Sample records for f factor

  1. E2F1 transcription factor and its impact on growth factor and cytokine signaling.

    PubMed

    Ertosun, Mustafa Gokhan; Hapil, Fatma Zehra; Osman Nidai, Ozes

    2016-10-01

    E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ). Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).

    PubMed

    Erlandsson, Maria; Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Jesper B; Petersen, Lars C; Madsen, Jacob; Kjaer, Andreas

    2015-05-15

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Analysis of E2F factors during epidermal differentiation.

    PubMed

    Chang, Wing Y; Dagnino, Lina

    2005-01-01

    The multigene E2F family of transcription factors is central in the control of cell cycle progression. The expression and activity of E2F proteins is tightly regulated transcriptionally and posttranslationally as a function of the proliferation and differentiation status of the cell. In this chapter, we review protocols designed to determine E2F mRNA abundance in tissues by in situ hybridization techniques. The ability to culture primary epidermal keratinocytes and maintain them as either undifferentiated or terminally differentiated cells allows the biochemical and molecular characterization of changes in E2F expression and activity. Thus, we also discuss in detail methods to analyze E2F protein abundance by immunoblot and their ability to bind DNA in cultured cells using electrophoretic mobility shift assays.

  4. Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

    PubMed

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

    2016-01-01

    Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

  5. Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal of factor Xa inhibitors.

    PubMed

    Tao, Jing; Bukanova, Elena N; Akhtar, Shamsuddin

    2018-01-01

    Although factor Xa inhibitors have become a popular choice for chronic oral anticoagulation, effective drug reversal remains difficult due to a lack of specific antidote. Currently, 4-factor prothrombin complex concentrate (4F-PCC) is considered the treatment of choice for factor Xa inhibitor-related major bleeding. However, safety of 4F-PCC and its risk of thrombosis when used for this off-label purpose remain unclear. The purpose of this retrospective study is to determine the rate of thromboembolism when 4F-PCC is used for the emergent reversal of factor Xa inhibitors. We conducted a single-center retrospective review of medical records between 2013 and 2017. Patients were included if they received 4F-PCC to reverse rivaroxaban, apixaban, or edoxaban for emergent invasive procedures or during episodes of major bleeding defined as bleeding with hemodynamic instability, fall in hemoglobin of 2 g/dL, or bleeding requiring blood transfusion. Thrombotic events including myocardial infarction, pulmonary embolism, deep vein thrombosis, cerebral vascular accident, and arterial thrombosis of the limb or mesentery were recorded if they occurred within 14 days of 4F-PCC administration. Data was analyzed using point and interval estimation to approximate the rate and confidence interval of thromboembolic events. Forty-three patients were identified in our review. Doses of 4F-PCC were determined by the treating physician and mainly ranged from 25 to 50 IU/kg. Twenty-two patients (51.2%) received both sequential compression devices (SCDs) and subcutaneous heparin for DVT prophylaxis. Twenty-one patients (48.8%) were placed on SCDs only. Three patients received concomitant FFP. Thrombotic events within 14 days of 4F-PCC administration occurred in 1 out of 43 patients (2.1%, 95% CI [0.1-12.3]). This thrombotic event was an upper extremity DVT which occurred 1 day after the patient received 1325 IU (25 IU/kg) of 4F-PCC to reverse rivaroxaban for traumatic intracranial

  6. Factors affecting expression of the recF gene of Escherichia coli K-12.

    PubMed

    Sandler, S J; Clark, A J

    1990-01-31

    This report describes four factors which affect expression of the recF gene from strong upstream lambda promoters under temperature-sensitive cIAt2-encoded repressor control. The first factor was the long mRNA leader sequence consisting of the Escherichia coli dnaN gene and 95% of the dnaA gene and lambda bet, N (double amber) and 40% of the exo gene. When most of this DNA was deleted, RecF became detectable in maxicells. The second factor was the vector, pBEU28, a runaway replication plasmid. When we substituted pUC118 for pBEU28, RecF became detectable in whole cells by the Coomassie blue staining technique. The third factor was the efficiency of initiation of translation. We used site-directed mutagenesis to change the mRNA leader, ribosome-binding site and the 3 bp before and after the translational start codon. Monitoring the effect of these mutational changes by translational fusion to lacZ, we discovered that the efficiency of initiation of translation was increased 30-fold. Only an estimated two- or threefold increase in accumulated levels of RecF occurred, however. This led us to discover the fourth factor, namely sequences in the recF gene itself. These sequences reduce expression of the recF-lacZ fusion genes 100-fold. The sequences responsible for this decrease in expression occur in four regions in the N-terminal half of recF. Expression is reduced by some sequences at the transcriptional level and by others at the translational level.

  7. Free factor XIII activation peptide (fAP-FXIII) is a regulator of factor XIII activity via factor XIII-B.

    PubMed

    Dodt, Johannes; Pasternack, Ralf; Seitz, Rainer; Volkers, Peter

    2016-02-01

    In a factor XIIIa (FXIIIa) generation assay with recombinant FXIII-A2 (rFXIII-A2 ) free FXIII activation peptide (fAP-FXII) prolonged the time to peak (TTP) but did not affect the area under the curve (AUC) or concentration at peak (CP). Addition of recombinant factorXIII-B2 (rFXIII-B2 ) restored the characteristics of the FXIIIa generation parameters (AUC, TTP and CP) to those observed for plasma FXIII (FXIII-A2 B2 ). FXIII-A2 B2 reconstituted from rFXIII-A2 and rFXIII-B2 showed a similar effect on AUC, TTP and CP in the presence of fAP-FXII as observed for plasma FXIII-A2 B2 , indicating a role for FXIII-B in this observation. An effect of fAP-FXIII on thrombin, the proteolytic activator of FXIII, was excluded by thrombin generation assays and clotting experiments. In a purified system, fAP-FXIII did not interfere with the FXIIIa activity development of thrombin-cleaved rFXIII-A2 (rFXIII-A2 ') also excluding direct inhibition of FXIIIa. However, FXIIIa activity development of FXIII-A2 'B2 was inhibited in a concentration-dependent manner by fAP-FXIII, indicating that an interaction between AP-FXIII and FXIII-B2 contributes to the overall stability of FXIII-A2 'B2 . In addition to its well-known role, FXIII-B also contributes to FXIII-A2 B2 stability or dissociation depending on fAP-FXIII and calcium concentrations. © 2015 John Wiley & Sons Ltd.

  8. EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

    PubMed

    Judah, David; Chang, Wing Y; Dagnino, Lina

    2010-11-10

    Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

  9. 49 CFR 192.111 - Design factor (F) for steel pipe.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Pipe Design § 192.111 Design factor (F... street, or a railroad; (3) Is supported by a vehicular, pedestrian, railroad, or pipeline bridge; or (4...

  10. E2F transcription factors and digestive system malignancies: how much do we know?

    PubMed

    Evangelou, Konstantinos; Havaki, Sophia; Kotsinas, Athanassios

    2014-08-07

    The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accumulating data suggest that there is no specific role for each individual E2F member. Instead, each E2F can exert a variety of cellular effects, some of which represent opposing ones. For instance, specific E2Fs can activate transcription and repression, promote or hamper cell proliferation, augment or inhibit apoptosis, all being dependent on the cellular context. This complexity reflects the importance that these transcription factors have on a cell's fate. Thus, delineating the specific role for each E2F member in specific malignancies, although not easy, is a challenging and continuously pursued task, especially in view of potential E2F targeted therapies. Therefore, several reviews are continuously trying to evaluate available data on E2F status in various malignancies. Such reviews have attempted to reach a consensus, often in the simplistic form of oncogenes or tumor suppressor genes for the E2Fs. However they frequently miss spatial and temporal alterations of these factors during tumor development, which should also be considered in conjunction with the status of the regulatory networks that these factors participate in. In the current ''Letter to the Editor'', we comment on the flaws, misinterpretations and omissions in one such review article published recently in the World Journal of Gastroenterology regarding the role of E2Fs in digestive system malignancies.

  11. Novel functions for the transcription factor E2F4 in development and disease

    PubMed Central

    Sage, Julien

    2016-01-01

    ABSTRACT The E2F family of transcription factors is a key determinant of cell proliferation in response to extra- and intra-cellular signals. Within this family, E2F4 is a transcriptional repressor whose activity is critical to engage and maintain cell cycle arrest in G0/G1 in conjunction with members of the retinoblastoma (RB) family. However, recent observations challenge this paradigm and indicate that E2F4 has a multitude of functions in cells besides this cell cycle regulatory role, including in embryonic and adult stem cells, during regenerative processes, and in cancer. Some of these new functions are independent of the RB family and involve direct activation of target genes. Here we review the canonical functions of E2F4 and discuss recent evidence expanding the role of this transcription factor, with a focus on cell fate decisions in tissue homeostasis and regeneration. PMID:27753528

  12. S-factor of 14 N (α, γ)18 F reaction at low-energies

    NASA Astrophysics Data System (ADS)

    Khalili, H.

    2018-06-01

    The astrophysical S-factor of the 14 N (α, γ)18 F reaction has been studied at range of bombarding energy 1-1.30 MeV. The 14 N (α, γ)18 F process is important in low energy astrophysics so that a possible source of energy in massive stars which have spent their hydrogen cycle. Using the Wood-saxon potential model, we have been calculated non resonances the astrophysical S-factors for the E 2 transition and our results for Eα = 0.0 MeV is S ≈ 0.5 MeV.b where from experimental is measured to Eα = 0.0 is S ≈ o . 7 MeV.b (Couch et al., 1971) that in comparison with our data good agreement is achieved for the astrophysical S-factor of this process.

  13. 49 CFR 192.111 - Design factor (F) for steel pipe.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Design factor (F) for steel pipe. 192.111 Section...) for steel pipe. (a) Except as otherwise provided in paragraphs (b), (c), and (d) of this section, the... less must be used in the design formula in § 192.105 for steel pipe in Class 1 locations that: (1...

  14. 49 CFR 192.111 - Design factor (F) for steel pipe.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Design factor (F) for steel pipe. 192.111 Section...) for steel pipe. (a) Except as otherwise provided in paragraphs (b), (c), and (d) of this section, the... less must be used in the design formula in § 192.105 for steel pipe in Class 1 locations that: (1...

  15. 49 CFR 192.111 - Design factor (F) for steel pipe.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Design factor (F) for steel pipe. 192.111 Section...) for steel pipe. (a) Except as otherwise provided in paragraphs (b), (c), and (d) of this section, the... less must be used in the design formula in § 192.105 for steel pipe in Class 1 locations that: (1...

  16. 49 CFR 192.111 - Design factor (F) for steel pipe.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Design factor (F) for steel pipe. 192.111 Section...) for steel pipe. (a) Except as otherwise provided in paragraphs (b), (c), and (d) of this section, the... less must be used in the design formula in § 192.105 for steel pipe in Class 1 locations that: (1...

  17. Theoretical studies of the dependence of EPR g-factors on local structure for the trigonal Er3+-VK centres in KMgF3 and KZnF3

    NASA Astrophysics Data System (ADS)

    Chai, Rui-Peng; Kuang, Xiao-Yu; Liang, Liang; Yu, Geng-Hua

    2015-05-01

    The dependence of the EPR g-factors on the local structural parameter for a 4f11 configuration ion Er3+ in a trigonal crystal-field has been studied by diagonalizing the 364×364 complete energy matrices. Our studies indicate that the EPR spectra of the trigonal Er3+-VK centers in KMgF3 and KZnF3 may be attributed to the translation of the cubic Kramers doublet Γ7. Furthermore, the EPR g-factors of the trigonal Er3+-VK centers may be interpreted reasonably by the shifts ΔZ≈0.340 Å and ΔZ≈0.303 Å of the Er3+ ions toward the charge compensator VK along the C3 axis for the KMgF3:Er3+ and the KZnF3:Er3+ systems respectively.

  18. Characterization of diverse subvariants of the meningococcal factor H (fH) binding protein for their ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies.

    PubMed

    Seib, Kate L; Brunelli, Brunella; Brogioni, Barbara; Palumbo, Emmanuelle; Bambini, Stefania; Muzzi, Alessandro; DiMarcello, Federica; Marchi, Sara; van der Ende, Arie; Aricó, Beatrice; Savino, Silvana; Scarselli, Maria; Comanducci, Maurizio; Rappuoli, Rino; Giuliani, Marzia M; Pizza, Mariagrazia

    2011-02-01

    Neisseria meningitidis is a commensal of the human nasopharynx but is also a major cause of septicemia and meningitis. The meningococcal factor H binding protein (fHbp) binds human factor H (fH), enabling downregulation of complement activation on the bacterial surface. fHbp is a component of two serogroup B meningococcal vaccines currently in clinical development. Here we characterize 12 fHbp subvariants for their level of surface exposure and ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies. Flow cytometry and Western analysis revealed that all strains examined expressed fHbp on their surface to different extents and bound fH in an fHbp-dependent manner. However, differences in fH binding did not always correlate with the level of fHbp expression, indicating that this is not the only factor affecting the amount of fH bound. To overcome the issue of strain variability in fHbp expression, the MC58ΔfHbp strain was genetically engineered to express different subvariants from a constitutive heterologous promoter. These recombinant strains were characterized for fH binding, and the data confirmed that each subvariant binds different levels of fH. Surface plasmon resonance revealed differences in the stability of the fHbp-fH complexes that ranged over 2 orders of magnitude, indicating that differences in residues between and within variant groups can influence fH binding. Interestingly, the level of survival in human sera of recombinant MC58 strains expressing diverse subvariants did not correlate with the level of fH binding, suggesting that the interaction of fHbp with fH is not the only function of fHbp that influences serum resistance. Furthermore, cross-reactive bactericidal activity was seen within each variant group, although the degree of activity varied, suggesting that amino acid differences within each variant group influence the bactericidal antibody response.

  19. Copy number variations of E2F1: a new genetic risk factor for testicular cancer.

    PubMed

    Rocca, Maria Santa; Di Nisio, Andrea; Marchiori, Arianna; Ghezzi, Marco; Opocher, Giuseppe; Foresta, Carlo; Ferlin, Alberto

    2017-03-01

    Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years, many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer. E2F1 is a transcription factor that plays an important role in regulating cell growth, differentiation, apoptosis and response to DNA damage. Therefore, deficiency or overexpression of this protein might significantly influence fundamental biological processes involved in cancer development and progression, including TGCT. We analyzed E2F1 CNVs in 261 cases with TGCT and 165 controls. We found no CNVs in controls, but 17/261 (6.5%) cases showed duplications in E2F1 Blot analysis demonstrated higher E2F1 expression in testicular samples of TGCT cases with three copies of the gene. Furthermore, we observed higher phosphorylation of Akt and mTOR in samples with E2F1 duplication. Interestingly, normal, non-tumoral testicular tissue in patient with E2F1 duplication showed lower expression of E2F1 and lower AKT/mTOR phosphorylation with respect to adjacent tumor tissue. Furthermore, increased expression of E2F1 obtained in vitro in NTERA-2 testicular cell line induced increased AKT/mTOR phosphorylation. This study suggests for the first time an involvement of E2F1 CNVs in TGCT susceptibility and supports previous preliminary data on the importance of AKT/mTOR signaling pathway in this cancer. © 2017 Society for Endocrinology.

  20. Human Factors Engineering #2 Crewstation Assessment for the OH-58F Helicopter

    DTIC Science & Technology

    2013-03-01

    1 ARMY RSCH LABORATORY – HRED (HC) HUMAN RSRCH AND ENGRNG DIRCTRT MCOE FIELD ELEMENT RDRL HRM DW C CARSTENS 6450 WAY ST BLDG 2839 RM... Human Factors Engineering #2 Crewstation Assessment for the OH-58F Helicopter by David B. Durbin, Jamison S. Hicks, Michael Sage Jessee...Research Laboratory Aberdeen Proving Ground, MD 21005 ARL-TR-6355 March 2013 Human Factors Engineering #2 Crewstation Assessment for the

  1. Crystal structure of the Vibrio cholerae colonization factor TcpF and identification of a functional immunogenic site.

    PubMed

    Megli, Christina J; Yuen, Alex S W; Kolappan, Subramaniapillai; Richardson, Malcolm R; Dharmasena, Madushini N; Krebs, Shelly J; Taylor, Ronald K; Craig, Lisa

    2011-06-03

    Vibrio cholerae relies on two main virulence factors--toxin-coregulated pilus (TCP) and cholera toxin--to cause the gastrointestinal disease cholera. TCP is a type IV pilus that mediates bacterial autoagglutination and colonization of the intestine. TCP is encoded by the tcp operon, which also encodes TcpF, a protein of unknown function that is secreted by V. cholerae in a TCP-dependent manner. Although TcpF is not required for TCP biogenesis, a tcpF mutant has a colonization defect in the infant mouse cholera model that is as severe as a pilus mutant. Furthermore, TcpF antisera protect against V. cholerae infection. TcpF has no apparent sequence homology to any known protein. Here, we report the de novo X-ray crystal structure of TcpF and the identification of an epitope that is critical for its function as a colonization factor. A monoclonal antibody recognizing this epitope is protective against V. cholerae challenge and adds to the protection provided by an anti-TcpA antibody. These data suggest that TcpF has a novel function in V. cholerae colonization and define a region crucial for this function. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Functional synergy between DP-1 and E2F-1 in the cell cycle-regulating transcription factor DRTF1/E2F.

    PubMed Central

    Bandara, L R; Buck, V M; Zamanian, M; Johnston, L H; La Thangue, N B

    1993-01-01

    It is widely believed that the cellular transcription factor DRTF1/E2F integrates cell cycle events with the transcription apparatus because during cell cycle progression in mammalian cells it interacts with molecules that are important regulators of cellular proliferation, such as the retinoblastoma tumour suppressor gene product (pRb), p107, cyclins and cyclin-dependent kinases. Thus, pRb, which negatively regulates early cell cycle progression and is frequently mutated in tumour cells, and the Rb-related protein p107, bind to and repress the transcriptional activity of DRTF1/E2F. Viral oncoproteins, such as adenovirus E1a and SV40 large T antigen, overcome such repression by sequestering pRb and p107 and in so doing are likely to activate genes regulated by DRTF1/E2F, such as cdc2, c-myc and DHFR. Two sequence-specific DNA binding proteins, E2F-1 and DP-1, which bind to the E2F site, contain a small region of similarity. The functional relationship between them has, however, been unclear. We report here that DP-1 and E2F-1 exist in a DNA binding complex in vivo and that they bind efficiently and preferentially as a heterodimer to the E2F site. Moreover, studies in yeast and Drosophila cells indicate that DP-1 and E2F-1 interact synergistically in E2F site-dependent transcriptional activation. Images PMID:8223441

  3. Forkhead Transcription Factor Fd3F Cooperates with Rfx to Regulate a Gene Expression Program for Mechanosensory Cilia Specialization

    PubMed Central

    Newton, Fay G.; zur Lage, Petra I.; Karak, Somdatta; Moore, Daniel J.; Göpfert, Martin C.; Jarman, Andrew P.

    2012-01-01

    Summary Cilia have evolved hugely diverse structures and functions to participate in a wide variety of developmental and physiological processes. Ciliary specialization requires differences in gene expression, but few transcription factors are known to regulate this, and their molecular function is unclear. Here, we show that the Drosophila Forkhead box (Fox) gene, fd3F, is required for specialization of the mechanosensory cilium of chordotonal (Ch) neurons. fd3F regulates genes for Ch-specific axonemal dyneins and TRPV ion channels, which are required for sensory transduction, and retrograde transport genes, which are required to differentiate their distinct motile and sensory ciliary zones. fd3F is reminiscent of vertebrate Foxj1, a motile cilia regulator, but fd3F regulates motility genes as part of a broader sensory regulation program. Fd3F cooperates with the pan-ciliary transcription factor, Rfx, to regulate its targets directly. This illuminates pathways involved in ciliary specialization and the molecular mechanism of transcription factors that regulate them. PMID:22698283

  4. Tumultuous Relationship between the Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) and the Human APOBEC-3G and APOBEC-3F Restriction Factors

    PubMed Central

    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-01-01

    Summary: The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive cells, possess strong anti-HIV-1 activity and are sufficient to confer a nonpermissive phenotype. Vif induces the degradation of hA3G and hA3F, suggesting that its main function is to counteract these cellular factors. Most studies focused on the hypermutation induced by the cytidine deaminase activity of hA3G and hA3F and on their Vif-induced degradation by the proteasome. However, recent studies suggested that several mechanisms are involved both in the antiviral activity of hA3G and hA3F and in the way Vif counteracts these antiviral factors. Attempts to reconcile the studies involving Vif in virus assembly and stability with these recent findings suggest that hA3G and hA3F partially exert their antiviral activity independently of their catalytic activity by destabilizing the viral core and the reverse transcription complex, possibly by interfering with the assembly and/or maturation of the viral particles. Vif could then counteract hA3G and hA3F by excluding them from the viral assembly intermediates through competition for the viral genomic RNA, by regulating the proteolytic processing of Pr55Gag, by enhancing the efficiency of the reverse transcription process, and by inhibiting the enzymatic activities of hA3G and hA3F. PMID:19487726

  5. Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors.

    PubMed

    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-06-01

    The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive cells, possess strong anti-HIV-1 activity and are sufficient to confer a nonpermissive phenotype. Vif induces the degradation of hA3G and hA3F, suggesting that its main function is to counteract these cellular factors. Most studies focused on the hypermutation induced by the cytidine deaminase activity of hA3G and hA3F and on their Vif-induced degradation by the proteasome. However, recent studies suggested that several mechanisms are involved both in the antiviral activity of hA3G and hA3F and in the way Vif counteracts these antiviral factors. Attempts to reconcile the studies involving Vif in virus assembly and stability with these recent findings suggest that hA3G and hA3F partially exert their antiviral activity independently of their catalytic activity by destabilizing the viral core and the reverse transcription complex, possibly by interfering with the assembly and/or maturation of the viral particles. Vif could then counteract hA3G and hA3F by excluding them from the viral assembly intermediates through competition for the viral genomic RNA, by regulating the proteolytic processing of Pr55(Gag), by enhancing the efficiency of the reverse transcription process, and by inhibiting the enzymatic activities of hA3G and hA3F.

  6. How the early sporulation sigma factor sigmaF delays the switch to late development in Bacillus subtilis.

    PubMed

    Karmazyn-Campelli, Céline; Rhayat, Lamya; Carballido-López, Rut; Duperrier, Sandra; Frandsen, Niels; Stragier, Patrick

    2008-03-01

    Sporulation in Bacillus subtilis is a primitive differentiation process involving two cell types, the forespore and the mother cell. Each cell implements two successive transcription programmes controlled by specific sigma factors. We report that activity of sigma(G), the late forespore sigma factor, is kept in check by Gin, the product of csfB, a gene controlled by sigma(F), the early forespore sigma factor. Gin abolishes sigma(G) transcriptional activity when sigma(G) is artificially synthesized during growth, but has no effect on sigma(F). Gin interacts strongly with sigma(G) but not with sigma(F) in a yeast two-hybrid experiment. The absence of Gin allows sigma(G) to be active during sporulation independently of the mother-cell development to which it is normally coupled. Premature sigma(G) activity leads to the formation of slow-germinating spores, and complete deregulation of sigma(G) synthesis is lethal when combined with gin inactivation. Gin allows sigma(F) to delay the switch to the late forespore transcription programme by preventing sigma(G) to take over before the cell has reached a critical stage of development. A similar strategy, following a completely unrelated route, is used by the mother cell.

  7. The Structure of RalF, an ADP-Ribosylation Factor Guanine Nucleotide Exchange Factor from Legionella pneumophila, Reveals the Presence of a Cap over the Active Site

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

    Amor,J.; Swails, J.; Zhu, X.

    2005-01-01

    The Legionella pneumophila protein RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine nucleotide exchange factors, has suggested that recruitment of Arf is an early step in pathogenesis. We have determined the crystal structure of RalF and of the isolated Sec7 domain and found that RalF is made up of two domains. The Sec7 domain is homologous to mammalian Sec7 domains. The C-terminal domain forms amore » cap over the active site in the Sec7 domain and contains a conserved folding motif, previously observed in adaptor subunits of vesicle coat complexes. The importance of the capping domain and of the glutamate in the 'glutamic finger,' conserved in all Sec7 domains, to RalF functions was examined using three different assays. These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities.« less

  8. Identification of a Kinase in Wheat Germ that Phosphorylates the Large Subunit of Initiation Factor 4F 1

    PubMed Central

    Humphreys, Jean; Browning, Karen S.; Ravel, Joanne M.

    1988-01-01

    A kinase has been isolated from wheat (Triticum aestivum) germ that phosphorylates the 220 kilodaltons (kD) subunit of wheat germ initiation factor (eIF) 4F, the 80 kD subunit of eIF-4B (an isozyme form of eIF-4F) and eIF-4G (the functional equivalent to mammalian eIF-4B). The kinase elutes from Sephacryl S-200 slightly in front of ovalbumin. The kinase phosphorylates casein and histone IIA to a small extent, but does not phosphorylate phosvitin. Of the wheat germ initiation factors, elongation factors, and small and large ribosomal subunits, only eIF-4F, eIF-4B, and eIF-4G are phosphorylated to a significant extent. The kinase phosphorylates eIF-4F to the extent of two phosphates per mole of the 220 kD subunit and phosphorylates eIF-4B to the extent of one phosphate per mole of the 80 kD subunit. The 26 kD subunit of eIF-4F and the 28 kD subunit of eIF-4B are not phosphorylated by the kinase. The kinase phosphorylates the 59 kD component of eIF-4G to the extent of 0.25 phosphate per mole of eIF-4G. Phosphorylation of eIF-4F and eIF-4B does not affect their ability to support the binding of mRNA to small ribosomal subunits in vitro. Images Fig. 2 Fig. 3 PMID:16666331

  9. E2F transcription factors and digestive system malignancies: how much do we know?

    PubMed

    Xanthoulis, Athanasios; Tiniakos, Dina G

    2013-06-07

    E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumor-promoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.

  10. The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F): Exploratory and Confirmatory Factor Analyses at Item Level

    ERIC Educational Resources Information Center

    Justicia, Fernando; Pichardo, M. Carmen; Cano, Francisco; Berben, A. B. G.; De la Fuente, Jesus

    2008-01-01

    The underlying structure of the Revised Two Factor version of the Study Process Questionnaire (R-SPQ-2F), a 20-item instrument for the evaluation of students' approaches to learning (SAL), was examined at item level using two independent groups of undergraduate students enrolled in the first (n = 314) and last (n = 522) years of their studies. The…

  11. Transcription factors ETF, E2F, and SP-1 are involved in cytokine-independent proliferation of murine hepatocytes.

    PubMed

    Zellmer, Sebastian; Schmidt-Heck, Wolfgang; Godoy, Patricio; Weng, Honglei; Meyer, Christoph; Lehmann, Thomas; Sparna, Titus; Schormann, Wiebke; Hammad, Seddik; Kreutz, Clemens; Timmer, Jens; von Weizsäcker, Fritz; Thürmann, Petra A; Merfort, Irmgard; Guthke, Reinhard; Dooley, Steven; Hengstler, Jan G; Gebhardt, Rolf

    2010-12-01

    The cellular basis of liver regeneration has been intensely investigated for many years. However, the mechanisms initiating hepatocyte "plasticity" and priming for proliferation are not yet fully clear. We investigated alterations in gene expression patterns during the first 72 hours of C57BL/6N mouse hepatocyte culture on collagen monolayers (CM), which display a high basal frequency of proliferation in the absence of cytokines. Although many metabolic genes were down-regulated, genes related to mitogen-activated protein kinase (MAPK) signaling and cell cycle were up-regulated. The latter genes showed an overrepresentation of transcription factor binding sites (TFBS) for ETF (TEA domain family member 2), E2F1 (E2F transcription factor 1), and SP-1 (Sp1 transcription factor) (P < 0.001), all depending on MAPK signaling. Time-dependent increase of ERK1/2 phosphorylation occurred during the first 48 hours (and beyond) in the absence of cytokines, accompanied by an enhanced bromodeoxyuridine labeling index of 20%. The MEK inhibitor PD98059 blunted these effects indicating MAPK signaling as major trigger for this cytokine-independent proliferative response. In line with these in vitro findings, liver tissue of mice challenged with CCl(4) displayed hepatocytes with intense p-ERK1/2 staining and nuclear SP-1 and E2F1 expression. Furthermore, differentially expressed genes in mice after partial hepatectomy contained overrepresented TFBS for ETF, E2F1, and SP-1 and displayed increased expression of E2F1. Cultivation of murine hepatocytes on CM primes cells for proliferation through cytokine-independent activation of MAPK signaling. The transcription factors ETF, E2F1, and SP-1 seem to play a pronounced role in mediating proliferation-dependent differential gene expression. Similar events, but on a shorter time-scale, occur very early after liver damage in vivo. Copyright © 2010 American Association for the Study of Liver Diseases.

  12. Influence of Environmental Factors on the Production of Penitrems A-F by Penicillium crustosum.

    PubMed

    Kalinina, Svetlana A; Jagels, Annika; Cramer, Benedikt; Geisen, Rolf; Humpf, Hans-Ulrich

    2017-07-01

    Filamentous fungi produce a multitude of secondary metabolites, some of them known as mycotoxins, which are toxic to vertebrates and other animal groups in low concentrations. Among them, penitrems, which belong to the group of indole-diterpene mycotoxins, are synthesized by Penicillium and Aspergillus genera and exhibit potent tremorgenic effects. This is the first complex study of the penitrems A-F production under the influence of different abiotic factors, e.g., media, incubation time, temperature, pH, light, water activity, and carbon and nitrogen source as well as oxidative and salt stress. For this purpose, penitrems A-F were isolated from Penicillium crustosum cultures and used as analytical standards. Among the carbon sources, glucose supplemented to the media at the concentration of 50 g/L, showed the strongest inducing effect on the biosynthesis of penitrems. Among nitrogen sources, glutamate was found to be the most favorable supplement, significantly increasing production of these secondary metabolites. CuSO4-promoted oxidative stress was also shown to remarkably stimulate biosynthesis of all penitrems. In contrast, the salt stress, caused by the elevated concentrations of NaCl, showed an inhibitory effect on the penitrem biosynthesis. Finally, cheese model medium elicited exceptionally high production of all members of the penitrems family. Obtained results give insides into the biosynthesis of toxicologically relevant penitrems A-F under different environmental factors and can be utilized to prevent food contamination.

  13. Host control of plasmid replication: requirement for the sigma factor sigma 32 in transcription of mini-F replication initiator gene.

    PubMed Central

    Wada, C; Imai, M; Yura, T

    1987-01-01

    Replication of F factor or mini-F plasmid is strongly inhibited in the rpoH (htpR) mutants of Escherichia coli deficient in the sigma factor (sigma 32) known to be required for heat shock gene expression. Transcription of the mini-F repE gene encoding a replication initiator protein (E protein) was examined by operon fusion and by direct determination of repE mRNA. The synthesis rate and the level of repE mRNA were found to increase transiently upon temperature upshift (30 degrees C to 42 degrees C) in wild-type cells but to decrease rapidly in the rpoH mutants. Thus sigma 32 appeared to be directly involved in transcription of repE whose product, E protein, in turn activates DNA replication from the mini-F ori2 region. This scheme of host-controlled plasmid replication is further supported by the analysis of transcription in vitro: RNA synthesis can be initiated from the repE promoter by a minor form of RNA polymerase containing sigma 32 but not by the major polymerase containing the normal sigma factor sigma 70. The sigma 32-mediated transcription from the repE promoter is strongly inhibited by the E protein. We conclude that transcription of the mini-F repE gene is mediated by the host transcription factor sigma 32 and is negatively controlled by its own product. Images PMID:2447584

  14. Krüppel-like factor 1 mutations and expression of hemoglobins F and A2 in homozygous hemoglobin E syndrome.

    PubMed

    Tepakhan, Wanicha; Yamsri, Supawadee; Fucharoen, Goonnapa; Sanchaisuriya, Kanokwan; Fucharoen, Supan

    2015-07-01

    The basis for variability of hemoglobin (Hb) F in homozygous Hb E disease is not well understood. We have examined multiple mutations of the Krüppel-like factor 1 (KLF1) gene; an erythroid specific transcription factor and determined their associations with Hbs F and A2 expression in homozygous Hb E. Four KLF1 mutations including G176AfsX179, T334R, R238H, and -154 (C-T) were screened using specific PCR assays on 461 subjects with homozygous Hb E and 100 normal controls. None of these four mutations were observed in 100 normal controls. Among 461 subjects with homozygous Hb E, 306 had high (≥5 %) and 155 had low (<5 %) Hb F. DNA analysis identified the KLF1 mutations in 35 cases of the former group with high Hb F, including the G176AfsX179 mutation (17/306 = 5.6 %), T334R mutation (9/306 = 2.9 %), -154 (C-T) mutation (7/306 = 2.3 %), and R328H mutation (2/306 = 0.7 %). Only two subjects in the latter group with low Hb F carried the G176AfsX179 and -154 (C-T) mutations. Significant higher Hb A2 level was observed in those of homozygous Hb E with the G176AfsX179 mutation as compared to those without KLF1 mutations. These results indicate that KLF1 is among the genetic factors associated with increased Hbs F and A2, and in combination with other factors could explain the variabilities of these Hb expression in Hb E syndrome.

  15. Bayesian switching factor analysis for estimating time-varying functional connectivity in fMRI.

    PubMed

    Taghia, Jalil; Ryali, Srikanth; Chen, Tianwen; Supekar, Kaustubh; Cai, Weidong; Menon, Vinod

    2017-07-15

    There is growing interest in understanding the dynamical properties of functional interactions between distributed brain regions. However, robust estimation of temporal dynamics from functional magnetic resonance imaging (fMRI) data remains challenging due to limitations in extant multivariate methods for modeling time-varying functional interactions between multiple brain areas. Here, we develop a Bayesian generative model for fMRI time-series within the framework of hidden Markov models (HMMs). The model is a dynamic variant of the static factor analysis model (Ghahramani and Beal, 2000). We refer to this model as Bayesian switching factor analysis (BSFA) as it integrates factor analysis into a generative HMM in a unified Bayesian framework. In BSFA, brain dynamic functional networks are represented by latent states which are learnt from the data. Crucially, BSFA is a generative model which estimates the temporal evolution of brain states and transition probabilities between states as a function of time. An attractive feature of BSFA is the automatic determination of the number of latent states via Bayesian model selection arising from penalization of excessively complex models. Key features of BSFA are validated using extensive simulations on carefully designed synthetic data. We further validate BSFA using fingerprint analysis of multisession resting-state fMRI data from the Human Connectome Project (HCP). Our results show that modeling temporal dependencies in the generative model of BSFA results in improved fingerprinting of individual participants. Finally, we apply BSFA to elucidate the dynamic functional organization of the salience, central-executive, and default mode networks-three core neurocognitive systems with central role in cognitive and affective information processing (Menon, 2011). Across two HCP sessions, we demonstrate a high level of dynamic interactions between these networks and determine that the salience network has the highest temporal

  16. F4/80 inhibits osteoclast differentiation via downregulation of nuclear factor of activated T cells, cytoplasmic 1.

    PubMed

    Kang, Ju-Hee; Sim, Jung-Sun; Zheng, Ting; Yim, Mijung

    2017-04-01

    Osteoclastogenesis is an essential process in bone metabolism, which can be induced by RANKL stimulation. The F4/80 glycoprotein is a member of the EGF-transmembrane 7 (TM7) family and has been established as a specific cell-surface marker for murine macrophages. This study aimed to identify the role of F4/80 in osteoclastogenesis. Using mouse bone marrow-derived macrophages (BMMs), we observed that the mRNA level of F4/80 was dramatically reduced as these cells differentiated into osteoclasts. Furthermore, osteoclastogenesis was decreased in F4/80 high BMMs compared to F4/80 -/low BMMs. The inhibitory effect of F4/80 was associated with decreased expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). Ectopic overexpression of a constitutively active form of NFATc1 rescued the anti-osteoclastogenic effect of F4/80 completely, suggesting that the anti-osteoclastogenic effect of F4/80 was mainly due to reduction in NFATc1 expression. As an underlying mechanism, we demonstrated that the presence of F4/80 abrogated the effect of RANKL on the phosphorylation of CREB and activated the expression of IFN-β, which are restored by cyclic AMP. Collectively, our results demonstrate that the presence of F4/80 suppresses RANKL-induced osteoclastogenesis by impairing the expression of NFATc1 via CREB and IFN-β. Therefore, F4/80 may hold therapeutic potential for bone destructive diseases.

  17. Reconstruction scenario in modified Horava-Lifshitz F( R) gravity with well-known scale factors

    NASA Astrophysics Data System (ADS)

    Jawad, Abdul; Rani, Shamaila

    2015-05-01

    In this paper, we analyze the behavior of pilgrim dark energy with G-O cutoff scale in modified Horava-Lifshitz F( R) gravity through correspondence scenario. We consider three well-known scale factors in which one scale factor describes the unification of matter dominated and accelerated phases and others are intermediate and bouncing forms. We obtain the models for these scale factors and obtain increasing behavior with the passage of time. We also extract equation of state parameter corresponding to these models. We observe that this parameter shows transition from phantom towards quintessence by crossing the phantom divide line in all cases. We also give comparison of our results of equation of state parameter with observational constraints.

  18. Increasing Polymer Solar Cell Fill Factor by Trap-Filling with F4-TCNQ at Parts Per Thousand Concentration.

    PubMed

    Yan, Han; Manion, Joseph G; Yuan, Mingjian; García de Arquer, F Pelayo; McKeown, George R; Beaupré, Serge; Leclerc, Mario; Sargent, Edward H; Seferos, Dwight S

    2016-08-01

    Intrinsic traps in organic semiconductors can be eliminated by trap-filling with F4-TCNQ. Photovoltaic tests show that devices with F4-TCNQ at parts per thousand concentration outperform control devices due to an improved fill factor. Further studies confirm the trap-filling pathway and demonstrate the general nature of this finding. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. [Psychosocial stressors and pain sensitivity in chronic pain disorder with somatic and psychological factors (F45.41)].

    PubMed

    Studer, M; Stewart, J; Egloff, N; Zürcher, E; von Känel, R; Brodbeck, J; Grosse Holtforth, M

    2017-02-01

    Increased pain sensitivity is characteristic for patients with chronic pain disorder with somatic and psychological factors (F45.41). Persistent stress can induce, sustain, and intensify pain sensitivity, thereby modulating pain perception. In this context, it would be favorable to investigate which psychosocial stressors are empirically linked to pain sensitivity. The aim of this study was to examine the relationship between psychosocial stressors and pain sensitivity in a naturalistic sample of patients with chronic pain disorder with somatic and psychological factors (F45.41). We assessed 166 patients with chronic pain disorder with somatic and psychological factors (F45.41) at entry into an inpatient pain clinic. Pain sensitivity was measured with a pain provocation test (Algopeg) at the middle finger and earlobe. Stressors assessed were exposure to war experiences, adverse childhood experiences, illness-related inability to work, relationship problems, and potentially life-threatening accidents. Correlation analyses and structural equation modeling were used to examine which stressors showed the strongest prediction of pain sensitivity. Patients exhibited generally heightened pain sensitivity. Both exposure to war and illness-related inability to work showed significant bivariate correlations with pain sensitivity. In addition to age, they also predicted a further increase in pain sensitivity in the structural equation model. Bearing in mind the limitations of this cross-sectional study, these findings may contribute to a better understanding of the link between psychosocial stressors and pain sensitivity.

  20. Substituting mouse transcription factor Pou4f2 with a sea urchin orthologue restores retinal ganglion cell development.

    PubMed

    Mao, Chai-An; Agca, Cavit; Mocko-Strand, Julie A; Wang, Jing; Ullrich-Lüter, Esther; Pan, Ping; Wang, Steven W; Arnone, Maria Ina; Frishman, Laura J; Klein, William H

    2016-03-16

    Pou domain transcription factor Pou4f2 is essential for the development of retinal ganglion cells (RGCs) in the vertebrate retina. A distant orthologue of Pou4f2 exists in the genome of the sea urchin (class Echinoidea) Strongylocentrotus purpuratus (SpPou4f1/2), yet the photosensory structure of sea urchins is strikingly different from that of the mammalian retina. Sea urchins have no obvious eyes, but have photoreceptors clustered around their tube feet disc. The mechanisms that are associated with the development and function of photoreception in sea urchins are largely unexplored. As an initial approach to better understand the sea urchin photosensory structure and relate it to the mammalian retina, we asked whether SpPou4f1/2 could support RGC development in the absence of Pou4f2. To answer this question, we replaced genomic Pou4f2 with an SpPou4f1/2 cDNA. In Pou4f2-null mice, retinas expressing SpPou4f1/2 were outwardly identical to those of wild-type mice. SpPou4f1/2 retinas exhibited dark-adapted electroretinogram scotopic threshold responses, indicating functionally active RGCs. During retinal development, SpPou4f1/2 activated RGC-specific genes and in S. purpuratus, SpPou4f2 was expressed in photoreceptor cells of tube feet in a pattern distinct from Opsin4 and Pax6. Our results suggest that SpPou4f1/2 and Pou4f2 share conserved components of a gene network for photosensory development and they maintain their conserved intrinsic functions despite vast morphological differences in mouse and sea urchin photosensory structures. © 2016 The Authors.

  1. An Arabidopsis F-box protein acts as a transcriptional co-factor to regulate floral development.

    PubMed

    Chae, Eunyoung; Tan, Queenie K-G; Hill, Theresa A; Irish, Vivian F

    2008-04-01

    Plants flower in response to both environmental and endogenous signals. The Arabidopsis LEAFY (LFY) transcription factor is crucial in integrating these signals, and acts in part by activating the expression of multiple floral homeotic genes. LFY-dependent activation of the homeotic APETALA3 (AP3) gene requires the activity of UNUSUAL FLORAL ORGANS (UFO), an F-box component of an SCF ubiquitin ligase, yet how this regulation is effected has remained unclear. Here, we show that UFO physically interacts with LFY both in vitro and in vivo, and this interaction is necessary to recruit UFO to the AP3 promoter. Furthermore, a transcriptional repressor domain fused to UFO reduces endogenous LFY activity in plants, supporting the idea that UFO acts as part of a transcriptional complex at the AP3 promoter. Moreover, chemical or genetic disruption of proteasome activity compromises LFY-dependent AP3 activation, indicating that protein degradation is required to promote LFY activity. These results define an unexpected role for an F-box protein in functioning as a DNA-associated transcriptional co-factor in regulating floral homeotic gene expression. These results suggest a novel mechanism for promoting flower development via protein degradation and concomitant activation of the LFY transcription factor. This mechanism may be widely conserved, as homologs of UFO and LFY have been identified in a wide array of plant species.

  2. Effects of age and cardiovascular risk factors on (18)F-FDG PET/CT quantification of atherosclerosis in the aorta and peripheral arteries.

    PubMed

    Pasha, Ahmed K; Moghbel, Mateen; Saboury, Babak; Gharavi, Mohammed H; Blomberg, Björn A; Torigian, Drew A; Kwee, Thomas C; Basu, Sandip; Mohler Iii, Emile R; Alavi, Abass

    2015-01-01

    To quantify fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the aorta and peripheral arteries and assess the variation of (18)F-FDG uptake with age and cardiovascular risk factors. The subject population of this retrospective study comprises melanoma patients who underwent whole-body (18)F-FDG PET/CT scans. The patients' medical records were examined for cardiovascular risk factors and for a history of coronary artery disease or peripheral artery disease. Fluorine-18-FDG uptake in the peripheral arteries (iliac and femoral) and aorta was semi-quantified as a weighted-average mean standardized uptake value (wA-SUVmean), while background noise was accounted for by measuring mean venous blood pool SUV (V-SUVmean) in the superior vena cava. Atherosclerosis was semi-quantified by the tissue-to-background ratio (TBR) (wA-SUVmean divided by V-SUVmean). A regression model and t-test were used to evaluate the effect of age and location on the degree of atherosclerosis. To assess the effect of cardiovascular risk factors on atherosclerotic burden, the wA-SUVmean of patients with at least one of these risk factors was compared to that of patients without any risk factors. A total of 76 patients (46 men, 30 women; 22-91 years old) were included in this study. The average TBR of the aorta and peripheral arteries were 2.68 and 1.43, respectively, and increased with age in both locations. In regression analysis, the beta coefficients of age for TBR in the aorta and peripheral arteries were 0.55 (P<0.001) and 0.03 (P<0.001), respectively. In all age groups, the TBR of the aorta was significantly greater than that of the peripheral arteries. The Pearson correlation coefficients between the four age groups and the TBR of the aorta and peripheral arteries were 0.83 (P<0.001) and 0.75 (P<0.001), respectively. The wA-SUVmean of patients with cardiovascular risk factors was only significant (P<0.05) in the aorta. An increase in (18)F-FDG uptake was observed in the peripheral

  3. HlyF Produced by Extraintestinal Pathogenic Escherichia coli Is a Virulence Factor That Regulates Outer Membrane Vesicle Biogenesis.

    PubMed

    Murase, Kazunori; Martin, Patricia; Porcheron, Gaëlle; Houle, Sébastien; Helloin, Emmanuelle; Pénary, Marie; Nougayrède, Jean-Philippe; Dozois, Charles M; Hayashi, Tetsuya; Oswald, Eric

    2016-03-01

    Escherichia coli can cause extraintestinal infections in humans and animals. The hlyF gene is epidemiologically associated with virulent strains of avian pathogenic E. coli and human neonatal meningitis-associated E. coli. We demonstrated that culture supernatants of E. coli expressing HlyF induced autophagy in eukaryotic cells. This phenotype coincided with an enhanced production of outer membrane vesicles (OMVs) by bacteria expressing HlyF. The HlyF protein displays a predicted catalytic domain of the short-chain dehydrogenase/reductase superfamily. This conserved domain was involved the ability of HlyF to promote the production of OMVs. The increased production of OMVs was associated with the release of toxins. hlyF was shown to be expressed during extraintestinal infection and to play a role in the virulence of extraintestinal pathogenic E. coli in a chicken model of colibacillosis. This is the first evidence that pathogenic bacteria produce a virulence factor directly involved in the production of OMVs. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Nonleptonic decays of B →(f1(1285 ),f1(1420 ))V in the perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Xiao, Zhen-Jun; Zou, Zhi-Tian

    2016-12-01

    We investigate the branching ratios, the polarization fractions, the direct C P -violating asymmetries, and the relative phases in 20 nonleptonic decay modes of B →f1V within the framework of the perturbative QCD approach at leading order with f1 including two 3P1-axial-vector states f1(1285 ) and f1(1420 ) . Here, B denotes B+, B0, and Bs0 mesons and V stands for the lightest vector mesons ρ , K*, ω , and ϕ , respectively. The Bs0→f1V decays are studied theoretically for the first time in the literature. Together with the angle ϕf1≈(24-2.7+3.2)∘ extracted from the measurement through Bd /s→J /ψ f1(1285 ) modes for the f1(1285 )-f1(1420 ) mixing system, it is of great interest to find phenomenologically some modes such as the tree-dominated B+→f1ρ+ and the penguin-dominated B+,0→f1K*+,0 , Bs0→f1ϕ with large branching ratios around O (10-6) or even O (10-5), which are expected to be measurable at the LHCb and/or the Belle-II experiments in the near future. The good agreement (sharp contrast) of branching ratios and decay pattern for B+→f1ρ+ , B+,0→f1(1285 )K*+,0[B+,0→f1(1420 )K*+,0] decays between QCD factorization and perturbative QCD factorization predictions can help us to distinguish these two rather different factorization approaches via precision measurements, which would also be helpful for us in exploring the annihilation decay mechanism through its important roles for the considered B →f1V decays.

  5. On the output factor measurements of the CyberKnife iris collimator small fields: Experimental determination of the k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors for microchamber and diode detectors

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

    Pantelis, E.; Moutsatsos, A.; Zourari, K.

    Purpose: To measure the output factors (OFs) of the small fields formed by the variable aperture collimator system (iris) of a CyberKnife (CK) robotic radiosurgery system, and determine the k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors for a microchamber and four diode detectors. Methods: OF measurements were performed using a PTW PinPoint 31014 microchamber, four diode detectors (PTW-60017, -60012, -60008, and the SunNuclear EDGE detector), TLD-100 microcubes, alanine dosimeters, EBT films, and polymer gels for the 5 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm irismore » collimators at 650 mm, 800 mm, and 1000 mm source to detector distance (SDD). The alanine OF measurements were corrected for volume averaging effects using the 3D dose distributions registered in polymer gel dosimeters. k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors for the PinPoint microchamber and the diode dosimeters were calculated through comparison against corresponding polymer gel, EBT, alanine, and TLD results. Results: Experimental OF results are presented for the array of dosimetric systems used. The PinPoint microchamber was found to underestimate small field OFs, and a k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factor ranging from 1.127 {+-} 0.022 (for the 5 mm iris collimator) to 1.004 {+-} 0.010 (for the 15 mm iris collimator) was determined at the reference SDD of 800 mm. The PinPoint k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factor was also found to increase with decreasing SDD; k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} values equal to 1.220 {+-} 0.028 and 1

  6. Allele frequency distribution of 1691G >A F5 (which confers Factor V Leiden) across Europe, including Slavic populations.

    PubMed

    Clark, Jeremy S C; Adler, Grażyna; Salkic, Nermin N; Ciechanowicz, Andrzej

    2013-11-01

    The allele 1691A F5, conferring Factor V Leiden, is a common risk factor in venous thromboembolism. The frequency distribution for this allele in Western Europe has been well documented; but here data from Central, Eastern and South-Eastern Europe has been included. In order to assess the significance of the collated data, a chi-squared test was applied, and Tukey tests and z-tests with Bonferroni correction were compared. A distribution with a North-Southeast band of high frequency of the 1691A F5 allele was discovered with a pocket including some Southern Slavic populations with low frequency. European countries/regions can be arbitrarily delimited into low (group 1, <2.8 %, mean 1.9 % 1691A F5 allele) or high (group 2, ≥2.8 %, mean 4.0 %) frequency groups, with many significant differences between groups, but only one intra-group difference (the Tukey test is suggested to be superior to the z-tests). In Europe a North-Southeast band of 1691A F5 high frequency has been found, clarified by inclusion of data from Central, Eastern and South-Eastern Europe, which surrounds a pocket of low frequency in the Balkans which could possibly be explained by Slavic migration. There seem to be no indications of variation in environmental selection due to geographical location.

  7. Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations.

    PubMed

    Loomans, J I; van Velzen, A S; Eckhardt, C L; Peters, M; Mäkipernaa, A; Holmstrom, M; Brons, P P; Dors, N; Haya, S; Voorberg, J; van der Bom, J G; Fijnvandraat, K

    2017-02-01

    Essentials Factor VIII levels vary in mild and moderate hemophilia A (MHA) patients with the same mutation. We aimed to estimate the variation and determinants of factor VIII levels among MHA patients. Age and genotype explain 59% of the observed inter-individual variation in factor VIII levels. Intra-individual variation accounted for 45% of the variation in the three largest mutation groups. Background The bleeding phenotype in patients with mild/moderate hemophilia A (MHA) is inversely associated with the residual plasma concentration of factor VIII (FVIII:C). Within a group of patients with the same F8 missense mutation, baseline FVIII:C may vary, because, in healthy individuals, von Willebrand factor (VWF) levels, ABO blood group and age are also known to influence baseline FVIII:C. Our understanding of the pathophysiologic process of the causative genetic event leading to reduced baseline FVIII:C in MHA patients is still limited. Objectives To estimate the variation and determinants of baseline FVIII:C among MHA patients with the same F8 missense mutation. Methods Three hundred and forty-six patients carrying mutations that were present in at least 10 patients in the cohort were selected from the INSIGHT and the RISE studies, which are cohort studies including data of 3534 MHA patients from Europe, Canada, and Australia. Baseline FVIII:C was measured with a one-stage clotting assay. We used Levene's test, univariate and multivariate linear regression, and mixed-model analyses. Results For 59% of patients, the observed variation in baseline FVIII:C was explained by age and genotype. Compared to FVIII:C in patients with Arg612Cys, FVIII:C was significantly different in patients with eight other F8 missense mutations. Intra-individual variation explained 45% of the observed variance in baseline FVIII:C among patients with the same mutation. Conclusion Our results indicate that baseline FVIII:C levels are not exclusively determined by F8 genotype in MHA patients

  8. Eukaryotic Initiation Factor (eIF) 4F Binding to Barley Yellow Dwarf Virus (BYDV) 3′-Untranslated Region Correlates with Translation Efficiency*

    PubMed Central

    Banerjee, Bidisha; Goss, Dixie J.

    2014-01-01

    Eukaryotic initiation factor (eIF) 4F binding to mRNA is the first committed step in cap-dependent protein synthesis. Barley yellow dwarf virus (BYDV) employs a cap-independent mechanism of translation initiation that is mediated by a structural BYDV translation element (BTE) located in the 3′-UTR of its mRNA. eIF4F bound the BTE and a translationally inactive mutant with high affinity, thus questioning the role of eIF4F in translation of BYDV. To examine the effects of eIF4F in BYDV translation initiation, BTE mutants with widely different in vitro translation efficiencies ranging from 5 to 164% compared with WT were studied. Using fluorescence anisotropy to obtain quantitative data, we show 1) the equilibrium binding affinity (complex stability) correlated well with translation efficiency, whereas the “on” rate of binding did not; 2) other unidentified proteins or small molecules in wheat germ extract prevented eIF4F binding to mutant BTE but not WT BTE; 3) BTE mutant-eIF4F interactions were found to be both enthalpically and entropically favorable with an enthalpic contribution of 52–90% to ΔG° at 25 °C, suggesting that hydrogen bonding contributes to stability; and 4) in contrast to cap-dependent and tobacco etch virus internal ribosome entry site interaction with eIF4F, poly(A)-binding protein did not increase eIF4F binding. Further, the eIF4F bound to the 3′ BTE with higher affinity than for either m7G cap or tobacco etch virus internal ribosome entry site, suggesting that the 3′ BTE may play a role in sequestering host cell initiation factors and possibly regulating the switch from replication to translation. PMID:24379412

  9. Genomic structure, expression pattern, and functional characterization of transcription factor E2F-2 from black tiger shrimp (Penaeus monodon)

    PubMed Central

    Zhao, Chao; Qiu, Lihua

    2017-01-01

    Transcription factor E2F-2 is a regulator of cell cycle. Researchers identified E2F-2 genes from yeasts to humans, but few reports investigated E2F-2 gene from black tiger shrimp. In the present study, we cloned E2F-2 gene from black tiger shrimp (Penaeus monodon). Full-length PmE2F-2 complementary DNA sequence measures 3,189 bp with an open reading frame of 1,371 bp. Complete PmE2F-2 genomic sequence (17,305 bp) of P. monodon contains nine exons, which are separated by eight introns. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that PmE2F-2 is highly expressed in hepatopancreas and ovaries of P. monodon. Highest PmE2F-2 expression levels were observed in stage III ovarian development of P. monodon. PmE2F-2 expression levels were significantly augmented in ovaries of P. monodon after 5-hydroxytryptamine injection and eyestalk ablation. RNA interference experiments were conducted to examine PmE2F-2, PmCDK2, and PmCyclin E expression profiles. PmE2F-2 was successfully knocked down in ovaries and hepatopancreas via double-stranded RNA (dsRNA)–E2F-2 injection. In the same organs, PmE2F-2 expression localization and level were investigated through in situ hybridization, which revealed consistent results with those of qRT-PCR. After dsRNA—E2F-2 injection, gonadosomatic index of shrimp was significantly lower than those following dsRNA—GFP and phosphate-buffered solution injections. Therefore, PmE2F-2 may be involved in ovarian maturation in P. monodon. PMID:28558060

  10. The astrophysical S-factor of the direct 18O(p, γ)19F capture by the ANC method

    NASA Astrophysics Data System (ADS)

    Burjan, V.; Hons, Z.; Kroha, V.; Mrázek, J.; Piskoř, Š.; Mukhamedzhanov, A. M.; Trache, L.; Tribble, R. E.; La Cognata, M.; Lamia, L.; Pizzone, G. R.; Romano, S.; Spitaleri, C.; Tumino, A.

    2018-01-01

    We attempted to determine the astrophysical S-factor of the direct part of the 18O(p, γ)19F capture by the indirect method of asymptotic normalization coefficients (ANC). We measured the differential cross section of the transfer reaction 18O(3He, d)19F at a 3He energy of 24.6 MeV. The measurement was realized on the cyclotron of the NPI in Řež, Czech Republic, with the gas target consisting of the high purity 18O (99.9 %). The reaction products were measured by eight ΔE-E telescopes composed from thin and thick silicon surface-barrier detectors. The parameters of the optical model for the input channel were deduced by means of the code ECIS and the analysis of transfer reactions to 12 levels of the 19F nucleus up to 8.014 MeV was made by the code FRESCO. The deduced ANCs were then used to specify the direct contribution to the 18O(p, γ)19F capture process and were compared with the mutually different results of two works.

  11. The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation.

    PubMed

    Zhou, Fangfang; Zhang, Long; Wang, Aijun; Song, Bo; Gong, Kai; Zhang, Lihai; Hu, Min; Zhang, Xiufang; Zhao, Nanming; Gong, Yandao

    2008-05-23

    It is widely acknowledged that E2F1 and GSK3beta are both involved in the process of cell differentiation. However, the relationship between E2F1 and GSK3beta in cell differentiation has yet to be discovered. Here, we provide evidence that in the differentiation of PC12 cells induced by nerve growth factor (NGF), GSK3beta was increased at both the mRNA and protein levels, whereas E2F1 at these two levels was decreased. Both wild-type GSK3beta and its kinase-defective mutant GSK3beta KM can inhibit E2F1 by promoting its ubiquitination through physical interaction. In addition, the colocalization of GSK3beta and E2F1 and their subcellular distribution, regulated by NGF, were observed in the process of PC12 differentiation. At the tissue level, GSK3beta colocalized and interacted with E2F1 in mouse hippocampus. Furthermore, GSK3beta facilitated neurite outgrowth by rescuing the promoter activities of Cdk inhibitors p21 and p15 from the inhibition caused by E2F1. To summarize, our findings suggest that GSK3beta can promote the ubiquitination of E2F1 via physical interaction and thus inhibit its transcription activity in a kinase activity independent manner, which plays an important role in the NGF-induced PC12 differentiation.

  12. Functional interaction of CCAAT/enhancer-binding-protein-α basic region mutants with E2F transcription factors and DNA.

    PubMed

    Kowenz-Leutz, Elisabeth; Schuetz, Anja; Liu, Qingbin; Knoblich, Maria; Heinemann, Udo; Leutz, Achim

    2016-07-01

    The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) regulates cell cycle arrest and terminal differentiation of neutrophils and adipocytes. Mutations in the basic leucine zipper domain (bZip) of C/EBPα are associated with acute myeloid leukemia. A widely used murine transforming C/EBPα basic region mutant (BRM2) entails two bZip point mutations (I294A/R297A). BRM2 has been discordantly described as defective for DNA binding or defective for interaction with E2F. We have separated the two BRM2 mutations to shed light on the intertwined reciprocity between C/EBPα-E2F-DNA interactions. Both, C/EBPα I294A and R297A retain transactivation capacity and interaction with E2F-DP. The C/EBPα R297A mutation destabilized DNA binding, whereas the C/EBPα I294A mutation enhanced binding to DNA. The C/EBPα R297A mutant, like BRM2, displayed enhanced interaction with E2F-DP but failed to repress E2F-dependent transactivation although both mutants were readily suppressed by E2F1 for transcription through C/EBP cis-regulatory sites. In contrast, the DNA binding enhanced C/EBPα I294A mutant displayed increased repression of E2F-DP mediated transactivation and resisted E2F-DP mediated repression. Thus, the efficient repression of E2F dependent S-phase genes and the activation of differentiation genes reside in the balanced DNA binding capacity of C/EBPα. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Increased F3-Isoprostanes in the Canadian Inuit Population Could Be Cardioprotective by Limiting F2-Isoprostane Production.

    PubMed

    Alkazemi, Dalal; Jackson, Robert L; Chan, Hing Man; Kubow, Stan

    2016-09-01

    F3-isoprostanes (F3-IsoPs), derived from peroxidation of eicosapentaenoic acid (C20:5n-3), could be cardioprotective by limiting production of F2-isoprostanes (F2-IsoPs), a cardiovascular disease risk factor. The objective of the study was to determine whether the n-3-polyunsaturated (PUFA)-rich Inuit diet is associated with a lower plasma ratio of F2-IsoPs to F3-IsoPs. This was a cross-sectional observational study. The study was conducted in 36 Canadian Arctic Inuit communities. Participants included a random subset (n = 233) of Inuit adults taken from a population-based survey. Plasma F2-IsoPs and F3-IsoPs, cardiometabolic risk factors (blood lipids, C-reactive protein, blood pressure, fasting glucose) and markers of dietary exposure (erythrocyte n-3 and n-6 PUFA, blood levels of Se, mercury, polychlorinated biphenyls) were measured. Inuit aged 40 years old and older vs younger Inuit showed higher concentrations of plasma F3-IsoPs and erythrocyte n-3 PUFA and lower plasma F2-IsoPs concentrations despite having higher blood lipids, fasting glucose, systolic blood pressure, and percentage body fat. Plasma F3-IsoPs were not associated with any cardiometabolic measures. When subjects were categorized into tertiles according to total n-3 PUFA erythrocyte concentrations, F3-IsoPs increased with increasing tertiles, whereas the F2-IsoP to F3-IsoP ratio was lowest at the highest n-3 tertile. The F2-IsoP to F3-IsoP ratio was significantly predicted by C20:5n-3 (β= -.365, P = .002); C20:4n-6:C20:5n-3 (β = .056, P = .006), blood mercury (β = -.812, P =.015), blood Se (β = -1.95, P = .015), and smoking (β = .745, P = .025). Plasma F3-IsoPs were not associated with cardiometabolic risk factors previously seen with F2-IsoPs. Higher n-3 fatty acid status was associated with lower plasma F2-IsoPs and higher plasma F3-IsoPs, which provides partial explanation to the cardioprotective effects of the n-3 PUFA-rich Inuit diet.

  14. Energy correction factors of LiF powder TLDs irradiated in high-energy electron beams and applied to mailed dosimetry for quality assurance networks.

    PubMed

    Marre, D; Ferreira, I H; Bridier, A; Björeland, A; Svensson, H; Dutreix, A; Chavaudra, J

    2000-12-01

    Absorbed dose determination with thermoluminescent dosimeters (TLDs) generally relies on calibration in 60Co gamma-ray reference beams. The energy correction factor fCo(E) for electron beams takes into account the difference between the response of the TLD in the beam of energy E and in the 60Co gamma-ray beam. In this work, fCo(E) was evaluated for an LiF powder irradiated in electron beams of 6 to 20 MeV (Varian 2300C/D) and 10 to 50 MeV (Racetrack MM50), and its variation with electron energy, TLD size and nature of the surrounding medium was also studied for LiF powder. The results have been applied to the ESTRO-EQUAL mailed dosimetry quality assurance network. Monte Carlo calculations (EGS4, PENELOPE) and experiments have been performed for the LiF powder (rho = 1.4 g cm3) (DTL937, Philitech, France), read on a home made reader and a PCL3 automatic reader (Fimel, France). The TLDs were calibrated using Fricke dosimetry and compared with three ionization chambers (NE2571, NACP02, ROOS). The combined uncertainties in the experimental fCo(E) factors determined in this work are less than about 0.4% (1 SD), which is appreciably smaller than the uncertainties up to 1.4% (1 SD) reported for other calculated values in the literature. Concerning the Varian 2300C/D beams, the measured fCo(E) values decrease from 1.065 to 1.049 +/- 0.004 (1 SD) when the energy at depth in water increases from 2.6 to 14.1 MeV; the agreement with Monte Carlo calculations is better than 0.5%. For the Racetrack MM50 pulsed-scanned beams, the average experimental value of fCo(E) is 1.071 +/- 0.005 (1 SD) for a mean electron energy at depth Ez ranging from 4.3 to 36.3 MeV: fCo(E) is up to 2% higher for the MM50 beams than for the 2300C/D beams in the range of the tested energies. The energy correction factor for LiF powder (3 mm diameter and 15 mm length) varies with beam quality and type (pulsed or pulsed-scanning), cavity size and nature of the surrounding medium. The fCo(E) values obtained

  15. Interpretation of F106B and CV580 in-flight lightning data and form factor determination

    NASA Technical Reports Server (NTRS)

    Rudolph, T.; Horembala, J.; Eriksen, F. J.; Weigel, H. S.; Elliott, J. R.; Parker, S. L.; Perala, R. A.

    1989-01-01

    Two topics of in-flight aircraft/lightning interaction are addressed. The first is the analysis of measured data from the NASA F106B Thunderstorm Research Aircraft and the CV580 research program run by the FAA and Wright-Patterson Air Force Base. The CV580 data was investigated in a mostly qualitative sense, while the F106B data was subjected to both statistical and quantitative analysis using linear triggered lightning finite difference models. The second main topic is the analysis of field mill data and the calibration of the field mill systems. The calibration of the F106B field mill system was investigated using an improved finite difference model of the aircraft having a spatial resolution of one-quarter meter. The calibration was applied to measured field mill data acquired during the 1985 thunderstorm season. The experimental determination of form factors useful for field mill calibration was also investigated both experimentally and analytically. The experimental effort involved the use of conducting scale models and an electrolytic tank. An analytic technique was developed to aid in the understanding of the experimental results.

