed

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

    2015-10-01

    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

  4. Hazard identification and risk characterization of bisphenols A, F and AF to aquatic organisms.

    PubMed

    Tišler, Tatjana; Krel, Alja; Gerželj, Urška; Erjavec, Boštjan; Dolenc, Marija Sollner; Pintar, Albin

    2016-05-01

    Production of bisphenol A (BPA) analogues such as bisphenol F (BPF) and bisphenol AF (BPAF) has recently increased, due to clear evidence of adverse effects of BPA on humans and wildlife. Bisphenols (BPs) have already been released into aquatic environment without previous available information about potential adverse effects of BPs and their potential risk to aquatic ecosystems. In this study, lethal and sublethal effects of BPF and BPAF to bacteria, algae, crustacea and fish embryos were investigated and the results were compared to the adverse effects obtained for BPA. We found that BPAF was the most toxic compound to Daphnia magna, Danio rerio and Desmodesmus subspicatus; the lowest 72 h EC50 (median effective concentration) and 21 d NOEC (no observed effect concentration) values were determined at 2.2 mg/L regarding zebrafish hatching success and 0.23 mg/L of BPAF obtained for growth and reproduction of water fleas, respectively. In most cases, BPA was more toxic to D. magna, D. rerio and D. subspicatus in comparison to BPF, but pigmentation of zebrafish embryos after 48 h of exposure and reproduction of water fleas after 21-day D. magna reproductive test exposure to BPF were much more impaired. Risk quotients (measured environmental concentration/21 d NOEC) showed that BPA, BPF and BPAF are recently not chronically hazardous to the survival, reproduction and growth of water fleas in surface waters. On the other hand, we importantly show that currently present BPAF concentrations in surface waters could cause a potential ecological risk to aquatic organisms. In the near future, higher concentrations of BPF and BPAF in surface waters are anticipated and for this reason further testing using test systems with various aquatic species and endpoints are needed to provide additional information about toxic impacts of BPF and BPAF on aquatic biota.

  5. 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

  6. Biotransformation of bisphenol AF to its major glucuronide metabolite reduces estrogenic activity.

    PubMed

    Li, Ming; Yang, Yunjia; Yang, Yi; Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  7. Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice.

    PubMed

    Palotai, Miklós; Telegdy, Gyula; Tanaka, Masaru; Bagosi, Zsolt; Jászberényi, Miklós

    2014-11-01

    Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a α1/α2β-adrenergic receptor antagonist, prazosin or a non-selective β-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice.

  8. Hazard identification and risk characterization of bisphenols A, F and AF to aquatic organisms.

    PubMed

    Tišler, Tatjana; Krel, Alja; Gerželj, Urška; Erjavec, Boštjan; Dolenc, Marija Sollner; Pintar, Albin

    2016-05-01

    Production of bisphenol A (BPA) analogues such as bisphenol F (BPF) and bisphenol AF (BPAF) has recently increased, due to clear evidence of adverse effects of BPA on humans and wildlife. Bisphenols (BPs) have already been released into aquatic environment without previous available information about potential adverse effects of BPs and their potential risk to aquatic ecosystems. In this study, lethal and sublethal effects of BPF and BPAF to bacteria, algae, crustacea and fish embryos were investigated and the results were compared to the adverse effects obtained for BPA. We found that BPAF was the most toxic compound to Daphnia magna, Danio rerio and Desmodesmus subspicatus; the lowest 72 h EC50 (median effective concentration) and 21 d NOEC (no observed effect concentration) values were determined at 2.2 mg/L regarding zebrafish hatching success and 0.23 mg/L of BPAF obtained for growth and reproduction of water fleas, respectively. In most cases, BPA was more toxic to D. magna, D. rerio and D. subspicatus in comparison to BPF, but pigmentation of zebrafish embryos after 48 h of exposure and reproduction of water fleas after 21-day D. magna reproductive test exposure to BPF were much more impaired. Risk quotients (measured environmental concentration/21 d NOEC) showed that BPA, BPF and BPAF are recently not chronically hazardous to the survival, reproduction and growth of water fleas in surface waters. On the other hand, we importantly show that currently present BPAF concentrations in surface waters could cause a potential ecological risk to aquatic organisms. In the near future, higher concentrations of BPF and BPAF in surface waters are anticipated and for this reason further testing using test systems with various aquatic species and endpoints are needed to provide additional information about toxic impacts of BPF and BPAF on aquatic biota. PMID:26957022

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

    PubMed Central

    2012-01-01

    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. PMID:23210797

  10. Electrophysiological Rotor Ablation in In-Silico Modeling of Atrial Fibrillation: Comparisons with Dominant Frequency, Shannon Entropy, and Phase Singularity

    PubMed Central

    Hwang, Minki; Song, Jun-Seop; Lee, Young-Seon; Li, Changyong; Shim, Eun Bo; Pak, Hui-Nam

    2016-01-01

    Background Although rotors have been considered among the drivers of atrial fibrillation (AF), the rotor definition is inconsistent. We evaluated the nature of rotors in 2D and 3D in- silico models of persistent AF (PeAF) by analyzing phase singularity (PS), dominant frequency (DF), Shannon entropy (ShEn), and complex fractionated atrial electrogram cycle length (CFAE-CL) and their ablation. Methods Mother rotor was spatiotemporally defined as stationary reentries with a meandering tip remaining within half the wavelength and lasting longer than 5 s. We generated 2D- and 3D-maps of the PS, DF, ShEn, and CFAE-CL during AF. The spatial correlations and ablation outcomes targeting each parameter were analyzed. Results 1. In the 2D PeAF model, we observed a mother rotor that matched relatively well with DF (>9 Hz, 71.0%, p<0.001), ShEn (upper 2.5%, 33.2%, p<0.001), and CFAE-CL (lower 2.5%, 23.7%, p<0.001). 2. The 3D-PeAF model also showed mother rotors that had spatial correlations with DF (>5.5 Hz, 39.7%, p<0.001), ShEn (upper 8.5%, 15.1%, p <0.001), and CFAE (lower 8.5%, 8.0%, p = 0.002). 3. In both the 2D and 3D models, virtual ablation targeting the upper 5% of the DF terminated AF within 20 s, but not the ablations based on long-lasting PS, high ShEn area, or lower CFAE-CL area. Conclusion Mother rotors were observed in both 2D and 3D human AF models. Rotor locations were well represented by DF, and their virtual ablation altered wave dynamics and terminated AF. PMID:26909492

  11. 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

  12. 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.

  13. 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.

  14. Improved Neurological Outcome by Intramuscular Injection of Human Amniotic Fluid Derived Stem Cells in a Muscle Denervation Model

    PubMed Central

    Su, Hong-Lin; Sheu, Meei-Ling; Lu, Zong-Han; Chiang, Chien-Yi; Yang, Dar-Yu; Sheehan, Jason; Pan, Hung-Chuan

    2015-01-01

    Purpose The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS) have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model. Materials and Methods Seventy two Sprague-Dawley rats weighing 200–250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups. Results NT-3 (Neurotrophin 3), BDNF (Brain derived neurotrophic factor), CNTF (Ciliary neurotrophic factor), and GDNF (Glia cell line derived neurotrophic factor) were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index) and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology. Conclusion Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection

  15. Single-Unit Activity during Natural Vision: Diversity, Consistency, and Spatial Sensitivity among AF Face Patch Neurons

    PubMed Central

    Russ, Brian E.; Elnaiem, Heba D.; Kurnikova, Anastasia I.; Leopold, David A.

    2015-01-01

    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. PMID:25855170

  16. 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

    2015-04-01

    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.

  17. 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

    2015-04-01

    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. PMID:25855170

  18. Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

    PubMed

    Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

    2014-04-01

    Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

  19. 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

  20. 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

  1. The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79.

    PubMed

    Chen, Shoudeng; Yang, Ze; Wilkinson, Alex W; Deshpande, Aniruddha J; Sidoli, Simone; Krajewski, Krzysztof; Strahl, Brian D; Garcia, Benjamin A; Armstrong, Scott A; Patel, Dinshaw J; Gozani, Or

    2015-10-15

    AF10, a DOT1L cofactor, is required for H3K79 methylation and cooperates with DOT1L in leukemogenesis. However, the molecular mechanism by which AF10 regulates DOT1L-mediated H3K79 methylation is not clear. Here we report that AF10 contains a "reader" domain that couples unmodified H3K27 recognition to H3K79 methylation. An AF10 region consisting of a PHD finger-Zn knuckle-PHD finger (PZP) folds into a single module that recognizes amino acids 22-27 of H3, and this interaction is abrogated by H3K27 modification. Structural studies reveal that H3 binding triggers rearrangement of the PZP module to form an H3(22-27)-accommodating channel and that the unmodified H3K27 side chain is encased in a compact hydrogen-bond acceptor-lined cage. In cells, PZP recognition of H3 is required for H3K79 dimethylation, expression of DOT1L-target genes, and proliferation of DOT1L-addicted leukemic cells. Together, our results uncover a pivotal role for H3K27-via readout by the AF10 PZP domain-in regulating the cancer-associated enzyme DOT1L.

  2. Comparing the Disinfecting Efficacies of Micro 10, Deconex, Alprocid and Microzid AF on the Microorganisms on Radiographic Equipments

    PubMed Central

    Ezoddini Ardakani, Fatemeh; Zandi, Hengameh; Mohammadi, Zahed; Ayatollahi, Jamshid; Ayatollahi, Fatemeh; Behniafar, Behnaz

    2008-01-01

    Background and aims The exposure and processing of dental radiographs are not routinely associated with the spatter of blood or saliva; however, infection control is still an issue resulting from contaminated equipment, supplies, film packets or cassettes. This study aimed at comparing the efficacy of four commercially available disinfectants on microorganisms present on the equipment of radiology department. Materials and methods Samples from twelve sites of the radiology department were collected using a sterile swab smeared with normal saline, which was then dipped in a test tube. Experimental surfaces were then disinfected by the spray-wipe-spray method using one of Micro 10, Deconex, Alprocid or Microzid AF disinfectants, followed by resampling. The samples were subsequently cultured on blood agar and EMB plates and the colonies were counted. Isolates were identified by biochemical tests. For statistical analysis, Wilcoxon signed ranks test, Kruskal-Wallis, Chi-square and Fisher exact tests were used. Results Staphylococcus aureus and coagulase-negative staphylococci had the highest and Lactobacillus spp. had the lowest prevalence before disinfection. There were significant differences between the cfu/mL of bacteria before and after disinfection with any of the four disinfectant solutions. There was a significant difference between efficacy of Deconex and Alprocid (P = 0.014), Deconex and Microzid AF (P = 0.001), and Deconex and Micro 10 (P = 0.001). Conclusion According to the results, Deconex has the highest disinfectant efficacy compared to other solutions. PMID:23289058

  3. L17A/F19A Substitutions Augment the α-Helicity of β-Amyloid Peptide Discordant Segment

    PubMed Central

    Wang, Chih-Ching; Chen, Yi-Ru; Chang, Chi-Fon; Shiao, Ming-Shi; Chen, Yi-Cheng; Lin, Ta-Hsien

    2016-01-01

    β-amyloid peptide (Aβ) aggregation has been thought to be associated with the pathogenesis of Alzheimer’s disease. Recently, we showed that L17A/F19A substitutions may increase the structural stability of wild-type and Arctic-type Aβ40 and decrease the rates of structural conversion and fibril formation. However, the underlying mechanism for the increase of structural stability as a result of the alanine substitutions remained elusive. In this study, we apply nuclear magnetic resonance and circular dichroism spectroscopies to characterize the Aβ40 structure, demonstrating that L17A/F19A substitutions can augment the α-helicity of the residues located in the α/β-discordant segment (resides 15 to 23) of both wild-type and Arctic-type Aβ40. These results provide a structural basis to link the α-helicity of the α/β-discordant segment with the conformational conversion propensity of Aβ. PMID:27104649

  4. Security-reliability performance of cognitive AF relay-based wireless communication system with channel estimation error

    NASA Astrophysics Data System (ADS)

    Gu, Qi; Wang, Gongpu; Gao, Li; Peng, Mugen

    2014-12-01

    In this paper, both the security and the reliability performance of the cognitive amplify-and-forward (AF) relay system are analyzed in the presence of the channel estimation error. The security and the reliability performance are represented by the outage probability and the intercept probability, respectively. Instead of perfect channel state information (CSI) predominantly assumed in the literature, a certain channel estimation algorithm and the influence of the corresponding channel estimation error are considered in this study. Specifically, linear minimum mean square error estimation (LMMSE) is utilized by the destination node and the eavesdropper node to obtain the CSI, and the closed form for the outage probability and that for the intercept probability are derived with the channel estimation error. It is shown that the transmission security (reliability) can be improved by loosening the reliability (security) requirement. Moreover, we compare the security and reliability performance of this relay-based cognitive radio system with those of the direct communication system without relay. Interestingly, it is found that the AF relay-based system has less reliability performance than the direct cognitive radio system; however, it can lower the sum of the outage probability and the intercept probability than the direct communication system. It is also found that there exists an optimal training number to minimize the sum of the outage probability and the intercept probability.

  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. Second-hand Smoke Increases Nitric Oxide and Alters the IgE Response in a Murine Model of Allergic Aspergillosis

    PubMed Central

    Seymour, Brian W. P.; Peake, Janice L.; Pinkerton, Kent E.; Kurup, Viswanath P.; Gershwin, Laurel J.

    2005-01-01

    This study was performed to determine the effects of environmental tobacco smoke (ETS) on nitric oxide (NO) and immunoglobulin (Ig) production in a murine model of allergic bronchopulmonary aspergillosis (ABPA). Adult BALB/c mice were exposed to aged and diluted sidestream cigarette smoke from day 0 through day 43 to simulate “second-hand smoke”. During exposure, mice were sensitized to soluble Aspergillus fumigatus (Af) antigen intranasally between day 14 and 24. All Af sensitized mice in ambient air (Af + AIR) made elevated levels of IgE, IgG1, IgM, IgG2a and IgA. Af sensitized mice housed in ETS (Af + ETS) made similar levels of immunoglobulins except for IgE that was significantly reduced in the serum and bronchoalveolar lavage (BAL). However, immunohistochemical evaluation of the lung revealed a marked accumulation of IgE positive cells in the lung parenchyma of these Af + ETS mice. LPS stimulation of BAL cells revealed elevated levels of NO in the Af + AIR group, which was further enhanced in the Af+ETS group. In vitro restimulation of the BAL cells on day 45 showed a TH0 response with elevated levels of IL3, 4, 5, 10 and IFN-γ. However, by day 28 the response shifted such that TH2 cytokines increased while IFN-γ decreased. The Af + ETS group showed markedly reduced levels in all cytokines tested, including the inflammatory cytokine IL6, when compared to the Af+AIR group. These results demonstrate that ETS affects ABPA by further enhancing the NO production and reduces the TH2 and the inflammatory cytokines while altering the pattern of IgE responses. PMID:16050142

  7. 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.

  8. DNA Methylation Is Linked to Deacetylation of Histone H3, but Not H4, on the Imprinted Genes Snrpn and U2af1-rs1

    PubMed Central

    Gregory, Richard I.; Randall, Tamzin E.; Johnson, Colin A.; Khosla, Sanjeev; Hatada, Izuho; O'Neill, Laura P.; Turner, Bryan M.; Feil, Robert

    2001-01-01

    The relationship between DNA methylation and histone acetylation at the imprinted mouse genes U2af1-rs1 and Snrpn is explored by chromatin immunoprecipitation (ChIP) and resolution of parental alleles using single-strand conformational polymorphisms. The U2af1-rs1 gene lies within a differentially methylated region (DMR), while Snrpn has a 5′ DMR (DMR1) with sequences homologous to the imprinting control center of the Prader-Willi/Angelman region. For both DMR1 of Snrpn and the 5′ untranslated region (5′-UTR) and 3′-UTR of U2af1-rs1, the methylated and nonexpressed maternal allele was underacetylated, relative to the paternal allele, at all H3 lysines tested (K14, K9, and K18). For H4, underacetylation of the maternal allele was exclusively (U2af1-rs1) or predominantly (Snrpn) at lysine 5. Essentially the same patterns of differential acetylation were found in embryonic stem (ES) cells, embryo fibroblasts, and adult liver from F1 mice and in ES cells from mice that were dipaternal or dimaternal for U2af1-rs1. In contrast, in a region within Snrpn that has biallelic methylation in the cells and tissues analyzed, the paternal (expressed) allele showed relatively increased acetylation of H4 but not of H3. The methyl-CpG-binding-domain (MBD) protein MeCP2 was found, by ChIP, to be associated exclusively with the maternal U2af1-rs1 allele. To ask whether DNA methylation is associated with histone deacetylation, we produced mice with transgene-induced methylation at the paternal allele of U2af1-rs1. In these mice, H3 was underacetylated across both the parental U2af1-rs1 alleles whereas H4 acetylation was unaltered. Collectively, these data are consistent with the hypothesis that CpG methylation leads to deacetylation of histone H3, but not H4, through a process that involves selective binding of MBD proteins. PMID:11463825

  9. A porcine model of early atrial fibrillation using a custom-built, radio transmission-controlled pacemaker.

    PubMed

    Schwarzl, Michael; Alogna, Alessio; Zweiker, David; Verderber, Jochen; Huber, Stefan; Manninger, Martin; Scherr, Daniel; Antoons, Gudrun; Pieske, Burkert M; Post, Heiner; Lueger, Andreas

    2016-01-01

    Mechanisms underlying atrial remodeling toward atrial fibrillation (AF) are incompletely understood. We induced AF in 16 pigs by 6weeks of rapid atrial pacing (RAP, 600bpm) using a custom-built, telemetrically controlled pacemaker. AF evolution was monitored three times per week telemetrically in unstressed, conscious animals. We established a dose-response relationship between RAP duration and occurrence of sustained AF >60minutes. Left atrial (LA) dilatation was present already at 2weeks of RAP. There was no evidence of left ventricular heart failure after 6weeks of RAP. As a proof-of-principle, arterial hypertension was induced in 5/16 animals by implanting desoxycorticosterone acetate (DOCA, an aldosterone-analog) subcutaneously to accelerate atrial remodeling. RAP+DOCA resulted in increased AF stability with earlier onset of sustained AF and accelerated anatomical atrial remodeling with more pronounced LA dilatation. This novel porcine model can serve to characterize effects of maladaptive stimuli or protective interventions specifically during early AF. PMID:26803554

  10. Phase transition of anisotropic frustrated Heisenberg model on the square lattice.

    PubMed

    Hu, Ai-Yuan; Wang, Huai-Yu

    2016-01-01

    We have investigated the J_{1}-J_{2} Heisenberg model with exchange anisotropy on a square lattice and focused on possible AF1-AF2 phase transition below the Néel point and its dependence on the exchange anisotropy, where AF1 and AF2 represent Néel state and collinear state, respectively. We use the double-time Green's-function method and adopt the random-phase approximation. The less the exchange anisotropy, the stronger the quantum fluctuation of the system will be. Both the Néel state and collinear state can exist and have the same Néel temperature for arbitrary anisotropy and spin quantum number S when J_{2}/J_{1}=0.5. Under such parameters, the calculated free energies show that there may occur a first-order phase transition between the Néel state and collinear state for an arbitrary S when anisotropy is not strong. PMID:26871025

  11. 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.