  16. Emerging Patterns in Transferring Assessment Practices from F2f to Online Environments

    ERIC Educational Resources Information Center

    Beebe, Ronald; Vonderwell, Selma; Boboc, Marius

    2010-01-01

    This study explores the transfer of assessment practices from f2f to online environments by college instructors, with a particular interest in the factors influencing assessment in online learning settings. Assessment is a critical aspect of the learning environment, and considerable research has suggested various methods of formative and…

  17. Alternative Sigma Factors SigF, SigE, and SigG Are Essential for Sporulation in Clostridium botulinum ATCC 3502

    PubMed Central

    Kirk, David G.; Zhang, Zhen; Korkeala, Hannu

    2014-01-01

    Clostridium botulinum produces heat-resistant endospores that may germinate and outgrow into neurotoxic cultures in foods. Sporulation is regulated by the transcription factor Spo0A and the alternative sigma factors SigF, SigE, SigG, and SigK in most spore formers studied to date. We constructed mutants of sigF, sigE, and sigG in C. botulinum ATCC 3502 and used quantitative reverse transcriptase PCR and electron microscopy to assess their expression of the sporulation pathway on transcriptional and morphological levels. In all three mutants the expression of spo0A was disrupted. The sigF and sigE mutants failed to induce sigG and sigK beyond exponential-phase levels and halted sporulation during asymmetric cell division. In the sigG mutant, peak transcription of sigE was delayed and sigK levels remained lower than that in the parent strain. The sigG mutant forespore was engulfed by the mother cell and possessed a spore coat but no peptidoglycan cortex. The findings suggest that SigF and SigE of C. botulinum ATCC 3502 are essential for early sporulation and late-stage induction of sigK, whereas SigG is essential for spore cortex formation but not for coat formation, as opposed to previous observations in B. subtilis sigG mutants. Our findings add to a growing body of evidence that regulation of sporulation in C. botulinum ATCC 3502, and among the clostridia, differs from the B. subtilis model. PMID:24928875

  18. Characterization of an apparently synonymous F5 mutation causing aberrant splicing and factor V deficiency.

    PubMed

    Nuzzo, F; Bulato, C; Nielsen, B I; Lee, K; Wielders, S J; Simioni, P; Key, N S; Castoldi, E

    2015-03-01

    Coagulation factor V (FV) deficiency is a rare autosomal recessive bleeding disorder. We investigated a patient with severe FV deficiency (FV:C < 3%) and moderate bleeding symptoms. Thrombin generation experiments showed residual FV expression in the patient's plasma, which was quantified as 0.7 ± 0.3% by a sensitive prothrombinase-based assay. F5 gene sequencing identified a novel missense mutation in exon 4 (c.578G>C, p.Cys193Ser), predicting the abolition of a conserved disulphide bridge, and an apparently synonymous variant in exon 8 (c.1281C>G). The observation that half of the patient's F5 mRNA lacked the last 18 nucleotides of exon 8 prompted us to re-evaluate the c.1281C>G variant for its possible effects on splicing. Bioinformatics sequence analysis predicted that this transversion would activate a cryptic donor splice site and abolish an exonic splicing enhancer. Characterization in a F5 minigene model confirmed that the c.1281C>G variant was responsible for the patient's splicing defect, which could be partially corrected by a mutation-specific morpholino antisense oligonucleotide. The aberrantly spliced F5 mRNA, whose stability was similar to that of the normal mRNA, encoded a putative FV mutant lacking amino acids 427-432. Expression in COS-1 cells indicated that the mutant protein is poorly secreted and not functional. In conclusion, the c.1281C>G mutation, which was predicted to be translationally silent and hence neutral, causes FV deficiency by impairing pre-mRNA splicing. This finding underscores the importance of cDNA analysis for the correct assessment of exonic mutations. © 2014 John Wiley & Sons Ltd.

  19. Downregulation of Homologous Recombination DNA Repair Genes by HDAC Inhibition in Prostate Cancer Is Mediated through the E2F1 Transcription Factor

    PubMed Central

    Kachhap, Sushant K.; Rosmus, Nadine; Collis, Spencer J.; Kortenhorst, Madeleine S. Q.; Wissing, Michel D.; Hedayati, Mohammad; Shabbeer, Shabana; Mendonca, Janet; Deangelis, Justin; Marchionni, Luigi; Lin, Jianqing; Höti, Naseruddin; Nortier, Johan W. R.; DeWeese, Theodore L.; Hammers, Hans; Carducci, Michael A.

    2010-01-01

    Background Histone deacetylase inhibitors (HDACis) re-express silenced tumor suppressor genes and are currently undergoing clinical trials. Although HDACis have been known to induce gene expression, an equal number of genes are downregulated upon HDAC inhibition. The mechanism behind this downregulation remains unclear. Here we provide evidence that several DNA repair genes are downregulated by HDAC inhibition and provide a mechanism involving the E2F1 transcription factor in the process. Methodology/Principal Findings Applying Analysis of Functional Annotation (AFA) on microarray data of prostate cancer cells treated with HDACis, we found a number of genes of the DNA damage response and repair pathways are downregulated by HDACis. AFA revealed enrichment of homologous recombination (HR) DNA repair genes of the BRCA1 pathway, as well as genes regulated by the E2F1 transcription factor. Prostate cancer cells demonstrated a decreased DNA repair capacity and an increased sensitization to chemical- and radio-DNA damaging agents upon HDAC inhibition. Recruitment of key HR repair proteins to the site of DNA damage, as well as HR repair capacity was compromised upon HDACi treatment. Based on our AFA data, we hypothesized that the E2F transcription factors may play a role in the downregulation of key repair genes upon HDAC inhibition in prostate cancer cells. ChIP analysis and luciferase assays reveal that the downregulation of key repair genes is mediated through decreased recruitment of the E2F1 transcription factor and not through active repression by repressive E2Fs. Conclusions/Significance Our study indicates that several genes in the DNA repair pathway are affected upon HDAC inhibition. Downregulation of the repair genes is on account of a decrease in amount and promoter recruitment of the E2F1 transcription factor. Since HDAC inhibition affects several pathways that could potentially have an impact on DNA repair, compromised DNA repair upon HDAC inhibition could

  20. [Chronic pain disorder with somatic and psychological factors (F45.41) : Validation criteria on operationalization of the ICD-10-GM diagnosis].

    PubMed

    Arnold, B; Lutz, J; Nilges, P; Pfingsten, M; Rief, Winfried; Böger, A; Brinkschmidt, T; Casser, H-R; Irnich, D; Kaiser, U; Klimczyk, K; Sabatowski, R; Schiltenwolf, M; Söllner, W

    2017-12-01

    In 2009 the diagnosis chronic pain disorder with somatic and psychological factors (F45.41) was integrated into the German version of the International Classification of Diseases, version 10 (ICD-10-GM). In 2010 Paul Nilges and Winfried Rief published operationalization criteria for this diagnosis. In the present publication the ad hoc commission on multimodal interdisciplinary pain therapy of the German Pain Society now presents a formula for a clear validation of these operationalization criteria of the ICD code F45.41.

  1. Diffusible signal factor (DSF) synthase RpfF of Xylella fastidiosa is a multifunction protein also required for response to DSF.

    PubMed

    Ionescu, Michael; Baccari, Clelia; Da Silva, Aline Maria; Garcia, Angelica; Yokota, Kenji; Lindow, Steven E

    2013-12-01

    Xylella fastidiosa, like related Xanthomonas species, employs an Rpf cell-cell communication system consisting of a diffusible signal factor (DSF) synthase, RpfF, and a DSF sensor, RpfC, to coordinate expression of virulence genes. While phenotypes of a ΔrpfF strain in Xanthomonas campestris could be complemented by its own DSF, the DSF produced by X. fastidiosa (XfDSF) did not restore expression of the XfDSF-dependent genes hxfA and hxfB to a ΔrpfF strain of X. fastidiosa, suggesting that RpfF is involved in XfDSF sensing or XfDSF-dependent signaling. To test this conjecture, rpfC and rpfF of X. campestris were replaced by those of X. fastidiosa, and the contribution of each gene to the induction of a X. campestris DSF-dependent gene was assessed. As in X. fastidiosa, XfDSF-dependent signaling required both X. fastidiosa proteins RpfF and RpfC. RpfF repressed RpfC signaling activity, which in turn was derepressed by XfDSF. A mutated X. fastidiosa RpfF protein with two substitutions of glutamate to alanine in its active site was incapable of XfDSF production yet enabled a response to XfDSF, indicating that XfDSF production and the response to XfDSF are two separate functions in which RpfF is involved. This mutant was also hypervirulent to grape, demonstrating the antivirulence effects of XfDSF itself in X. fastidiosa. The Rpf system of X. fastidiosa is thus a novel example of a quorum-sensing signal synthase that is also involved in the response to the signal molecule that it synthesizes.

  2. Diffusible Signal Factor (DSF) Synthase RpfF of Xylella fastidiosa Is a Multifunction Protein Also Required for Response to DSF

    PubMed Central

    Ionescu, Michael; Baccari, Clelia; Da Silva, Aline Maria; Garcia, Angelica; Yokota, Kenji

    2013-01-01

    Xylella fastidiosa, like related Xanthomonas species, employs an Rpf cell-cell communication system consisting of a diffusible signal factor (DSF) synthase, RpfF, and a DSF sensor, RpfC, to coordinate expression of virulence genes. While phenotypes of a ΔrpfF strain in Xanthomonas campestris could be complemented by its own DSF, the DSF produced by X. fastidiosa (XfDSF) did not restore expression of the XfDSF-dependent genes hxfA and hxfB to a ΔrpfF strain of X. fastidiosa, suggesting that RpfF is involved in XfDSF sensing or XfDSF-dependent signaling. To test this conjecture, rpfC and rpfF of X. campestris were replaced by those of X. fastidiosa, and the contribution of each gene to the induction of a X. campestris DSF-dependent gene was assessed. As in X. fastidiosa, XfDSF-dependent signaling required both X. fastidiosa proteins RpfF and RpfC. RpfF repressed RpfC signaling activity, which in turn was derepressed by XfDSF. A mutated X. fastidiosa RpfF protein with two substitutions of glutamate to alanine in its active site was incapable of XfDSF production yet enabled a response to XfDSF, indicating that XfDSF production and the response to XfDSF are two separate functions in which RpfF is involved. This mutant was also hypervirulent to grape, demonstrating the antivirulence effects of XfDSF itself in X. fastidiosa. The Rpf system of X. fastidiosa is thus a novel example of a quorum-sensing signal synthase that is also involved in the response to the signal molecule that it synthesizes. PMID:24056101

  3. Synergistic effect of factor VII gene polymorphisms causing mild factor VII deficiency in a case of severe factor X deficiency.

    PubMed

    Deshpande, Rutuja; Ghosh, Kanjaksha; Shetty, Shrimati

    2017-01-01

    Congenital combined deficiency of coagulation factors VII and X are mainly attributed to large deletions involving both the genes in chromosome 13 or occasionally due to the coincidental occurrence of independently occurring mutations. We report the molecular basis of congenital combined deficiency of factors VII and X in a 6-year-old female child. Direct DNA sequencing of both factor VII (F7) and factor X (F10) genes showed a novel homozygous missense mutation p.Cys90Tyr (c.307G>A) in exon 4 of F10. No mutations were detected in F7; however, the patient was homozygous for three polymorphic alleles known to be associated with reduced factor VII levels. The present case illustrates the synergistic effect of multiple polymorphisms resulting in phenotypic factor VII deficiency in the absence of a pathogenic mutation.

  4. Use of MgF2 and LiF photocathodes in the extreme ultraviolet.

    NASA Technical Reports Server (NTRS)

    Lapson, L. B.; Timothy, J. G.

    1973-01-01

    The photoelectric yields of 2000-A thick samples of MgF2 and LiF have been measured at wavelengths in the range from 1216 to 461 A. Peak values of 43 and 34%, respectively, were obtained at wavelengths around 550 A at 45 deg incidence. Coating the cathode of a channel electron multiplier with 3000 A of MgF2 produced no significant deterioration in the electrical properties and increased the sensitivity by factors of 1.62, 2.76, and 2.60 at wavelengths of 742, 584, and 461 A, respectively. Since the stability of response of the MgF2 photocathodes appears to be equal to that of conventional metallic and semiconducting cathodes, it is concluded that MgF2 would be a practical, high-efficiency photocathode for use in the extreme ultraviolet.

  5. Nopaline-type Ti plasmid of Agrobacterium encodes a VirF-like functional F-box protein.

    PubMed

    Lacroix, Benoît; Citovsky, Vitaly

    2015-11-20

    During Agrobacterium-mediated genetic transformation of plants, several bacterial virulence (Vir) proteins are translocated into the host cell to facilitate infection. One of the most important of such translocated factors is VirF, an F-box protein produced by octopine strains of Agrobacterium, which presumably facilitates proteasomal uncoating of the invading T-DNA from its associated proteins. The presence of VirF also is thought to be involved in differences in host specificity between octopine and nopaline strains of Agrobacterium, with the current dogma being that no functional VirF is encoded by nopaline strains. Here, we show that a protein with homology to octopine VirF is encoded by the Ti plasmid of the nopaline C58 strain of Agrobacterium. This protein, C58VirF, possesses the hallmarks of functional F-box proteins: it contains an active F-box domain and specifically interacts, via its F-box domain, with SKP1-like (ASK) protein components of the plant ubiquitin/proteasome system. Thus, our data suggest that nopaline strains of Agrobacterium have evolved to encode a functional F-box protein VirF.

  6. Multicomponent diffusion in molten salt NaF-ZrF4: Dynamical correlations and Maxwell-Stefan diffusivities

    NASA Astrophysics Data System (ADS)

    Baig, Mohammad Saad; Chakraborty, Brahmananda; Ramaniah, Lavanya M.

    2016-05-01

    NaF-ZrF4 is used as a waste incinerator and as a coolant in Generation IV reactors.Structural and dynamical properties of molten NaF-ZrF4 system were studied along with Onsagercoefficients and Maxwell-Stefan (MS) Diffusivities applying Green-Kubo formalism and molecular dynamics (MD) simulations. The zirconium ions are found to be 8 fold coordinated with fluoride ions for all temperatures and concentrations. All the diffusive flux correlations show back-scattering. Even though the MS diffusivities are expected to depend very lightly on the composition because of decoupling of thermodynamic factor, the diffusivity ĐNa-F shows interesting behavior with the increase in concentration of ZrF4. This is because of network formation in NaF-ZrF4. Positive entropy constraints have been plotted to authenticate negative diffusivities observed.

  7. Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.

    PubMed

    Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

    2014-03-01

    The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

  8. Virulence Factor NSs of Rift Valley Fever Virus Recruits the F-Box Protein FBXO3 To Degrade Subunit p62 of General Transcription Factor TFIIH

    PubMed Central

    Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas

    2014-01-01

    ABSTRACT The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. IMPORTANCE Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity. PMID:24403578

  9. Interaction of Arabidopsis Trihelix-Domain Transcription Factors VFP3 and VFP5 with Agrobacterium Virulence Protein VirF

    PubMed Central

    García-Cano, Elena; Magori, Shimpei; Sun, Qi; Ding, Zehong; Lazarowitz, Sondra G.; Citovsky, Vitaly

    2015-01-01

    Agrobacterium is a natural genetic engineer of plants that exports several virulence proteins into host cells in order to take advantage of the cell machinery to facilitate transformation and support bacterial growth. One of these effectors is the F-box protein VirF, which presumably uses the host ubiquitin/proteasome system (UPS) to uncoat the packaging proteins from the invading bacterial T-DNA. By analogy to several other bacterial effectors, VirF most likely has several functions in the host cell and, therefore, several interacting partners among host proteins. Here we identify one such interactor, an Arabidopsis trihelix-domain transcription factor VFP3, and further show that its very close homolog VFP5 also interacted with VirF. Interestingly, interactions of VirF with either VFP3 or VFP5 did not activate the host UPS, suggesting that VirF might play other UPS-independent roles in bacterial infection. To better understand the potential scope of VFP3 function, we used RNAi to reduce expression of the VFP3 gene. Transcriptome profiling of these VFP3-silenced plants using high-throughput cDNA sequencing (RNA-seq) revealed that VFP3 substantially affected plant gene expression; specifically, 1,118 genes representing approximately 5% of all expressed genes were significantly either up- or down-regulated in the VFP3 RNAi line compared to wild-type Col-0 plants. Among the 507 up-regulated genes were genes implicated in the regulation of transcription, protein degradation, calcium signaling, and hormone metabolism, whereas the 611 down-regulated genes included those involved in redox regulation, light reactions of photosynthesis, and metabolism of lipids, amino acids, and cell wall. Overall, this pattern of changes in gene expression is characteristic of plants under stress. Thus, VFP3 likely plays an important role in controlling plant homeostasis. PMID:26571494

  10. Using a minigene approach to characterize a novel splice site mutation in human F7 gene causing inherited factor VII deficiency in a Chinese pedigree.

    PubMed

    Yu, T; Wang, X; Ding, Q; Fu, Q; Dai, J; Lu, Y; Xi, X; Wang, H

    2009-11-01

    Factor VII deficiency which transmitted as an autosomal recessive disorder is a rare haemorrhagic condition. The aim of this study was to identify the molecular genetic defect and determine its functional consequences in a Chinese pedigree with FVII deficiency. The proband was diagnosed as inherited coagulation FVII deficiency by reduced plasma levels of FVII activity (4.4%) and antigen (38.5%). All nine exons and their flanking sequence of F7 gene were amplified by polymerase chain reaction (PCR) for the proband and the PCR products were directly sequenced. The compound heterozygous mutations of F7 (NM_000131.3) c.572-1G>A and F7 (NM_000131.3) c.1165T>G; p.Cys389Gly were identified in the proband's F7 gene. To investigate the splicing patterns associated with F7 c.572-1G>A, ectopic transcripts in leucocytes of the proband were analyzed. F7 minigenes, spanning from intron 4 to intron 7 and carrying either an A or a G at position -1 of intron 5, were constructed and transiently transfected into human embryonic kidney (HEK) 293T cells, followed by RT-PCR analysis. The aberrant transcripts from the F7 c.572-1G>A mutant allele were not detected by ectopic transcription study. Sequencing of the RT-PCR products from the mutant transfectant demonstrated the production of an erroneously spliced mRNA with exon 6 skipping, whereas a normal splicing occurred in the wide type transfectant. The aberrant mRNA produced from the F7 c.572-1G>A mutant allele is responsible for the factor VII deficiency in this pedigree.

  11. Evaluation of [(18)F]gefitinib as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in malignant tumors.

    PubMed

    Su, Helen; Seimbille, Yann; Ferl, Gregory Z; Bodenstein, Claudia; Fueger, Barbara; Kim, Kevin J; Hsu, Yu-Tien; Dubinett, Steven M; Phelps, Michael E; Czernin, Johannes; Weber, Wolfgang A

    2008-06-01

    Gefitinib, an inhibitor of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK), has shown potent effects in a subset of patients carrying specific EGFR-TK mutations in advanced non-small-cell lung cancer. In this study, we asked whether PET with [(18)F]gefitinib may be used to study noninvasively the pharmacokinetics of gefitinib in vivo and to image the EGFR status of cancer cells. Synthesis of [(18)F]gefitinib has been previously described. The biodistribution and metabolic stability of [(18)F]gefitinib was assessed in mice and vervet monkeys for up to 2 h post injection by both micropositron emission tomography (PET)/computed tomography (CT) scans and postmortem ex vivo tissue harvesting. Uptake levels of radiolabeled gefitinib in EGFR-expressing human cancer cell lines with various levels of EGFR expression or mutation status were evaluated both in vivo and in vitro. MicroPET/CT scans in two species demonstrated a rapid and predominantly hepatobiliary clearance of [(18)F]gefitinib in vivo. However, uptake levels of radiolabeled gefitinib, both in vivo and in vitro, did not correlate with EGFR expression levels or functional status. This unexpected observation was due to high nonspecific, nonsaturable cellular uptake of gefitinib. The biodistribution of the drug analogue [(18)F]gefitinib suggests that it may be used to assess noninvasively the pharmacokinetics of gefitinib in patients by PET imaging. This is of clinical relevance, as insufficient intratumoral drug concentrations are considered to be a factor for resistance to gefitinib therapy. However, the highly nonspecific cellular binding of [(18)F]gefitinib may preclude the use of this imaging probe for noninvasive assessment of EGFR receptor status in patients.

  12. The role of ZIP transporters and group F bZIP transcription factors in the Zn-deficiency response of wheat (Triticum aestivum).

    PubMed

    Evens, Nicholas P; Buchner, Peter; Williams, Lorraine E; Hawkesford, Malcolm J

    2017-10-01

    Understanding the molecular basis of zinc (Zn) uptake and transport in staple cereal crops is critical for improving both Zn content and tolerance to low-Zn soils. This study demonstrates the importance of group F bZIP transcription factors and ZIP transporters in responses to Zn deficiency in wheat (Triticum aestivum). Seven group F TabZIP genes and 14 ZIPs with homeologs were identified in hexaploid wheat. Promoter analysis revealed the presence of Zn-deficiency-response elements (ZDREs) in a number of the ZIPs. Functional complementation of the zrt1/zrt2 yeast mutant by TaZIP3, -6, -7, -9 and -13 supported an ability to transport Zn. Group F TabZIPs contain the group-defining cysteine-histidine-rich motifs, which are the predicted binding site of Zn 2+ in the Zn-deficiency response. Conservation of these motifs varied between the TabZIPs suggesting that individual TabZIPs may have specific roles in the wheat Zn-homeostatic network. Increased expression in response to low Zn levels was observed for several of the wheat ZIPs and bZIPs; this varied temporally and spatially suggesting specific functions in the response mechanism. The ability of the group F TabZIPs to bind to specific ZDREs in the promoters of TaZIPs indicates a conserved mechanism in monocots and dicots in responding to Zn deficiency. In support of this, TabZIPF1-7DL and TabZIPF4-7AL afforded a strong level of rescue to the Arabidopsis hypersensitive bzip19 bzip23 double mutant under Zn deficiency. These results provide a greater understanding of Zn-homeostatic mechanisms in wheat, demonstrating an expanded repertoire of group F bZIP transcription factors, adding to the complexity of Zn homeostasis. © 2017 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  13. Characterization of solid polymer dispersions of active pharmaceutical ingredients by 19F MAS NMR and factor analysis

    NASA Astrophysics Data System (ADS)

    Urbanova, Martina; Brus, Jiri; Sedenkova, Ivana; Policianova, Olivia; Kobera, Libor

    In this contribution the ability of 19F MAS NMR spectroscopy to probe structural variability of poorly water-soluble drugs formulated as solid dispersions in polymer matrices is discussed. The application potentiality of the proposed approach is demonstrated on a moderately sized active pharmaceutical ingredient (API, Atorvastatin) exhibiting extensive polymorphism. In this respect, a range of model systems with the API incorporated in the matrix of polvinylpyrrolidone (PVP) was prepared. The extent of mixing of both components was determined by T1(1H) and T1ρ(1H) relaxation experiments, and it was found that the API forms nanosized domains. Subsequently it was found out that the polymer matrix induces two kinds of changes in 19F MAS NMR spectra. At first, this is a high-frequency shift reaching 2-3 ppm which is independent on molecular structure of the API and which results from the long-range polarization of the electron cloud around 19F nucleus induced by electrostatic fields of the polymer matrix. At second, this is broadening of the signals and formation of shoulders reflecting changes in molecular arrangement of the API. To avoid misleading in the interpretation of the recorded 19F MAS NMR spectra, because both the contributions act simultaneously, we applied chemometric approach based on multivariate analysis. It is demonstrated that factor analysis of the recorded spectra can separate both these spectral contributions, and the subtle structural differences in the molecular arrangement of the API in the nanosized domains can be traced. In this way 19F MAS NMR spectra of both pure APIs and APIs in solid dispersions can be directly compared. The proposed strategy thus provides a powerful tool for the analysis of new formulations of fluorinated pharmaceutical substances in polymer matrices.

  14. Dual acquisition of 18F-FMISO and 18F-FDOPA

    NASA Astrophysics Data System (ADS)

    Bell, Christopher; Rose, Stephen; Puttick, Simon; Pagnozzi, Alex; Poole, Christopher M.; Gal, Yaniv; Thomas, Paul; Fay, Michael; Jeffree, Rosalind L.; Dowson, Nicholas

    2014-07-01

    Metabolic imaging using positron emission tomography (PET) has found increasing clinical use for the management of infiltrating tumours such as glioma. However, the heterogeneous biological nature of tumours and intrinsic treatment resistance in some regions means that knowledge of multiple biological factors is needed for effective treatment planning. For example, the use of 18F-FDOPA to identify infiltrative tumour and 18F-FMISO for localizing hypoxic regions. Performing multiple PET acquisitions is impractical in many clinical settings, but previous studies suggest multiplexed PET imaging could be viable. The fidelity of the two signals is affected by the injection interval, scan timing and injected dose. The contribution of this work is to propose a framework to explicitly trade-off signal fidelity with logistical constraints when designing the imaging protocol. The particular case of estimating 18F-FMISO from a single frame prior to injection of 18F-FDOPA is considered. Theoretical experiments using simulations for typical biological scenarios in humans demonstrate that results comparable to a pair of single-tracer acquisitions can be obtained provided protocol timings are carefully selected. These results were validated using a pre-clinical data set that was synthetically multiplexed. The results indicate that the dual acquisition of 18F-FMISO and 18F-FDOPA could be feasible in the clinical setting. The proposed framework could also be used to design protocols for other tracers.

  15. Wheat transcription factor TaWRKY70 is positively involved in high-temperature seedling-plant resistance to Puccinia striiformis f. sp. tritici

    USDA-ARS?s Scientific Manuscript database

    Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease of wheat (Triticum aestivum) worldwide. Wheat high-temperature seedling-plant (HTSP) resistance to Pst is non-race-specific and durable. WRKY transcription factors have proven to play important roles in ...

  16. F-spondin inhibits migration and differentiation of osteoclastic precursors.

    PubMed

    Oka, Hiroko; Mori, Maya; Kihara, Hisae

    2011-12-01

    Clinically, severe cemental resorption is a rare consequence of periodontitis, although alveolar bone resorption by osteoclasts is one of the main pathologic changes. F-spondin is a secreted neuronal glycoprotein that localizes to the cementum. F-spondin is among the cementum-specific factors in periodontal tissue that have been reported. However, the effects of F-spondin on osteoclastogenesis have not yet been established. We examined the effects of F-spondin on stages of osteoclastogenesis, migration, and differentiation in a mouse osteoclastic precursor model, RAW 264 cells. RAW 264 cells were treated with recombinant F-spondin. Macrophage colony stimulating factor (M-CSF)-induced cell migration was examined by migration assay performed with cell culture inserts. Osteoclastic differentiation was measured by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. In a transmigration assay, F-spondin significantly downregulated M-CSF-induced cell migration. Further, F-spondin significantly reduced the number of receptor activator of nuclear factor-kappa B ligand-induced TRAP-positive multinucleated cells. The receptor-associated protein, an antagonist of the low-density lipoprotein (LDL) receptor family, blocked the effects of F-spondin on M-CSF-induced migration. The suppressive effect of F-spondin on M-CSF-induced cell migration was blocked by knockdown of LDL receptor-related protein 8 (LRP8), a member of the LDL receptor family. Our findings suggest that F-spondin downregulates recruitment to the root side of periodontal tissue via LRP8 and inhibits differentiation of osteoclastic precursors. It is suggested that F-spondin is essential to protect the root surface from resorption.

  17. Multicomponent diffusion in molten salt LiF-BeF2: Dynamical correlations and Maxwell-Stefan diffusivities

    NASA Astrophysics Data System (ADS)

    Chakraborty, Brahmananda; Ramaniah, Lavanya M.

    2015-06-01

    Applying Green-Kubo formalism and equilibrium molecular dynamics (MD) simulations, we have studied the dynamic correlation, Onsager coeeficients and Maxwell-Stefan (MS) Diffusivities of molten salt LiF-BeF2, which is used as coolant in high temperature reactor. All the diffusive flux correlations show back-scattering or cage dynamics which becomes pronouced at higher temperature. Although the MS diffusivities are expected to depend very lightly on the composition due to decoupling of thermodynamic factor, the diffusivity ĐLi-F and ĐBe-F decreases sharply for higher concentration of LiF and BeF2 respectively. Interestingly, all three MS diffusivities have highest magnitude for eutectic mixture at 1000K (except ĐBe-F at lower LiF mole fraction) which is desirable from coolant point of view. Although the diffusivity for positive-positive ion pair is negative it is not in violation of the second law of thermodynamics as it satisfies the non-negative entropic constraints.

  18. Optimized conditions for selective gold flotation by ToF-SIMS and ToF-LIMS

    NASA Astrophysics Data System (ADS)

    Chryssoulis, S. L.; Dimov, S. S.

    2004-06-01

    This work describes a comprehensive characterization of the factors controlling the floatability of free gold from flotation test using reagents (collectors) at plant concentration levels. A relationship between the collectors loadings on gold particles and their surface composition has been established. The findings of this study show that silver activates gold flotation and there is a strong correlation between the surface concentration of silver and the loading of certain collectors. The organic surface analysis was done by ToF-SIMS while the inorganic surface analysis was carried out by time-of-flight laser ionization mass spectrometry (ToF-LIMS). The developed testing protocol based on ToF-LIMS and ToF-SIMS complementary surface analysis allows for optimization of the flotation scheme and hence improved gold recovery.

  19. F-prostanoid receptor regulation of fibroblast growth factor 2 signaling in endometrial adenocarcinoma cells.

    PubMed

    Sales, Kurt J; Boddy, Sheila C; Williams, Alistair R W; Anderson, Richard A; Jabbour, Henry N

    2007-08-01

    Prostaglandin (PG) F(2alpha) is a potent bioactive lipid in the female reproductive tract, and exerts its function after coupling with its heptahelical G-protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of fibroblast growth factor (FGF) 2, FGF receptor 1 (FGFR1), and FP receptor, colocalized within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF(2alpha)-FP receptor interaction in modulating FGF2 expression and signaling using an endometrial adenocarcinoma cell line stably expressing the FP receptor to the levels detected in endometrial adenocarcinomas (FPS cells) and endometrial adenocarcinoma tissue explants. PGF(2alpha)-FP receptor activation rapidly induced FGF2 mRNA expression, and elevated FGF2 protein expression and secretion into the culture medium in FPS cells and endometrial adenocarcinoma explants. The effect of PGF(2alpha) on the expression and secretion of FGF2 could be abolished by treatment of FPS cells and endometrial tissues with an FP receptor antagonist (AL8810) and inhibitor of ERK (PD98059). Furthermore, we have shown that FGF2 can promote the expression of FGF2 and cyclooxygenase-2, and enhance proliferation of endometrial adenocarcinoma cells via the FGFR1 and ERK pathways, thereby establishing a positive feedback loop to regulate neoplastic epithelial cell function in endometrial adenocarcinomas.

  20. Rotational Mode Specificity in the F(-) + CH3Y [Y = F and Cl] SN2 Reactions.

    PubMed

    Szabó, István; Czakó, Gábor

    2015-12-17

    More than 12 million quasiclassical trajectories are computed for the F(-) + CH3Y(v = 0, JK) [Y = F and Cl] SN2 reactions using full-dimensional ab initio analytical potential energy surfaces. The initial (J, K = 0) and (J, K = J) [J = 0, 2, 4, 6, 8] rotational state specific cross sections are obtained at different collision energies (Ecoll) in the 1-20 kcal mol(-1) range, and the scattering angle and initial attack angle distributions as well as the mechanism-specific opacity functions are reported at Ecoll = 10 kcal mol(-1). The tumbling rotation (K = 0) inhibits the F(-) + CH3F reaction by a factor of 3 for J = 8 at Ecoll = 10 kcal mol(-1). This tumbling rotational effect becomes smaller at low and high Ecoll, and the tumbling motion affects the cross sections of F(-) + CH3Cl by only a few percent. The spinning rotation (K = J) hinders both reactions by factors in the 1.3-1.7 range for J = 8 at low Ecoll, whereas slight promotion is found as the Ecoll increases. The tumbling rotation may counteract the attractive ion-dipole forces, and the spinning motion hinders the complex formation, thereby decreasing the reactivity.

  1. E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells.

    PubMed

    Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

    2015-01-01

    E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

  2. E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

    PubMed Central

    Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

    2015-01-01

    E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells. PMID:25892555

  3. The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

    PubMed Central

    Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

    2008-01-01

    Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

  4. Multiple factor indices of protection or risk towards disease.

    PubMed

    Belfiore, F; Iannello, S

    2001-02-01

    In order to combine several factors entailing protection or risk towards disease and to calculate a Protection Multiple Factor Index (PMFI) or, conversely, a Risk Multiple Factor Index (RMFI), we propose the following formulae: (1) PMFI = 2/[(mF)2 + 1] and (2) RMFI = 2/[(imF)2 + 1], where mF is the mean value of the factors considered and imF is the inverse (or reciprocal) of mF. In calculating mF, the value of each 'risk factor' observed in the patient under study (Vp) is expressed by taking the mean normal value (Vmn) as the unit, i.e. by calculating the ratio Vp/Vmn, whereas each 'protection factor' is expressed as the reciprocal of this ratio, i.e. as Vmn/Vp. The 'weight' of the various factors can be changed through multiplication by a number > 1 or < 1. Values of both PMFI and RMFI are always close to 1 in normal subjects, with extreme variations among patients between 0 and 2. The sum of the values of PMFI and RMFI is always equal to 2, so that one index can be deduced from the other. When factors are only two (F1 and F2), the formulae may be simplified as follows: PMFI = 2/[F1 x F2) + 1] and RMFI = 2/[(iF1 x iF2) + 1], where iF = 1/F, with only minimal changes in results.

  5. Experimental determination of field factors (\\Omega _{{{Q}_{\\text{clin}}},{{Q}_{\\text{msr}}}}^{{{f}_{\\text{clin}}},{{f}_{\\text{msr}}}} ) for small radiotherapy beams using the daisy chain correction method

    NASA Astrophysics Data System (ADS)

    Lárraga-Gutiérrez, José Manuel

    2015-08-01

    Recently, Alfonso et al proposed a new formalism for the dosimetry of small and non-standard fields. The proposed new formalism is strongly based on the calculation of detector-specific beam correction factors by Monte Carlo simulation methods, which accounts for the difference in the response of the detector between the small and the machine specific reference field. The correct calculation of the detector-specific beam correction factors demands an accurate knowledge of the linear accelerator, detector geometry and composition materials. The present work shows that the field factors in water may be determined experimentally using the daisy chain correction method down to a field size of 1 cm  ×  1 cm for a specific set of detectors. The detectors studied were: three mini-ionization chambers (PTW-31014, PTW-31006, IBA-CC01), three silicon-based diodes (PTW-60018, IBA-SFD and IBA-PFD) and one synthetic diamond detector (PTW-60019). Monte Carlo simulations and experimental measurements were performed for a 6 MV photon beam at 10 cm depth in water with a source-to-axis distance of 100 cm. The results show that the differences between the experimental and Monte Carlo calculated field factors are less than 0.5%—with the exception of the IBA-PFD—for field sizes between 1.5 cm  ×  1.5 cm and 5 cm  ×  5 cm. For the 1 cm  ×  1 cm field size, the differences are within 2%. By using the daisy chain correction method, it is possible to determine measured field factors in water. The results suggest that the daisy chain correction method is not suitable for measurements performed with the IBA-PFD detector. The latter is due to the presence of tungsten powder in the detector encapsulation material. The use of Monte Carlo calculated k{{Q\\text{clin}},{{Q}\\text{msr}}}{{f\\text{clin}},{{f}\\text{msr}}} is encouraged for field sizes less than or equal to 1 cm  ×  1 cm for the dosimeters used in this work.

  6. Ambient observations of hygroscopic growth factor and f(RH) below 1: Case studies from surface and airborne measurements

    NASA Astrophysics Data System (ADS)

    Shingler, Taylor; Sorooshian, Armin; Ortega, Amber; Crosbie, Ewan; Wonaschütz, Anna; Perring, Anne E.; Beyersdorf, Andreas; Ziemba, Luke; Jimenez, Jose L.; Campuzano-Jost, Pedro; Mikoviny, Tomas; Wisthaler, Armin; Russell, Lynn M.

    2016-11-01

    This study reports a detailed set of ambient observations of optical/physical shrinking of particles from exposure to water vapor with consistency across different instruments and regions. Data have been utilized from (i) a shipboard humidified tandem differential mobility analyzer during the Eastern Pacific Emitted Aerosol Cloud Experiment in 2011, (ii) multiple instruments on the NASA DC-8 research aircraft during the Studies of Emissions, Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys in 2013, and (iii) the Differential Aerosol Sizing and Hygroscopicity Spectrometer Probe during ambient measurements in Tucson, Arizona, during summer 2014 and winter 2015. Hygroscopic growth factor (ratio of humidified-to-dry diameter, GF = Dp,wet/Dp,dry) and f(RH) (ratio of humidified-to-dry scattering coefficients) values below 1 were observed across the range of relative humidity (RH) investigated (75-95%). A commonality of observations of GF and f(RH) below 1 in these experiments was the presence of particles enriched with carbonaceous matter, especially from biomass burning. Evidence of externally mixed aerosol, and thus multiple GFs with at least one GF < 1, was observed concurrently with f(RH) < 1 during smoke periods. Possible mechanisms responsible for observed shrinkage are discussed and include particle restructuring, volatilization effects, and refractive index modifications due to aqueous processing resulting in optical size modification. To further investigate ambient observations of GFs and f(RH) values less than 1, it is recommended to add an optional prehumidification bypass module to hygroscopicity instruments, to preemptively collapse particles prior to controlled RH measurements.

  7. Apple EIN3 BINDING F-box 1 inhibits the activity of three apple EIN3-like transcription factors

    PubMed Central

    Tacken, Emma J.; Ireland, Hilary S.; Wang, Yen-Yi; Putterill, Jo; Schaffer, Robert J.

    2012-01-01

    Background and aims Fruit ripening in Malus× domestica (apple) is controlled by ethylene. Work in model species has shown that following the detection of ethylene, the ETHYLENE INSENSITIVE 3 (EIN3) transcription factor is stabilized, leading to an increase in transcript accumulation of ethylene-responsive genes, such as POLYGALACTURONASE1 (PG1). In the absence of ethylene, the EIN3 BINDING F-box (EBF) proteins rapidly degrade EIN3 via the ubiquitination/SCF (Skp, Cullin, F-Box) proteasome pathway. In this study, we aim to identify and characterize the apple EBF genes, and test their activity against apple EIN3-like proteins (EILs). Methodology The apple genome sequence was mined for EBF-like genes. The expression of EBF-like genes was measured during fruit development. Using a transient assay in Nicotiana benthamiana leaves, the activity of three apple EILs was tested against the PG1 promoter, with and without ethylene and EBF1. Principal results Four EBF-like genes in apple were identified and grouped into two sub-clades. Sub-clade I genes had constant expression over fruit development while sub-clade II genes increased in expression at ripening. EBF1 was shown to reduce the transactivation of the apple PG1 promoter by the EIL1, EIL2 and EIL3 transcription factors in the presence of ethylene. Conclusions The apple EBF1 gene identified here is likely to be a functionally conserved EBF orthologue, modulating EIL activity in apples. The activity of EBF1 suggests that it is not specific to a single EIL, instead acting as a global regulator of apple EIL transcription factors. PMID:23585922

  8. F-22 cockpit avionics: a systems integration success story

    NASA Astrophysics Data System (ADS)

    Greeley, Kevin W.; Schwartz, Richard J.

    2000-08-01

    The F-22 'Raptor' is being developed and manufactured as multi-role fighter aircraft for the 'air dominance' mission. The F-22 team is led by Lockheed Martin, with Boeing and Pratt & Whitney as partners. The F-22 weapons system combines supersonic cruise, maneuverability, stealth, and an extensive suite of tightly integrated sensors to achieve a high level of lethality and invulnerability against current and projected threat systems such as fighter aircraft and surface to air missiles. Despite high automation of the complex systems installed in the F-22, the pilot is heavily tasked for air battle management. Response timelines are compressed due to supersonic cruise velocities. These factors challenge the Pilot Vehicle Interface (PVI) design. This paper discusses the team's response to these challenges, describing the physical cockpit layout, its controls and displays, and the hardware architecture, software tools, and development process used to mature the F-22 'Raptor' weapons system, including a review of Human Factors design considerations for F-22 displays.

  9. Activation of Ftz-F1-Responsive Genes through Ftz/Ftz-F1 Dependent Enhancers

    PubMed Central

    Field, Amanda; Xiang, Jie; Anderson, W. Ray; Graham, Patricia; Pick, Leslie

    2016-01-01

    The orphan nuclear receptor Ftz-F1 is expressed in all somatic nuclei in Drosophila embryos, but mutations result in a pair-rule phenotype. This was explained by the interaction of Ftz-F1 with the homeodomain protein Ftz that is expressed in stripes in the primordia of segments missing in either ftz-f1 or ftz mutants. Ftz-F1 and Ftz were shown to physically interact and coordinately activate the expression of ftz itself and engrailed by synergistic binding to composite Ftz-F1/Ftz binding sites. However, attempts to identify additional target genes on the basis of Ftz-F1/ Ftz binding alone has met with only limited success. To discern rules for Ftz-F1 target site selection in vivo and to identify additional target genes, a microarray analysis was performed comparing wildtype and ftz-f1 mutant embryos. Ftz-F1-responsive genes most highly regulated included engrailed and nine additional genes expressed in patterns dependent on both ftz and ftz-f1. Candidate enhancers for these genes were identified by combining BDTNP Ftz ChIP-chip data with a computational search for Ftz-F1 binding sites. Of eight enhancer reporter genes tested in transgenic embryos, six generated expression patterns similar to the corresponding endogenous gene and expression was lost in ftz mutants. These studies identified a new set of Ftz-F1 targets, all of which are co-regulated by Ftz. Comparative analysis of enhancers containing Ftz/Ftz-F1 binding sites that were or were not bona fide targets in vivo suggested that GAF negatively regulates enhancers that contain Ftz/Ftz-F1 binding sites but are not actually utilized. These targets include other regulatory factors as well as genes involved directly in morphogenesis, providing insight into how pair-rule genes establish the body pattern. PMID:27723822

  10. Actin assembly factors regulate the gelation kinetics and architecture of F-actin networks.

    PubMed

    Falzone, Tobias T; Oakes, Patrick W; Sees, Jennifer; Kovar, David R; Gardel, Margaret L

    2013-04-16

    Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Genetic mapping of secretion and functional determinants of the Vibrio cholerae TcpF colonization factor.

    PubMed

    Krebs, Shelly J; Kirn, Thomas J; Taylor, Ronald K

    2009-06-01

    Colonization of the human small intestine by Vibrio cholerae requires the type IV toxin-coregulated pilus (TCP). TcpF, which is encoded within the tcp operon, is secreted from the bacterial cell by the TCP apparatus and is also essential for colonization. Bacteria lacking tcpF are deficient in colonization, and anti-TcpF antibodies are protective in the infant mouse cholera model. In order to elucidate the regions of the protein that are required for secretion through the TCP apparatus and for its function in colonization, random mutagenesis of tcpF was performed. Analysis of these mutants suggests that multiple regions throughout the protein influence extracellular secretion and that determinants near the C terminus are important for the function of TcpF in colonization. The TcpF proteins of certain environmental V. cholerae isolates with 31% to 66% identity to pathogenic V. cholerae TcpF showed higher similarity in regions identified as secretion determinants but diverged in regions found to be important for colonization. These environmental TcpF proteins are secreted from the pathogenic strain; however, they do not mediate colonization in the infant mouse model. Here we provide genetic evidence pointing toward regions of TcpF that influence secretion, as well as regions that play an important role in in vivo colonization.

  12. The F-theory geometry with most flux vacua

    DOE PAGES

    Taylor, Washington; Wang, Yi -Nan

    2015-12-28

    Applying the Ashok-Denef-Douglas estimation method to elliptic Calabi-Yau fourfolds suggests that a single elliptic fourfold M max gives rise to O(10 272,000) F-theory flux vacua, and that the sum total of the numbers of flux vacua from all other F-theory geometries is suppressed by a relative factor of O(10 –3000). The fourfold M max arises from a generic elliptic fibration over a specific toric threefold base B max, and gives a geometrically non-Higgsable gauge group of E 8 9 × F 4 8 × (G 2 × SU(2)) 16, of which we expect some factors to be broken by G-fluxmore » to smaller groups. It is not possible to tune an SU(5) GUT group on any further divisors in M max, or even an SU(2) or SU(3), so the standard model gauge group appears to arise in this context only from a broken E 8 factor. Furthermore, the results of this paper can either be interpreted as providing a framework for predicting how the standard model arises most naturally in F-theory and the types of dark matter to be found in a typical F-theory compactification, or as a challenge to string theorists to explain why other choices of vacua are not exponentially unlikely compared to F-theory compactifications on M max.« less

  13. The F-theory geometry with most flux vacua

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

    Taylor, Washington; Wang, Yi -Nan

    Applying the Ashok-Denef-Douglas estimation method to elliptic Calabi-Yau fourfolds suggests that a single elliptic fourfold M max gives rise to O(10 272,000) F-theory flux vacua, and that the sum total of the numbers of flux vacua from all other F-theory geometries is suppressed by a relative factor of O(10 –3000). The fourfold M max arises from a generic elliptic fibration over a specific toric threefold base B max, and gives a geometrically non-Higgsable gauge group of E 8 9 × F 4 8 × (G 2 × SU(2)) 16, of which we expect some factors to be broken by G-fluxmore » to smaller groups. It is not possible to tune an SU(5) GUT group on any further divisors in M max, or even an SU(2) or SU(3), so the standard model gauge group appears to arise in this context only from a broken E 8 factor. Furthermore, the results of this paper can either be interpreted as providing a framework for predicting how the standard model arises most naturally in F-theory and the types of dark matter to be found in a typical F-theory compactification, or as a challenge to string theorists to explain why other choices of vacua are not exponentially unlikely compared to F-theory compactifications on M max.« less

  14. Insulation of the σF Regulatory System in Bacillus subtilis

    PubMed Central

    Carniol, Karen; Kim, Tae-Jong; Price, Chester W.; Losick, Richard

    2004-01-01

    The transcription factors σF and σB are related RNA polymerase sigma factors that govern dissimilar networks of adaptation to stress conditions in Bacillus subtilis. The two factors are controlled by closely related regulatory pathways, involving protein kinases and phosphatases. We report that insulation of the σF pathway from the σB pathway involves the integrated action of both the cognate kinase and the cognate phosphatase. PMID:15205443

  15. Successful Pregnancy in a Patient with Combined Deficiency of Factor V and Factor VIII.

    PubMed

    El Adib, Ahmed Ghassan; Majdi, Farah; Dilai, Mohamed Othmane; Asmouki, Hamid; Bassir, Ahlam; Harou, Karam; Soumani, Abderraouf; Younous, Said; Mahmal, Lahoucine

    2014-01-01

    Inherited combined factor V and factor VIII deficiency (F5F8D) is autosomal recessive transmission disorder. Epistaxis, postsurgical bleeding, and menorrhagia are the most common symptoms. The risk of miscarriage and placental abruption is consequent. We report a case of successful pregnancy in a patient with F5F8D. 20-year-old woman, born of consanguineous parents, third gestate, first parity, two miscarriages, admitted for child birth of a spontaneous pregnancy estimated at 38 weeks and was diagnosed with F5F8D. At admission, patient was hemodynamically stable, with good obstetric conditions. The biologic results showed low levels of PT (52%), factor V (7%), and factor VIII (5%), and the activated partial thromboplastin time was prolonged (68,6%). Parturient was admitted in intensive care unit, maternal and fetal monitoring was performed. Fresh frozen plasma (FFP) and factor VIII concentrates were perfused at the induction of labor. Analgesia used fentanyl titration. The delivery gave birth to a newborn male, with Apgar 10/10 and 3000 g. The puerperium was simple without any important bleeding. Laboratory tests for the newborn were acceptable. Little literature is available on this subject and there are no guidelines available concerning pregnancy; we chose to prescribe a combination of factor VIII concentrate and FFP in pre-, per- and postpartum. The same protocol was successfully used in a patient before dental extraction and prostatectomy. Vaginal delivery is possible, as our case. Management by multidisciplinary team is recommended.

  16. Multicomponent diffusion in molten salt LiF-BeF{sub 2}: Dynamical correlations and Maxwell–Stefan diffusivities

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

    Chakraborty, Brahmananda, E-mail: brahma@barc.gov.in; Ramaniah, Lavanya M.

    2015-06-24

    Applying Green–Kubo formalism and equilibrium molecular dynamics (MD) simulations, we have studied the dynamic correlation, Onsager coeeficients and Maxwell–Stefan (MS) Diffusivities of molten salt LiF-BeF{sub 2}, which is used as coolant in high temperature reactor. All the diffusive flux correlations show back-scattering or cage dynamics which becomes pronouced at higher temperature. Although the MS diffusivities are expected to depend very lightly on the composition due to decoupling of thermodynamic factor, the diffusivity Đ{sub Li-F} and Đ{sub Be-F} decreases sharply for higher concentration of LiF and BeF{sub 2} respectively. Interestingly, all three MS diffusivities have highest magnitude for eutectic mixture atmore » 1000K (except Đ{sub Be-F} at lower LiF mole fraction) which is desirable from coolant point of view. Although the diffusivity for positive-positive ion pair is negative it is not in violation of the second law of thermodynamics as it satisfies the non-negative entropic constraints.« less

  17. Comparative expression analysis of POU4F1, POU4F2 and ISL1 in developing mouse cochleovestibular ganglion neurons

    PubMed Central

    Deng, Min; Yang, Hua; Xie, Xiaoling; Liang, Guoqing; Gan, Lin

    2014-01-01

    POU-homeodomain and LIM-homeodomain transcription factors are expressed in developing projection neurons within retina, inner ear, dorsal root ganglion, and trigeminal ganglion, and play synergistic roles in their differentiation and survival. Here, using immunohistochemistry, we present a comparative analysis of the spatiotemporal expression pattern of POU4F1, POU4F2, and ISL1 during the development of cochleovestibular ganglion (CVG) neurons in mouse inner ear. At early stages, when otic neurons are first detected in the otic epithelium (OE) and migrate into periotic mesenchyme to form the CVG, POU4F1 and ISL1 are co-expressed in a majority of the delaminated CVG neurons, which are marked by NEUROD1 expression, but POU4F1 is absent in the otic epithelium. The onset of POU4F2 expression starts after that of POU4F1 and ISL1, and is observed in the NEUROD1-negative, post-mitotic CVG neurons. When the CVG neurons innervate the vestibular and cochlear sensory organs, the expression of POU4F1, POU4F2, and ISL1 continues in both vestibular and spiral ganglion cells. Later in development, POU4F1 expression becomes down-regulated in a majority of spiral ganglion (SG) neurons and more neurons express POU4F2 expression while ISL1 expression is maintained. The differential as well as overlapping expression of POU4F1, POU4F2, and ISL1 combined with previous studies suggests possible functional interaction and regulatory relationship of these transcription factors in the development of inner ear neurons. PMID:24709358

  18. Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-β pathways in a dihydrotestosterone-induced mouse model.

    PubMed

    Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Mavlonov, Gafurjon Turdalievich; Yi, Tae-Hoo

    2014-01-01

    This study was conducted to test whether ginsenoside F2 can reduce hair loss by influencing sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and the transforming growth factor beta (TGF-β) pathway of apoptosis in dihydrotestosterone (DHT)-treated hair cells and in a DHT-induced hair loss model in mice. Results for ginsenoside F2 were compared with finasteride. DHT inhibits proliferation of hair cells and induces androgenetic alopecia and was shown to activate an apoptosis signal pathway both in vitro and in vivo. The cell-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the proliferation rates of DHT-treated human hair dermal papilla cells (HHDPCs) and HaCaTs increased by 48% in the ginsenoside F2-treated group and by 12% in the finasteride-treated group. Western blot analysis showed that ginsenoside F2 decreased expression of TGF-β2 related factors involved in hair loss. The present study suggested a hair loss related pathway by changing SCAP related apoptosis pathway, which has been known to control cholesterol metabolism. SCAP, sterol regulatory element-binding protein (SREBP) and caspase-12 expression in the ginsenoside F2-treated group were decreased compared to the DHT and finasteride-treated group. C57BL/6 mice were also prepared by injection with DHT and then treated with ginsenoside F2 or finasteride. Hair growth rate, density, thickness measurements and tissue histotological analysis in these groups suggested that ginsenoside F2 suppressed hair cell apoptosis and premature entry to catagen more effectively than finasteride. Our results indicated that ginsenoside F2 decreased the expression of TGF-β2 and SCAP proteins, which have been suggested to be involved in apoptosis and entry into catagen. This study provides evidence those factors in the SCAP pathway could be targets for hair loss prevention drugs.

  19. Pair creation energy and Fano factor of silicon measured at 185 K using 55 F e X-rays

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

    Kotov, Ivan V.; Neal, H.; O'Connor, P.

    Here, the pair creation energy, ωω and the Fano factor of silicon were measured using a CCD sensor and X-rays from an 55Fe source. The measurements were performed at a sensor temperature of 185K. The pair creation energy was measured for X-rays in the 1.7–6.5 keV range. The measured pair creation energy is ω=(3.650 ± 0.009) eV at the MnK α line energy. The Fano factor at this energy is F = 0.128±0.001. The agreement with theory and previous measurements is satisfactory. The system gain was obtained from flat field exposures using the Poisson distribution properties. These results and themore » details of our measurement procedure are presented below.« less

  20. Pair creation energy and Fano factor of silicon measured at 185 K using 55 F e X-rays

    DOE PAGES

    Kotov, Ivan V.; Neal, H.; O'Connor, P.

    2018-06-14

    Here, the pair creation energy, ωω and the Fano factor of silicon were measured using a CCD sensor and X-rays from an 55Fe source. The measurements were performed at a sensor temperature of 185K. The pair creation energy was measured for X-rays in the 1.7–6.5 keV range. The measured pair creation energy is ω=(3.650 ± 0.009) eV at the MnK α line energy. The Fano factor at this energy is F = 0.128±0.001. The agreement with theory and previous measurements is satisfactory. The system gain was obtained from flat field exposures using the Poisson distribution properties. These results and themore » details of our measurement procedure are presented below.« less

  1. Identification of a novel large deletion in a patient with severe factor V deficiency using an in-house F5 MLPA assay.

    PubMed

    Nuzzo, F; Paraboschi, E M; Straniero, L; Pavlova, A; Duga, S; Castoldi, E

    2015-01-01

    Factor V (FV) deficiency is a rare autosomal recessive bleeding disorder caused by mutations in the F5 gene. FV-deficient patients in whom no mutation or only one mutation is found may harbour large gene rearrangements, which are not detected by conventional mutation screening strategies. The aim of this study was to develop and validate a multiplex ligation-dependent probe amplification (MLPA) assay for the detection of large deletions and duplications in the F5 gene. Twenty-two MLPA probes targeting 19 of the 25 exons and the upstream and downstream regions of the F5 gene were designed and tested in 10 normal controls, a patient with a known heterozygous deletion of F5 exons 1-7 (positive control) and 14 genetically unexplained FV-deficient patients. MLPA results were confirmed by digital PCR on a QuantStudio(™) 3D Digital PCR System. The F5-specific probes yielded a reproducible peak profile in normal controls, correctly detected the known deletion in the positive control and suggested the presence of a novel deletion of exons 9-10 in a patient with undetectable FV levels and only one identified mutation. Follow-up by chip-based digital PCR, long-range PCR and direct sequencing confirmed that this patient carried a heterozygous F5 deletion of 1823 bp extending from intron 8 to intron 10. Bioinformatics sequence analysis pinpointed repetitive elements that might have originated the deletion. In conclusion, we have developed and validated an MLPA assay for the detection of gross F5 gene rearrangements. This assay may represent a valuable tool for the molecular diagnosis of FV deficiency. © 2014 John Wiley & Sons Ltd.

  2. Body Mass Index, Metabolic Factors, and Striatal Activation During Stressful and Neutral-Relaxing States: An fMRI Study

    PubMed Central

    Jastreboff, Ania M; Potenza, Marc N; Lacadie, Cheryl; Hong, Kwangik A; Sherwin, Robert S; Sinha, Rajita

    2011-01-01

    Stress is associated with alterations in neural motivational-reward pathways in the ventral striatum (VS), hormonal/metabolic changes, and weight increases. The relationship between these different factors is not well understood. We hypothesized that body mass index (BMI) status and hormonal/metabolic factors would be associated with VS activation. We used functional magnetic resonance imaging (fMRI) to compare brain responses of overweight and obese (OW/OB: BMI ⩾25 kg/m2: N=27) individuals with normal weight (NW: BMI<18.5–24.9 kg/m2: N=21) individuals during exposure to personalized stress, alcohol cue, and neutral-relaxing situations using a validated, autobiographical, script-driven, guided-imagery paradigm. Metabolic factors, including fasting plasma glucose (FPG), insulin, and leptin, were examined for their association with VS activation. Consistent with previous studies, stress and alcohol cue exposure each increased activity in cortico-limbic regions. Compared with NW individuals, OW/OB individuals showed greater VS activation in the neutral-relaxing and stress conditions. FPG was correlated with VS activation. Significant associations between VS activation and metabolic factors during stress and relaxation suggest the involvement of metabolic factors in striatal dysfunction in OW/OB individuals. This relationship may contribute to non-homeostatic feeding in obesity. PMID:21048702

  3. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

    PubMed

    Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

    2004-05-01

    E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

  4. On the origin of POU5F1

    PubMed Central

    2013-01-01

    Background Pluripotency is a fundamental property of early mammalian development but it is currently unclear to what extent its cellular mechanisms are conserved in vertebrates or metazoans. POU5F1 and POU2 are the two principle members constituting the class V POU domain family of transcription factors, thought to have a conserved role in the regulation of pluripotency in vertebrates as well as germ cell maintenance and neural patterning. They have undergone a complex pattern of evolution which is poorly understood and controversial. Results By analyzing the sequences of POU5F1, POU2 and their flanking genes, we provide strong indirect evidence that POU5F1 originated at least as early as a common ancestor of gnathostomes but became extinct in a common ancestor of teleost fishes, while both POU5F1 and POU2 survived in the sarcopterygian lineage leading to tetrapods. Less divergent forms of POU5F1 and POU2 appear to have persisted among cartilaginous fishes. Conclusions Our study resolves the controversial evolutionary relationship between teleost pou2 and tetrapod POU2 and POU5F1, and shows that class V POU transcription factors have existed at least since the common ancestor of gnathostome vertebrates. It provides a framework for elucidating the basis for the lineage-specific extinctions of POU2 and POU5F1. PMID:23659605

  5. Xanthomonas campestris RpfB is a Fatty Acyl-CoA Ligase Required to Counteract the Thioesterase Activity of the RpfF Diffusible Signal Factor (DSF) Synthase

    PubMed Central

    Bi, Hongkai; Yu, Yonghong; Dong, Huijuan; Wang, Haihong; Cronan, John E.

    2014-01-01

    SUMMARY In Xanthomonas campestris pv. campestris (Xcc), the proteins encoded by the rpf (regulator of pathogenicity factor) gene cluster produce and sense a fatty acid signal molecule called diffusible signaling factor (DSF, 2(Z)-11-methyldodecenoic acid). RpfB was reported to be involved in DSF processing and was predicted to encode an acyl-CoA ligase. We report that RpfB activates a wide range of fatty acids to their CoA esters in vitro. Moreover, RpfB can functionally replace the paradigm bacterial acyl-CoA ligase, Escherichia coli FadD, in the E. coli β-oxidation pathway and deletion of RpfB from the Xcc genome results in a strain unable to utilize fatty acids as carbon sources. An essential RpfB function in the pathogenicity factor pathway was demonstrated by the properties of a strain deleted for both the rpfB and rpfC genes. The ΔrpfB ΔrpfC strain grew poorly and lysed upon entering stationary phase. Deletion of rpfF, the gene encoding the DSF synthetic enzyme, restored normal growth to this strain. RpfF is a dual function enzyme that synthesizes DSF by dehydration of a 3-hydroxyacyl-acyl carrier protein (ACP) fatty acid synthetic intermediate and also cleaves the thioester bond linking DSF to ACP. However, the RpfF thioesterase activity is of broad specificity and upon elimination of its RpfC inhibitor RpfF attains maximal activity and its thioesterase activity proceeds to block membrane lipid synthesis by cleavage of acyl-ACP intermediates. This resulted in release of the nascent acyl chains to the medium as free fatty acids. This lack of acyl chains for phospholipid synthesis results in cell lysis unless RpfB is present to counteract the RpfF thioesterase activity by catalyzing uptake and activation of the free fatty acids to give acyl-CoAs that can be utilized to restore membrane lipid synthesis. Heterologous expression of a different fatty acid activating enzyme, the Vibrio harveyi acyl-ACP synthetase, replaced RpfB in counteracting the effects of

  6. Nd3+-doped TeO2-PbF2-AlF3 glasses for laser applications

    NASA Astrophysics Data System (ADS)

    Lalla, E. A.; Rodríguez-Mendoza, U. R.; Lozano-Gorrín, A. D.; Sanz-Arranz, A.; Rull, F.; Lavín, V.

    2016-01-01

    A study of the optical properties of Nd3+ ion in TeO2-PbF2-AlF3 glasses has been carried out for different Nd3+ concentrations. Based on the Judd-Ofelt theory, intensity parameters and radiative properties were determined from the absorption spectra. Focusing on the suitability of this host for laser applications, the spectroscopic quality factor χ was obtained with a value of 1.07, a value of the order of other compositions proposed as laser hosts. For the most intense emission corresponding with the 4F3/2 → 4I11/2 transition (1.06 μm), the absorption and emission and have been calculated with values of 1.20 × 10-20 cm2, 2.08 × 10-20 cm2. A positive value for the gain cross-sections has been found for a population inversion factor γ of 0.4 in the spectral range from 1060 to 1110 nm. All these results suggest the potentially use of this system as a laser host.

  7. Resistivity Correction Factor for the Four-Probe Method: Experiment II

    NASA Astrophysics Data System (ADS)

    Yamashita, Masato; Yamaguchi, Shoji; Nishii, Toshifumi; Kurihara, Hiroshi; Enjoji, Hideo

    1989-05-01

    Experimental verification of the theoretically derived resistivity correction factor F is presented. Factor F can be applied to a system consisting of a disk sample and a four-probe array. Measurements are made on isotropic graphite disks and crystalline ITO films. Factor F can correct the apparent variations of the data and lead to reasonable resistivities and sheet resistances. Here factor F is compared to other correction factors; i.e. FASTM and FJIS.

  8. Jahn-Teller effect on the [TiF 4F 4F int] 6-(C 4v) and [NiF 4F 4F int] 7-(C 4v) clusters embedded into SrF 2 crystals

    NASA Astrophysics Data System (ADS)

    Ulanov, V. A.; Zhiteitcev, E. R.; Varlamov, A. G.

    2007-07-01

    By means of EPR method the associative [TiF 4F 4F int] 6-(C 4v) and [NiF 4F 4F int] 7-(C 4v) centers were revealed in the fluorite type SrF 2:Ti and SrF 2:Ni crystals grown by Bridgman method in helium atmosphere containing some amount of a fluorine gas. It was found that at low temperatures the local structures of these associative centers were exposed to a static rhombic distortion. The reasons of such distortions were accounted for by the assumption that the E ⊗ ( b1 + b2) vibronic interaction became effective due to that the ground orbital states of the [TiF 4F 4F int] 6-(C 4v) and [NiF 4F 4F int] 7-(C 4v) centers occurred to be doubly degenerated.

  9. Thermodynamic assessment of the LiF-NaF-BeF2-ThF4-UF4 system

    NASA Astrophysics Data System (ADS)

    Capelli, E.; Beneš, O.; Konings, R. J. M.

    2014-06-01

    The present study describes the full thermodynamic assessment of the LiF-NaF-BeF2-ThF4-UF4 system which is one of the key systems considered for a molten salt reactor fuel. The work is an extension of the previously assessed LiF-NaF-ThF4-UF4 system with addition of BeF2 which is characterized by very low neutron capture cross section and a relatively low melting point. To extend the database the binary BeF2-ThF4 and BeF2-UF4 systems were optimized and the novel data were used for the thermodynamic assessment of BeF2 containing ternary systems for which experimental data exist in the literature. The obtained database is used to optimize the molten salt reactor fuel composition and to assess its properties with the emphasis on the melting behaviour.

  10. Effect of postponed treatment with an anti-tumour necrosis factor (TNF) F(ab')2 fragment on endotoxin-induced cytokine and neutrophil responses in chimpanzees.

    PubMed Central

    van der Poll, T; Levi, M; ten Cate, H; Jansen, J; Biemond, B J; Haagmans, B L; Eerenberg, A; van Deventer, S J; Hack, C E; ten Cate, J W

    1995-01-01

    TNF is considered to be an intermediate factor in endotoxin-induced release of other cytokines and endotoxin-induced neutrophil degranulation. Little is known about the effect of postponed treatment with anti-TNF in primate endotoxin models. To assess the effect of delayed treatment with anti-TNF in endotoxaemia, six healthy adult chimpanzees were intravenously injected with Escherichia coli endotoxin (4 ng/kg). In three of these animals the administration of endotoxin was followed after 30 min by a bolus i.v. injection of the anti-TNF F(ab')2 fragment MAK 195F (0.1 mg/kg). Post-treatment with MAK 195F completely prevented the appearance of TNF activity in serum elicited by endotoxin, and markedly reduced the rises in the serum concentrations of IL-6 and IL-8. In addition, the endotoxin-induced increases in the type I and type II soluble TNF receptors were also profoundly inhibited by MAK 195F, suggesting that TNF is involved in the release of its own soluble receptors in endotoxaemia. Neutrophilic leucocytosis was not affected by MAK 195F. In contrast, MAK 195F did significantly abrogate neutrophil degranulation, as measured by the plasma concentrations of lactoferrin. These results indicate that treatment with anti-TNF 30 min after the administration of endotoxin is still effective in attenuating the induction of the cytokine network and of neutrophil degranulation. PMID:7697917

  11. Polyadenylation proteins CstF-64 and τCstF-64 exhibit differential binding affinities for RNA polymers

    PubMed Central

    Monarez, Roberto R.; Macdonald, Clinton C.; Dass, Brinda

    2006-01-01

    CstF-64 (cleavage stimulation factor-64), a major regulatory protein of polyadenylation, is absent during male meiosis. Therefore a paralogous variant, τCstF-64 is expressed in male germ cells to maintain normal spermatogenesis. Based on sequence differences between τCstF-64 and CstF-64, and on the high incidence of alternative polyadenylation in testes, we hypothesized that the RBDs (RNA-binding domains) of τCstF-64 and CstF-64 have different affinities for RNA elements. We quantified Kd values of CstF-64 and τCstF-64 RBDs for various ribopolymers using an RNA cross-linking assay. The two RBDs had similar affinities for poly(G)18, poly(A)18 or poly(C)18, with affinity for poly(C)18 being the lowest. However, CstF-64 had a higher affinity for poly(U)18 than τCstF-64, whereas it had a lower affinity for poly(GU)9. Changing Pro-41 to a serine residue in the CstF-64 RBD did not affect its affinity for poly(U)18, but changes in amino acids downstream of the C-terminal α-helical region decreased affinity towards poly(U)18. Thus we show that the two CstF-64 paralogues differ in their affinities for specific RNA sequences, and that the region C-terminal to the RBD is important in RNA sequence recognition. This supports the hypothesis that τCstF-64 promotes germ-cell-specific patterns of polyadenylation by binding to different downstream sequence elements. PMID:17029590

  12. Actin Assembly Factors Regulate the Gelation Kinetics and Architecture of F-actin Networks

    PubMed Central

    Falzone, Tobias T.; Oakes, Patrick W.; Sees, Jennifer; Kovar, David R.; Gardel, Margaret L.