  12. 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.

  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. Stabilization of Long-Range Order by Additional Anisotropic Spins in Two-Dimensional Isotropic Heisenberg Antiferromagnets —A Possible Model of an Organic Compound with Magnetic Anions—

    NASA Astrophysics Data System (ADS)

    Shimahara, Hiroshi; Ito, Kazuhiro

    2014-11-01

    We examine a two-dimensional (2D) coupled antiferromagnetic (AF) Heisenberg model that consists of two subsystems: an isotropic S = 1/2 spin subsystem with strong AF exchange interactions (main system), and a uniaxial S = 5/2 spin subsystem with weak exchange interactions. This model is an example in which additional semiclassical degrees of freedom affect a quantum system; it also describes a possible stabilization mechanism of AF long-range order (LRO) in the 2D organic compound λ-(BETS)2FeCl4, where BETS stands for bis(ethylenedithio)tetraselenafulvalene. Previous experimental studies have revealed that 3d spins on FeCl4 anions passively follow the AF LRO of the π-electron system in the BETS layers, although the AF LRO is stabilized by the 3d spins themselves. To explain this paradoxical behavior, we examine a scenario in which the uniaxial anisotropy of the 3d spins stabilizes the AF LRO on an isotropic 2D π-spin system. We extend Green's function theory, called the Tyablikov approximation, to the present system, which describes spin-wave excitations and is consistent with the Mermin-Wagner theorem. It is shown that even extremely weak interactions with the uniaxial subsystem efficiently stabilize the AF LRO in the main system, even in the absence of AF exchange interactions in the uniaxial subsystem. The AF LRO is triggered by the uniaxial subsystem, but the sublattice magnetization remains smaller than that of the main system in the high-temperature region. These results are consistent with experimental data for λ-(BETS)2FeCl4 and λ-(BETS)2GaCl4; the latter does not have the 3d spins and does not exhibit the AF LRO.

  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. Ceylonamides A-F, Nitrogenous Spongian Diterpenes That Inhibit RANKL-Induced Osteoclastogenesis, from the Marine Sponge Spongia ceylonensis.

    PubMed

    El-Desoky, Ahmed H; Kato, Hikaru; Angkouw, Esther D; Mangindaan, Remy E P; de Voogd, Nicole J; Tsukamoto, Sachiko

    2016-08-26

    Seven new spongian diterpenes, ceylonamides A-F (1-6) and 15α,16-dimethoxyspongi-13-en-19-oic acid (7), were isolated from the Indonesian marine sponge Spongia ceylonensis along with eight known spongian diterpenes, 8-15. Compounds 1-6 were determined to be nitrogenous spongian diterpenes. The isolated compounds were examined for the inhibition of RANKL-induced osteoclastogenesis in RAW264 macrophages. Ceylonamide A (1) exhibited the most potent inhibitory activity with an IC50 value of 13 μM, followed by ceylonamide B (2) (IC50, 18 μM). An examination of the structure-activity relationships of the isolated compounds revealed that the position of the carbonyl group of the γ-lactam ring and bulkiness of the substituent at its nitrogen atom were important for inhibitory activity. PMID:27526327

  17. Proteasome Inhibitors Evoke Latent Tumor Suppression Programs in Pro-B MLL Leukemias Through MLL-AF4

    PubMed Central

    Liu, Han; Westergard, Todd D.; Cashen, Amanda; Piwnica-Worms, David R.; Kunkle, Lori; Vij, Ravi; Pham, Can G.; DiPersio, John; Cheng, Emily H.; Hsieh, James J.

    2014-01-01

    SUMMARY Chromosomal translocations disrupting MLL generate MLL-fusion proteins that induce aggressive leukemias. Unexpectedly, MLL-fusion proteins are rarely observed at high levels, suggesting excessive MLL-fusions may be incompatible with a malignant phenotype. Here, we used clinical proteasome inhibitors, bortezomib and carfilzomib, to reduce the turnover of endogenous MLL-fusions and discovered that accumulated MLL-fusions induce latent, context-dependent tumor suppression programs. Specifically, in MLL pro-B lymphoid, but not myeloid, leukemias, proteasome inhibition triggers apoptosis and cell cycle arrest involving activation cleavage of BID by Caspase-8 and upregulation of p27, respectively. Furthermore, proteasome inhibition conferred preliminary benefit to MLL-AF4 leukemia patients. Hence, feasible strategies to treat cancer-type and oncogene specific cancers can be improvised through harnessing inherent tumor suppression properties of individual oncogenic fusions. PMID:24735925

  18. VizieR Online Data Catalog: Rotation in A-F stars (Ammler-von Eiff+, 2012)

    NASA Astrophysics Data System (ADS)

    Ammler-von Eiff, M.; Reiners, A.

    2012-04-01

    Measurements of projected rotational velocities and the rotational profile of stars with spectral types A-F are presented. This work completes previous measurements by line profile analysis. New spectra with high signal-to-noise ratio were taken with the high-resolution CES and FEROS spectrographs operated by ESO at La Silla, Chile. Stellar rotation is studied in inverse wavelength space analysing the first two zeros of the Fourier transform of the overall broadening profile. Rigid and differential rotation can be distinguished in the case of rapid rotation. New and previous measurements are compiled and made available. The data are supplemented by a homogeneous compilation of basic stellar data from photometry. Data are flagged when there are indications of multiplicity. (2 data files).

  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. Relay-and-antenna selection and digital transceiver design for two-way AF-MIMO multiple-relay systems

    NASA Astrophysics Data System (ADS)

    Hu, Chia-Chang; Su, Hao-Hsian; Tang, Kang-Tsao

    2014-09-01

    This paper considers a two-way multiple-input multiple-output (MIMO) relaying system with multiple relays between two terminals nodes. The relay antenna selection scheme based on channel singular valued decomposition (SVD) is used to reduce energy consumption. To enhance the system performance, we apply a SVD-based algorithm with MSE criterion which calculates optimal linear transceivers precoding jointly at the source nodes and relay nodes for amplify-and-forward (AF) protocols. In computer simulations, we use an iteration method to compute the non-convex function of joint source and relays power allocation. The simulation results show the SVD-based precoding design with SVD-based relay and antenna selection scheme can achieve a superior system bit error rate (BER) performance and reduce the power consume of relay antennas.

  1. Versixanthones A-F, Cytotoxic Xanthone-Chromanone Dimers from the Marine-Derived Fungus Aspergillus versicolor HDN1009.

    PubMed

    Wu, Guangwei; Yu, Guihong; Kurtán, Tibor; Mándi, Attila; Peng, Jixing; Mo, Xiaomei; Liu, Ming; Li, Hui; Sun, Xinhua; Li, Jing; Zhu, Tianjiao; Gu, Qianqun; Li, Dehai

    2015-11-25

    Six unusual xanthone-chromanone dimers, versixanthones A-F (1-6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1-6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone-chromanone dimers and supported the assignments of their absolute configurations. Compounds 1-6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 μM. Compound 5 showed further inhibitory activity against topoisomerase I. PMID:26506221

  2. 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.

  3. Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628

    PubMed Central

    Finnema, Sjoerd J.; Stepanov, Vladimir; Takano, Akihiro; Tóth, Miklós; Svedberg, Marie; Møller Nielsen, Søren; Khanzhin, Nikolay A.; Juhl, Karsten; Bang-Andersen, Benny; Halldin, Christer; Farde, Lars

    2016-01-01

    Background: Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein. Methods: A novel neurokinin 3 receptor radioligand, [18F]Lu AF10628 ((S)-N-(cyclobutyl(3-fluorophenyl)methyl)-8-fluoro-2-((3-[18F]-fluoropropyl)amino)-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey. Results: The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding. Conclusion: Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties. PMID:26993630

  4. Production of an extracellular alkaline metalloprotease from a newly isolated, moderately halophile, Salinivibrio sp. strain AF-2004.

    PubMed

    Ali Amoozegar, Mohammad; Zahra Fatemi, Azadeh; Reza Karbalaei-Heidari, Hamid; Reza Razavi, Mohamad

    2007-01-01

    An extracellular protease was produced under stress conditions of high temperature and high salinity by a newly isolated moderate halophile, Salinivibrio sp. strain AF-2004 in a basal medium containing peptone, beef extract, glucose and NaCl. A modification of Kunitz method was used for protease assay. The isolate was capable of producing protease in the presence of sodium chloride, sodium sulfate, sodium nitrate, sodium nitrite, potassium chloride, sodium acetate and sodium citrate. The maximum protease was secreted in the presence of 7.5 to 10% (w/v) sodium sulfate or 3% (w/v) sodium acetate (4.6 U ml(-1)). Various carbon sources including glucose, lactose, casein and peptone were capable of inducing enzyme production. The optimum pH, temperature and aeration for enzyme production were 9.0, 32 degrees C and 220 rpm, respectively. The enzyme production corresponded with growth and reached a maximum level during the mid-stationary phase. Maximum protease activity was exhibited in the medium containing 1% (w/v) NaCl at 60 degrees C, with 18% and 41% activity reductions at temperature 50 and 70 degrees C, respectively. The optimum pH for enzyme activity was 8.5, with 86% and 75% residual activities at pH 10 and 6, respectively. The activity of enzyme was inhibited by EDTA. These results suggest that the protease secreted by Salinivibrio sp. strain AF-2004 is industrially important from the perspectives of its activity at a broad pH ranges (5.0-10.0), its moderate thermoactivity in addition to its high tolerance to a wide range of salt concentration (0-10% NaCl).

  5. Characterization of Silver Nanoparticles under Environmentally Relevant Conditions Using Asymmetrical Flow Field-Flow Fractionation (AF4)

    PubMed Central

    Jang, Min-Hee; Lee, Seungho; Hwang, Yu Sik

    2015-01-01

    The development of methods to monitor manufactured nanomaterials in the environment is one of the crucial areas for the assessment of their risk. More specifically, particle size analysis is a key element, because many properties of nanomaterial are size dependent. The sizing of nanomaterials in real environments is challenging due to their heterogeneity and reactivity with other environmental components. In this study, the fractionation and characterization of a mixture of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) of three different sizes were investigated using asymmetrical flow field-flow fractionation (AF4) coupled with UV-Vis spectrophotometry. In particular, the effects of electrolyte composition and natural organic matter (NOM) on the particle size and stability were evaluated. The fractogram peaks (i.e., stability) of three different AgNPs decreased in the presence of both 10 mM NaCl and 10mM CaCl2, while increased with increasing concentration of humic acid (HA). In addition, the hydrodynamic diameters of AgNPs in both electrolytes slightly increased with an increase of HA concentration, suggesting the adsorption (coating) of HA onto the particle surface. It is also interesting to note that an increase in the particle size depended on the types of electrolyte, which could be explained by the conformational characteristics of the adsorbed HA layers. Consistent these results, AgNPs suspended in lake water containing relatively high concentration of organic carbon (TOC) showed higher particle stability and larger particle size (i.e., by approximately 4nm) than those in river water. In conclusion, the application of AF4 coupled with highly sensitive detectors could be a powerful method to characterize nanoparticles in natural waters. PMID:26575993

  6. Characterization of Silver Nanoparticles under Environmentally Relevant Conditions Using Asymmetrical Flow Field-Flow Fractionation (AF4).

    PubMed

    Jang, Min-Hee; Lee, Seungho; Hwang, Yu Sik

    2015-01-01

    The development of methods to monitor manufactured nanomaterials in the environment is one of the crucial areas for the assessment of their risk. More specifically, particle size analysis is a key element, because many properties of nanomaterial are size dependent. The sizing of nanomaterials in real environments is challenging due to their heterogeneity and reactivity with other environmental components. In this study, the fractionation and characterization of a mixture of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) of three different sizes were investigated using asymmetrical flow field-flow fractionation (AF4) coupled with UV-Vis spectrophotometry. In particular, the effects of electrolyte composition and natural organic matter (NOM) on the particle size and stability were evaluated. The fractogram peaks (i.e., stability) of three different AgNPs decreased in the presence of both 10 mM NaCl and 10 mM CaCl2, while increased with increasing concentration of humic acid (HA). In addition, the hydrodynamic diameters of AgNPs in both electrolytes slightly increased with an increase of HA concentration, suggesting the adsorption (coating) of HA onto the particle surface. It is also interesting to note that an increase in the particle size depended on the types of electrolyte, which could be explained by the conformational characteristics of the adsorbed HA layers. Consistent these results, AgNPs suspended in lake water containing relatively high concentration of organic carbon (TOC) showed higher particle stability and larger particle size (i.e., by approximately 4 nm) than those in river water. In conclusion, the application of AF4 coupled with highly sensitive detectors could be a powerful method to characterize nanoparticles in natural waters. PMID:26575993

  7. 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

  8. Phase Diagram of the Antiferromagnetic Blume-Capel Model on Triangular Lattice

    NASA Astrophysics Data System (ADS)

    Park, Sojeong; Kwak, Wooseop

    2016-08-01

    We perform Monte-Carlo simulations of the anti-ferromagnetic (AF) spin-1 Blume- Capel (BC) model and the AF Ising model on triangular lattice. We estimate the exact critical magnetic fields for both models at zero temperature using the Wang-Landau sampling method. We also show the phase diagrams and the critical lines for the models using the joint density functions. We find that the shapes of critical lines for the models are identical, but the phase transitions across the critical lines are different.

  9. 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

    ... potential costs or burdens, explain how you arrived at your estimate in sufficient detail to allow for it to... enforcement of environmental laws, regulations, and policies. To help address potential environmental justice... residues of the antifungal ] agent, Aspergillus flavus AF36, in or on corn food and feed commodities....

  10. 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.

  11. 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.

  12. Alteration of the SETBP1 Gene and Splicing Pathway Genes SF3B1, U2AF1, and SRSF2 in Childhood Acute Myeloid Leukemia

    PubMed Central

    Choi, Hyun-Woo; Kim, Hye-Ran; Baek, Hee-Jo; Kook, Hoon; Cho, Duck; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook

    2015-01-01

    Background Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. Methods Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. Results Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. Conclusions Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood. PMID:25553291

  13. 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.

  14. 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.

  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. Gestational and lactational exposure to bisphenol AF in maternal rats increases testosterone levels in 23-day-old male offspring.

    PubMed

    Li, Jing; Sheng, Nan; Cui, Ruina; Feng, Yixing; Shao, Bing; Guo, Xuejiang; Zhang, Hongxia; Dai, Jiayin

    2016-11-01

    During prenatal and postnatal development, exposure to environmental chemicals with estrogenic activity, such as bisphenol AF (BPAF), may result in reproductive disorders. Currently, the mechanisms behind such disorders in male offspring induced by gestational and lactational exposure to BPAF remain poorly understood. Here, female rats from gestational day (GD) 3-19 were exposed to 100 mg BPAF/kg/day by oral gavage. On the day of birth (postnatal day (PD) 0), cross-fostering took place between treated and control litters, and cross-fostered mother rats were given BPAF 100 mg/kg/day during the postnatal period (PD 3 to PD 19). HPLC-MS/MS analysis showed that BPAF was transferred via cord blood and lactation, finally bio-accumulating in the offspring testes. Pups exposed to BPAF both prenatally and postnatally showed a significant increase in testis testosterone levels compared with that of the control, while all pups exposed to BPAF showed a significant decrease in testis inhibin B (INHB) levels. Compared with the control, RNA-seq revealed that 279 genes were significantly differentially expressed in the testes of pups exposed to BPAF both prenatally and postnatally, including genes involved in cell differentiation and meiosis. These results indicate that gestational and lactational exposure to BPAF in the mother can impair reproductive function in male offspring. PMID:27567155

  18. Rhizovarins A-F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189.

    PubMed

    Gao, Shu-Shan; Li, Xiao-Ming; Williams, Katherine; Proksch, Peter; Ji, Nai-Yun; Wang, Bin-Gui

    2016-08-26

    Genome mining of the fungus Mucor irregularis (formerly known as Rhizomucor variabilis) revealed the presence of various gene clusters for secondary metabolite biosynthesis, including several terpene-based clusters. Investigation into the chemical diversity of M. irregularis QEN-189, an endophytic fungus isolated from the fresh inner tissue of the marine mangrove plant Rhizophora stylosa, resulted in the discovery of 20 structurally diverse indole-diterpenes including six new compounds, namely, rhizovarins A-F (1-6). Among them, compounds 1-3 represent the most complex members of the reported indole-diterpenes. The presence of an unusual acetal linked to a hemiketal (1) or a ketal (2 and 3) in an unprecedented 4,6,6,8,5,6,6,6,6-fused indole-diterpene ring system makes them chemically unique. Their structures and absolute configurations were elucidated by spectroscopic analysis, modified Mosher's method, and chemical calculations. Each of the isolated compounds was evaluated for antitumor activity against HL-60 and A-549 cell lines. PMID:27462726

  19. 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.

  20. 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

  1. Uptake, depuration and bioconcentration of bisphenol AF (BPAF) in whole-body and tissues of zebrafish (Danio rerio).

    PubMed

    Shi, Jiachen; Yang, Yunjia; Zhang, Jing; Feng, Yixing; Shao, Bing

    2016-10-01

    Bisphenol AF (BPAF) is an analog of Bisphenol A (BPA) and is widely used as a raw material in the plastics industry. However, an understanding of the potential risks posed by BPAF in the aquatic environment is lacking. The bioconcentration factor (BCF) is a measure used to assess the secondary poisoning potential as well as risks to human health. In this work we measured the accumulation and elimination of BPAF in the whole-body and in liver, muscle and gonad tissues of zebrafish. BPAF uptake was relatively rapid with equilibrium concentrations reached after 24-72h of exposure. We observed gender differences both in whole-body and in tissue accumulation. Muscle was the primary BPAF storage tissue during the uptake phase in this study. In the elimination phase, BPAF concentrations declined rapidly during depuration, especially during the initial 2h, and the rate of elimination in males was faster than females from the whole-body and from tissues. The appearance of BPAF glucuronide (BPAF-G) at the start of the uptake phase indicated the rapid biotransformation of BPAF to BPAF-G in vivo. The high lipid content of female gonad could act to delay the diffusion of the xenobiotic within the body in a contaminated environment, but it also acts to delay xenobiotic elimination from the body. PMID:27362491

  2. Gestational and lactational exposure to bisphenol AF in maternal rats increases testosterone levels in 23-day-old male offspring.

    PubMed

    Li, Jing; Sheng, Nan; Cui, Ruina; Feng, Yixing; Shao, Bing; Guo, Xuejiang; Zhang, Hongxia; Dai, Jiayin

    2016-11-01

    During prenatal and postnatal development, exposure to environmental chemicals with estrogenic activity, such as bisphenol AF (BPAF), may result in reproductive disorders. Currently, the mechanisms behind such disorders in male offspring induced by gestational and lactational exposure to BPAF remain poorly understood. Here, female rats from gestational day (GD) 3-19 were exposed to 100 mg BPAF/kg/day by oral gavage. On the day of birth (postnatal day (PD) 0), cross-fostering took place between treated and control litters, and cross-fostered mother rats were given BPAF 100 mg/kg/day during the postnatal period (PD 3 to PD 19). HPLC-MS/MS analysis showed that BPAF was transferred via cord blood and lactation, finally bio-accumulating in the offspring testes. Pups exposed to BPAF both prenatally and postnatally showed a significant increase in testis testosterone levels compared with that of the control, while all pups exposed to BPAF showed a significant decrease in testis inhibin B (INHB) levels. Compared with the control, RNA-seq revealed that 279 genes were significantly differentially expressed in the testes of pups exposed to BPAF both prenatally and postnatally, including genes involved in cell differentiation and meiosis. These results indicate that gestational and lactational exposure to BPAF in the mother can impair reproductive function in male offspring.

  3. 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.

  4. 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.

  5. Cloning, overexpression and biocatalytic exploration of a novel Baeyer-Villiger monooxygenase from Aspergillus fumigatus Af293

    PubMed Central

    2013-01-01

    The presence of several putative Baeyer-Villiger Monooxygenases (BVMOs) encoding genes in Aspergillus fumigatus Af293 was demonstrated for the first time. One of the identified BVMO-encoding genes was cloned and successfully overexpressed fused to the cofactor regenerating enzyme phosphite dehydrogenase (PTDH). The enzyme named BVMOAf1 was extensively characterized in terms of its substrate scope and essential kinetic features. It showed high chemo-, regio- and stereoselectivity not only in the oxidation of asymmetric sulfides, (S)-sulfoxides were obtained with 99% ee, but also in the kinetic resolution of bicyclo[3.2.0]hept-2-en-6-one. This kinetic resolution process led to the production of (1S,5R) normal lactone and (1R,5S) abnormal lactone with a regioisomeric ratio of 1:1 and 99% ee each. Besides, different reaction conditions, such as pH, temperature and the presence of organic solvents, have been tested, revealing that BVMOAf1 is a relatively robust biocatalyst. PMID:23767684

  6. 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. PMID:25059187

  7. Measurement of the electric charge of the top quark in tt xAF events

    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.; 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.; 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, V. N.; Fauré, A.; Feng, L.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Fortner, M.; Fox, H.; 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.; 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.; 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

    2014-09-01

    We present a measurement of the electric charge of top quarks using tt ¯ events produced in pp ¯ collisions at the Tevatron. The analysis is based on fully reconstructed tt ¯ pairs in lepton+jets final states. Using data corresponding to 5.3 fb-1 of integrated luminosity, we exclude the hypothesis that the top quark has a charge of Q =-4/3e at a significance greater than 5 standard deviations. We also place an upper limit of 0.46 on the fraction of such quarks that can be present in an admixture with the standard model top quarks (Q =+2/3e) at a 95% confidence level.

  8. 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.

  9. RUNX1 Is a Key Target in t(4;11) Leukemias that Contributes to Gene Activation through an AF4-MLL Complex Interaction

    PubMed Central

    Wilkinson, Adam C.; Ballabio, Erica; Geng, Huimin; North, Phillip; Tapia, Marta; Kerry, Jon; Biswas, Debabrata; Roeder, Robert G.; Allis, C. David; Melnick, Ari; de Bruijn, Marella F.T.R.; Milne, Thomas A.

    2013-01-01

    Summary The Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in humans. Individual MLL fusion proteins have distinct leukemic phenotypes even when expressed in the same cell type, but how this distinction is delineated on a molecular level is poorly understood. Here, we highlight a unique molecular mechanism whereby the RUNX1 gene is directly activated by MLL-AF4 and the RUNX1 protein interacts with the product of the reciprocal AF4-MLL translocation. These results support a mechanism of transformation whereby two oncogenic fusion proteins cooperate by activating a target gene and then modulating the function of its downstream product. PMID:23352661

  10. Pathogenetic, Clinical, and Prognostic Features of Adult t(4;11)(q21;q23)/MLL-AF4 Positive B-Cell Acute Lymphoblastic Leukemia

    PubMed Central

    Marchesi, F.; Girardi, K.; Avvisati, G.

    2011-01-01

    Translocation t(4;11)(q21;q23) leading to formation of MLL-AF4 fusion gene is found in about 10% of newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in adult patients. Patients expressing this chromosomal aberration present typical biological, immunophenotypic, and clinical features. This form of leukemia is universally recognized as high-risk leukemia and treatment intensification with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR) could be a valid option to improve prognosis, but data obtained from the literature are controversial. In this review, we briefly describe pathogenetic, clinical, and prognostic characteristics of adult t(4;11)(q21;q23)/MLL-AF4 positive ALL and provide a review of the clinical outcome reported by the most important cooperative groups worldwide. PMID:22190943

  11. 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

  12. 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.

  13. Anti-leukemic activity of Newcastle disease virus strains AF2240 and V4-UPM in murine myelomonocytic leukemia in vivo.

    PubMed

    Alabsi, Aied M; Ali, Rola; Ideris, Aini; Omar, Abdul Rahman; Bejo, Mohd Hair; Yusoff, Khatijah; Ali, Abdul Manaf

    2012-05-01

    Newcastle disease virus (NDV) is a member of the Paramyxoviridae that has caused severe economic losses in poultry industry worldwide. Several strains of NDV were reported to induce cytolysis to cancerous cell lines. It has prompted much interest as anticancer agent because it can replicate up to 10,000 times better in human cancer cells than in most normal cells. In this study, two NDV strains, viserotropic-velogenic strain AF2240 and lentogenic strain V4-UPM, showed cytolytic activity and apoptosis induction against Mouse myelomoncytic leukemia (WEHI 3B). The cytolytic effects of NDV strains were determined using microtetrazolium (MTT) assay. The cytolytic dose - fifty percent (CD(50)) were 2 and 8HAU for AF2240 and V4-UPM strains, respectively. Cells treated with NDV strains showed apoptotic features compared to the untreated cells under fluorescence microscope. NDV induced activation of caspase-3 and DNA laddering in agarose gel electrophoresis which confirmed the apoptosis. The anti-leukemic activity of both strains was evaluated on myelomoncytic leukemia BALB/c mice. The results indicated that both NDV strains significantly decreased liver and spleen weights. It also decreased blasts cell percentage in blood, bone marrow and spleen smears of treated mice (p<0.05). Histopathological studies for spleen and liver confirmed the hematological results of blood and bone marrow. From the results obtained, the exposure to both NDV stains AF2240 and V4-UPM showed similar results for Ara-c. In conclusion NDV strains AF2240 and V4-UPM can affect WEHI 3B leukemia cells in vitro and in vivo.

  14. Ligand- and coactivator-mediated transactivation function (AF2) of the androgen receptor ligand-binding domain is inhibited by the cognate hinge region.

    PubMed

    Wang, Q; Lu, J; Yong, E L

    2001-03-01

    Transactivation functions (AF2) in the ligand-binding domains (LBD) of many steroid receptors are well characterized, but there is little evidence to support such a function for the LBD of the androgen receptor (AR). We report a mutant AR, with residues 628-646 in the hinge region deleted, which exhibited transactivation activity that was more than double that of the wild type (WT) AR. Although no androgen-dependent AF2 activity could be observed for the WT ARLBD fused to a heterologous DNA-binding domain, the mutant ARLBD(Delta628-646) was 30-40 times more active than the WT ARLBD. In the presence of the p160 coactivator TIF2, AR(Delta628-646) was significantly more active than similarly treated WT AR. Deletion of residues 628-646 also enhanced TIF2-ARLBD activity 8-fold, an effect not present when the LBD-interacting LXXLL motifs of TIF2 were mutated, suggesting that the negative modulatory activity of residues 628-646 were exerted via coactivator pathways. Although the AP-1 (c-Jun/c-Fos) system and NcoR have been reported to interact with and repress the activity of some steroid receptors, c-Jun, c-Fos, c-Jun/c-Fos, nor NcoR function was consistently affected by the absence or presence of residues 628-646, implying that the AR hinge region exerts its silencing effects in a manner independent of these corepressors. Our data provide evidence for the novel finding that strong androgen-dependent AF2 exists in the ARLBD and is the first report of a negative regulatory domain in the AR. Because mutations in this region are commonly associated with prostate cancer, it is important to characterize the mechanisms by which the hinge region exerts its repressor effect on ligand-activated and coactivator-mediated AF2 activity of the ARLBD.

  15. AF-DX 116, a presynaptic muscarinic receptor antagonist, potentiates the effects of glucose and reverses the effects of insulin on memory.

    PubMed

    Kopf, S R; Boccia, M M; Baratti, C M

    1998-11-01

    Male Swiss mice were tested 24 h after training in a one-trial step-through inhibitory avoidance task. Low subeffective doses of d-(+)-glucose (10 mg/kg, ip), but not its stereoisomer l-(-)-glucose (30 mg/kg,ip), administered immediately after training, and AF-DX 116 (0.3 mg/kg,ip), a presynaptic muscarinic receptor antagonist, given 10 min after training, interact to improve retention. Insulin (8 IU/kg, ip) impaired retention when injected immediately after training, and the effects were reversed, in a dose-related manner, by AF-DX 116 (0.3, 1.0, or 3.0 mg/kg, ip) administered 10 min following insulin. Since AF-DX 116 possibly blocks autoreceptors mediating the inhibition of acetylcholine release from cholinergic nerve terminals, the present data support the view that changes in the central nervous system glucose availability, subsequent to modification of circulating glucose levels, influence the activity of central cholinergic mechanisms involved in memory storage of an inhibitory avoidance response in mice. PMID:9774523

  16. Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product.

    PubMed Central

    Domer, P H; Fakharzadeh, S S; Chen, C S; Jockel, J; Johansen, L; Silverman, G A; Kersey, J H; Korsmeyer, S J

    1993-01-01

    A chromosomal translocation, t(4;11)-(q21;q23), is associated with an aggressive mixed-lineage leukemia. A yeast artificial chromosome was used to clone the chromosomal breakpoint of this translocation in the RS4;11 cell line. The breakpoint sequences revealed an inverted repeat bordered by a consensus site for topoisomerase II binding and cleavage as well as chi-like elements. The der(11) chromosome encodes a fusion RNA and predicted chimeric protein between the 11q23 gene MLL and a 4q21 gene designated AF4. The sequence of the complete open reading frame for this fusion transcript reveals the MLL protein to have homology with DNA methyltransferase, the Drosophila trithorax gene product, and the "AT-hook" motif of high-mobility-group proteins. An alternative splice that deletes the AT-hook region of MLL was identified. AF4 is a serine- and proline-rich putative transcription factor with a glutamine-rich carboxyl terminus. The composition of the complete MLL-AF4 fusion product argues that it may act through either a gain-of-function or a dominant negative mechanism in leukemogenesis. Images Fig. 3 PMID:7689231

  17. AF-DX 116, a presynaptic muscarinic receptor antagonist, potentiates the effects of glucose and reverses the effects of insulin on memory.

    PubMed

    Kopf, S R; Boccia, M M; Baratti, C M

    1998-11-01

    Male Swiss mice were tested 24 h after training in a one-trial step-through inhibitory avoidance task. Low subeffective doses of d-(+)-glucose (10 mg/kg, ip), but not its stereoisomer l-(-)-glucose (30 mg/kg,ip), administered immediately after training, and AF-DX 116 (0.3 mg/kg,ip), a presynaptic muscarinic receptor antagonist, given 10 min after training, interact to improve retention. Insulin (8 IU/kg, ip) impaired retention when injected immediately after training, and the effects were reversed, in a dose-related manner, by AF-DX 116 (0.3, 1.0, or 3.0 mg/kg, ip) administered 10 min following insulin. Since AF-DX 116 possibly blocks autoreceptors mediating the inhibition of acetylcholine release from cholinergic nerve terminals, the present data support the view that changes in the central nervous system glucose availability, subsequent to modification of circulating glucose levels, influence the activity of central cholinergic mechanisms involved in memory storage of an inhibitory avoidance response in mice.

  18. Integrated Autofluorescence Characterization of a Modified-Diet Liver Model with Accumulation of Lipids and Oxidative Stress

    PubMed Central

    Croce, Anna Cleta; Tarantola, Eleonora

    2014-01-01

    Oxidative stress in fatty livers is mainly generated by impaired mitochondrial β-oxidation, inducing tissue damages and disease progression. Under suitable excitation, light liver endogenous fluorophores can give rise to autofluorescence (AF) emission, the properties of which depend on the organ morphofunctional state. In this work, we characterized the AF properties of a rat liver model of lipid accumulation and oxidative stress, induced by a 1–9-week hypercaloric methionine-choline deficient (MCD) diet administration. The AF analysis (excitation at 366 nm) was performed in vivo, via fiber optic probe, or ex vivo. The contribution of endogenous fluorophores involved in redox reactions and in tissue organization was estimated through spectral curve fitting analysis, and AF results were validated by means of different histochemical and biochemical assays (lipids, collagen, vitamin A, ROS, peroxidised proteins, and lipid peroxidation -TBARS-, GSH, and ATP). In comparison with the control, AF spectra changes found already at 1 week of MCD diet reflect alterations both in tissue composition and organization (proteins, lipopigments, and vitamin A) and in oxidoreductive pathway engagement (NAD(P)H, flavins), with a subsequent attempt to recover redox homeostasis. These data confirm the AF analysis potential to provide a comprehensive diagnostic information on negative effects of oxidative metabolism alteration. PMID:25006587

  19. 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.

  20. 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. PMID:27030660

  1. Changes in Global and Regional Mechanics Due to Atrial Fibrillation: Insights From a Coupled Finite-Element and Circulation Model

    PubMed Central

    Moyer, Christian B.; Norton, Patrick T.; Ferguson, John D.; Holmes, Jeffrey W.

    2015-01-01

    Atrial fibrillation (AF) is a rhythm disorder with rapidly increasing prevalence due to the aging of the population. AF triggers structural remodeling and a gradual loss of function; however, the relative contributions of specific features of AF-induced remodeling to changes in atrial mechanical function are unclear. We constructed and validated a finite-element model (FEM) of the normal human left atrium using anatomic information from cardiac MRI, material properties and fiber orientations from published studies, and an iterative algorithm to estimate unloaded geometry. We coupled the FEM to a circuit model to capture hemodynamic interactions between the atrium, pulmonary circulation, and left ventricle. The normal model reproduced measured volumes within 1 SD, as well as most metrics of regional mechanics. Using this validated human model as a starting point, we explored the impact of individual features of atrial remodeling on atrial mechanics and found that a combination of dilation, increased pressure, and fibrosis can explain most of the observed changes in mechanics in patients with paroxysmal AF. However, only impaired ventricular relaxation could reproduce the increased reliance on active emptying we observed in these patients. The resulting model provides new insight into the mechanics of AF and a platform for exploring future therapies. PMID:25631205

  2. Changes in Global and Regional Mechanics Due to Atrial Fibrillation: Insights from a Coupled Finite-Element and Circulation Model.

    PubMed

    Moyer, Christian B; Norton, Patrick T; Ferguson, John D; Holmes, Jeffrey W

    2015-07-01

    Atrial fibrillation (AF) is a rhythm disorder with rapidly increasing prevalence due to the aging of the population. AF triggers structural remodeling and a gradual loss of function; however, the relative contributions of specific features of AF-induced remodeling to changes in atrial mechanical function are unclear. We constructed and validated a finite-element model (FEM) of the normal human left atrium using anatomic information from cardiac magnetic resonance imaging, material properties and fiber orientations from published studies, and an iterative algorithm to estimate unloaded geometry. We coupled the FEM to a circuit model to capture hemodynamic interactions between the atrium, pulmonary circulation, and left ventricle. The normal model reproduced measured volumes within 1 SD, as well as most metrics of regional mechanics. Using this validated human model as a starting point, we explored the impact of individual features of atrial remodeling on atrial mechanics and found that a combination of dilation, increased pressure, and fibrosis can explain most of the observed changes in mechanics in patients with paroxysmal AF. However, only impaired ventricular relaxation could reproduce the increased reliance on active emptying we observed in these patients. The resulting model provides new insight into the mechanics of AF and a platform for exploring future therapies.

  3. The application of ICP-SMS, GF-AAS and HG-AFS to the analysis of water and sediment samples from a temperate stratified estuary.