    2013-01-01

    Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. PMID:23601318

  13. Logamediate Inflation in f(T) Teleparallel Gravity

    NASA Astrophysics Data System (ADS)

    Rezazadeh, Kazem; Abdolmaleki, Asrin; Karami, Kayoomars

    2017-02-01

    We study logamediate inflation in the context of f(T) teleparallel gravity. f(T)-gravity is a generalization of the teleparallel gravity which is formulated on the Weitzenbock spacetime, characterized by the vanishing curvature tensor (absolute parallelism) and the non-vanishing torsion tensor. We consider an f(T)-gravity model which is sourced by a canonical scalar field. Assuming a power-law f(T) function in the action, we investigate an inflationary universe with a logamediate scale factor. Our results show that, although logamediate inflation is completely ruled out by observational data in the standard inflationary scenario based on Einstein gravity, it can be compatible with the 68% confidence limit joint region of Planck 2015 TT,TE,EE+lowP data in the framework of f(T)-gravity.

  14. E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.

    PubMed

    Li, Yuncheng; Sturgis, Erich M; Zhu, Lijun; Cao, Xiaoli; Wei, Qingyi; Zhang, Hua; Li, Guojun

    2017-04-01

    Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P < 0.001) and lower SCCOP recurrence risk (HR, 0.4, 95% CI, 0.3-0.6 and HR, 0.3, 95% CI, 0.2-0.5, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of E2F2-rs2742976 and E2F2-rs3218123 had better disease-free survival rates (both log-rank, P < 0.001) and lower recurrence risk (HR, 0.1, 95% CI, 0.1-0.4 and HR, 0.1, 95% CI, 0.0-0.2, respectively) than patients with variant genotypes. However, no significant differences were found for the other three polymorphisms. After combining the risk genotypes of the five polymorphisms and using the high-risk group (2-5 risk genotypes) as the reference group, we found that the low-risk groups (0 or 1 risk genotype) had significantly lower recurrence risk among all patients (HR, 0.4, 95% CI, 0.3-0.6) and among HPV16-positive patients (HR, 0.2, 95% CI, 0.1-0.5). Our findings suggest that E2F2 polymorphisms may individually or jointly modify SCCOP recurrence risk, particularly for SCCOP patients with HPV16-positive tumors. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Factors, fiction and endothelium-derived hyperpolarizing factor.

    PubMed

    Sandow, Shaun L

    2004-09-01

    1. The principal mediators of vascular tone are neural, endothelial and physical stimuli that result in the initiation of dilator and constrictor responses to facilitate the control of blood pressure. Two primary vasodilatory stimuli produced by the endothelium are nitric oxide (NO) and prostaglandins. An additional endothelium-dependent vasodilatory mechanism is characterized as the hyperpolarization-mediated relaxation that remains after the inhibition of the synthesis of NO and prostaglandins. This mechanism is due to the action of a so-called endothelium-derived hyperpolarizing factor (EDHF) and is dependent on either the release of diffusible factor(s) and/or to a direct contact-mediated mechanism. 2. Most evidence supports the concept that 'EDHF' activity is dependent on contact-mediated mechanisms. This involves the transfer of an endothelium-derived electrical current, as an endothelium-derived hyperpolarization (EDH), through direct heterocellular coupling of endothelial cells and smooth muscle cells via myoendothelial gap junctions (MEGJ). However, there is a lack of consensus with regard to the nature and mechanism of action of EDHF/EDH (EDH(F)), which has been shown to vary within and between vascular beds, as well as among species, strains, sex and during development, ageing and disease. 3. In addition to actual heterogeneity in EDH(F), further heterogeneity has resulted from the less-than-optimal design, analysis and interpretation of data in some key papers in the EDHF literature; with such views being perpetuated in the subsequent literature. 4. The focus of the present brief review is to examine what factors are proposed as EDH(F) and highlight the correlative structural and functional studies from our laboratory that demonstrate an integral role for MEGJ in the conduction of EDH, which account for the heterogeneity in EDH(F), while incorporating the reported diffusible mechanisms in the regulation of this activity. Furthermore, in addition to the

  16. Electronic sputtering of LiF, CaF2, LaF3 and UF4 with 197 MeV Au ions. Is the stoichiometry of atom emission preserved?

    NASA Astrophysics Data System (ADS)

    Toulemonde, M.; Assmann, W.; Muller, D.; Trautmann, C.

    2017-09-01

    Sputtering experiments with swift heavy ions in the electronic energy loss regime were performed by using the catcher technique in combination with elastic recoil detection analysis. Four different fluoride targets, LiF, CaF2, LaF3 and UF4 were irradiated in the electronic energy loss regime using 197 MeV Au ions. The angular distribution of particles sputtered from the surface of freshly cleaved LiF and CaF2 single crystals is composed of a broad cosine distribution superimposed by a jet-like peak that appears perpendicular to the surface independent of the angle of beam incidence. For LiF, the particle emission in the entire angular distribution (jet plus broad cosine component) is stoichiometric, whereas for CaF2 the ratio of the sputtered F to Ca particles is at large angles by a factor of two smaller than the stoichiometry of the crystal. For single crystalline LaF3 no jet component is observed and the angular distribution is non-stoichiometric with the number of sputtered F particles being slightly larger than the number of sputtered La particles. In the case of UF4, the target was polycrystalline and had a much rougher surface compared to cleaved crystals. This destroys the appearance of a possible jet component leading to a broad angular distribution. The ratio of sputtered U atoms compared to F atoms is in the order of 1-2, i.e. the number of collected particles on the catcher is also non-stoichiometric. Such unlike behavior of particles sputtered from different fluoride crystals creates new questions.

  17. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    PubMed

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  18. Visualization of highly dynamic F-actin plus ends in growing phaseolus vulgaris root hair cells and their responses to Rhizobium etli nod factors.

    PubMed

    Zepeda, Isaac; Sánchez-López, Rosana; Kunkel, Joseph G; Bañuelos, Luis A; Hernández-Barrera, Alejandra; Sánchez, Federico; Quinto, Carmen; Cárdenas, Luis

    2014-03-01

    Legume plants secrete signaling molecules called flavonoids into the rhizosphere. These molecules activate the transcription of rhizobial nod genes, which encode proteins involved in the synthesis of signaling compounds named Nod factors (NFs). NFs, in turn, trigger changes in plant gene expression, cortical cell dedifferentiation and mitosis, depolarization of the root hair cell membrane potential and rearrangement of the actin cytoskeleton. Actin polymerization plays an important role in apical growth in hyphae and pollen tubes. Using sublethal concentrations of fluorescently labeled cytochalasin D (Cyt-Fl), we visualized the distribution of filamentous actin (F-actin) plus ends in living Phaseolus vulgaris and Arabidopsis root hairs during apical growth. We demonstrated that Cyt-Fl specifically labeled the newly available plus ends of actin microfilaments, which probably represent sites of polymerization. The addition of unlabeled competing cytochalasin reduced the signal, suggesting that the labeled and unlabeled forms of the drug bind to the same site on F-actin. Exposure to Rhizobium etli NFs resulted in a rapid increase in the number of F-actin plus ends in P. vulgaris root hairs and in the re-localization of F-actin plus ends to infection thread initiation sites. These data suggest that NFs promote the formation of F-actin plus ends, which results in actin cytoskeleton rearrangements that facilitate infection thread formation.

  19. Correlation between 18F-FDG Positron-Emission Tomography 18F-FDG Uptake Levels at Diagnosis and Histopathologic and Immunohistochemical Factors in Patients with Breast Cancer

    PubMed Central

    Uğurluer, Gamze; Yavuz, Sinan; Çalıkuşu, Züleyha; Seyrek, Ertuğrul; Kibar, Mustafa; Serin, Meltem; Ersöz, Canan; Demircan, Orhan

    2016-01-01

    Objective In this study, we aimed to determine the correlation between pretreatment-staging 18F-FDG total body positron-emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) levels and histopathologic and immunohistochemical predictive and prognostic factors in patients with breast cancer. Materials and Methods One hundred thirty-nine women with breast cancer who were treated between 2009 and 2015 at our hospital and who had pretreatment-staging PET/CT were included in the study. SUVmax levels and histopathologic and immunohistochemical results were compared. Results The median age was 48 years (range, 29–79 years). The mean tumor diameter was 33.4 mm (range, 7–120 mm). The histology was invasive ductal carcinoma in 80.6% of the patients. In the univariate analysis, SUVmax levels were significantly higher in patients with invasive ductal carcinoma; in patients with a maximum tumor diameter more than 2 cm; patients who were estrogen, progesterone, and combined hormone receptor-negative, triple-negative patients, and in tumors with higher grades (p<0.05). In HER2-positive patients, SUVmax levels were higher even if it was not statistically significant. There was no correlation between lymph node metastases and pathologic stage. In multivariate analysis, tumor diameter was an independent factor. Conclusion SUVmax levels are correlated with known histopathologic and immunohistochemical prognostic factors. PET/CT could be useful in preoperative evaluation of patients with breast cancer to predict biologic characteristics of tumors and prognosis. PMID:28331746

  20. fMRI reliability: influences of task and experimental design.

    PubMed

    Bennett, Craig M; Miller, Michael B

    2013-12-01

    As scientists, it is imperative that we understand not only the power of our research tools to yield results, but also their ability to obtain similar results over time. This study is an investigation into how common decisions made during the design and analysis of a functional magnetic resonance imaging (fMRI) study can influence the reliability of the statistical results. To that end, we gathered back-to-back test-retest fMRI data during an experiment involving multiple cognitive tasks (episodic recognition and two-back working memory) and multiple fMRI experimental designs (block, event-related genetic sequence, and event-related m-sequence). Using these data, we were able to investigate the relative influences of task, design, statistical contrast (task vs. rest, target vs. nontarget), and statistical thresholding (unthresholded, thresholded) on fMRI reliability, as measured by the intraclass correlation (ICC) coefficient. We also utilized data from a second study to investigate test-retest reliability after an extended, six-month interval. We found that all of the factors above were statistically significant, but that they had varying levels of influence on the observed ICC values. We also found that these factors could interact, increasing or decreasing the relative reliability of certain Task × Design combinations. The results suggest that fMRI reliability is a complex construct whose value may be increased or decreased by specific combinations of factors.

  1. The OsO(3)F(+) and mu-F(OsO(3)F)(2)(+) cations: their syntheses and study by Raman and (19)F NMR spectroscopy and electron structure calculations and X-ray crystal structures of [OsO(3)F][PnF(6)] (Pn = As, Sb), [OsO(3)F][HF](2)[AsF(6)], [OsO(3)F][HF][SbF(6)], and [OsO(3)F][Sb(3)F(16)].

    PubMed

    Gerken, Michael; Dixon, David A; Schrobilgen, Gary J

    2002-01-28

    The fluoride ion donor properties of OsO(3)F(2) have been investigated. The salts [OsO(3)F][AsF(6)], [OsO(3)F][HF](2)[AsF(6)], mu-F(OsO(3)F)(2)[AsF(6)], [OsO(3)F][HF](2)[SbF(6)], and [OsO(3)F][HF][SbF(6)] have been prepared by reaction of OsO(3)F(2) with AsF(5) and SbF(5) in HF solvent and have been characterized in the solid state by Raman spectroscopy. The single-crystal X-ray diffraction studies of [OsO(3)F][AsF(6)] (P2(1)/n, a = 7.0001(11) A, c = 8.8629(13) A, beta = 92.270(7) degrees, Z = 4, and R(1) = 0.0401 at -126 degrees C), [OsO(3)F][SbF(6)] (P2(1)/c, a = 5.4772(14) A, b = 10.115(3) A, c = 12.234(3) A, beta = 99.321(5) degrees, Z = 4, and R(1) = 0.0325 at -173 degrees C), [OsO(3)F][HF](2)[AsF(6)] (P2(1)/n, a = 5.1491(9) A, b = 8.129(2) A, c = 19.636(7) A, beta = 95.099(7) degrees, Z = 4, and R(1) = 0.0348 at -117 degrees C), and [OsO(3)F][HF][SbF(6)] (Pc, a = 5.244(4) A, b = 9.646(6) A, c = 15.269(10) A, beta = 97.154(13) degrees, Z = 4, and R(1) = 0.0558 at -133 degrees C) have shown that the OsO(3)F(+) cations exhibit strong contacts to the anions and HF solvent molecules giving rise to cyclic, dimeric structures in which the osmium atoms have coordination numbers of 6. The reaction of OsO(3)F(2) with neat SbF(5) yielded [OsO(3)F][Sb(3)F(16)], which has been characterized by (19)F NMR spectroscopy in SbF(5) and SO(2)ClF solvents and by Raman spectroscopy and single-crystal X-ray diffraction in the solid state (P4(1)m, a = 10.076(6) A, c = 7.585(8) A, Z = 2, and R(1) = 0.0858 at -113 degrees C). The weak fluoride ion basicity of the Sb(3)F(16)(-) anion resulted in an OsO(3)F(+) cation (C(3)(v) point symmetry) that is well isolated from the anion and in which the osmium is four-coordinate. The geometrical parameters and vibrational frequencies of OsO(3)F(+), ReO(3)F, mu-F(OsO(3)F)(2)(+), (FO(3)Os--FPnF(5))(2), and (FO(3)Os--(HF)(2)--FPnF(5))(2) (Pn = As, Sb) have been calculated using density functional theory methods.

  2. Antibody production of wild-type and enzyme V279F variants of PAF-AH as a risk factor for Cardiovascular disease

    NASA Astrophysics Data System (ADS)

    Ramadhani, Anggia N.; Puspitarini, Sapti; Sari, Anissa N.; Widodo

    2017-11-01

    Coronary artery disease (CAD) has emerged as a leading cause of death in Indonesia nowadays. WHO data in 2012 revealed that 37% of the Indonesian population died from this disease. CAD occurs because of endothelial dysfunction in the arteries. Lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor acetylhydrolase (PAF-AH), is a phospholipase A2 enzyme, encoded by the PLA2G7 gene. This protein is predicted to be involved in inflammatory phospholipid metabolism so it can be used as a biomarker of CAD in the early phase. Thus, the purpose of this research is to discover the difference in antibody production between wild-type and mutant V279F. The PAF-AH enzyme was isolated from mice lymphocyte cells in order to develop this enzyme as a biomarker of cardiovascular disease. PAF-AH migrates at 55kDa according to SDS-PAGE analysis. Flow cytometry analysis showed that mutant PAF-AH (V279F) is more antigenic than wild-type PAF-AH. The missense mutation of V279F PAF-AH means this enzyme cannot catabolize the acetyl group at the sn-2 position of PAF.

  3. HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology.

    PubMed

    Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A

    2016-01-01

    Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease.

  4. Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

    PubMed

    Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

    2009-12-15

    Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

  5. F2-isoprostanes and F4-neuroprostanes as markers of intracranial aneurysm development.

    PubMed

    Syta-Krzyżanowska, Anna; Jarocka-Karpowicz, Iwona; Kochanowicz, Jan; Turek, Grzegorz; Rutkowski, Robert; Gorbacz, Krzysztof; Mariak, Zenon; Skrzydlewska, Elżbieta

    2018-04-24

    Intracranial aneurysms are common, occurring in about 1-2% of the population. Saccular aneurysm is a pouch-like pathological dilatation of an intracranial artery that develops when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. The aim of this study was to determine whether the development of intracranial aneurysms and subarachnoid hemorrhage (SAH) affects neuronal phospholipid metabolism, and what influence different invasive treatments have on brain free radical phospholipid metabolism. The level of polyunsaturated fatty acid (PUFA) cyclization products - F2-isoprostanes and F4-neuroprostanes - was examined using liquid chromatography - mass spectrometry (LC-MS) in the plasma of patients with brain aneurysm and resulting subarachnoid hemorrhage. It was revealed that an aneurysm leads to the enhancement of lipid peroxidation with a significant increase in plasma F2-isoprostanes and F4-neuroprostanes (more than 3-fold and 11-fold, respectively) in comparison to healthy subjects. The rupture of an aneurysm results in hemorrhage and an additional increase in examined prostaglandin derivatives. The embolization and clipping of aneurysms contribute to a gradual restoration of metabolic homeostasis in brain cells, which is visible in the decrease in PUFA cyclization products. The results indicate that aneurysm development is associated with enhanced inflammation and oxidative stress, factors which favor lipid peroxidation, particularly in neurons, whose membranes are rich in docosahexaenoic acid, a precursor of F4-neuroprostanes.

  6. Arrangement of the Clostridium baratii F7 Toxin Gene Cluster with Identification of a σ Factor That Recognizes the Botulinum Toxin Gene Cluster Promoters

    DOE PAGES

    Dover, Nir; Barash, Jason R.; Burke, Julianne N.; ...

    2014-05-22

    Botulinum neurotoxin (BoNT) is the most poisonous substances known and its eight toxin types (A to H) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. Infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the United States. It results from swallowed spores of Clostridium botulinum (or rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) that germinate and temporarily colonize the lumen of the large intestine, where, as vegetative cells, they produce botulinum toxin. Botulinum neurotoxin is encoded by the bontmore » gene that is part of a toxin gene cluster that includes several accessory genes. In this paper, we sequenced for the first time the complete botulinum neurotoxin gene cluster of nonproteolytic C. baratii type F7. Like the type E and the nonproteolytic type F6 botulinum toxin gene clusters, the C. baratii type F7 had an orfX toxin gene cluster that lacked the regulatory botR gene which is found in proteolytic C. botulinum strains and codes for an alternative σ factor. In the absence of botR, we identified a putative alternative regulatory gene located upstream of the C. baratii type F7 toxin gene cluster. This putative regulatory gene codes for a predicted σ factor that contains DNA-binding-domain homologues to the DNA-binding domains both of BotR and of other members of the TcdR-related group 5 of the σ 70 family that are involved in the regulation of toxin gene expression in clostridia. We showed that this TcdR-related protein in association with RNA polymerase core enzyme specifically binds to the C. baratii type F7 botulinum toxin gene cluster promoters. Finally, this TcdR-related protein may therefore be involved in regulating the expression of the genes of the botulinum toxin gene cluster in neurotoxigenic C. baratii.« less

  7. Pulsed and cw laser oscillations in LiF:F-2 color center crystal under laser diode pumping.

    PubMed

    Basiev, Tasoltan T; Vassiliev, Sergey V; Konjushkin, Vasily A; Gapontsev, Valentin P

    2006-07-15

    Continuous-wave laser oscillations in LiF:F-2 crystal optically pumped by a laser diode at 970 nm were demonstrated for what is believed to be the first time. The slope efficiency of 14% and conversion efficiency of 5.5% were achieved for 80 micros pump pulse duration and 5 Hz pulse repetition rate. An efficiency twice as low was measured at a 6.25 kHz pulse repetition rate (50% off-duty factor) and in cw mode of laser operation.

  8. Substituent effects in a series of 1,7-C[subscript 60](R[subscript F])[subscript 2] compounds (R[subscript F] = CF[subscript 3], C[subscript 2]F[subscript 5], n-C[subscrip 3]F[subscript 7], i-C[subscript 3]F[subscript 7], n-C[subscript 4]F[subscript 9], s-C[subscript 4]F[subscript 9], n-C[subscript 8]F[subscript 17]): electron affinities, reduction potentials and E(LUMO) values are not always correlated

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

    Kuvychko, Igor V.; Whitaker, James B.; Larson, Bryon W.

    2013-04-08

    A series of seven structurally-similar compounds with different pairs of R{sub F} groups were prepared, characterized spectroscopically, and studied by electrochemical methods (cyclic and square-wave voltammetry), low-temperature anion photoelectron spectroscopy, and DFT calculations (five of the compounds are reported here for the first time). This is the first time that a set of seven R{sub F} groups have been compared with respect to their relative effects on E{sub 1/2}(0/-), electron affinity (EA), and the DFT-calculated LUMO energy. The compounds, 1,7-C{sub 60}(R{sub F}){sub 2} (R{sub F} = CF{sub 3}, C{sub 2}F{sub 5}, i-C{sub 3}F{sub 7}, n-C{sub 3}F{sub 7}, s-C{sub 4}F{sub 9},more » n-C{sub 4}F{sub 9} and n-C{sub 8}F{sub 21}), were found to have statistically different electron affinities (EA), at the {+-}10 meV level of uncertainty, but virtually identical first reduction potentials, at the {+-}10 mV level of uncertainty. The lack of a correlation between EA and E{sub 1/2}(0/-), and between E(LUMO) and E{sub 1/2}(0/-), for such similar compounds is unprecedented and suggests that explanations for differences in figures of merit for materials and/or devices that are based on equating easily measurable E{sub 1/2}(0/-) values with EAs or E(LUMO) values should be viewed with caution. The solubilities of the seven compounds in toluene varied by nearly a factor of six, but in an unpredictable way, with the C{sub 2}F{sub 5} and s-C{sub 4}F{sub 9} compounds being the most soluble and the i-C{sub 3}F{sub 7} compound being the least soluble. The effects of the different R{sub F} groups on EAs, E(LUMO) values, and solubilities should help fluorine chemists choose the right R{sub F} group to design new materials with improved morphological, electronic, optical, and/or magnetic properties.« less

  9. Syntheses, Raman spectra, and X-ray crystal structures of [XeF(5)][mu-F(OsO(3)F(2))(2)] and [M][OsO(3)F(3)] (M = XeF(5)(+), Xe(2)F(11)(+)).

    PubMed

    Hughes, Michael J; Mercier, Hélène P A; Schrobilgen, Gary J

    2010-04-05

    Stoichiometric amounts of XeF(6) and (OsO(3)F(2))(infinity) react at 25-50 degrees C to form salts of the known XeF(5)(+) and Xe(2)F(11)(+) cations, namely, [XeF(5)][mu-F(OsO(3)F(2))(2)], [XeF(5)][OsO(3)F(3)], and [Xe(2)F(11)][OsO(3)F(3)]. Although XeF(6) is oxophilic toward a number of transition metal and main-group oxides and oxide fluorides, fluoride/oxide metathesis was not observed. The series provides the first examples of noble-gas cations that are stabilized by metal oxide fluoride anions and the first example of a mu-F(OsO(3)F(2))(2)(-) salt. Both [XeF(5)][mu-F(OsO(3)F(2))(2)] and [Xe(2)F(11)][OsO(3)F(3)] are orange solids at room temperature. The [XeF(5)][OsO(3)F(3)] salt is an orange liquid at room temperature that solidifies at 5-0 degrees C. When the salts are heated at 50 degrees C under 1 atm of N(2) for more than 2 h, significant XeF(6) loss occurs. The X-ray crystal structures (-173 degrees C) show that the salts exist as discrete ion pairs and that the osmium coordination spheres in OsO(3)F(3)(-) and mu-F(OsO(3)F(2))(2)(-) are pseudo-octahedral OsO(3)F(3)-units having facial arrangements of oxygen and fluorine atoms. The mu-F(OsO(3)F(2))(2)(-) anion is comprised of two symmetry-related OsO(3)F(2)-groups that are fluorine-bridged to one another. Ion pairing results from secondary bonding interactions between the fluorine/oxygen atoms of the anions and the xenon atom of the cation, with the Xe...F/O contacts occurring opposite the axial fluorine and from beneath the equatorial XeF(4)-planes of the XeF(5)(+) and Xe(2)F(11)(+) cations so as to avoid the free valence electron lone pairs of the xenon atoms. The xenon atoms of [XeF(5)][mu-F(OsO(3)F(2))(2)] and [Xe(2)F(11)][OsO(3)F(3)] are nine-coordinate and the xenon atom of [XeF(5)][OsO(3)F(3)] is eight-coordinate. Quantum-chemical calculations at SVWN and B3LYP levels of theory were used to obtain the gas-phase geometries, vibrational frequencies, and NBO bond orders, valencies, and NPA charges of

  10. Genetic and environmental overlap between borderline personality disorder traits and psychopathy: evidence for promotive effects of factor 2 and protective effects of factor 1.

    PubMed

    Hunt, E; Bornovalova, M A; Patrick, C J

    2015-05-01

    Previous studies have reported strong genetic and environmental overlap between antisocial-externalizing (factor 2; F2) features of psychopathy and borderline personality disorder (BPD) tendencies. However, this line of research has yet to examine etiological associations of affective-interpersonal (factor 1, F1) features of psychopathy with BPD tendencies. The current study investigated differential phenotypic and genetic overlap of psychopathy factors 1 and 2 with BPD tendencies in a sample of over 250 male and female community-recruited adult twin pairs. Consistent with previous research, biometric analyses revealed strong genetic and non-shared environmental correlations of F2 with BPD tendencies, suggesting that common genetic and non-shared environmental factors contribute to both phenotypes. In contrast, negative genetic and non-shared environmental correlations were observed between F1 and BPD tendencies, indicating that the genetic factors underlying F1 serve as protective factors against BPD. No gender differences emerged in the analyses. These findings provide further insight into associations of psychopathic features - F1 as well as F2 - and BPD tendencies. Implications for treatment and intervention are discussed, along with how psychopathic traits may differentially influence the manifestation of BPD tendencies.

  11. Novel and easy access to highly luminescent Eu and Tb doped ultra-small CaF2, SrF2 and BaF2 nanoparticles - structure and luminescence.

    PubMed

    Ritter, Benjamin; Haida, Philipp; Fink, Friedrich; Krahl, Thoralf; Gawlitza, Kornelia; Rurack, Knut; Scholz, Gudrun; Kemnitz, Erhard

    2017-02-28

    A universal fast and easy access at room temperature to transparent sols of nanoscopic Eu 3+ and Tb 3+ doped CaF 2 , SrF 2 and BaF 2 particles via the fluorolytic sol-gel synthesis route is presented. Monodisperse quasi-spherical nanoparticles with sizes of 3-20 nm are obtained with up to 40% rare earth doping showing red or green luminescence. In the beginning luminescence quenching effects are only observed for the highest content, which demonstrates the unique and outstanding properties of these materials. From CaF 2 :Eu10 via SrF 2 :Eu10 to BaF 2 :Eu10 a steady increase of the luminescence intensity and lifetime occurs by a factor of ≈2; the photoluminescence quantum yield increases by 29 to 35% due to the lower phonon energy of the matrix. The fast formation process of the particles within fractions of seconds is clearly visualized by exploiting appropriate luminescence processes during the synthesis. Multiply doped particles are also available by this method. Fine tuning of the luminescence properties is achieved by variation of the Ca-to-Sr ratio. Co-doping with Ce 3+ and Tb 3+ results in a huge increase (>50 times) of the green luminescence intensity due to energy transfer Ce 3+ → Tb 3+ . In this case, the luminescence intensity is higher for CaF 2 than for SrF 2 , due to a lower spatial distance of the rare earth ions.

  12. Synergistic effects of Mo and F doping on the quality factor of ZnO thin films prepared by a fully automated home-made nebulizer spray technique

    NASA Astrophysics Data System (ADS)

    Ravichandran, K.; Dineshbabu, N.; Arun, T.; Manivasaham, A.; Sindhuja, E.

    2017-01-01

    Transparent conducting oxide films of undoped, Mo doped, Mo + F co-doped ZnO were deposited using a facile homemade nebulizer spray pyrolysis technique. The effects of Mo and F doping on the structural, optical, electrical and surface morphological properties were investigated using XRD, UV-vis-NIR spectroscopy, I-V and Hall probe techniques, FESEM and AFM, and XPS, respectively. The XRD analysis confirms that all the films are well crystallized with hexagonal wurtzite structure. All the synthesized samples exhibit high transmittance (above 85%) in the visible region. The current-voltage (I-V) characteristics show the ohmic conduction nature of the films. The Hall probe measurements show that the synergistic effects of Mo and F doping cause desirable improvements in the quality factor of the ZnO films. A minimum resistivity of 5.12 × 10-3 Ω cm with remarkably higher values of mobility and carrier concentration is achieved for Mo (2 at.%) + F (15 at.%) co-doped ZnO films. A considerable variation in the intensity of deep level emission caused by Mo and F doping is observed in the photoluminescence (PL) studies. The presence of the constituent elements in the samples is confirmed by XPS analysis.

  13. What Is Happening at Spectral Type F5 in Hyades F Stars?

    NASA Technical Reports Server (NTRS)

    Boehm-Vitense, Erika; Robinson, Richard; Carpenter, Kenneth; Mena-Werth, Jose

    2002-01-01

    Aiming at a better understanding of the mechanisms heating the chromospheres, transition regions, and coronae of cool stars, we study ultraviolet, low-resolution Hubble Space Telescope/Space Telescope Imaging Spectrograph spectra of Hyades main-sequence F stars. We study the B-V dependence(s) of the chromospheric and transition layer emission line fluxes and their dependences on rotational velocities. We find that the transition layer emission line fluxes and also those of strong chromospheric lines decrease steeply between B-V = 0.42 and 0.45, i.e., at spectral type F5, for which the rotational velocities also decrease steeply. The magnitude of the line-flux decrease increases for lines of ions with increasing degree of ionization. This shows that the line-flux decrease is not due to a change in the surface filling factor but rather due to a change of the relative importance of different heating mechanisms. For early F stars with B-V < 0.42 we find for the transition layer emission lines increasing fluxes for increasing v sin i, indicating magnetohydrodynamic heating. The v sin i dependence is strongest for the high-ionization lines. On the other hand, the low chromospheric lines show no dependence on v sin i, indicating acoustic shock heating for these layers. This also contributes to the heating of the transition layers. The Mg II and Ca II lines show decreasing fluxes for increasing v sin i, as long as v sin i is less than approx. 40 km/s. The coronal X-ray emission also decreases for increasing v sin i, except for v sin i larger than approx. 100 km/s. We have at present no explanation for this behavior. For late F stars the chromospheric lines show v sin i dependences similar to those observed for early F stars, again indicating acoustic heating for these layers. We were unable to determine the v sin i dependence of the transition layer lines because of too few single star targets. The decrease of emission line fluxes at the spectral type F5, with steeply

  14. The phase transition of Pb8F14I2.

    PubMed

    Weil, Matthias

    2017-01-01

    The reversible phase transition of Pb 8 F 14 I 2 is of continuous type and takes place at about 107 °C as monitored by temperature-dependent single crystal and powder X-ray diffraction measurements, optical microscopy, and differential scanning calorimetry. The low-temperature ferroelastic phase crystallizes in the orthorhombic crystal system (23 °C, Bmmb , Z  = 2, a  = 6.0699(6) Å, b  = 6.0165(6) Å, c  = 25.077(2) Å, 1487 structure factors, 41 parameter, R ( F 2 ) = 0.0346, wR ( F 2 ) = 0.0771) and changes its symmetry to the tetragonal crystal system into the high-temperature paraelastic phase (130 °C, I 4/ mmm , Z  = 1, a  = 4.2667(12) Å, c  = 25.388(7) Å, 430 structure factors, 303 parameter, R ( F 2 ) = 0.0575, wR ( F 2 ) = 0.1564). Group-subgroup relationships between the two structures and a hypothetical intermediate structure are presented.

  15. Pou1f1, the key transcription factor related to somatic growth in tilapia (Orechromis niloticus), is regulated by two independent post-transcriptional regulation mechanisms.

    PubMed

    Wang, Dongfang; Qin, Jingkai; Jia, Jirong; Yan, Peipei; Li, Wensheng

    2017-01-29

    This study aims to determine the post-transcriptional regulation mechanism of the transcription factor pou1f1 (pou class 1 homeobox 1), which is the key gene for pituitary development, somatic growth in vertebrates, and transcription of several hormone genes in teleost fish. MicroRNA miR-223-3p was identified as a bona fide target of pou1f; overexpression of miR-223-3p in primary pituitary cells led to the down-regulation of pou1f1 and downstream genes, and inhibition of miR-223-3p led to the up-regulation of pou1f1 in Nile tilapia dispersed primary pituitary cells. An adenylate-uridylate-rich element (AU-Rich element) was found in the 3'UTR of pou1f1 mRNA, and deletion of the AU-Rich element led to slower mRNA decay and therefore more protein output. A potential mutual relationship between miR-223-3p and the AU-rich element was also investigated, and the results demonstrated that with or without the AU-Rich element, miR-223-3p induced the up-regulation of a reporter system under serum starvation conditions, indicating that miR-223-3p and the AU-Rich element function independent of each other. This study is the first to investigate the post-transcriptional mechanism of pou1f1, which revealed that miR-223-3p down-regulated pou1f1 and downstream gene expressions, and the AU-Rich element led to rapid decay of pou1f1 mRNA. MicroRNA miR-223-3p and the AU-Rich element co-regulated the post-transcriptional expression of pou1f1 independently in Nile tilapia, demonstrating that pou1f1 is under the control of a dual post-transcription regulation mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Thermodynamic assessment of the LiF-ThF4-PuF3-UF4 system

    NASA Astrophysics Data System (ADS)

    Capelli, E.; Beneš, O.; Konings, R. J. M.

    2015-07-01

    The LiF-ThF4-PuF3-UF4 system is the reference salt mixture considered for the Molten Salt Fast Reactor (MSFR) concept started with PuF3. In order to obtain the complete thermodynamic description of this quaternary system, two binary systems (ThF4-PuF3 and UF4-PuF3) and two ternary systems (LiF-ThF4-PuF3 and LiF-UF4-PuF3) have been assessed for the first time. The similarities between CeF3/PuF3 and ThF4/UF4 compounds have been taken into account for the presented optimization as well as in the experimental measurements performed, which have confirmed the temperatures predicted by the model. Moreover, the experimental results and the thermodynamic database developed have been used to identify potential compositions for the MSFR fuel and to evaluate the influence of partial substitution of ThF4 by UF4 in the salt.

  17. Naphthalene Acetic Acid Potassium Salt (NAA-K+) Affects Conidial Germination, Sporulation, Mycelial Growth, Cell Surface Morphology, and Viability of Fusarium oxysporum f. sp. radici-lycopersici and F. oxysporum f. sp. cubense in Vitro.

    PubMed

    Manzo-Valencia, María Karina; Valdés-Santiago, Laura; Sánchez-Segura, Lino; Guzmán-de-Peña, Dora Linda

    2016-11-09

    The response to exogenous addition of naphthalene acetic acid potassium salt (NAA-K + ) to Fusarium oxysporum f. sp radici-lycopersici ATCC 60095 and F. oxysporum f. sp. cubense isolated from Michoacan Mexico soil is reported. The in vitro study showed that NAA-K + might be effective in the control of Fusarium oxysporum. Exogenous application of NAA-K + affected both spores and mycelium stages of the fungi. Viability testing using acridine orange and propidium iodide showed that NAA-K + possesses fungal killing properties, doing it effectively in the destruction of conidia of this phytopathogenic fungi. Analysis of treated spores by scanning electron microscopy showed changes in the shape factor and fractal dimension. Moreover, NAA-K + repressed the expression of brlA and fluG genes. The results disclosed here give evidence of the use of this synthetic growth factor as a substance of biocontrol that presents advantages, and the methods of application in situ should be explored.

  18. F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency. Results from a genotype-phenotype study.

    PubMed

    Quintavalle, Gabriele; Riccardi, Federica; Rivolta, Gianna Franca; Martorana, Davide; Di Perna, Caterina; Percesepe, Antonio; Tagliaferri, Annarita

    2017-08-01

    Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:C<50 %. One hundred twenty-three probands were genotyped for F7 mutations and three polymorphic variants and classified according to recently published clinical scores. Forty out of 123 patients (33 %) were symptomatic (43 bleedings). A severe bleeding tendency was observed only in patients with FVII:C<0.10 %. Epistaxis (11 %) and menorrhagia (32 % of females in fertile age) were the most frequent bleedings. Molecular analysis detected 48 mutations, 20 not reported in the F7 international databases. Most mutations (62 %) were missense, large deletions were 6.2 %. Compound heterozygotes/homozygotes for mutations presented lower FVII:C levels compared to the other classes (Chi 2 =43.709, p<0,001). The polymorphisms distribution was significantly different among the three F7 genotypic groups (Chi 2 =72.289, p<0,001). The presence of truncating mutations was associated with lowest FVII:C levels (Chi 2 =21.351, p=0.002). This study confirms the clinical and molecular variability of the disease and the type of symptoms. It shows a good correlation between the type of F7 mutation and/or polymorphisms and FVII:C levels, without a direct link between FVII:C and bleeding tendency. The results suggest that large deletions are underestimated and that they represent a common mechanism of F7 gene inactivation which should always be investigated in the diagnostic testing for FVII deficiency.

  19. Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization.

    PubMed

    Qi, Qian-Rong; Zhao, Xu-Yu; Zuo, Ru-Juan; Wang, Tong-Song; Gu, Xiao-Wei; Liu, Ji-Long; Yang, Zeng-Ming

    2015-01-01

    Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polyploidization of decidual cells. E2F8-mediated polyploidization is a response to stresses which are accompanied by decidualization. Interestingly, polyploidization is not detected during human decidualization with the down-regulation of E2F8, indicating differential expression of E2F8 may lead to the difference of decidual cell polyploidization between mice and humans.

  20. Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization

    PubMed Central

    Qi, Qian-Rong; Zhao, Xu-Yu; Zuo, Ru-Juan; Wang, Tong-Song; Gu, Xiao-Wei; Liu, Ji-Long; Yang, Zeng-Ming

    2015-01-01

    Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polyploidization of decidual cells. E2F8-mediated polyploidization is a response to stresses which are accompanied by decidualization. Interestingly, polyploidization is not detected during human decidualization with the down-regulation of E2F8, indicating differential expression of E2F8 may lead to the difference of decidual cell polyploidization between mice and humans. PMID:25892397

  1. PCDD/F and Aromatic Emissions from Simulated Forest and Grassland Fires

    EPA Science Inventory

    Emissions of polychlorinated dibenzodioxin and polychlorinated dibenzofuran (PCDD/F) from simulated grassland and forest fires were quantitatively sampled to derive emission factors in support of PCDD/F inventory development. Grasses from Kentucky and Minnesota; forest shrubs fro...

  2. The Osmium(VIII) Oxofluoro Cations OsO(2)F(3)(+) and F(cis-OsO(2)F(3))(2)(+): Syntheses, Characterization by (19)F NMR Spectroscopy and Raman Spectroscopy, X-ray Crystal Structure of F(cis-OsO(2)F(3))(2)(+)Sb(2)F(11)(-), and Density Functional Theory Calculations of OsO(2)F(3)(+), ReO(2)F(3), and F(cis-OsO(2)F(3))(2)(+).

    PubMed

    Casteel, William J.; Dixon, David A.; Mercier, Hélène P. A.; Schrobilgen, Gary J.

    1996-07-17

    Osmium dioxide tetrafluoride, cis-OsO(2)F(4), reacts with the strong fluoride ion acceptors AsF(5) and SbF(5) in anhydrous HF and SbF(5) solutions to form orange salts. Raman spectra are consistent with the formation of the fluorine-bridged diosmium cation F(cis-OsO(2)F(3))(2)(+), as the AsF(6)(-) and Sb(2)F(11)(-) salts, respectively. The (19)F NMR spectra of the salts in HF solution are exchange-averaged singlets occurring at higher frequency than those of the fluorine environments of cis-OsO(2)F(4). The F(cis-OsO(2)F(3))(2)(+)Sb(2)F(11)(-) salt crystallizes in the orthorhombic space group Imma. At -107 degrees C, a = 12.838(3) Å, b = 10.667(2) Å, c = 11.323(2) Å, V = 1550.7(8) Å(3), and Z = 4. Refinement converged with R = 0.0469 [R(w) = 0.0500]. The crystal structure consists of discrete fluorine-bridged F(cis-OsO(2)F(3))(2)(+) and Sb(2)F(11)(-) ions in which the fluorine bridge of the F(cis-OsO(2)F(3))(2)(+) cation is trans to an oxygen atom (Os-O 1.676 Å) of each OsO(2)F(3) group. The angle at the bridge is 155.2(8) degrees with a bridging Os---F(b) distance of 2.086(3) Å. Two terminal fluorine atoms (Os-F 1.821 Å) are cis to the two oxygen atoms (Os-O 1.750 Å), and two terminal fluorine atoms of the OsO(2)F(3) group are trans to one another (1.813 Å). The OsO(2)F(3)(+) cation was characterized by (19)F NMR and by Raman spectroscopy in neat SbF(5) solution but was not isolable in the solid state. The NMR and Raman spectroscopic findings are consistent with a trigonal bipyramidal cation in which the oxygen atoms and a fluorine atom occupy the equatorial plane and two fluorine atoms are in axial positions. Density functional theory calculations show that the crystallographic structure of F(cis-OsO(2)F(3))(2)(+) is the energy-minimized structure and the energy-minimized structures of the OsO(2)F(3)(+) cation and ReO(2)F(3) are trigonal bipyramidal having C(2)(v)() point symmetry. Attempts to prepare the OsOF(5)(+) cation by oxidative fluorination of cis

  3. Ab initio study of the diatomic fluorides FeF, CoF, NiF, and CuF.

    PubMed

    Koukounas, Constantine; Mavridis, Aristides

    2008-11-06

    The late-3d transition-metal diatomic fluorides MF = FeF, CoF, NiF, and CuF have been studied using variational multireference (MRCI) and coupled-cluster [RCCSD(T)] methods, combined with large to very large basis sets. We examined a total of 35 (2S+1)|Lambda| states, constructing as well 29 full potential energy curves through the MRCI method. All examined states are ionic, diabatically correlating to M(+)+F(-)((1)S). Notwithstanding the "eccentric" character of the 3d transition metals and the difficulties to accurately be described with all-electron ab initio methods, our results are, in general, in very good agreement with available experimental numbers.

  4. Resistivity Correction Factor for the Four-Probe Method: Experiment III

    NASA Astrophysics Data System (ADS)

    Yamashita, Masato; Nishii, Toshifumi; Kurihara, Hiroshi; Enjoji, Hideo; Iwata, Atsushi

    1990-04-01

    Experimental verification of the theoretically derived resistivity correction factor F is presented. Factor F is applied to a system consisting of a rectangular parallelepiped sample and a square four-probe array. Resistivity and sheet resistance measurements are made on isotropic graphites and crystalline ITO films. Factor F corrects experimental data and leads to reasonable resistivity and sheet resistance.

  5. MO-F-CAMPUS-I-02: Accuracy in Converting the Average Breast Dose Into the Mean Glandular Dose (MGD) Using the F-Factor in Cone Beam Breast CT- a Monte Carlo Study Using Homogeneous and Quasi-Homogeneous Phantoms

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

    Lai, C; Zhong, Y; Wang, T

    2015-06-15

    Purpose: To investigate the accuracy in estimating the mean glandular dose (MGD) for homogeneous breast phantoms by converting from the average breast dose using the F-factor in cone beam breast CT. Methods: EGSnrc-based Monte Carlo codes were used to estimate the MGDs. 13-cm in diameter, 10-cm high hemi-ellipsoids were used to simulate pendant-geometry breasts. Two different types of hemi-ellipsoidal models were employed: voxels in quasi-homogeneous phantoms were designed as either adipose or glandular tissue while voxels in homogeneous phantoms were designed as the mixture of adipose and glandular tissues. Breast compositions of 25% and 50% volume glandular fractions (VGFs), definedmore » as the ratio of glandular tissue voxels to entire breast voxels in the quasi-homogeneous phantoms, were studied. These VGFs were converted into glandular fractions by weight and used to construct the corresponding homogeneous phantoms. 80 kVp x-rays with a mean energy of 47 keV was used in the simulation. A total of 109 photons were used to image the phantoms and the energies deposited in the phantom voxels were tallied. Breast doses in homogeneous phantoms were averaged over all voxels and then used to calculate the MGDs using the F-factors evaluated at the mean energy of the x-rays. The MGDs for quasi-homogeneous phantoms were computed directly by averaging the doses over all glandular tissue voxels. The MGDs estimated for the two types of phantoms were normalized to the free-in-air dose at the iso-center and compared. Results: The normalized MGDs were 0.756 and 0.732 mGy/mGy for the 25% and 50% VGF homogeneous breasts and 0.761 and 0.733 mGy/mGy for the corresponding quasi-homogeneous breasts, respectively. The MGDs estimated for the two types of phantoms were similar within 1% in this study. Conclusion: MGDs for homogeneous breast models may be adequately estimated by converting from the average breast dose using the F-factor.« less

  6. Generalized ghost pilgrim dark energy in F(T,TG) cosmology

    NASA Astrophysics Data System (ADS)

    Sharif, M.; Nazir, Kanwal

    2016-07-01

    This paper is devoted to study the generalized ghost pilgrim dark energy (PDE) model in F(T,TG) gravity with flat Friedmann-Robertson-Walker (FRW) universe. In this scenario, we reconstruct F(T,TG) models and evaluate the corresponding equation of state (EoS) parameter for different choices of the scale factors. We assume power-law scale factor, scale factor for unification of two phases, intermediate and bouncing scale factor. We study the behavior of reconstructed models and EoS parameters graphically. It is found that all the reconstructed models show decreasing behavior for PDE parameter u = -2. On the other hand, the EoS parameter indicates transition from dust-like matter to phantom era for all choices of the scale factor except intermediate for which this is less than - 1. We conclude that all the results are in agreement with PDE phenomenon.

  7. PCDD/F EMISSIONS FROM FOREST FIRES

    EPA Science Inventory

    Polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (PCDD/F) emissions from combustion of forest biomass were sampled to obtain an estimated emission factor for forest fires. An equal composition of live shoot and litter biomass from Oregon and North Carolina was bu...

  8. f(Lovelock) theories of gravity

    NASA Astrophysics Data System (ADS)

    Bueno, Pablo; Cano, Pablo A.; Óscar Lasso, A.; Ramírez, Pedro F.

    2016-04-01

    f(Lovelock) gravities are simple generalizations of the usual f( R) and Lovelock theories in which the gravitational action depends on some arbitrary function of the corresponding dimensionally-extended Euler densities. In this paper we study several aspects of these theories in general dimensions. We start by identifying the generalized boundary term which makes the gravitational variational problem well-posed. Then, we show that these theories are equivalent to certain scalar-tensor theories and how this relation is characterized by the Hessian of f. We also study the linearized equations of the theory on general maximally symmetric backgrounds. Remarkably, we find that these theories do not propagate the usual ghost-like massive gravitons characteristic of higher-derivative gravities on such backgrounds. In some non-trivial cases, the additional scalar associated to the trace of the metric perturbation is also absent, being the usual graviton the only dynamical field. In those cases, the linearized equations are exactly the same as in Einstein gravity up to an overall factor, making them appealing as holographic toy models. We also find constraints on the couplings of a broad family of five-dimensional f(Lovelock) theories using holographic entanglement entropy. Finally, we construct new analytic asymptotically flat and AdS/dS black hole solutions for some classes of f(Lovelock) gravities in various dimensions.

  9. E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution.

    PubMed

    Iglesias-Ara, A; Zenarruzabeitia, O; Buelta, L; Merino, J; Zubiaga, A M

    2015-10-01

    Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53(-/-) mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy.

  10. Potential Novel Antibiotics from HTS Targeting the Virulence-regulating Transcription Factor, VirF, from Shigella flexneri

    PubMed Central

    Emanuele, Anthony A.; Adams, Nancy E.; Chen, Yi-Chen; Maurelli, Anthony T.; Garcia, George A.

    2014-01-01

    VirF is an AraC-type transcriptional regulator responsible for activating the transcription of virulence genes required for the intracellular invasion and cell-to-cell spread of Shigella flexneri. Gene disruption studies have validated VirF as a potential target for an anti-virulence therapy to treat shigellosis by determining that VirF is necessary for virulence, but not required for bacterial viability. Using a bacteria-based, β-galactosidase reporter assay we completed a high-throughput screening (HTS) campaign monitoring VirF activity in the presence of over 140,000 small molecules. From our screening campaign we identified five lead compounds to pursue in tissue-culture-based invasion and cell-to-cell spread assays and toxicity screens. Our observations of activity in these models for infection have validated our approach of targeting virulence regulation and have allowed us to identify a promising chemical scaffold from our HTS for hit-to-lead development. Interestingly, differential effects on invasion versus cell-to-cell spread suggest that the compounds’ efficacies may depend, in part, on the specific promoter that VirF is recognizing. PMID:24549153

  11. Precision controllability of the F-15 airplane

    NASA Technical Reports Server (NTRS)

    Sisk, T. R.; Matheny, N. W.

    1979-01-01

    A flying qualities evaluation conducted on a preproduction F-15 airplane permitted an assessment to be made of its precision controllability in the high subsonic and low transonic flight regime over the allowable angle of attack range. Precision controllability, or gunsight tracking, studies were conducted in windup turn maneuvers with the gunsight in the caged pipper mode and depressed 70 mils. This evaluation showed the F-15 airplane to experience severe buffet and mild-to-moderate wing rock at the higher angles of attack. It showed the F-15 airplane radial tracking precision to vary from approximately 6 to 20 mils over the load factor range tested. Tracking in the presence of wing rock essentially doubled the radial tracking error generated at the lower angles of attack. The stability augmentation system affected the tracking precision of the F-15 airplane more than it did that of previous aircraft studied.

  12. Regulating the ethylene response of a plant by modulation of F-box proteins

    DOEpatents

    Guo, Hongwei [Beijing, CN; Ecker, Joseph R [Carlsbad, CA

    2014-01-07

    The relationship between F-box proteins and proteins invovled in the ethylene response in plants is described. In particular, F-box proteins may bind to proteins involved in the ethylene response and target them for degradation by the ubiquitin/proteasome pathway. The transcription factor EIN3 is a key transcription factor mediating ethylne-regulated gene expression and morphological responses. EIN3 is degraded through a ubiquitin/proteasome pathway mediated by F-box proteins EBF1 and EBF2. The link between F-box proteins and the ethylene response is a key step in modulating or regulating the response of a plant to ethylene. Described herein are transgenic plants having an altered sensitivity to ethylene, and methods for making transgenic plant haing an althered sensitivity to ethylene by modulating the level of activity of F-box proteins. Methods of altering the ethylene response in a plant by modulating the activity or expression of an F-box protein are described. Also described are methods of identifying compounds that modulate the ethylene response in plants by modulating the level of F-box protein expression or activity.

  13. Virulence factors associated with cytotoxic necrotizing factor type two in bovine diarrheic and septicemic strains of Escherichia coli.

    PubMed Central

    Oswald, E; de Rycke, J; Lintermans, P; van Muylem, K; Mainil, J; Daube, G; Pohl, P

    1991-01-01

    Forty-three bovine isolates of Escherichia coli producing a second type of cytotoxic necrotizing factor (CNF2) and three K-12 strains carrying different Vir plasmids coding for CNF2 were tested for the presence of several virulence factors. Most of the strains were serum resistant (79%), produced an aerobactin (70%), and adhered to calf villi (53%); some of them produced a colicin (32%) and a hemolysin (9%). These strains were also tested by a colony hybridization assay with gene probes for six toxins (classical heat-stable [STaP and STb] and heat-labile [LT-I and LT-IIa] enterotoxins and Shiga-like toxins [SLT-I and SLT-II]) and five adhesion factors (K99, K88, 987P, F17, and F41). Only two gene probes, LT-IIa (9%) and F17A (53%), hybridized with the CNF2 strains. However, antibodies raised against F17 fimbriae did not agglutinate the strains hybridizing with the F17A probe. In contrast, all except one of these strains adhered to calf villi. Interestingly, these two properties, F17A positivity and adherence to calf villi, were the only ones expressed by the K-12 strains carrying different Vir plasmids. In conclusion, this study confirmed that CNF2-producing strains are unrelated to previously described toxigenic E. coli strains and also demonstrated that in half of the strains the production of CNF2 was associated with an adhesion factor genetically related to, but different from, F17, which is more than likely encoded by Vir plasmids. PMID:1774259

  14. 1/f noise application in reflexotherapy

    NASA Astrophysics Data System (ADS)

    Ostrova, S. O.; Bulgakov, A. E.; Klyushkin, I. V.; Abdullina, A. M.

    1993-08-01

    The instruments and methods which make it possible to apply 1/f noise in reflexotherapy by action of physical factors on biologically active points are dealt with. The efficiency of their application was shown on the example of treatment of gastric and duodenal ulcers without medicaments.

  15. Reactive Oxygen Species-Inducible ECF σ Factors of Bradyrhizobium japonicum

    PubMed Central

    Masloboeva, Nadezda; Reutimann, Luzia; Stiefel, Philipp; Follador, Rainer; Leimer, Nadja; Hennecke, Hauke; Mesa, Socorro; Fischer, Hans-Martin

    2012-01-01

    Extracytoplasmic function (ECF) σ factors control the transcription of genes involved in different cellular functions, such as stress responses, metal homeostasis, virulence-related traits, and cell envelope structure. The genome of Bradyrhizobium japonicum, the nitrogen-fixing soybean endosymbiont, encodes 17 putative ECF σ factors belonging to nine different ECF σ factor families. The genes for two of them, ecfQ (bll1028) and ecfF (blr3038), are highly induced in response to the reactive oxygen species hydrogen peroxide (H2O2) and singlet oxygen (1O2). The ecfF gene is followed by the predicted anti-σ factor gene osrA (blr3039). Mutants lacking EcfQ, EcfF plus OsrA, OsrA alone, or both σ factors plus OsrA were phenotypically characterized. While the symbiotic properties of all mutants were indistinguishable from the wild type, they showed increased sensitivity to singlet oxygen under free-living conditions. Possible target genes of EcfQ and EcfF were determined by microarray analyses, and candidate genes were compared with the H2O2-responsive regulon. These experiments disclosed that the two σ factors control rather small and, for the most part, distinct sets of genes, with about half of the genes representing 13% of the members of H2O2-responsive regulon. To get more insight into transcriptional regulation of both σ factors, the 5′ ends of ecfQ and ecfF mRNA were determined. The presence of conserved sequence motifs in the promoter region of ecfQ and genes encoding EcfQ-like σ factors in related α-proteobacteria suggests regulation via a yet unknown transcription factor. By contrast, we have evidence that ecfF is autoregulated by transcription from an EcfF-dependent consensus promoter, and its product is negatively regulated via protein-protein interaction with OsrA. Conserved cysteine residues 129 and 179 of OsrA are required for normal function of OsrA. Cysteine 179 is essential for release of EcfF from an EcfF-OsrA complex upon H2O2 stress while

  16. Detection of osseous metastasis by 18F-NaF/18F-FDG PET/CT versus CT alone.

    PubMed

    Sampath, Srinath C; Sampath, Srihari C; Mosci, Camila; Lutz, Amelie M; Willmann, Juergen K; Mittra, Erik S; Gambhir, Sanjiv S; Iagaru, Andrei

    2015-03-01

    Sodium fluoride PET (18F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered 18F-NaF and 18F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer 18F-NaF18/F-FDG PET/CT with CT alone for detection of osseous metastasis. Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined 18F-NaF/18F-FDG PET/CT and diagnostic CT scans. PET/CT as well as CT only images were reviewed in blinded fashion and compared with the results of clinical, imaging, or histological follow-up as a truth standard. Sensitivity of the combined 18F-NaF/18F-FDG PET/CT was higher than that of CT alone (97.4% vs 66.7%). CT and 18F-NaF/18F-FDG PET/CT were concordant in 73% of studies. Of 20 discordant cases, 18F-NaF/18F-FDG PET/CT was correct in 19 (95%). Three cases were interpreted concordantly but incorrectly, and all 3 were false positives. A single case of osseous metastasis was detected by CT alone, but not by 18F-NaF/18F-FDG PET/CT. Combined 18F-NaF/18F-FDG PET/CT outperforms CT alone and is highly sensitive and specific for detection of osseous metastases. The concordantly interpreted false-positive cases demonstrate the difficulty of distinguishing degenerative from malignant disease, whereas the single case of metastasis seen on CT but not PET highlights the need for careful review of CT images in multimodality studies.

  17. Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis.

    PubMed

    Martin-Fernandez, Laura; Gavidia-Bovadilla, Giovana; Corrales, Irene; Brunel, Helena; Ramírez, Lorena; López, Sonia; Souto, Juan Carlos; Vidal, Francisco; Soria, José Manuel

    2017-01-01

    Venous thromboembolism is a complex disease with a high heritability. There are significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that might account for the variability of FXI levels. The KNG1 and F11 loci were sequenced completely in 110 unrelated individuals from the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project using Next Generation Sequencing on an Illumina MiSeq. The GAIT-2 Project is a study of 935 individuals in 35 extended Spanish families selected through a proband with idiopathic thrombophilia. Among the 110 individuals, a subset of 40 individuals was chosen as a discovery sample for identifying variants. A total of 762 genetic variants were detected. Several significant associations were established among common variants and low-frequency variants sets in KNG1 and F11 with FXI levels using the PLINK and SKAT packages. Among these associations, those of rs710446 and five low-frequency variant sets in KNG1 with FXI level variation were significant after multiple testing correction and permutation. Also, two putative pathogenic mutations related to high and low FXI levels were identified by data filtering and in silico predictions. This study of KNG1 and F11 loci should help to understand the connection between genotypic variation and variation in FXI levels. The functional genetic variants should be useful as markers of thromboembolic risk.

  18. Th17 master transcription factors RORα and RORγ regulate the expression of IL-17C, IL-17D and IL-17F in Cynoglossus semilaevis.

    PubMed

    Chi, Heng; Bøgwald, Jarl; Dalmo, Roy Ambli; Zhang, Wenjie; Hu, Yong-hua

    2016-02-01

    The RAR-related orphan receptors (RORs) are members of the nuclear receptor family of intracellular transcription factors. In this study, we examined the regulatory properties of RORα (CsRORα) and RORγ (CsRORγ) in tongue sole (Cynoglossus semilaevis). CsRORα and CsRORγ expression was detected in major lymphoid organs and altered to significant extents after bacterial and viral infection. CsRORα enhanced the activities of CsIL-17C, CsIL-17D, and CsIL-17F promoters, which contain CsRORα and CsRORγ binding sites. CsRORγ also upregulated the promoter activities of CsIL-17D and CsIL-17F but not CsIL-17C. CsRORα and CsRORγ proteins were detected in the nucleus, and overexpression of CsRORα in tongue sole significantly increased the expression of CsIL-17C, CsIL-17D, and CsIL-17F, whereas overexpression of CsRORγ significantly increased the expression of CsIL-17C and CsIL-17F but no CsIL-17D. These results indicate that RORα and RORγ in teleost regulate the expression of IL-17 members in different manners. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Unresolved issues in the analysis of F2-isoprostanes, F4-neuroprostanes, isofurans, neurofurans, and F2-dihomo-isoprostanes in body fluids and tissue using gas chromatography/negative-ion chemical-ionization mass spectrometry.

    PubMed

    Yen, H-C; Wei, H-J; Lin, C-L

    2015-01-01

    F2-isoprostanes (F2-IsoPs) generated from arachidonic acid (AA) have been recognized as the most reliable marker of nonenzymatic lipid peroxidation in vivo. F2-IsoPs are initially produced in esterified form on phospholipids, and then released into body fluids in free form. The same mechanism can lead to generation of F4-neuroprostanes (F4-NPs) and F2-dihomo-IsoPs from docosahexaenoic acid (DHA) and adrenic acid, respectively. In addition, isofurans (IsoFs) and neurofurans (NFs) may be preferentially produced from AA and DHA, respectively, under high oxygen tension. The detection of F2-IsoPs using gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) has been widely employed, which is important for human body fluids containing low quantity of free-form F2-IsoPs. F4-NPs have also been detected using GC/NICI-MS, but multiple peaks need to be quantified. In this paper, we summarize the basic workflow of the GC/NICI-MS method for analyzing F2-IsoPs and F4-NPs, and various formats of assays conducted by different groups. We then discuss the feasibility of simultaneous analysis of IsoFs, NFs, and F2-dihomo-IsoPs with F2-IsoPs or F4-NPs. Representative GC chromatograms for analyzing these markers in human body fluids and rat brain tissue are demonstrated. Furthermore, we discuss several factors that may affect the performance of the analysis, such as those related to the sample processing steps, interference from specimens, types of GC liners used, and the addition of electron multiplier voltage in the method setting for the MS detector. Finally, we question the appropriateness of measuring total (free plus esterified) levels of these markers in body fluids.

  20. Dual-TRACER: High resolution fMRI with constrained evolution reconstruction.

    PubMed

    Li, Xuesong; Ma, Xiaodong; Li, Lyu; Zhang, Zhe; Zhang, Xue; Tong, Yan; Wang, Lihong; Sen Song; Guo, Hua

    2018-01-01

    fMRI with high spatial resolution is beneficial for studies in psychology and neuroscience, but is limited by various factors such as prolonged imaging time, low signal to noise ratio and scarcity of advanced facilities. Compressed Sensing (CS) based methods for accelerating fMRI data acquisition are promising. Other advanced algorithms like k-t FOCUSS or PICCS have been developed to improve performance. This study aims to investigate a new method, Dual-TRACER, based on Temporal Resolution Acceleration with Constrained Evolution Reconstruction (TRACER), for accelerating fMRI acquisitions using golden angle variable density spiral. Both numerical simulations and in vivo experiments at 3T were conducted to evaluate and characterize this method. Results show that Dual-TRACER can provide functional images with a high spatial resolution (1×1mm 2 ) under an acceleration factor of 20 while maintaining hemodynamic signals well. Compared with other investigated methods, dual-TRACER provides a better signal recovery, higher fMRI sensitivity and more reliable activation detection. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Essential but partially redundant roles for POU4F1/Brn-3a and POU4F2/Brn-3b transcription factors in the developing heart

    PubMed Central

    Maskell, Lauren J; Qamar, Kashif; Babakr, Aram A; Hawkins, Thomas A; Heads, Richard J; Budhram-Mahadeo, Vishwanie S

    2017-01-01

    Congenital heart defects contribute to embryonic or neonatal lethality but due to the complexity of cardiac development, the molecular changes associated with such defects are not fully understood. Here, we report that transcription factors (TFs) Brn-3a (POU4F1) and Brn-3b (POU4F2) are important for normal cardiac development. Brn-3a directly represses Brn-3b promoter in cardiomyocytes and consequently Brn-3a knockout (KO) mutant hearts express increased Brn-3b mRNA during mid-gestation, which is linked to hyperplastic growth associated with elevated cyclin D1, a known Brn-3b target gene. However, during late gestation, Brn-3b can cooperate with p53 to enhance transcription of pro-apoptotic genes e.g. Bax, thereby increasing apoptosis and contribute to morphological defects such as non-compaction, ventricular wall/septal thinning and increased crypts/fissures, which may cause lethality of Brn-3a KO mutants soon after birth. Despite this, early embryonic lethality in e9.5 double KO (Brn-3a−/− : Brn-3b−/−) mutants indicate essential functions with partial redundancy during early embryogenesis. High conservation between mammals and zebrafish (ZF) Brn-3b (87%) or Brn-3a (76%) facilitated use of ZF embryos to study potential roles in developing heart. Double morphant embryos targeted with morpholino oligonucleotides to both TFs develop significant cardiac defects (looping abnormalities and valve defects) suggesting essential roles for Brn-3a and Brn-3b in developing hearts. PMID:28594399

  2. The influence of prophylactic factor VIII in severe hemophilia A

    PubMed Central

    Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E

    2013-01-01

    Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from <1% to 22%. Thrombin generation (maximum level and rate) in both empirical and computational systems increased as the level of fVIII increased. FXIII activation rates also increased as the fVIII level increased. Upon suppression of fVIII, thrombin generation became comparable in both systems. Plasma composition analysis showed a negative correlation between bleeding history and computational thrombin generation in the absence of fVIII. Conclusion Residual prophylactic fVIII directly causes an increase in thrombin generation and fibrin cross-linking in individuals with clinically severe hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

  3. Compressed Sensing for fMRI: Feasibility Study on the Acceleration of Non-EPI fMRI at 9.4T

    PubMed Central

    Kim, Seong-Gi; Ye, Jong Chul

    2015-01-01

    Conventional functional magnetic resonance imaging (fMRI) technique known as gradient-recalled echo (GRE) echo-planar imaging (EPI) is sensitive to image distortion and degradation caused by local magnetic field inhomogeneity at high magnetic fields. Non-EPI sequences such as spoiled gradient echo and balanced steady-state free precession (bSSFP) have been proposed as an alternative high-resolution fMRI technique; however, the temporal resolution of these sequences is lower than the typically used GRE-EPI fMRI. One potential approach to improve the temporal resolution is to use compressed sensing (CS). In this study, we tested the feasibility of k-t FOCUSS—one of the high performance CS algorithms for dynamic MRI—for non-EPI fMRI at 9.4T using the model of rat somatosensory stimulation. To optimize the performance of CS reconstruction, different sampling patterns and k-t FOCUSS variations were investigated. Experimental results show that an optimized k-t FOCUSS algorithm with acceleration by a factor of 4 works well for non-EPI fMRI at high field under various statistical criteria, which confirms that a combination of CS and a non-EPI sequence may be a good solution for high-resolution fMRI at high fields. PMID:26413503

  4. E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution

    PubMed Central

    Iglesias-Ara, A; Zenarruzabeitia, O; Buelta, L; Merino, J; Zubiaga, A M

    2015-01-01

    Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53−/− mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy. PMID:25656653

  5. Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion

    PubMed Central

    Rennoll-Bankert, Kristen E.; Rahman, M. Sayeedur; Gillespie, Joseph J.; Guillotte, Mark L.; Kaur, Simran J.; Lehman, Stephanie S.; Beier-Sexton, Magda; Azad, Abdu F.

    2015-01-01

    Bacterial Sec7-domain-containing proteins (RalF) are known only from species of Legionella and Rickettsia, which have facultative and obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS) effector, is a guanine nucleotide exchange factor (GEF) of ADP-ribosylation factors (Arfs), activating and recruiting host Arf1 to the Legionella-containing vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus Group) RalF is a functional Arf-GEF that localizes to the host plasma membrane and interacts with the actin cytoskeleton via a unique C-terminal domain. As RalF is differentially encoded across Rickettsia species (e.g., pseudogenized in all Spotted Fever Group species), it may function in lineage-specific biology and pathogenicity. Herein, we demonstrate RalF of R. typhi (Typhus Group) interacts with the Rickettsia T4SS coupling protein (RvhD4) via its proximal C-terminal sequence. RalF is expressed early during infection, with its inactivation via antibody blocking significantly reducing R. typhi host cell invasion. For R. typhi and R. felis (Transitional Group), RalF ectopic expression revealed subcellular localization with the host plasma membrane and actin cytoskeleton. Remarkably, R. bellii (Ancestral Group) RalF showed perinuclear localization reminiscent of ectopically expressed Legionella RalF, for which it shares several structural features. For R. typhi, RalF co-localization with Arf6 and PI(4,5)P2 at entry foci on the host plasma membrane was determined to be critical for invasion. Thus, we propose recruitment of PI(4,5)P2 at entry foci, mediated by RalF activation of Arf6, initiates actin remodeling and ultimately facilitates bacterial invasion. Collectively, our characterization of RalF as an invasin suggests that, despite carrying a similar Arf-GEF unknown from other bacteria, different intracellular lifestyles across Rickettsia and Legionella species have driven divergent roles for RalF

  6. Synaptic Vesicle Mobility and Presynaptic F-Actin Are Disrupted in a N-ethylmaleimide–sensitive Factor Allele of Drosophila

    PubMed Central

    Nunes, Paula; Haines, Nicola; Kuppuswamy, Venkat; Fleet, David J.