    PubMed

    Townsend, A T; O'Sullivan, J; Featherstone, A M; Butler, E C; Mackey, D J

    2001-02-01

    Three atomic spectrometry techniques, namely sector field inductively coupled plasma mass spectroscopy, graphite furnace atomic absorption spectrometry and hydride generation atomic fluorescence spectroscopy (ICP-SMS, GF-AAS and HG-AFS, respectively), housed at separate independent laboratories, were used to analyse water and sediment samples collected from the Huon River Estuary, SE Tasmania (Australia) in the Austral spring 1998. A dithiocarbamate-chelation/back-extraction technique was used to separate and preconcentrate Co, Ni, Cu, Zn, Cd and Pb from eight collected water samples prior to analysis by ICP-SMS and GF-AAS. A number of other elements in the waters were analysed directly (Mn, Fe and Zn by GF-AAS; As by HG-AFS), or following sample dilution (1 + 19: V, Mn, Fe, As, Mo, Ba and U by ICP-SMS). Where possible, previously corroborated GF-AAS and HG-AFS techniques were used to verify obtained ICP-SMS results. From the analysis of four reference waters (SLEW-1 and -2, SLRS-3 and NASS-5), good agreement, to within +/- 10-20%, was typically found between certified (or information only values) and measured results (irrespective of analytical technique). Exceptions included Zn (and sometimes Fe) that could not be quantified by ICP-SMS due to elevated blank signals, and As which was found to lie below ICP-SMS detection limits. For Huon Estuary water samples, inter-method agreement was within +/- 10-20% (for those elements amenable to analysis by more than one technique). Nitric acid extracts of two certified reference materials (Buffalo River Sediment and BCSS-1) and six Huon Estuary sediments were analysed by ICP-SMS (for Al, Sc, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd and Pb) and HG-AFS (for As). Results from the certified reference materials indicated extraction efficiencies of 60 70% (for most elements). A close correlation between ICP-SMS and HG-AFS was obtained for leachable As in the sediments. In terms of potential inorganic contaminants, the Huon Estuary

  4. Amniotic Fluid-Derived Mesenchymal Stem Cells Prevent Fibrosis and Preserve Renal Function in a Preclinical Porcine Model of Kidney Transplantation

    PubMed Central

    Baulier, Edouard; Favreau, Frederic; Le Corf, Amélie; Jayle, Christophe; Schneider, Fabrice; Goujon, Jean-Michel; Feraud, Olivier; Bennaceur-Griscelli, Annelise; Turhan, Ali G.

    2014-01-01

    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. PMID:24797827

  5. [Determination of Total Selenium and Arsenic in Coal by Wet Digestion Hydride Generation Atomic Fluorescence Spectrometry (HG-AFS)].

    PubMed

    Ni, Run-xiang; Luo, Kun-li

    2015-05-01

    In the present work we presented a new method for determination of total Se and As in coal by electric hot plate-mixed acids-hydride generation atomic fluorescence spectrometry (HG-AFS), the wet digestion method. The detailed operation procedures of the new method are as follows: About 0. 05~0. 10 g of powdered (200 mesh) coal sample was placed in a glass beaker, 10 mL of nitric acid (HNO3) and 2 mL of perchloric acid (HClO4) were added to the beaker in sequence, then the beaker was covered with a watching glass and placed in a fume cupboard standing overnight. The beaker was placed on an electric hot plate (180 °C) for sample decomposition the next day. The beaker was moved away from the electric hot plate when white smoke arose in the beaker, the sample color turned white or grey and the solution turned clear. Three milliliter of hydrochloric acid (HCl) solution (6 mol . L-1) was added to the beaker after the temperature of the beaker returned to room temperature. The beaker was heated on the electric hot plate again, and then moved away when white smoke started arising again. One milliliter of HCI was added in the beaker after the temperature of the beaker returned to room temperature. After that, the digested sample was transferred to a 25 mL test tube which was filled with ultrapure water to the tube's full volume. This solution was used for Se determination directly. Three milliliter of the Se test solution prepared above was transferred to a 15 mL glass test tube, 1 mL of thiourea/ascorbic acid solution (2. 5 g . mL-1) and 1 mL of the concentrated HCl was added to the 15 mL test tube. The test tube was then filled with ultrapure water to its full volume. The solution was used for As determination after shaking well and 40 min standing. Finally, Se and As concentrations in these prepared solutions were measured by using the AFS-9780 instrument (Beijing Haiguang Instrument Co. , LTD, Beijing, China). Two Chinese Coal Certified Reference Materials (GBW11115

  6. The Contribution of Ionic Currents to Rate-Dependent Action Potential Duration and Pattern of Reentry in a Mathematical Model of Human Atrial Fibrillation

    PubMed Central

    Lee, Young-Seon; Hwang, Minki; Song, Jun-Seop; Li, Changyong; Joung, Boyoung; Sobie, Eric A.; Pak, Hui-Nam

    2016-01-01

    Persistent atrial fibrillation (PeAF) in humans is characterized by shortening of action potential duration (APD) and attenuation of APD rate-adaptation. However, the quantitative influences of particular ionic current alterations on rate-dependent APD changes, and effects on patterns of reentry in atrial tissue, have not been systematically investigated. Using mathematical models of human atrial cells and tissue and performing parameter sensitivity analysis, we evaluated the quantitative contributions to action potential (AP) shortening and APD rate-adaptation of ionic current remodeling seen with PeAF. Ionic remodeling in PeAF was simulated by reducing L-type Ca2+ channel current (ICaL), increasing inward rectifier K+ current (IK1) and modulating five other ionic currents. Parameter sensitivity analysis, which quantified how each ionic current influenced APD in control and PeAF conditions, identified interesting results, including a negative effect of Na+/Ca2+ exchange on APD only in the PeAF condition. At high pacing rate (2 Hz), electrical remodeling in IK1 alone accounts for the APD reduction of PeAF, but at slow pacing rate (0.5 Hz) both electrical remodeling in ICaL alone (-70%) and IK1 alone (+100%) contribute equally to the APD reduction. Furthermore, AP rate-adaptation was affected by IKur in control and by INaCa in the PeAF condition. In a 2D tissue model, a large reduction (-70%) of ICaL becomes a dominant factor leading to a stable spiral wave in PeAF. Our study provides a quantitative and unifying understanding of the roles of ionic current remodeling in determining rate-dependent APD changes at the cellular level and spatial reentry patterns in tissue. PMID:26964092

  7. [Comparison of soil heavy metals determined by AAS/AFS and portable X-ray fluorescence analysis].

    PubMed

    Ran, Jing; Wang, De-Jian; Wang, Can; Bo, Lu-Ji; Zheng, Ji-Cheng; Yao, Li-Peng

    2014-11-01

    Total concentrations of Cu, Pb, As, Cr, Ni and Zn were determined for 53 soil samples using portable X-ray fluorescence (PXRF) system in in-situ and ex-situ (Lab.) conditions. PXRF metal concentrations were statistically compared with analytical results from traditional AAS/AFS analysis. The ability of PXRF instrument to produce comparable analytical results to the reference method was assessed by linear regression. To investgate the effects of soil moisture on PXRF, the in-situ moisture content of all soil samples was quantified and the metal concentrations of selected samples with known moisture contents were measured too. The results showed that the detection limits of PXRF for Cu, Pb, As, Cr, Ni and Zn were 10.6, 8.1, 5.7, 22.5, 21.6 and 10.4 mg kg(-1) respectively. A good degree of linearity was found for Pb, Cr, Ni and Zn in in-situ condition. While in ex-situ condition, quantitative level data were achieved across the entire range of samples tested for Cu, Pb, Cr, Ni and Zn. X-ray fluorescence spectrometry was shown to be an effective tool for quantification and rapid assessment of heavy metals in soils. Soil moisture content did affected the performance of PXRF, the mean percent difference for soil samples in-situ with moisture content less than 15% and higher than 25% was -17% and -31% respectively. In ex-situ condition, as the soil moisture content increased from air dried level to 30%, the mean percent difference decreased from 10% to -24%. The dilution effect of moisture in soils may cause discrepancies with conventional analytical results and induce worse data quality, and it should be controlled within 0-25% in in-situ condition.

  8. 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.

  9. In vivo diagnosis of colonic precancer and cancer using near-infrared autofluorescence spectroscopy and biochemical modeling.

    PubMed

    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. PMID:21721826

  10. 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.

  11. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial

    PubMed Central

    Mahaffey, Kenneth W.; Stevens, Susanna R.; White, Harvey D.; Nessel, Christopher C.; Goodman, Shaun G.; Piccini, Jonathan P.; Patel, Manesh R.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Califf, Robert M.; Fox, Keith A.A.; Breithardt, Günter

    2014-01-01

    Aims We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. Methods and results In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73–1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59–3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Conclusion Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events. PMID:24132190

  12. Pseudoxylallemycins A-F, Cyclic Tetrapeptides with Rare Allenyl Modifications Isolated from Pseudoxylaria sp. X802: A Competitor of Fungus-Growing Termite Cultivars.

    PubMed

    Guo, Huijuan; Kreuzenbeck, Nina B; Otani, Saria; Garcia-Altares, Maria; Dahse, Hans-Martin; Weigel, Christiane; Aanen, Duur K; Hertweck, Christian; Poulsen, Michael; Beemelmanns, Christine

    2016-07-15

    Based on fungus-fungus pairing assays and HRMS-based dereplication strategy, six new cyclic tetrapeptides, pseudoxylallemycins A-F (1-6), were isolated from the termite-associated fungus Pseudoxylaria sp. X802. Structures were characterized using NMR spectroscopy, HRMS, and Marfey's reaction. Pseudoxylallemycins B-D (2-4) possess a rare and chemically accessible allene moiety amenable for synthetic modifications, and derivatives A-D showed antimicrobial activity against Gram-negative human-pathogenic Pseudomonas aeruginosa and antiproliferative activity against human umbilical vein endothelial cells and K-562 cell lines. PMID:27341414

  13. 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

  14. Localization of tritiated 1-(2, 4-dichlorobenzyl)-/sup 1/H-indazole-3-carboxylic acid ((/sup 3/H) AF 1890) in rat testis using freeze-drying autoradiography

    SciTech Connect

    Hilderbrandt-Stark, H.E.; Mills, J.W.; Fawcett, D.W.

    1982-09-01

    Tritiated 1-(2, 4-dichlorobenzyl)-/sup 1/H-indazole-3-carboxylic acid ((/sup 3/H)AF 1890) was localized within rat testis using freeze-drying autoradiographic techniques. Ligated seminiferous tubule preparations were exposed in vitro to 80 microCi of (/sup 3/H)AF 1890 in the absence or presence of excess unlabeled AF 1890 for 30 min at 31 degrees C. Autoradiographs showed a generalized distribution of silver grains over the seminiferous epithelium, in the tubular lumen, and in the interstitial spaces. In addition, clusters of grains were concentrated over the seminiferous epithelium in regions of spermatid heads and tails and in the basal portion of the Sertoli cell cytoplasm, and over Leydig cells in the interstitial space. The generalized distribution was reduced and the grain clusters eliminated by incubation in an excess of unlabeled AF 1890. (/sup 3/H)inulin was used to assess the effectiveness of the tubular ligation because inulin does not normally penetrate the blood-testis barrier. This extracellular marker was not localized in the tubular lumen or in the seminiferous epithelium. Therefore, the labeling observed with (/sup 3/H)AF 1890 indicates that this compound crosses the blood-testis barrier.

  15. 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.

  16. 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 Central

    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. PMID:24699529

  17. Supporting Treatment decision making to Optimise the Prevention of STROKE in Atrial Fibrillation: The STOP STROKE in AF study. Protocol for a cluster randomised controlled trial

    PubMed Central

    2012-01-01

    Background Suboptimal uptake of anticoagulation for stroke prevention in atrial fibrillation has persisted for over 20 years, despite high-level evidence demonstrating its effectiveness in reducing the risk of fatal and disabling stroke. Methods The STOP STROKE in AF study is a national, cluster randomised controlled trial designed to improve the uptake of anticoagulation in primary care. General practitioners from around Australia enrolling in this ‘distance education’ program are mailed written educational materials, followed by an academic detailing session delivered via telephone by a medical peer, during which participants discuss patient de-identified cases. General practitioners are then randomised to receive written specialist feedback about the patient de-identified cases either before or after completing a three-month posttest audit. Specialist feedback is designed to provide participants with support and confidence to prescribe anticoagulation. The primary outcome is the proportion of patients with atrial fibrillation receiving oral anticoagulation at the time of the posttest audit. Discussion The STOP STROKE in AF study aims to evaluate a feasible intervention via distance education to prevent avoidable stroke due to atrial fibrillation. It provides a systematic test of augmenting academic detailing with expert feedback about patient management. Trial registration Australian Clinical Trials Registry Registration Number: ACTRN12611000076976. PMID:22770423

  18. 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.

  19. 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.

  20. A Mathematical Model of Neonatal Rat Atrial Monolayers with Constitutively Active Acetylcholine-Mediated K+ Current.

    PubMed

    Majumder, Rupamanjari; Jangsangthong, Wanchana; Feola, Iolanda; Ypey, Dirk L; Pijnappels, Daniël A; Panfilov, Alexander V

    2016-06-01

    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

  1. 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

  2. Inducibility of human atrial fibrillation in an in silico model reflecting local acetylcholine distribution and concentration.

    PubMed

    Hwang, Minki; Lee, Hyun-Seung; Pak, Hui-Nam; Shim, Eun Bo

    2016-01-01

    Vagal nerve activity has been known to play a crucial role in the induction and maintenance of atrial fibrillation (AF). However, it is unclear how the distribution and concentration of local acetylcholine (ACh) promotes AF. In this study, we investigated the effect of the spatial distribution and concentration of ACh on fibrillation patterns in an in silico human atrial model. A human atrial action potential model with an ACh-dependent K(+) current (IKAch) was used to examine the effect of vagal activation. A simulation of cardiac wave dynamics was performed in a realistic 3D model of the atrium. A model of the ganglionated plexus (GP) and nerve was developed based on the "octopus hypothesis". The pattern of cardiac wave dynamics was examined by applying vagal activation to the GP areas or randomly. AF inducibility in the octopus hypothesis-based GP and nerve model was tested. The effect of the ACh concentration level was also examined. In the single cell simulation, an increase in the ACh concentration shortened APD90 and increased the maximal slope of the restitution curve. In the 3D simulation, a random distribution of vagal activation promoted wavebreaks while ACh secretion limited to the GP areas did not induce a noticeable change in wave dynamics. The octopus hypothesis-based model of the GP and nerve exhibited AF inducibility at higher ACh concentrations. In conclusion, a 3D in silico model of the GP and parasympathetic nerve based on the octopus model exhibited higher AF inducibility with higher ACh concentrations. PMID:26807030

  3. Solution conformation of [AF]dG opposite a -1 deletion site in a DNA duplex: intercalation of the covalently attached aminofluorene ring into the helix with base displacement of the C8-modified Syn guanine into the major groove.

    PubMed

    Mao, B; Cosman, M; Hingerty, B E; Broyde, S; Patel, D J

    1995-05-01

    This paper reports on the solution structure of the [AF]dG adduct positioned opposite a deletion site in a DNA oligomer duplex that defines the alignment of the covalent aminofluorene--C8-guanine adduct relative to the deletion site. The combined NMR molecular mechanics computational studies were undertaken on the [AF]dG adduct embedded in the d(C5-[AF]G6-C7).d(G16-G17) sequence context in a duplex containing 11 residues on the modified strand and 10 on the partner, with no base opposite the modification. The exchangeable and nonexchangeable protons of the aminofluorene moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. The solution conformation of the [AF]G.del 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space. The aminofluorene ring of [AF]dG6 is intercalated between intact Watson-Crick dC5.dG17 and dC7.dG16 base pairs with the guanine base of [AF]dG6 in a syn alignment displaced into the major groove. The syn glycosidic torsion angle at [AF]dG6 is supported by both carbon and proton chemical shift data for the sugar resonances of the modified guanine residue. The long axis of the aminofluorene ring is parallel to the long axis of the flanking dG.dC base pairs with the AF ring undergoing rapid 180 degrees flips on the NMR time scale. The intercalation site is wedge shaped with a pronounced propeller-twisting and buckling of the dC5.dG17 base pair. The guanine base of [AF]dG6, which is positioned in the major groove, is inclined relative to the helix axis and stacks over the 5'-flanking dC5 residue in the solution structure. The intercalative-base displacement structure of the [AF]dG.del 11-mer duplex exhibits several unusually shifted proton resonances that can be readily accounted for by the ring current

  4. 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. PMID:27561277

  5. 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

  6. 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

  7. Direct online HPLC-CV-AFS method for traces of methylmercury without derivatisation: a matrix-independent method for urine, sediment and biological tissue samples.

    PubMed

    Brombach, Christoph-Cornelius; Gajdosechova, Zuzana; Chen, Bin; Brownlow, Andrew; Corns, Warren T; Feldmann, Jörg; Krupp, Eva M

    2015-01-01

    Mercury (Hg) is a global pollutant which occurs in different species, with methylmercury (MeHg) being the critical compound due to its neurotoxicity and bioaccumulation through the food chain. Methods for trace speciation of MeHg are therefore needed for a vast range of sample matrices, such as biological tissues, fluids, soils or sediments. We have previously developed an ultra-trace speciation method for methylmercury in water, based on a preconcentration HPLC cold vapour atomic fluorescence spectrometry (HPLC-CV-AFS) method. The focus of this work is mercury speciation in a variety of sample matrices to assess the versatility of the method. Certified reference materials were used where possible, and samples were spiked where reference materials were not available, e.g. human urine. Solid samples were submitted for commonly used digestion or extraction processes to obtain a liquid sample for injection into the analytical system. For MeHg in sediment samples, an extraction procedure was adapted to accommodate MeHg separation from high amounts of Hg(2+) to avoid an overload of the column. The recovery for MeHg determination was found to be in the range of 88-104% in fish reference materials (DOLT-2, DOLT-4, DORM-3), lobster (TORT-2), seaweed (IAEA-140/TM), sediments (ERM(®)-CC580) and spiked urine and has been proven to be robust, reliable, virtually matrix-independent and relatively cost-effective. Applications in the ultra-trace concentration range are possible using the preconcentration up to 200 mL, while for higher MeHg-containing samples, lower volumes can be applied. A comparison was carried out between species-specific isotope dilution gas chromatography inductively coupled plasma mass spectrometry (SSID-GC-ICP-MS) as the gold standard and HPLC-CV-AFS for biological tissues (liver, kidney and muscle of pilot whales), showing a slope of 1.008 and R (2) = 0.97, which indicates that the HPLC-CV-AFS method achieves well-correlated results for MeHg in

  8. Direct online HPLC-CV-AFS method for traces of methylmercury without derivatisation: a matrix-independent method for urine, sediment and biological tissue samples.

    PubMed

    Brombach, Christoph-Cornelius; Gajdosechova, Zuzana; Chen, Bin; Brownlow, Andrew; Corns, Warren T; Feldmann, Jörg; Krupp, Eva M

    2015-01-01

    Mercury (Hg) is a global pollutant which occurs in different species, with methylmercury (MeHg) being the critical compound due to its neurotoxicity and bioaccumulation through the food chain. Methods for trace speciation of MeHg are therefore needed for a vast range of sample matrices, such as biological tissues, fluids, soils or sediments. We have previously developed an ultra-trace speciation method for methylmercury in water, based on a preconcentration HPLC cold vapour atomic fluorescence spectrometry (HPLC-CV-AFS) method. The focus of this work is mercury speciation in a variety of sample matrices to assess the versatility of the method. Certified reference materials were used where possible, and samples were spiked where reference materials were not available, e.g. human urine. Solid samples were submitted for commonly used digestion or extraction processes to obtain a liquid sample for injection into the analytical system. For MeHg in sediment samples, an extraction procedure was adapted to accommodate MeHg separation from high amounts of Hg(2+) to avoid an overload of the column. The recovery for MeHg determination was found to be in the range of 88-104% in fish reference materials (DOLT-2, DOLT-4, DORM-3), lobster (TORT-2), seaweed (IAEA-140/TM), sediments (ERM(®)-CC580) and spiked urine and has been proven to be robust, reliable, virtually matrix-independent and relatively cost-effective. Applications in the ultra-trace concentration range are possible using the preconcentration up to 200 mL, while for higher MeHg-containing samples, lower volumes can be applied. A comparison was carried out between species-specific isotope dilution gas chromatography inductively coupled plasma mass spectrometry (SSID-GC-ICP-MS) as the gold standard and HPLC-CV-AFS for biological tissues (liver, kidney and muscle of pilot whales), showing a slope of 1.008 and R (2) = 0.97, which indicates that the HPLC-CV-AFS method achieves well-correlated results for MeHg in

  9. Model-based assist feature placement for 32nm and 22nm technology nodes using inverse mask technology

    NASA Astrophysics Data System (ADS)

    Poonawala, Amyn; Painter, Benjamin; Kerchner, Chip

    2009-10-01

    Inverse imaging has been long known to provide a true mathematical solution to the mask design problem. However, it is often times marred by problems like high run-time, mask manufacturability costs, and non-invertible models. In this paper, we propose a mask synthesis flow for advanced lithography nodes, which capitalizes on the inverse mask solution while still overcoming all the above problems. Our technique uses inverse mask technology (IMT) to calculate an inverse mask field containing all the useful information about the AF solution. This field is fed to a polygon placement algorithm to obtain initial AF placements, which are then cooptimized with the main features during an OPC/AF print-fix routine to obtain the final mask solution. The proposed flow enables process window maximization via IMT while guaranteeing fully MRC compliant masks. We present several results demonstrating the superiority of this approach. We also compare our IMT-AFs with the best AF solution obtained using extensive brute-force search (via a first principles simulator, S-litho), and prove that our solution is optimum.

  10. 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

  11. Functional dissection of an enhancer-like element located within the second intron of the human U2AF1L4 gene.

    PubMed

    Didych, D A; Smirnov, N A; Kotova, E S; Akopov, S B; Nikolaev, L G; Sverdlov, E D

    2011-08-01

    A detailed functional and evolutionary analysis of an enhancer element of the human genome (enhancer 12) located in the second intron of the U2AF1L4 gene, which we identified earlier, is presented. Overlapping fragments of the studied genome region were analyzed for enhancer activity, and the site responsible for the activity of this element was identified using transient transfections of HeLa cells. Comparison of the enhancer 12 sequence with orthologous sequences from seven primate species revealed the existence of evolutionarily conserved sequences within this element. One of the identified conservative regions is likely responsible for the enhancer activity and is able to specifically interact in vitro with proteins of HeLa cell nuclear extract. The ability of orthologous primate sequences to compete with enhancer 12 for binding with HeLa cell nuclear extract proteins and to enhance the activity of the reporter gene in transient transfection of HeLa cells is demonstrated. PMID:22022969

  12. Band-Renormalization Effects and Predominant Antiferromagnetic Order in Two-Dimensional Hubbard Model

    NASA Astrophysics Data System (ADS)

    Sato, Ryo; Yokoyama, Hisatoshi

    2016-07-01

    Band renormalization effects (BRE) are comprehensively studied for a mixed state of dx2 - y2-wave superconducting (d-SC) and antiferromagnetic (AF) orders, in addition to simple d-SC, AF, and normal (paramagnetic) states, by applying a variational Monte Carlo method to a two-dimensional Hubbard (t-t'-U) model. In a weakly correlated regime (U/t ≲ 6), BRE are negligible on all the states studied. As previously shown, the effective band of d-SC is greatly renormalized but the modifications of physical quantities, including energy improvement, are negligible. In contrast, BRE on the AF state considerably affects various features of the system. Because the energy is markedly improved for t'/t < 0, the AF state occupies almost the whole underdoped regime in phase diagrams. A doped metallic AF state undergoes a kind of Lifshitz transition at t' = t'{L} ˜ - 0.05t as t'/t varies, irrespective of the values of U/t and δ (doping rate). Pocket Fermi surfaces arise around (π ,0) [(π /2,π /2)] for t' > t'{L} [t' < t'{L}], which corresponds to the electron-hole asymmetry observed in angle-resolved photoemission spectroscopy (ARPES) spectra. The coexistent state of the two orders is possible basically for t' > t'{L}, because the existence of Fermi surfaces near (π ,0) is a requisite for the electron scattering of {q} = (π ,π ). Actually, the coexistent state appears mainly for t'{L}/t < t'/t ≲ 0.2 in the mixed state. Nevertheless, the AF and coexisting states become unstable toward phase separation for - 0.05 ≲ t'/t ≲ 0.2 but become stable at other values of t'/t owing to the energy reduction by the diagonal hopping of doped holes. We show that this instability does not directly correlate with the strength of d-SC.

  13. A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD

    PubMed Central

    Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Wei, Chenchen; Ma, Zhenxing; Wu, Bo; Yuan, Ruozhen; Tang, Hehan; Liu, Ming

    2016-01-01

    Abstract Calcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs. Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs. Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (≤2.15 mmol/L) than in patients with higher serum calcium levels. Lower serum calcium levels (≤2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population. PMID:27368027

  14. LXXLL motifs and AF-2 domain mediate SHP (NR0B2) homodimerization and DAX1 (NR0B1)-DAX1A heterodimerization.

    PubMed

    Iyer, Anita K; Zhang, Yao-Hua; McCabe, Edward R B

    2007-01-01

    Small heterodimer partner (SHP; NR0B2) is an unusual orphan member of the nuclear receptor superfamily that functions as a corepressor of other nuclear receptors through heterodimeric interactions. Mutations in SHP are associated with mild obesity and insulin resistance. The protein domain structure of SHP is similar to Dosage-sensitive sex reversal adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1 (DAX1; NR0B1). Mutations in DAX1 cause AHC with associated hypogonadotropic hypogonadism. DAX1A is an alternatively spliced isoform of DAX1 that lacks the last 80 amino acids of the DAX1 C-terminal repressor domain and is replaced by a novel 10-amino acid motif. We have previously shown homodimerization of SHP and DAX1 individually, heterodimerization of DAX1 with SHP, and heterodimerization of DAX1 with DAX1A. In these studies, we investigated the domains and residues of SHP involved in SHP homodimerization and DAX1-SHP heterodimerization and also further characterized DAX1-DAX1 homodimerization and DAX1-DAX1A heterodimerization. We showed involvement of the SHP LXXLL motifs and AF-2 domain in SHP homodimerization and DAX1-SHP heterodimerization. We demonstrated redundancy of the LXXLL motifs in DAX1 homodimerization. While DAX1A subcellular localization is mostly cytoplasmic, DAX1-DAX1A heterodimers existed in the nucleus, suggesting differential functions for DAX1A in each compartment. We showed that the AF-2 domain of DAX1 is involved in DAX1-DAX1A heterodimerization. These results indicate that NR0B family members use similar mechanisms for homodimerization as well as heterodimerization. These resemble coactivator-receptor interactions that may have potential functional consequences for molecular mechanisms of the NR0B family. PMID:17686645

  15. Modeling

    SciTech Connect

    Loth, E.; Tryggvason, G.; Tsuji, Y.; Elghobashi, S. E.; Crowe, Clayton T.; Berlemont, A.; Reeks, M.; Simonin, O.; Frank, Th; Onishi, Yasuo; Van Wachem, B.

    2005-09-01

    Slurry flows occur in many circumstances, including chemical manufacturing processes, pipeline transfer of coal, sand, and minerals; mud flows; and disposal of dredged materials. In this section we discuss slurry flow applications related to radioactive waste management. The Hanford tank waste solids and interstitial liquids will be mixed to form a slurry so it can be pumped out for retrieval and treatment. The waste is very complex chemically and physically. The ARIEL code is used to model the chemical interactions and fluid dynamics of the waste.

  16. The gap junction modifier, GAP-134 [(2S,4R)-1-(2-aminoacetyl)-4-benzamido-pyrrolidine-2-carboxylic acid], improves conduction and reduces atrial fibrillation/flutter in the canine sterile pericarditis model.

    PubMed

    Rossman, Eric I; Liu, Kun; Morgan, Gwen A; Swillo, Robert E; Krueger, Julie A; Gardell, Stephen J; Butera, John; Gruver, Matthew; Kantrowitz, Joel; Feldman, Hal S; Petersen, Jørgen S; Haugan, Ketil; Hennan, James K

    2009-06-01

    Gap junction uncoupling can alter conduction pathways and promote cardiac re-entry mechanisms that potentiate many supraventricular arrhythmias, such as atrial fibrillation (AF) and atrial flutter (AFL). Our objective was to determine whether GAP-134 [(2S,4R)-1-(2-aminoacetyl)-4-benzamido-pyrrolidine-2-carboxylic acid], a small dipeptide gap junction modifier, can improve conduction and ultimately prevent AF/AFL. In rat atrial strips subjected to metabolic stress, GAP-134 prevented significantly conduction velocity slowing at 10 nM compared with vehicle (p < 0.01). In the canine sterile pericarditis model, conduction time (CT; n = 5), atrial effective refractory period (AERP; n = 3), and AF/AFL duration/inducibility (n = 16) were measured 2 to 3 days postoperatively in conscious dogs. CT was significantly faster after GAP-134 infusion (average plasma concentration, 250 nM) at cycle lengths of 300 ms (66.2 +/- 1.0 versus 62.0 +/- 1.0 ms; p < 0.001) and 200 ms (64.4 +/- 0.9 versus 61.0 +/- 1.3 ms; p < 0.001). No significant changes in AERP were noted after GAP-134 infusion. The mean number of AF/AFL inductions per animal was significantly decreased after GAP-134 infusion (2.7 +/- 0.6 versus 1.6 +/- 0.8; p < 0.01), with total AF/AFL burden being decreased from 12,280 to 6063 s. Western blot experiments showed no change in connexin 43 expression. At concentrations exceeding those described in the AF/AFL experiments, GAP-134 had no effect on heart rate, blood pressure, or any electrocardiogram parameters. In conclusion, GAP-134 shows consistent efficacy on measures of conduction and AF/AFL inducibility in the canine sterile pericarditis model. These findings, along with its oral bioavailability, underscore its potential antiarrhythmic efficacy.

  17. 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.

  18. A vector model for off-axis hysteresis loops using anisotropy field

    NASA Astrophysics Data System (ADS)

    Jamali, Ali; Torre, Edward Della; Cardelli, Ermanno; ElBidweihy, Hatem; Bennett, Lawrence H.

    2016-11-01

    A model for the off-axis vector magnetization of a distribution of uniaxial particles is presented. Recent work by the authors decomposed the magnetization into two components and modeled the total vector magnetization as their vector sum. In this paper, to account for anisotropy, the direction of the reversible magnetization component is specified by the vector sum of the applied field and an effective anisotropy field. The formulation of the new anisotropy field (AF) model is derived and its results are discussed considering (i) oscillation and rotational modes, (ii) lag angle, and (iii) unitary magnetization. The advantages of the AF model are outlined by comparing its results to the results of the classical Stoner-Wohlfarth model.

  19. 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%.

  20. 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.

  1. A revised dosimetric model of the head and brain

    SciTech Connect

    Bolch, W.E.; Poston, J.W. Sr.

    1995-05-01

    The use of PET and SPECT radiopharmaceuticals in brain imaging has greatly expanded over the past several years. Many of these agents localize within particular subregions of the brain, thus allowing for detailed physiologic and metabolic imaging. Dosimetric models to support these advances in nuclear medicine have been lacking. For example, the brain within the phantom of MIRD Pamphlet No. 5 Revised is modeled simply as a single ellipsoid of tissue with no differentiation of its internal structures. To address this need, the MIRD Committee established a Task Group in 1992 to construct a revised dosimetric model of the brain to include the following subregions: the cerebral cortex, the white matter, the cerebellum, the thalamus, the caudate nucleus, the lentiform nucleus (putamen and globus pallidus), the cerebral spinal fluid (within the subarachnoid space of the brain), the lateral ventricles, and the third ventricle. Estimates of both electron and photon absorbed fractions (AF) were subsequently calculated using the EGS4 radiation transport code. For most of the internal brain structures, electron AFs are shown to fall fellow unity for all regions within the energy range of {approximately}200 keV to 4 MeV. For example, AFs for the caudate nucleus as both a source and target region and estimated as 0.98, 0.84, 0.39 for 200-keV, 1-MeV, and 4-MeV electron sources, respectively. Corresponding AFs within the white matter as a source and target region are estimated as 1.0, 0.95, and 0.79 for these same electron energies. Revised S values were subsequently calculated for a variety of beta-particle and positron emitters used in brain imaging.

  2. The high affinity ligand binding conformation of the nuclear 1,25-dihydroxyvitamin D3 receptor is functionally linked to the transactivation domain 2 (AF-2).

    PubMed Central

    Nayeri, S; Kahlen, J P; Carlberg, C

    1996-01-01

    The nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), VDR, is a transcription factor that mediates all genomic actions of the hormone. The activation of VDR by ligand induces a conformational change within its ligand binding domain (LBD). Due to the lack of a crystal structure analysis, biochemical methods have to be applied in order to investigate the details of this receptor-ligand interaction. The limited protease digestion assay can be used as a tool for the determination of a functional dissociation constant (K(df)) of VDR with any potential ligand. This method provided with the natural hormone VD two protease-resistant fragments of the VDR LBD and with the 20-epi conformation of VD, known as MC1288, even an additional fragment of intermediate size. These fragments were interpreted as different receptor conformations and their decreasing size was found to be associated with decreasing ligand binding affinity. A critical amino acid for VDR's high ligand binding conformation has been identified by C-terminal receptor truncations and point mutations as phenylalanine 422. This amino acid appears to directly contact the ligand and belongs to the ligand-inducible activation function-2 (AF-2) domain. Moreover, functional assays supported the observation that high affinity ligand binding is directly linked to transactivation function. PMID:8948643

  3. Talaromycolides A-C, Novel Phenyl-Substituted Phthalides Isolated from the Green Chinese Onion-Derived Fungus Talaromyces pinophilus AF-02.

    PubMed

    Zhai, Ming-Ming; Niu, Hai-Tao; Li, Jie; Xiao, Hui; Shi, Yan-Ping; Di, Duo-Long; Crews, Phillip; Wu, Quan-Xiang

    2015-11-01

    The green Chinese onion (Allium fistulosum L.), which is widely cultivated and has been naturalized in many places, is an important spice and vegetable in East and Southeast Asia. It is used to treat the common cold in China. In the ongoing search for antibacterial activity in fungi derived from natural, pungently scented vegetables, the secondary metabolites of Talaromyces pinophilus AF-02, which was isolated from the stem of the green Chinese onion, were investigated. The genus Talaromyces (Trichocomaceae) is an important fungal genus because of its ubiquity and the role of many of its species in food and agriculture production. Three new phthalide derivatives, talaromycolides A-C, 1-3; a new long-chain dicarboxylic acid, 11; and 12 known compounds were isolated from methanolic extracts of this fungus. Their structures were determined via extensive NMR, HR-ESI-MS, and CD spectroscopic analyses. Compounds 1-3 are rare phthalide derivatives with a novel linkage position between the phenyl and phthalide moieties. The biological properties of 1-16 were evaluated using six different bacteria, and 1-3, 5, and 11 exhibited significant antibacterial activity in response to some of the tested strains. PMID:26466717

  4. 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.

  5. Simultaneous Determination of Se and Te in Ores by HG-AFS After Online Preconcentration with Nano-TiO2 Immobilized on Silica Gel.

    PubMed

    Zhou, Jing-rong; Deng, Dong-yan; Huang, Ke; Tian, Yun-fei; Hou, Xian-deng

    2015-09-01

    A simple, sensitive and interference-free method was established for simultaneous determination of trace selenium and tellurium in ore samples by HG-AFS, by using nano-TiO2 immobilized on a silica gel packed microcolumn for online preconcentration. Selenium and tellurium were selectively adsorbed to the microcolumn in acidic condition and then completely eluted with 2% (m/v) NaOH solution. The experimental conditions for hydride generation, adsorption, elution and potential interference were investigated in detail. Under the optimum conditions, the detection limits of selenium and tellurium by the proposed method with 180 s sampling time were 4.0 and 3.6 ng · L(-1), with sensitivity enhancement of 20- and 13-fold compared to conventional hydride generation method, respectively. The relative standard deviation (RSD, n=5) of this method for 1 μg · L(-1) Se(IV) and Te(IV) were 0.7% and 2.3%, respectively. This method was applied to determination of selenium and tellurium in several ore samples. PMID:26669138

  6. Simultaneous determination of endocrine disrupting compounds bisphenol F and bisphenol AF using carboxyl functionalized multi-walled carbon nanotubes modified electrode.