    2006-01-01

    N-ethylmaleimide sensitive factor (NSF) can dissociate the soluble NSF attachment receptor (SNARE) complex, but NSF also participates in other intracellular trafficking functions by virtue of SNARE-independent activity. Drosophila that express a neural transgene encoding a dominant-negative form of NSF2 show an 80% reduction in the size of releasable synaptic vesicle pool, but no change in the number of vesicles in nerve terminal boutons. Here we tested the hypothesis that vesicles in the NSF2 mutant terminal are less mobile. Using a combination of genetics, pharmacology, and imaging we find a substantial reduction in vesicle mobility within the nerve terminal boutons of Drosophila NSF2 mutant larvae. Subsequent analysis revealed a decrease of filamentous actin in both NSF2 dominant-negative and loss-of-function mutants. Lastly, actin-filament disrupting drugs also decrease vesicle movement. We conclude that a factor contributing to the NSF mutant phenotype is a reduction in vesicle mobility, which is associated with decreased presynaptic F-actin. Our data are consistent with a model in which actin filaments promote vesicle mobility and suggest that NSF participates in establishing or maintaining this population of actin. PMID:16914524

  7. Singlet vs Nonsinglet Perturbative Renormalization factors of Staggered Fermion Bilinears

    NASA Astrophysics Data System (ADS)

    Panagopoulos, Haralambos; Spanoudes, Gregoris

    2018-03-01

    In this paper we present the perturbative computation of the difference between the renormalization factors of flavor singlet (Σfψ¯fΓψf', f : flavor index) and nonsinglet (ψ¯f1Γψf2,f1 ≠ f2) bilinear quark operators (where Γ = 𝟙, γ5, γ µ, γ5 γ µ, γ5 σµv on the lattice. The computation is performed to two loops and to lowest order in the lattice spacing, using Symanzik improved gluons and staggered fermions with twice stout-smeared links. The stout smearing procedure is also applied to the definition of bilinear operators. A significant part of this work is the development of a method for treating some new peculiar divergent integrals stemming from the staggered formalism. Our results can be combined with precise simulation results for the renormalization factors of the nonsinglet operators, in order to obtain an estimate of the renormalization factors for the singlet operators. The results have been published in Physical Review D [1].

  8. Targeting tissue factor-expressing tumor angiogenesis and tumors with EF24 conjugated to factor VIIa.

    PubMed

    Shoji, Mamoru; Sun, Aiming; Kisiel, Walter; Lu, Yang J; Shim, Hyunsuk; McCarey, Bernard E; Nichols, Christopher; Parker, Ernest T; Pohl, Jan; Mosley, Cara A; Alizadeh, Aaron R; Liotta, Dennis C; Snyder, James P

    2008-04-01

    Tissue factor (TF) is aberrantly expressed on tumor vascular endothelial cells (VECs) and on cancer cells in many malignant tumors, but not on normal VECs, making it a promising target for cancer therapy. As a transmembrane receptor for coagulation factor VIIa (fVIIa), TF forms a high-affinity complex with its cognate ligand, which is subsequently internalized through receptor-mediated endocytosis. Accordingly, we developed a method for selectively delivering EF24, a potent synthetic curcumin analog, to TF-expressing tumor vasculature and tumors using fVIIa as a drug carrier. EF24 was chemically conjugated to fVIIa through a tripeptide-chloromethyl ketone. After binding to TF-expressing targets by fVIIa, EF24 will be endocytosed along with the drug carrier and will exert its cytotoxicity. Our results showed that the conjugate inhibits vascular endothelial growth factor-induced angiogenesis in a rabbit cornea model and in a Matrigel model in athymic nude mice. The conjugate-induced apoptosis in tumor cells and significantly reduced tumor size in human breast cancer xenografts in athymic nude mice as compared with the unconjugated EF24. By conjugating potent drugs to fVIIa, this targeted drug delivery system has the potential to enhance therapeutic efficacy, while reducing toxic side effects. It may also prove to be useful for treating drug-resistant tumors and micro-metastases in addition to primary tumors.

  9. RpfF-dependent regulon of Xylella fastidiosa.

    PubMed

    Wang, Nian; Li, Jian-Liang; Lindow, Steven E

    2012-11-01

    ABSTRACT Xylella fastidiosa regulates traits important to both virulence of grape as well as colonization of sharpshooter vectors via its production of a fatty acid signal molecule known as DSF whose production is dependent on rpfF. Although X. fastidiosa rpfF mutants exhibit increased virulence to plants, they are unable to be spread from plant to plant by insect vectors. To gain more insight into the traits that contribute to these processes, a whole-genome Agilent DNA microarray for this species was developed and used to determine the RpfF-dependent regulon by transcriptional profiling. In total, 446 protein coding genes whose expression was significantly different between the wild type and an rpfF mutant (false discovery rate < 0.05) were identified when cells were grown in PW liquid medium. Among them, 165 genes were downregulated in the rpfF mutant compared with the wild-type strain whereas 281 genes were over-expressed. RpfF function was required for regulation of 11 regulatory and σ factors, including rpfE, yybA, PD1177, glnB, rpfG, PD0954, PD0199, PD2050, colR, rpoH, and rpoD. In general, RpfF is required for regulation of genes involved in attachment and biofilm formation, enhancing expression of hemagglutinin genes hxfA and hxfB, and suppressing most type IV pili and gum genes. A large number of other RpfF-dependent genes that might contribute to virulence or insect colonization were also identified such as those encoding hemolysin and colicin V, as well as genes with unknown functions.

  10. PCDD/F EMISSIONS FROM FOREST FIRE SIMULATIONS

    EPA Science Inventory

    Polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (PCDD/F) emissions from combustion of forest biomass were sampled to obtain an estimated emission factor for forest fires. An equal composition of live shoot and litter biomass from Oregon and North Carolina was b...

  11. Detection of Hearing Loss Using 2f2-f1 and 2f1-f2 Distortion-Product Otoacoustic Emissions

    ERIC Educational Resources Information Center

    Fitzgerald, Tracy S.; Prieve, Beth A.

    2005-01-01

    Although many distortion-product otoacoustic emissions (DPOAEs) may be measured in the ear canal in response to 2 pure tone stimuli, the majority of clinical studies have focused exclusively on the DPOAE at the frequency 2f1-f2. This study investigated another DPOAE, 2f2-f1, in an attempt to determine the following: (a) the optimal stimulus…

  12. 1 / f α noise and generalized diffusion in random Heisenberg spin systems

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

    Agarwal, Kartiek; Demler, Eugene; Martin, Ivar

    2015-11-01

    We study the “flux-noise” spectrum of random-bond quantum Heisenberg spin systems using a real-space renormalization group (RSRG) procedure that accounts for both the renormalization of the system Hamiltonian and of a generic probe that measures the noise. For spin chains, we find that the dynamical structure factor Sq (f ), at finite wave vector q, exhibits a power-law behavior both at high and low frequencies f , with exponents that are connected to one another and to an anomalous dynamical exponent through relations that differ at T = 0 and T =∞. The low-frequency power-law behavior of the structure factormore » is inherited by any generic probe with a finite bandwidth and is of the form 1/f α with 0.5 < α < 1. An analytical calculation of the structure factor, assuming a limiting distribution of the RG flow parameters (spin size, length, bond strength) confirms numerical findings.More generally, we demonstrate that this form of the structure factor, at high temperatures, is a manifestation of anomalous diffusionwhich directly follows from a generalized spin-diffusion propagator.We also argue that 1/f -noise is intimately connected to many-body-localization at finite temperatures. In two dimensions, the RG procedure is less reliable; however, it becomes convergent for quasi-one-dimensional geometries where we find that one-dimensional 1/f α behavior is recovered at low frequencies; the latter configurations are likely representative of paramagnetic spin networks that produce 1/f α noise in SQUIDs.« less

  13. Transcription factor FBI-1 acts as a dual regulator in adipogenesis by coordinated regulation of cyclin-A and E2F-4.

    PubMed

    Laudes, Matthias; Bilkovski, Roman; Oberhauser, Frank; Droste, Andrea; Gomolka, Matthias; Leeser, Uschi; Udelhoven, Michael; Krone, Wilhelm

    2008-05-01

    Generation of new adipocytes plays a major role in the development of obesity. We previously have shown that transcriptional repressor factor that binds to IST (FBI)-1 exerts a dual effect in the process of adipogenesis by inhibiting proliferation and promoting differentiation of preadipocytes. The aim of the present study was to identify FBI-1 regulated molecular effectors that could account for these effects. Overexpressing FBI-1 in preadipocytes resulted in reduced expression of the cell cycle regulator cyclin A, which may explain FBI-1 induced inhibition of proliferation. Interestingly, FBI-1 repressed cyclin A promoter activity through an indirect mechanisms that did not involve direct binding of FBI-1 to the promoter sequence, but rather FBI-1 inhibition of transcriptional activator Sp1 binding to a regulatory element at -452 to -443. We also show that FBI-1 promotes terminal preadipocyte differentiation through a mechanism involving decreased levels of expression of the PPARgamma inhibitor E2F-4. FBI-1 significantly reduced E2F-4 promoter activity. Contrary to cyclin A, we found FBI-1-induced repression of E2F-4 is mediated by a direct mechanism via a FBI-1 regulatory element at -11 to -5. As function of transcriptional repressors normally depends on the presence of regulatory co-factors we also performed expression profiling of potential FBI-1 co-repressors throughout adipogenesis. In these experiments Sin3A and histon deacetylase (HDAC)-1 showed a similar expression pattern compared to FBI-1. Strikingly, co-immunoprecipitation studies revealed that FBI-1 binds Sin3A and HDAC-1 to form a repressor complex. Furthermore, by mutational analysis the amino terminal Poxvirus (POZ) domain of FBI-1 was found to be important for Sin3A and HDAC-1 binding. Taken together, FBI-1 is the first transcriptional repressor shown to act as a dual regulator in adipogenesis exerting repressor activities on target genes by both, direct and indirect mechanisms.

  14. Proton irradiation of [18O]O2: production of [18F]F2 and [18F]F2 + [18F] OF2.

    PubMed

    Bishop, A; Satyamurthy, N; Bida, G; Hendry, G; Phelps, M; Barrio, J R

    1996-04-01

    The production of 18F electrophilic reagents via the 18O(p,n)18F reaction has been investigated in small-volume target bodies made of aluminum, copper, gold-plated copper and nickel, having straight or conical bore shapes. Three irradiation protocols-single-step, two-step and modified two-step-were used for the recovery of the 18F activity. The single-step irradiation protocol was tested in all the target bodies. Based on the single-step performance, aluminum targets were utilized extensively in the investigation of the two-step and modified two-step irradiation protocols. With an 11-MeV cyclotron and using the two-step irradiation protocol, > 1Ci [18F]F2 was recovered reproducibly from an aluminum target body. Probable radical mechanisms for the formation of OF2 and FONO2 (fluorine nitrate) in the single-step and modified two-step targets are proposed based on the amount of ozone generated and the nitrogen impurity present in the target gases, respectively.

  15. Differential Regulation of Macrophage Glucose Metabolism by Macrophage Colony-stimulating Factor and Granulocyte-Macrophage Colony-stimulating Factor: Implications for 18F FDG PET Imaging of Vessel Wall Inflammation

    PubMed Central

    Tavakoli, Sina; Short, John D.; Downs, Kevin; Nguyen, Huynh Nga; Lai, Yanlai; Zhang, Wei; Jerabek, Paul; Goins, Beth; Sadeghi, Mehran M.

    2017-01-01

    Purpose To determine the divergence of immunometabolic phenotypes of macrophages stimulated with macrophage colony-stimulating factor (M-CSF) and granulocyte-M-CSF (GM-CSF) and its implications for fluorine 18 (18F) fluorodeoxyglucose (FDG) imaging of atherosclerosis. Materials and Methods This study was approved by the animal care committee. Uptake of 2-deoxyglucose and various indexes of oxidative and glycolytic metabolism were evaluated in nonactivated murine peritoneal macrophages (MΦ0) and macrophages stimulated with M-CSF (MΦM-CSF) or GM-CSF (MΦGM-CSF). Intracellular glucose flux was measured by using stable isotope tracing of glycolytic and tricyclic acid intermediary metabolites. 18F-FDG uptake was evaluated in murine atherosclerotic aortas after stimulation with M-CSF or GM-CSF by using quantitative autoradiography. Results Despite inducing distinct activation states, GM-CSF and M-CSF stimulated progressive but similar levels of increased 2-deoxyglucose uptake in macrophages that reached up to sixfold compared with MΦ0. The expression of glucose transporters, oxidative metabolism, and mitochondrial biogenesis were induced to similar levels in MΦM-CSF and MΦGM-CSF. Unexpectedly, there was a 1.7-fold increase in extracellular acidification rate, a 1.4-fold increase in lactate production, and overexpression of several critical glycolytic enzymes in MΦM-CSF compared with MΦGM-CSF with associated increased glucose flux through glycolytic pathway. Quantitative autoradiography demonstrated a 1.6-fold induction of 18F-FDG uptake in murine atherosclerotic plaques by both M-CSF and GM-CSF. Conclusion The proinflammatory and inflammation-resolving activation states of macrophages induced by GM-CSF and M-CSF in either cell culture or atherosclerotic plaques may not be distinguishable by the assessment of glucose uptake. © RSNA, 2016 Online supplemental material is available for this article. PMID:27849433

  16. The IP vs. VDE competition as a key factor determining the stability of the MgBX 5 (X = F, Cl) compounds

    NASA Astrophysics Data System (ADS)

    Sikorska, Celina; Skurski, Piotr

    2010-11-01

    The explanation of the MgBX 5 (X = F, Cl) systems existence and stability is provided on the basis of theoretical considerations supported by ab initio calculations. The equilibrium structures and most probable fragmentation processes of 26 (including isomers) MgBX 5 molecules and six OBX 5 compounds (for comparison) were examined and discussed. The competition between the ionization potential (IP) of the MgX subunit and the electron binding energy (VDE) of the BX 4 fragment was found to be the key factor determining the ability to form a stable compound of MgBX 5 type.

  17. Immune-Enhancing Effect of Nanometric Lactobacillus plantarum nF1 (nLp-nF1) in a Mouse Model of Cyclophosphamide-Induced Immunosuppression.

    PubMed

    Choi, Dae-Woon; Jung, Sun Young; Kang, Jisu; Nam, Young-Do; Lim, Seong-Il; Kim, Ki Tae; Shin, Hee Soon

    2018-02-28

    Nanometric Lactobacillus plantarum nF1 (nLp-nF1) is a biogenics consisting of dead L. plantarum cells pretreated with heat and a nanodispersion process. In this study, we investigated the immune-enhancing effects of nLp-nF1 in vivo and in vitro. To evaluate the immunostimulatory effects of nLp-nF1, mice immunosuppressed by cyclophosphamide (CPP) treatment were administered with nLp-nF1. As expected, CPP restricted the immune response of mice, whereas oral administration of nLp-nF1 significantly increased the total IgG in the serum, and cytokine production (interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α)) in bone marrow cells. Furthermore, nLp-nF1 enhanced the production of splenic cytokines such as IL-12, TNF-α, and interferon gamma (IFN-γ). In vitro, nLp-nF1 stimulated the immune response by enhancing the production of cytokines such as IL-12, TNF-α, and IFN-γ. Moreover, nLp-nF1 given a food additive enhanced the immune responses when combined with various food materials in vitro. These results suggest that nLp-nF1 could be used to strengthen the immune system and recover normal immunity in people with a weak immune system, such as children, the elderly, and patients.

  18. Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

    PubMed

    Cronin, Katherine R; Mangan, Thomas P; Carew, Josephine A

    2012-01-01

    Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

  19. f(R)-gravity from Killing tensors

    NASA Astrophysics Data System (ADS)

    Paliathanasis, Andronikos

    2016-04-01

    We consider f(R)-gravity in a Friedmann-Lemaître-Robertson-Walker spacetime with zero spatial curvature. We apply the Killing tensors of the minisuperspace in order to specify the functional form of f(R) and for the field equations to be invariant under Lie-Bäcklund transformations, which are linear in momentum (contact symmetries). Consequently, the field equations to admit quadratic conservation laws given by Noether’s theorem. We find three new integrable f(R)-models, for which, with the application of the conservation laws, we reduce the field equations to a system of two first-order ordinary differential equations. For each model we study the evolution of the cosmological fluid. We find that for each integrable model the cosmological fluid has an equation of state parameter, in which there is linear behavior in terms of the scale factor which describes the Chevallier, Polarski and Linder parametric dark energy model.

  20. Human umbilical cord blood-derived f-macrophages retain pluripotentiality after thrombopoietin expansion

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

    Zhao Yong; Mazzone, Theodore

    2005-11-01

    We have previously characterized a new type of stem cell from human peripheral blood, termed fibroblast-like macrophage (f-M{phi}). Here, using umbilical cord blood as a source, we identified cells with similar characteristics including expression of surface markers (CD14, CD34, CD45, CD117, and CD163), phagocytosis, and proliferative capacity. Further, thrombopoietin (TPO) significantly stimulated the proliferation of cord blood-derived f-M{phi} (CB f-M{phi}) at low dosage without inducing a megakaryocytic phenotype. Additional experiments demonstrated that TPO-expanded cord blood-derived f-M{phi} (TCB f-M{phi}) retained their surface markers and differentiation ability. Treatment with vascular endothelial cell growth factor (VEGF) gave rise to endothelial-like cells, expressing Flt-1,more » Flk-1, von Willebrand Factor (vWF), CD31, acetylated low density lipoprotein internalization, and the ability to form endothelial-like cell chains. In the presence of lipopolyssacharide (LPS) and 25 mM glucose, the TCB f-M{phi} differentiated to express insulin mRNA, C-peptide, and insulin. In vitro functional analysis demonstrated that these insulin-positive cells could release insulin in response to glucose and other secretagogues. These findings demonstrate a potential use of CB f-M{phi} and may lead to develop new therapeutic strategy for treating dominant disease.« less

  1. Dynamics of f(R) gravity models and asymmetry of time

    NASA Astrophysics Data System (ADS)

    Verma, Murli Manohar; Yadav, Bal Krishna

    We solve the field equations of modified gravity for f(R) model in metric formalism. Further, we obtain the fixed points of the dynamical system in phase-space analysis of f(R) models, both with and without the effects of radiation. The stability of these points is studied against the perturbations in a smooth spatial background by applying the conditions on the eigenvalues of the matrix obtained in the linearized first-order differential equations. Following this, these fixed points are used for analyzing the dynamics of the system during the radiation, matter and acceleration-dominated phases of the universe. Certain linear and quadratic forms of f(R) are determined from the geometrical and physical considerations and the behavior of the scale factor is found for those forms. Further, we also determine the Hubble parameter H(t), the Ricci scalar R and the scale factor a(t) for these cosmic phases. We show the emergence of an asymmetry of time from the dynamics of the scalar field exclusively owing to the f(R) gravity in the Einstein frame that may lead to an arrow of time at a classical level.

  2. Optimizing a 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer

    PubMed Central

    Simoncic, Urban; Perlman, Scott; Liu, Glenn; Jeraj, Robert

    2015-01-01

    Background The 18F-NaF/18F-FDG cocktail PET/CT imaging has been proposed for patients with osseous metastases. This work aimed to optimize the cocktail composition for patients with metastatic castrate-resistant prostate cancer (mCRPC). Materials and methods Study was done on 6 patients with mCRPC that had analyzed a total of 26 lesions. Patients had 18F-NaF and 18F-FDG injections separated in time. Dynamic PET/CT imaging recorded uptake time course for both tracers into osseous metastases. 18F-NaF and 18F-FDG uptakes were decoupled by kinetic analysis, which enabled calculation of 18F-NaF and 18F-FDG Standardized Uptake Value (SUV) images. Peak, mean and total SUVs were evaluated for both tracers and all visible lesions. The 18F-NaF/18F-FDG cocktail was optimized under the assumption that contribution of both tracers to the image formation should be equal. SUV images for combined 18F-NaF/18F-FDG cocktail PET/CT imaging were generated for cocktail compositions with 18F-NaF:18F-FDG ratio varying from 1:8 to 1:2. Results The 18F-NaF peak and mean SUVs were on average 4-5 times higher than the 18F-FDG peak and mean SUVs, with inter-lesion coefficient-of-variations (COV) of 20%. 18F-NaF total SUV was on average 7 times higher than the 18F-FDG total SUV. When the 18F-NaF:18F-FDG ratio changed from 1:8 to 1:2, typical SUV on generated PET images increased by 50%, while change in uptake visual pattern was hardly noticeable. Conclusion The 18F-NaF/18F-FDG cocktail has equal contributions of both tracers to the image formation when the 18F-NaF:18F-FDG ratio is 1:5. Therefore we propose this ratio as the optimal cocktail composition for mCRPC patients. We also urge to strictly control the 18F-NaF/18F-FDG cocktail composition in any 18F-NaF/18F-FDG cocktail PET/CT exams. PMID:26378490

  3. Impact of haze-fog days to radon progeny equilibrium factor and discussion of related factors.

    PubMed

    Hou, Changsong; Shang, Bing; Zhang, Qingzhao; Cui, Hongxing; Wu, Yunyun; Deng, Jun

    2015-11-01

    The equilibrium factor F between radon and its short-lived progenies is an important parameter to estimate radon exposure of humans. Therefore, indoor and outdoor concentrations of radon and its short-lived radon progeny were measured in Beijing area using a continuously measuring device, in an effort to obtain information on the F value. The results showed that the mean values of F were 0.58 ± 0.13 (0.25-0.95, n = 305) and 0.52 ± 0.12 (0.31-0.91, n = 64) for indoor and outdoor, respectively. The indoor F value during haze-fog days was higher than the typical value of 0.4 recommended by the United Nations Scientific Committee on the Effects of Atomic Radiation, and it was also higher than the values of 0.47 and 0.49 reported in the literature. A positive correlation was observed between indoor F values and PM2.5 concentrations (R (2) = 0.71). Since 2013, owing to frequent heavy haze-fog events in Beijing and surrounding areas, the number of the days with severe pollution remains at a high level. Future studies on the impact of the ambient fine particulate matter on indoor radon progeny equilibrium factor F could be important.

  4. F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity.

    PubMed

    Miller, C H; Benson, J; Ellingsen, D; Driggers, J; Payne, A; Kelly, F M; Soucie, J M; Craig Hooper, W

    2012-05-01

    Both genetic and treatment-related risk factors contribute to the development of inhibitors in haemophilia. An inhibitor surveillance system piloted at 12 US sites has the goal of assessing risk factors through prospective data collection. This report examines the relationship of genotype and race/ethnicity to history of inhibitor in a large cohort of US haemophilia patients. Mutation analysis was performed on 676 haemophilia A (HA) and 153 haemophilia B (HB) patients by sequencing, Multiplex Ligation-dependent Probe Amplification, and PCR for inversions in F8 introns 22 (inv22) and 1 (inv1). Two HB patients with deletions had history of inhibitor. In severe HA, frequency of history of inhibitor was: large deletion 57.1%, splice site 35.7%, inv22 26.8%, nonsense 24.5%, frameshift 12.9%, inv1 11.1% and missense 9.5%. In HA, 19.6% of 321 White non-Hispanics (Whites), 37.1% of 35 Black non-Hispanics (Blacks) and 46.9% of 32 Hispanics had history of inhibitor (P = 0.0003). Mutation types and novel mutation rates were similar across ethnicities. When F8 haplotypes were constructed, Whites and Hispanics showed only H1 and H2. Within H1, history of inhibitor was 12.4% in Whites, 40.0% in Blacks (P = 0.009) and 32.4% in Hispanics (P = 0.002). Inhibitor frequency is confirmed to vary by mutation type and race in a large US population. White patients with history of inhibitor did not exhibit rare F8 haplotypes. F8 gene analysis did not reveal a cause for the higher inhibitor frequencies in Black and Hispanic patients. © 2011 Blackwell Publishing Ltd.

  5. Symmetry boost of the fidelity of Shor factoring

    NASA Astrophysics Data System (ADS)

    Nam, Y. S.; Blümel, R.

    2018-05-01

    In Shor's algorithm quantum subroutines occur with the structure F U F-1 , where F is a unitary transform and U is performing a quantum computation. Examples are quantum adders and subunits of quantum modulo adders. In this paper we show, both analytically and numerically, that if, in analogy to spin echoes, F and F-1 can be implemented symmetrically when executing Shor's algorithm on actual, imperfect quantum hardware, such that F and F-1 have the same hardware errors, a symmetry boost in the fidelity of the combined F U F-1 quantum operation results when compared to the case in which the errors in F and F-1 are independently random. Running the complete gate-by-gate implemented Shor algorithm, we show that the symmetry-induced fidelity boost can be as large as a factor 4. While most of our analytical and numerical results concern the case of over- and under-rotation of controlled rotation gates, in the numerically accessible case of Shor's algorithm with a small number of qubits, we show explicitly that the symmetry boost is robust with respect to more general types of errors. While, expectedly, additional error types reduce the symmetry boost, we show explicitly, by implementing general off-diagonal SU (N ) errors (N =2 ,4 ,8 ), that the boost factor scales like a Lorentzian in δ /σ , where σ and δ are the error strengths of the diagonal over- and underrotation errors and the off-diagonal SU (N ) errors, respectively. The Lorentzian shape also shows that, while the boost factor may become small with increasing δ , it declines slowly (essentially like a power law) and is never completely erased. We also investigate the effect of diagonal nonunitary errors, which, in analogy to unitary errors, reduce but never erase the symmetry boost. Going beyond the case of small quantum processors, we present analytical scaling results that show that the symmetry boost persists in the practically interesting case of a large number of qubits. We illustrate this result

  6. Improved Radio-Frequency Magneto-Optical Trap of SrF Molecules.

    PubMed

    Steinecker, Matthew H; McCarron, Daniel J; Zhu, Yuqi; DeMille, David

    2016-11-18

    We report the production of ultracold, trapped strontium monofluoride (SrF) molecules with number density and phase-space density significantly higher than previously achieved. These improvements are enabled by three distinct changes to our recently-demonstrated scheme for radio-frequency magneto-optical trapping of SrF: modification of the slowing laser beam geometry, addition of an optical pumping laser, and incorporation of a compression stage to the magneto-optical trap. With these improvements, we observe a trapped sample of SrF molecules at density 2.5×10 5  cm -3 and phase-space density 6×10 -14 , each a factor of 4 greater than in previous work. Under different experimental conditions, we observe trapping of up to 10 4 molecules, a factor of 5 greater than in previous work. Finally, by reducing the intensity of the applied trapping light, we observe molecular temperatures as low as 250 μK. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Decomposing interference during Stroop performance into different conflict factors: an event-related fMRI study.

    PubMed

    Melcher, Tobias; Gruber, Oliver

    2009-02-01

    In the current event-related functional magnetic resonance imaging (fMRI) study, we sought to trace back Stroop-interference to circumscribed properties of task-irrelevant word information - response-incompatibility, semantic incongruency and task-reference - that we conceive as conflict factors. Thereby, we particularly wanted to disentangle intermingled contributions of semantic conflict and response conflict to the overall Stroop-interference effect. To delineate neural substrates of single factors, we referred to the logics of cognitive subtraction and cognitive conjunction. Moreover, in a second step, we conducted correlation analyses to determine the relationship between neural activations and behavioral interference costs (i.e., conflict-related reaction time (RT) slowing) so as to further elucidate the functional role of the respective brain regions in conflict processing. Response-incompatibility was associated with activation in the left premotor cortex which can be interpreted as indicating motor competition or conflict, i.e., the presence of competing response tendencies. Accordingly, this activation was positively correlated with behavioral conflict costs. Semantic incongruency exhibited specific activation in the anterior cingulate cortex (ACC), the bilateral insula, and thalamus as well as in left somatosensory cortex. As supported by the consistent negative correlation with behavioral conflict costs, these activations most probably reflect strengthened control efforts to overcome interference and to ensure adequate task performance. Finally, task-reference elicited activation in the left temporo-polar cortex (TPC) and the right medial superior as well as in left rostroventral prefrontal cortex (rvPFC, sub-threshold activation). As strongly supported by prior studies' findings, this neural activation pattern may underlie residual semantic processing of the task-irrelevant word information.

  8. Finding P-Values for F Tests of Hypothesis on a Spreadsheet.

    ERIC Educational Resources Information Center

    Rochowicz, John A., Jr.

    The calculation of the F statistic for a one-factor analysis of variance (ANOVA) and the construction of an ANOVA tables are easily implemented on a spreadsheet. This paper describes how to compute the p-value (observed significance level) for a particular F statistic on a spreadsheet. Decision making on a spreadsheet and applications to the…

  9. Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

    PubMed

    Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

    2005-04-26

    Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

  10. F+ and F⁻ affinities of simple N(x)F(y) and O(x)F(y) compounds.

    PubMed

    Grant, Daniel J; Wang, Tsang-Hsiu; Vasiliu, Monica; Dixon, David A; Christe, Karl O

    2011-03-07

    Atomization energies at 0 K and heats of formation at 0 and 298 K are predicted for the neutral and ionic N(x)F(y) and O(x)F(y) systems using coupled cluster theory with single and double excitations and including a perturbative triples correction (CCSD(T)) method with correlation consistent basis sets extrapolated to the complete basis set (CBS) limit. To achieve near chemical accuracy (±1 kcal/mol), three corrections to the electronic energy were added to the frozen core CCSD(T)/CBS binding energies: corrections for core-valence, scalar relativistic, and first order atomic spin-orbit effects. Vibrational zero point energies were computed at the CCSD(T) level of theory where possible. The calculated heats of formation are in good agreement with the available experimental values, except for FOOF because of the neglect of higher order correlation corrections. The F(+) affinity in the N(x)F(y) series increases from N(2) to N(2)F(4) by 63 kcal/mol, while that in the O(2)F(y) series decreases by 18 kcal/mol from O(2) to O(2)F(2). Neither N(2) nor N(2)F(4) is predicted to bind F(-), and N(2)F(2) is a very weak Lewis acid with an F(-) affinity of about 10 kcal/mol for either the cis or trans isomer. The low F(-) affinities of the nitrogen fluorides explain why, in spite of the fact that many stable nitrogen fluoride cations are known, no nitrogen fluoride anions have been isolated so far. For example, the F(-) affinity of NF is predicted to be only 12.5 kcal/mol which explains the numerous experimental failures to prepare NF(2)(-) salts from the well-known strong acid HNF(2). The F(-) affinity of O(2) is predicted to have a small positive value and increases for O(2)F(2) by 23 kcal/mol, indicating that the O(2)F(3)(-) anion might be marginally stable at subambient temperatures. The calculated adiabatic ionization potentials and electron affinities are in good agreement with experiment considering that many of the experimental values are for vertical processes. © 2011

  11. Ectopic Expression of Xylella fastidiosa rpfF Conferring Production of Diffusible Signal Factor in Transgenic Tobacco and Citrus Alters Pathogen Behavior and Reduces Disease Severity.

    PubMed

    Caserta, R; Souza-Neto, R R; Takita, M A; Lindow, S E; De Souza, A A

    2017-11-01

    The pathogenicity of Xylella fastidiosa is associated with its ability to colonize the xylem of host plants. Expression of genes contributing to xylem colonization are suppressed, while those necessary for insect vector acquisition are increased with increasing concentrations of diffusible signal factor (DSF), whose production is dependent on RpfF. We previously demonstrated that transgenic citrus plants ectopically expressing rpfF from a citrus strain of X. fastidiosa subsp. pauca exhibited less susceptibility to Xanthomonas citri subsp. citri, another pathogen whose virulence is modulated by DSF accumulation. Here, we demonstrate that ectopic expression of rpfF in both transgenic tobacco and sweet orange also confers a reduction in disease severity incited by X. fastidiosa and reduces its colonization of those plants. Decreased disease severity in the transgenic plants was generally associated with increased expression of genes conferring adhesiveness to the pathogen and decreased expression of genes necessary for active motility, accounting for the reduced population sizes achieved in the plants, apparently by limiting pathogen dispersal through the plant. Plant-derived DSF signal molecules in a host plant can, therefore, be exploited to interfere with more than one pathogen whose virulence is controlled by DSF signaling.

  12. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    PubMed

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  13. 18F-FDG PET/CT Imaging of Primary Gastric Lymphoma.

    PubMed

    Davis, Brady S; Thompson, Trevor A; Wolin, Ely A

    2016-12-01

    Primary gastric lymphoma (PGL) accounts for less than 4% of gastric neoplasms. 18 F-FDG PET with simultaneously acquired CT ( 18 F-FDG PET/CT) allows for staging and differentiation from other gastric cancers. Rapid diagnosis and staging are important because chemotherapeutic response is generally favorable. We describe a case of an 83-y-old woman with stage II 1 PGL. 18 F-FDG PET/CT can be helpful to differentiate various gastric masses and is an important factor in the staging of PGL. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. 18F-FLT PET/CT in the Evaluation of Pheochromocytomas and Paragangliomas: A Pilot Study.

    PubMed

    Blanchet, Elise M; Taieb, David; Millo, Corina; Martucci, Victoria; Chen, Clara C; Merino, Maria; Herscovitch, Peter; Pacak, Karel

    2015-12-01

    (18)F-FDG PET/CT has been proven to be a highly sensitive method for pheochromocytomas/paragangliomas (PHEOs/PGLs) associated with succinate dehydrogenase (SDH) mutations. This finding has been attributed to altered tumor cell metabolism resulting from these mutations and does not provide additional prognostic information to genotype. Therefore, identification of new biomarkers for aggressiveness is needed. A high Ki-67 index was proposed to be an additional prognostic factor. This pilot study aimed to evaluate 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET/CT, a PET proliferation tracer, as a potential imaging agent in a series of 12 PHEO/PGL patients with different genetic backgrounds, to compare (18)F-FLT uptake with (18)F-FDG PET/CT, and to evaluate classic factors of aggressiveness. Twelve patients (7 metastatic and 5 nonmetastatic) were prospectively evaluated with (18)F-FDG and (18)F-FLT and followed for at least 2 y after the initial imaging work-up. Uptake was assessed at a lesion level, visually and quantitatively by maximum standardized uptake values (SUVmax) for both tracers. (18)F-FLT uptake was compared with risk factors known to be linked with a poor prognosis in PGLs (SDHB-mutated status, lesion size, dopaminergic phenotype) and with (18)F-FDG uptake. In 12 patients, 77 lesions were assessed. All lesions had low (18)F-FLT uptake (median SUVmax, 2.25; range, 0.7-4.5). There was no apparent superiority of (18)F-FLT uptake in progressive lesions, and most of the lesions showed a mismatch, with high (18)F-FDG uptake (median SUVmax, 10.8; range, 1.1-79.0) contrasting with low (18)F-FLT uptake. This study suggests that PHEOs/PGLs-even those that progress-do not exhibit intense (18)F-FLT uptake. It provides the first in vivo demonstration that proliferation may not be a major determinant of (18)F-FDG uptake in these tumors. These findings provide new insight into the biologic behavior of PGL and suggest that antiproliferative agents may be suboptimal

  15. Regional Variability of Lifestyle Factors and Hypertension with Prediabetes and Newly Diagnosed Type 2 Diabetes Mellitus: The Population-Based KORA-F4 and SHIP-TREND Studies in Germany.

    PubMed

    Stöckl, Doris; Rückert-Eheberg, Ina-Maria; Heier, Margit; Peters, Annette; Schipf, Sabine; Krabbe, Christine; Völzke, Henry; Tamayo, Teresa; Rathmann, Wolfgang; Meisinger, Christa

    2016-01-01

    Type 2 diabetes mellitus (T2D) shows regional differences in Germany. The purpose of the project was to compare the prevalence of prediabetes and undiagnosed T2D in two regions in Germany, the Northeast and the South, and to evaluate their associations with regional variations in lifestyle factors and hypertension. Data from the KORA-F4 study (South Germany, 2006-2008) and the SHIP-TREND study (Northeast Germany, 2008-2012) were used. Participants aged 35-79 years without T2D with an overnight fasting of more than 8 hours and an oral glucose tolerance test were included: KORA-F4: n = 2,616 and SHIP-TREND: n = 1,968. The prevalence of prediabetes/newly diagnosed T2D was especially high in men (about 60%) and women (about 50%) in the Northeast, followed by men (about 50%) and women (about 30%) in the South. Lifestyle factors associated with T2D varied between the regions: more participants in the Northeast were active smokers and the percentages of people with overweight or obesity were greater than in their southern counterparts. However, these differences could not explain the striking disparity in prediabetes/newly diagnosed T2D. The frequency of hypertension was also distinctly higher in the Northeast than in the South and clearly associated with prediabetes/newly diagnosed T2D. Especially in men living in the Northeast, screening individuals with blood pressure ≥ 140/90mmHg might reveal up to 70% of those with prediabetes/newly diagnosed T2D. Knowledge about regional variability in T2D and related risk factors is important for the planning of diabetes prevention programs. In our analyses, common lifestyle factors did not nearly explain these variations between the northern SHIP-TREND and the southern KORA-F4 studies. Further examinations of regional socioeconomic, political, environmental and other aspects are needed. Meanwhile, targeted diabetes prevention strategies with a special focus on men living in the northern parts of Germany are reasonable.

  16. Regional Variability of Lifestyle Factors and Hypertension with Prediabetes and Newly Diagnosed Type 2 Diabetes Mellitus: The Population-Based KORA-F4 and SHIP-TREND Studies in Germany

    PubMed Central

    Heier, Margit; Peters, Annette; Schipf, Sabine; Krabbe, Christine; Völzke, Henry; Tamayo, Teresa; Rathmann, Wolfgang; Meisinger, Christa

    2016-01-01

    Objective Type 2 diabetes mellitus (T2D) shows regional differences in Germany. The purpose of the project was to compare the prevalence of prediabetes and undiagnosed T2D in two regions in Germany, the Northeast and the South, and to evaluate their associations with regional variations in lifestyle factors and hypertension. Methods Data from the KORA-F4 study (South Germany, 2006–2008) and the SHIP-TREND study (Northeast Germany, 2008–2012) were used. Participants aged 35–79 years without T2D with an overnight fasting of more than 8 hours and an oral glucose tolerance test were included: KORA-F4: n = 2,616 and SHIP-TREND: n = 1,968. Results The prevalence of prediabetes/newly diagnosed T2D was especially high in men (about 60%) and women (about 50%) in the Northeast, followed by men (about 50%) and women (about 30%) in the South. Lifestyle factors associated with T2D varied between the regions: more participants in the Northeast were active smokers and the percentages of people with overweight or obesity were greater than in their southern counterparts. However, these differences could not explain the striking disparity in prediabetes/newly diagnosed T2D. The frequency of hypertension was also distinctly higher in the Northeast than in the South and clearly associated with prediabetes/newly diagnosed T2D. Especially in men living in the Northeast, screening individuals with blood pressure ≥ 140/90mmHg might reveal up to 70% of those with prediabetes/newly diagnosed T2D. Conclusions Knowledge about regional variability in T2D and related risk factors is important for the planning of diabetes prevention programs. In our analyses, common lifestyle factors did not nearly explain these variations between the northern SHIP-TREND and the southern KORA-F4 studies. Further examinations of regional socioeconomic, political, environmental and other aspects are needed. Meanwhile, targeted diabetes prevention strategies with a special focus on men living in the

  17. Upregulation of the Coagulation Factor VII Gene during Glucose Deprivation Is Mediated by Activating Transcription Factor 4

    PubMed Central

    Cronin, Katherine R.; Mangan, Thomas P.; Carew, Josephine A.

    2012-01-01

    Background Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Methodology/Principal Findings Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/− SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/−15% to 188+/−27% and 100+/−8.8% to 176.3+/−17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Conclusions/Significance Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress. PMID:22848420

  18. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults.

    PubMed

    Tsvetanov, Kamen A; Henson, Richard N A; Tyler, Lorraine K; Davis, Simon W; Shafto, Meredith A; Taylor, Jason R; Williams, Nitin; Cam-Can; Rowe, James B

    2015-06-01

    In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task

  19. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults

    PubMed Central

    Henson, Richard N. A.; Tyler, Lorraine K.; Davis, Simon W.; Shafto, Meredith A.; Taylor, Jason R.; Williams, Nitin; Cam‐CAN; Rowe, James B.

    2015-01-01

    Abstract In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood‐oxygenation level‐dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting‐state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath‐hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age‐related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population‐based Cambridge Centre for Ageing and Neuroscience cohort (Cam‐CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task‐based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects

  20. Qualitative analysis of ionospheric disorders in Solok earthquake (March 6, 2007) viewed from anomalous critical frequency of layer F (f0F2) and genesis spread F

    NASA Astrophysics Data System (ADS)

    Pujiastuti, D.; Daniati, S.; Taufiqurrahman, E.; Mustafa, B.; Ednofri

    2018-03-01

    A qualitative analysis has been conducted by comparing the critical frequency anomalies of layer F (f0F2) and Spread F events to see the correlation with seismic activity before the Solok earthquake (March 6, 2007) in West Sumatra. The ionospherics data used was taken using the FMCW ionosonde at LAPAN SPD Kototabang, Palupuah, West Sumatra. The process of ionogramme scaling is done first to get the daily value of f0F2. The value of f0F2 is then compared with its monthly median to see the daily variations that appear. Anomalies of f0F2 and Spread F events were observed from February 20, 2007 to March 6, 2007. The presence of f0F2 anomalies was the negative deviation and the presence of Spread F before earthquake events were recommended as Solok earthquake precursors as they occurred when geomagneticsics and solar activities were normal.

  1. Effect of NaF, SnF(2), and TiF(4) Toothpastes on Bovine Enamel and Dentin Erosion-Abrasion In Vitro.

    PubMed

    Comar, Lívia Picchi; Gomes, Marina Franciscon; Ito, Naiana; Salomão, Priscila Aranda; Grizzo, Larissa Tercília; Magalhães, Ana Carolina

    2012-01-01

    The aim of this study was to compare the effect of toothpastes containing TiF(4), NaF, and SnF(2) on tooth erosion-abrasion. Bovine enamel and dentin specimens were distributed into 10 groups (n = 12): experimental placebo toothpaste (no F); NaF (1450 ppm F); TiF(4) (1450 ppm F); SnF(2) (1450 ppm F); SnF(2) (1100 ppm F) + NaF (350 ppm F); TiF(4) (1100 ppm F) + NaF (350 ppm F); commercial toothpaste Pro-Health (SnF(2)-1100 ppm F + NaF-350 ppm F, Oral B); commercial toothpaste Crest (NaF-1.500 ppm F, Procter & Gamble); abrasion without toothpaste and only erosion. The erosion was performed 4 × 90 s/day (Sprite Zero). The toothpastes' slurries were applied and the specimens abraded using an electric toothbrush 2 × 15 s/day. Between the erosive and abrasive challenges, the specimens remained in artificial saliva. After 7 days, the tooth wear was evaluated using contact profilometry (μm). The experimental toothpastes with NaF, TiF(4), SnF(2), and Pro-Health showed a significant reduction in enamel wear (between 42% and 54%). Pro-Health also significantly reduced the dentin wear. The toothpastes with SnF(2)/NaF and TiF(4)/NaF showed the best results in the reduction of enamel wear (62-70%) as well as TiF(4), SnF(2), SnF(2)/NaF, and TiF(4)/NaF for dentin wear (64-79%) (P < 0.05). Therefore, the experimental toothpastes containing both conventional and metal fluoride seem to be promising in reducing tooth wear.

  2. Perceived social-ecological factors associated with fruit and vegetable purchasing, preparation, and consumption among young adults.

    PubMed

    Graham, Dan J; Pelletier, Jennifer E; Neumark-Sztainer, Dianne; Lust, Katherine; Laska, Melissa N

    2013-10-01

    Most young adults do not consume recommended levels of fruits and vegetables (F/V), and interventions to increase F/V-related behaviors among this understudied population are needed. Therefore, it is important to identify correlates of F/V intake among young adults to guide intervention development. This cross-sectional study used data from an online survey to identify factors related to young adults' F/V purchasing, preparation, and consumption, and to explore between-factor relationships using mediation analysis. In 2010, 1,201 college students in Minnesota completed questionnaires assessing F/V behaviors as well as perceptions of F/V-related individual, social, and environmental factors. Factor analysis identified questionnaire items assessing similar constructs. Seven factors were identified (personal barriers, F/V knowledge, family, friends, neighborhood, access barriers, and campus) and evaluated for relationships with F/V purchasing, preparation, and consumption using linear regression. Results revealed that perceived personal barriers (eg, lacking cooking skills) were inversely related to all F/V outcomes. Perception that family and friends eat healthfully and neighborhood access to F/V were positively related to all outcomes. Individual-, social-, and environment-level perceptions were related to purchasing, preparation, and consumption, and the effects of these factors were similar when accounting for mediated effects. Factors at all three levels and the ways in which these various factors operate together may be important to consider in future efforts to improve F/V behaviors among young adults. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  3. Properties of an R Factor from Pseudomonas aeruginosa

    PubMed Central

    Datta, Naomi; Hedges, R. W.; Shaw, Elizabeth J.; Sykes, R. B.; Richmond, M. H.

    1971-01-01

    An R factor from Pseudomonas aeruginosa, which confers resistance to penicillins, kanamycin, and tetracycline, was studied in Escherichia coli K-12. The R factor could coexist with F-like or I-like plasmids and therefore constituted a novel compatibility group. The R factor was transferable from E. coli to bacterial genera outside the Enterobacteriaceae (Pseudomonas and members of the Rhizobiaceae) to which transfer of F-like and I-like plasmids could not be demonstrated. PMID:4945193

  4. Double temporal sparsity based accelerated reconstruction of compressively sensed resting-state fMRI.

    PubMed

    Aggarwal, Priya; Gupta, Anubha

    2017-12-01

    A number of reconstruction methods have been proposed recently for accelerated functional Magnetic Resonance Imaging (fMRI) data collection. However, existing methods suffer with the challenge of greater artifacts at high acceleration factors. This paper addresses the issue of accelerating fMRI collection via undersampled k-space measurements combined with the proposed method based on l 1 -l 1 norm constraints, wherein we impose first l 1 -norm sparsity on the voxel time series (temporal data) in the transformed domain and the second l 1 -norm sparsity on the successive difference of the same temporal data. Hence, we name the proposed method as Double Temporal Sparsity based Reconstruction (DTSR) method. The robustness of the proposed DTSR method has been thoroughly evaluated both at the subject level and at the group level on real fMRI data. Results are presented at various acceleration factors. Quantitative analysis in terms of Peak Signal-to-Noise Ratio (PSNR) and other metrics, and qualitative analysis in terms of reproducibility of brain Resting State Networks (RSNs) demonstrate that the proposed method is accurate and robust. In addition, the proposed DTSR method preserves brain networks that are important for studying fMRI data. Compared to the existing methods, the DTSR method shows promising potential with an improvement of 10-12 dB in PSNR with acceleration factors upto 3.5 on resting state fMRI data. Simulation results on real data demonstrate that DTSR method can be used to acquire accelerated fMRI with accurate detection of RSNs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Serum levels of interleukin-22, cardiometabolic risk factors and incident type 2 diabetes: KORA F4/FF4 study.

    PubMed

    Herder, Christian; Kannenberg, Julia M; Carstensen-Kirberg, Maren; Huth, Cornelia; Meisinger, Christa; Koenig, Wolfgang; Peters, Annette; Rathmann, Wolfgang; Roden, Michael; Thorand, Barbara

    2017-01-31

    Interleukin-22 (IL-22) has beneficial effects on body weight, insulin resistance and inflammation in different mouse models, but its relevance for the development of type 2 diabetes in humans is unknown. We aimed to identify correlates of serum IL-22 levels and to test the hypothesis that higher IL-22 levels are associated with lower diabetes incidence. Cross-sectional associations between serum IL-22, cardiometabolic risk factors and glucose tolerance status were investigated in 1107 persons of the population-based KORA F4 study. The prospective association between serum IL-22 and incident type 2 diabetes was assessed in 504 initially non-diabetic study participants in both the KORA F4 study and its 7-year follow-up examination KORA FF4, 76 of whom developed diabetes. Male sex, current smoking, lower HDL cholesterol, lower estimated glomerular filtration rate and higher serum interleukin-1 receptor antagonist were associated with higher IL-22 levels after adjustment for confounders (all P < 0.05). Serum IL-22 showed no associations with glucose tolerance status, prediabetes or type 2 diabetes. Baseline serum IL-22 levels (median, 25th/75th percentiles) for incident type 2 diabetes cases and non-cases were 6.28 (1.95; 12.35) and 6.45 (1.95; 11.80) pg/ml, respectively (age and sex-adjusted P = 0.744). The age and sex-adjusted OR (95% CI) per doubling of IL-22 for incident type 2 diabetes of 1.02 (0.85; 1.23) was almost unchanged after consideration of further confounders. High serum levels of IL-22 were positively rather than inversely associated with several cardiometabolic risk factors. However, these associations did not translate into an increased risk for type 2 diabetes. Thus, our data argue against the utility of IL-22 as biomarker for prevalent or incident type 2 diabetes in humans, but identify potential determinants of IL-22 levels which merits further research in the context of cardiovascular diseases.

  6. F-35 Joint Strike Fighter Aircraft (F-35)

    DTIC Science & Technology

    2015-12-01

    Selected Acquisition Report ( SAR ) RCS: DD-A&T(Q&A)823-198 F-35 Joint Strike Fighter Aircraft (F-35) As of FY 2017 President’s Budget Defense...Acquisition Management Information Retrieval (DAMIR) March 21, 2016 08:47:09 UNCLASSIFIED F-35 December 2015 SAR March 21, 2016 08:47:09 UNCLASSIFIED 2...Document OSD - Office of the Secretary of Defense O&S - Operating and Support PAUC - Program Acquisition Unit Cost F-35 December 2015 SAR March 21

  7. Comparative uptake of ¹⁸F-FEN-DPAZn2, ¹⁸F-FECH, ¹⁸F-fluoride, and ¹⁸F-FDG in fibrosarcoma and aseptic inflammation.

    PubMed

    Liang, Xiang; Tang, Ganghua; Wang, Hongliang; Hu, Kongzhen; Tang, Xiaolan; Nie, Dahong; Sun, Ting; Huang, Tingting

    2014-08-01

    The aim of this study is to evaluate uptake of 2-(18)F-fluoroethyl-bis(zinc(II)-dipicolylamine) ((18)F-FEN-DPAZn2) as a promising cell death imaging agent, a choline analog (18)F-fluoroethylcholine ((18)F-FECH), (18)F-fluoride as a bone imaging agent, and a glucose analog 2-(18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG) in the combined S180 fibrosarcoma and turpentine-induced inflammation mice models. The results showed that (18)F-FDG had the highest tumor-to-blood uptake ratio and tumor-to-muscle ratio, and high inflammation-to-blood ratio and inflammation-to-muscle ratio. (18)F -FECH showed moderate tumor-to-blood ratio and tumor-to-muscle ratio, and low inflammation-to-blood ratio and inflammation-to-muscle ratio. However, accumulation of (18)F FEN-DPAZn2 in tumor was similar to that in normal muscle. Also, (18)F-FEN-DPAZn2 and (18)F-fluoride exhibited the best selectivity to inflammation. (18)F-FECH positron emission tomography (PET) imaging demonstrates some advantages over (18)F-FDG PET for the differentiation of tumor from inflammation. (18)F FEN-DPAZn2 and (18)F-fluoride can be used for PET imaging of aseptic inflammation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding.

    PubMed

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2011-09-01

    Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.

  9. Solubility of uranium oxide in molten salt electrolysis bath of LiF-BaF2 with LaF3 additive

    NASA Astrophysics Data System (ADS)

    Alangi, Nagaraj; Mukherjee, Jaya; Gantayet, L. M.

    2016-03-01

    The solubility of UO2 in the molten mixtures of equimolar LiF-BaF2(1:1) with LaF3 as additive was studied in the range of 1423 K-1523 K. The molten fluoride salt mixture LiF-BaF2 LaF3 was equilibrated with a sintered uranium oxide pellet at 1423 K, 1473 K, 1523 K and the salt samples were collected after equilibration. Studies were conducted in the range of 10%-50% by weight additions of LaF3 in the equimolar LiF-BaF2(1:1) base fluoride salt bath. Solubility of UO2 increased with rise in LaF3 concentration in the molten fluoride in the temperature range of 1423 K-1523 K. At a given concentration of LaF3, the UO2 solubility increased monotonously with temperature. With mixed solvent, when UF4 was added as a replacement of part of LaF3 in LiF-BaF2(1:1)-10 wt% LaF3 and LiF-BaF2(1:1)-30 wt% LaF3, there was an enhancement of solubility of UO2.

  10. Comparative Persistence of Subgroups of F-Specific RNA Phages in River Water

    PubMed Central

    Yang, Yongheng

    2013-01-01

    F-specific (F+) RNA phages are widely used as indicators for the presence of fecal contamination and/or enteric viruses in water, and identifying subgroups of F+ RNA phages provides an approach for microbial source tracking. Different survival characteristics of the F+ RNA phage subgroups result in a misinterpretation of their original proportion in water, thus giving misleading information when they are used for microbial source tracking. This study investigated the comparative persistence of subgroups of F+ RNA phages in river water under different conditions. Results suggested that temperature and pH are the major factors affecting the persistence of F+ RNA phages in river water, and organic substances promote phage survival. The comparative persistence patterns of subgroups of F+ RNA phages varied and may bias extrapolation of their initial proportions in surface water. Thus, the characteristics of water should be taken into consideration and the results should be carefully interpreted when F+ RNA phages are used for microbial source tracking. PMID:23686274

  11. Individual, work-, and flight-related issues in F-16 pilots reporting neck pain.

    PubMed

    De Loose, Veerle; Van den Oord, Marieke; Burnotte, Frédéric; Van Tiggelen, Damien; Stevens, Veerle; Cagnie, Barbara; Witvrouw, Erik; Danneels, Lieven

    2008-08-01

    Neck pain is a common problem in F-16 pilots. A cross-sectional survey was used to determine the self-reported 1-yr prevalence of neck pain and to compare individual, work-related, and flight-related characteristics in F-16 pilots with and without neck pain. There were 90 male F-16 pilots of the Belgian Air Force and The Royal Netherlands Air Force who voluntarily completed an anonymous survey. The 1-yr prevalence of neck pain was 18.9%. Pilots were divided into two groups: healthy (HG) and neck pain group (NPG). This study could not identify individual or specific flight-related differences between these two groups. High force demands, often sitting for a long time, frequently holding the neck in a forward bent posture, and being physically tired were all physical work-related factors that were reported significantly more often in the NPG. The NPG also reported significantly more psychosocial factors, such as being mentally tired at the end of the day and being annoyed by others at the workplace. Since the specific flight-related factors were not significantly different between the HG and the NPG, physical and psychosocial factors could have been important factors in the development or maintenance of neck pain in F-16 pilots. The results of this study highlight for the first time that, in addition to flight-related issues, other aspects must be considered in analyzing neck pain. These other aspects stress the importance of a broader approach when considering neck pain, even in this population that is exposed to very high loads during flight.

  12. Die Interhalogenkationen [Br2F5]+ und [Br3F8].

    PubMed

    Ivlev, Sergei; Karttunen, Antti; Buchner, Magnus; Conrad, Matthias; Kraus, Florian

    2018-05-02

    Wir berichten über die Synthese und Charakterisierung der bislang einzigen Polyhalogenkationen, in denen verbrückende Fluoratome vorliegen. Das [Br2F5]+-Kation enthält eine symmetrische [F2Br-µ-F-BrF2]-Brücke, das [Br3F8]+-Kation enthält unsymmetrische µ-F-Brücken. Die Fluoronium-Ionen wurden in Form ihrer [SbF6]--Salze erhalten und Raman-, und 19F-NMR-spektroskopisch, sowie durch Röntgenbeugung am Einkristall untersucht. Quantenchemische Rechnungen, sowohl für die isolierten Kationen in der Gasphase, als auch für die Festkörper selbst, wurden durchgeführt. Populationsanalysen zeigen, dass die µ-F-Atome die am stärksten negativ partialgeladenen Atome der Kationen sind. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Theoretical Study of Decomposition Pathways for HArF and HKrF

    NASA Technical Reports Server (NTRS)

    Chaban, Galina M.; Lundell, Jan; Gerber, R. Benny; Kwak, Donchan (Technical Monitor)

    2002-01-01

    To provide theoretical insights into the stability and dynamics of the new rare gas compounds HArF and HKrF, reaction paths for decomposition processes HRgF to Rg + HF and HRgF to H + Rg + F (Rg = Ar, Kr) are calculated using ab initio electronic structure methods. The bending channels, HRgF to Rg + HF, are described by single-configurational MP2 and CCSD(T) electronic structure methods, while the linear decomposition paths, HRgF to H + Rg + F, require the use of multi-configurational wave functions that include dynamic correlation and are size extensive. HArF and HKrF molecules are found to be energetically stable with respect to atomic dissociation products (H + Rg + F) and separated by substantial energy barriers from Rg + HF products, which ensure their kinetic stability. The results are compatible with experimental data on these systems.

  14. Fluorine Kα X-Ray Emission Spectra of MgF2, CaF2, SrF2 and BaF2

    NASA Astrophysics Data System (ADS)

    Sugiura, Chikara; Konishi, Wataru; Shoji, Shizuko; Kojima, Shinjiro

    1990-11-01

    The fluorine Kα emission spectra in fluorescence from a series of alkaline-earth fluorides MF2 (M=Mg, Ca, Sr and Ba) are measured with a high-resolution two-crystal vacuum spectrometer. An anomalously low intensity of the K1L1 satellite peak arising from 1s-1(2s2p)-1 initial states is observed for SrF2. The measured emission spectra are presented along with the UPS spectra of the F- 2p valence bands obtained by Poole et al. and the fluorine K absorption-edge spectra by Oizumi et al. By using these spectra, the first peak or shoulder in the fluorine K absorption-edge spectra is identified as being due to a core exciton which is formed below the bottom of the conduction band. The binding energy of the exciton is estimated to be 1.3(± 0.3), 1.1(± 0.2), 1.0(± 0.2) and 1.7(± 0.2) eV for MgF2, CaF2, SrF2 and BaF2, respectively.

  15. The eIF4F and eIFiso4F Complexes of Plants: An Evolutionary Perspective

    PubMed Central

    Patrick, Ryan M.; Browning, Karen S.

    2012-01-01

    Translation initiation in eukaryotes requires a number of initiation factors to recruit the assembled ribosome to mRNA. The eIF4F complex plays a key role in initiation and is a common target point for regulation of protein synthesis. Most work on the translation machinery of plants to date has focused on flowering plants, which have both the eIF4F complex (eIF4E and eIF4G) as well as the plant-specific eIFiso4F complex (eIFiso4E and eIFiso4G). The increasing availability of plant genome sequence data has made it possible to trace the evolutionary history of these two complexes in plants, leading to several interesting discoveries. eIFiso4G is conserved throughout plants, while eIFiso4E only appears with the evolution of flowering plants. The eIF4G N-terminus, which has been difficult to annotate, appears to be well conserved throughout the plant lineage and contains two motifs of unknown function. Comparison of eIFiso4G and eIF4G sequence data suggests conserved features unique to eIFiso4G and eIF4G proteins. These findings have answered some questions about the evolutionary history of the two eIF4F complexes of plants, while raising new ones. PMID:22611336

  16. Factor H-binding protein, a unique meningococcal vaccine antigen.

    PubMed

    Pizza, Mariagrazia; Donnelly, John; Rappuoli, Rino

    2008-12-30

    GNA1870, also named factor H-binding protein (fHbp) or rLP-2086, is a genome-derived antigen and one of the components of a rationally designed vaccine against Neisseria meningitidis serogroup B, which has entered phase III clinical trials. It has been classified into three main non-cross-protective variant groups. GNA1870 has also been termed fHbp because of its ability to bind factor H, a key regulatory component of the alternative complement pathway. fHbp is important for survival in human blood, human sera, and in presence of antimicrobial peptides, independently of its expression level. All these properties make fHbp a unique vaccine antigen.

  17. Stability of the Kasner universe in f (T ) gravity

    NASA Astrophysics Data System (ADS)

    Paliathanasis, Andronikos; Said, Jackson Levi; Barrow, John D.

    2018-02-01

    f (T ) gravity theory offers an alternative context in which to consider gravitational interactions where torsion, rather than curvature, is the mechanism by which gravitation is communicated. We investigate the stability of the Kasner solution with several forms of the arbitrary Lagrangian function examined within the f (T ) context. This is a Bianchi type-I vacuum solution with anisotropic expansion factors. In the f (T ) gravity setting, the solution must conform to a set of conditions in order to continue to be a vacuum solution of the generalized field equations. With this solution in hand, the perturbed field equations are determined for power-law and exponential forms of the f (T ) function. We find that the point which describes the Kasner solution is a saddle point which means that the singular solution is unstable. However, we find the de Sitter universe is a late-time attractor. In general relativity, the cosmological constant drives the isotropization of the spacetime while in this setting the extra f (T ) contributions now provide this impetus.

  18. Piracy of Decay-Accelerating Factor (CD55) Signal Transduction by the Diffusely Adhering Strain Escherichia coli C1845 Promotes Cytoskeletal F-Actin Rearrangements in Cultured Human Intestinal INT407 Cells

    PubMed Central

    Peiffer, Isabelle; Servin, Alain L.; Bernet-Camard, Marie-Françoise

    1998-01-01

    Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cγ, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry. PMID:9712744

  19. Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children.

    PubMed

    Centeno, Maria; Tierney, Tim M; Perani, Suejen; Shamshiri, Elhum A; StPier, Kelly; Wilkinson, Charlotte; Konn, Daniel; Banks, Tina; Vulliemoz, Serge; Lemieux, Louis; Pressler, Ronit M; Clark, Christopher A; Cross, J Helen; Carmichael, David W

    2016-01-01

    Early surgical intervention in children with drug resistant epilepsy has benefits but requires using tolerable and minimally invasive tests. EEG-fMRI studies have demonstrated good sensitivity for the localization of epileptic focus but a poor yield although the reasons for this have not been systematically addressed. While adults EEG-fMRI studies are performed in the "resting state"; children are commonly sedated however, this has associated risks and potential confounds. In this study, we assessed the impact of the following factors on the tolerability and results of EEG-fMRI in children: viewing a movie inside the scanner; movement; occurrence of interictal epileptiform discharges (IED); scan duration and design efficiency. This work's motivation is to optimize EEG-fMRI parameters to make this test widely available to paediatric population. Forty-six children with focal epilepsy and 20 controls (6-18) underwent EEG-fMRI. For two 10 minutes sessions subjects were told to lie still with eyes closed, as it is classically performed in adult studies ("rest sessions"), for another two sessions, subjects watched a child friendly stimulation i.e. movie ("movie sessions"). IED were mapped with EEG-fMRI for each session and across sessions. The resulting maps were classified as concordant/discordant with the presumed epileptogenic focus for each subject. Movement increased with scan duration, but the movie reduced movement by ~40% when played within the first 20 minutes. There was no effect of movie on the occurrence of IED, nor in the concordance of the test. Ability of EEG-fMRI to map the epileptogenic region was similar for the 20 and 40 minute scan durations. Design efficiency was predictive of concordance. A child friendly natural stimulus improves the tolerability of EEG-fMRI and reduces in-scanner movement without having an effect on IED occurrence and quality of EEG-fMRI maps. This allowed us to scan children as young as 6 and obtain localising information without

  20. Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB

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

    Burles, Kristin, E-mail: burles@ualberta.ca; Buuren, Nicholas van; Barry, Michele

    2014-11-15

    A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NFκB nuclear translocation, and thismore » inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB. - Highlights: • Ectromelia virus encodes four Ank/F-box proteins, EVM002, EVM005, EVM154 and EVM165. • The Ank/F-box proteins inhibit NFκB nuclear translocation, dependent on the F-box. • The Ank/F-box proteins prevent IκBα degradation, suggesting they target the SCF. • Deletion of a single Ank/F-box gene from ECTV does not prevent viral NFκB inhibition. • This study identifies a new mechanism by which ectromelia virus inhibits NFκB.« less

  1. Non-methane organic gas emissions from biomass burning: identification, quantification, and emission factors from PTR-ToF during the FIREX 2016 laboratory experiment

    NASA Astrophysics Data System (ADS)

    Koss, Abigail R.; Sekimoto, Kanako; Gilman, Jessica B.; Selimovic, Vanessa; Coggon, Matthew M.; Zarzana, Kyle J.; Yuan, Bin; Lerner, Brian M.; Brown, Steven S.; Jimenez, Jose L.; Krechmer, Jordan; Roberts, James M.; Warneke, Carsten; Yokelson, Robert J.; de Gouw, Joost

    2018-03-01

    Volatile and intermediate-volatility non-methane organic gases (NMOGs) released from biomass burning were measured during laboratory-simulated wildfires by proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF). We identified NMOG contributors to more than 150 PTR ion masses using gas chromatography (GC) pre-separation with electron ionization, H3O+ chemical ionization, and NO+ chemical ionization, an extensive literature review, and time series correlation, providing higher certainty for ion identifications than has been previously available. Our interpretation of the PTR-ToF mass spectrum accounts for nearly 90 % of NMOG mass detected by PTR-ToF across all fuel types. The relative contributions of different NMOGs to individual exact ion masses are mostly similar across many fires and fuel types. The PTR-ToF measurements are compared to corresponding measurements from open-path Fourier transform infrared spectroscopy (OP-FTIR), broadband cavity-enhanced spectroscopy (ACES), and iodide ion chemical ionization mass spectrometry (I- CIMS) where possible. The majority of comparisons have slopes near 1 and values of the linear correlation coefficient, R2, of > 0.8, including compounds that are not frequently reported by PTR-MS such as ammonia, hydrogen cyanide (HCN), nitrous acid (HONO), and propene. The exceptions include methylglyoxal and compounds that are known to be difficult to measure with one or more of the deployed instruments. The fire-integrated emission ratios to CO and emission factors of NMOGs from 18 fuel types are provided. Finally, we provide an overview of the chemical characteristics of detected species. Non-aromatic oxygenated compounds are the most abundant. Furans and aromatics, while less abundant, comprise a large portion of the OH reactivity. The OH reactivity, its major contributors, and the volatility distribution of emissions can change considerably over the course of a fire.

  2. Investigation of the 2f1-f2 and 2f2-f1 distortion product otoacoustic emissions using a computational model of the gerbil ear.