    PubMed

    Yang, Jichun; Wang, Xin; Zhang, Danfeng; Wang, Lingling; Li, Qi; Zhang, Lei

    2014-12-01

    A novel, simple and selective electrochemical method was developed for simultaneous determination of bisphenol F (BPF) and bisphenol AF (BPAF) in aqueous media (phosphate buffer solution, pH 6.0) on carboxyl functionalized multi-walled carbon nanotubes modified glassy carbon electrode (MWCNT-COOH/GCE) using differential pulse voltammetry (DPV). In DPV, MWCNT-COOH/GCE could separate the oxidation peak potentials of BPF and BPAF present in the same solution though, at the bare GCE, the peak potentials were indistinguishable. The results showed that the electrochemical sensor exhibited excellent electrocatalytic activity towards the oxidation of the two analytes. The peak current in DPV of BPF and BPAF increased linearly with their concentration in the ranges of 0.6-1.6 mmol/L BPF and 0.6-1.6 mmol/L BPAF. The detection limits were 0.1243 mmol/L and 0.1742 mmol/L (S/N=3) correspondingly. The modified electrode was successfully used to simultaneously determine BPF and BPAF in real samples.

  7. 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.

  8. The plant pathogen Streptomyces scabies 87-22 has a functional pyochelin biosynthetic pathway that is regulated by TetR- and AfsR-family proteins.

    PubMed

    Seipke, Ryan F; Song, Lijiang; Bicz, Joanna; Laskaris, Paris; Yaxley, Alice M; Challis, Gregory L; Loria, Rosemary

    2011-09-01

    Siderophores are high-affinity iron-chelating compounds produced by bacteria for iron uptake that can act as important virulence determinants for both plant and animal pathogens. Genome sequencing of the plant pathogen Streptomyces scabies 87-22 revealed the presence of a putative pyochelin biosynthetic gene cluster (PBGC). Liquid chromatography (LC)-MS analyses of culture supernatants of S. scabies mutants, in which expression of the cluster is upregulated and which lack a key biosynthetic gene from the cluster, indicated that pyochelin is a product of the PBGC. LC-MS comparisons with authentic standards on a homochiral stationary phase confirmed that pyochelin and not enantio-pyochelin (ent-pyochelin) is produced by S. scabies. Transcription of the S. scabies PBGC occurs via ~19 kb and ~3 kb operons and transcription of the ~19 kb operon is regulated by TetR- and AfsR-family proteins encoded by the cluster. This is the first report, to our knowledge, of pyochelin production by a Gram-positive bacterium; interestingly regulation of pyochelin production is distinct from characterized PBGCs in Gram-negative bacteria. Though pyochelin-mediated iron acquisition by Pseudomonas aeruginosa is important for virulence, in planta bioassays failed to demonstrate that pyochelin production by S. scabies is required for development of disease symptoms on excised potato tuber tissue or radish seedlings. PMID:21757492

  9. 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. PMID:26660322

  10. 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

  11. The allosteric interaction of otenzepad (AF-DX 116) at muscarinic M2 receptors in guinea pig atria.

    PubMed

    Lanzafame, A; Christopoulos, A; Mitchelson, F

    2001-03-30

    The effects of the muscarinic receptor antagonist, otenzepad, in combination with the competitive antagonists N-methylscopolamine, dexetimide and atropine, or the allosteric modulators, C(7)/3'-phth, gallamine and alcuronium, were measured in the guinea pig electrically driven left atrium using the agonists, carbachol or acetylcholine. Otenzepad, in combination with C(7)/3'-phth or gallamine, gave concentration-ratios close to additive and in agreement with theoretical model predictions for combination of two allosteric modulators acting at a common site. However, when otenzepad was combined with alcuronium, dexetimide or N-methylscopolamine, supra-additive effects were observed. For either competitive antagonist in combination with otenzepad, the degree of supra-additivity was more evident after 2-h equilibration than after 40 min. When otenzepad was combined with atropine, no supra-additivity was observed with carbachol as the agonist, but was evident with acetylcholine. Otenzepad was also unable to fully inhibit [3H]N-methylscopolamine binding when the radioligand was employed at a concentration of approximately 100 x K(D). It is concluded that the action of otenzepad involves an allosteric site and a number of possibilities are discussed for its location. PMID:11290374

  12. 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

  13. Extending simulation-based acquisition (SBA) to the warfighter with the Air Force Joint Synthetic Battlespace (JSB-AF)

    NASA Astrophysics Data System (ADS)

    Faye, Phil; Andrew, Emily B.; Lee, Jayson

    2001-09-01

    The Air Force has vectored in a new direction to expand its investment in advanced simulation technologies to improve our readiness, lower costs, and dominate the battles of tomorrow. One of the critical initiatives in this direction is the Joint Synthetic Battlespace (JSB). The JSB will provide an integrated Modeling and Simulation (M&S) environment that brings together analysis, training, and simulations into a coherent whole. The ultimate goal is to develop a JSB simulation capability that will provide a new level of realism in synthetic mission and battlespace environments. This capability will be used to evaluate not only specific systems characteristics but also the associated tactics and procedures. The feature that distinguishes the JSB will be the its ability to realistically represent the real-world mission environment and provide the warfighter with real-time feedback on a system's expected performance. This unprecedented level of realism and response will enable the warfighter to evaluate mission effectiveness and conduct course of action analyses. At the same time, the JSB will increase the acquisition community's ability to build or modify systems to meet users' needs and expectations by making the warfighter the focus and direct participant in the acquisition process. As a detailed engineering and trades tool, the JSB will provide a completely scaleable environment for controlled executions of experiments to support analyses that require repeatability and controlled variations in the simulated environment. The government will also be able to ensure the configuration, control, and consistency of the JSB environment, while the users will develop their own plans and scenarios for their analyses. This will provide a standardized synthetic environment for acquisition programs that can be used as either a distributed or stand-alone application.

  14. 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.

  15. 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

  16. Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation.

    PubMed

    Gundacker, Claudia; Dolznig, Helmut; Mikula, Mario; Rosner, Margit; Brandau, Oliver; Hengstschläger, Markus

    2012-03-01

    Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem (AFS) cells as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.

  17. Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

    PubMed Central

    Gundacker, Claudia; Dolznig, Helmut; Mikula, Mario; Rosner, Margit; Brandau, Oliver; Hengstschläger, Markus

    2012-01-01

    Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem (AFS) cells as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity. PMID:22231297

  18. 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.

  19. 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.

  20. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    PubMed Central

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

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

  1. Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population

    PubMed Central

    Nakamura, Minoru; Nishida, Nao; Kawashima, Minae; Aiba, Yoshihiro; Tanaka, Atsushi; Yasunami, Michio; Nakamura, Hitomi; Komori, Atsumasai; Nakamuta, Makoto; Zeniya, Mikio; Hashimoto, Etsuko; Ohira, Hiromasa; Yamamoto, Kazuhide; Onji, Morikazu; Kaneko, Shuichi; Honda, Masao; Yamagiwa, Satoshi; Nakao, Kazuhiko; Ichida, Takafumi; Takikawa, Hajime; Seike, Masataka; Umemura, Takeji; Ueno, Yoshiyuki; Sakisaka, Shotaro; Kikuchi, Kentaro; Ebinuma, Hirotoshi; Yamashiki, Noriyo; Tamura, Sumito; Sugawara, Yasuhiko; Mori, Akira; Yagi, Shintaro; Shirabe, Ken; Taketomi, Akinobu; Arai, Kuniaki; Monoe, Kyoko; Ichikawa, Tatsuki; Taniai, Makiko; Miyake, Yasuhiro; Kumagi, Teru; Abe, Masanori; Yoshizawa, Kaname; Joshita, Satoru; Shimoda, Shinji; Honda, Koichi; Takahashi, Hiroki; Hirano, Katsuji; Takeyama, Yasuaki; Harada, Kenichi; Migita, Kiyoshi; Ito, Masahiro; Yatsuhashi, Hiroshi; Fukushima, Nobuyoshi; Ota, Hajime; Komatsu, Tatsuji; Saoshiro, Takeo; Ishida, Jinya; Kouno, Hirotsugu; Kouno, Hirotaka; Yagura, Michiyasu; Kobayashi, Masakazu; Muro, Toyokichi; Masaki, Naohiko; Hirata, Keiichi; Watanabe, Yukio; Nakamura, Yoko; Shimada, Masaaki; Hirashima, Noboru; Komeda, Toshiki; Sugi, Kazuhiro; Koga, Michiaki; Ario, Keisuke; Takesaki, Eiichi; Maehara, Yoshihiko; Uemoto, Shinji; Kokudo, Norihiro; Tsubouchi, Hirohito; Mizokami, Masashi; Nakanuma, Yasuni; Tokunaga, Katsushi; Ishibashi, Hiromi

    2012-01-01

    For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10−14 for rs4979462, and combined OR = 1.39, p = 2.38 × 10−8 for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10−8, 3.66 × 10−9, and 3.04 × 10−9, respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10−6 and 1.42 × 10−7, respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals. PMID:23000144

  2. Generation and characterization of bioluminescent xenograft mouse models of MLL-related acute leukemias and in vivo evaluation of luciferase-targeting siRNA nanoparticles.

    PubMed

    Fazzina, Raffaella; Lombardini, Lorenza; Mezzanotte, Laura; Roda, Aldo; Hrelia, Patrizia; Pession, Andrea; Tonelli, Roberto

    2012-08-01

    Chromosomal translocations involving the MLL gene on 11q23 present frequent abnormalities in pediatric, adult and therapy-related acute leukemias, and are generally associated with aggressive disease and poor prognosis. Here, we report bioluminescent acute leukemia xenograft mouse models of the most frequent and aggressive MLL-related acute leukemias (infant and adult MLL-AF9, MLL-ENL, MLL-AF4). Four acute leukemia cell lines carrying MLL-related translocations were stably transduced with a firefly luciferase transgene and injected intravenously into NOD/SCID mice. Leukemia progression was monitored by in vivo bioluminescence imaging (BLI). All mice developed MLL-related acute leukemia. The four MLL-related acute leukemia models showed a different course of infant and adult MLL-AF9 acute myeloid leukemia, and a rapid aggressiveness of MLL-ENL acute lymphoblastic leukemia and MLL-AF4 acute biphenotypic leukemia. Tissue analysis and RT-PCR of bone marrow, spleen and liver from the mice confirmed the BL results. To validate BLI for the detection of a therapeutic response, systemic treatment with an anti-luciferase-targeting siRNA (siLuc) complexed with cationic nanoparticles was administered to mice with MLL-AF4 acute lymphoblastic leukemia. The BLI signal showed a reduction following treatment with siLuc compared to the control mice. These mouse models present MLL-related acute leukemia evolution similar to the human counterparts. Moreover, they are non-invasive, rapid and sensitive models, suitable for the in vivo study of MLL-related acute leukemias. Finally, BLI showed in vivo luminescence down modulation obtained by systemic treatment with luciferase-targeting siRNA nanoparticle complexes, confirming that these MLL-related leukemia mouse models are optimal for the evaluation and selection of delivery systems for siRNA and other new biotechnological pharmaceuticals.

  3. 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.

  4. The Attentional Field Revealed by Single-Voxel Modeling of fMRI Time Courses

    PubMed Central

    DeYoe, Edgar A.

    2015-01-01

    The spatial topography of visual attention is a distinguishing and critical feature of many theoretical models of visuospatial attention. Previous fMRI-based measurements of the topography of attention have typically been too crude to adequately test the predictions of different competing models. This study demonstrates a new technique to make detailed measurements of the topography of visuospatial attention from single-voxel, fMRI time courses. Briefly, this technique involves first estimating a voxel's population receptive field (pRF) and then “drifting” attention through the pRF such that the modulation of the voxel's fMRI time course reflects the spatial topography of attention. The topography of the attentional field (AF) is then estimated using a time-course modeling procedure. Notably, we are able to make these measurements in many visual areas including smaller, higher order areas, thus enabling a more comprehensive comparison of attentional mechanisms throughout the full hierarchy of human visual cortex. Using this technique, we show that the AF scales with eccentricity and varies across visual areas. We also show that voxels in multiple visual areas exhibit suppressive attentional effects that are well modeled by an AF having an enhancing Gaussian center with a suppressive surround. These findings provide extensive, quantitative neurophysiological data for use in modeling the psychological effects of visuospatial attention. PMID:25810532

  5. 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.

  6. 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…

  7. AFS Orientation Handbook. Third Edition.

    ERIC Educational Resources Information Center

    AFS International/Intercultural Programs, Inc., New York, NY.

    Designed for persons involved in cross-cultural training sessions for international high school student exchange programs, this handbook features orientation resources developed in North and South America, Europe, and Asia. Following a brief introduction, Section 2 describes volunteer training seminars in Argentina which covered publicity, local…

  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. 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.

  10. The E-MS Algorithm: Model Selection with Incomplete Data

    PubMed Central

    Jiang, Jiming; Nguyen, Thuan; Rao, J. Sunil

    2014-01-01

    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. PMID:26783375

  11. Localized corrosion susceptibility of Al-Li-Cu-Mg-Zn alloy AF/C458 due to interrupted quenching from solutionizing temperature

    NASA Astrophysics Data System (ADS)

    Kertz, J. E.; Gouma, P. I.; Buchheit, R. G.

    2001-10-01

    Isothermal time-temperature-localized corrosion-behavior curves were determined for the Al-1.8Li-2.70Cu-0.6Mg-0.3Zn alloy AF/C458, to understand the effect of slow or delayed quenching on localized corrosion susceptibility. Alloy samples were subject to a series of systematic interrupted quenching experiments conducted at temperatures ranging from 480 °C to 230 °C for times ranging from 5 to 1000 seconds. Individual samples were then exposed to an oxidizing aqueous chloride solution consisting of 57 g/L NaCl plus 10 mL/L H2O2 to induce localized attack. The localized corrosion mode was characterized by optical microscopy. Additionally, the microstructure of selected samples was characterized by transmission electron microscopy (TEM) to relate the corrosion mode and morphology to microstructural features. Results showed that only pitting attack was exhibited by samples subjected to isothermal treatment at temperatures greater than 430 °C. At temperatures ranging from 280 °C to 430 °C, isothermal treatment tended to induce susceptibility to intergranular attack (IGA) and intersubgranular attack (ISGA) for all treatment times investigated. For isothermal treatments at temperatures lower than 280 °C, only pitting was observed for treatment times less than about 30 seconds, while IGA and ISGA were observed for longer treatment times. Comparisons showed that the time-temperature domains for IGA and ISGA were virtually coincident. Based on this finding and the results from TEM characterization, IGA and ISGA appear to be related to the precipitation of a Zn-modified T 1 (Al2(Cu,Zn)Li) precipitate, which can occur both on low-angle and high-angle grain boundaries in this alloy. When the alloy is resistant to IGA and ISGA, the grain boundaries are decorated by θ' (Al2Cu), and T B (Al7Cu4Li) phase particles, or subgrain boundaries are populated by a comparatively low density of T 1 precipitates. It is, therefore, speculated that θ' and T B are more corrosion

  12. 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

  13. 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.

  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

    Wei, Yong; Xu, Juan; 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. 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

  17. Rationale and design of a study exploring the efficacy of once-daily oral rivaroxaban (X-TRA) on the outcome of left atrial/left atrial appendage thrombus in nonvalvular atrial fibrillation or atrial flutter and a retrospective observational registry providing baseline data (CLOT-AF).

    PubMed

    Lip, Gregory Y H; Hammerstingl, Christoph; Marin, Francisco; Cappato, Riccardo; Meng, Isabelle Ling; Kirsch, Bodo; Morandi, Eolo; van Eickels, Martin; Cohen, Ariel

    2015-04-01

    There are still many unresolved issues concerning patient outcomes and prognostic factors in patients with atrial fibrillation (AF) and left atrial/left atrial appendage (LA/LAA) thrombi. Rivaroxaban (Xarelto®), a potent and highly selective oral, direct factor Xa inhibitor, is a new therapeutic option in this setting. The planned study program will consist of a prospective interventional study (X-TRA) and a retrospective observational registry (CLOT-AF). The primary objective of the X-TRA study is to explore the efficacy of rivaroxaban in the treatment of LA/LAA thrombi in patients with nonvalvular AF or atrial flutter, scheduled to undergo cardioversion or AF ablation, in whom an LA/LAA thrombus has been found on transesophageal echocardiography (TEE) before the procedure. The primary end point is the complete LA/LAA thrombus resolution rate at 6 weeks of end of treatment confirmed by TEE. The secondary objectives are to describe categories of thrombus outcome in patients (resolved, reduced, unchanged, larger, or new) confirmed on TEE at the end of treatment (after 6 weeks of treatment), incidence of the composite of stroke and noncentral nervous system systemic embolism at the end of treatment and during follow-up, and incidence of all bleeding at the end of treatment and during follow-up. The objective of the CLOT-AF registry is to provide retrospective thrombus-related patient outcome data after standard-of-care anticoagulant treatment in patients with nonvalvular AF or atrial flutter, who have TEE-documented LA/LAA thrombi. The data will be used as a reference for the prospective X-TRA study. In conclusion, X-TRA and CLOT-AF will provide some answers to the many unresolved issues concerning patient outcomes and prognostic factors in patients with AF and LAA thrombi. Results from this study program would provide the first prospective interventional study (X-TRA) and a large international retrospective observational registry (CLOT-AF) on the prevalence and

  18. 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.

  19. Estrogen receptor activation function 2 (AF-2) is essential for hormone-dependent transactivation and cell transformation induced by a v-Jun DNA binding domain-estrogen receptor chimera.