    PubMed

    Wen, Haiqi; Bowling, Thomas; Meaud, Julien

    2018-05-19

    In this work, a three-dimensional computational model of the gerbil ear is used to investigate the generation of the 2f 1 -f 2 and 2f 2 -f 1 distortion product otoacoustic emissions (DPOAEs). In order to predict both the distortion and reflection sources, cochlear roughness is modeled by introducing random inhomogeneities in the outer hair cell properties. The model was used to simulate the generation of DPOAEs in response to a two-tone stimulus for various primary stimulus levels and frequency ratios. As in published experiments, the 2f 1 -f 2 DPOAEs are mostly dominated by the distortion component while the 2f 2 -f 1 DPOAEs are dominated by the reflection component; furthermore, the influence of the levels and frequency ratio of the primaries are consistent with measurements. Analysis of the intracochlear response shows that the distortion component has the highest magnitude at all longitudinal locations for the 2f 1 -f 2 distortion product (DP) while the distortion component only dominates close to the DP best place in the case of the 2f 2 -f 1 DP. Decomposition of the intracochlear DPs into forward and reverse waves demonstrates that the 2f 1 -f 2 DP generates reverse waves for both the distortion and reflection components; however, a reverse wave is only generated for the reflection component in the case of the 2f 2 -f 1 DP. As in experiments in the gerbil, the group delay of the reflection component of the DPOAE is between 1× and 2× the forward group delay, which is consistent with the propagation of DP towards the stapes as slow reverse waves. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. On Analytical Solutions of f(R) Modified Gravity Theories in FLRW Cosmologies

    NASA Astrophysics Data System (ADS)

    Domazet, Silvije; Radovanović, Voja; Simonović, Marko; Štefančić, Hrvoje

    2013-02-01

    A novel analytical method for f(R) modified theories without matter in Friedmann-Lemaitre-Robertson-Walker (FLRW) spacetimes is introduced. The equation of motion for the scale factor in terms of cosmic time is reduced to the equation for the evolution of the Ricci scalar R with the Hubble parameter H. The solution of equation of motion for actions of the form of power law in Ricci scalar R is presented with a detailed elaboration of the action quadratic in R. The reverse use of the introduced method is exemplified in finding functional forms f(R), which leads to specified scale factor functions. The analytical solutions are corroborated by numerical calculations with excellent agreement. Possible further applications to the phases of inflationary expansion and late-time acceleration as well as f(R) theories with radiation are outlined.

  4. Waterborne Viruses and F-Specific Coliphages in Mixed-Use Watersheds: Microbial Associations, Host Specificities, and Affinities with Environmental/Land Use Factors

    PubMed Central

    Jones, Tineke H.; Brassard, Julie; Topp, Edward; Wilkes, Graham

    2016-01-01

    ABSTRACT From the years 2008 to 2014, a total of 1,155 water samples were collected (spring to fall) from 24 surface water sampling sites located in a mixed-used but predominantly agricultural (i.e., dairy livestock production) river basin in eastern Ontario, Canada. Water was analyzed for viable F-specific DNA (F-DNA) and F-specific RNA (F-RNA) (genogroup I [GI] to GIV) coliphage and a suite of molecularly detected viruses (norovirus [GI to GIV], torque teno virus [TTV], rotavirus, kobuvirus, adenovirus, astrovirus, hepatitis A, and hepatitis E). F-DNA and F-RNA coliphage were detected in 33 and 28% of the samples at maximum concentrations of 2,000 and 16,300 PFU · 100 ml−1, respectively. Animal TTV, human TTV, kobuvirus, astrovirus, and norovirus GIII were the most prevalent viruses, found in 23, 20, 13, 12, and 11% of samples, respectively. Viable F-DNA coliphage was found to be a modest positive indicator of molecularly detected TTV. F-RNA coliphage, unlike F-DNA coliphage, was a modest positive predictor of norovirus and rotavirus. There were, however, a number of significant negative associations among F-specific coliphage and viruses. F-DNA coliphage densities of >142 PFU · 100 ml−1 delineated conditions when ∼95% of water samples contained some type of virus. Kobuvirus was the virus most strongly related to detection of any other virus. Land use had some associations with virus/F-specific coliphage detection, but season and surface water flow were the variables that were most important for broadly delineating detection. Higher relative levels of detection of human viruses and human F-RNA coliphage were associated with higher relative degrees of upstream human land development in a catchment. IMPORTANCE This study is one of the first, to our knowledge, to evaluate relationships among F-specific coliphages and a large suite of enteric viruses in mixed-use but agriculturally dominated surface waters in Canada. This study suggested that relationships

  5. Waterborne Viruses and F-Specific Coliphages in Mixed-Use Watersheds: Microbial Associations, Host Specificities, and Affinities with Environmental/Land Use Factors.

    PubMed

    Jones, Tineke H; Brassard, Julie; Topp, Edward; Wilkes, Graham; Lapen, David R

    2017-02-01

    From the years 2008 to 2014, a total of 1,155 water samples were collected (spring to fall) from 24 surface water sampling sites located in a mixed-used but predominantly agricultural (i.e., dairy livestock production) river basin in eastern Ontario, Canada. Water was analyzed for viable F-specific DNA (F-DNA) and F-specific RNA (F-RNA) (genogroup I [GI] to GIV) coliphage and a suite of molecularly detected viruses (norovirus [GI to GIV], torque teno virus [TTV], rotavirus, kobuvirus, adenovirus, astrovirus, hepatitis A, and hepatitis E). F-DNA and F-RNA coliphage were detected in 33 and 28% of the samples at maximum concentrations of 2,000 and 16,300 PFU · 100 ml -1 , respectively. Animal TTV, human TTV, kobuvirus, astrovirus, and norovirus GIII were the most prevalent viruses, found in 23, 20, 13, 12, and 11% of samples, respectively. Viable F-DNA coliphage was found to be a modest positive indicator of molecularly detected TTV. F-RNA coliphage, unlike F-DNA coliphage, was a modest positive predictor of norovirus and rotavirus. There were, however, a number of significant negative associations among F-specific coliphage and viruses. F-DNA coliphage densities of >142 PFU · 100 ml -1 delineated conditions when ∼95% of water samples contained some type of virus. Kobuvirus was the virus most strongly related to detection of any other virus. Land use had some associations with virus/F-specific coliphage detection, but season and surface water flow were the variables that were most important for broadly delineating detection. Higher relative levels of detection of human viruses and human F-RNA coliphage were associated with higher relative degrees of upstream human land development in a catchment. This study is one of the first, to our knowledge, to evaluate relationships among F-specific coliphages and a large suite of enteric viruses in mixed-use but agriculturally dominated surface waters in Canada. This study suggested that relationships between viable F

  6. Monte Carlo calculated correction factors for diodes and ion chambers in small photon fields.

    PubMed

    Czarnecki, D; Zink, K

    2013-04-21

    The application of small photon fields in modern radiotherapy requires the determination of total scatter factors Scp or field factors Ω(f(clin), f(msr))(Q(clin), Q(msr)) with high precision. Both quantities require the knowledge of the field-size-dependent and detector-dependent correction factor k(f(clin), f(msr))(Q(clin), Q(msr)). The aim of this study is the determination of the correction factor k(f(clin), f(msr))(Q(clin), Q(msr)) for different types of detectors in a clinical 6 MV photon beam of a Siemens KD linear accelerator. The EGSnrc Monte Carlo code was used to calculate the dose to water and the dose to different detectors to determine the field factor as well as the mentioned correction factor for different small square field sizes. Besides this, the mean water to air stopping power ratio as well as the ratio of the mean energy absorption coefficients for the relevant materials was calculated for different small field sizes. As the beam source, a Monte Carlo based model of a Siemens KD linear accelerator was used. The results show that in the case of ionization chambers the detector volume has the largest impact on the correction factor k(f(clin), f(msr))(Q(clin), Q(msr)); this perturbation may contribute up to 50% to the correction factor. Field-dependent changes in stopping-power ratios are negligible. The magnitude of k(f(clin), f(msr))(Q(clin), Q(msr)) is of the order of 1.2 at a field size of 1 × 1 cm(2) for the large volume ion chamber PTW31010 and is still in the range of 1.05-1.07 for the PinPoint chambers PTW31014 and PTW31016. For the diode detectors included in this study (PTW60016, PTW 60017), the correction factor deviates no more than 2% from unity in field sizes between 10 × 10 and 1 × 1 cm(2), but below this field size there is a steep decrease of k(f(clin), f(msr))(Q(clin), Q(msr)) below unity, i.e. a strong overestimation of dose. Besides the field size and detector dependence, the results reveal a clear dependence of the

  7. Structure of the Newcastle disease virus F protein in the post-fusion conformation

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

    Swanson, Kurt; Wen, Xiaolin; Leser, George P.

    2010-11-17

    The paramyxovirus F protein is a class I viral membrane fusion protein which undergoes a significant refolding transition during virus entry. Previous studies of the Newcastle disease virus, human parainfluenza virus 3 and parainfluenza virus 5 F proteins revealed differences in the pre- and post-fusion structures. The NDV Queensland (Q) F structure lacked structural elements observed in the other two structures, which are key to the refolding and fusogenic activity of F. Here we present the NDV Australia-Victoria (AV) F protein post-fusion structure and provide EM evidence for its folding to a pre-fusion form. The NDV AV F structure containsmore » heptad repeat elements missing in the previous NDV Q F structure, forming a post-fusion six-helix bundle (6HB) similar to the post-fusion hPIV3 F structure. Electrostatic and temperature factor analysis of the F structures points to regions of these proteins that may be functionally important in their membrane fusion activity.« less

  8. Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB.

    PubMed

    Burles, Kristin; van Buuren, Nicholas; Barry, Michele

    2014-11-01

    A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NFκB) pathway. NFκB is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, IκBα, for degradation. IκBα is recruited to the SCF by the F-box domain-containing protein βTrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NFκB nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent IκBα degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NFκB. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Sodium 18F-Fluoride PET/CT of Bone, Joint and Other Disorders

    PubMed Central

    Jadvar, Hossein; Desai, Bhushan; Conti, Peter S.

    2014-01-01

    The use of 18F-sodium fluoride (18F-NaF) with positron emission tomography-computed tomography (PET/CT) is increasing. This resurgence of an old tracer has been fueled by several factors including superior diagnostic performance over standard 99mTc-based bone scintigraphy, growth in the availability of PET/CT imaging systems, increase in the number of regional commercial distribution centers for PET radiotracers, the recent concerns about potential chronic shortages with 99mTc based radiotracers, and the recent decision by the Centers for Medicare and Medicaid Services to reimburse for 18F-NaF PET/CT for evaluation of patients with known or suspected bone metastases through the National Oncologic PET Registry. The major goal of this article is to review the current evidence on the diagnostic utility of 18F-NaF in the imaging assessment of bone and joint in a variety of clinical conditions. PMID:25475379

  10. NbF5 and TaF5: Assignment of 19F NMR resonances and chemical bond analysis from GIPAW calculations

    NASA Astrophysics Data System (ADS)

    Biswal, Mamata; Body, Monique; Legein, Christophe; Sadoc, Aymeric; Boucher, Florent

    2013-11-01

    The 19F isotropic chemical shifts (δiso) of two isomorphic compounds, NbF5 and TaF5, which involve six nonequivalent fluorine sites, have been experimentally determined from the reconstruction of 1D 19F MAS NMR spectra. In parallel, the corresponding 19F chemical shielding tensors have been calculated using the GIPAW method for both experimental and DFT-optimized structures. Furthermore, the [M4F20] units of NbF5 and TaF5 being held together by van der Waals interactions, the relevance of Grimme corrections to the DFT optimization processes has been evaluated. However, the semi-empirical dispersion correction term introduced by such a method does not show any significant improvement. Nonetheless, a complete and convincing assignment of the 19F NMR lines of NbF5 and TaF5 is obtained, ensured by the linearity between experimental 19F δiso values and calculated 19F isotropic chemical shielding σiso values. The effects of the geometry optimizations have been carefully analyzed, confirming among other matters, the inaccuracy of the experimental structure of NbF5. The relationships between the fluorine chemical shifts, the nature of the fluorine atoms (bridging or terminal), the position of the terminal ones (opposite or perpendicular to the bridging ones), the fluorine charges, the ionicity and the length of the M-F bonds have been established. Additionally, for three of the 19F NMR lines of NbF5, distorted multiplets, arising from 1J-coupling and residual dipolar coupling between the 19F and 93Nb nuclei, were simulated yielding to values of 93Nb-19F 1J-coupling for the corresponding fluorine sites.

  11. "L.I.F.E.": A School-Based Heart-Health Screening and Intervention Program

    ERIC Educational Resources Information Center

    Northrup, Karen L.; Cottrell, Lesley A.; Wittberg, Richard A.

    2008-01-01

    This article describes the development and growth of "Lifestyle Improvements in the Family Environment" ("L.I.F.E."), a school-based heart-health screening and intervention program. The primary goals of "L.I.F.E." through three rounds of grant funding remained constant: (a) to identify cardiovascular risk factors in…

  12. A putative functional MYB transcription factor induced by low temperature regulates anthocyanin biosynthesis in purple kale (Brassica Oleracea var. acephala f. tricolor).

    PubMed

    Zhang, Bin; Hu, Zongli; Zhang, Yanjie; Li, Yali; Zhou, Shuang; Chen, Guoping

    2012-02-01

    The purple kale (Brassica Oleracea var. acephala f. tricolor) is a mutation in kales, giving the mutant phenotype of brilliant purple color in the interior. Total anthocyanin analysis showed that the amount of anthocyanins in the purple kale was up to 1.73 mg g(-1) while no anthocyanin was detected in the white kale. To elucidate the molecular mechanism of the anthocyanin biosynthesis in the purple kale, we analyzed the expression of structural genes and some transcription factors associated with anthocyanin biosynthesis in the purple cultivar "Red Dove" and the white cultivar "White Dove". The result showed that nearly all the anthocyanin biosynthetic genes showed higher expression levels in the purple cultivar than in the white cultivar, especially for DFR and ANS, they were barely detected in the white cultivar. Interestingly, the fact that a R2R3 MYB transcription factor named BoPAP1 was extremely up-regulated in the purple kale and induced by low temperature attracted our attention. Further sequence analysis showed that BoPAP1 shared high similarity with AtPAP1 and BoMYB1. In addition, the anthocyanin accumulation in the purple kale is strongly induced by the low temperature stress. The total anthocyanin contents in the purple kale under low temperature were about 50-fold higher than the plants grown in the greenhouse. The expression of anthocyanin biosynthetic genes C4H, F3H, DFR, ANS and UFGT were all enhanced under the low temperature. These evidences strongly suggest that BoPAP1 may play an important role in activating the anthocyanin structural genes for the abundant anthocyanin accumulation in the purple kale.

  13. The role of the F spin-orbit excited state in the F+H(2) and F+HD reactions

    NASA Astrophysics Data System (ADS)

    Tzeng, Yi-Ren

    In this dissertation we study the role of the F spin-orbit excited state (F*) in the F + H2 and F + HD reactions using quantum mechanical calculations. The calculations involve multiple potential energy surfaces (the Alexander-Stark-Werner, or ASW, PESs), and include an accurate treatment of the couplings (non-adiabatic, spin-orbit, and Coriolis) among all three electronic states. For the F + H2 reaction, we calculate the center-of-mass differential cross sections and laboratory-frame angular distributions at the four different combinations of collision energies and hydrogen isotopomer investigated in the experiments of Neumark et al. [J. Chem. Phys., 82, 3045 (1985)]. Comparisons with the calculations on the Stark-Werner (SW) and Hartke-Stark-Werner (HSW) PESs, which are limited to the lowest electronically adiabatic state, show that non-adiabatic couplings greatly reduce backward scattering. Surprisingly, we find the shapes of both the CM DCSs and LAB ADs are insensitive to the fraction of F* presented in the F beam. For the F + HD reaction, we calculate the excitation functions and product translational energy distribution functions to study the reactivity of F*. Comparisons with the experiment by Liu and co-workers [J. Chem. Phys., 113, 3633 (2000)] confirm the relatively low reactivity of spin-orbit excited state (F*) atoms. Excellent agreement with the experiment is obtained under the assumption that the F*:F concentration ratio equals 0.16:0.84 in the molecular beam, which corresponds to a thermal equilibrium of the two spin-orbit states at the experimental temperature (600K). From the accurate calculation of the F* reactivity and its relatively small contribution to the overall reactivity of the reaction, we attribute discrepancies between calculation and experiment to an inadequacy in the simulation of the reactivity of the F ground state, likely a result of the residual errors in the ground electronic potential energy surface.

  14. First insights into the pleiotropic role of vrf (yedF), a newly characterized gene of Salmonella Typhimurium.

    PubMed

    Ballesté-Delpierre, Clara; Fernandez-Orth, Dietmar; Ferrer-Navarro, Mario; Díaz-Peña, Ramón; Odena-Caballol, Antonia; Oliveira, Eliandre; Fàbrega, Anna; Vila, Jordi

    2017-11-10

    Salmonella possesses virulence determinants that allow replication under extreme conditions and invasion of host cells, causing disease. Here, we examined four putative genes predicted to encode membrane proteins (ydiY, ybdJ, STM1441 and ynaJ) and a putative transcriptional factor (yedF). These genes were identified in a previous study of a S. Typhimurium clinical isolate and its multidrug-resistant counterpart. For STM1441 and yedF a reduced ability to interact with HeLa cells was observed in the knock-out mutants, but an increase in this ability was absent when these genes were overexpressed, except for yedF which phenotype was rescued when yedF was restored. In the absence of yedF, decreased expression was seen for: i) virulence-related genes involved in motility, chemotaxis, attachment and survival inside the host cell; ii) global regulators of the invasion process (hilA, hilC and hilD); and iii) factors involved in LPS biosynthesis. In contrast, an increased expression was observed for anaerobic metabolism genes. We propose yedF is involved in the regulation of Salmonella pathogenesis and contributes to the activation of the virulence machinery. Moreover, we propose that, when oxygen is available, yedF contributes sustained repression of the anaerobic pathway. Therefore, we recommend this gene be named vrf, for virulence-related factor.

  15. fMRI Validation of fNIRS Measurements During a Naturalistic Task

    PubMed Central

    Noah, J. Adam; Ono, Yumie; Nomoto, Yasunori; Shimada, Sotaro; Tachibana, Atsumichi; Zhang, Xian; Bronner, Shaw; Hirsch, Joy

    2015-01-01

    We present a method to compare brain activity recorded with near-infrared spectroscopy (fNIRS) in a dance video game task to that recorded in a reduced version of the task using fMRI (functional magnetic resonance imaging). Recently, it has been shown that fNIRS can accurately record functional brain activities equivalent to those concurrently recorded with functional magnetic resonance imaging for classic psychophysical tasks and simple finger tapping paradigms. However, an often quoted benefit of fNIRS is that the technique allows for studying neural mechanisms of complex, naturalistic behaviors that are not possible using the constrained environment of fMRI. Our goal was to extend the findings of previous studies that have shown high correlation between concurrently recorded fNIRS and fMRI signals to compare neural recordings obtained in fMRI procedures to those separately obtained in naturalistic fNIRS experiments. Specifically, we developed a modified version of the dance video game Dance Dance Revolution (DDR) to be compatible with both fMRI and fNIRS imaging procedures. In this methodology we explain the modifications to the software and hardware for compatibility with each technique as well as the scanning and calibration procedures used to obtain representative results. The results of the study show a task-related increase in oxyhemoglobin in both modalities and demonstrate that it is possible to replicate the findings of fMRI using fNIRS in a naturalistic task. This technique represents a methodology to compare fMRI imaging paradigms which utilize a reduced-world environment to fNIRS in closer approximation to naturalistic, full-body activities and behaviors. Further development of this technique may apply to neurodegenerative diseases, such as Parkinson’s disease, late states of dementia, or those with magnetic susceptibility which are contraindicated for fMRI scanning. PMID:26132365

  16. CHClF2 (F-22) in the Earth's atmosphere

    NASA Astrophysics Data System (ADS)

    Rasmussen, R. A.; Khalil, M. A. K.; Penkett, S. A.; Prosser, N. J. D.

    1980-10-01

    Recent global measurements of CHClF2 (F-22) are reported. Originally, GC/MS techniques were used to obtain these data. Since then, significant advances using an O2-doped electron capture detector have been made in the analytical techniques, so that F-22 can be measured by EC/GC methods at ambient concentrations. The atmospheric burden of F-22 calculated from these measurements (average mixing ratio, mid-1979, ˜45 pptv) is considerably greater than that expected from the estimates of direct industrial emissions (average mixing ratio, mid-1979, ˜30 pptv). This difference is probably due to underestimates of F-22 emissions.

  17. CHClF2 /F-22/ in the earth's atmosphere

    NASA Technical Reports Server (NTRS)

    Rasmussen, R. A.; Khalil, M. A. K.; Penkett, S. A.; Prosser, N. J. D.

    1980-01-01

    Recent global measurements of CHClF2 (F-22) are reported. Originally, GC/MS techniques were used to obtain these data. Since then, significant advances using an O2-doped electron capture detector have been made in the analytical techniques, so that F-22 can be measured by EC/GC methods at ambient concentrations. The atmospheric burden of F-22 calculated from these measurements (average mixing ratio, mid-1979, approximately 45 pptv) is considerably greater than that expected from the estimates of direct industrial emissions (average mixing ratio, mid-1979, approximately 30 pptv). This difference is probably due to underestimates of F-22 emissions.

  18. Improved process for generating ClF/sub 3/ from ClF and F/sub 2/

    DOEpatents

    Reiner, R.H.; Pashley, J.H.; Barber, E.J.

    The invention is an improvement in the process for producing gaseous ClF/sub 3/ by reacting ClF and F/sub 2/ at elevated temperature. The improved process comprises conducting the reaction in the presence of NiF/sub 2/, which preferably is in the form of particles or in the form of a film or layer on a particulate substrate. The nickel fluoride acts as a reaction catalyst, significantly increasing the reaction rate and thus permitting valuable reductions in process temperature, pressure, and/or reactor volume.

  19. The chemo-mechanical coupled model for F(1)F(0)-motor.

    PubMed

    Xu, Lizhong; Liu, Fang

    2012-04-01

    F(1)F(0)-motor (ATP synthase) is the universal enzyme in biological energy conversion that is present in the membranes of mitochondria, chloroplasts and bacteria. It uses the energy of the proton gradient across the membrane to synthesize ATP. Previous theory and model about rotation of the ATP synthase is reviewed, then a novel chemo-mechanical coupled model for rotation of the F(1)F(0)-motor is proposed. In the model, more events are considered simultaneously that includes the movement of F(1), the movement of F(0), reactions at F(1) and reactions at F(0). Using the model, the possible substep modes of the rotation for F(1)F(0) are predicted, the dependence of the motor efficiency and its rotation rate on the rigidity of the γ shaft is investigated. We conclude that the γ shaft has a large rotation rate for a limited driving potential because two ends of the γ shaft can rotate alternately for its flexibility. The flexibility also makes the efficiency of F(1)F(0) drop because elastic twisting deformation power is needed during alternate rotation of the γ shaft at two ends. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Dirac Quasinormal Modes of Static f(R) de Sitter Black Holes

    NASA Astrophysics Data System (ADS)

    Ma, Hong

    2018-02-01

    Quasinormal modes (QNMs) for Dirac perturbations of f(R) black holes (BHs) are described in this paper, involving two types of f(R) solution: f(R) (Schwarzschild) BHs and f(R) (Maxwell) BHs. With the finite difference method, the stability of the f(R) black holes (BHs) is analysed and the threshold range of f(R) (Schwarzschild) BHs and f(R) (Maxwell) BHs is defined respectively. The results show that due to the presence of the correction factor R0, the damping rate of Dirac field decreases. Meanwhile, the influence of angular quantum number values |k| on the f(R) BHs is investigated. The results indicate that the QNMs oscillation becomes tenser and damping speed slowly decreases with |k| increasing. Furthermore, under the Dirac perturbation, the stability of f(R) solutions can be reflected in the manner of Dirac QNMs. The relationships between the QNMs and the parameters (|k|, charge Q and mass m) are discussed in massless, and massive cases, by contrast to the classical BHs. Supported by FAPESP No. 2012/08934-0, National Natural Science Foundation of China under Grant Nos. 11205254, 11178018, 11375279, 11605015, and the Natural Science Foundation Project of CQ CSTC 2011BB0052, and the Fundamental Research Funds for the Central Universities 106112016CDJXY300002 and CDJRC10300003

  1. Congenital hypopituitarism due to POU1F1 gene mutation.

    PubMed

    Lee, Ni-Chung; Tsai, Wen-Yu; Peng, Shinn-Forng; Tung, Yi-Ching; Chien, Yin-Hsiu; Hwu, Wuh-Liang

    2011-01-01

    POU1F1 (Pit-1; Gene ID 5449) is an anterior pituitary transcriptional factor, and POU1F1 mutation is known to cause anterior pituitary hypoplasia, growth hormone and prolactin deficiency and various degree of hypothyroidism. We report here a patient who presented with growth failure and central hypothyroidism since early infancy. However, treatment with thyroxine gave no effect and he subsequently developed calf muscle pseudohypertrophy (Kocher-Debre-Semelaigne syndrome), elevation of creatinine kinase, dilated cardiomyopathy and pericardial effusion. Final diagnosis was made by combined pituitary function test and sequencing analysis that revealed POU1F1 gene C.698T > C (p.F233S) mutation. The rarity of the disease can result in delayed diagnosis and treatment. Copyright © 2011 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

  2. ZnO:Zn/6LiF scintillator-A low afterglow alternative to ZnS:Ag/6LiF for thermal neutron detection

    NASA Astrophysics Data System (ADS)

    Sykora, G. Jeff; Schooneveld, Erik M.; Rhodes, Nigel J.

    2018-03-01

    Current ZnS:Ag/6LiF based scintillation detectors are often count rate limited by the long lifetime afterglow in the scintillator. Despite this drawback, new instruments at neutron scattering facilities, like ISIS in the UK, would still like to use ZnS:Ag/6LiF detectors due to their low gamma sensitivity, high light output, simplicity of detector design and relatively inexpensive production. One particular advantage of ZnS:Ag/6LiF detectors is their ability to provide strong pulse shape discrimination between neutrons and gammas. Despite the advantages of these detectors, it is becoming clear that new and upgraded instruments will be limited by the count rate capability of ZnS:Ag/6LiF, so an alternative scintillator technology with equivalent simplicity is being sought. ZnO:Zn/6LiF is investigated here as a low afterglow alternative to ZnS:Ag/6LiF. Basic scintillation properties of ZnO:Zn are studied and are discussed. Pulse shape discrimination between neutrons and gammas is explored and taken advantage of through simple single photon counting methods. A further step toward a realistic detector for neutron scattering is also taken by fiber coupling the ZnO:Zn/6LiF to a PMT. In an initial study of this fiber coupled configuration, 60Co gamma sensitivity of ∼ 7 × 10-6 is shown and improvements in count rate capability of at least a factor of 6 over ZnS:Ag/6LiF based neutron detectors are demonstrated.

  3. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

    PubMed

    Abadjieva, Desislava; Kistanova, Elena

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris.

  4. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring

    PubMed Central

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers’ oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris. PMID:26928288

  5. X-ray photoelectron spectroscopy as detection tool for coordinated or uncoordinated fluorine atoms demonstrated on fluoride systems NaF, K2TaF7, K3TaF8, K2ZrF6, Na7Zr6F31 and K3ZrF7

    NASA Astrophysics Data System (ADS)

    Boča, Miroslav; Barborík, Peter; Mičušík, Matej; Omastová, Mária

    2012-07-01

    While systems K3TaF8 and K3ZrF7 were prepared by modified molten salt method modified wet pathway was used for reproducible preparation of Na7Zr6F31. Its congruently melting character was demonstrated on simultaneous TG/DSC measurements and XRD patterns. X-ray photoelectron spectroscopy was applied for identification of differently bonded fluorine atoms in series of compounds NaF, K2TaF7, K3TaF8, K2ZrF6, Na7Zr6F31 and K3ZrF7. Three different types of fluorine atoms were described qualitatively and quantitatively. Uncoordinated fluorine atoms (F-) provide signals at lowest binding energies, followed by signals from terminally coordinated fluorine atoms (M-F) and then bridging fluorine atoms (M-F-M) at highest energy. Based on XPS F 1s signals assigned to fluorine atoms in compounds with correctly determined structure it was suggested that fluorine atoms in K3ZrF7 have partially bridging character.

  6. E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair.

    PubMed

    Singh, Randeep K; Dagnino, Lina

    2016-05-03

    Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis.

  7. E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair

    PubMed Central

    Singh, Randeep K.; Dagnino, Lina

    2016-01-01

    Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis. PMID:27028861

  8. Discrete symmetries in Heterotic/F-theory duality and mirror symmetry

    DOE PAGES

    Cvetič, Mirjam; Grassi, Antonella; Poretschkin, Maximilian

    2017-06-30

    We study aspects of Heterotic/F-theory duality for compacti cations with Abelian discrete gauge symmetries. We consider F-theory compacti cations on genus-one bered Calabi-Yau manifolds with n-sections, associated with the Tate-Shafarevich group Z n. Such models are obtained by studying rst a speci c toric set-up whose associated Heterotic vector bundle has structure group Z n. By employing a conjectured Heterotic/Ftheory mirror symmetry we construct dual geometries of these original toric models, where in the stable degeneration limit we obtain a discrete gauge symmetry of order two and three, for compacti cations to six dimensions. We provide explicit constructions of mirrorpairsmore » for symmetric examples with Z 2 and Z 3, in six dimensions. The Heterotic models with symmetric discrete symmetries are related in eld theory to a Higgsing of Heterotic models with two symmetric abelian U(1) gauge factors, where due to the Stuckelberg mechanism only a diagonal U(1) factor remains massless, and thus after Higgsing only a diagonal discrete symmetry of order n is present in the Heterotic models and detected via Heterotic/F-theory duality. These constructions also provide further evidence for the conjectured mirror symmetry in Heterotic/F-theory at the level of brations with torsional sections and those with multi-sections.« less

  9. Discrete symmetries in Heterotic/F-theory duality and mirror symmetry

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

    Cvetič, Mirjam; Grassi, Antonella; Poretschkin, Maximilian

    We study aspects of Heterotic/F-theory duality for compacti cations with Abelian discrete gauge symmetries. We consider F-theory compacti cations on genus-one bered Calabi-Yau manifolds with n-sections, associated with the Tate-Shafarevich group Z n. Such models are obtained by studying rst a speci c toric set-up whose associated Heterotic vector bundle has structure group Z n. By employing a conjectured Heterotic/Ftheory mirror symmetry we construct dual geometries of these original toric models, where in the stable degeneration limit we obtain a discrete gauge symmetry of order two and three, for compacti cations to six dimensions. We provide explicit constructions of mirrorpairsmore » for symmetric examples with Z 2 and Z 3, in six dimensions. The Heterotic models with symmetric discrete symmetries are related in eld theory to a Higgsing of Heterotic models with two symmetric abelian U(1) gauge factors, where due to the Stuckelberg mechanism only a diagonal U(1) factor remains massless, and thus after Higgsing only a diagonal discrete symmetry of order n is present in the Heterotic models and detected via Heterotic/F-theory duality. These constructions also provide further evidence for the conjectured mirror symmetry in Heterotic/F-theory at the level of brations with torsional sections and those with multi-sections.« less

  10. Insulin Inhibits Nrf2 Gene Expression via Heterogeneous Nuclear Ribonucleoprotein F/K in Diabetic Mice

    PubMed Central

    Ghosh, Anindya; Abdo, Shaaban; Zhao, Shuiling; Wu, Chin-Han; Shi, Yixuan; Lo, Chao-Sheng; Chenier, Isabelle; Alquier, Thierry; Filep, Janos G.; Ingelfinger, Julie R.; Zhang, Shao-Ling

    2017-01-01

    Oxidative stress induces endogenous antioxidants via nuclear factor erythroid 2–related factor 2 (Nrf2), potentially preventing tissue injury. We investigated whether insulin affects renal Nrf2 expression in type 1 diabetes (T1D) and studied its underlying mechanism. Insulin normalized hyperglycemia, hypertension, oxidative stress, and renal injury; inhibited renal Nrf2 and angiotensinogen (Agt) gene expression; and upregulated heterogeneous nuclear ribonucleoprotein F and K (hnRNP F and hnRNP K) expression in Akita mice with T1D. In immortalized rat renal proximal tubular cells, insulin suppressed Nrf2 and Agt but stimulated hnRNP F and hnRNP K gene transcription in high glucose via p44/42 mitogen-activated protein kinase signaling. Transfection with small interfering RNAs of p44/42 MAPK, hnRNP F, or hnRNP K blocked insulin inhibition of Nrf2 gene transcription. Insulin curbed Nrf2 promoter activity via a specific DNA-responsive element that binds hnRNP F/K, and hnRNP F/K overexpression curtailed Nrf2 promoter activity. In hyperinsulinemic-euglycemic mice, renal Nrf2 and Agt expression was downregulated, whereas hnRNP F/K expression was upregulated. Thus, the beneficial actions of insulin in diabetic nephropathy appear to be mediated, in part, by suppressing renal Nrf2 and Agt gene transcription and preventing Nrf2 stimulation of Agt expression via hnRNP F/K. These findings identify hnRNP F/K and Nrf2 as potential therapeutic targets in diabetes. PMID:28324005

  11. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

    PubMed Central

    Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias

    2015-01-01

    BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased

  12. Cosmography of f(R)-brane cosmology

    NASA Astrophysics Data System (ADS)

    Bouhmadi-López, Mariam; Capozziello, Salvatore; Cardone, Vincenzo F.

    2010-11-01

    Cosmography is a useful tool to constrain cosmological models, in particular, dark energy models. In the case of modified theories of gravity, where the equations of motion are generally quite complicated, cosmography can contribute to select realistic models without imposing arbitrary choices a priori. Indeed, its reliability is based on the assumptions that the universe is homogeneous and isotropic on large scale and luminosity distance can be “tracked” by the derivative series of the scale factor a(t). We apply this approach to induced gravity brane-world models where an f(R) term is present in the brane effective action. The virtue of the model is to self-accelerate the normal and healthy Dvali-Gabadadze-Porrati branch once the f(R) term deviates from the Hilbert-Einstein action. We show that the model, coming from a fundamental theory, is consistent with the ΛCDM scenario at low redshift. We finally estimate the cosmographic parameters fitting the Union2 Type Ia Supernovae data set and the distance priors from baryon acoustic oscillations and then provide constraints on the present day values of f(R) and its second and third derivatives.

  13. United States Air Force F-35A Operational Basing Environmental Impact Statement. Appendix E: Responses

    DTIC Science & Technology

    2013-09-01

    R0287, R0549, R0662, R0740 Concerned that the afterburner was not factored into the noise zone equation. Afterburner takeoffs were factored into...the noise assessment. The F-35s at Burlington International Airport are proposed to use afterburners on only 5 percent of their takeoffs (vice the...90 percent done now by F-16s). However, the afterburner would be turned off shortly after the aircraft becomes airborne, much prior to crossing the

  14. Platelet binding sites for factor VIII in relation to fibrin and phosphatidylserine

    PubMed Central

    Novakovic, Valerie A.; Shi, Jialan; Rasmussen, Jan; Pipe, Steven W.

    2015-01-01

    Thrombin-stimulated platelets expose very little phosphatidylserine (PS) but express binding sites for factor VIII (fVIII), casting doubt on the role of exposed PS as the determinant of binding sites. We previously reported that fVIII binding sites are increased three- to sixfold when soluble fibrin (SF) binds the αIIbβ3 integrin. This study focuses on the hypothesis that platelet-bound SF is the major source of fVIII binding sites. Less than 10% of fVIII was displaced from thrombin-stimulated platelets by lactadherin, a PS-binding protein, and an fVIII mutant defective in PS-dependent binding retained platelet affinity. Therefore, PS is not the determinant of most binding sites. FVIII bound immobilized SF and paralleled platelet binding in affinity, dependence on separation from von Willebrand factor, and mediation by the C2 domain. SF also enhanced activity of fVIII in the factor Xase complex by two- to fourfold. Monoclonal antibody (mAb) ESH8, against the fVIII C2 domain, inhibited binding of fVIII to SF and platelets but not to PS-containing vesicles. Similarly, mAb ESH4 against the C2 domain, inhibited >90% of platelet-dependent fVIII activity vs 35% of vesicle-supported activity. These results imply that platelet-bound SF is a component of functional fVIII binding sites. PMID:26162408

  15. Combinatorial compatibility as habit-controlling factor in lysozyme crystallization I. Monomeric and tetrameric F faces derived graph-theoretically

    NASA Astrophysics Data System (ADS)

    Strom, C. S.; Bennema, P.

    1997-03-01

    A series of two articles discusses possible morphological evidence for oligomerization of growth units in the crystallization of tetragonal lysozyme, based on a rigorous graph-theoretic derivation of the F faces. In the first study (Part I), the growth layers are derived as valid networks satisfying the conditions of F slices in the context of the PBC theory using the graph-theoretic method implemented in program FFACE [C.S. Strom, Z. Krist. 172 (1985) 11]. The analysis is performed in monomeric and alternative tetrameric and octameric formulations of the unit cell, assuming tetramer formation according to the strongest bonds. F (flat) slices with thickness Rdhkl ( {1}/{2} < R ≤ 1 ) are predicted theoretically in the forms 1 1 0, 0 1 1, 1 1 1. The relevant energies are established in the broken bond model. The relation between possible oligomeric specifications of the unit cell and combinatorially feasible F slice compositions in these orientations is explored.

  16. Dynamic causal modelling on infant fNIRS data: A validation study on a simultaneously recorded fNIRS-fMRI dataset.

    PubMed

    Bulgarelli, Chiara; Blasi, Anna; Arridge, Simon; Powell, Samuel; de Klerk, Carina C J M; Southgate, Victoria; Brigadoi, Sabrina; Penny, William; Tak, Sungho; Hamilton, Antonia

    2018-04-12

    Tracking the connectivity of the developing brain from infancy through childhood is an area of increasing research interest, and fNIRS provides an ideal method for studying the infant brain as it is compact, safe and robust to motion. However, data analysis methods for fNIRS are still underdeveloped compared to those available for fMRI. Dynamic causal modelling (DCM) is an advanced connectivity technique developed for fMRI data, that aims to estimate the coupling between brain regions and how this might be modulated by changes in experimental conditions. DCM has recently been applied to adult fNIRS, but not to infants. The present paper provides a proof-of-principle for the application of this method to infant fNIRS data and a demonstration of the robustness of this method using a simultaneously recorded fMRI-fNIRS single case study, thereby allowing the use of this technique in future infant studies. fMRI and fNIRS were simultaneously recorded from a 6-month-old sleeping infant, who was presented with auditory stimuli in a block design. Both fMRI and fNIRS data were preprocessed using SPM, and analysed using a general linear model approach. The main challenges that adapting DCM for fNIRS infant data posed included: (i) the import of the structural image of the participant for spatial pre-processing, (ii) the spatial registration of the optodes on the structural image of the infant, (iii) calculation of an accurate 3-layer segmentation of the structural image, (iv) creation of a high-density mesh as well as (v) the estimation of the NIRS optical sensitivity functions. To assess our results, we compared the values obtained for variational Free Energy (F), Bayesian Model Selection (BMS) and Bayesian Model Average (BMA) with the same set of possible models applied to both the fMRI and fNIRS datasets. We found high correspondence in F, BMS, and BMA between fMRI and fNIRS data, therefore showing for the first time high reliability of DCM applied to infant fNIRS data

  17. Simplified one-pot synthesis of [.sup.18F]SFB for radiolabeling

    DOEpatents

    Olma, Sebastian; Shen, Clifton Kwang-Fu

    2015-08-04

    A non-aqueous single pot synthesis of [.sup.18F]SFB is set forth. The [.sup.18F]SFB produced with this method is then used, for example, to label a peptide or an engineered antibody fragment (diabody) targeting human epidermal growth factor receptor 2 (HER2) as representative examples of labeled compounds for use as an injectable composition to locate abnormal tissue, specifically tumors within an animal or human using a PET scan.

  18. Simplified one-pot synthesis of [.sup.18F]SFB for radiolabeling

    DOEpatents

    Olma, Sebastian; Shen, Clifton Kwang-Fu

    2013-07-16

    A non-aqueous single pot synthesis of [.sup.18F]SFB is set forth. The [.sup.18F]SFB produced with this method is then used, for example, to label a peptide or an engineered antibody fragment (diabody) targeting human epidermal growth factor receptor 2 (HER2) as representative examples of labeled compounds for use as an injectable composition to locate abnormal tissue, specifically tumors within an animal or human using a PET scan.

  19. Measurement of direct f0(980) photoproduction on the proton.

    PubMed

    Battaglieri, M; De Vita, R; Szczepaniak, A P; Adhikari, K P; Aghasyan, M; Amaryan, M J; Ambrozewicz, P; Anghinolfi, M; Asryan, G; Avakian, H; Bagdasaryan, H; Baillie, N; Ball, J P; Baltzell, N A; Batourine, V; Bedlinskiy, I; Bellis, M; Benmouna, N; Berman, B L; Bibrzycki, L; Biselli, A S; Bookwalter, C; Bouchigny, S; Boiarinov, S; Bradford, R; Branford, D; Briscoe, W J; Brooks, W K; Bültmann, S; Burkert, V D; Calarco, J R; Careccia, S L; Carman, D S; Casey, L; Chen, S; Cheng, L; Clinton, E; Cole, P L; Collins, P; Crabb, D; Crannell, H; Crede, V; Cummings, J P; Dale, D; Daniel, A; Dashyan, N; De Masi, R; De Sanctis, E; Degtyarenko, P V; Deur, A; Dhamija, S; Dharmawardane, K V; Dickson, R; Djalali, C; Dodge, G E; Donnelly, J; Doughty, D; Dugger, M; Dzyubak, O P; Egiyan, H; Egiyan, K S; El Fassi, L; Elouadrhiri, L; Eugenio, P; Fedotov, G; Fersch, R; Forest, T A; Fradi, A; Gabrielyan, M Y; Gan, L; Garçon, M; Gasparian, A; Gavalian, G; Gevorgyan, N; Gilfoyle, G P; Giovanetti, K L; Girod, F X; Glamazdin, O; Goett, J; Goetz, J T; Gohn, W; Golovatch, E; Gordon, C I O; Gothe, R W; Graham, L; Griffioen, K A; Guidal, M; Guler, N; Guo, L; Gyurjyan, V; Hadjidakis, C; Hafidi, K; Hakobyan, H; Hakobyan, R S; Hanretty, C; Hardie, J; Hassall, N; Heddle, D; Hersman, F W; Hicks, K; Hleiqawi, I; Holtrop, M; Hyde, C E; Ilieva, Y; Ireland, D G; Ishkhanov, B S; Isupov, E L; Ito, M M; Jenkins, D; Jo, H S; Johnstone, J R; Joo, K; Juengst, H G; Kageya, T; Kalantarians, N; Keller, D; Kellie, J D; Khandaker, M; Khetarpal, P; Kim, W; Klein, A; Klein, F J; Klimenko, A V; Konczykowski, P; Kossov, M; Krahn, Z; Kramer, L H; Kubarovsky, V; Kuhn, J; Kuhn, S E; Kuleshov, S V; Kuznetsov, V; Lachniet, J; Laget, J M; Langheinrich, J; Lawrence, D; Lee, T; Lesniak, L; Li, Ji; Livingston, K; Lowry, M; Lu, H Y; Maccormick, M; Malace, S; Markov, N; Mattione, P; McCracken, M E; McKinnon, B; Mecking, B A; Melone, J J; Mestayer, M D; Meyer, C A; Mibe, T; Mikhailov, K; Mineeva, T; Minehart, R; Mirazita, M; Miskimen, R; Mochalov, V; Mokeev, V; Moreno, B; Moriya, K; Morrow, S A; Moteabbed, M; Munevar, E; Mutchler, G S; Nadel-Turonski, P; Nakagawa, I; Nasseripour, R; Niccolai, S; Niculescu, G; Niculescu, I; Niczyporuk, B B; Niroula, M R; Niyazov, R A; Nozar, M; Osipenko, M; Ostrovidov, A I; Park, K; Park, S; Pasyuk, E; Paris, M; Paterson, C; Pereira, S Anefalos; Pierce, J; Pivnyuk, N; Pocanic, D; Pogorelko, O; Pozdniakov, S; Price, J W; Prok, Y; Protopopescu, D; Raue, B A; Riccardi, G; Ricco, G; Ripani, M; Ritchie, B G; Rosner, G; Rossi, P; Sabatié, F; Saini, M S; Salamanca, J; Salgado, C; Sandorfi, A; Santoro, J P; Sapunenko, V; Schott, D; Schumacher, R A; Serov, V S; Sharabian, Y G; Sharov, D; Shvedunov, N V; Smith, E S; Smith, L C; Sober, D I; Sokhan, D; Starostin, A; Stavinsky, A; Stepanyan, S; Stepanyan, S S; Stokes, B E; Stoler, P; Stopani, K A; Strakovsky, I I; Strauch, S; Taiuti, M; Tedeschi, D J; Teymurazyan, A; Tkabladze, A; Tkachenko, S; Todor, L; Tur, C; Ungaro, M; Vineyard, M F; Vlassov, A V; Watts, D P; Wei, X; Weinstein, L B; Weygand, D P; Williams, M; Wolin, E; Wood, M H; Yegneswaran, A; Yurov, M; Zana, L; Zhang, J; Zhao, B; Zhao, Z W

    2009-03-13

    We report on the results of the first measurement of exclusive f_{0}(980) meson photoproduction on protons for E_{gamma}=3.0-3.8 GeV and -t=0.4-1.0 GeV2. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. The resonance was detected via its decay in the pi;{+}pi;{-} channel by performing a partial wave analysis of the reaction gammap-->ppi;{+}pi;{-}. Clear evidence of the f_{0}(980) meson was found in the interference between P and S waves at M_{pi;{+}pi;{-}} approximately 1 GeV. The S-wave differential cross section integrated in the mass range of the f_{0}(980) was found to be a factor of about 50 smaller than the cross section for the rho meson. This is the first time the f_{0}(980) meson has been measured in a photoproduction experiment.

  20. Measurement of Direct f0(980) Photoproduction on the Proton

    NASA Astrophysics Data System (ADS)

    Battaglieri, M.; de Vita, R.; Szczepaniak, A. P.; Adhikari, K. P.; Aghasyan, M.; Amaryan, M. J.; Ambrozewicz, P.; Anghinolfi, M.; Asryan, G.; Avakian, H.; Bagdasaryan, H.; Baillie, N.; Ball, J. P.; Baltzell, N. A.; Batourine, V.; Bedlinskiy, I.; Bellis, M.; Benmouna, N.; Berman, B. L.; Bibrzycki, L.; Biselli, A. S.; Bookwalter, C.; Bouchigny, S.; Boiarinov, S.; Bradford, R.; Branford, D.; Briscoe, W. J.; Brooks, W. K.; Bültmann, S.; Burkert, V. D.; Calarco, J. R.; Careccia, S. L.; Carman, D. S.; Casey, L.; Chen, S.; Cheng, L.; Clinton, E.; Cole, P. L.; Collins, P.; Crabb, D.; Crannell, H.; Crede, V.; Cummings, J. P.; Dale, D.; Daniel, A.; Dashyan, N.; de Masi, R.; de Sanctis, E.; Degtyarenko, P. V.; Deur, A.; Dhamija, S.; Dharmawardane, K. V.; Dickson, R.; Djalali, C.; Dodge, G. E.; Donnelly, J.; Doughty, D.; Dugger, M.; Dzyubak, O. P.; Egiyan, H.; Egiyan, K. S.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fedotov, G.; Fersch, R.; Forest, T. A.; Fradi, A.; Gabrielyan, M. Y.; Gan, L.; Garçon, M.; Gasparian, A.; Gavalian, G.; Gevorgyan, N.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Glamazdin, O.; Goett, J.; Goetz, J. T.; Gohn, W.; Golovatch, E.; Gordon, C. I. O.; Gothe, R. W.; Graham, L.; Griffioen, K. A.; Guidal, M.; Guler, N.; Guo, L.; Gyurjyan, V.; Hadjidakis, C.; Hafidi, K.; Hakobyan, H.; Hakobyan, R. S.; Hanretty, C.; Hardie, J.; Hassall, N.; Heddle, D.; Hersman, F. W.; Hicks, K.; Hleiqawi, I.; Holtrop, M.; Hyde, C. E.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Ito, M. M.; Jenkins, D.; Jo, H. S.; Johnstone, J. R.; Joo, K.; Juengst, H. G.; Kageya, T.; Kalantarians, N.; Keller, D.; Kellie, J. D.; Khandaker, M.; Khetarpal, P.; Kim, W.; Klein, A.; Klein, F. J.; Klimenko, A. V.; Konczykowski, P.; Kossov, M.; Krahn, Z.; Kramer, L. H.; Kubarovsky, V.; Kuhn, J.; Kuhn, S. E.; Kuleshov, S. V.; Kuznetsov, V.; Lachniet, J.; Laget, J. M.; Langheinrich, J.; Lawrence, D.; Lee, T.; Lesniak, L.; Li, Ji; Livingston, K.; Lowry, M.; Lu, H. Y.; MacCormick, M.; Malace, S.; Markov, N.; Mattione, P.; McCracken, M. E.; McKinnon, B.; Mecking, B. A.; Melone, J. J.; Mestayer, M. D.; Meyer, C. A.; Mibe, T.; Mikhailov, K.; Mineeva, T.; Minehart, R.; Mirazita, M.; Miskimen, R.; Mochalov, V.; Mokeev, V.; Moreno, B.; Moriya, K.; Morrow, S. A.; Moteabbed, M.; Munevar, E.; Mutchler, G. S.; Nadel-Turonski, P.; Nakagawa, I.; Nasseripour, R.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Niczyporuk, B. B.; Niroula, M. R.; Niyazov, R. A.; Nozar, M.; Osipenko, M.; Ostrovidov, A. I.; Park, K.; Park, S.; Pasyuk, E.; Paris, M.; Paterson, C.; Pereira, S. Anefalos; Pierce, J.; Pivnyuk, N.; Pocanic, D.; Pogorelko, O.; Pozdniakov, S.; Price, J. W.; Prok, Y.; Protopopescu, D.; Raue, B. A.; Riccardi, G.; Ricco, G.; Ripani, M.; Ritchie, B. G.; Rosner, G.; Rossi, P.; Sabatié, F.; Saini, M. S.; Salamanca, J.; Salgado, C.; Sandorfi, A.; Santoro, J. P.; Sapunenko, V.; Schott, D.; Schumacher, R. A.; Serov, V. S.; Sharabian, Y. G.; Sharov, D.; Shvedunov, N. V.; Smith, E. S.; Smith, L. C.; Sober, D. I.; Sokhan, D.; Starostin, A.; Stavinsky, A.; Stepanyan, S.; Stepanyan, S. S.; Stokes, B. E.; Stoler, P.; Stopani, K. A.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tedeschi, D. J.; Teymurazyan, A.; Tkabladze, A.; Tkachenko, S.; Todor, L.; Tur, C.; Ungaro, M.; Vineyard, M. F.; Vlassov, A. V.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Weygand, D. P.; Williams, M.; Wolin, E.; Wood, M. H.; Yegneswaran, A.; Yurov, M.; Zana, L.; Zhang, J.; Zhao, B.; Zhao, Z. W.

    2009-03-01

    We report on the results of the first measurement of exclusive f0(980) meson photoproduction on protons for Eγ=3.0-3.8GeV and -t=0.4-1.0GeV2. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. The resonance was detected via its decay in the π+π- channel by performing a partial wave analysis of the reaction γp→pπ+π-. Clear evidence of the f0(980) meson was found in the interference between P and S waves at Mπ+π-˜1GeV. The S-wave differential cross section integrated in the mass range of the f0(980) was found to be a factor of about 50 smaller than the cross section for the ρ meson. This is the first time the f0(980) meson has been measured in a photoproduction experiment.

  1. Psychopathy Factor Interactions and Co-Occurring Psychopathology: Does Measurement Approach Matter?

    PubMed Central

    Hunt, Elizabeth; Bornovalova, Marina A.; Kimonis, Eva R.; Lilienfeld, Scott O.; Poythress, Norman G.

    2014-01-01

    The two dimensions of psychopathy as operationalized by various measurement tools show differential associations with psychopathology; however, evidence suggests that the statistical interaction of Factor 1 (F1) and Factor 2 (F2) may be important in understanding associations with psychopathology. Findings regarding the interactive effects of F1 and F2 are mixed, as both potentiating and protective effects have emerged. Moreover, approaches to measuring F1 (e.g. clinical interview versus self-report) are based on different conceptualizations of F1, which may influence the interactive effects. The current study aims to 1) elucidate the influence of F1 and F2 on psychopathology by using both variable-centered and person-centered approaches and 2) determine if the measurement of F1 influences the interactive effects of F1 and F2 by comparing the strength of interactive effects across F1 measures in a sample of over 1,500 offenders. Across analytic methods, there were very few cases in which F1 statistically influenced the association between F2 and psychopathology, such that F1 failed to evidence either potentiating or protective effects on F2. Furthermore, the conceptualization of F1 across psychopathy measures did not impact the interactive effects of F1 and F2. These findings suggest that F2 is probably driving the relations between psychopathy and other forms of psychopathology, and that F1 may play less of a role in interacting with F2 than previously believed. PMID:25580612

  2. NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR.

    PubMed

    Kainulainen, Markus; Lau, Simone; Samuel, Charles E; Hornung, Veit; Weber, Friedemann

    2016-07-01

    Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we demonstrate that NSs

  3. NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR

    PubMed Central

    Kainulainen, Markus; Lau, Simone; Samuel, Charles E.; Hornung, Veit

    2016-01-01

    ABSTRACT Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. IMPORTANCE Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we

  4. Influence of the Size and Structural Factors on the Magnetism of Multilayer Films Based on 3 d and 4 f Metals

    NASA Astrophysics Data System (ADS)

    Svalov, A. V.; Vas'kovskiy, V. O.; Kurlyandskaya, G. V.

    2017-12-01

    This work has presented some data on the layer structuring of films of 3 d and 4 f metals and their alloys, which have potential for practical use in magnetic sensors. The decrease in the thickness of magnetic layers with this structuring entails natural worsening of the crystallinity and leads to a degradation of magnetic ordering. However, the manifestation of these tendencies depends to a great extent on the conditions of preparation, the composition, and the sequence of the deposition of the contacting layers in the multilayer structures. The combination of these factors makes it possible to realize an optimum composition and optimum structural states of the films, which in a number of cases lead to the appearance of new combinations of functional properties.

  5. What Does f[subscript xx]f[subscript yy] - f[superscript 2][subscript xy] Greater than 0 "Really" Mean?

    ERIC Educational Resources Information Center

    McCartin, Brian J.

    2008-01-01

    This note presents geometric and physical interpretations of the sufficient condition for a critical point to be a strict relative extremum: f[subscript xx]f[subscript yy] - f[superscript 2][subscript xy] greater than 0. The role of the double derivative f[subscript xy] in this inequality will be highlighted in these interpretations. (Contains 14…

  6. Seasonal and Solar Activity Variations of f3 Layer and StF-4 F-Layer Quadruple Stratification) Near the Equatorial Region

    NASA Astrophysics Data System (ADS)

    Tardelli, A.; Fagundes, P. R.; Pezzopane, M.; Kavutarapu, V.

    2016-12-01

    The ionospheric F-layer shape and electron density peak variations depend on local time, latitude, longitude, season, solar cycle, geomagnetic activity, and electrodynamic conditions. In particular, the equatorial and low latitude F-layer may change its shape and peak height in a few minutes due to electric fields induced by propagation of medium-scale traveling ionospheric disturbances (MSTIDs) or thermospheric - ionospheric coupling. This F-layer electrodynamics feature characterizing the low latitudes is one of the most remarkable ionospheric physics research field. The study of multiple-stratification of the F-layer has the initial records in the mid of the 20th century. Since then, many studies were focused on F3 layer. The diurnal, seasonal and solar activity variations of the F3 layer characteristics have been investigated by several researchers. Recently, investigations on multiple-stratifications of F-layer received an important boost after the quadruple stratification (StF-4) was observed at Palmas (10.3°S, 48.3°W; dip latitude 5.5°S - near equatorial region), Brazil (Tardelli & Fagundes, JGR, 2015). This study present the latest findings related with the seasonal and solar activity characteristics of the F3 layer and StF-4 near the equatorial region during the period from 2002 to 2006. A significant connection between StF-4 and F3 layer has been noticed, since the StF-4 is always preceded and followed by an F3 layer appearance. However, the F3 layer and StF-4 present different seasonal and solar cycle variations. At a near equatorial station Palmas, the F3 layer shows the maximum and minimum occurrence during summer and winter seasons respectively. On the contrary, the StF-4 presents the maximum and minimum occurrence during winter and summer seasons respectively. While the F3 layer occurrence is not affected by solar cycle, the StF-4 appearance is instead more frequent during High Solar Activity (HSA).

  7. High susceptibility prevalence for F4+ and F18+Escherichia coli in Flemish pigs.

    PubMed

    Nguyen, Ut V; Coddens, Annelies; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Poucke, Mario Van; Peelman, Luc; Cox, Eric

    2017-04-01

    F4 and/or F18 enterotoxigenic Escherichia coli (F4 + /F18 + ETEC) are responsible for diarrhea while F18 + verotoxigenic E. coli (F18 + VTEC) cause edema disease in pigs. Both infections can result in severe economic losses, which are mainly the result of the medication, growth retardation and mortality. The susceptibility of piglets to these pathogens is determined by the presence of F4 and F18 receptors (F4R and F18R). Understanding the composition of the susceptibility phenotypes of pigs is useful for animal health and breeding management. This study aimed to determine the prevalence of the F4 ETEC susceptibility phenotypes and F18 + E. coli susceptibility among Flemish pig breeds by using the in vitro villous adhesion assay. In this study, seven F4 ETEC susceptibility phenotypes were found, namely A (F4 ab R + , ac R + , ad R + ; 59.16%), B (F4 ab R + , ac R + , ad R - ; 6.28%), C (F4 ab R + , ac R - , ad R + ; 2.62%), D (F4 ab R - , ac R - , ad R + ; 6.28%), E (F4 ab R - , ac R - , ad R - ; 24.08%), F (F4 ab R + , ac R - , ad R - ; 1.05%) and G (F4 ab R - , ac R + , ad R - ; 0.52%). F4ab and F4ac E. coli showed a stronger degree of adhesion to the intestinal villi (53.40% and 52.88% strong adhesion, respectively), compared to F4ad E. coli (43.46% strong adhesion). Furthermore, the correlation between F4ac and F4ab adhesion was higher (r=0.78) than between F4ac and F4ad adhesion (r=0.41) and between F4ab and F4ad adhesion (r=0.57). For F18 + E. coli susceptibility, seven out of 82 pigs were F18R negative (8.54%), but only two of these seven pigs (2.44%) were also negative for F4R. As such, the chance to identify a pig that is positive for a F4 ETEC variant or F18 + E. coli is 97.56%. Therefore, significant economic losses will arise due to F4 + and/or F18 + E. coli infections in the Flemish pig population due to the high susceptibility prevalence. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. The Regulation of Vascular Endothelial Growth Factor by Hypoxia and Prostaglandin F2α during Human Endometrial Repair

    PubMed Central

    Maybin, Jacqueline A.; Hirani, Nikhil; Brown, Pamela; Jabbour, Henry N.

    2011-01-01

    Context: The human endometrium has an exceptional capacity for repeated repair after menses, but its regulation remains undefined. Premenstrually, progesterone levels fall and prostaglandin (PG) F2α synthesis increases, causing spiral arteriole constriction. We hypothesized that progesterone withdrawal, PGF2α, and hypoxia increase vascular endothelial growth factor (VEGF), an endometrial repair factor. Design and Results: Endometrial biopsies were collected (n = 47) with ethical approval and consent. VEGF mRNA, quantified by quantitative RT-PCR, was increased during menstruation (P < 0.01).VEGF protein was maximally secreted from proliferative endometrial explants. Treatment of an endometrial epithelial cell line and primary human endometrial stromal cells with 100 nm PGF2α or hypoxia (0.5% O2) resulted in significant increases in VEGF mRNA and protein. VEGF was maximal when cells were cotreated with PGF2α and hypoxia simultaneously (P < 0.05–0.001). Secretory-phase endometrial explants also showed an increase in VEGF with cotreatment (P < 0.05). However, proliferative-phase explants showed no increase in VEGF on treatment with PGF2α and/or hypoxia. Proliferative tissue was induced to increase VEGF mRNA expression when exposed to progesterone and its withdrawal in vitro but only in the presence of hypoxia and PG. Hypoxia-inducible factor-1α (HIF-1α) silencing with RNA interference suppressed hypoxia-induced VEGF expression in endometrial cells but did not alter PGF2α-induced VEGF expression. Conclusions: Endometrial VEGF is increased at the time of endometrial repair. Progesterone withdrawal, PGF2α, and hypoxia are necessary for this perimenstrual VEGF expression. Hypoxia acts via HIF-1α to increase VEGF, whereas PGF2α acts in a HIF-1α-independent manner. Hence, two pathways regulate the expression of VEGF during endometrial repair. PMID:21677035

  9. The SigF Regulon in Mycobacterium smegmatis Reveals Roles in Adaptation to Stationary Phase, Heat, and Oxidative Stress▿ ‡

    PubMed Central

    Hümpel, Anja; Gebhard, Susanne; Cook, Gregory M.; Berney, Michael

    2010-01-01

    SigF is an alternative sigma factor that is highly conserved among species of the genus Mycobacterium. In this study we identified the SigF regulon in Mycobacterium smegmatis using whole-genome microarray and promoter consensus analyses. In total, 64 genes in exponential phase and 124 genes in stationary phase are SigF dependent (P < 0.01, >2-fold expression change). Our experimental data reveal the SigF-dependent promoter consensus GTTT-N(15-17)-GGGTA for M. smegmatis, and we propose 130 potential genes under direct control of SigF, of which more than 50% exhibited reduced expression in a ΔsigF strain. We previously reported an increased susceptibility of the ΔsigF strain to heat and oxidative stress, and our expression data indicate a molecular basis for these phenotypes. We observed SigF-dependent expression of several genes purportedly involved in oxidative stress defense, namely, a heme-containing catalase, a manganese-containing catalase, a superoxide dismutase, the starvation-induced DNA-protecting protein MsDps1, and the biosynthesis genes for the carotenoid isorenieratene. Our data suggest that SigF regulates the biosynthesis of the thermoprotectant trehalose, as well as an uptake system for osmoregulatory compounds, and this may explain the increased heat susceptibility of the ΔsigF strain. We identified the regulatory proteins SigH3, PhoP, WhiB1, and WhiB4 as possible genes under direct control of SigF and propose four novel anti-sigma factor antagonists that could be involved in the posttranslational regulation of SigF in M. smegmatis. This study emphasizes the importance of this sigma factor for stationary-phase adaptation and stress response in mycobacteria. PMID:20233930

  10. Vector and Axial Form Factors Applied to Neutrino Quasielastic Scattering

    NASA Astrophysics Data System (ADS)

    Budd, H.; Bodek, A.; Arrington, J.

    2005-02-01

    We calculate the quasielastic cross sections for neutrino scattering on nucleons using up to date fits to the nucleon elastic electromagnetic form factors GEp, GEn, GMp, GMn, and weak form factors. We show the extraction of F(q). We show the that F(q) has a different contribution to the anti-neutrino cross section, and how the anti-neutrino data can be used to check F(q) extracted from neutrino scattering. (Presented by Howard Budd at NuInt04, Mar. 2004, Laboratori Nazionali del Gran Sasso - INFN - Assergi, Italy [ http://nuint04.lngs.infn.it/])

  11. ''1/f noise'' in music: Music from 1/f noise

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

    Voss, R.F.; Clarke, J.

    1978-01-01

    The spectral density of fluctuations in the audio power of many musical selections and of English speech varies approximately as 1/f (f is the frequency) down to a frequency of 5 x 10/sup -4/ Hz. This result implies that the audio-power fluctuations are correlated over all times in the same manner as ''1/f noise'' in electronic components. The frequency fluctuations of music also have a 1/f spectral density at frequencies down to the inverse of the length of the piece of music. The frequency fluctuations of English speech have a quite different behavior, with a single characteristic time of aboutmore » 0.1 s, the average length of a syllable. The observations on music suggest that 1/f noise is a good choice for stochastic composition. Compositions in which the frequency and duration of each note were determined by 1/f noise sources sounded pleasing. Those generated by white-noise sources sounded too random, while those generated by 1/f/sup 2/ noise sounded too correlated.« less

  12. Prognostic stratification model for patients with stage I non-small cell lung cancer adenocarcinoma treated with surgical resection without adjuvant therapies using metabolic features measured on F-18 FDG PET and postoperative pathologic factors.

    PubMed

    Kang, Yeon-Koo; Song, Yoo Sung; Cho, Sukki; Jheon, Sanghoon; Lee, Won Woo; Kim, Kwhanmien; Kim, Sang Eun

    2018-05-01

    In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SUL max ) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SUL max on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SUL max  ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SUL max> 1.9 and observed STAS. This model exhibited significant predictive power for RFS. We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Improving the Optical Quality Factor of the WGM Resonator

    NASA Technical Reports Server (NTRS)

    Savchenkov, Anatoliy; Matsko, Andrey; Iltchenko, Vladimir

    2008-01-01

    Resonators usually are characterized with two partially dependent values: finesse (F) and quality factor (Q). The finesse of an empty Fabry-Perot (FP) resonator is defined solely by the quality of its mirrors and is calculated as F=piR(exp 1/2)/(1-R). The maximum up-to-date value of reflectivity R approximately equal to 1 - 1.6 x 10(exp -6) is achieved with dielectric mirrors. An FP resonator made with the mirrors has finesse F=1.9 x 10(exp 6). Further practical increase of the finesse of FP resonators is problematic because of the absorption and the scattering of light in the mirror material through fundamental limit on the reflection losses given by the internal material losses and by thermodynamic density fluctuations on the order of parts in 109. The quality factor of a resonator depends on both its finesse and its geometrical size. A one-dimensional FP resonator has Q=2 F L/lambda, where L is the distance between the mirrors and lambda is the wavelength. It is easy to see that the quality factor of the resonator is unlimited because L is unlimited. F and Q are equally important. In some cases, finesse is technically more valuable than the quality factor. For instance, buildup of the optical power inside the resonator, as well as the Purcell factor, is proportional to finesse. Sometimes, however, the quality factor is more valuable. For example, inverse threshold power of intracavity hyperparametric oscillation is proportional to Q(exp 2) and efficiency of parametric frequency mixing is proportional to Q(exp 3). Therefore, it is important to know both the maximally achievable finesse and quality factor values of a resonator. Whispering gallery mode (WGM) resonators are capable of achieving larger finesse compared to FP resonators. For instance, fused silica resonators with finesse 2.3 x 10(exp 6) and 2.8 x 10(exp 6) have been demonstrated. Crystalline WGM resonators reveal even larger finesse values, F=6.3 x 10(exp 6), because of low attenuation of light in the

  14. CHClF/sub 2/ (F-22) in the earth's atmosphere

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

    Rasmussen, R.A.; Khalil, M.A.K.; Penkett, S.A.

    1980-10-01

    Recent global measurements of CHClF/sub 2/ (F-22) are reported. Originally, GC/MS techniques were used to obtain these data. Since then, significant advances using an O/sub 2/-doped electron capture detector have been made in the analytical techniques, so that F-22 can be measured by EC/GC methods at ambient concentrations. The atmospheric burden of F-22 calculated from these measurements (average mixing ratio, mid-1979, approx.45 pptv) is considerably greater than that expected from the estimates of direct industrial emissions (average mixing ratio, mid-1979, approx.30 pptv). This difference is probably due to underestimates of F-22 emissions.

  15. Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

    PubMed

    de Moerloose, P; Schved, J-F; Nugent, D

    2016-07-01

    Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

  16. ATLAS F MISSILE FIELDS IN THE UNITED STATES, ATLAS F ...

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

    ATLAS F MISSILE FIELDS IN THE UNITED STATES, ATLAS F- TEXAS RING OF TWELVE - Dyess Air Force Base, Atlas F Missle Site S-8, Approximately 3 miles east of Winters, 500 feet southwest of Highway 177, Winters, Runnels County, TX

  17. Spread-F occurrences and relationships with foF2 and h'F at low- and mid-latitudes in China

    NASA Astrophysics Data System (ADS)

    Wang, Ning; Guo, Lixin; Zhao, Zhenwei; Ding, Zonghua; Lin, Leke

    2018-04-01

    Ionospheric irregularities are an important phenomenon in scientific studies and applications of radio-wave propagation. Spread-F echoes in ionograms are a type of high-frequency band irregularities that include frequency spread-F (FSF), range spread-F (RSF), and mixed spread-F (MSF) events. In this study, we obtained spread-F data from four ionosondes at low- and mid-latitudes near the 120°E chain in China during the 23rd solar cycle. We used these data to investigate spread-F occurrence percentages and variations with local time, season, latitude, and solar activity. The four ionosondes were located at Haikou (HK) (20°N, 110.34°E), Guangzhou (GZ) (23.14°N, 113.36°E), Beijing (BJ) (40.11°N, 116.28°E), and Changchun (CC) (43.84°N, 125.28°E). We also present possible correlations between spread-Fs and other ionospheric parameters, such as the critical frequency of the F2-layer (foF2) and the virtual height of the bottom-side F-layer (h'F). In particular, we investigated the possible threshold of the foF2 affecting the FSF and the relationship between the h'F and the RSF. The main conclusions are as follows: (a) the FSF occurrence percentages were anti-correlated with solar activity at all four sites; meanwhile, RSF occurrence rates increased with the increase in solar activity at HK, but not at the other three sites; (b) FSF occurrence rates were larger at the mid-latitudes than expected, while FSFs occurred more often after midnight; (c) the highest FSF occurrence rates mostly appeared during the summer months, while RSFs occurred mostly in the equinoctial months of 2000-2002 at HK and GZ; (d) a lower foF2 was suitable for FSF events; nevertheless, h'F and RSF occurrences satisfied the parabolic relationship; (e) the foF2 thresholds for FSFs were 15, 14, 7.6, and 7.8 MHz at HK, GZ, BJ, and CC, respectively. The h'Fs occurring between 240 and 290 km were more favorable for RSF occurrences. These results are important for understanding ionospheric

  18. Comparison of ionospheric F2 peak parameters foF2 and hmF2 with IRI2001 at Hainan

    NASA Astrophysics Data System (ADS)

    Wang, X.; Shi, J. K.; Wang, G. J.; Gong, Y.

    2009-06-01

    Monthly median values of foF2, hmF2 and M(3000)F2 parameters, with quarter-hourly time interval resolution for the diurnal variation, obtained with DPS4 digisonde at Hainan (19.5°N, 109.1°E; Geomagnetic coordinates: 178.95°E, 8.1°N) are used to investigate the low-latitude ionospheric variations and comparisons with the International Reference Ionosphere (IRI) model predictions. The data used for the present study covers the period from February 2002 to April 2007, which is characterized by a wide range of solar activity, ranging from high solar activity (2002) to low solar activity (2007). The results show that (1) Generally, IRI predictions follow well the diurnal and seasonal variation patterns of the experimental values of foF2, especially in the summer of 2002. However, there are systematic deviation between experimental values and IRI predictions with either CCIR or URSI coefficients. Generally IRI model greatly underestimate the values of foF2 from about noon to sunrise of next day, especially in the afternoon, and slightly overestimate them from sunrise to about noon. It seems that there are bigger deviations between IRI Model predictions and the experimental observations for the moderate solar activity. (2) Generally the IRI-predicted hmF2 values using CCIR M(3000)F2 option shows a poor agreement with the experimental results, but there is a relatively good agreement in summer at low solar activity. The deviation between the IRI-predicted hmF2 using CCIR M(3000)F2 and observed hmF2 is bigger from noon to sunset and around sunrise especially at high solar activity. The occurrence time of hmF2 peak (about 1200 LT) of the IRI model predictions is earlier than that of observations (around 1500 LT). The agreement between the IRI hmF2 obtained with the measured M(3000)F2 and the observed hmF2 is very good except that IRI overestimates slightly hmF2 in the daytime in summer at high solar activity and underestimates it in the nighttime with lower values near

  19. F-104 in flight

    NASA Technical Reports Server (NTRS)

    1988-01-01

    F-104G (N826NA) in flight over the Mojave Desert in January 1988. This aircraft was the last of eleven F-104s delivered to the Dryden Flight Research Center over a period of four decades. The initial group of four (a YF-104A, two F-104As and a two-seat F-104B) arrived between August 1956 and December 1959. One of the F-104As was returned to the Air Force in 1961, and the other was lost in a non-fatal accident in 1962. To support X-15 activities, three special F-104Ns went to NASA in 1963. One crashed in the XB-70 midair collision, and it was replaced by an F-104A/G. (This was an F-104A modified to a G configuration.) As the initial F-104 fleet aged, a pair of two-seat TF-104Gs and a single-seat F-104G joined the Dryden inventory in June 1975. F-104G N826NA, shown in the photo, was one of these. Between 1975 and 1990, the older F-104s were retired - the YF-104A in November 1975, the F-104A/G in June 1977, the F-104B in June 1983, and the two F-104Ns in January 1987 and October 1990. As the F-104s phased out, the replacement F-18s started arriving at Dryden in 1984. F-104s N826NA made its 1,415th and last flight on February 3, 1994. The last two TF-104s ended service in September 1995, ending a 39 year involvement with the aircraft by the NACA and NASA.

  20. Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families.

    PubMed

    Colakoglu, Seyma; Bayhan, Turan; Tavil, Betül; Keskin, Ebru Yılmaz; Cakir, Volkan; Gümrük, Fatma; Çetin, Mualla; Aytaç, Selin; Berber, Ergul

    2018-01-01

    Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients' families. Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients' F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson's correlation coefficient and the nonparametric Mann-Whitney test. Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues with high fibrinolytic activity.

  1. Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families

    PubMed Central

    Colakoglu, Seyma; Bayhan, Turan; Tavil, Betül; Keskin, Ebru Yılmaz; Cakir, Volkan; Gümrük, Fatma; Çetin, Mualla; Aytaç, Selin; Berber, Ergul

    2018-01-01

    Background Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients’ families. Material and methods Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients’ F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson’s correlation coefficient and the nonparametric Mann-Whitney test. Results Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. Discussion Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues

  2. Structural, spectroscopic and cytotoxicity studies of TbF3@CeF3 and TbF3@CeF3@SiO2 nanocrystals.

    PubMed

    Grzyb, Tomasz; Runowski, Marcin; Dąbrowska, Krystyna; Giersig, Michael; Lis, Stefan

    2013-01-01

    Terbium fluoride nanocrystals, covered by a shell, composed of cerium fluoride were synthesized by a co-precipitation method. Their complex structure was formed spontaneously during the synthesis. The surface of these core/shell nanocrystals was additionally modified by silica. The properties of TbF 3 @CeF 3 and TbF 3 @CeF 3 @SiO 2 nanocrystals, formed in this way, were investigated. Spectroscopic studies showed that the differences between these two groups of products resulted from the presence of the SiO 2 shell. X-ray diffraction patterns confirmed the trigonal crystal structure of TbF 3 @CeF 3 nanocrystals. High resolution transmission electron microscopy in connection with energy-dispersive X-ray spectroscopy showed a complex structure of the formed nanocrystals. Crystallized as small discs, 'the products', with an average diameter around 10 nm, showed an increase in the concentration of Tb 3+ ions from surface to the core of nanocrystals. In addition to photo-physical analyses, cytotoxicity studies were performed on HSkMEC (Human Skin Microvascular Endothelial Cells) and B16F0 mouse melanoma cancer cells. The cytotoxicity of the nanomaterials was neutral for the investigated cells with no toxic or antiproliferative effect in the cell cultures, either for normal or for cancer cells. This fact makes the obtained nanocrystals good candidates for biological applications and further modifications of the SiO 2 shell. .

  3. Structural, spectroscopic and cytotoxicity studies of TbF3@CeF3 and TbF3@CeF3@SiO2 nanocrystals

    NASA Astrophysics Data System (ADS)

    Grzyb, Tomasz; Runowski, Marcin; Dąbrowska, Krystyna; Giersig, Michael; Lis, Stefan

    2013-10-01

    Terbium fluoride nanocrystals, covered by a shell, composed of cerium fluoride were synthesized by a co-precipitation method. Their complex structure was formed spontaneously during the synthesis. The surface of these core/shell nanocrystals was additionally modified by silica. The properties of TbF3@CeF3 and TbF3@CeF3@SiO2 nanocrystals, formed in this way, were investigated. Spectroscopic studies showed that the differences between these two groups of products resulted from the presence of the SiO2 shell. X-ray diffraction patterns confirmed the trigonal crystal structure of TbF3@CeF3 nanocrystals. High resolution transmission electron microscopy in connection with energy-dispersive X-ray spectroscopy showed a complex structure of the formed nanocrystals. Crystallized as small discs, `the products', with an average diameter around 10 nm, showed an increase in the concentration of Tb3+ ions from surface to the core of nanocrystals. In addition to photo-physical analyses, cytotoxicity studies were performed on HSkMEC (Human Skin Microvascular Endothelial Cells) and B16F0 mouse melanoma cancer cells. The cytotoxicity of the nanomaterials was neutral for the investigated cells with no toxic or antiproliferative effect in the cell cultures, either for normal or for cancer cells. This fact makes the obtained nanocrystals good candidates for biological applications and further modifications of the SiO2 shell.

  4. Validation of a Framework for Measuring Hospital Disaster Resilience Using Factor Analysis

    PubMed Central

    Zhong, Shuang; Clark, Michele; Hou, Xiang-Yu; Zang, Yuli; FitzGerald, Gerard

    2014-01-01

    Hospital disaster resilience can be defined as “the ability of hospitals to resist, absorb, and respond to the shock of disasters while maintaining and surging essential health services, and then to recover to its original state or adapt to a new one.” This article aims to provide a framework which can be used to comprehensively measure hospital disaster resilience. An evaluation framework for assessing hospital resilience was initially proposed through a systematic literature review and Modified-Delphi consultation. Eight key domains were identified: hospital safety, command, communication and cooperation system, disaster plan, resource stockpile, staff capability, disaster training and drills, emergency services and surge capability, and recovery and adaptation. The data for this study were collected from 41 tertiary hospitals in Shandong Province in China, using a specially designed questionnaire. Factor analysis was conducted to determine the underpinning structure of the framework. It identified a four-factor structure of hospital resilience, namely, emergency medical response capability (F1), disaster management mechanisms (F2), hospital infrastructural safety (F3), and disaster resources (F4). These factors displayed good internal consistency. The overall level of hospital disaster resilience (F) was calculated using the scoring model: F = 0.615F1 + 0.202F2 + 0.103F3 + 0.080F4. This validated framework provides a new way to operationalise the concept of hospital resilience, and it is also a foundation for the further development of the measurement instrument in future studies. PMID:24945190

  5. Neutral kaon mixing beyond the Standard Model with n f = 2 + 1 chiral fermions. Part 2: non perturbative renormalisation of the Δ F = 2 four-quark operators

    NASA Astrophysics Data System (ADS)

    Boyle, Peter A.; Garron, Nicolas; Hudspith, Renwick J.; Lehner, Christoph; Lytle, Andrew T.

    2017-10-01

    We compute the renormalisation factors ( Z-matrices) of the Δ F = 2 four-quark operators needed for Beyond the Standard Model (BSM) kaon mixing. We work with n f = 2+1 flavours of Domain-Wall fermions whose chiral-flavour properties are essential to maintain a continuum-like mixing pattern. We introduce new RI-SMOM renormalisation schemes, which we argue are better behaved compared to the commonly-used corresponding RI-MOM one. We find that, once converted to \\overline{MS} , the Z-factors computed through these RI-SMOM schemes are in good agreement but differ significantly from the ones computed through the RI-MOM scheme. The RI-SMOM Z-factors presented here have been used to compute the BSM neutral kaon mixing matrix elements in the companion paper [1]. We argue that the renormalisation procedure is responsible for the discrepancies observed by different collaborations, we will investigate and elucidate the origin of these differences throughout this work.

  6. Comparison of three dimeric 18F-AlF-NOTA-RGD tracers.

    PubMed

    Guo, Jinxia; Lang, Lixin; Hu, Shuo; Guo, Ning; Zhu, Lei; Sun, Zhongchan; Ma, Ying; Kiesewetter, Dale O; Niu, Gang; Xie, Qingguo; Chen, Xiaoyuan

    2014-04-01

    RGD peptide-based radiotracers are well established as integrin αvβ3 imaging probes to evaluate tumor angiogenesis or tissue remodeling after ischemia or infarction. In order to optimize the labeling process and pharmacokinetics of the imaging probes, we synthesized three dimeric RGD peptides with or without PEGylation and performed in vivo screening. Radiolabeling was achieved through the reaction of F-18 aluminum-fluoride complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Three imaging probes were synthesized as (18)F-AlF-NOTA-E[c(RGDfK)]2, (18)F-AlF-NOTA-PEG4-E[c(RGDfK)]2, and (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2. The receptor binding affinity was determined by competitive cell binding assay, and the stability was evaluated by mouse serum incubation. Tumor uptake and whole body distribution of the three tracers were compared through direct tissue sampling and PET quantification of U87MG tumor-bearing mice. All three compounds remained intact after 120 min incubation with mouse serum. They all had a rapid and relatively high tracer uptake in U87MG tumors with good target-to-background ratios. Compared with the other two tracers, (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2 had the highest tumor uptake and the lowest accumulation in the liver. The integrin receptor specificity was confirmed by co-injection of unlabeled dimeric RGD peptide. The rapid one-step radiolabeling strategy by the complexation of (18)F-aluminum fluoride with NOTA-peptide conjugates was successfully applied to synthesize three dimeric RGD peptides. Among the three probes developed, (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2 with relatively low liver uptake and high tumor accumulation appears to be a promising candidate for further translational research.

  7. Clostridium botulinum strains producing BoNT/F4 or BoNT/F5.

    PubMed

    Raphael, Brian H; Bradshaw, Marite; Kalb, Suzanne R; Joseph, Lavin A; Lúquez, Carolina; Barr, John R; Johnson, Eric A; Maslanka, Susan E

    2014-05-01

    Botulinum neurotoxin type F (BoNT/F) may be produced by Clostridium botulinum alone or in combination with another toxin type such as BoNT/A or BoNT/B. Type F neurotoxin gene sequences have been further classified into seven toxin subtypes. Recently, the genome sequence of one strain of C. botulinum (Af84) was shown to contain three neurotoxin genes (bont/F4, bont/F5, and bont/A2). In this study, eight strains containing bont/F4 and seven strains containing bont/F5 were examined. Culture supernatants produced by these strains were incubated with BoNT/F-specific peptide substrates. Cleavage products of these peptides were subjected to mass spectral analysis, allowing detection of the BoNT/F subtypes present in the culture supernatants. PCR analysis demonstrated that a plasmid-specific marker (PL-6) was observed only among strains containing bont/F5. Among these strains, Southern hybridization revealed the presence of an approximately 242-kb plasmid harboring bont/F5. Genome sequencing of four of these strains revealed that the genomic backgrounds of strains harboring either bont/F4 or bont/F5 are diverse. None of the strains analyzed in this study were shown to produce BoNT/F4 and BoNT/F5 simultaneously, suggesting that strain Af84 is unusual. Finally, these data support a role for the mobility of a bont/F5-carrying plasmid among strains of diverse genomic backgrounds.

  8. A European Database of Fusarium graminearum and F. culmorum Trichothecene Genotypes

    PubMed Central

    Pasquali, Matias; Beyer, Marco; Logrieco, Antonio; Audenaert, Kris; Balmas, Virgilio; Basler, Ryan; Boutigny, Anne-Laure; Chrpová, Jana; Czembor, Elżbieta; Gagkaeva, Tatiana; González-Jaén, María T.; Hofgaard, Ingerd S.; Köycü, Nagehan D.; Hoffmann, Lucien; Lević, Jelena; Marin, Patricia; Miedaner, Thomas; Migheli, Quirico; Moretti, Antonio; Müller, Marina E. H.; Munaut, Françoise; Parikka, Päivi; Pallez-Barthel, Marine; Piec, Jonathan; Scauflaire, Jonathan; Scherm, Barbara; Stanković, Slavica; Thrane, Ulf; Uhlig, Silvio; Vanheule, Adriaan; Yli-Mattila, Tapani; Vogelgsang, Susanne

    2016-01-01

    Fusarium species, particularly Fusarium graminearum and F. culmorum, are the main cause of trichothecene type B contamination in cereals. Data on the distribution of Fusarium trichothecene genotypes in cereals in Europe are scattered in time and space. Furthermore, a common core set of related variables (sampling method, host cultivar, previous crop, etc.) that would allow more effective analysis of factors influencing the spatial and temporal population distribution, is lacking. Consequently, based on the available data, it is difficult to identify factors influencing chemotype distribution and spread at the European level. Here we describe the results of a collaborative integrated work which aims (1) to characterize the trichothecene genotypes of strains from three Fusarium species, collected over the period 2000–2013 and (2) to enhance the standardization of epidemiological data collection. Information on host plant, country of origin, sampling location, year of sampling and previous crop of 1147 F. graminearum, 479 F. culmorum, and 3 F. cortaderiae strains obtained from 17 European countries was compiled and a map of trichothecene type B genotype distribution was plotted for each species. All information on the strains was collected in a freely accessible and updatable database (www.catalogueeu.luxmcc.lu), which will serve as a starting point for epidemiological analysis of potential spatial and temporal trichothecene genotype shifts in Europe. The analysis of the currently available European dataset showed that in F. graminearum, the predominant genotype was 15-acetyldeoxynivalenol (15-ADON) (82.9%), followed by 3-acetyldeoxynivalenol (3-ADON) (13.6%), and nivalenol (NIV) (3.5%). In F. culmorum, the prevalent genotype was 3-ADON (59.9%), while the NIV genotype accounted for the remaining 40.1%. Both, geographical and temporal patterns of trichothecene genotypes distribution were identified. PMID:27092107

  9. PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

    PubMed

    Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

    2015-11-01

    Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

  10. Probing new physics in B→f0(980)K decays

    NASA Astrophysics Data System (ADS)

    Giri, A. K.; Mawlong, B.; Mohanta, R.

    2006-12-01

    We study the hadronic decay modes B±(0)→f0(980)K±(0), involving a scalar and a pseudoscalar meson in the final state. These decay modes are dominated by the loop induced b→sq¯q(q=s,u,d) penguins along with a small b→u tree level transition (for B+→f0K+) and annihilation diagrams. Therefore, the standard model expectation of direct CP violation is negligibly small and the mixing-induced CP violation parameter in the mode B0→f0KS is expected to give the same value of sin⁡(2β), as extracted from B0→J/ψKS but with opposite sign. Using the generalized factorization approach we find the direct CP violation in the decay mode B+→f0K+ to be of the order of few percent. We then study the effect of the R-parity violating supersymmetric model and show that the direct CP violating asymmetry in B+→f0(980)K+ could be as large as ˜80% and the mixing-induced CP asymmetry in B0→f0KS (i.e., -Sf0KS) could deviate significantly from that of sin⁡(2β)J/ψKS.

  11. Remaining Sites Verification Package for the 100-F-26:10, 1607-F3 Sanitary Sewer Pipelines (182-F, 183-F, and 151-F Sanitary Sewer Lines), Waste Site Reclassification Form 2007-028

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

    L. M. Dittmer

    2007-12-03

    The 100-F-26:10 waste site includes sanitary sewer lines that serviced the former 182-F, 183-F, and 151-F Buildings. In accordance with this evaluation, the verification sampling results support a reclassification of this site to Interim Closed Out. The results of verification sampling show that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also demonstrate that residual contaminant concentrations are protective of groundwater and the Columbia River.

  12. Exposure Factors Handbook (1997, Final Report)

    EPA Science Inventory

    The "Exposure Factors Handbook" (EFH or "Handbook") provides a summary of the available statistical data on various factors used in assessing human exposure. This report is addressed to exposure assessors inside the Agency as well as outside, who need to obtain data on standard f...

  13. Combining a semantic differential with fMRI to investigate brands as cultural symbols

    PubMed Central

    Rotte, Michael

    2010-01-01

    Traditionally, complex cultural symbols like brands are investigated with psychological approaches. Often this is done by using semantic differentials, in which participants are asked to rate a brand regarding different pairs of adjectives. Only recently, functional magnetic resonance imaging (fMRI) has been used to examine brands. In the current work we used fMRI in combination with a semantic differential to cross-validate both methods and to improve the characterization of the basic factors constituting the semantic space. To this end we presented pictures of brands while recording subject's brain activity during an fMRI experiment. Results of the semantic differential arranged the brands in a semantic space illustrating their relationships to other cultural symbols. FMRI results revealed activation of the medial prefrontal cortex for brands that loaded high on the factor ‘social competence’, suggesting an involvement of a cortical network associated with social cognitions. In contrast, brands closely related to the factor ‘potency’ showed decreased activity in the superior frontal gyri, possibly related to working memory during task performance. We discuss the results as a different engagement of the prefrontal cortex when perceiving brands as cultural symbols. PMID:20080877

  14. Spectroscopic investigations of ThF and ThF+.

    PubMed

    Barker, Beau J; Antonov, Ivan O; Heaven, Michael C; Peterson, Kirk A

    2012-03-14

    The electronic spectra of ThF and ThF(+) have been examined using laser induced fluorescence and resonant two-photon ionization techniques. The results from high-level ab initio calculations have been used to guide the assignment of these data. Spectra for ThF show that the molecule has an X (2)Δ(3/2) ground state. The upper spin-orbit component, X (2)Δ(5/2) was found at an energy of 2575(15) cm(-1). The low-lying states of ThF(+) were probed using dispersed fluorescence and pulsed field ionization-zero kinetic energy (PFI-ZEKE) photoelectron spectroscopy. Vibronic progressions belonging to four electronic states were identified. The lowest energy states were clearly (1)Σ(+) and (3)Δ(1). Although the energy ordering could not be rigorously determined, the evidence favors assignment of (1)Σ(+) as the ground state. The (3)Δ(1) state, of interest for investigation of the electron electric dipole moment, is just 315.0(5) cm(-1) above the ground state. The PFI-ZEKE measurements for ThF yielded an ionization energy of 51 581(3) cm(-1). Molecular constants show that the vibrational constant increases and the bond length shortens on ionization. This is consistent with removal of a non-bonding Th-centered 6d or 7s electron. Laser excitation of ThF(+) was used to probe electronically excited states in the range of 19,000-21,500 cm(-1).

  15. Algorithmic universality in F-theory compactifications

    NASA Astrophysics Data System (ADS)

    Halverson, James; Long, Cody; Sung, Benjamin

    2017-12-01

    We study universality of geometric gauge sectors in the string landscape in the context of F-theory compactifications. A finite time construction algorithm is presented for 4/3 ×2.96 ×10755 F-theory geometries that are connected by a network of topological transitions in a connected moduli space. High probability geometric assumptions uncover universal structures in the ensemble without explicitly constructing it. For example, non-Higgsable clusters of seven-branes with intricate gauge sectors occur with a probability above 1 - 1.01 ×10-755 , and the geometric gauge group rank is above 160 with probability 0.999995. In the latter case there are at least 10 E8 factors, the structure of which fixes the gauge groups on certain nearby seven-branes. Visible sectors may arise from E6 or S U (3 ) seven-branes, which occur in certain random samples with probability ≃1 /200 .

  16. Determination of small-field correction factors for cylindrical ionization chambers using a semiempirical method

    NASA Astrophysics Data System (ADS)

    Park, Kwangwoo; Bak, Jino; Park, Sungho; Choi, Wonhoon; Park, Suk Won

    2016-02-01

    A semiempirical method based on the averaging effect of the sensitive volumes of different air-filled ionization chambers (ICs) was employed to approximate the correction factors for beam quality produced from the difference in the sizes of the reference field and small fields. We measured the output factors using several cylindrical ICs and calculated the correction factors using a mathematical method similar to deconvolution; in the method, we modeled the variable and inhomogeneous energy fluence function within the chamber cavity. The parameters of the modeled function and the correction factors were determined by solving a developed system of equations as well as on the basis of the measurement data and the geometry of the chambers. Further, Monte Carlo (MC) computations were performed using the Monaco® treatment planning system to validate the proposed method. The determined correction factors (k{{Q\\text{msr}},Q}{{f\\text{smf}}, {{f}\\text{ref}}} ) were comparable to the values derived from the MC computations performed using Monaco®. For example, for a 6 MV photon beam and a field size of 1  ×  1 cm2, k{{Q\\text{msr}},Q}{{f\\text{smf}}, {{f}\\text{ref}}} was calculated to be 1.125 for a PTW 31010 chamber and 1.022 for a PTW 31016 chamber. On the other hand, the k{{Q\\text{msr}},Q}{{f\\text{smf}}, {{f}\\text{ref}}} values determined from the MC computations were 1.121 and 1.031, respectively; the difference between the proposed method and the MC computation is less than 2%. In addition, we determined the k{{Q\\text{msr}},Q}{{f\\text{smf}}, {{f}\\text{ref}}} values for PTW 30013, PTW 31010, PTW 31016, IBA FC23-C, and IBA CC13 chambers as well. We devised a method for determining k{{Q\\text{msr}},Q}{{f\\text{smf}}, {{f}\\text{ref}}} from both the measurement of the output factors and model-based mathematical computation. The proposed method can be useful in case the MC simulation would not be applicable for the clinical settings.

  17. NbF{sub 5} and TaF{sub 5}: Assignment of {sup 19}F NMR resonances and chemical bond analysis from GIPAW calculations

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

    Biswal, Mamata, E-mail: Mamata.Biswal-Susanta_Kumar_Nayak.Etu@univ-lemans.fr; Body, Monique, E-mail: monique.body@univ-lemans.fr; Legein, Christophe, E-mail: christophe.legein@univ-lemans.fr

    2013-11-15

    The {sup 19}F isotropic chemical shifts (δ{sub iso}) of two isomorphic compounds, NbF{sub 5} and TaF{sub 5}, which involve six nonequivalent fluorine sites, have been experimentally determined from the reconstruction of 1D {sup 19}F MAS NMR spectra. In parallel, the corresponding {sup 19}F chemical shielding tensors have been calculated using the GIPAW method for both experimental and DFT-optimized structures. Furthermore, the [M{sub 4}F{sub 20}] units of NbF{sub 5} and TaF{sub 5} being held together by van der Waals interactions, the relevance of Grimme corrections to the DFT optimization processes has been evaluated. However, the semi-empirical dispersion correction term introduced bymore » such a method does not show any significant improvement. Nonetheless, a complete and convincing assignment of the {sup 19}F NMR lines of NbF{sub 5} and TaF{sub 5} is obtained, ensured by the linearity between experimental {sup 19}F δ{sub iso} values and calculated {sup 19}F isotropic chemical shielding σ{sub iso} values. The effects of the geometry optimizations have been carefully analyzed, confirming among other matters, the inaccuracy of the experimental structure of NbF{sub 5}. The relationships between the fluorine chemical shifts, the nature of the fluorine atoms (bridging or terminal), the position of the terminal ones (opposite or perpendicular to the bridging ones), the fluorine charges, the ionicity and the length of the M–F bonds have been established. Additionally, for three of the {sup 19}F NMR lines of NbF{sub 5}, distorted multiplets, arising from {sup 1}J-coupling and residual dipolar coupling between the {sup 19}F and {sup 93}Nb nuclei, were simulated yielding to values of {sup 93}Nb–{sup 19}F {sup 1}J-coupling for the corresponding fluorine sites. - Graphical abstract: The complete assignment of the {sup 19}F NMR lines of NbF{sub 5} and TaF{sub 5} allow establishing relationships between the {sup 19}F δ{sub iso} values, the nature of the fluorine

  18. WE-H-207A-05: Spatial Co-Localization of F-18 NaF Vs. F-18 FDG Defined Disease Volumes

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

    Ferjancic, P; Harmon, S; Jeraj, R

    Purpose: Both [F-18]NaF and [F-18]FDG show promise for quantitative PET/CT assessment in metastatic prostate cancer to bone. Broad agreement between the tracers has been shown but voxel-wise correspondence has not been explored in depth. This study evaluates the spatial co-localization of [F-18]NaF PET and [F-18]FDG PET in bone lesions. Methods: Seventy-three lesion contours were identified in six patients receiving dynamic NaF PET/CT and FDG PET/CT scans two hours apart using identical fields-of-view. Tracer uptake (SUV) reflecting 60 minutes post-injection was modeled from kinetic parameters. Lesions were segmented by a physician separately on NaF PET and FDG PET. PET images weremore » rigidly aligned using skeletal references on CT images. Lesion size, degree of overlap, voxel-wise tracer uptake values (SUV), and CT density distributions were compared using Dice coefficient, Positive Predictive Value (PPV), and Spearman rank correlation tests. Results: Across all patients, 42 lesions were identified on NaF PET (median 1.4 cm{sup 3}, range <1–204 cm{sup 3}) compared to 31 using FDG PET (median 1.8 cm{sup 3}, range <1–244 cm{sup 3}). Spatial cooccurrence was found in 25 lesion pairs. Lesions on NaF PET had PPV of 0.91 and on FDG a PPV of 0.65. Overall, NaF-defined lesions were 47% (±24%) larger by volume with moderate overlap to FDG, resulting in mean Dice coefficient of 34% (±22%). In areas of overlap, voxel-wise correlation of NaF and FDG SUV was moderate (ρ=0.56). Expanding to regions of non-spatial overlap, voxels contained in FDG-only contours were almost exclusively low HU (median 118), compared to dense regions of NaF-only voxels (median 250). In sclerotic sub-volumes (HU > 300) NaF-defined contours encompassed 83% of total FDG volume. Conclusion: Moderate voxel-wise correlation of FDG and NaF PET/CT uptake was observed. Spatial discrepancies in FDG and NaF PET/CT imaging of boney metastases could be influenced by poor sensitivity of FDG PET/CT in

  19. Stabilization of primary mobile radiation defects in MgF2 crystals

    NASA Astrophysics Data System (ADS)

    Lisitsyn, V. M.; Lisitsyna, L. A.; Popov, A. I.; Kotomin, E. A.; Abuova, F. U.; Akilbekov, A.; Maier, J.

    2016-05-01

    Non-radiative decay of the electronic excitations (excitons) into point defects (F-H pairs of Frenkel defects) is main radiation damage mechanism in many ionic (halide) solids. Typical time scale of the relaxation of the electronic excitation into a primary, short-lived defect pair is about 1-50 ps with the quantum yield up to 0.2-0.8. However, only a small fraction of these primary defects are spatially separated and survive after transformation into stable, long-lived defects. The survival probability (or stable defect accumulation efficiency) can differ by orders of magnitude, dependent on the material type; e.g. ∼10% in alkali halides with f.c.c. or b.c.c. structure, 0.1% in rutile MgF2 and <0.001% in fluorides MeF2 (Me: Ca, Sr, Ba). The key factor determining accumulation of stable radiation defects is stabilization of primary defects, first of all, highly mobile hole H centers, through their transformation into more complex immobile defects. In this talk, we present the results of theoretical calculations of the migration energies of the F and H centers in poorely studied MgF2 crystals with a focus on the H center stabilization in the form of the interstitial F2 molecules which is supported by presented experimental data.

  20. Optimization of Blocked Designs in fMRI Studies

    ERIC Educational Resources Information Center

    Maus, Barbel; van Breukelen, Gerard J. P.; Goebel, Rainer; Berger, Martijn P. F.

    2010-01-01

    Blocked designs in functional magnetic resonance imaging (fMRI) are useful to localize functional brain areas. A blocked design consists of different blocks of trials of the same stimulus type and is characterized by three factors: the length of blocks, i.e., number of trials per blocks, the ordering of task and rest blocks, and the time between…

  1. E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism.

    PubMed

    Blanchet, Emilie; Annicotte, Jean-Sébastien; Pradelli, Ludivine A; Hugon, Gérald; Matecki, Stéfan; Mornet, Dominique; Rivier, François; Fajas, Lluis

    2012-09-01

    E2F1 deletion leads to increased mitochondrial number and function, increased body temperature in response to cold and increased resistance to fatigue with exercise. Since E2f1-/- mice show increased muscle performance, we examined the effect of E2f1 genetic inactivation in the mdx background, a mouse model of Duchenne muscular dystrophy (DMD). E2f1-/-;mdx mice demonstrated a strong reduction of physiopathological signs of DMD, including preservation of muscle structure, decreased inflammatory profile, increased utrophin expression, resulting in better endurance and muscle contractile parameters, comparable to normal mdx mice. E2f1 deficiency in the mdx genetic background increased the oxidative metabolic gene program, mitochondrial activity and improved muscle functions. Interestingly, we observed increased E2F1 protein levels in DMD patients, suggesting that E2F1 might represent a promising target for the treatment of DMD.

  2. 18F-labeled norepinephrine transporter tracer [18F]NS12137: radiosynthesis and preclinical evaluation.

    PubMed

    Kirjavainen, Anna K; Forsback, Sarita; López-Picón, Francisco R; Marjamäki, Päivi; Takkinen, Jatta; Haaparanta-Solin, Merja; Peters, Dan; Solin, Olof

    2018-01-01

    Several psychiatric and neurodegenerative diseases are associated with malfunction of brain norepinephrine transporter (NET). However, current clinical evaluations of NET function are limited by the lack of sufficiently sensitive methods of detection. To this end, we have synthesized exo-3-[(6-[ 18 F]fluoro-2-pyridyl)oxy]-8-azabicyclo[3.2.1]-octane ([ 18 F]NS12137) as a radiotracer for positron emission tomography (PET) and have demonstrated that it is highly specific for in vivo detection of NET-rich regions of rat brain tissue. We applied two methods of electrophilic, aromatic radiofluorination of the precursor molecule, exo-3-[(6-trimethylstannyl-2-pyridyl)oxy]-8-azabicyclo-[3.2.1]octane-8-carboxylate: (1) direct labeling with [ 18 F]F 2 , and (2) labeling with [ 18 F]Selectfluor, a derivative of [ 18 F]F 2 , using post-target produced [ 18 F]F 2 . The time-dependent distribution of [ 18 F]NS12137 in brain tissue of healthy, adult Sprague-Dawley rats was determined by ex vivo autoradiography. The specificity of [ 18 F]NS12137 binding was demonstrated on the basis of competitive binding by nisoxetine, a known NET antagonist of high specificity. [ 18 F]NS12137 was successfully synthesized with radiochemical yields of 3.9% ± 0.3% when labeled with [ 18 F]F 2 and 10.2% ± 2.7% when labeled with [ 18 F]Selectfluor. The molar activity of radiotracer was 8.8 ± 0.7 GBq/μmol with [ 18 F]F 2 labeling and 6.9 ± 0.4 GBq/μmol with [ 18 F]Selectfluor labeling at the end of synthesis of [ 18 F]NS12137. Uptake of [ 18 F]NS12137 in NET-rich areas in rat brain was demonstrated with the locus coeruleus (LCoe) having the highest regional uptake. Prior treatment of rats with nisoxetine showed no detectable [ 18 F]NS12137 in the LCoe. Analyses of whole brain samples for radiometabolites showed only the parent compound [ 18 F]NS12137. Uptake of 18 F-radioactivity in bone increased with time. The two electrophilic 18 F-labeling methods proved to be suitable for synthesis of [ 18 F

  3. WE-H-207A-04: Impact of Lesion Location On the Repeatability of 18F-NaF PET/CT

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

    Lin, C; Perk, T; Harmon, S

    Purpose: Quantifying the repeatability of imaging biomarkers is critical for assessing therapeutic response. While {sup 18}F-NaF PET/CT has shown to be a repeatable imaging method, research has not shown which factors may influence its repeatability. The purpose of this study was to evaluate whether the location of the lesion impacts the repeatability of quantitative {sup 18}F-NaF PET-derived SUV metrics. Methods: Metastatic castrate-resistant prostate cancer patients with multiple bone lesions received whole-body test-retest NaF PET/CT scans. Malignant bone lesions of PET-defined volume greater than 1.5 cm{sup 3} were identified by a nuclear medicine physician and automatically delineated using a SUV>15 threshold.more » The maximum (SUVmax), average (SUVmean), and total (SUVtotal) SUV were extracted from each lesion. Atlas-based segmentation was used to divide each patient skeleton into 25 skeletal regions. Test-retest repeatability of each SUV metric was assessed with coefficient of variation (CV). Results: A total of 265 malignant bone lesions from 18 patients were identified by nuclear medicine physician. The largest proportion of bone lesions were localized to the spine (41%), with 41% of those lesions localized to the thoracic spine. One-way ANOVA showed that measurement differences differed significantly for all three metrics across locations (p<0.01 for each metrics). Overall, CV was smallest for SUVmean at 5.3%, followed by SUVmax at 11.5% and SUVtotal at 20.4%. Lesions in the pubis were consistently the most repeatable (CV(SUVmax)= 5.6%, CV(SUVmean)= 0.6%, CV(SUVtotal)= 2.9%). According to SUVmean, repeatability was poorest in the cervical spine (CV = 6.2%), whereas according to SUVmax and SUVtotal, repeatability was poorest in the ribs (CV(SUVmax)= 15.0%, CV(SUVtotal)= 29.8%). Conclusion: Location of the lesion affects the repeatability of {sup 18}F-NaF PET/CT, with the ribs and cervical spine having the lowest repeatability and the pubis having the

  4. Potential proteins targeted by let-7f-5p in HeLa cells.

    PubMed

    Wang, Yu; Chen, Xiujuan; Zhang, Yi; Song, Jiandong

    2017-07-24

    MicroRNAs are a class of small, endogenous, non-coding RNAs mediating posttranscriptional gene silencing. The current authors hypothesized that let-7f-5p is likely involved in cell invasion and proliferation by regulating the expression of target genes. The current study combined let-7f-5p with iTRAQ to assess its effect on gene expression in HeLa cells. Results indicated that 164 proteins were expressed at different levels in HeLa cells overexpressing let-7f-5p and negative controls and that 172 proteins were expressed at different levels in let-7f-5p-silenced HeLa cells and negative controls. Results indicated that let-7f-5p may suppress insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in HeLa cells.

  5. Connective Tissue Growth Factor (CTGF) as a Regulator of Lactogenic Differentiation

    DTIC Science & Technology

    2009-06-09

    1 1.62 Myeloid leukemia factor 1, Mlf1 1.57 ADAMTS-l4 1.55 E2F transcription factor, E2F2 1.44 Tensin 4 -1.5 BCL2/adenovirus E1B interacting... Mlf1 1.57 ADAMTS-l4 1.55 Ras homolog gene family, member B, RhoB 1.48 Cell Differentiation-associated Wingless-type MMTV integration site family...B, relB 1.92 Myeloid leukemia factor 1, Mlf1 1.57 Growth Factor, Catalytic Activity-associated Dual specificity protein phosphatase 8, Dusp8

  6. F4/80: the macrophage-specific adhesion-GPCR and its role in immunoregulation.

    PubMed

    Lin, Hsi-Hsien; Stacey, Martin; Stein-Streilein, Joan; Gordon, Siamon

    2010-01-01

    As a macrophage-restricted reagent, the generation and application of the F4/80 mAb has greatly benefited the phenotypic characterization of mouse tissue macrophages for three decades. Following the molecular identification of the F4/80 antigen as an EGF-TM7 member of the adhesion-GPCR family, great interest was ignited to understand its cell type-specific expression pattern as well as its functional role in macrophage biology. Recent studies have shown that the F4/80 gene is regulated by a novel set of transcription factors that recognized a unique promoter sequence. Gene targeting experiments have produced two F4/80 knock out animal models and showed that F4/80 is not required for normal macrophage development. Nevertheless, the F4/80 receptor was found to be necessary for the induction of efferent CD8+ regulatory T cells responsible for peripheral immune tolerance. The identification of cellular ligands for F4/80 and delineation of its signaling pathway remain elusive but are critical to understand the in vivo role of this macrophage-specific adhesion-GPCR.

  7. Parameters to Maximize 2f2-f1 Distortion Product Otoacoustic Emission Levels

    ERIC Educational Resources Information Center

    Horn, Jennifer H.; Pratt, Shiela R.; Durrant, John D.

    2008-01-01

    Purpose: Past research has established parameters for the 2f1-f2 distortion product otoacoustic emissions (DPOAEs) that enhance response levels (e.g., L1 - L2 = 10 dB; f2/f1 = 1.22; L1, L2 = 65, 55 dB SPL). These same parameters do not optimize 2f2-f1 DPOAEs. Therefore, this study was conducted to evaluate more completely those parameters that…

  8. Important Mutations Contributing to High-Level Penicillin Resistance in Taiwan19F-14, Taiwan23F-15, and Spain23F-1 of Streptococcus pneumoniae Isolated from Taiwan.

    PubMed

    Liu, Esther Yip-Mei; Chang, Jen-Chang; Lin, Jung-Chung; Chang, Feng-Yee; Fung, Chang-Phone

    2016-12-01

    Penicillin-resistant Streptococcus pneumoniae is a serious concern worldwide. In this study, we analyzed the cause of β-lactam resistance in pandemic multidrug-resistant clones. A total of 41 penicillin-nonsusceptible clinical isolates were collected from 1996 to 2012. Sero- and molecular typing confirmed that these isolates were clonal types of Taiwan 19F -14, Taiwan 23F -15, and Spain 23F -1. Sero-switching was found in four isolates. All isolates were multidrug resistant. Sequencing analysis of the penicillin binding proteins (PBPs) was performed on PBP1a, 2b, and 2x, and a large number of mutations were identified in comparing to clinical penicillin-susceptible isolates and the recipient strain R6 used for homologous recombination. The T 451 A substitution was the key amino acid in PBP2b that contributed to penicillin resistance. T 338 A in PBP2x played a role in resistance and reached the highest level of resistance when combined with other mutations in PBP2x. High-level penicillin resistance could not be obtained without the combination of mutations in PBP1a with PBP2b and 2x. The amino acid substitutions in PBP1a, 2b, and 2x were the crucial factors for β-lactam resistance.

  9. Quantitative imaging reveals real-time Pou5f3–Nanog complexes driving dorsoventral mesendoderm patterning in zebrafish

    PubMed Central

    Perez-Camps, Mireia; Tian, Jing; Chng, Serene C; Sem, Kai Pin; Sudhaharan, Thankiah; Teh, Cathleen; Wachsmuth, Malte; Korzh, Vladimir; Ahmed, Sohail; Reversade, Bruno

    2016-01-01

    Formation of the three embryonic germ layers is a fundamental developmental process that initiates differentiation. How the zebrafish pluripotency factor Pou5f3 (homologous to mammalian Oct4) drives lineage commitment is unclear. Here, we introduce fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy to assess the formation of Pou5f3 complexes with other transcription factors in real-time in gastrulating zebrafish embryos. We show, at single-cell resolution in vivo, that Pou5f3 complexes with Nanog to pattern mesendoderm differentiation at the blastula stage. Later, during gastrulation, Sox32 restricts Pou5f3–Nanog complexes to the ventrolateral mesendoderm by binding Pou5f3 or Nanog in prospective dorsal endoderm. In the ventrolateral endoderm, the Elabela / Aplnr pathway limits Sox32 levels, allowing the formation of Pou5f3–Nanog complexes and the activation of downstream BMP signaling. This quantitative model shows that a balance in the spatiotemporal distribution of Pou5f3–Nanog complexes, modulated by Sox32, regulates mesendoderm specification along the dorsoventral axis. DOI: http://dx.doi.org/10.7554/eLife.11475.001 PMID:27684073

  10. NiF2/NaF:CaF2/Ca Solid-State High-Temperature Battery Cells

    NASA Technical Reports Server (NTRS)

    West, William; Whitacre, Jay; DelCastillo, Linda

    2009-01-01

    Experiments and theoretical study have demonstrated the promise of all-solid-state, high-temperature electrochemical battery cells based on NiF2 as the active cathode material, CaF2 doped with NaF as the electrolyte material, and Ca as the active anode material. These and other all-solid-state cells have been investigated in a continuing effort to develop batteries for instruments that must operate in environments much hotter than can be withstood by ordinary commercially available batteries. Batteries of this type are needed for exploration of Venus (where the mean surface temperature is about 450 C), and could be used on Earth for such applications as measuring physical and chemical conditions in geothermal wells and oil wells. All-solid-state high-temperature power cells are sought as alternatives to other high-temperature power cells based, variously, on molten anodes and cathodes or molten eutectic salt electrolytes. Among the all-solid-state predecessors of the present NiF2/NaF:CaF2/Ca cells are those described in "Solid-State High-Temperature Power Cells" (NPO-44396), NASA Tech Briefs, Vol. 32, No. 5 (May 2008), page 40. In those cells, the active cathode material is FeS2, the electrolyte material is a crystalline solid solution of equimolar amounts of Li3PO4 and LiSiO4, and the active anode material is Li contained within an alloy that remains solid in the intended high operational temperature range.

  11. Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography

    PubMed Central

    Bruijnen, Stefan T G; Verweij, Nicki J F; van Duivenvoorde, Leonie M; Bravenboer, Nathalie; Baeten, Dominique L P; van Denderen, Christiaan J; van der Horst-Bruinsma, Irene E; Voskuyl, Alexandre E; Custers, Martijn; van de Ven, Peter M; Bot, Joost C J; Boden, Bouke J H; Lammertsma, Adriaan A; Hoekstra, Otto S H; Raijmakers, Pieter G H M; van der Laken, Conny J

    2018-01-01

    Abstract Objectives Excessive bone formation is an important hallmark of AS. Recently it has been demonstrated that axial bony lesions in AS patients can be visualized using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F-fluoride uptake in clinically active AS patients is related to focal bone formation in spine biopsies and is sensitive to change during anti-TNF treatment. Methods Twelve anti-TNF-naïve AS patients [female 7/12; age 39 years (SD 11); BASDAI 5.5 ± 1.1] were included. 18 F-fluoride PET-CT scans were performed at baseline and in two patients, biopsies were obtained from PET-positive and PET-negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually by two blinded expert readers. In addition, 18F-fluoride uptake was quantified using the standardized uptake value corrected for individual integrated whole blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined according to a ⩾ 20% improvement in Assessment of SpondyloArthritis international Society criteria at 24 weeks. Results At baseline, all patients showed at least one axial PET-positive lesion. Histological analysis of PET-positive lesions in the spine confirmed local osteoid formation. PET-positive lesions were found in the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes (20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12 weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased significantly in the costovertebral (mean SUVAUC −1.0; P < 0.001) and SI joints (mean SUVAUC −1.2; P = 0.03) in contrast to non-responders. Conclusions 18F-fluoride PET-CT identified bone formation, confirmed by histology, in the spine and SI joints of AS patients and demonstrated alterations in bone formation during anti-TNF treatment. PMID:29329443

  12. Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography.

    PubMed

    Bruijnen, Stefan T G; Verweij, Nicki J F; van Duivenvoorde, Leonie M; Bravenboer, Nathalie; Baeten, Dominique L P; van Denderen, Christiaan J; van der Horst-Bruinsma, Irene E; Voskuyl, Alexandre E; Custers, Martijn; van de Ven, Peter M; Bot, Joost C J; Boden, Bouke J H; Lammertsma, Adriaan A; Hoekstra, Otto S H; Raijmakers, Pieter G H M; van der Laken, Conny J

    2018-04-01

    Excessive bone formation is an important hallmark of AS. Recently it has been demonstrated that axial bony lesions in AS patients can be visualized using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F-fluoride uptake in clinically active AS patients is related to focal bone formation in spine biopsies and is sensitive to change during anti-TNF treatment. Twelve anti-TNF-naïve AS patients [female 7/12; age 39 years (SD 11); BASDAI 5.5 ± 1.1] were included. 18 F-fluoride PET-CT scans were performed at baseline and in two patients, biopsies were obtained from PET-positive and PET-negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually by two blinded expert readers. In addition, 18F-fluoride uptake was quantified using the standardized uptake value corrected for individual integrated whole blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined according to a ⩾ 20% improvement in Assessment of SpondyloArthritis international Society criteria at 24 weeks. At baseline, all patients showed at least one axial PET-positive lesion. Histological analysis of PET-positive lesions in the spine confirmed local osteoid formation. PET-positive lesions were found in the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes (20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12 weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased significantly in the costovertebral (mean SUVAUC -1.0; P < 0.001) and SI joints (mean SUVAUC -1.2; P = 0.03) in contrast to non-responders. 18F-fluoride PET-CT identified bone formation, confirmed by histology, in the spine and SI joints of AS patients and demonstrated alterations in bone formation during anti-TNF treatment.

  13. E2F function in muscle growth is necessary and sufficient for viability in Drosophila

    PubMed Central

    Zappia, Maria Paula; Frolov, Maxim V.

    2016-01-01

    The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. PMID:26823289

  14. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors.

    PubMed

    Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias; Stummer, Walter

    2016-03-01

    Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether

  15. Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells.

    PubMed

    Le Goffic, Ronan; Bouguyon, Edwige; Chevalier, Christophe; Vidic, Jasmina; Da Costa, Bruno; Leymarie, Olivier; Bourdieu, Christiane; Decamps, Laure; Dhorne-Pollet, Sophie; Delmas, Bernard

    2010-10-15

    The PB1-F2 protein of the influenza A virus (IAV) contributes to viral pathogenesis by a mechanism that is not well understood. PB1-F2 was shown to modulate apoptosis and to be targeted by the CD8(+) T cell response. In this study, we examined the downstream effects of PB1-F2 protein during IAV infection by measuring expression of the cellular genes in response to infection with wild-type WSN/33 and PB1-F2 knockout viruses in human lung epithelial cells. Wild-type virus infection resulted in a significant induction of genes involved in innate immunity. Knocking out the PB1-F2 gene strongly decreased the magnitude of expression of cellular genes implicated in antiviral response and MHC class I Ag presentation, suggesting that PB1-F2 exacerbates innate immune response. Biological network analysis revealed the IFN pathway as a link between PB1-F2 and deregulated genes. Using quantitative RT-PCR and IFN-β gene reporter assay, we determined that PB1-F2 mediates an upregulation of IFN-β expression that is dependent on NF-κB but not on AP-1 and IFN regulatory factor-3 transcription factors. Recombinant viruses knocked out for the PB1-F2 and/or the nonstructural viral protein 1 (the viral antagonist of the IFN response) genes provide further evidence that PB1-F2 increases IFN-β expression and that nonstructural viral protein 1 strongly antagonizes the effect of PB1-F2 on the innate response. Finally, we compared the effect of PB1-F2 variants taken from several IAV strains on IFN-β expression and found that PB1-F2-mediated IFN-β induction is significantly influenced by its amino acid sequence, demonstrating its importance in the host cell response triggered by IAV infection.

  16. Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients.

    PubMed

    Jansen, Nathalie L; Suchorska, Bogdana; Wenter, Vera; Eigenbrod, Sabina; Schmid-Tannwald, Christine; Zwergal, Andreas; Niyazi, Maximilian; Drexler, Mark; Bartenstein, Peter; Schnell, Oliver; Tonn, Jörg-Christian; Thon, Niklas; Kreth, Friedrich-Wilhelm; la Fougère, Christian

    2014-02-01

    Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II). Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P < 0.001). Absence of (18)F-FET uptake in newly diagnosed astrocytic low-grade glioma does not generally indicate an indolent disease course. Among the (18)F-FET-positive gliomas, decreasing time-activity curves in dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

  17. Risk stratification of gallbladder polyps (1-2 cm) for surgical intervention with 18F-FDG PET/CT.

    PubMed

    Lee, Jaehoon; Yun, Mijin; Kim, Kyoung-Sik; Lee, Jong-Doo; Kim, Chun K

    2012-03-01

    We assessed the value of (18)F-FDG uptake in the gallbladder polyp (GP) in risk stratification for surgical intervention and the optimal cutoff level of the parameters derived from GP (18)F-FDG uptake for differentiating malignant from benign etiologies in a select, homogeneous group of patients with 1- to 2-cm GPs. Fifty patients with 1- to 2-cm GPs incidentally found on the CT portion of PET/CT were retrospectively analyzed. All patients had histologic diagnoses. GP (18)F-FDG activity was visually scored positive (≥liver) or negative (F-FDG-related parameters in risk stratification. Twenty GPs were classified as malignant and 30 as benign. Multivariate analyses showed that the age and all parameters (visual criteria, SUVgp, and GP/L) related to (18)F-FDG uptake were significant risk factors, with the GP/L being the most significant. The sex, size of GPs, and presence of concurrent gallstones were found to be insignificant. (18)F-FDG uptake in a GP is a strong risk factor that can be used to determine the necessity of surgical intervention more effectively than other known risk factors. However, all criteria derived from (18)F-FDG uptake presented in this series may be applicable to the assessment of 1- to 2-cm GPs.

  18. String duality transformations in f(R) gravity from Noether symmetry approach

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

    Capozziello, Salvatore; Gionti, Gabriele S.J.; Vernieri, Daniele, E-mail: capozziello@na.inf.it, E-mail: ggionti@as.arizona.edu, E-mail: vernieri@iap.fr

    2016-01-01

    We select f(R) gravity models that undergo scale factor duality transformations. As a starting point, we consider the tree-level effective gravitational action of bosonic String Theory coupled with the dilaton field. This theory inherits the Busher's duality of its parent String Theory. Using conformal transformations of the metric tensor, it is possible to map the tree-level dilaton-graviton string effective action into f(R) gravity, relating the dilaton field to the Ricci scalar curvature. Furthermore, the duality can be framed under the standard of Noether symmetries and exact cosmological solutions are derived. Using suitable changes of variables, the string-based f(R) Lagrangians aremore » shown in cases where the duality transformation becomes a parity inversion.« less

  19. Laser cooling of BH and GaF: insights from an ab initio study.

    PubMed

    Gao, Yu-feng; Gao, Tao

    2015-04-28

    The feasibility of laser cooling BH and GaF is investigated using ab initio quantum chemistry. The ground state X (1)Σ(+) and first two excited states (3)Π and (1)Π of BH and GaF are calculated using the multireference configuration interaction (MRCI) level of theory. For GaF, the spin-orbit coupling effect is also taken into account in the electronic structure calculations at the MRCI level. Calculated spectroscopic constants for BH and GaF show good agreement with available theoretical and experimental results. The highly diagonal Franck-Condon factors (BH: f00 = 0.9992, f11 = 0.9908, f22 = 0.9235; GaF: f00 = 0.997, f11 = 0.989, f22 = 0.958) for the (1)Π (v' = 0-2) → X (1)Σ(+) (v = 0-2) transitions in BH and GaF are determined, which are found to be in good agreement with the theoretical and experimental data. Radiative lifetime calculations of the (1)Π (v' = 0-2) state (BH: 131, 151, and 187 ns; GaF: 2.26, 2.36, and 2.48 ns) are found to be short enough for rapid laser cooling. The proposed laser cooling schemes that drive the (1)Π (v' = 0) → X (1)Σ(+) (v = 0) transition use just one laser wavelength λ00 (BH: 436 nm, GaF: 209 nm). Though the cooling wavelength of GaF is deep in the UVC, a frequency quadrupled Ti:sapphire laser (189-235 nm) could be capable of generating useful quantities of light at this wavelength. The present results indicate that BH and GaF are two good choices of molecules for laser cooling.

  20. Role of plasma-induced defects in the generation of 1/f noise in graphene

    NASA Astrophysics Data System (ADS)

    Cultrera, Alessandro; Callegaro, Luca; Marzano, Martina; Ortolano, Massimo; Amato, Giampiero

    2018-02-01

    It has already been reported that 1/f noise in graphene can be dominated by fluctuations of charge carrier mobility. We show here that the increasing damage induced by oxygen plasma on graphene samples result in two trends: at low doses, the magnitude of the 1/f noise increases with the dose; and at high doses, it decreases with the dose. This behaviour is interpreted in the framework of 1/f noise generated by carrier mobility fluctuations where the concentration of mobility fluctuation centers and the mean free path of the carriers are competing factors.

  1. Anti-proliferative effects of gold nanoparticles functionalized with Semaphorin 3F

    NASA Astrophysics Data System (ADS)

    Tan, Gamze; Onur, Mehmet Ali

    2017-08-01

    The new vessel formations play a vital role in growth and spread of cancer. Current anti-angiogenic therapies, predominantly based on vascular endothelial growth factor (VEGF) inhibition, can inhibit vascular development; however, they are usually ineffective against the primary tumor occurrence. The aim of this study was to assess anti-angiogenic effects of gold nanoparticles (AuNPs) functionalized with Semaphorin (Sema) 3F protein. The polyethylene glycol (PEG)-coated AuNPs were covalently functionalized with Sema 3F and labeled with the TAMRA fluorescent dye. The effect of the NPs on human umbilical vein endothelial cells (HUVECs) is probed in the way of internalization and viability assays. AuNP-Sema 3F bioconjugates showed great endothelial cell uptake. AuNP-Sema 3F bioconjugates reduced VEGF165-induced endothelial cell proliferation more effectively than Sema 3F alone, suggesting that the therapeutic effects of Sema 3F can be improved by conjugation to AuNPs. Also, no significant toxicity effect was induced by bioconjugates. This is the first study that reports a covalent binding of full length Sema 3F to NPs. The exogenously administration of Sema 3F, which has both anti-angiogenic and anti-tumoral activity, to tumor vasculature via a carrying platform may not only lead to more effective anti-angiogenic treatment but also may make current approach more applicable in clinical use like drug delivery system. [Figure not available: see fulltext.

  2. Modified QCD ghost f(T,TG) gravity

    NASA Astrophysics Data System (ADS)

    Jawad, Abdul; Rani, Shamaila; Chattopadhyay, Surajit

    2015-12-01

    In this paper, we explore the reconstruction scenario of modified QCD ghost dark energy model and newly proposed f(T,TG) gravity in flat FRW universe. We consider the well-known assumption of scale factor, i.e., power law form. We construct the f(T,TG) model and discuss its cosmological consequences through various cosmological parameters such as equation of state parameter, squared speed of sound and ω_{DE}-ω '_{DE}. The equation of state parameter provides the quintom-like behavior of the universe. The squared speed of sound exhibits the stability of model in the later time. Also, ω_{DE}- ω '_{DE} corresponds to freezing as well as thawing regions. It is also interesting to remark here that the results of equation of state parameter and w_{DE}-w'_{DE} coincide with the observational data.

  3. Concurrent fNIRS-fMRI measurement to validate a method for separating deep and shallow fNIRS signals by using multidistance optodes

    PubMed Central

    Funane, Tsukasa; Sato, Hiroki; Yahata, Noriaki; Takizawa, Ryu; Nishimura, Yukika; Kinoshita, Akihide; Katura, Takusige; Atsumori, Hirokazu; Fukuda, Masato; Kasai, Kiyoto; Koizumi, Hideaki; Kiguchi, Masashi

    2015-01-01

    Abstract. It has been reported that a functional near-infrared spectroscopy (fNIRS) signal can be contaminated by extracerebral contributions. Many algorithms using multidistance separations to address this issue have been proposed, but their spatial separation performance has rarely been validated with simultaneous measurements of fNIRS and functional magnetic resonance imaging (fMRI). We previously proposed a method for discriminating between deep and shallow contributions in fNIRS signals, referred to as the multidistance independent component analysis (MD-ICA) method. In this study, to validate the MD-ICA method from the spatial aspect, multidistance fNIRS, fMRI, and laser-Doppler-flowmetry signals were simultaneously obtained for 12 healthy adult males during three tasks. The fNIRS signal was separated into deep and shallow signals by using the MD-ICA method, and the correlation between the waveforms of the separated fNIRS signals and the gray matter blood oxygenation level–dependent signals was analyzed. A three-way analysis of variance (signal depth×Hb kind×task) indicated that the main effect of fNIRS signal depth on the correlation is significant [F(1,1286)=5.34, p<0.05]. This result indicates that the MD-ICA method successfully separates fNIRS signals into spatially deep and shallow signals, and the accuracy and reliability of the fNIRS signal will be improved with the method. PMID:26157983

  4. POU2F2-oriented network promotes human gastric cancer metastasis

    PubMed Central

    Wang, Si-Meng; Tie, Jun; Wang, Wen-Lan; Hu, Si-Jun; Yin, Ji-Peng; Yi, Xiao-Fang; Tian, Zu-Hong; Zhang, Xiang-Yuan; Li, Meng-Bin; Li, Zeng-Shan; Nie, Yong-Zhan; Wu, Kai-Chun; Fan, Dai-Ming

    2016-01-01

    Background and aims Aberrant upregulation of POU2F2 expression has been discovered in metastatic gastric cancer (GC). However, the mechanisms underlying the aberrant upregulation and the potential functions of POU2F2 remain uncertain. Design The role and mechanism of POU2F2 in GC metastasis were investigated in gastric epithelial cells, GC cell lines and an experimental metastasis animal model by gain of function and loss of function. Upstream and downstream targets of POU2F2 were selected by bioinformatics and identified by luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation PCR. The influence of miR-218 on its putative target genes (POU2F2, ROBO1 and IKK-β) and GC metastasis was further explored via in vitro and in vivo approaches. Results Increased POU2F2 expression was detected in metastatic GC cell lines and patient samples. POU2F2 was induced by the activation of nuclear factor (NF)-κB and, in turn, regulated ROBO1 transcription, thus functionally contributing to GC metastasis. Finally, miR-218 was found to suppress GC metastasis by simultaneously mediating multiple molecules in the POU2F2-oriented network. Conclusions This study demonstrated that NF-κB and the SLIT2/ROBO1 interaction network with POU2F2 as the central part may exert critical effects on tumour metastasis. Blocking the activation of the POU2F2-oriented metastasis network using miR-218 precursors exemplified a promising approach that sheds light on new strategies for GC treatment. PMID:26019213

  5. The effect of FeF2 on the magneto-optic response in FeF2/Fe/FeF2 sandwiches

    NASA Astrophysics Data System (ADS)

    Pištora, J.; Lesňák, M.; Lišková, E.; Višňovský, Š.; Harward, I.; Maslankiewicz, P.; Balin, K.; Celinski, Z.; Mistrík, J.; Yamaguchi, T.; Lopusnik, R.; Vlček, J.

    2010-04-01

    The room temperature optical constants n and k of MBE grown FeF2 films are reported. Because of poor chemical stability, FeF2 had to be coated with a protective Au layer. Reflection spectral ellipsometry in the photon energy range between 1.3 and 5.2 eV was performed on structures with a typical profile Au(0.5 nm)/FeF2(120 nm)/Au(30 nm)/Ag(20 nm)/Fe(0.6 nm) grown on GaAs(0 0 1) substrate. The spectra of n and k in FeF2 were subsequently employed in the design of FeF2/Fe/FeF2 sandwiches considered as magneto-optic (MO) sensors for weak microwave currents. Their MO response was evaluated using reflection MO (Kerr) spectroscopy at polar magnetization. The present results may be of interest in MO studies of magnetic nanostructures with Fe/FeF2/Fe, including MO magnetometry and MO magnetic domain imaging.

  6. KELCH F-BOX protein positively influences Arabidopsis seed germination by targeting PHYTOCHROME-INTERACTING FACTOR1

    USDA-ARS?s Scientific Manuscript database

    Seeds employ sensory systems that assess various environmental cues over time to maximize the successful transition from embryo to seedling. Here, we show that the Arabidopsis F-Box protein Cold Temperature-Germinating (CTG)-10, identified by activation tagging, is a positive regulator during this p...

  7. A Window into the Brain: Advances in Psychiatric fMRI

    PubMed Central

    Zhan, Xiaoyan

    2015-01-01

    Functional magnetic resonance imaging (fMRI) plays a key role in modern psychiatric research. It provides a means to assay differences in brain systems that underlie psychiatric illness, treatment response, and properties of brain structure and function that convey risk factor for mental diseases. Here we review recent advances in fMRI methods in general use and progress made in understanding the neural basis of mental illness. Drawing on concepts and findings from psychiatric fMRI, we propose that mental illness may not be associated with abnormalities in specific local regions but rather corresponds to variation in the overall organization of functional communication throughout the brain network. Future research may need to integrate neuroimaging information drawn from different analysis methods and delineate spatial and temporal patterns of brain responses that are specific to certain types of psychiatric disorders. PMID:26413531

  8. F-100A on lakebed

    NASA Technical Reports Server (NTRS)

    1955-01-01

    North American F-100A (52-5778) Super Sabre on the Rogers Dry Lakebed in a 1955 photograph. NACA High-Speed Flight Station, Edwards, California, flew this F-100 Super Sabre from 1954 to 1960 to investigate stability and control features of the then-new supersonic Air Force fighter. The program was part of NACA's support to the test and development program of the new 'century series' of aircraft -- F-100, F-101, F-102, F-104, F-105, F-106, and F-107.

  9. Preliminary Study on LiF4-ThF4-PuF4 Utilization as Fuel Salt of miniFUJI Molten Salt Reactor

    NASA Astrophysics Data System (ADS)

    Waris, Abdul; Aji, Indarta K.; Pramuditya, Syeilendra; Widayani; Irwanto, Dwi

    2016-08-01

    miniFUJI reactor is molten salt reactor (MSR) which is one type of the Generation IV nuclear energy systems. The original miniFUJI reactor design uses LiF-BeF2-ThF4-233UF4 as a fuel salt. In the present study, the use of LiF4-ThF4-PuF4 as fuel salt instead of LiF-BeF2-ThF4-UF4 will be discussed. The neutronics cell calculation has been performed by using PIJ (collision probability method code) routine of SRAC 2006 code, with the nuclear data library is JENDL-4.0. The results reveal that the reactor can attain the criticality condition with the plutonium concentration in the fuel salt is equal to 9.16% or more. The conversion ratio diminishes with the enlarging of plutonium concentration in the fuel. The neutron spectrum of miniFUJI MSR with plutonium fuel becomes harder compared to that of the 233U fuel.

  10. Bmal1 is a direct transcriptional target of the orphan nuclear receptor, NR2F1

    USDA-ARS?s Scientific Manuscript database

    Orphan nuclear receptor NR2F1 (also known as COUP-TFI, Chicken Ovalbumin Upstream Promoter Transcription Factor I) is a highly conserved member of the nuclear receptor superfamily. NR2F1 plays a critical role during embryonic development, particularly in the central and peripheral nervous systems a...