    PubMed

    Dunn, Catherine A; Clark, William; Black, Elizabeth J; Gillespie, David A F

    2003-08-25

    A chimeric protein consisting of the estrogen receptor alpha ligand binding domain (ER-alpha LBD) fused to the DNA binding domain (DBD) of the v-Jun oncoprotein, deltavJ-hER, was previously shown to elicit estradiol-dependent transcriptional activation and cell transformation. Remarkably, in the unliganded state deltavJ-hER is not inert, but rather inhibits cell proliferation. To understand the molecular basis for these opposite effects on cell growth, we investigated the effect of estradiol on deltavJ-hER function. We find that deltavJ-hER is localised to the cell nucleus and capable of binding TPA-response element (TRE) DNA recognition sites in the presence and absence of estradiol, indicating that these properties are unlikely to be the targets of hormonal regulation. In contrast, a mutant derivative of deltavJ-hER in which amino acid substitutions selectively disrupt activation function 2 (AF-2) function is unable to elicit estradiol-dependent transcription or cell transformation, even though DNA binding is not impaired. Taken together, these observations establish that estrogen receptor AF-2 activity is essential for cell transformation by deltavJ-hER. PMID:12932827

  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. Substrate size as a determinant of fibrillatory activity maintenance in a mathematical model of canine atrium.

    PubMed

    Zou, Renqiang; Kneller, James; Leon, L Joshua; Nattel, Stanley

    2005-09-01

    Tissue size has been considered an important determinant of atrial fibrillation (AF), but recent work has questioned the critical size hypothesis. Here, we use a previously developed mathematical model of the two-dimensional canine atrium with realistic action potential, ionic, and conduction properties to address substrate size effects on the maintenance of fibrillatory activity. Cholinergic AF was simulated at different acetylcholine (ACh) concentrations ([ACh]) and distributions, with substrate area varied 11.1-fold. Automated phase singularity detection was used to facilitate the analysis of arrhythmic activity. The duration of activity induced by a single extrastimulus increased with increasing substrate dimensions. Two general mechanisms underlying activity were observed and were differentially affected by substrate size. For large mean [ACh], single primary rotors anchored in low-[ACh] zones maintained activity and substrate dimensions were not critical. At lower mean [ACh], extensive spiral wave meander prevented the emergence of single stable rotors. Prolonged activity was favored when substrate size permitted a sufficiently large number of simultaneous longer-lasting rotors that extinction of all was unlikely. Thus either single dominant rotor or multiple reentrant spiral generator mechanisms could maintain fibrillatory activity in this model and were differentially dependent on substrate size. These results speak to recent debates about the role in AF of single driver rotors versus multiple reentrant circuit mechanisms by suggesting that either may maintain fibrillatory atrial activity depending on atrial size and electrophysiological properties.

  2. Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.

    PubMed

    Lombardo, Daniel M; Fenton, Flavio H; Narayan, Sanjiv M; Rappel, Wouter-Jan

    2016-08-01

    Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP) morphology, action potential duration (APD) restitution and conduction velocity (CV) restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy. PMID:27494252

  3. Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties

    PubMed Central

    Fenton, Flavio H.; Narayan, Sanjiv M.; Rappel, Wouter-Jan

    2016-01-01

    Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP) morphology, action potential duration (APD) restitution and conduction velocity (CV) restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy. PMID:27494252

  4. Rationale and design of the ODIn-AF Trial: randomized evaluation of the prevention of silent cerebral thromboembolism by oral anticoagulation with dabigatran after pulmonary vein isolation for atrial fibrillation.

    PubMed

    Schrickel, Jan W; Linhart, Markus; Bänsch, Dietmar; Thomas, Daniel; Nickenig, Georg

    2016-02-01

    Oral anticoagulation treatment following clinically successful catheter ablation of atrial fibrillation is controversial. Recent guidelines recommend continuation of oral anticoagulation in all patients with CHA2DS2VASc score ≥ 2 even if there is no evidence of recurrent atrial fibrillation. Due to lack of prospective data, the net clinical benefit of oral anticoagulation after successful ablation in these patients is unclear. As oral anticoagulation bears the risk of severe bleeding events, the ODIn-AF study aims to evaluate the effect of oral anticoagulation on the incidence of silent cerebral embolic events in patients with a high risk for embolic events, but free from symptomatic atrial fibrillation after successful pulmonary vein ablation. PMID:26514352

  5. [Expression of SM30 (A-F) Genes Encoding Spicule Matrix Proteins in Intact and Damaged Sea Urchin Strongylocentrotus intermedius (A. Agassiz, 1863) at the Six-Arm Pluteus].

    PubMed

    Sharmankina, V V; Kiselev, K V

    2016-03-01

    In this study we investigated expression of the SM30(A-F) gene family encoding Strongylocentrotus intermedius spicule matrix proteins during the normal and regenerative pluteus II stage (three pairs of arms). We found that SiSM30A and SiSM30B genes are expressed at high levels in the normal pluteus II sea urchin. SiSM30A is expression was also significantly upregulated in the reparative pluteus II stage 3 hours after damage. Conversely, SiSM30B was downregulated during the reparative pluteus II stage. Our findings reveal a substantial similarity between the activity of SiSM30A and SiSM30B activity in the processes of regenerative growth during the pluteus II stage and during normal development at the prism stage in Strongylocentrotus purpuratus. On the basis of our findings, we propose that normal developmental mechanisms corresponding to the preceding developmental stage are reactivated during pluteus regeneration.

  6. 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

  7. Hematopoietic stem cell transplantation for pediatric mature B-cell acute lymphoblastic leukemia with non-L3 morphology and MLL-AF9 gene fusion: three case reports and review of the literature.

    PubMed

    Sarashina, Takeo; Iwabuchi, Haruko; Miyagawa, Naoyuki; Sekimizu, Masahiro; Yokosuka, Tomoko; Fukuda, Kunio; Hamanoue, Satoshi; Iwasaki, Fuminori; Goto, Shoko; Shiomi, Masae; Imai, Chihaya; Goto, Hiroaki

    2016-07-01

    Mature B-cell acute lymphoblastic leukemia (B-ALL) is typically associated with French-American-British (FAB)-L3 morphology and MYC gene rearrangement. However, rare cases of mature B-ALL with non-L3 morphology and MLL-AF9 fusion have been reported, and such cases are characterized by a rapid and aggressive clinical course. We here report three such cases of pediatric mature B-ALL in female patients respectively aged 15 months, 4 years, and 4 months. Bone marrow smears at diagnosis showed FAB-L1 morphology in all patients. Immunophenotypically, they were positive for cluster of differentiation (CD)10, CD19, CD20 (or CD22), Human Leukocyte Antigen-DR, and surface immunoglobulin λ. No evidence of MYC rearrangement was detected in any of the cases by fluorescent in situ hybridization (FISH) analysis. However, MLL rearrangement was detected by FISH, and MLL-AF9 fusion was confirmed by reverse transcriptase-polymerase chain reaction. All patients achieved complete remission after conventional chemotherapy and subsequently underwent hematopoietic stem cell transplantation as high-risk ALL; patient 3 for infantile ALL with MLL rearrangement and the others for ALL with MLL rearrangement and hyperleukocytosis (white blood cell count at diagnosis >50 × 10(9)/L). At the latest follow-up for each case (12-98 months post-transplantation), complete remission was maintained. Moreover, we discuss the clinical, genetic, and immunophenotypic features of this rare disease. PMID:27084248

  8. Neural Basis of Language: An Overview of An Evolving Model.

    PubMed

    Fujii, Masazumi; Maesawa, Satoshi; Ishiai, Sumio; Iwami, Kenichiro; Futamura, Miyako; Saito, Kiyoshi

    2016-07-15

    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

  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. Phase structure of the anisotropic antiferromagnetic Heisenberg model on a layered triangular lattice: Spiral state and deconfined spin liquid

    SciTech Connect

    Nakane, Kazuya; Kamijo, Takeshi; Ichinose, Ikuo

    2011-02-01

    In the present paper, we study a spin-1/2 antiferromagnetic (AF) Heisenberg model on layered anisotropic triangular lattice and obtain its phase structure. We use the Schwinger bosons for representing spin operators and also a coherent-state path integral for calculating physical quantities. Finite-temperature properties of the system are investigated by means of the numerical Monte-Carlo simulations. A detailed phase diagram of the system is obtained by calculating internal energy, specific heat, spin correlation functions, etc. There are AF Neel, paramagnetic, and spiral states. Turning on the plaquette term (i.e., the Maxwell term on a lattice) of an emergent U(1) gauge field that flips a pair of parallel spin-singlet bonds, we found that there appears a phase that is regarded as a deconfined spin-liquid state, though 'transition' to this phase from the paramagnetic phase is not of second order but a crossover. In that phase, the emergent gauge boson is a physical gapless excitation coupled with spinons. These results support our previous study on an AF Heisenberg model on a triangular lattice at vanishing temperature.

  11. 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.

  12. 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.

  13. Anisotropic Multishell Analytical Modeling of an Intervertebral Disk Subjected to Axial Compression.

    PubMed

    Demers, Sébastien; Nadeau, Sylvie; Bouzid, Abdel-Hakim

    2016-04-01

    Studies on intervertebral disk (IVD) response to various loads and postures are essential to understand disk's mechanical functions and to suggest preventive and corrective actions in the workplace. The experimental and finite-element (FE) approaches are well-suited for these studies, but validating their findings is difficult, partly due to the lack of alternative methods. Analytical modeling could allow methodological triangulation and help validation of FE models. This paper presents an analytical method based on thin-shell, beam-on-elastic-foundation and composite materials theories to evaluate the stresses in the anulus fibrosus (AF) of an axisymmetric disk composed of multiple thin lamellae. Large deformations of the soft tissues are accounted for using an iterative method and the anisotropic material properties are derived from a published biaxial experiment. The results are compared to those obtained by FE modeling. The results demonstrate the capability of the analytical model to evaluate the stresses at any location of the simplified AF. It also demonstrates that anisotropy reduces stresses in the lamellae. This novel model is a preliminary step in developing valuable analytical models of IVDs, and represents a distinctive groundwork that is able to sustain future refinements. This paper suggests important features that may be included to improve model realism. PMID:26833355

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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. PMID:27362546

  19. 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.

  20. 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

  1. [Expression of SM30 (A-F) Genes Encoding Spicule Matrix Proteins in Intact and Damaged Sea Urchin Strongylocentrotus intermedius (A. Agassiz, 1863) at the Six-Arm Pluteus].

    PubMed

    Sharmankina, V V; Kiselev, K V

    2016-03-01

    In this study we investigated expression of the SM30(A-F) gene family encoding Strongylocentrotus intermedius spicule matrix proteins during the normal and regenerative pluteus II stage (three pairs of arms). We found that SiSM30A and SiSM30B genes are expressed at high levels in the normal pluteus II sea urchin. SiSM30A is expression was also significantly upregulated in the reparative pluteus II stage 3 hours after damage. Conversely, SiSM30B was downregulated during the reparative pluteus II stage. Our findings reveal a substantial similarity between the activity of SiSM30A and SiSM30B activity in the processes of regenerative growth during the pluteus II stage and during normal development at the prism stage in Strongylocentrotus purpuratus. On the basis of our findings, we propose that normal developmental mechanisms corresponding to the preceding developmental stage are reactivated during pluteus regeneration. PMID:27281854

  2. 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

  3. 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

  4. Influence of face-centered-cubic texturing of Co2Fe6B2 pinned layer on tunneling magnetoresistance ratio decrease in Co2Fe6B2/MgO-based p-MTJ spin valves stacked with a [Co/Pd]n-SyAF layer

    NASA Astrophysics Data System (ADS)

    Takemura, Yasutaka; Lee, Du-Yeong; Lee, Seung-Eun; Chae, Kyo-Suk; Shim, Tae-Hun; Lian, Guoda; Kim, moon; Park, Jea-Gun

    2015-05-01

    The TMR ratio of Co2Fe6B2/MgO-based p-MTJ spin valves stacked with a [Co/Pd]n-SyAF layer decreased rapidly when the ex situ magnetic annealing temperature (Tex) was increased from 275 to 325 °C, and this decrease was associated with degradation of the Co2Fe6B2 pinned layer rather than the Co2Fe6B2 free layer. At a Tex above 325 °C the amorphous Co2Fe6B2 pinned layer was transformed into a face-centered-cubic (fcc) crystalline layer textured from [Co/Pd]n-SyAF, abruptly reducing the Δ1 coherence tunneling of perpendicular-spin-torque electrons between the (100) MgO tunneling barrier and the fcc Co2Fe6B2 pinned layer.

  5. B →K*l+l-: Zeros of angular observables as test of standard model

    NASA Astrophysics Data System (ADS)

    Kumar, Girish; Mahajan, Namit

    2016-03-01

    We calculate the zeros of angular observables P4' and P5' of the angular distribution of 4-body decay B →K*(→K π )l+l- where LHCb, in its analysis of form-factor independent angular observables, has found deviations from the standard model predictions. In the large recoil region, we obtain relations between the zeros of P4' , P5' and the zero (s^0) of forward-backward asymmetry of lepton pair, AF B. These relations are independent of hadronic uncertainties and depend only on the Wilson coefficients. We also construct a new observable, OTL ,R, whose zero in the standard model coincides with s^0, but in the presence of new physics contributions will show different behavior. Moreover, the profile of the new observable, even within the standard model, is very different from AF B. We point out that precise measurements of these zeros in the near future would provide a crucial test of the standard model and would be useful in distinguishing between different possible new physics contributions to the Wilson coefficients.

  6. 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.

  7. Conventional versus single-ladder-splitting contributions to double parton scattering production of two quarkonia, two Higgs bosons, and cc xAFcc xAF

    NASA Astrophysics Data System (ADS)

    Gaunt, Jonathan R.; Maciuła, Rafał; Szczurek, Antoni

    2014-09-01

    The double parton distributions (dPDF), both conventional (i.e. double ladder) and those corresponding to 1→2 ladder splitting, are calculated and compared for different two-parton combinations. The conventional and splitting dPDFs have very similar shape in x1 and x2. We make a first quantitative evaluation of the single-ladder-splitting contribution to double parton scattering (DPS) production of two S- or P-wave quarkonia, two Higgs bosons and cc ¯cc ¯. The ratio of the single-ladder-splitting to conventional (i.e. double ladder against double ladder) contributions is discussed as a function of center-of-mass energy, mass of the produced system and other kinematical variables. Using a simple model for the dependence of the conventional two-parton distribution on transverse parton separation (Gaussian and independent of xi and scales), we find that the single-ladder-splitting (or 2v1) contribution is as big as the conventional (or 2v2) contribution discussed in recent years in the literature. In many experimental studies of DPS, one extracts the quantity 1/σeff=σDPS/(σSPS ,1σSPS,2), with σSPS ,1 and σSPS ,2 being the single scattering cross sections for the two subprocesses in the DPS process. Many past phenomenological studies of DPS have only considered the conventional contribution and have obtained values a factor of ˜2 too small for 1/σeff. Our analysis shows that it is important also to consider the ladder-splitting mechanism, and that this might resolve the discrepancy (this was also pointed out in a recent study by Blok et al.). The differential distributions in rapidity and transverse momenta calculated for conventional and single-ladder-splitting DPS processes are however very similar which causes their experimental separation to be rather difficult, if not impossible. The direct consequence of the existence of the two components (conventional and splitting) is the energy and process dependence of the empirical parameter σeff. This is

  8. 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. PMID:26627013

  9. Final report on process modeling of cupola furnaces

    SciTech Connect

    Not Available

    1990-07-01

    This report describes the first phase of the AFS/DOE program on mathematical modeling of cupola behavior, covering the period May 19, 1989 to July 19, 1990. The objective of the program is to develop a comprehensive mathematical model of the cupola furnace for on-line and off-line process control and optimization. The work is being carried out by five organizations: Massachusetts Institute of Technology with responsibility for heat transfer and fluid flow modeling, and incorporation of the chemical models being developed by the University of Michigan team. Modern Equipment Company has the responsibility of compiling information on needed sensors for monitoring operation and providing materials data to be used for cupola input. General Motors, Central Foundry Division, is investigating the potential to augment the mathematical models with artificial intelligence programs. Lastly, General Motors Research laboratories are charged with providing accurate cupola operational data to test the models being developed. To date, a one-dimensional steady state model has been developed which considers heat transfer, fluid flow and important chemical processes: combustion, iron composition development, limestone calcination and iron oxidation. The model is based on established physico-chemical principles and data available in the literature. Model predictions compare favorably with data obtained in a production sale cupola, operating under carefully controlled, but realistic, conditions. At the present time, the chemical sub-models are being incorporated into the master program, and a complete working cupola model is expected by September 1990. 43 refs.

  10. 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

  11. Dysconnectivity Within the Default Mode in First-Episode Schizophrenia: A Stochastic Dynamic Causal Modeling Study With Functional Magnetic Resonance Imaging

    PubMed Central

    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. PMID:24939881

  12. Rate Control Management of Atrial Fibrillation: May a Mathematical Model Suggest an Ideal Heart Rate?

    PubMed Central

    Anselmino, Matteo; Scarsoglio, Stefania; Camporeale, Carlo; Saglietto, Andrea; Gaita, Fiorenzo; Ridolfi, Luca

    2015-01-01

    Background Despite the routine prescription of rate control therapy for atrial fibrillation (AF), clinical evidence demonstrating a heart rate target is lacking. Aim of the present study was to run a mathematical model simulating AF episodes with a different heart rate (HR) to predict hemodynamic parameters for each situation. Methods The lumped model, representing the pumping heart together with systemic and pulmonary circuits, was run to simulate AF with HR of 50, 70, 90, 110 and 130 bpm, respectively. Results Left ventricular pressure increased by 57%, from 33.92±37.56 mmHg to 53.15±47.56 mmHg, and mean systemic arterial pressure increased by 27%, from 82.66±14.04 mmHg to 105.3±7.6 mmHg, at the 50 and 130 bpm simulations, respectively. Stroke volume (from 77.45±8.50 to 39.09±8.08 mL), ejection fraction (from 61.10±4.40 to 39.32±5.42%) and stroke work (SW, from 0.88±0.04 to 0.58±0.09 J) decreased by 50, 36 and 34%, at the 50 and 130 bpm simulations, respectively. In addition, oxygen consumption indexes (rate pressure product – RPP, tension time index per minute – TTI/min, and pressure volume area per minute – PVA/min) increased from the 50 to the 130 bpm simulation, respectively, by 186% (from 5598±1939 to 15995±3219 mmHg/min), 56% (from 2094±265 to 3257±301 mmHg s/min) and 102% (from 57.99±17.90 to 117.4±26.0 J/min). In fact, left ventricular efficiency (SW/PVA) decreased from 80.91±2.91% at 50 bpm to 66.43±3.72% at the 130 bpm HR simulation. Conclusion Awaiting compulsory direct clinical evidences, the present mathematical model suggests that lower HRs during permanent AF relates to improved hemodynamic parameters, cardiac efficiency, and lower oxygen consumption. PMID:25764321

  13. Comparison of FACSCount AF system, Improved Neubauer hemocytometer, Corning 254 photometer, SpermVision, UltiMate and NucleoCounter SP-100 for determination of sperm concentration of boar semen.