  11. The Global Signal in fMRI: Nuisance or Information?

    PubMed Central

    Nalci, Alican; Falahpour, Maryam

    2017-01-01

    The global signal is widely used as a regressor or normalization factor for removing the effects of global variations in the analysis of functional magnetic resonance imaging (fMRI) studies. However, there is considerable controversy over its use because of the potential bias that can be introduced when it is applied to the analysis of both task-related and resting-state fMRI studies. In this paper we take a closer look at the global signal, examining in detail the various sources that can contribute to the signal. For the most part, the global signal has been treated as a nuisance term, but there is growing evidence that it may also contain valuable information. We also examine the various ways that the global signal has been used in the analysis of fMRI data, including global signal regression, global signal subtraction, and global signal normalization. Furthermore, we describe new ways for understanding the effects of global signal regression and its relation to the other approaches. PMID:28213118

  12. Biodistribution, pharmacokinetics and PET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc in a sarcoma- and inflammation-bearing mouse model.

    PubMed

    Liu, Ren-Shyan; Chou, Ta-Kai; Chang, Chih-Hsien; Wu, Chun-Yi; Chang, Chi-Wei; Chang, Tsui-Jung; Wang, Shih-Jen; Lin, Wuu-Jyh; Wang, Hsin-Ell

    2009-04-01

    2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), [(18)F]fluoroacetate ([(18)F]FAc) and [(18)F]fluoromisonidazole ([(18)F]FMISO) were all considered to be positron emission tomography (PET) probes for tumor diagnosis, though based on different rationale of tissue uptake. This study compared the biodistribution, pharmacokinetics and imaging of these three tracers in a sarcoma- and inflammation-bearing mouse model. C3H mice were inoculated with 2x10(5) KHT sarcoma cells in the right thigh on Day 0. Turpentine oil (0.1 ml) was injected in the left thigh on Day 11 to induce inflammatory lesion. Biodistribution, pharmacokinetics and microPET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc were performed on Day 14 after tumor inoculation. The inflammatory lesions were clearly visualized by [(18)F]FDG/microPET and autoradiography at 3 days after turpentine oil injection. The tumor-to-muscle and inflammatory lesion-to-muscle ratios derived from microPET imaging were 6.79 and 1.48 for [(18)F]FMISO, 8.12 and 4.69 for [(18)F]FDG and 3.72 and 3.19 for [(18)F]FAc at 4 h post injection, respectively. Among these, the tumor-to-inflammation ratio was the highest (4.57) for [(18)F]FMISO compared with that of [(18)F]FDG (1.73) and [(18)F]FAc (1.17), whereas [(18)F]FAc has the highest bioavailability (area under concentration of radiotracer vs. time curve, 116.2 hxpercentage of injected dose per gram of tissue). MicroPET images and biodistribution studies showed that the accumulation of [(18)F]FMISO in the tumor is significantly higher than that in inflammatory lesion at 4 h post injection. [(18)F]FDG and [(18)F]FAc delineated both tumor and inflammatory lesions. Our results demonstrated the potential of [(18)F]FMISO/PET in distinguishing tumor from inflammatory lesion.

  13. Calculation of k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} for several small detectors and for two linear accelerators using Monte Carlo simulations

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

    Francescon, P.; Cora, S.; Satariano, N.

    2011-12-15

    Purpose: The scope of this study was to determine a complete set of correction factors for several detectors in static small photon fields for two linear accelerators (linacs) and for several detectors. Methods: Measurements for Monte Carlo (MC) commissioning were performed for two linacs, Siemens Primus and Elekta Synergy. After having determined the source parameters that best fit the measurements of field specific output factors, profiles, and tissue-phantom ratio, the generalized version of the classical beam quality correction factor for static small fields, k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}},more » were determined for several types of detectors by using the egs{sub c}hamber Monte Carlo user code which can accurately reproduce the geometry and the material composition of the detector. The influence of many parameters (energy and radial FWHM of the electron beam source, field dimensions, type of accelerator) on the value of k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} was evaluated. Moreover, a MC analysis of the parameters that influence the change of k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} as a function of field dimension was performed. A detailed analysis of uncertainties related to the measurements of the field specific output factor and to the Monte Carlo calculation of k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} was done. Results: The simulations demonstrated that the correction factor k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} can be considered independent from the quality beam factor Q in the range 0.68 {+-} 0.01 for all the detectors analyzed. The k{sub Q{sub c{sub l{sub i

  14. Antihuman factor VIII C2 domain antibodies in hemophilia A mice recognize a functionally complex continuous spectrum of epitopes dominated by inhibitors of factor VIII activation

    PubMed Central

    Meeks, Shannon L.; Healey, John F.; Parker, Ernest T.; Barrow, Rachel T.

    2007-01-01

    The diversity of factor VIII (fVIII) C2 domain antibody epitopes was investigated by competition enzyme-linked immunosorbent assay (ELISA) using a panel of 56 antibodies. The overlap patterns produced 5 groups of monoclonal antibodies (MAbs), designated A, AB, B, BC, and C, and yielded a set of 18 distinct epitopes. Group-specific loss of antigenicity was associated with mutations at the Met2199/Phe2200 phospholipid binding β-hairpin (group AB MAbs) and at Lys2227 (group BC MAbs), which allowed orientation of the epitope structure as a continuum that covers one face of the C2 β-sandwich. MAbs from groups A, AB, and B inhibit the binding of fVIIIa to phospholipid membranes. Group BC was the most common group and displayed the highest specific fVIII inhibitor activities. MAbs in this group are type II inhibitors that inhibit the activation of fVIII by either thrombin or factor Xa and poorly inhibit the binding of fVIII to phospholipid membranes or von Willebrand factor (VWF). Group BC MAbs are epitopically and mechanistically distinct from the extensively studied group C MAb, ESH8. These results reveal the structural and functional complexity of the anti-C2 domain antibody response and indicate that interference with fVIII activation is a major attribute of the inhibitor landscape. PMID:17848617

  15. Histopathology of type C liver disease for determining hepatocellular carcinoma risk factors.

    PubMed

    Matsumura, Hiroshi; Nirei, Kazushige; Nakamura, Hitomi; Higuchi, Teruhisa; Arakawa, Yasuo; Ogawa, Masahiro; Tanaka, Naohide; Moriyama, Mitsuhiko

    2013-08-14

    To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma (HCC). We studied 232 patients, who underwent liver biopsy for type C chronic liver disease between 1992 and 2009, with sustained virological response (SVR) after interferon therapy. The patients were divided into two groups according to the F stage 0 + 1 + 2 group (n = 182) and F3 + 4 group (n = 50). We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0 + 1 + 2 and F3 + 4 groups. Then, the background factors and liver histopathological findings, including the degree of fibrosis, F stage, inflammation, necrosis, bile duct obstruction, fat deposition, and degree of irregular regeneration (IR) of hepatocytes, were correlated with the risk of developing HCC. HCC developed in three of 182 (1.6%) patients in the F0 + 1 + 2 group, and four of 50 (8.0%) in the F3 + 4 group. The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3 + 4 group (log rank test P = 0.0224). The presence of atypical hepatocytes among IR of hepatocytes in the F3 + 4 group resulted in a higher cumulative incidence of HCC, and was significantly correlated with risk of HCC development (RR = 20.748, 95%CI: 1.335-322.5, P = 0.0303). Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.

  16. Measurement of 17F(d ,n )18Ne and the impact on the 17F(p ,γ )18Ne reaction rate for astrophysics

    NASA Astrophysics Data System (ADS)

    Kuvin, S. A.; Belarge, J.; Baby, L. T.; Baker, J.; Wiedenhöver, I.; Höflich, P.; Volya, A.; Blackmon, J. C.; Deibel, C. M.; Gardiner, H. E.; Lai, J.; Linhardt, L. E.; Macon, K. T.; Rasco, B. C.; Quails, N.; Colbert, K.; Gay, D. L.; Keeley, N.

    2017-10-01

    Background: The 17F(p ,γ )18Ne reaction is part of the astrophysical "hot CNO" cycles that are important in astrophysical environments like novas. Its thermal reaction rate is low owing to the relatively high energy of the resonances and therefore is dominated by direct, nonresonant capture in stellar environments at temperatures below 0.4 GK. Purpose: An experimental method is established to extract the proton strength to bound and unbound states in experiments with radioactive ion beams and to determine the parameters of direct and resonant capture in the 17F(p ,γ )18Ne reaction. Method: The 17F(d ,n )18Ne reaction is measured in inverse kinematics using a beam of the short-lived isotope 17F and a compact setup of neutron, proton, γ -ray, and heavy-ion detectors called resoneut. Results: The spectroscopic factors for the lowest l =0 proton resonances at Ec .m .=0.60 and 1.17 MeV are determined, yielding results consistent within 1.4 σ of previous proton elastic-scattering measurements. The asymptotic normalization coefficients of the bound 21+ and 22+ states in 18Ne are determined and the resulting direct-capture reaction rates are extracted. Conclusions: The direct-capture component of the 17F(p ,γ )18Ne reaction is determined for the first time from experimental data on 18Ne.

  17. Impact of genetic factors (VKORC1, CYP2C9, CYP4F2 and EPHX1) on the anticoagulation response to fluindione

    PubMed Central

    Lacut, Karine; Ayme-Dietrich, Estelle; Gourhant, Lenaick; Poulhazan, Elise; Andro, Marion; Becquemont, Laurent; Mottier, Dominique; Le Gal, Gregoire; Verstuyft, Celine

    2012-01-01

    AIM Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9) and of a key pharmacologic target of vitamin K antagonists, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to coumarin derivatives. The role of these variants in fluindione response is unknown. Our aim was to assess whether genetic factors contribute to the variability in the response to fluindione. METHODS Four hundred sixty-five patients with a venous thromboembolic event treated by fluindione for at least 3 months with a target international normalized ratio (INR) of 2.0 to 3.0 were studied. VKORC1, CYP2C9, CYP4F2 and EPHX1 genotypes were assessed. INR checks, fluindione doses and bleeding events were collected. RESULTS VKORC1 genotype had a significant impact on early anticoagulation (INR value ≥2 after the first two intakes) (P < 0.0001), on the time required to reach a first INR within the therapeutic range (P < 0.0001) and on the time to obtain a first INR value > 4 (P = 0.0002). The average daily dose of fluindione during the first period of stability was significantly associated with the VKORC1 genotype: 19.8 mg (±5.5) for VKORC1 CC, 14.7 mg (±6.2) for VKORC1 CT and 8.2 mg (±2.5) for VKORC1 TT (P < 0.0001). CYP2C9, CYP4F2 and EPHX1 genotypes did not significantly influence the response to fluindione. CONCLUSIONS VKORC1 genotype strongly affected anticoagulation induced by fluindione whereas CYP2C9, CYP4F2 and EPHX1 genotypes seemed less determining. PMID:21883387

  18. Properties of AlF3 and LaF3 films at 193nm

    NASA Astrophysics Data System (ADS)

    Xue, Chunrong; Shao, Jianda

    2010-10-01

    In order to develop low loss, high-performance 193nm Fluoride HR mirrors and anti-reflection coatings, LaF3 and AlF3 materials, used for a single-layer coating, were deposited by a molybdenum boat evaporation process. Various microstructures that formed under different substrate temperatures and with deposition rates were investigated. The relation between these microstructures (including cross section morphology, surface roughness and crystalline structure), the optical properties (including refractive index and optical loss) and mechanical properties (stress) were investigated. Furthermore, AlF3 used as a low-index material and LaF3 used as a high-index material were designed and deposited for multilayer coatings. Transmittance, reflectance, stress, and the laser-induced damage threshold (LIDT) were studied. It is shown that AlF3 and LaF3 thin films, deposited on the substrate at a temperature of 300 °C, obtained good quality thin films with high transmittance and little optical loss at 193 nm. For multilayer coatings, the absorption mainly comes from LaF3. Based on these studies, The thickness of 193nm films was controled by a 1/3 baffle with pre-coating technology. the LaF3/AlF3 AR coantings and HR mirrors at 193nm were designed and deposited. Under the present experimental conditions, the reflectance of LaF3/AlF3 HR mirror is up to 96%, and its transmittance is 1.5%. the LaF3/AlF3 AR coanting's residual reflectance is less than 0.14%, and single-sided transmittance is 93.85%. To get a high-performance 193nm AR coating, super-polished substrate is the best choice.

  19. Evaluation and comparison of absorbed dose for electron beams by LiF and diamond dosimeters

    NASA Astrophysics Data System (ADS)

    Mosia, G. J.; Chamberlain, A. C.

    2007-09-01

    The absorbed dose response of LiF and diamond thermoluminescent dosimeters (TLDs), calibrated in 60Co γ-rays, has been determined using the MCNP4B Monte Carlo code system in mono-energetic megavoltage electron beams from 5 to 20 MeV. Evaluation of the dose responses was done against the dose responses of published works by other investigators. Dose responses of both dosimeters were compared to establish if any relation exists between them. The dosimeters were irradiated in a water phantom with the centre of their top surfaces (0.32×0.32 cm 2), placed at dmax perpendicular to the radiation beam on the central axis. For LiF TLD, dose responses ranged from 0.945±0.017 to 0.997±0.011. For the diamond TLD, the dose response ranged from 0.940±0.017 to 1.018±0.011. To correct for dose responses by both dosimeters, energy correction factors were generated from dose response results of both TLDs. For LiF TLD, these correction factors ranged from 1.003 up to 1.058 and for diamond TLD the factors ranged from 0.982 up to 1.064. The results show that diamond TLDs can be used in the place of the well-established LiF TLDs and that Monte Carlo code systems can be used in dose determinations for radiotherapy treatment planning.

  20. Reconstructing f(R) modified gravity with dark energy parametrization

    NASA Astrophysics Data System (ADS)

    Morita, Masaaki; Takahashi, Hirotaka

    2014-03-01

    We demonstrate the reconstruction of f(R) modified gravity theory with late-time accelerated cosmic expansion. A second-order differential equation for Lagrangian density is obtained from the field equation, and is solved as a function of the cosmic scale factor in two cases. First we begin with the case of a wCDM cosmological model, in which a dark-energy equation-of-state parameter w is constant, for simplicity. Next we extend the method to a case in which the parameter w is epoch-dependent and is expressed as the Chevallier-Polarski-Linder parametrization. Thus we can represent Lagrangian density of f(R) modified gravity theory in terms of dark energy parameters.

  1. Agronomic performance of F1, F2 and F3 hybrids between weedy rice and transgenic glufosinate-resistant rice.

    PubMed

    Song, Xiaoling; Wang, Zhou; Qiang, Sheng

    2011-08-01

    Studies of hybrid fitness, of which agronomic performance may be an indicator, can help in evaluating the potential for introgression of a transgene from a transgenic crop to wild relatives. The objective of this study was to assess the agronomic performance of reciprocal hybrids between two transgenic glufosinate-resistant rice lines, Y0003 and 99-t, and two weedy rice accessions, WR1 and WR2, in the greenhouse. F1 hybrids displayed heterosis in height, flag leaf area and number of spikelets per panicle. The agronomic performance of F1 between WR1 and Y0003 was not affected by crossing direction. The tiller and panicle numbers of F1 individuals were higher than their F2 counterparts. However, these traits did not change significantly from the F2 to the F3 generation or in hybrids with weedy rice as maternal or paternal plants. For all hybrids, the in vitro germination rates of fresh pollen were similar and significantly lower than those of their parents, seed sets were similar to or of lower value than those of weedy rice parents and seed shattering characteristics were partially suppressed, but the survival of hybrids over winter in the field was similar to that of weedy rice parents. All F1, F2 and F3 hybrids had similar composite agronomic performance to weedy rice parents. There was no significant decrease in the composite agronomic performance of any of the hybrids compared with weedy rice. This implies that gene flow from transgenic cultivated rice to weedy rice could occur under natural conditions. Copyright © 2011 Society of Chemical Industry.

  2. F-aggregate centers formation in BaLiF3 crystals

    NASA Astrophysics Data System (ADS)

    Prado, L.; Gomes, L.; Baldochi, S. L.; Morato, S. P.; Vieira, N. D.

    The kinetics of F-aggregate centers formation is investigated in the inverted fluoroperovskite of BaLiF3 submitted to electron-irradiation. By studies of the changes in the absorption spectra during storage of samples in the dark, at room temperature, it was possible to verify a surprising and interesting dependence on defect formation with the crystal growth direction. In spite of its cubic structure, crystals grown in the <100> and <111> directions and submitted to the same conditions of irradiation, showed in particular, to enhance the production of a defect absorbing at 630 nm in <100> crystals which we believe to correspond to F+2-centers in BaLiF3

  3. FLRW cosmological models with quark and strange quark matters in f(R,T) gravity

    NASA Astrophysics Data System (ADS)

    Nagpal, Ritika; Singh, J. K.; Aygün, S.

    2018-06-01

    In this paper, we have studied the magnetized quark matter (QM) and strange quark matter (SQM) distributions in the presence of f(R,T) gravity in the background of Friedmann-Lemaître-Robertson-Walker (FLRW) metric. To get exact solutions of modified field equations we have used f(R,T ) = R + 2 f(T) model given by Harko et al. with two different parametrization of geometrical parameters i.e. the parametrization of the deceleration parameter q , and the scale factor a in hybrid expansion form. Also, we have obtained Einstein Static Universe (ESU) solutions for QM and SQM distributions in f(R,T) gravity and General Relativity (GR). All models in f(R,T) gravity and GR for FRW and ESU Universes with QM also SQM distributions, we get zero magnetic field. These results agree with the solutions of Aktaş and Aygün in f(R,T) gravity. However, we have also discussed the physical consequences of our obtained models.

  4. Prospective study of the clinical performance of three BACTEC media in a modern emergency department: Plus Aerobic/F, Plus Anaerobic/F, and Anaerobic Lytic/F.

    PubMed

    Rocchetti, Andrea; Di Matteo, Luigi; Bottino, Paolo; Foret, Benjamin; Gamalero, Elisa; Calabresi, Alessandra; Guido, Gianluca; Casagranda, Ivo

    2016-11-01

    The performance of 3 blood culture bottles (BACTEC Plus Aerobic/F, Plus Anaerobic/F, and Anaerobic Lytic/F) were analyzed with clinical specimens collected from 688 Emergency Department patients. A total of 270 strains belonging to 33 species were identified, with E. coli and S. aureus as the most frequently detected. Overall recovery rate (RR) of bacteria and yeast was equivalent in the Plus Aerobic/F vials (208 of 270 isolates; 77.0%) and Anaerobic Lytic/F vials (206 isolates; 76.3%) and significantly better than in the Plus Anaerobic/F vials (189 isolates; 70.0%). Median time to detection (TTD) was earliest with the Anaerobic Lytic/F vials (12.0h) compared with the Plus Aerobic/F (14.6h) and Plus Anaerobic/F vials (15.4h). Positivity rate (PR) was similar for Anaerobic Lytic/F vials (76.9%) and Plus Aerobic/F vials (76.5%), but better if compared with Plus Anaerobic/F vials (69.4%). The PR and TTD for the combination of Plus Aerobic/F with Anaerobic Lytic/F (94.5% and 12.3h, respectively) was significantly better than with Plus Aerobic/F with Plus Anaerobic/F (87.8% and 14.1h). Copyright © 2016 Elsevier B.V. All rights reserved.

  5. How Accurately do Leading and Lagging Indictors Predict F-16 Aircraft Availability (AA)

    DTIC Science & Technology

    2016-08-01

    Predictions AU/ACSC/2016 vi PREFACE As the F-16 fleet continues to age, and budgets continue to shrink , United States Air Force (USAF... shrinking budgets, it is imperative for maintenance leaders to use all tools available to them to improve the amount of aircraft available for operations...remarkable considering the overall F-16 fleet shrinking at a steady pace (see table 2 for information). AA is one of the most critical factors that

  6. Risk factors for chronic subdural haematoma formation do not account for the established male bias.

    PubMed

    Marshman, Laurence A G; Manickam, Appukutty; Carter, Danielle

    2015-04-01

    The 'subdural space' is an artefact of inner dural border layer disruption: it is not anatomical but always pathological. A male bias has long been accepted for chronic subdural haematomas (CSDH), and increased male frequencies of trauma and/or alcohol abuse are often cited as likely explanations: however, no study has validated this. We investigated to see which risk factors accounted for the male bias with CSDH. Retrospective review of prospectively collected data. A male bias (M:F 97:58) for CSDH was confirmed in n=155 patients. The largest risk factor for CSDH was cerebral atrophy (M:F 94% vs. 91%): whilst a male bias prevailed in mild-moderate cases (M:F 58% vs. 41%), a female bias prevailed for severe atrophy (F:M 50% vs. 36%) (χ(2)=3.88, P=0.14). Risk factors for atrophy also demonstrated a female bias, some approached statistical significance: atrial fibrillation (P=0.05), stroke/TIA (P=0.06) and diabetes mellitus (P=0.07). There was also a trend for older age in females (F:M 72±13 years vs. 68±15 years, P=0.09). The third largest risk factor, after atrophy and trauma (i.e. anti-coagulant and anti-platelet use) was statistically significantly biased towards females (F:M 50% vs. 33%, P=0.04). No risk factor accounted for the established male bias with CSDH. In particular, a history of trauma (head injury or fall [M:F 50% vs. 57%, P=0.37]), and alcohol abuse (M:F 17% vs. 16%, P=0.89) was remarkably similar between genders. No recognised risk factor for CSDH formation accounted for the established male bias: risk factor trends generally favoured females. In particular, and in contrast to popular belief, a male CSDH bias did not relate to increased male frequencies of trauma and/or alcohol abuse. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  7. ^2H(^18F,p)^19F Study at 6 MeV/u

    NASA Astrophysics Data System (ADS)

    Kozub, R. L.; Nesaraja, C. D.; Moazen, B. H.; Scott, J. P.; Bardayan, D. W.; Blackmon, J. C.; Gross, C. J.; Shapira, D.; Smith, M. S.; Batchelder, J. C.; Brune, C. R.; Champagne, A. E.; Sahin, L.; Cizewski, J. A.; Thomas, J. S.; Davinson, T.; Woods, P. J.; Greife, U.; Jewett, C.; Livesay, R. J.; Ma, Z.; Parker, P. D.

    2003-04-01

    The degree to which the (p,α) and (p,γ) reactions destroy ^18F at temperatures ˜1-4 x 10^8 K is important for understanding the synthesis of nuclei in nova explosions and for using ^18F as a monitor of nova mechanisms in gamma ray astronomy. The reactions are dominated by low-lying proton resonances near the ^18F+p threshold (E_x=6.411 MeV excitation energy in ^19Ne). To gain further information about these resonances, we have used the inverse ^18F(d,p)^19F neutron transfer reaction at the Holifield Radioactive Ion Beam Facility to selectively populate corresponding mirror states in ^19F. Proton angular distributions were measured for states in ^19F in the excitation energy range 0-9 MeV. Results and implications for the ^18F+p reactions and nuclear structure will be presented. ^1Supported by DOE. ^2ORNL is managed by UT-Battelle, LLC, for the USDOE.

  8. Mental stress assessment using simultaneous measurement of EEG and fNIRS

    PubMed Central

    Al-Shargie, Fares; Kiguchi, Masashi; Badruddin, Nasreen; Dass, Sarat C.; Hani, Ahmad Fadzil Mohammad; Tang, Tong Boon

    2016-01-01

    Previous studies reported mental stress as one of the major contributing factors leading to various diseases such as heart attack, depression and stroke. An accurate stress assessment method may thus be of importance to clinical intervention and disease prevention. We propose a joint independent component analysis (jICA) based approach to fuse simultaneous measurement of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) on the prefrontal cortex (PFC) as a means of stress assessment. For the purpose of this study, stress was induced by using an established mental arithmetic task under time pressure with negative feedback. The induction of mental stress was confirmed by salivary alpha amylase test. Experiment results showed that the proposed fusion of EEG and fNIRS measurements improves the classification accuracy of mental stress by +3.4% compared to EEG alone and +11% compared to fNIRS alone. Similar improvements were also observed in sensitivity and specificity of proposed approach over unimodal EEG/fNIRS. Our study suggests that combination of EEG (frontal alpha rhythm) and fNIRS (concentration change of oxygenated hemoglobin) could be a potential means to assess mental stress objectively. PMID:27867700

  9. E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

    PubMed

    Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

    2009-05-01

    E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

  10. Origin of Abelian gauge symmetries in heterotic/F-theory duality

    DOE PAGES

    Cvetič, Mirjam; Grassi, Antonella; Klevers, Denis; ...

    2016-04-07

    Here, we study aspects of heterotic/F-theory duality for compactifications with Abelian gauge symmetries. We consider F-theory on general Calabi-Yau manifolds with a rank one Mordell-Weil group of rational sections. By rigorously performing the stable degeneration limit in a class of toric models, and also derive both the Calabi-Yau geometry and the spectral cover describing the vector bundle in the heterotic dual theory. We carefully investigate the spectral cover employing the group law on the elliptic curve in the heterotic theory. We find in explicit examples that there are three different classes of heterotic duals that have U(1) factors in theirmore » low energy effective theories: split spectral covers describing bundles with S(U(m) x U(1)) structure group, spectral covers containing torsional sections that seem to give rise to bundles with SU(m) x Z_k structure group and bundles with purely non-Abelian structure groups having a centralizer in E_8 containing a U(1) factor. In the former two cases, it is required that the elliptic fibration on the heterotic side has a non-trivial Mordell-Weil group. And while the number of geometrically massless U(1)'s is determined entirely by geometry on the F-theory side, on the heterotic side the correct number of U(1)'s is found by taking into account a Stuckelberg mechanism in the lower-dimensional effective theory. Finally, in geometry, this corresponds to the condition that sections in the two half K3 surfaces that arise in the stable degeneration limit of F-theory can be glued together globally.« less

  11. Characterization of a genetically engineered mouse model of hemophilia A with complete deletion of the F8 gene.

    PubMed

    Chao, B N; Baldwin, W H; Healey, J F; Parker, E T; Shafer-Weaver, K; Cox, C; Jiang, P; Kanellopoulou, C; Lollar, P; Meeks, S L; Lenardo, M J

    2016-02-01

    ESSENTIALS: Anti-factor VIII (FVIII) inhibitory antibody formation is a severe complication in hemophilia A therapy. We genetically engineered and characterized a mouse model with complete deletion of the F8 coding region. F8(TKO) mice exhibit severe hemophilia, express no detectable F8 mRNA, and produce FVIII inhibitors. The defined background and lack of FVIII in F8(TKO) mice will aid in studying FVIII inhibitor formation. The most important complication in hemophilia A treatment is the development of inhibitory anti-Factor VIII (FVIII) antibodies in patients after FVIII therapy. Patients with severe hemophilia who express no endogenous FVIII (i.e. cross-reacting material, CRM) have the greatest incidence of inhibitor formation. However, current mouse models of severe hemophilia A produce low levels of truncated FVIII. The lack of a corresponding mouse model hampers the study of inhibitor formation in the complete absence of FVIII protein. We aimed to generate and characterize a novel mouse model of severe hemophilia A (designated the F8(TKO) strain) lacking the complete coding sequence of F8 and any FVIII CRM. Mice were created on a C57BL/6 background using Cre-Lox recombination and characterized using in vivo bleeding assays, measurement of FVIII activity by coagulation and chromogenic assays, and anti-FVIII antibody production using ELISA. All F8 exonic coding regions were deleted from the genome and no F8 mRNA was detected in F8(TKO) mice. The bleeding phenotype of F8(TKO) mice was comparable to E16 mice by measurements of factor activity and tail snip assay. Similar levels of anti-FVIII antibody titers after recombinant FVIII injections were observed between F8(TKO) and E16 mice. We describe a new C57BL/6 mouse model for severe hemophilia A patients lacking CRM. These mice can be directly bred to the many C57BL/6 strains of genetically engineered mice, which is valuable for studying the impact of a wide variety of genes on FVIII inhibitor formation on a

  12. Formation of metal nanoparticles in MgF2, CaF2 and BaF2 crystals under the electron beam irradiation

    NASA Astrophysics Data System (ADS)

    Bochkareva, Elizaveta S.; Sidorov, Alexander I.; Yurina, Uliana V.; Podsvirov, Oleg A.

    2017-07-01

    It is shown experimentally that electron beam action with electrons energies of 50 and 70 keV on MgF2, CaF2 and BaF2 crystals results in local formation in the crystal near-surface layer of Mg, Ca or Ba nanoparticles which possess plasmon resonance. In the case of MgF2 spheroidal nanoparticles are formed, in the cases of CaF2 and BaF2 - spherical. The formation of metal nanoparticles is confirmed by computer simulation in dipole quasistatic approximation. The dependence of absorption via electron irradiation dose is non-linear. It is caused by the increase of nanoparticles concentration and by the increase of nanoparticles sizes during irradiation. In the irradiated zones of MgF2 crystals, for irradiation doses less than 80 mC/cm2, the intense luminescence in a visible range appears. The practical application of fabricated composite materials for multilevel optical information recording is discussed.

  13. 17 CFR 240.15c3-1f - Optional market and credit risk requirements for OTC derivatives dealers (Appendix F to 17 CFR...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... less than six months. Historical data sets must be updated at least every three months and reassessed... model which at a minimum must adhere to the criteria set forth in paragraph (e) of this Appendix F. The... theoretical pricing model contains the minimum pricing factors set forth in Appendix A (§ 240.15c3-1a). The...

  14. F-14 #991 cockpit

    NASA Image and Video Library

    1980-07-02

    View of the cockpit of NASA's F-14, tail number 991. This aircraft was the first of a series of post-Vietnam fighters, followed by the F-15, F-16, and F-18. They were designed for maneuverability in air-to-air combat. The F-14s had a spin problem that posed problems for its ability to engage successfully in a dogfight, since it tended to depart from controlled flight at the high angles of attack that frequently occur in close-in engagements.

  15. Distribution of Attenuation Factor Beneath the Japanese Islands

    NASA Astrophysics Data System (ADS)

    Fujihara, S.; Hashimoto, M.

    2001-12-01

    In this research, we tried to estimate the distribution of attenuation factor of seismic wave, which is closely related to the above-mentioned inelastic parameters. Here the velocity records of events from the Freesia network and the J-array network were used. The events were selected based on the following criteria: (a) events with JMA magnitudes from 3.8 to 5.0 and hypocentral distance from 20km to 200km, (b) events with JMA magnitudes from 5.1 to 6.8 and hypocentral distance from 200km to 10_?, (c) Depth of all events is greater than 30km with S/N ratio greater than 2. After correcting the instrument response, P-wave spectra were estimated. Following Boatwright (1991), the observed spectra were modeled by the theoretical spectra by assuming the following relation; Aij(f) = Si(f) Pij(f) Cj(f). Brune's model (1970) was assumed for the source model. Aij(f), Si(f), Pij(f), and Cj(f) are defined as observed spectrum, source spectrum, propagation effect, and site effect, respectively. Frequency dependence of attenuation factor was not assumed here. The global standard velocity model (AK135) is used for ray tracing. Ellipticity corrections and station elevation corrections are also done. The block sizes are 50km by 50km laterally and increase vertically. As the results of analysis, the attenuation structure beneath Japanese Islands up to the depth of 180km was reconstructed with relatively good resolution. The low Q distribution is clearly seen in central Hokkaido, western Hokkaido, Tohoku region, Hida region, Izu region, and southern Kyushu. The relatively sharp decrease in Q associated with asthenosphere can be seen below the depth of 70km.

  16. Atypical E2f functions are critical for pancreas polyploidization

    PubMed Central

    Moreno, Eva; Toussaint, Mathilda J. M.; Tooten, Peter C. J.; van Essen, Saskia C.; van Liere, Elsbeth A.; Youssef, Sameh A.; Bongiovanni, Laura; de Bruin, Alain

    2018-01-01

    The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age. PMID:29329320

  17. Atypical E2f functions are critical for pancreas polyploidization.

    PubMed

    Matondo, Ramadhan B; Moreno, Eva; Toussaint, Mathilda J M; Tooten, Peter C J; van Essen, Saskia C; van Liere, Elsbeth A; Youssef, Sameh A; Bongiovanni, Laura; de Bruin, Alain

    2018-01-01

    The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

  18. Is prophylaxis required for delivery in women with factor VII deficiency?

    PubMed Central

    Baumann Kreuziger, Lisa M.; Morton, Colleen T.; Reding, Mark T.

    2013-01-01

    Introduction Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant hemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is unclear whether prophylaxis is necessary prior to delivery. Aim To define management, hemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Methods Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using “factor VII deficiency” and “pregnancy” or “surgery.” Overall 34 articles, 4 abstracts, and 3 institutional cases were reviewed. Results Literature from 1953–2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Hemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 cesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing cesarean section compared to vaginal delivery. Post-partum hemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. Conclusion We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum hemorrhage was seen in deliveries with and without prophylaxis. Therefore we recommend that rfVIIa be available in the case of hemorrhage or surgical intervention, but not as mandatory prophylaxis. PMID:23607277

  19. Is prophylaxis required for delivery in women with factor VII deficiency?

    PubMed

    Baumann Kreuziger, L M; Morton, Colleen T; Reding, Mark T

    2013-11-01

    Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant haemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is not clear whether prophylaxis is necessary prior to delivery. The aim of this study was to define management, haemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using "factor VII deficiency" and "pregnancy" or "surgery." Overall 34 articles, four abstracts, and three institutional cases were reviewed. Literature from 1953 to 2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Haemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 caesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing caesarean section compared to vaginal delivery. Post-partum haemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum haemorrhage was seen in deliveries with and without prophylaxis. Therefore, we recommend that rfVIIa be available in the case of haemorrhage or surgical intervention, but not as mandatory prophylaxis. © 2013 John Wiley & Sons Ltd.

  20. Nicotine, IFN-γ and retinoic acid mediated induction of MUC4 in pancreatic cancer requires E2F1 and STAT-1 transcription factors and utilize different signaling cascades.

    PubMed

    Kunigal, Sateesh; Ponnusamy, Moorthy P; Momi, Navneet; Batra, Surinder K; Chellappan, Srikumar P

    2012-04-26

    The membrane-bound mucins are thought to play an important biological role in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce the expression of MUC4 in pancreatic cancer cell lines CD18, CAPAN2, AsPC1 and BxPC3. Chromatin immunoprecipitation assays and real-time PCR showed that transcription factors E2F1 and STAT1 can positively regulate MUC4 expression at the transcriptional level. IFN-γ and RA could collaborate with nicotine in elevating the expression of MUC4, utilizing E2F1 and STAT1 transcription factors. Depletion of STAT1 or E2F1 abrogated the induction of MUC4; nicotine-mediated induction of MUC4 appeared to require α7-nicotinic acetylcholine receptor subunit. Further, Src and ERK family kinases also mediated the induction of MUC4, since inhibiting these signaling molecules prevented the induction of MUC4. MUC4 was also found to be necessary for the nicotine-mediated invasion of pancreatic cancer cells, suggesting that induction of MUC4 by nicotine and other agents might contribute to the genesis and progression of pancreatic cancer. Our studies show that agents that can promote the growth and invasion of pancreatic cancer cells induce the MUC4 gene through multiple pathways and this induction requires the transcriptional activity of E2F1 and STAT1. Further, the Src as well as ERK signaling pathways appear to be involved in the induction of this gene. It appears that targeting these signaling pathways

  1. Nicotine, IFN-γ and retinoic acid mediated induction of MUC4 in pancreatic cancer requires E2F1 and STAT-1 transcription factors and utilize different signaling cascades

    PubMed Central

    2012-01-01

    Background The membrane-bound mucins are thought to play an important biological role in cell–cell and cell–matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce the expression of MUC4 in pancreatic cancer cell lines CD18, CAPAN2, AsPC1 and BxPC3. Results Chromatin immunoprecipitation assays and real-time PCR showed that transcription factors E2F1 and STAT1 can positively regulate MUC4 expression at the transcriptional level. IFN-γ and RA could collaborate with nicotine in elevating the expression of MUC4, utilizing E2F1 and STAT1 transcription factors. Depletion of STAT1 or E2F1 abrogated the induction of MUC4; nicotine-mediated induction of MUC4 appeared to require α7-nicotinic acetylcholine receptor subunit. Further, Src and ERK family kinases also mediated the induction of MUC4, since inhibiting these signaling molecules prevented the induction of MUC4. MUC4 was also found to be necessary for the nicotine-mediated invasion of pancreatic cancer cells, suggesting that induction of MUC4 by nicotine and other agents might contribute to the genesis and progression of pancreatic cancer. Conclusions Our studies show that agents that can promote the growth and invasion of pancreatic cancer cells induce the MUC4 gene through multiple pathways and this induction requires the transcriptional activity of E2F1 and STAT1. Further, the Src as well as ERK signaling pathways appear to be involved in the induction of this gene. It appears that

  2. Psychosocial factors and tooth wear with a significant component of attrition.

    PubMed

    da Silva, A M; Oakley, D A; Hemmings, K W; Newman, H N; Watkins, S

    1997-06-01

    Pathological tooth wear is often associated with bruxism, which appears in turn to be influenced by psychosocial factors. This study investigated putative relationships between psychosocial factors (total and average perceived stress, state and trait anxiety) and tooth wear, comparing 45 patients exhibiting tooth wear with a significant component of attrition to 45 controls. Groups were matched for gender and age. Subjects completed the Modified and Perceived Stress Scale and the State-Trait Anxiety Inventory. A between-groups multivariate analysis of variance indicated that the two groups did not differ significantly on the combined psychosocial factors, F(4,85) = 1.16, P > 0.05. However, a univariate F-test showed that tooth-wear patients presented significantly more trait anxiety than controls, F(1,88) = 4.15, P < 0.05. Further research is indicated to clarify the importance of trait anxiety and other psychosocial factors in the progression of tooth wear with a significant component of attrition.

  3. New Dioxaborolane Chemistry Enables [(18)F]-Positron-Emitting, Fluorescent [(18)F]-Multimodality Biomolecule Generation from the Solid Phase.

    PubMed

    Rodriguez, Erik A; Wang, Ye; Crisp, Jessica L; Vera, David R; Tsien, Roger Y; Ting, Richard

    2016-05-18

    New protecting group chemistry is used to greatly simplify imaging probe production. Temperature and organic solvent-sensitive biomolecules are covalently attached to a biotin-bearing dioxaborolane, which facilitates antibody immobilization on a streptavidin-agarose solid-phase support. Treatment with aqueous fluoride triggers fluoride-labeled antibody release from the solid phase, separated from unlabeled antibody, and creates [(18)F]-trifluoroborate-antibody for positron emission tomography and near-infrared fluorescent (PET/NIRF) multimodality imaging. This dioxaborolane-fluoride reaction is bioorthogonal, does not inhibit antigen binding, and increases [(18)F]-specific activity relative to solution-based radiosyntheses. Two applications are investigated: an anti-epithelial cell adhesion molecule (EpCAM) monoclonal antibody (mAb) that labels prostate tumors and Cetuximab, an anti-epidermal growth factor receptor (EGFR) mAb (FDA approved) that labels lung adenocarcinoma tumors. Colocalized, tumor-specific NIRF and PET imaging confirm utility of the new technology. The described chemistry should allow labeling of many commercial systems, diabodies, nanoparticles, and small molecules for dual modality imaging of many diseases.

  4. Calculations of total electron-impact ionization cross sections for Fluoroketone C5F10O and Fluoronitrile C4F7N using modified Deutsch-Märk formula

    NASA Astrophysics Data System (ADS)

    Xiong, Jiayu; Li, Xingwen; Wu, Jian; Guo, Xiaoxue; Zhao, Hu

    2017-11-01

    Both fluoroketone C5F10O and fluoronitrile C4F7N are promising substitute gases for SF6. The electron-impact ionization cross sections for these two gases are calculated using the Deutsch-Märk (DM) formula and its modified method. The necessary molecular geometry optimization and electron population were determined by ab initio calculation, which was performed with quantum chemistry code. The level of calculation, including the theoretical method and basis-set, are carefully determined. To eliminate the drawbacks of the DM formula, a modified DM formula is set in this paper. The modified DM formula, of which the weighting factors are changed, has a better agreement with the experimental data on both the peak and shape of the cross-section curves. The results calculated by DM formula and modified DM formula are given as references to fill in gaps in further research into C5F10O and C4F7N.

  5. Creating effective variable message signs : human factors issues.

    DOT National Transportation Integrated Search

    1998-01-01

    This report addresses the human factors issues related to the reading and comprehension of variable message sign (VMS) messages. A review of the literature was conducted on factors that affect how people read VMSs. Several topics were reviewed. The f...

  6. [Process of meiosis in interspecific hybrid F1 Lycopersicon esculentum Mill. x Lycopersicon chilense Dun].

    PubMed

    Montvid, P Iu; Samovol, O P; Miroshnychenko, V P

    2011-01-01

    The investigation concerns meiosis behaviour in embryo-culture-obtained Lycopersicon esculentum Mill. (mutant seedline Mo 638) x L. chilense Dun. F1 hybrid and its parental forms. It was determined that chiasma frequency decreased while univalent and meiotic disorder frequencies increased in F1 plants in comparison with parents forms. Univalent number and the percent of main disorders lowered with bud tier increasing. The conclusion was made about meiosis regularity connection with the influence of environment factors and heterozygous genotype of F1 plants Lycopersicon esculentum x L. chilense.

  7. 18F-FDOPA PET/CT imaging of MAX-related pheochromocytoma.

    PubMed

    Taïeb, David; Jha, Abhishek; Guerin, Carole; Pang, Ying; Adams, Karen T; Chen, Clara C; Romanet, Pauline; Roche, Philippe; Essamet, Wassim; Ling, Alexander; Quezado, Martha M; Castinetti, Frédéric; Sebag, Fréderic; Pacak, Karel

    2018-03-08

    MYC associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of approximately 40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO. The objective of this study was to present our experience with contrast-enhanced CT and 18F-FDOPA PET/CT imaging in 6 consecutive patients (4 at initial diagnosis and 2 at follow-up evaluation) with rare but clinically important MAX-related PHEOs. In 5 patients, 18F-FDOPA was also compared to other radiopharmaceuticals. Patients had 5 different mutations in the MAX gene that caused disruption of Max/Myc interaction and/or abolished interaction with DNA based on in-silico analyses. All but one patient developed bilateral PHEOs during their lifetime. In all cases, 18F-FDOPA PET/CT accurately visualized PHEOs that were often multiple within the same gland or bilateral and detected more adrenal and extradrenal lesions than CT (per lesion sensitivity 90.5% vs 52.4% for CT/MRI). The 2 missed PHEO on 18F-FDOPA PET/CT were <1cm, corresponding to nodular adrenomedullary hyperplasia. 68Ga-DOTATATE PET/CT detected fewer lesions than 18F-FDOPA PET/CT in 1/3 patients and 18F-FDG PET/CT was only faintly positive in 2/4 patients with underestimation of extraadrenal lesions in 1 patient. MAX-related PHEO exihibit a marked 18F-FDOPA uptake, a finding that illustrates the common well-differentiated chromaffin pattern of PHEO associated with activation of kinase signaling pathways. 18F-FDOPA PET/CT should be considered as the first-line functional imaging modality for diagnostic or follow-up evaluation in these patients.

  8. Antisense-based RNA therapy of factor V deficiency: in vitro and ex vivo rescue of a F5 deep-intronic splicing mutation.

    PubMed

    Nuzzo, Francesca; Radu, Claudia; Baralle, Marco; Spiezia, Luca; Hackeng, Tilman M; Simioni, Paolo; Castoldi, Elisabetta

    2013-11-28

    Antisense molecules are emerging as a powerful tool to correct splicing defects. Recently, we identified a homozygous deep-intronic mutation (F5 c.1296+268A>G) activating a cryptic donor splice site in a patient with severe coagulation factor V (FV) deficiency and life-threatening bleeding episodes. Here, we assessed the ability of 2 mutation-specific antisense molecules (a morpholino oligonucleotide [MO] and an engineered U7 small nuclear RNA [snRNA]) to correct this splicing defect. COS-1 and HepG2 cells transfected with a F5 minigene construct containing the patient's mutation expressed aberrant messenger RNA (mRNA) in excess of normal mRNA. Treatment with mutation-specific antisense MO (1-5 µM) or a construct expressing antisense U7snRNA (0.25-2 µg) dose-dependently increased the relative amount of correctly spliced mRNA by 1 to 2 orders of magnitude, whereas control MO and U7snRNA were ineffective. Patient-derived megakaryocytes obtained by differentiation of circulating progenitor cells did not express FV, but became positive for FV at immunofluorescence staining after administration of antisense MO or U7snRNA. However, treatment adversely affected cell viability, mainly because of the transfection reagents used to deliver the antisense molecules. Our data provide in vitro and ex vivo proof of principle for the efficacy of RNA therapy in severe FV deficiency, but additional cytotoxicity studies are warranted.

  9. Development of f2/f1 ratio functions in humans

    NASA Astrophysics Data System (ADS)

    Vento, Barbara A.; Durrant, John D.; Sabo, Diane L.; Boston, J. Robert

    2004-05-01

    Otoacoustic emissions (OAEs) presumably represent active processes within the cochlea fundamental to frequency-selectivity in peripheral auditory function. Maturation of the cochlear amplifier, vis-a-vis frequency encoding or selectivity, has yet to be fully characterized in humans. The purpose of this study was to further investigate the maturation of features of the f2/f1 frequency ratio (Distortion Product OAE amplitude X f2/f1 ratio) presumed to reflect cochlear frequency selectivity. A cross-sectional, multivariate study was completed comparing three age groups: pre-term infants, term infants and young adult subjects. Frequency ratio functions were analyzed at three f2 frequencies-2000, 4000 and 6000 Hz. An analysis included an estimation of the optimal ratio (OR) and a bandwidth-like measure (Q3). Analysis revealed significant interactions of age x frequency x gender for optimal ratio and a significant interaction of age x frequency for Q3. Consistent and statistically significant differences for both OR and Q3 were found in female subjects and when f2=2 or 6 kHz. This supports research by others [Abdala, J. Acoust. Soc. Am. 114, 3239-3250 (2003)] suggesting that the development of cochlear active mechanisms may still be somewhat in flux at least through term birth Furthermore, OAEs appear to demonstrate gender differences in the course of such maturational changes.

  10. The Holographic F Theorem

    NASA Astrophysics Data System (ADS)

    Taylor, Marika; Woodhead, William

    2017-12-01

    The F theorem states that, for a unitary three dimensional quantum field theory, the F quantity defined in terms of the partition function on a three sphere is positive, stationary at fixed point and decreases monotonically along a renormalization group flow. We construct holographic renormalization group flows corresponding to relevant deformations of three-dimensional conformal field theories on spheres, working to quadratic order in the source. For these renormalization group flows, the F quantity at the IR fixed point is always less than F at the UV fixed point, but F increases along the RG flow for deformations by operators of dimension between 3/2 and 5/2. Therefore the strongest version of the F theorem is in general violated.

  11. F-35 Joint Strike Fighter Aircraft (F-35)

    DTIC Science & Technology

    2013-12-01

    Critical Design Review; announcing the decision to terminate development of an alternate Helmet Mounted Display System (HMDS); completing the 2nd F-35B...the 100th aircraft from the production facility at Fort Worth, Texas; and resolving lingering technical design shortfalls to include the F-35C...emphasis on: regular design reviews, systems engineering discipline, software development planning with baseline review boards, and focused metrics

  12. A synthetic mechano-growth factor E peptide promotes rat tenocyte migration by lessening cell stiffness and increasing F-actin formation via the FAK-ERK1/2 signaling pathway

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

    Zhang, Bingyu; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Mao, Xinjian

    Tendon injuries are common in sports and are frequent reasons for orthopedic consultations. The management of damaged tendons is one of the most challenging problems in orthopedics. Mechano-growth factor (MGF), a recently discovered growth repair factor, plays positive roles in tissue repair through the improvement of cell proliferation and migration and the protection of cells against injury-induced apoptosis. However, it remains unclear whether MGF has the potential to accelerate tendon repair. We used a scratch wound assay in this study to demonstrate that MGF-C25E (a synthetic mechano-growth factor E peptide) promotes the migration of rat tenocytes and that this promotionmore » is accompanied by an elevation in the expression of the following signaling molecules: focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2). Inhibitors of the FAK and ERK1/2 pathways inhibited the MGF-C25E-induced tenocyte migration, indicating that MGF-C25E promotes tenocyte migration through the FAK-ERK1/2 signaling pathway. The analysis of the mechanical properties showed that the Young's modulus of tenocytes was decreased through treatment of MGF-C25E, and an obvious formation of pseudopodia and F-actin was observed in MGF-C25E-treated tenocytes. The inhibition of the FAK or ERK1/2 signals restored the decrease in Young's modulus and inhibited the formation of pseudopodia and F-actin. Overall, our study demonstrated that MGF-C25E promotes rat tenocyte migration by lessening cell stiffness and increasing pseudopodia formation via the FAK-ERK1/2 signaling pathway. - Highlights: • Mechano-growth factor E peptide (MGF-C25E) promotes migration of rat tenocytes. • MGF-C25E activates the FAK-ERK1/2 pathway in rat tenocytes. • MGF-C25E induces the actin remodeling and the formation of pseudopodia, and decreases the stiffness in rat tenocytes. • MGF-C25E promotes tenocyte migration via altering stiffness and forming pseudopodia by the activation of the

  13. Modifications of exposure to ambient particulate matter: Tackling bias in using ambient concentration as surrogate with particle infiltration factor and ambient exposure factor.

    PubMed

    Shi, Shanshan; Chen, Chen; Zhao, Bin

    2017-01-01

    Numerous epidemiological studies explored health risks attributed to outdoor particle pollution. However, a number of these studies routinely utilized ambient concentration as a surrogate for personal exposure to ambient particles. This simplification ignored the difference between indoor and outdoor concentrations of outdoor originated particles and may bias the estimate of particle-health associations. Intending to avoid the bias, particle infiltration factor (F inf ), which describes the penetration of outdoor particles in indoor environment, and ambient exposure factor (α), which represents the fraction of outdoor particles people are truly exposed to, are utilized as modification factors to modify outdoor particle concentration. In this study, the probabilistic distributions of annually-averaged and seasonally-averaged F inf and α were assessed for residences and residents in Beijing. F inf of a single residence and α of an individual was estimated based on the mechanisms governing particle outdoor-to-indoor migration and human time-activity pattern. With this as the core deterministic model, probabilistic distributions of F inf and α were estimated via Monte Carlo Simulation. Annually-averaged F inf of PM 2.5 and PM 10 for residences in Beijing tended to be log-normally distributed as lnN(-0.74,0.14) and lnN(-0.94,0.15) with geometric mean value as 0.47 and 0.39, respectively. Annually-averaged α of PM 2.5 and PM 10 for Beijing residents also tended to be log-normally distributed as lnN(-0.59,0.12) and lnN(-0.73,0.13) with geometric mean value as 0.55 and 0.48, respectively. As for seasonally-averaged results, F inf and α of PM 2.5 and PM 10 were largest in summer and smallest in winter. The obvious difference between these modification factors and unity suggested that modifications of ambient particle concentration need to be considered in epidemiological studies to avoid misclassifications of personal exposure to ambient particles. Moreover

  14. A novel coil array for combined TMS/fMRI experiments at 3 T.

    PubMed

    Navarro de Lara, Lucia I; Windischberger, Christian; Kuehne, Andre; Woletz, Michael; Sieg, Jürgen; Bestmann, Sven; Weiskopf, Nikolaus; Strasser, Bernhard; Moser, Ewald; Laistler, Elmar

    2015-11-01

    To overcome current limitations in combined transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) studies by employing a dedicated coil array design for 3 Tesla. The state-of-the-art setup for concurrent TMS/fMRI is to use a large birdcage head coil, with the TMS between the subject's head and the MR coil. This setup has drawbacks in sensitivity, positioning, and available imaging techniques. In this study, an ultraslim 7-channel receive-only coil array for 3 T, which can be placed between the subject's head and the TMS, is presented. Interactions between the devices are investigated and the performance of the new setup is evaluated in comparison to the state-of-the-art setup. MR sensitivity obtained at the depth of the TMS stimulation is increased by a factor of five. Parallel imaging with an acceleration factor of two is feasible with low g-factors. Possible interactions between TMS and the novel hardware were investigated and were found negligible. The novel coil array is safe, strongly improves signal-to-noise ratio in concurrent TMS/fMRI experiments, enables parallel imaging, and allows for flexible positioning of the TMS on the head while ensuring efficient TMS stimulation due to its ultraslim design. © 2014 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  15. F1030, F1031, and F1032 Sugarbeet Germplasms Selected from Crosses between L19 and three Cultivated/Wild Germplasms

    USDA-ARS?s Scientific Manuscript database

    F1030 (PI 671774), F1031 (PI 671775), and F1032 (PI 671776) sugarbeet, Beta vulgaris subsp. vulgaris (L.), germplasm lines were released by the USDA-ARS in 2013. All three lines were selected primarily for sucrose concentration from populations formed by crossing a high-sugar line with three previo...

  16. Simultaneous real-time PCR detection of Fusarium asiaticum, F. ussurianum and F. vorosii, representing the Asian clade of the F. graminearum species complex.

    PubMed

    Fernández-Ortuño, Dolores; Waalwijk, Cees; Van der Lee, Theo; Fan, Jieru; Atkins, Sarah; West, Jonathan S; Fraaije, Bart A

    2013-08-16

    Due to the repeated discovery of new members of the Fusarium graminearum species complex (FGSC), some of the F. graminearum sensu stricto (s.s.)-specific qPCR assays developed to date have since been shown to be non-specific. In this study, a probe-based qPCR method was developed, targeting a sterol 14-alpha demethylase (CYP51) paralogue, CYP51C unique to the genus Fusarium, for the simultaneous detection of F. asiaticum, F. ussurianum and F. vorosii. Specificity of the assay was demonstrated for a wide range of Fusarium species, including all tested FGSC members (n=6), originating from different hosts and geographic regions. Alongside a previously published assay for detection of F. graminearum, we were able to show that members of the Asian clade of the FGSC (i.e. F. asiaticum, F. ussurianum and F. vorosii) were the primary etiological agent in wheat seeds samples originating from Central-East China. The grain samples from the UK tested negative for the presence of the FGSC's Asian clade and positive for presence of F. graminearum. It is likely that only F. graminearum s.s. is present in the UK, but the presence of other FGSC members cannot be ruled out and need further investigation. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.

    PubMed

    Chen, Wei; Cloughesy, Timothy; Kamdar, Nirav; Satyamurthy, Nagichettiar; Bergsneider, Marvin; Liau, Linda; Mischel, Paul; Czernin, Johannes; Phelps, Michael E; Silverman, Daniel H S

    2005-06-01

    3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a recently developed PET tracer to image tumor cell proliferation. We characterized (18)F-FLT PET of brain gliomas and compared (18)F-FLT with (18)F-FDG PET in side-by-side studies of the same patients. Twenty-five patients with newly diagnosed or previously treated glioma underwent PET with (18)F-FLT and (18)F-FDG on consecutive days. Three stable patients in long-term remission were included as negative control subjects. Tracer kinetics in normal brain and tumor were measured. Uptake of (18)F-FLT and (18)F-FDG was quantified by the standardized uptake value (SUV) and the tumor-to-normal tissue (T/N) ratio. The accuracy of (18)F-FLT and (18)F-FDG PET in evaluating newly diagnosed and recurrent gliomas was compared. More than half of the patients underwent resection after the PET study and correlations between PET uptake and the Ki-67 proliferation index were examined. Patients were monitored for a mean of 15.4 mo (range, 12-20 mo). The predictive power of PET for tumor progression and survival was analyzed using Kaplan-Meier statistics. (18)F-FLT uptake in tumors was rapid, peaking at 5-10 min after injection and remaining stable up to 75 min. Hence, a 30-min scan beginning at 5 min after injection was sufficient for imaging. (18)F-FLT visualized all high-grade (grade III or IV) tumors. Grade II tumor did not show appreciable (18)F-FLT uptake and neither did the stable lesions. The absolute uptake of (18)F-FLT was low (maximum-pixel SUV [SUV(max)], 1.33) but image contrast was better than with (18)F-FDG (T/N ratio, 3.85 vs. 1.49). (18)F-FDG PET studies were negative in 5 patients with recurrent high-grade glioma who subsequently suffered tumor progression within 1-3 mo. (18)F-FLT SUV(max) correlated more strongly with Ki-67 index (r = 0.84; P < 0.0001) than (18)F-FDG SUV(max) (r = 0.51; P = 0.07). (18)F-FLT uptake also had more significant predictive power with respect to tumor progression and survival (P = 0

  18. Ultralow-threshold Raman lasing with CaF2 resonators.

    PubMed

    Grudinin, Ivan S; Maleki, Lute

    2007-01-15

    We demonstrate efficient Raman lasing with CaF2 whispering-gallery-mode resonators. Continuous-wave emission threshold is shown to be possible below 1 microW with a 5mm cavity, which is to our knowledge orders of magnitude lower than in any other Raman source. Low-threshold lasing is made possible by the ultrahigh optical quality factor of the cavity, of the order of Q=5x10(10). Stokes components of up to the fifth order were observed at a pump power of 160 microW, and up to the eighth order at 1 mW. A lasing threshold of 15 microW was also observed in a 100 microm CaF2 microcavity. Potential applications are discussed.

  19. Authoritarianism Revisited: Evidence for an Aggression Factor.

    ERIC Educational Resources Information Center

    Raden, David

    1981-01-01

    Performed a principal components factor analysis on scores of 245 undergraduates to a short version of the F Scale and measures of prejudice, attitude toward welfare, toleration of political deviance, punitiveness toward criminals, and support of the Vietnam War. Analysis produced two factors: authoritarian aggression and attitude toward welfare.…

  20. Human body area factors for radiation exchange analysis: standing and walking postures

    NASA Astrophysics Data System (ADS)

    Park, Sookuk; Tuller, Stanton E.

    2011-09-01

    Effective radiation area factors ( f eff) and projected area factors ( f p) of unclothed Caucasians' standing and walking postures used in estimating human radiation exchange with the surrounding environment were determined from a sample of adults in Canada. Several three-dimensional (3D) computer body models were created for standing and walking postures. Only small differences in f eff and f p values for standing posture were found between gender (male or female) and body type (normal- or over-weight). Differences between this study and previous studies were much larger: ≤0.173 in f p and ≤0.101 in f eff. Directionless f p values for walking posture also had only minor differences between genders and positions in a stride. However, the differences of mean directional f p values of the positions dependent on azimuth angles were large enough, ≤0.072, to create important differences in modeled radiation receipt. Differences in f eff values were small: 0.02 between the normal-weight male and female models and up to 0.033 between positions in a stride. Variations of directional f p values depending on solar altitudes for walking posture were narrower than those for standing posture. When both standing and walking postures are considered, the mean f eff value, 0.836, of standing (0.826) and walking (0.846) could be used. However, f p values should be selected carefully because differences between directional and directionless f p values were large enough that they could influence the estimated level of human thermal sensation.

  1. Factors discriminating gymnasts by competitive level.

    PubMed

    Vandorpe, B; Vandendriessche, J; Vaeyens, R; Pion, J; Lefevre, J; Philippaerts, R; Lenoir, M

    2011-08-01

    This study examined the relationship between the performance level as evaluated by expert coaches and the results on a multidimensional test battery in female gymnastics. 4 coaches assigned 168 female gymnasts aged 6-8 years into 2 groups (Elite-level potential, n=103 and Sub-elite-level potential, n=65) based upon their technical evaluation of the gymnastics abilities on the 4 apparatus. Moreover, anthropometric, physical and coordinative characteristics were assessed. ANOVA with age as fixed factor revealed that results on all aforementioned characteristics, except body fat%, sit-and-reach, rope climbing and a motor coordination test, significantly improved with increasing age. MANCOVA with competitive level as fixed factor and age and maturity as covariates indicated that all gymnasts portrayed a similar athletic built (Wilks' lambda=0.95, F=2.20, p=0.071), but the elite-level potential gymnasts outperformed the less gifted gymnasts on all physical (Wilks' lambda=0.65, F=8.00, p<0.001) and coordinative variables (Wilks' lambda=0.79, F=22.10, p<0.001). Discriminant analysis revealed motor coordination to be the most important factor in discriminating between young female elite and sub-elite gymnasts. A test battery measuring multidimensional performance characteristics is valuable in addition to the coaches' technical judgment in the search of young gifted female gymnasts. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Evaluation of TcpF-A2-CTB Chimera and Evidence of Additive Protective Efficacy of Immunizing with TcpF and CTB in the Suckling Mouse Model of Cholera

    PubMed Central

    Price, Gregory A.; Holmes, Randall K.

    2012-01-01

    The secreted colonization factor, TcpF, which is produced by Vibrio cholerae 01 and 0139, has generated interest as a potential protective antigen in the development of a subunit vaccine against cholera. This study evaluated immunogenicity/protective efficacy of a TcpF holotoxin-like chimera (TcpF-A2-CTB) following intraperitoneal immunization compared to TcpF alone, a TcpF+CTB mixture, or CTB alone. Immunization with the TcpF-A2-CTB chimera elicited significantly greater amounts of anti-TcpF IgG than immunization with the other antigens (P<0.05). Protective efficacy was measured using 6-day-old pups reared from immunized dams and orogastrically challenged with a lethal dose of El Tor V. cholerae 01 Inaba strain N16961. Protection from death, and weight loss analysis at 24 and 48 hours post-infection demonstrated that immunization with TcpF alone was poorly protective. However, immunization with TcpF+CTB was highly protective and showed a trend toward greater protection than immunization with CTB alone (82% vs 64% survival). Immunization with the TcpF-A2-CTB chimera demonstrated less protection (50% survival) than immunization with the TcpF+CTB mixture. The TcpF-A2-CTB chimera used for this study contained the heterologous classical CTB variant whereas the El Tor CTB variant (expressed by the challenge strain) was used in the other immunization groups. For all immunization groups that received CTB, quantitative ELISA data demonstrated that the amounts of serum IgG directed against the homologous immunizing CTB antigen was statistically greater than the amount to the heterologous CTB antigen (P≤0.003). This finding provides a likely explanation for the poorer protection observed following immunization with the TcpF-A2-CTB chimera and the relatively high level of protection seen after immunization with homologous CTB alone. Though immunization with TcpF alone provided no protection, the additive protective effect when TcpF was combined with CTB demonstrates its

  3. A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

    PubMed

    Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

    2007-09-01

    E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

  4. Improving fMRI reliability in presurgical mapping for brain tumours.

    PubMed

    Stevens, M Tynan R; Clarke, David B; Stroink, Gerhard; Beyea, Steven D; D'Arcy, Ryan Cn

    2016-03-01

    Functional MRI (fMRI) is becoming increasingly integrated into clinical practice for presurgical mapping. Current efforts are focused on validating data quality, with reliability being a major factor. In this paper, we demonstrate the utility of a recently developed approach that uses receiver operating characteristic-reliability (ROC-r) to: (1) identify reliable versus unreliable data sets; (2) automatically select processing options to enhance data quality; and (3) automatically select individualised thresholds for activation maps. Presurgical fMRI was conducted in 16 patients undergoing surgical treatment for brain tumours. Within-session test-retest fMRI was conducted, and ROC-reliability of the patient group was compared to a previous healthy control cohort. Individually optimised preprocessing pipelines were determined to improve reliability. Spatial correspondence was assessed by comparing the fMRI results to intraoperative cortical stimulation mapping, in terms of the distance to the nearest active fMRI voxel. The average ROC-r reliability for the patients was 0.58±0.03, as compared to 0.72±0.02 in healthy controls. For the patient group, this increased significantly to 0.65±0.02 by adopting optimised preprocessing pipelines. Co-localisation of the fMRI maps with cortical stimulation was significantly better for more reliable versus less reliable data sets (8.3±0.9 vs 29±3 mm, respectively). We demonstrated ROC-r analysis for identifying reliable fMRI data sets, choosing optimal postprocessing pipelines, and selecting patient-specific thresholds. Data sets with higher reliability also showed closer spatial correspondence to cortical stimulation. ROC-r can thus identify poor fMRI data at time of scanning, allowing for repeat scans when necessary. ROC-r analysis provides optimised and automated fMRI processing for improved presurgical mapping. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

  5. C_7F_16/He rf plasma CVD of a-C:F films

    NASA Astrophysics Data System (ADS)

    Hokoi, Kohji; Akazawa, Masamichi; Sugawara, Hirotake; Sakai, Yosuke

    2000-10-01

    Fluorinated carbon is one of the most promissing materials with low dielectric constant ɛr and high dielectric strength V_b. We have deposited a-C:F films by rf (13.56 MHz) plasma enhanced CVD method using the following liquid materials; C_7F_16, (C_3F_7)_3N/(C_4F_9)_3N and C_8F_18/C_8F_16O.(C. P. Lungu et al.), Jpn. J. Appl. Phys. 38, L1544--6 (1999) The films showed ɛr values in a range of 1.9--3.0 and V_b>2 MV/cm. In this work, we added He (3 Pa) to C_7F_16 (60 Pa) plasmas, expecting that He atoms in the metastable excited state (He*, 19.8 eV) would promote C_7F_16 decomposition in gas phase or activation of the film surface during deposition. The films with the thickness up to 2300 nm were deposited on unheated Si substrate with an rf power of 100 W. The deposition rate derived from the film thickness measurement by SEM and ellipsometry was about 230 nm/min. This value is roughly two times as large as that of the films deposited by C_7F_16 (60 Pa) plasmas without He. We discuss the mechanism that leads to such a significant increase in the deposition rate.

  6. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Registration of F1025, F1026, and F1027 sugarbeet germplasm with low concentrations of sodium, potassium, or amino-nitrogen

    USDA-ARS?s Scientific Manuscript database

    F1025 (Reg. No. GP-xxx, PI xxxxxx), F1026 (Reg. No. GP-xxx, PI xxxxxx), and F1027 (Reg. No. GP-xxx, PI xxxxxx) sugarbeet (Beta vulgaris L.) germplasm lines, selected for low concentrations of sodium, potassium, and amino-nitrogen, respectively, in the roots, were released by the USDA-ARS and the Nor...

  8. 45 CFR Appendix F to Part 1355 - Appendix F to Part 1355

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Appendix F to Part 1355 F Appendix F to Part 1355 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE...