    PubMed

    Hansen, C; Vermeiden, T; Vermeiden, J P W; Simmet, C; Day, B C; Feitsma, H

    2006-12-01

    Current research aims at reducing the number of sperm per insemination dose thereby making measurement of sperm concentration in raw semen and the production of uniform insemination doses much more crucial. The present study evaluated the determination of sperm concentration using FACSCount AF System (FACS), Improved Neubauer hemocytometer (HEMO), Corning 254 photometer (Photo C254), SpermVision CASA System (SpermVision), UltiMate CASA System (UltiMate) and NucleoCounter SP-100 (SP-100). The instruments were evaluated with respect to repeatability and to establishing the regression curve towards both HEMO and FACS. Repeatability for the instruments was 2.7, 7.1, 10.4, 8.1, 5.4 and 3.1% for FACS, HEMO, Photo C254, SpermVision, UltiMate and SP-100, respectively. Correlation between instruments was highest between FACS and SP-100. This was made possible due to the high repeatability for both instruments. The agreement between the instruments and HEMO as the gold standard was lower than expected as the largest difference in estimation of concentration was -25 to +50%. The largest percentage difference was observed for measurements of dilute semen. It was clear that percentage difference between instruments depended on sperm concentration. In comparison to the gold standard, agreement was highest between SpermVision and HEMO for dilute semen, but for concentrated semen, agreement was highest between SP-100 and HEMO. However, the agreement between HEMO and all other instruments was not as good as expected. The reason may lie within the presence of agglutinated sperm, preventing proper HEMO counts. PMID:16920186

  14. Long-term effects of bisphenol AF (BPAF) on hormonal balance and genes of hypothalamus-pituitary-gonad axis and liver of zebrafish (Danio rerio), and the impact on offspring.

    PubMed

    Shi, Jiachen; Jiao, Zhihao; Zheng, Sai; Li, Ming; Zhang, Jing; Feng, Yixing; Yin, Jie; Shao, Bing

    2015-06-01

    Bisphenol AF (BPAF) is one of the analogues of bisphenol A (BPA) and is widely used as a raw material in the plastics industry. The potential toxicity to fish from exposure to BPAF in the aquatic environment is largely unknown. In this study, zebrafish (Danio rerio) were exposed to BPAF at 5, 25 and 125 μg L(-1), from 4 hour-post-fertilization (hpf) to 120 day-post-fertilization (dpf), representing the period from embryo to adult. The levels of plasma hormones were measured and the expression of selected representative genes along the hypothalamus-pituitary-gonad (HPG) axis and liver were examined. The concentration of 17β-estradiol (E2) was significantly increased in male and female fish and a significant decrease of testosterone (T) was observed in male fish. The mRNA expression of genes along the HPG axis and in liver tissues in F0 generation fish demonstrated that the steroid hormonal balances of zebrafish were modulated through the alteration of steroidgenesis. The significant decrease of egg fertilization among offspring indicates the possibility of sperm deterioration of parent following exposure to BPAF. The higher occurrence of malformation and lower survival rate in the offspring from the exposure group suggested a possibility of maternal transfer of BPAF, which could be responsible for the increased prevalence of adverse health signs in the offspring. The hatching delay in 5 μg L(-1) BPAF indicated that parental exposure to environmentally relevant concentration of BPAF would result in delayed hatching of the offspring. A potential consequence of adverse effects in the offspring by BPAF deserves further investigation. PMID:25723718

  15. Evaluation of the nucleation and coarsening kinetic behavior of the secondary hardening carbide of Fe-HCo-10Ni-1Mo-0.16C steel at two chromium levels, using an analytical and modeling approach: Part II

    NASA Astrophysics Data System (ADS)

    Oh, Y.; Machmeier, P. M.; Matuszewski, T.; Ayer, R.

    1997-06-01

    The effect of 1 % Cr addition on the resistivity during preaging and peak aging of an AF1410 based steel was examined by analytical and modeling approaches. The increased kinetics of aging resulting from a chromium addition, due to a variety of complex microstructural changes,was analyzed by Avrami-Mehl and Wert-Zener formulations, which were modified so that the exponent was a function of time. Using a eneralized Avrami equation, it was shown that the nucleation rate, N(t), at short aging times was large but became a rapidly declining function as N(t) approaches zero in a supersaturated system. A mathematical solution, using AF1410 steel carbide growth data at 510 °C, confirmed reported experimental evidence of second-stage carbide nucleation at 1 to 2 h.

  16. 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

  17. 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.

  18. 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.

  19. Laboratory Experiments Concerning Upwellings From the Slab-Graveyard: Implications For Geochemical and Seismic Models

    NASA Astrophysics Data System (ADS)

    Harris, A. C.; Kincaid, C.; Hall, P.

    2005-12-01

    The ongoing plume debate appears to focus on upwellings characterized by large heads and smaller tails, that form from a deep or basal thermal boundary layer (BTBL), which are driven by temperature excesses in the range of 200° C. We use 3-D laboratory experiments to explore how upwellings might differ from this common plume description when BTBLs are influenced by subducted plates. An important aspect of the models is the representation of ridge chemical differentiation processes resulting in slabs with two distinct layers; a lighter, depleted upper mantle component (Harzburgite:H) and a heavier, iron-rich crustal component (Basalt/Eclogite:B/E). Laboratory experiments utilize a working fluid of glucose syrup with temperature dependent density and viscosity. Compositionally distinct mantle reservoirs are represented through isothermal density/viscosity contrasts controlled by water content. The ambient fluid (AF) is contained within a rectangular tank that is heated from below and cooled from above to produce background convection with a Rayleigh number of 10-5-10-6. Highly viscous, tabular slabs are produced by pouring compositionally distinct syrup from two slab reservoirs (B/E and H) into a mold which is chilled to -5° C. The viscous layered slab is emplaced at the fluid surface and subsequently sinks through, stalls and spreads within a BTBL roughly twice the slab thickness (1 cm). Results show that a wide variety in upwelling morphologies form when layered slabs reside within the BTBL and that plume heads/tails are largely dissimilar to those of the standard plume model. The manner in which the slab laminae vs. AF in the BTBL combine (or segregate) within upwellings depends on viscosity/density contrasts, how slabs collapse in the BTBL, and time. End-member regimes include: experiments dominated by a very light H-slab component with early, cold H-plumes and late, hot B/E-AF plumes and experiments where density differences between H, B/E and AF are small and

  20. 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.

  1. 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

    2016-01-01

    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.

  2. Fundus Autofluorescence and Photoreceptor Cell Rosettes in Mouse Models

    PubMed Central

    Flynn, Erin; Ueda, Keiko; Auran, Emily; Sullivan, Jack M.; Sparrow, Janet R.

    2014-01-01

    Purpose. This study was conducted to study correlations among fundus autofluorescence (AF), RPE lipofuscin accumulation, and photoreceptor cell degeneration and to investigate the structural basis of fundus AF spots. Methods. Fundus AF images (55° lens; 488-nm excitation) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired in pigmented Rdh8−/−/Abca4−/− mice (ages 1–9 months) with a confocal scanning laser ophthalmoscope (cSLO). For quantitative fundus AF (qAF), gray levels (GLs) were calibrated to an internal fluorescence reference. Retinal bisretinoids were measured by quantitative HPLC. Histometric analysis of outer nuclear layer (ONL) thicknesses was performed, and cryostat sections of retina were examined by fluorescence microscopy. Results. Quantified A2E and qAF intensities increased until age 4 months in the Rdh8−/−/Abca4−/− mice. The A2E levels declined after 4 months of age, but qAF intensity values continued to rise. The decline in A2E levels in the Rdh8−/−/Abca4−/− mice paralleled reduced photoreceptor cell viability as reflected in ONL thinning. Hyperautofluorescent puncta in fundus AF images corresponded to photoreceptor cell rosettes in SD-OCT images and histological sections stained with hematoxylin and eosin. The inner segment/outer segment–containing core of the rosette emitted an autofluorescence detected by fluorescence microscopy. Conclusions. When neural retina is disordered, AF from photoreceptor cells can contribute to noninvasive fundus AF images. Hyperautofluorescent puncta in fundus AF images are attributable, in at least some cases, to photoreceptor cell rosettes. PMID:25015357

  3. 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.

  4. [Pulmonary surfactants: in vivo structure and in vitro biophysical models for investigation and its perspectives].

    PubMed

    Lalchev, Z; Khristova, E; Vasiliev, Kh; Todorov, R; Ekserova, D

    2007-01-01

    The metabolism, composition, structure and functions of the alveolar surfactant (AS) are described. The most adequate biophysical models for investigation of AS are considered. The principals and possibilities of three mostly used models are described in details: Monolayers, Spinning drop method and Thin liquid films. Some of the studies of Bulgarian biophysical, physicochemical, biochemical and medical groups on the structure and mechanism of action of AS in vivo using samples of amniotic fluid (AF), animal pulmonary lavages (PL) and tracheal aspirates (TA) of newborns and adults are summarized. The role of specific surfactant proteins (SP-A, SP-B, SP-C and SP-D) on the properties and function of AS is demonstrated. The opportunities of the model investigations for application in laboratory pre- and postnatal diagnosis of the respiratory distress syndrome (RDS), as well as for the efficiency of RDS therapy during exogenous surfactant therapy with ALEC (UK), Survanta (USA), Exosurf (USA), Curosurf (Italy) u Alveofact (Germany) are considered.

  5. Chemical-decomposition models for the thermal explosion of confined HMX, TATB, RDX, and TNT explosives

    SciTech Connect

    McGuire, R.R.; Tarver, C.M.

    1981-03-26

    Chemical decomposition models have been deduced from the available chemical kinetic data on the thermal decomposition of HMX, TATB, RDX, and TNT. A thermal conduction model is used in which the thermal conductivity of the reacting explosive decreases linearly with the mass fraction reacted to that of the gaseous products. These reactive heat flow models are used to predict the time to explosion versus reciprocal temperature curves from several heavily confined explosive tests. Good agreement is obtained between experimental and calculated explosion times for the pure explosives HMX, TATB, RDX, and TNT, mixtures such as RX-26-AF (HMX/TATB), Octol (HMX/TNT), and Comp B (RDX/TNT), and for PBX 9404, an HMX-based explosive containing an energetic nitrocellulose binder.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Morphology and growth of murine cell lines on model biomaterials.

    PubMed

    Godek, Marisha L; Duchsherer, Nichole L; McElwee, Quinn; Grainger, David W

    2004-01-01

    All biomaterial implants are assaulted by the host "foreign body" immune response. Understanding the complex, dynamic relationship between cells, biomaterials and milieu is an important first step towards controlling this reaction. Material surface chemistry dictates protein adsorption, and thus subsequent cell interactions. The cell-implant is a microenvironment involving 1) proteins that coat the surface and 2) cells that interact with these proteins. Macrophages and fibroblasts are two cell types that interact with proteins on biomaterials surfaces and play different related, but equally important, roles in biomaterials rejection and implant failure. Growth characteristics of four murine cell lines on model biomaterials surfaces were examined. Murine monocyte-macrophages (RAW 264.7 and J774A.1), murine macrophage (IC-21) and murine fibroblast (NIH 3T3) cell lines were tested to determine whether differences exist in adhesion, proliferation, differentiation, spreading, and fusion (macrophage lineages only) on these surfaces. Differences were observed in the ability of cells to adhere to and subsequently proliferate on polymer surfaces. (Monocyte-) macrophages grew well on all surfaces tested and growth rates were measured on three representative polymer biomaterials surfaces: tissue culture polystyrene (TCPS), polystyrene, and Teflon-AF. J774A.1 cultures grown on TCPS and treated with exogenous cytokines IL-4 and GM-CSF were observed to contain multinucleate cells with unusual morphologies. Thus, (monocyte-) macrophage cell lines were found to effectively attach to and interrogate each surface presented, with evidence of extensive spreading on Teflon-AF surfaces, particularly in the IC-21 cultures. The J774A.1 line was able to proliferate and/or differentiate to more specialized cell types (multinucleate/dendritic-like cells) in the presence of soluble chemokine cues. PMID:15133927

  11. Leadership Models.

    ERIC Educational Resources Information Center

    Freeman, Thomas J.

    This paper discusses six different models of organizational structure and leadership, including the scalar chain or pyramid model, the continuum model, the grid model, the linking pin model, the contingency model, and the circle or democratic model. Each model is examined in a separate section that describes the model and its development, lists…

  12. 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.

  13. 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

  14. 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. PMID:25871413

  15. 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

  16. 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.

  17. 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. PMID:26774440

  18. 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

  19. Chemical models for cytochrome P450 as a biomimetic metabolic activation system in mutation assays.

    PubMed

    Inami, Keiko; Mochizuki, Masataka

    2002-08-26

    DNA damage is a critical factor in carcinogenesis. The Ames assay is a short-term test that screens for DNA-damaging agents. To be detected in the assay, most carcinogens require oxidation by cytochrome P450, a component of the liver homogenate preparation (S9 mix) that is traditionally used to metabolize promutagens to an active form in vitro. A combination of iron(III) porphyrin plus an oxidant activates many promutagens by mimicking cytochrome P450 metabolism. We previously reported that the mutagenicity of the N-nitrosodialkylamines was detected following reaction with tetrakis(pentafluorophenyl)porphyrinatoiron(III) chloride (Fe(F(5)P)Cl) plus tert-butyl hydroperoxide (t-BuOOH), which yielded the same alcohols and aldehydes as the enzymatic reaction. In the present study, to extend the scope of biomimetic models, we tested the mutagenicity of other carcinogens exposed to chemical oxidation systems.We investigated the optimal assay conditions for the models in Salmonella typhimurium TA1538, a strain sensitive to frame-shift mutagens. We activated 2-aminofluorene (AF), benzo[a]pyrene (B[a]P), a tryptophane pyrolysate 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), and 2-acetylaminofluorene (AAF) with Fe(F(5)P)Cl plus an oxidant-t-BuOOH, m-chloroperoxybenzoic acid (mCPBA), or magnesium monoperoxyphthalate (MPPT)-and we noted the effect of three solvents-acetonitrile (CH(3)CN),1,4-dioxane, and N,N-dimethylformamide (DMF)-on AF activation. All the promutagens became mutagenic in the presence of Fe(F(5)P)Cl plus an oxidant, with the effectiveness of the oxidant varying with the chemical. Aromatic amines, for example, showed the strongest mutagenicity with t-BuOOH whereas polycyclic hydrocarbons showed the strongest mutagenicity with mCPBA. All the promutagens were mutagenic in the presence of Fe(F(5)P)Cl plus MPPT. For AF activation, the order of effectiveness of the solvents was CH(3)CN>1,4-dioxane>DMF. The results suggested that these systems would serve as

  20. Reply to: Discussion of Rennie, A.F. and Hansom, J.D. (2011) 'Sea level trend reversal: land uplift outpaced by sea level rise on Scotland's coast'. Geomorphology, 125 (1), 193-202. By S. Dawson, V.A. Powell, R.W. Duck and D.J. McGlashan, and by I. Shennan

    NASA Astrophysics Data System (ADS)

    Rennie, A. F.; Hansom, J. D.

    2013-09-01

    It is accepted that relative sea-level change is not the reverse of vertical land (crustal) movement, and that the interpretation of an observed reduction in isostatic rebound on the basis of the data presented in Rennie, A.F. and Hansom, J.D. (2011) 'Sea level trend reversal: land uplift outpaced by sea level rise on Scotland's coast' Geomorphology 125, 193-202, is not clearly justified. Nevertheless, we believe the paper to be useful in pointing out the high rates of Scottish relative sea-level rise over the last few decades and we repeat the warning that short-term rates may prove to be inaccurate estimators of the long-term rates needed for coastal infrastructure investment.

  1. Chiral spin density wave order on the frustrated honeycomb and bilayer triangle lattice hubbard model at half-filling.

    PubMed

    Jiang, Kun; Zhang, Yi; Zhou, Sen; Wang, Ziqiang

    2015-05-29

    We study the Hubbard model on the frustrated honeycomb lattice with nearest-neighbor hopping t_{1} and second nearest-neighbor hopping t_{2}, which is isomorphic to the bilayer triangle lattice, using the SU(2)-invariant slave boson theory. We show that the Coulomb interaction U induces antiferromagnetic (AF) chiral spin density wave (χSDW) order in a wide range of κ=t_{2}/t_{1} where both the two-sublattice AF order at small κ and the decoupled three-sublattice 120° order at large κ are strongly frustrated, leading to three distinct phases with different anomalous Hall responses. We find a continuous transition from a χSDW semimetal with the anomalous Hall effect to a topological chiral Chern insulator exhibiting the quantum anomalous Hall effect, followed by a discontinuous transition to a χSDW insulator with a zero total Chern number but an anomalous ac Hall effect. The χSDW is likely a generic phase of strongly correlated and highly frustrated hexagonal lattice electrons. PMID:26066448

  2. Translation of an Engineered Nanofibrous Disc-like Angle Ply Structure for Intervertebral Disc Replacement in a Small Animal Model

    PubMed Central

    Martin, John T.; Milby, Andrew H.; Chiaro, Joseph A.; Kim, Dong Hwa; Hebela, Nader M.; Smith, Lachlan J.; Elliott, Dawn M.; Mauck, Robert L.

    2015-01-01

    Intervertebral disc degeneration has been implicated in the etiology of low back pain; however the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF), and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, have functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilize the motion segment by external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space, and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. PMID:24560621

  3. Chiral spin density wave order on the frustrated honeycomb and bilayer triangle lattice hubbard model