  9. 40 CFR Figure F-1 to Subpart F of... - Designation Testing Checklist

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... tests must be performed:§ 53.62 - Full Wind Tunnel § 53.63 - Inlet Aspiration § 53.64 - Static... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Designation Testing Checklist F Figure F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  10. 40 CFR Figure F-1 to Subpart F of... - Designation Testing Checklist

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... tests must be performed:§ 53.62 - Full Wind Tunnel § 53.63 - Inlet Aspiration § 53.64 - Static... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Designation Testing Checklist F Figure F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  11. 40 CFR Figure F-1 to Subpart F of... - Designation Testing Checklist

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... tests must be performed:§ 53.62 - Full Wind Tunnel § 53.63 - Inlet Aspiration § 53.64 - Static... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Designation Testing Checklist F Figure F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  12. 40 CFR Figure F-1 to Subpart F of... - Designation Testing Checklist

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... tests must be performed:§ 53.62 - Full Wind Tunnel § 53.63 - Inlet Aspiration § 53.64 - Static... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Designation Testing Checklist F Figure F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  13. 40 CFR Figure F-1 to Subpart F of... - Designation Testing Checklist

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... tests must be performed:§ 53.62 - Full Wind Tunnel § 53.63 - Inlet Aspiration § 53.64 - Static... 40 Protection of Environment 6 2012-07-01 2012-07-01 false Designation Testing Checklist F Figure F-1 to Subpart F of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  14. A class of simple bouncing and late-time accelerating cosmologies in f(R) gravity

    NASA Astrophysics Data System (ADS)

    Kuiroukidis, A.

    We consider the field equations for a flat FRW cosmological model, given by Eq. (??), in an a priori generic f(R) gravity model and cast them into a, completely normalized and dimensionless, system of ODEs for the scale factor and the function f(R), with respect to the scalar curvature R. It is shown that under reasonable assumptions, namely for power-law functional form for the f(R) gravity model, one can produce simple analytical and numerical solutions describing bouncing cosmological models where in addition there are late-time accelerating. The power-law form for the f(R) gravity model is typically considered in the literature as the most concrete, reasonable, practical and viable assumption [see S. D. Odintsov and V. K. Oikonomou, Phys. Rev. D 90 (2014) 124083, arXiv:1410.8183 [gr-qc

  15. HTLV-1 bZIP factor protein targets the Rb/E2F-1 pathway to promote proliferation and apoptosis of primary CD4+ T cells

    PubMed Central

    Kawatsuki, A; Yasunaga, J-i; Mitobe, Y; Green, PL; Matsuoka, M

    2016-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that induces a fatal T-cell malignancy, adult T-cell leukemia (ATL). Among several regulatory/accessory genes in HTLV-1, HTLV-1 bZIP factor (HBZ) is the only viral gene constitutively expressed in infected cells. Our previous study showed that HBZ functions in two different molecular forms, HBZ protein and HBZ RNA. In this study, we show that HBZ protein targets retinoblastoma protein (Rb), which is a critical tumor suppressor in many types of cancers. HBZ protein interacts with the Rb/E2F-1 complex and activates the transcription of E2F-target genes associated with cell cycle progression and apoptosis. Mouse primary CD4+ T cells transduced with HBZ show accelerated G1/S transition and apoptosis, and importantly, T cells from HBZ transgenic (HBZ-Tg) mice also demonstrate enhanced cell proliferation and apoptosis. To evaluate the functions of HBZ protein alone in vivo, we generated a new transgenic mouse strain that expresses HBZ mRNA altered by silent mutations but encoding intact protein. In these mice, the numbers of effector/memory and Foxp3+ T cells were increased, and genes associated with proliferation and apoptosis were upregulated. This study shows that HBZ protein promotes cell proliferation and apoptosis in primary CD4+ T cells through activation of the Rb/E2F pathway, and that HBZ protein also confers onto CD4+ T-cell immunophenotype similar to those of ATL cells, suggesting that HBZ protein has important roles in dysregulation of CD4+ T cells infected with HTLV-1. PMID:26804169

  16. Nonstoichiometry in inorganic fluorides: 2. Ionic conductivity of nonstoichiometric M 1 - x R xF2 + x and R 1 - y M yF3 - y crystals ( M = Ca, Sr, Ba; R are rare earth elements)

    NASA Astrophysics Data System (ADS)

    Sobolev, B. P.; Sorokin, N. I.

    2014-11-01

    The peak manifestation of nonstoichiometry in fluoride systems in the number of phases with valuable properties and wide homogeneity ranges is 45 MF2- RF3 systems, where M = Ca, Sr, Ba and R are 15 rare earth elements from La to Lu and Y (with Pm and Sc excluded). A deviation from stoichiometry in crystals of the M 1 - x R xF2 + x (CaF2 fluorite type) and R 1 - y M yF3 - y (LaF3 tysonite type) phases is responsible for the fluorine superionic conductivity σ. The range of variation in σ with changes in the qualitative ( M, R) and quantitative ( x, y) compositions in both structure types is very wide. The σ value changes by a factor of 108 in the M 1 - x R xF2 + x phases (at 500 K) and by a factor of 106 in the R 1 - y M yF3 - y phases (at 293 K). Changing compositions, one can also obtain crystals with σ values large enough for their use as fluorine-conducting solid electrolytes. Phases promising for solid electrolytes were revealed in the MFm- RFn systems ( m < n ≤ 4), which were studied within the program of searching for new multicomponent fluoride materials at the Institute of Crystallography, Russian Academy of Sciences (IC RAS). Superionic conductivity is one of the peak manifestations of the influence of defect structure of nonstoichiometric crystals on their properties. The subject of this review is the results of the studies performed at the IC RAS on the ionic conductivity of single crystals of the M 1 - x R xF2 + x and R 1 - y M yF3 - y nonstoichiometric phases.

  17. Simultaneous Multi-Slice fMRI using Spiral Trajectories

    PubMed Central

    Zahneisen, Benjamin; Poser, Benedikt A.; Ernst, Thomas; Stenger, V. Andrew

    2014-01-01

    Parallel imaging methods using multi-coil receiver arrays have been shown to be effective for increasing MRI acquisition speed. However parallel imaging methods for fMRI with 2D sequences show only limited improvements in temporal resolution because of the long echo times needed for BOLD contrast. Recently, Simultaneous Multi-Slice (SMS) imaging techniques have been shown to increase fMRI temporal resolution by factors of four and higher. In SMS fMRI multiple slices can be acquired simultaneously using Echo Planar Imaging (EPI) and the overlapping slices are un-aliased using a parallel imaging reconstruction with multiple receivers. The slice separation can be further improved using the “blipped-CAIPI” EPI sequence that provides a more efficient sampling of the SMS 3D k-space. In this paper a blipped-spiral SMS sequence for ultra-fast fMRI is presented. The blipped-spiral sequence combines the sampling efficiency of spiral trajectories with the SMS encoding concept used in blipped-CAIPI EPI. We show that blipped spiral acquisition can achieve almost whole brain coverage at 3 mm isotropic resolution in 168 ms. It is also demonstrated that the high temporal resolution allows for dynamic BOLD lag time measurement using visual/motor and retinotopic mapping paradigms. The local BOLD lag time within the visual cortex following the retinotopic mapping stimulation of expanding flickering rings is directly measured and easily translated into an eccentricity map of the cortex. PMID:24518259

  18. Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., sp. nov., Starmerella opuntiae f.a., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a., sp. nov., isolated from flowers and bees, and transfer of related Candida species to the genus Starmerella as new combinations.

    PubMed

    Santos, Ana Raquel O; Leon, Marina P; Barros, Katharina O; Freitas, Larissa F D; Hughes, Alice F S; Morais, Paula B; Lachance, Marc-André; Rosa, Carlos A

    2018-04-01

    Six novel yeast species, Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., Starmerella opuntiae f.a., sp. nov., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a, sp. nov. are proposed to accommodate 19 isolates recovered from ephemeral flowers or bees in Brazil, Costa Rica and Belize. Sequence analysis of the ITS-5.8S region (when available) and the D1/D2 domains of the large subunit of the rRNA gene showed that the six novel yeasts are phylogenetically related to several species of the Starmerella clade. The type strains are Starmerella camargoi f.a., sp. nov. UFMG-CM-Y595 T (=CBS 14130 T ; Mycobank number MB 822640), Starmerella ilheusensis f.a., sp. nov. UFMG-CM-Y596 T (=CBS CBS14131 T ; MB 822641), Starmerella litoralis f.a., sp. nov. UFMG-CM-Y603 T (=CBS14104 T ; MB 822642), Starmerella opuntiae f.a., sp. nov. UFMG-CM-Y286 T (=CBS 13466 T ; MB 822643), Starmerella roubikii f.a., sp. nov. UWOPS 01-191.1 (=CBS 15148; MB 822645) and Starmerella vitae f.a., sp. nov. UWOPS 00-107.2 (=CBS 15147 T ; MB 822646). In addition, 25 species currently assigned to the genus Candida are reassigned formally to the genus Starmerella.

  19. Sibling rivalry in the E2F family.

    PubMed

    Trimarchi, Jeffrey M; Lees, Jacqueline A

    2002-01-01

    The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators. The individual E2Fs can be divided into distinct subgroups that act in direct opposition to one another to promote either cellular proliferation or cell-cycle exit and terminal differentiation. What is the underlying molecular basis of this 'push-me-pull-you' regulation, and what are its biological consequences?

  20. Nonlinear maneuver autopilot for the F-15 aircraft

    NASA Technical Reports Server (NTRS)

    Menon, P. K. A.; Badgett, M. E.; Walker, R. A.

    1989-01-01

    A methodology is described for the development of flight test trajectory control laws based on singular perturbation methodology and nonlinear dynamic modeling. The control design methodology is applied to a detailed nonlinear six degree-of-freedom simulation of the F-15 and results for a level accelerations, pushover/pullup maneuver, zoom and pushover maneuver, excess thrust windup turn, constant thrust windup turn, and a constant dynamic pressure/constant load factor trajectory are presented.

  1. Determination of the k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors for detectors used with an 800 MU/min CyberKnife{sup ®} system equipped with fixed collimators and a study of detector response to small photon beams using a Monte Carlo method

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

    Moignier, C., E-mail: cyril.moignier@free.fr; Huet, C.; Makovicka, L.

    Purpose: In a previous work, output ratio (OR{sub det}) measurements were performed for the 800 MU/min CyberKnife{sup ®} at the Oscar Lambret Center (COL, France) using several commercially available detectors as well as using two passive dosimeters (EBT2 radiochromic film and micro-LiF TLD-700). The primary aim of the present work was to determine by Monte Carlo calculations the output factor in water (OF{sub MC,w}) and the k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors. The secondary aim was to study the detector response in small beams using Monte Carlomore » simulation. Methods: The LINAC head of the CyberKnife{sup ®} was modeled using the PENELOPE Monte Carlo code system. The primary electron beam was modeled using a monoenergetic source with a radial gaussian distribution. The model was adjusted by comparisons between calculated and measured lateral profiles and tissue-phantom ratios obtained with the largest field. In addition, the PTW 60016 and 60017 diodes, PTW 60003 diamond, and micro-LiF were modeled. Output ratios with modeled detectors (OR{sub MC,det}) and OF{sub MC,w} were calculated and compared to measurements, in order to validate the model for smallest fields and to calculate k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors, respectively. For the study of the influence of detector characteristics on their response in small beams; first, the impact of the atomic composition and the mass density of silicon, LiF, and diamond materials were investigated; second, the material, the volume averaging, and the coating effects of detecting material on the detector responses were estimated. Finally, the influence of the size of silicon chip on diode response was investigated. Results: Looking at measurement ratios (uncorrected output factors) compared to the OF{sub MC,w}, the PTW

  2. Fluoride ion donor properties of cis-OsO(2)F(4): synthesis, raman spectroscopic study, and X-ray crystal structure of [OsO(2)F(3)][Sb(2)F(11)].

    PubMed

    Hughes, Michael J; Mercier, Hélène P A; Schrobilgen, Gary J

    2010-01-04

    The salt, [OsO(2)F(3)][Sb(2)F(11)], has been synthesized by dissolution of cis-OsO(2)F(4) in liquid SbF(5), followed by removal of excess SbF(5) at 0 degrees C to yield orange, crystalline [OsO(2)F(3)][Sb(2)F(11)]. The X-ray crystal structure (-173 degrees C) consists of an OsO(2)F(3)(+) cation fluorine bridged to an Sb(2)F(11)(-) anion. The light atoms of OsO(2)F(3)(+) and the bridging fluorine atom form a distorted octahedron around osmium in which the osmium atom is displaced from its center toward an oxygen atom and away from the trans-fluorine bridge atom. As in other transition metal dioxofluorides, the oxygen ligands are cis to one another and the fluorine bridge atom is trans to an oxygen ligand and cis to the remaining oxygen ligand. The Raman spectrum (-150 degrees C) of solid [OsO(2)F(3)][Sb(2)F(11)] was assigned on the basis of the ion pair observed in the low-temperature crystal structure. Under dynamic vacuum, [OsO(2)F(3)][Sb(2)F(11)] loses SbF(5), yielding the known [mu-F(OsO(2)F(3))(2)][Sb(2)F(11)] salt with no evidence for [OsO(2)F(3)][SbF(6)] formation. Attempts to synthesize [OsO(2)F(3)][SbF(6)] by the reaction of [OsO(2)F(3)][Sb(2)F(11)] with an equimolar amount of cis-OsO(2)F(4) or by a 1:1 stoichiometric reaction of cis-OsO(2)F(4) with SbF(5) in anhydrous HF yielded only [mu-F(OsO(2)F(3))(2)][Sb(2)F(11)]. Quantum-chemical calculations at the SVWN and B3LYP levels of theory and natural bond orbital analyses were used to calculate the gas-phase geometries, vibrational frequencies, natural population analysis charges, bond orders, and valencies of OsO(2)F(3)(+), [OsO(2)F(3)][Sb(2)F(11)], [OsO(2)F(3)][SbF(6)], and Sb(2)F(11)(-). The relative thermochemical stabilities of [OsO(2)F(3)][SbF(6)], [OsO(2)F(3)][Sb(2)F(11)], [OsO(2)F(3)][AsF(6)], [mu-F(OsO(2)F(3))(2)][SbF(6)], [mu-F(OsO(2)F(3))(2)][Sb(2)F(11)], and [mu-F(OsO(2)F(3))(2)][AsF(6)] were assessed using the appropriate Born-Haber cycles to account for the preference for [mu-F(OsO(2)F(3

  3. Further study on the solar activity variation of daytime NmF2

    NASA Astrophysics Data System (ADS)

    Chen, Yiding; Liu, Libo

    2010-12-01

    The ionosonde observations in the East Asia-Australia sector are collected to further investigate the solar activity variation of daytime (0800 ˜ 1600 LT) NmF2. The linear increase rate of NmF2 with F10.7 at lower solar activity levels is remarkably dependent on latitude, season, and local time. The rate is largest in equinoxes (with an equinoctial asymmetry) and higher in the morning (afternoon) in local winter (summer) at geomagnetic midlatitudes; particularly, the maximum rates in local winter are obviously larger than those in local summer at northern midlatitudes. In the equatorial ionization anomaly (EIA) crest regions, the rates in equinoxes and December (June) solstice are remarkably higher than those in June (December) solstice at the northern (southern) EIA crest, and the rate grows from the morning sector to the afternoon sector. The variation trend of NmF2 with F10.7 also shows latitudinal, seasonal, and local time dependences. The saturation effect dominates in all seasons in the EIA regions; at midlatitudes, NmF2 nearly increases linearly with F10.7 in local winter so that a linear fit is a good approximation for NmF2 modeling, while the saturation effect still dominates in other seasons. The saturation effect is more significant in the afternoon, and the strongest saturation effect appears at the EIA crest latitudes in equinox afternoon. Discussions indicate that the variations of neutral atmosphere and hmF2 are responsible for the seasonal and local time dependences of the linear increase rate of NmF2 with F10.7 at midlatitudes, and the seasonal variation of neutral atmosphere is the primary reason for the seasonal dependence of the variation trend of NmF2 with F10.7, while dynamics processes are the more important factors controlling the linear increase rate and the variation trend of NmF2 with F10.7 at low latitudes. Furthermore, dynamics processes are important for the saturation effect, and the fountain effect is related to the strongest

  4. Interleukin-17 A and F gene polymorphisms affect the risk of tuberculosis: An updated meta-analysis.

    PubMed

    Eskandari-Nasab, Ebrahim; Moghadampour, Mehdi; Tahmasebi, Arezoo; Asadi-Saghandi, Abolghasem

    2018-07-01

    Cytokines are fundamental elements in mediating and stimulating the immune response against tuberculosis (TB). Growing evidence indicated that polymorphisms in the interleukin-17 (IL-17) A and F genes are implicated in TB. This meta-analysis was aimed to re-evaluate and update the relationship between IL-17A rs2275913 G/A and IL17F rs763780 T/C polymorphisms and TB risk. Using inclusive searches of the PubMed, MEDLINE, EMBASE, Web of Science and Elsevier Science Direct, we identified outcome data from all articles estimating the association between IL-17 A and F polymorphisms and TB risk. A total of 15 studies comprising 7130 patients and 7540 controls were included. Our pooled analysis demonstrated that the IL-17A rs2275913 G/A SNP was not associated with the risk of TB in overall, or in Asians and Caucasians, but it conferred resistance to TB in Latin Americans using allele (OR=0.53), codominant (OR=0.53 and 0.38), dominant (OR=0.49) and recessive (OR=0.46) inheritance models. For IL-17F rs763780 T/C, the pooled evidence indicated that this variation was a risk factor for TB in allele (C vs T) and dominant (TC+CC vs TT) models in overall (OR of 1.35) and among Asians (OR=1.40), but not in Caucasians. In summary, our meta-analysis suggested that the IL-17A rs2275913 was a protective factor against TB, but -17F rs763780 T/C was a risk factor for TB. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  5. Virulence Factors of Streptococcus mutans.

    DTIC Science & Technology

    1986-08-01

    763512/715242 Final Report U VIRULENCE FACTORS OF STREPTOCOCCUS MUTANS U Samuel Rosen Department of Oral Biology For the Period April 1, 1983 - June 30...00 FINAL REPORT VIRULENCE FACTORS OF STREPTOCOCCUS MUTANS Sam Rosen, Irving Shklair, E. X. Beck and F. M. Beck Ohio State University Columbus,Oh and...206-212. Johnson CP, Gorss S, Hillman JD (1978). Cariogenic properties of LDH deficient mutants of streptococcus mutans . J Dent Res 57, Special Issue

  6. Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma.

    PubMed

    Beuthien-Baumann, B; Strumpf, A; Zessin, J; Bredow, J; Kotzerke, J

    2007-10-01

    In patients with medullary thyroid carcinoma (MTC), rising levels of the tumour markers calcitonin and CEA after primary surgery indicate tumour recurrence or metastases. The only chance of cure is the resection of localised tumour tissue. For positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) and (18)F-dihydroxyphenylalanine ((18)F-DOPA), sensitivities of 78% and 63% have been reported, but in a considerable percentage of MTC patients the source of tumour marker elevation is not detected. The aim of this retrospective data evaluation was to compare the value of PET with (18)F-FDG, (18)F-DOPA and the amino acid tracer 3-O-methyl-6-[(18)F]fluoro-DOPA ((18)F-OMFD) in the detection of MTC recurrence. Fifteen patients with elevated calcitonin were investigated with PET as part of their individual clinical work-up. All patients underwent (18)F-FDG PET and (18)F-DOPA PET, and ten patients underwent (18)F-OMFD PET. With (18)F-FDG, seven patients showed foci in the neck, mediastinum, upper abdomen or bone. In seven patients, (18)F-DOPA revealed suspicious foci; five of these seven patients showed partially corresponding uptake of (18)F-FDG in the neck and mediastinum. Two of these patients underwent surgery and metastases were verified. With (18)F-OMFD, a small focus in the liver was suspected in one patient without a correlate on (18)F-FDG PET, (18)F-DOPA PET or conventional imaging. (18)F-FDG and (18)F-DOPA showed foci that were highly suspicious for local recurrence or metastasis of MTC, although histological verification in these patients with numerous previous surgical interventions was performed in only two patients. The amino acid tracer (18)F-OMFD had no diagnostic impact in these patients.

  7. CIP-13F, a novel aminopeptidase N (APN/CD13) inhibitor, inhibits Lewis lung carcinoma growth and metastasis in mice.

    PubMed

    Pei, Ke-Ling; Yuan, Yi; Qin, San-Hai; Wang, Yan; Zhou, Ling; Zhang, Hou-Li; Qu, Xian-Jun; Cui, Shu-Xiang

    2012-04-01

    Aminopeptidase N (APN/CD13) is highly expressed on the surface of cancer cells and is thought to be involved in cancer growth and metastasis. The research of APN/CD13 inhibitors is considered as a strategy of cancer treatment. We aimed to evaluate the efficacy of CIP-13F, a novel APN/CD13 inhibitor, using a Lewis lung carcinoma (LLC) implantation mouse model. C57BL/6 mice were subcutaneously inoculated with LLC cells in anterior flank. Then, 0, 50 and 100 mg/kg of CIP-13F were injected via vena caudalis. Bestatin was used as the positive control. Administration of CIP-13F or bestatin was performed daily for 3 consecutive weeks. Mice were killed, and the tumors in anterior flank and metastasis nodules in lungs were examined. The assays of immunohistochemical staining, immunofluorescent flow cytometry and western blotting were performed to estimate the expression of APN/CD13 in LLC cells. We carried out the experiments of Annexin-V/PI staining, DNA fragmentation analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining to determine apoptotic cells in LLC tissues. Using immunohistochemical staining with CD34, the antiangiogenesis of CIP-13F was evaluated in LLC tissue sections. CIP-13F treatment resulted in a significant delay of LLC growth in anterior flank. Examination of lungs showed that the number of metastatic nodules of LLC was also markedly decreased. The inhibitory effect of CIP-13F on LLC growth was further evidenced by the induction of LLC apoptosis, showing the increases in Annexin-V/PI staining cells, DNA fragmentation and TUNEL staining cells. Molecular analyses of LLC tissues in CIP-13F-treated mice suggested that the decrease in APN/CD13 expression by CIP-13F might account for its actions of mechanism. Further, the inhibition of angiogenesis in LLC tissues was determined, showing the decreases in microvessel density (MVD) and angiogenic factors including vascular endothelial growth factor (VEGF), basic

  8. Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

    PubMed Central

    Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E.; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

    2010-01-01

    Background Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. Design and Methods We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. Results All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. Conclusions The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms. PMID:20179087

  9. Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function.

    PubMed

    Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

    2010-06-01

    Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms.

  10. Identification of Drosophila melanogaster yellow-f and yellow-f2 proteins as dopachrome-conversion enzymes.

    PubMed Central

    Han, Qian; Fang, Jianmin; Ding, Haizhen; Johnson, Jody K; Christensen, Bruce M; Li, Jianyong

    2002-01-01

    This study describes the identification of Drosophila yellow-f and yellow-f2 as dopachrome-conversion enzymes responsible for catalysing the conversion of dopachrome into 5,6-dihydroxyindole in the melanization pathway. Drosophila yellow -y gene and yellow -b, -c, -f and -f2 genes were expressed in an insect cell/baculovirus expression system and their corresponding recombinant proteins were screened for dopachrome-conversion enzyme activity. Among the yellow and yellow -related genes, the yellow -f and yellow -f2 genes were identified as the genes coding for Drosophila dopachrome-conversion enzyme based on the high activity of their recombinant proteins in catalysing the production of 5,6-dihydroxyindole from dopachrome. Both yellow-f and yellow-f2 are capable of mediating a decarboxylative structural rearrangement of dopachrome, as well as an isomerization/tautomerization of dopamine chrome and dopa methyl ester chrome. Northern hybridization revealed the transcription of yellow -f in larvae and pupae, but a high abundance of mRNA was observed in later larval and early pupal stages. In contrast, yellow-f2 transcripts were present at all stages, but high abundance of its mRNA was observed in later-stage pupae and adults. These data indicate that yellow-f and yellow-f2 complement each other during Drosophila development and that the yellow-f is involved in larval and pupal melanization, and yellow-f2 plays a major role in melanization reactions in Drosophila during later pupal and adult development. Results from this study provide the groundwork towards a better understanding of the physiological roles of the Drosophila yellow gene family. PMID:12164780

  11. Ab initio investigation of the ground and low-lying states of the diatomic fluorides TiF, VF, CrF, and MnF

    NASA Astrophysics Data System (ADS)

    Koukounas, Constantine; Kardahakis, Stavros; Mavridis, Aristides

    2004-06-01

    The electronic structure of the ground and low-lying states of the diatomic fluorides TiF, VF, CrF, and MnF was examined by multireference and coupled cluster methods in conjunction with extended basis sets. For a total of 34 states we report binding energies, spectroscopic constants, dipole moments, separation energies, and charge distributions. In addition, for all states we have constructed full potential curves. The suggested ground state binding energies of TiF(X 4Φ), VF(X 5Π), CrF(X 6Σ+), and MnF(X 7Σ+) are 135, 130, 110, and 108 kcal/mol, respectively, with first excited states A 4Σ-, A 5Δ, A 6Π, and a 5Σ+ about 2, 3, 23, and 19 kcal/mol higher. In essence all our numerical findings are in harmony with experimental results. For all molecules and states studied it is clear that the in situ metal atom (M) shows highly ionic character, therefore the binding is described realistically by M+F-.

  12. Ab initio investigation of the ground and low-lying states of the diatomic fluorides TiF, VF, CrF, and MnF.

    PubMed

    Koukounas, Constantine; Kardahakis, Stavros; Mavridis, Aristides

    2004-06-22

    The electronic structure of the ground and low-lying states of the diatomic fluorides TiF, VF, CrF, and MnF was examined by multireference and coupled cluster methods in conjunction with extended basis sets. For a total of 34 states we report binding energies, spectroscopic constants, dipole moments, separation energies, and charge distributions. In addition, for all states we have constructed full potential curves. The suggested ground state binding energies of TiF(X (4)Phi), VF(X (5)Pi), CrF(X (6)Sigma(+)), and MnF(X (7)Sigma(+)) are 135, 130, 110, and 108 kcal/mol, respectively, with first excited states A (4)Sigma(-), A (5)Delta, A (6)Pi, and a (5)Sigma(+) about 2, 3, 23, and 19 kcal/mol higher. In essence all our numerical findings are in harmony with experimental results. For all molecules and states studied it is clear that the in situ metal atom (M) shows highly ionic character, therefore the binding is described realistically by M(+)F(-). (c) 2004 American Institute of Physics.

  13. F4+ enterotoxigenic Escherichia coli (ETEC) adhesion mediated by the major fimbrial subunit FaeG.

    PubMed

    Xia, Pengpeng; Song, Yujie; Zou, Yajie; Yang, Ying; Zhu, Guoqiang

    2015-09-01

    The FaeG subunit is the major constituent of F4(+) fimbriae, associated with glycoprotein and/or glycolipid receptor recognition and majorly contributes to the pathogen attachment to the host cells. To investigate the key factor involved in the fimbrial binding of F4(+) Escherichia coli, both the recombinant E. coli SE5000 strains carrying the fae operon gene clusters that express the different types of fimbriae in vitro, named as rF4ab, rF4ac, and rF4ad, respectively, corresponding to the fimbrial types F4ab, F4ac, and F4ad, and the three isogenic in-frame faeG gene deletion mutants were constructed. The adhesion assays and adhesion inhibition assays showed that ΔfaeG mutants had a significant reduction in the binding to porcine brush border as well as the intestinal epithelial cell lines, while the complemented strain ΔfaeG/pfaeG restored the adhesion function. The recombinant bacterial strains rF4ab, rF4ac, and rF4ad have the same binding property as wild-type F4(+) E. coli strains do and improvement in terms of binding to porcine brush border and the intestinal epithelial cells, and the adherence was blocked by the monoclonal antibody anti-F4 fimbriae. These data demonstrate that the fimbrial binding of F4(+) E. coli is directly mediated by the major FaeG subunit. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Beta reduction factors for protective clothing at the Oak Ridge National Laboratory

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

    Franklin, G.L.; Gonzalez, P.L.

    1998-12-31

    Beta reduction factors (f{sub {beta}}) for protective clothing (PC) at the Oak Ridge National Laboratory (ORNL) have been determined for a variety of protective clothing combinations. Data was collected to determine the experimental f{sub {beta}} for several combinations of PCs under laboratory conditions. Radiation dose rates were measured with an open window Bicron{reg_sign} RSO-5 ion chamber for two distinct beta energy groups (E{sub max} = 1.218 {times} 10{sup {minus}13} J(0.860 MeV) and 3.653 {times} 10{sup {minus}13} J (2.280 MeV)). Data points determined, as the ratio of unattenuated (no PCs) to attenuated (PCs), were used to derive a set of equationsmore » using the Microsoft{reg_sign} Excel Linet function. Field comparison tests were then conducted to determine the validity of these beta reduction factors. The f{sub {beta}} from the field tests were significantly less than the experimental f{sub {beta}}, indicating that these factors will yield conservative results.« less

  15. Hsp27 and F-box protein β-TrCP promote degradation of mRNA decay factor AUF1.

    PubMed

    Li, Mei-Ling; Defren, Jennifer; Brewer, Gary

    2013-06-01

    Activation of the mitogen-activated protein (MAP) pathway kinases p38 and MK2 induces phosphorylation of the chaperone Hsp27 and stabilization of mRNAs containing AU-rich elements (AREs) (ARE-mRNAs). Likewise, expression of phosphomimetic mutant forms of Hsp27 also stabilizes ARE-mRNAs. It appears to perform this function by promoting degradation of the ARE-mRNA decay factor AUF1 by proteasomes. In this study, we examined the molecular mechanism linking Hsp27 phosphorylation to AUF1 degradation by proteasomes. AUF1 is a target of β-TrCP, the substrate recognition subunit of the E3 ubiquitin ligase Skp1-cullin-F-box protein complex, SCF(β-TrCP). Depletion of β-TrCP stabilized AUF1. In contrast, overexpression of β-TrCP enhanced ubiquitination and degradation of AUF1 and led to stabilization of reporter mRNAs containing cytokine AREs. Enhanced AUF1 degradation required expression of phosphomimetic mutant forms of both Hsp27 and AUF1. Our results suggest that a signaling axis composed of p38 MAP kinase-MK2-Hsp27-β-TrCP may promote AUF1 degradation by proteasomes and stabilization of cytokine ARE-mRNAs.

  16. New Chelators for Low Temperature Al(18)F-Labeling of Biomolecules.

    PubMed

    Cleeren, Frederik; Lecina, Joan; Billaud, Emilie M F; Ahamed, Muneer; Verbruggen, Alfons; Bormans, Guy M

    2016-03-16

    The Al(18)F labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in aqueous solution. However, the chelation of the {Al(18)F}(2+) core with the macrocyclic chelators NOTA or NODA requires heating to 100-120 °C. Therefore, we have developed new polydentate ligands for the complexation of {Al(18)F}(2+) with good radiochemical yields at a temperature of 40 °C. The stability of the new Al(18)F-complexes was tested in phosphate buffered saline (PBS) at pH 7.4 and in rat serum. The stability of the Al(18)F-L3 complex was found to be comparable to that of the previously reported Al(18)F-NODA complex up to 60 min in rat serum. Moreover, the biodistribution of Al(18)F-L3 in healthy mice showed the absence of in vivo defluorination since no significant bone uptake was observed, whereas the major fraction of activity at 60 min p.i. was observed in liver and intestines, indicating hepatobiliary clearance of the radiolabeled ligand. The acyclic chelator H3L3 proved to be a good lead candidate for labeling of heat-sensitive biomolecules with fluorine-18. In order to obtain a better understanding of the different factors influencing the formation and stability of the complex, we carried out more in-depth experiments with ligand H3L3. As a proof of concept, we successfully conjugated the new AlF-chelator with the urea-based PSMA inhibitor Glu-NH-CO-NH-Lys to form Glu-NH-CO-NH-Lys(Ahx)L3, and a biodistribution study in healthy mice was performed with the Al(18)F-labeled construct. This new class of AlF-chelators may have a great impact on PET radiochemical space as it will stimulate the rapid development of new fluorine-18 labeled peptides and other heat-sensitive biomolecules.

  17. An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

    PubMed

    Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

    2016-06-24

    Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

  18. EPA Positive Matrix Factorization (PMF) 5.0 Fundamentals and User Guide

    EPA Science Inventory

    PMF is a multivariate factor analysis tool that decomposes a matrix of speciated sample data into two matrices: factor contributions (G) and factor profiles (F). These factor profiles need to be interpreted by the user to identify the source types that may be contributing to the ...

  19. The Chapel Hill hemophilia A dog colony exhibits a factor VIII gene inversion

    PubMed Central

    Lozier, Jay N.; Dutra, Amalia; Pak, Evgenia; Zhou, Nan; Zheng, Zhili; Nichols, Timothy C.; Bellinger, Dwight A.; Read, Marjorie; Morgan, Richard A.

    2002-01-01

    In the Chapel Hill colony of factor VIII-deficient dogs, abnormal sequence (ch8, for canine hemophilia 8, GenBank no. AF361485) follows exons 1–22 in the factor VIII transcript in place of exons 23–26. The canine hemophilia 8 locus (ch8) sequence was found in a 140-kb normal dog genomic DNA bacterial artificial chromosome (BAC) clone that was completely outside the factor VIII gene, but not in BAC clones containing the factor VIII gene. The BAC clone that contained ch8 also contained a homologue of F8A (factor 8 associated) sequence, which participates in a common inversion that causes severe hemophilia A in humans. Fluorescence in situ hybridization analysis indicated that exons 1–26 normally proceed sequentially from telomere to centromere at Xq28, and ch8 is telomeric to the factor VIII gene. The appearance of an “upstream” genomic sequence element (ch8) at the end of the aberrant factor VIII transcript suggested that an inversion of genomic DNA replaced factor VIII exons 22–26 with ch8. The F8A sequence appeared also in overlapping normal BAC clones containing factor VIII sequence. We hypothesized that homologous recombination between copies of canine F8A inside and outside the factor VIII gene had occurred, as in human hemophilia A. High-resolution fluorescent in situ hybridization on hemophilia A dog DNA revealed a pattern consistent with this inversion mechanism. We also identified a HindIII restriction fragment length polymorphism of F8A fragments that distinguished hemophilia A, carrier, and normal dogs' DNA. The Chapel Hill hemophilia A dog colony therefore replicates the factor VIII gene inversion commonly seen in humans with severe hemophilia A. PMID:12242334

  20. F(R) cosmology via Noether symmetry and Λ-Chaplygin Gas like model

    NASA Astrophysics Data System (ADS)

    Fazlollahi, H. R.

    2018-06-01

    In this work, we consider f (R) alternative theories of gravity with an eye to Noether symmetry through the gauge theorem. For non-vacuum models, one finds Λ like gravity with energy density of Chaplygin Gas. We also obtain the effective equation of state parameter for corresponding cosmology and scale factor behavior with respect to cosmic time which show that the model provides viable EoS and scale factor with respect to observational data.

  1. Male endocrine response to seasonally varying environmental and social factors in a neotropical primate, Cebus capucinus.

    PubMed

    Schoof, Valérie A M; Bonnell, Tyler R; Jack, Katharine M; Ziegler, Toni E; Melin, Amanda D; Fedigan, Linda M

    2016-04-01

    Circannual variation in reproduction is pervasive in birds and mammals. In primates, breeding seasonality is variable, with seasonal birth peaks occurring even in year-round breeders. Environmental seasonality is reportedly an important contributor to the observed variation in reproductive seasonality. Given that food availability is the primary factor constraining female reproduction, predictions concerning responsiveness to environmental seasonality focus on females, with studies of males focusing primarily on social factors. We examined the influence of both environmental and social factors on male fecal testosterone (fT) and glucocorticoids (fGC) in moderately seasonally breeding white-faced capuchin monkeys (Cebus capucinus) in Costa Rica. Over 17 months, we collected 993 fecal samples from 14 males in three groups. We used LMM to simultaneously examine the relative effects of photoperiod, fruit biomass, rainfall, temperature, female reproductive status (i.e., number of periovulatory periods, POPs), and male age and dominance rank on monthly fT and fGC levels. Male age and rank had large effects on fT and fGC. Additionally, some hormone variation was explained by environmental factors: photoperiod in the previous month (i.e., lagged photoperiod) was the best environmental predictor of monthly fT levels, whereas fGC levels were best explained by lagged photoperiod, fruit biomass, and rainfall. POPs predicted monthly fT and fGC, but this effect was reduced when all variables were considered simultaneously, possibly because lagged photoperiod and POP were highly correlated. Males may use photoperiod as a cue predicting circannual trends in the temporal distribution of fertile females, while also fine-tuning short-term hormone increases to the actual presence of ovulatory females, which may occur at any time during the year. © 2016 Wiley Periodicals, Inc.

  2. Male Endocrine Response to Seasonally Varying Environmental and Social Factors in a Neotropical Primate, Cebus capucinus

    PubMed Central

    Schoof, Valérie A. M.; Bonnell, Tyler R.; Jack, Katharine M.; Ziegler, Toni E.; Melin, Amanda D.; Fedigan, Linda M.

    2018-01-01

    Objective Circannual variation in reproduction is pervasive in birds and mammals. In primates, breeding seasonality is variable, with seasonal birth peaks occurring even in year-round breeders. Environmental seasonality is reportedly an important contributor to the observed variation in reproductive seasonality. Given that food availability is the primary factor constraining female reproduction, predictions concerning responsiveness to environmental seasonality focus on females, with studies of males focusing primarily on social factors. We examined the influence of both environmental and social factors on male fecal testosterone (fT) and glucocorticoids (fGC) in moderately seasonally breeding white-faced capuchin monkeys (Cebus capucinus) in Costa Rica. Methods Over 17 months, we collected 993 fecal samples from 14 males in three groups. We used LMM to simultaneously examine the relative effects of photoperiod, fruit biomass, rainfall, temperature, female reproductive status (i.e., number of periovulatory periods, POPs), and male age and dominance rank on monthly fT and fGC levels. Results Male age and rank had large effects on fT and fGC. Additionally, some hormone variation was explained by environmental factors: photoperiod in the previous month (i.e., lagged photoperiod) was the best environmental predictor of monthly fT levels, whereas fGC levels were best explained by lagged photoperiod, fruit biomass, and rainfall. POPs predicted monthly fT and fGC, but this effect was reduced when all variables were considered simultaneously, possibly because lagged photoperiod and POP were highly correlated. Conclusions Males may use photoperiod as a cue predicting circannual trends in the temporal distribution of fertile females, while also fine-tuning short-term hormone increases to the actual presence of ovulatory females, which may occur at any time during the year. PMID:26739266

  3. Association between F508 deletion in CFTR and chronic pancreatitis risk.

    PubMed

    Zhao, Dong; Xu, Yanzhen; Li, Jiatong; Fu, Shien; Xiao, Feifan; Song, Xiaowei; Xie, Zhibin; Jiang, Min; He, Yan; Liu, Chengwu; Wen, Qiongxian; Yang, Xiaoli

    2017-09-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) has been reported to influence individual susceptibility to chronic pancreatitis (CP), but the results of previous studies are controversial. We performed a study to demonstrate the relationship between CFTR and CP. We searched PubMed, Scopus, and Embase for studies of patients with CP. Seven studies from 1995 to 2016 were identified, and included 64,832 patients. Pooled prevalence and 95% confidence intervals (CIs) were calculated. F508 deletion in CFTR was significantly positively associated with CP risk in the overall analysis (odds ratio [OR]=3.20, 95% CI: 2.30-4.44, I 2 =31.7%). In subgroup analysis stratified by ethnicity, F508 deletion was significantly associated with CP risk in Indian populations, using a fixed effects model (ORs=5.45, 95% CI: 2.52-11.79, I 2 =0.0%), and in non-Indian populations, using a random effects model (ORs=3.59, 95% CI: 1.73-7.48, I 2 =60.9%). At the same time, we found that Indians with F508 deletion had much higher CP prevalence than non-Indians. Interestingly, F508 deletion was also associated with CP and idiopathic CP risk in subgroup analysis stratified by aeitiology, using the fixed effects model. Based on current evidence, F508 deletion is a risk factor for CP, and Indians with F508 deletion have much higher CP morbidity. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  4. Elucidation of the biosynthesis of the methane catalyst coenzyme F430

    PubMed Central

    Moore, Simon J.; Sowa, Sven T.; Schuchardt, Christopher; Deery, Evelyne; Lawrence, Andrew D.; Ramos, José Vazquez; Billig, Susan; Birkemeyer, Claudia; Chivers, Peter T.; Howard, Mark J.; Rigby, Stephen E. J.; Layer, Gunhild; Warren, Martin J.

    2017-01-01

    Summary Methane biogenesis in methanogens is mediated by methyl-coenzyme M reductase, an enzyme that is also responsible for the utilisation of methane through anaerobic methane oxidation. The enzyme employs an ancillary factor called coenzyme F430, a nickel-containing modified tetrapyrrole that promotes catalysis through a novel methyl radical/Ni(II)-thiolate intermediate. However, the biosynthesis of coenzyme F430 from the common primogenitor uroporphyrinoge III, incorporating 11 steric centres into the macrocycle, has remained poorly understood although the pathway must involve chelation, amidation, macrocyclic ring reduction, lactamisation and carbocyclic ring formation. We have now identified the proteins that catalyse coenzyme F430 biosynthesis from sirohydrochlorin, termed CfbA-E, and shown their activity. The research completes our understanding of how nature is able to construct its repertoire of tetrapyrrole-based life pigments, permitting the development of recombinant systems to utilise these metalloprosthetic groups more widely. PMID:28225763

  5. Northrop F-5F shark nose development

    NASA Technical Reports Server (NTRS)

    Edwards, O. R.

    1978-01-01

    During spin susceptibility testing of the Northrop F-5F airplane, two erect spin entries were obtained from purely longitudinal control inputs at low speed. Post flight analysis of the data showed that the initial yaw departure occurred at zero sideslip, and review of wind tunnel data showed significant yawing moments present at angles of attack well above stall. Further analysis of this wind tunnel data indicated that the yawing moments were being generated by the long slender nose of the airplane. Redesign of the nose was accomplished, resulting in a nose configuration which completely alleviated the asymmetric yawing moments.

  6. Superbounce and loop quantum ekpyrotic cosmologies from modified gravity: F(R) , F(G) and F(T) theories

    NASA Astrophysics Data System (ADS)

    Odintsov, S. D.; Oikonomou, V. K.; Saridakis, Emmanuel N.

    2015-12-01

    We investigate the realization of two bouncing paradigms, namely of the superbounce and the loop quantum cosmological ekpyrosis, in the framework of various modified gravities. In particular, we focus on the F(R) , F(G) and F(T) gravities, and we reconstruct their specific subclasses which lead to such universe evolutions. These subclasses constitute from power laws, polynomials, or hypergeometric ansatzes, which can be approximated by power laws. The qualitative similarity of the different effective gravities which realize the above two bouncing cosmologies, indicates that a universality might be lying behind the bounce. Finally, performing a linear perturbation analysis, we show that the obtained solutions are conditionally or fully stable.

  7. Biophysical, histopathological and pharmacological characterization of crotamine isoforms F22 and F32.

    PubMed

    Toyama, Marcos H; Marangoni, Sérgio; Novello, José C; Leite, Gildo B; Prado-Franceschi, Julia; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

    2003-03-01

    Two major crotamine isoforms (F22 and F32) were obtained after three chromatographic steps and were assayed in mouse phrenic nerve-diaphragm preparations. F32 and F22 (0.5 microg/ml, n=4) produced a facilitatory effect, which increased isometric twitch-tension by 300 and 230%, respectively, after a 120 min incubation. At a concentration of 0.1 microg/ml, both isoforms increased the twitch-tension by about 160%. However, when the isoforms were co-incubated (final concentration, 0.5 microg/ml) for 30 min prior to testing, they did not cause the facilitation seen with > or =0.1 microg/ml of each isoform alone. Histologically, F32 and F22 at 0.5 and 1 microg/ml were quantitatively alike in inducing tissue myonecrosis. However, a mixture of the two isoforms (final concentration, 0.5 microg/ml) significantly attenuated the damage seen with either toxin alone. Mass spectrometry analysis showed that the isoforms had the same molecular mass (4.8 kDa) and that they existed as monomers with a highly stable structure. These results indicate that F22 and F32 acted on muscle cells of the mouse phrenic-nerve diaphragm preparation through similar mechanisms. Since the isoforms did not produce the expected summation in the increase in muscle twitch-tension, it is possible that they may have different affinities for the sodium channel subunits.

  8. Electromagnetic moments of 22F

    NASA Astrophysics Data System (ADS)

    Mihara, M.; Matsuta, K.; Komurasaki, J.; Hirano, H.; Nishimura, D.; Momota, S.; Ohtsubo, T.; Izumikawa, T.; Shimbara, Y.; Kubo, T.; Kameda, D.; Zhou, Dongmei; Zheng, Yongnan; Yuan, Daqing; Zhu, Shengyun; Kitagawa, A.; Kanazawa, M.; Torikoshi, M.; Sato, S.; Nagatomo, T.; Matsumiya, R.; Ishikawa, D.; Fukuda, M.; Minamisono, T.; Nojiri, Y.; Alonso, J. R.; Crebs, G. F.; Symons, T. J. M.

    2010-03-01

    The magnetic dipole (μ) and electric quadrupole (Q) moments of short-lived nucleus 22F (Iπ=4+, T=4.2s) have been measured for the first time by means of the β-NMR technique. A spin polarized 22F beam was produced through the charge exchange reaction of 22Ne and was implanted into single crysltals of NaF and MgF2 for μ and Q measurements, respectively. As a result, |μ(F22)|=(2.69443±0.00039)μ and |Q(F22)|=(3±2)mb was obtained. These values are well reproduced by the shell model calculations.

  9. A neutron scintillator based on transparent nanocrystalline CaF{sub 2}:Eu glass ceramic

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

    Struebing, Christian; Kang, Zhitao, E-mail: zhitao.kang@gtri.gatech.edu; School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332

    2016-04-11

    There are no efficient Eu{sup 2+} doped glass neutron scintillators reported due to low doping concentrations of Eu{sup 2+} and the amorphous nature of the glass matrix. In this work, an efficient CaF{sub 2}:Eu glass ceramic neutron scintillator was prepared by forming CaF{sub 2}:Eu nanocrystals in a {sup 6}Li-containing glass matrix. Through appropriate thermal treatments, the scintillation light yield of the transparent glass ceramic was increased by a factor of at least 46 compared to the as-cast amorphous glass. This improvement was attributed to more efficient energy transfer from the CaF{sub 2} crystals to the Eu{sup 2+} emitting centers. Furthermore » light yield improvement is expected if the refractive index of the glass matrix can be matched to the CaF{sub 2} crystal.« less

  10. Probe-Specific Procedure to Estimate Sensitivity and Detection Limits for 19F Magnetic Resonance Imaging.

    PubMed

    Taylor, Alexander J; Granwehr, Josef; Lesbats, Clémentine; Krupa, James L; Six, Joseph S; Pavlovskaya, Galina E; Thomas, Neil R; Auer, Dorothee P; Meersmann, Thomas; Faas, Henryk M

    2016-01-01

    Due to low fluorine background signal in vivo, 19F is a good marker to study the fate of exogenous molecules by magnetic resonance imaging (MRI) using equilibrium nuclear spin polarization schemes. Since 19F MRI applications require high sensitivity, it can be important to assess experimental feasibility during the design stage already by estimating the minimum detectable fluorine concentration. Here we propose a simple method for the calibration of MRI hardware, providing sensitivity estimates for a given scanner and coil configuration. An experimental "calibration factor" to account for variations in coil configuration and hardware set-up is specified. Once it has been determined in a calibration experiment, the sensitivity of an experiment or, alternatively, the minimum number of required spins or the minimum marker concentration can be estimated without the need for a pilot experiment. The definition of this calibration factor is derived based on standard equations for the sensitivity in magnetic resonance, yet the method is not restricted by the limited validity of these equations, since additional instrument-dependent factors are implicitly included during calibration. The method is demonstrated using MR spectroscopy and imaging experiments with different 19F samples, both paramagnetically and susceptibility broadened, to approximate a range of realistic environments.

  11. Recovering task fMRI signals from highly under-sampled data with low-rank and temporal subspace constraints.

    PubMed

    Chiew, Mark; Graedel, Nadine N; Miller, Karla L

    2018-07-01

    Recent developments in highly accelerated fMRI data acquisition have employed low-rank and/or sparsity constraints for image reconstruction, as an alternative to conventional, time-independent parallel imaging. When under-sampling factors are high or the signals of interest are low-variance, however, functional data recovery can be poor or incomplete. We introduce a method for improving reconstruction fidelity using external constraints, like an experimental design matrix, to partially orient the estimated fMRI temporal subspace. Combining these external constraints with low-rank constraints introduces a new image reconstruction model that is analogous to using a mixture of subspace-decomposition (PCA/ICA) and regression (GLM) models in fMRI analysis. We show that this approach improves fMRI reconstruction quality in simulations and experimental data, focusing on the model problem of detecting subtle 1-s latency shifts between brain regions in a block-design task-fMRI experiment. Successful latency discrimination is shown at acceleration factors up to R = 16 in a radial-Cartesian acquisition. We show that this approach works with approximate, or not perfectly informative constraints, where the derived benefit is commensurate with the information content contained in the constraints. The proposed method extends low-rank approximation methods for under-sampled fMRI data acquisition by leveraging knowledge of expected task-based variance in the data, enabling improvements in the speed and efficiency of fMRI data acquisition without the loss of subtle features. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. 17 CFR 200.80f - Appendix F-Records control schedule.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Securities Investor Protection Corporation assessment payment or overpayments (Rule 17a-5). (Non-public) For...- Applications for exemption from section 13(f) 10 years. 28- Reports by institutional investment managers of... requirements, annual reports to shareholders, F-6 waiver, proxy 10 years. 89- Other waivers for foreign issuers...

  13. 17 CFR 200.80f - Appendix F-Records control schedule.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Securities Investor Protection Corporation assessment payment or overpayments (Rule 17a-5). (Non-public) For...- Applications for exemption from section 13(f) 10 years. 28- Reports by institutional investment managers of... requirements, annual reports to shareholders, F-6 waiver, proxy 10 years. 89- Other waivers for foreign issuers...

  14. 17 CFR 200.80f - Appendix F-Records control schedule.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Securities Investor Protection Corporation assessment payment or overpayments (Rule 17a-5). (Non-public) For...- Applications for exemption from section 13(f) 10 years. 28- Reports by institutional investment managers of... requirements, annual reports to shareholders, F-6 waiver, proxy 10 years. 89- Other waivers for foreign issuers...

  15. Leptonic-decay-constant ratio f(K+)/f(π+) from lattice QCD with physical light quarks.

    PubMed

    Bazavov, A; Bernard, C; DeTar, C; Foley, J; Freeman, W; Gottlieb, Steven; Heller, U M; Hetrick, J E; Kim, J; Laiho, J; Levkova, L; Lightman, M; Osborn, J; Qiu, S; Sugar, R L; Toussaint, D; Van de Water, R S; Zhou, R

    2013-04-26

    A calculation of the ratio of leptonic decay constants f(K+)/f(π+) makes possible a precise determination of the ratio of Cabibbo-Kobayashi-Maskawa (CKM) matrix elements |V(us)|/|V(ud)| in the standard model, and places a stringent constraint on the scale of new physics that would lead to deviations from unitarity in the first row of the CKM matrix. We compute f(K+)/f(π+) numerically in unquenched lattice QCD using gauge-field ensembles recently generated that include four flavors of dynamical quarks: up, down, strange, and charm. We analyze data at four lattice spacings a ≈ 0.06, 0.09, 0.12, and 0.15 fm with simulated pion masses down to the physical value 135 MeV. We obtain f(K+)/f(π+) = 1.1947(26)(37), where the errors are statistical and total systematic, respectively. This is our first physics result from our N(f) = 2+1+1 ensembles, and the first calculation of f(K+)/f(π+) from lattice-QCD simulations at the physical point. Our result is the most precise lattice-QCD determination of f(K+)/f(π+), with an error comparable to the current world average. When combined with experimental measurements of the leptonic branching fractions, it leads to a precise determination of |V(us)|/|V(ud)| = 0.2309(9)(4) where the errors are theoretical and experimental, respectively.

  16. A novel coil array for combined TMS/fMRI experiments at 3 T

    PubMed Central

    Navarro de Lara, Lucia I.; Windischberger, Christian; Kuehne, Andre; Woletz, Michael; Sieg, Jürgen; Bestmann, Sven; Weiskopf, Nikolaus; Strasser, Bernhard; Moser, Ewald

    2014-01-01

    Purpose To overcome current limitations in combined transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) studies by employing a dedicated coil array design for 3 Tesla. Methods The state‐of‐the‐art setup for concurrent TMS/fMRI is to use a large birdcage head coil, with the TMS between the subject's head and the MR coil. This setup has drawbacks in sensitivity, positioning, and available imaging techniques. In this study, an ultraslim 7‐channel receive‐only coil array for 3 T, which can be placed between the subject's head and the TMS, is presented. Interactions between the devices are investigated and the performance of the new setup is evaluated in comparison to the state‐of‐the‐art setup. Results MR sensitivity obtained at the depth of the TMS stimulation is increased by a factor of five. Parallel imaging with an acceleration factor of two is feasible with low g‐factors. Possible interactions between TMS and the novel hardware were investigated and were found negligible. Conclusion The novel coil array is safe, strongly improves signal‐to‐noise ratio in concurrent TMS/fMRI experiments, enables parallel imaging, and allows for flexible positioning of the TMS on the head while ensuring efficient TMS stimulation due to its ultraslim design. Magn Reson Med 74:1492–1501, 2015. © 2014 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID:25421603

  17. Thermoluminescence dosimetric characteristics on cubic fluoroperovskite single crystal (KMgF3:Eu2+, Ce3+)

    NASA Astrophysics Data System (ADS)

    Joseph Daniel, D.; Madhusoodanan, U.; Annalakshmi, O.; Jose, M. T.; Ramasamy, P.

    2015-07-01

    This paper describes investigation of thermoluminescence radiation dosimetry characteristics of Eu2+ doped Potassium Magnesium Fluoride (KMgF3) single crystal co-doped with Ce3+ ions. The perovskite-like KMgF3 polycrystalline compounds were synthesized by standard solid state reaction technique. Phase purity of the synthesized compounds was analyzed by powder X-ray diffraction technique. Single crystals of KMgF3 have been grown from melt by using a vertical Bridgman-Stockbarger method. Thermoluminescence (TL) characteristics of KMgF3 samples doped with Eu2+ and Ce3+ have been studied after β-ray irradiation at room temperature. Order of kinetics (b), activation energy (E), and frequency factor (s) were determined by Chen's method and variable heating rate method. Results show that the TL glow peak of the KMgF3 samples obeys second-order kinetics. Analysis of the main dosimetric peak by using the methods mentioned above revealed that activation energy (E) is about 1.2 eV and the frequency factor (s) is in the range 1010-1011 s-1. The TL glow curve structure of the sample remained stable for higher doses of 90Sr/90Y beta source and it shows linearity up to 180 Gy. The time dependent fading behavior of the TL characteristics has also been investigated and is found to be quite stable over long time duration. The characteristic Eu2+ emissions are observed in the TL emission spectra.

  18. Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes.

    PubMed

    Grant, Michael; Larijani, Mani

    2017-09-12

    APOBEC3G (A3G) and APOBEC3F (A3F) are DNA-mutating enzymes expressed in T cells, dendritic cells and macrophages. A3G/F have been considered innate immune host factors, based on reports that they lethally mutate the HIV genome in vitro. In vivo, A3G/F effectiveness is limited by viral proteins, entrapment in inactive complexes and filtration of mutations during viral life cycle. We hypothesized that the impact of sub-lethal A3G/F action could extend beyond the realm of innate immunity confined to the cytoplasm of infected cells. We measured recognition of wild type and A3G/F-mutated epitopes by cytotoxic T lymphocytes (CTL) from HIV-infected individuals and found that A3G/F-induced mutations overwhelmingly diminished CTL recognition of HIV peptides, in a human histocompatibility-linked leukocyte antigen (HLA)-dependent manner. Furthermore, we found corresponding enrichment of A3G/F-favored motifs in CTL epitope-encoding sequences within the HIV genome. These findings illustrate that A3G/F-mediated mutations mediate immune evasion by HIV in vivo. Therefore, we suggest that vaccine strategies target T cell or antibody epitopes that are not poised for mutation into escape variants by A3G/F action.

  19. Proton-induced degradation of VUV transmission of LiF and MgF2

    NASA Technical Reports Server (NTRS)

    Reft, C. S.; Becher, J.; Kernell, R. L.

    1980-01-01

    Proton-induced degradation of vacuum ultraviolet (VUV) transmittance of LiF and MgF2 was measured for 85- and 600-MeV protons for a fluence up to 2.8 x 10 to the 13th p/sq cm. Transmittances were measured from 105 to 210 nm. When the irradiation level for a given material is expressed in terms of absorbed energy per unit of volume of crystal, 85- and 600-MeV protons produce the same degradation. MgF2 is substantially more radiation resistant than LiF in the VUV. Irradiation of LiF with 1.8 x 10 to the 13th p/sq cm at 85 MeV changed the transmittance of the hydrogen Ly-alpha line at 121.6 nm from 55 to 23%. The corresponding change for MgF2 was from 52 to 42% for 2.8 x 10 to the 13th p/sq cm.

  20. Depicting changes in tumor biology in response to cetuximab mono- or combination therapy by apoptosis and proliferation imaging using 18F-ICMT-11 and 3'-Deoxy-3'-[18F]Fluorothymidine (18F-FLT) PET.

    PubMed

    Heinzmann, Kathrin; Nguyen, Quang-De; Honess, Davina Jean; Smith, Donna-Michelle; Stribbling, Stephen; Brickute, Diana; Barnes, Christopher; Griffiths, John Richard; Aboagye, Eric Ofori

    2018-05-24

    Imaging biomarkers must demonstrate their value in monitoring treatment. Two PET tracers, the caspase-3/7-specific isatin-5-sulfonamide 18 F-ICMT-11 and 3'-Deoxy-3'-[ 18 F]Fluorothymidine ( 18 F-FLT), were employed to detect early treatment-induced changes in tumor biology and whether any changes indicate response to cetuximab, administered as mono- or combination therapy with gemcitabine. Methods: Effects of single or repeated doses of the anti-Epidermal Growth Factor Receptor (EGFR) antibody cetuximab (10mg/kg on day 1 only or day 1 and 2) and/or a single dose of gemcitabine (125mg/kg; day 2) were investigated in mice bearing cetuximab-sensitive H1975 tumors (non-small cell lung cancer) by 18 F-ICMT-11 or 18 F-FLT-PET (day 3). Imaging was also performed in mice bearing cetuximab-insensitive HCT116 tumors (colorectal cancer) after two doses of cetuximab (day 1 and 2). For imaging/histology comparison, tumors were evaluated for proliferation (Ki67; thymidine kinase 1, TK1), cell death (cleaved caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)) and target engagement (EGFR expression) by immunohistochemistry, immunofluorescence and immunoblot, respectively. Tumor and plasma were analysed for thymidine and gemcitabine metabolites by liquid chromatography-mass spectrometry. Results: Retention of both tracers was sensitive to cetuximab in H1975 tumors. 18 F-ICMT-11 uptake and ex vivo cleaved caspase-3 staining notably increased in tumors treated with repeated doses of cetuximab- (75%) and combination-treatment (46%). While one dose of cetuximab was insufficient to induce apoptosis it did affect proliferation. Significant reduction in tumor 18 F-FLT uptake (44 to 50%; P < 0.001) induced by cetuximab mono- and combination-therapy were paralleled with a clear decrease in proliferation (%Ki67 decrease: 72 to 95%; P < 0.0001) and followed by marked tumor growth delay. TK1 expression and tumor thymidine concentrations were profoundly

  1. Characteristics of PCDD/F emissions from secondary copper smelting industry.

    PubMed

    Hung, Pao Chen; Chang, Chia Chia; Chang, Shu Hao; Chang, Moo Been

    2015-01-01

    Characteristics and mechanisms of PCDD/F formation with different feed materials in secondary copper smelting industry are investigated. The results indicate that PCDD/Fs are significantly formed even with the reaction time less than 0.1s, especially when the material containing high residues (Cu3) is fed. High copper content (65±2%) in the feed material enhances PCDD/F formation rate. Memory effect and de novo synthesis are two important mechanisms leading to PCDD/F formation. PCDD/F concentrations at the cyclone's inlet are between 2.92 and 12.4ng-TEQNm(-3) and increase with increasing residue content in the feed material. Two regions are identified for high potential of PCDD/F formation including the brass melt surface of the induction furnace and piping before the induced draft fan of the inlet hood. PCDD/Fs in flue gas are effectively removed with a cyclone and bag filter at low operating temperatures (<60°C) to meet the emission limit of 1.0ng-TEQNm(-3). 1,2,3,4,6,7,8-HpCDF has the largest mass fraction of PCDD/Fs and can serve as a fingerprint for emissions from secondary copper smelting processes. The total emission factor of PCDD/Fs from flue gas, residual and fly ash in the secondary copper smelting process investigated is 22.01μg-TEQtonne(-1). Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. New Dioxaborolane Chemistry Enables [18F]-Positron-Emitting, Fluorescent [18F]-Multimodality Biomolecule Generation from the Solid Phase

    PubMed Central

    Crisp, Jessica L.; Vera, David R.; Tsien, Roger Y.; Ting, Richard

    2016-01-01

    New protecting group chemistry is used to greatly simplify imaging probe production. Temperature and organic solvent-sensitive biomolecules are covalently attached to a biotin-bearing dioxaborolane, which facilitates antibody immobilization on a streptavidin-agarose solid-phase support. Treatment with aqueous fluoride triggers fluoride-labeled antibody release from the solid phase, separated from unlabeled antibody, and creates [18F]-trifluoroborate-antibody for positron emission tomography and near-infrared fluorescent (PET/NIRF) multimodality imaging. This dioxaborolane-fluoride reaction is bioorthogonal, does not inhibit antigen binding, and increases [18F]-specific activity relative to solution-based radiosyntheses. Two applications are investigated: an anti-epithelial cell adhesion molecule (EpCAM) monoclonal antibody (mAb) that labels prostate tumors and Cetuximab, an anti-epidermal growth factor receptor (EGFR) mAb (FDA approved) that labels lung adenocarcinoma tumors. Colocalized, tumor-specific NIRF and PET imaging confirm utility of the new technology. The described chemistry should allow labeling of many commercial systems, diabodies, nanoparticles, and small molecules for dual modality imaging of many diseases. PMID:27064381

  3. The Levenson Self-Report Psychopathy Scale: An Examination of the Personality Traits and Disorders Associated with the LSRP Factors

    ERIC Educational Resources Information Center

    Miller, Joshua D.; Gaughan, Eric T.; Pryor, Lauren R.

    2008-01-01

    There are several self-report measures of psychopathy, most of which use a two-factor structure. There is debate regarding the convergence of these factors, particularly with regard to Factor 1 (F1), which is related to the interpersonal and affective aspects of psychopathy; Factor 2 (F2) is related to the social deviance associated with…

  4. Reconstruction of f(T)-gravity in the absence of matter

    NASA Astrophysics Data System (ADS)

    El Hanafy, W.; Nashed, G. G. L.

    2016-06-01

    We derive an exact f(T) gravity in the absence of ordinary matter in Friedmann-Robertson-Walker (FRW) universe, where T is the teleparallel torsion scalar. We show that vanishing of the energy-momentum tensor {T}^{μ ν } of matter does not imply vanishing of the teleparallel torsion scalar, in contrast to general relativity, where the Ricci scalar vanishes. The theory provides an exponential ( inflationary) scale factor independent of the choice of the sectional curvature. In addition, the obtained f(T) acts just like cosmological constant in the flat space model. Nevertheless, it is dynamical in non-flat models. In particular, the open universe provides a decaying pattern of the f(T) contributing directly to solve the fine-tuning problem of the cosmological constant. The equation of state (EoS) of the torsion vacuum fluid has been studied in positive and negative Hubble regimes. We study the case when the torsion is made of a scalar field ( tlaplon) which acts as torsion potential. This treatment enables to induce a tlaplon field sensitive to the symmetry of the spacetime in addition to the reconstruction of its effective potential from the f(T) theory. The theory provides six different versions of inflationary models. The real solutions are mainly quadratic, the complex solutions, remarkably, provide Higgs-like potential.

  5. 18F-FDG or 3'-deoxy-3'-18F-fluorothymidine to detect transformation of follicular lymphoma.

    PubMed

    Wondergem, Marielle J; Rizvi, Saiyada N F; Jauw, Yvonne; Hoekstra, Otto S; Hoetjes, Nikie; van de Ven, Peter M; Boellaard, Ronald; Chamuleau, Martine E D; Cillessen, Saskia A G M; Regelink, Josien C; Zweegman, Sonja; Zijlstra, Josée M

    2015-02-01

    Considering the different treatment strategy for transformed follicular lymphoma (TF) as opposed to follicular lymphoma (FL), diagnosing transformation early in the disease course is important. There is evidence that (18)F-FDG has utility as a biomarker of transformation. However, quantitative thresholds may require inclusion of homogeneous non-Hodgkin lymphoma subtypes to account for differences in tracer uptake per subtype. Moreover, because proliferation is a hallmark of transformation, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) might be superior to (18)F-FDG in this setting. To define the best tracer for detection of TF, we performed a prospective a head-to-head comparison of (18)F-FDG and (18)F-FLT in patients with FL and TF. (18)F-FDG and (18)F-FLT PET scans were obtained in 17 patients with FL and 9 patients with TF. We measured the highest maximum standardized uptake value (SUVmax), defined as the lymph node with the highest uptake per patient, and SUVrange, defined as the difference between the SUVmax of the lymph node with the highest and lowest uptake per patient. To reduce partial-volume effects, only lymph nodes larger than 3 cm(3) (A50 isocontour) were analyzed. Scans were acquired 1 h after injection of 185 MBq of (18)F-FDG or (18)F-FLT. To determine the discriminative ability of SUVmax and SUVrange of both tracers for TF, receiver-operating-characteristic curve analysis was performed. The highest SUVmax was significantly higher for TF than FL for both (18)F-FDG and (18)F-FLT (P < 0.001). SUVrange was significantly higher for TF than FL for (18)F-FDG (P = 0.029) but not for (18)F-FLT (P = 0.075). The ability of (18)F-FDG to discriminate between FL and TF was superior to that of (18)F-FLT for both the highest SUVmax (P = 0.039) and the SUVrange (P = 0.012). The cutoff value for the highest SUVmax of (18)F-FDG aiming at 100% sensitivity with a maximum specificity was found to be 14.5 (corresponding specificity, 82%). For (18)F-FLT, these values were

  6. 17 CFR 200.80f - Appendix F-Records control schedule.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ORGANIZATION; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS Information and Requests § 200.80f Appendix F... in purchasing new issues of securities from underwriters 6 years. 821- Reports by registered small... state or federal laws in the purchase and sale of securities Until date of last reported action plus 10...

  7. Resonant transfer excitation in collisions of F6+ and Mg9+ with H2

    NASA Astrophysics Data System (ADS)

    Bernstein, E. M.; Kamal, A.; Zaharakis, K. E.; Clark, M. W.; Tanis, J. A.; Ferguson, S. M.; Badnell, N. R.

    1991-10-01

    Experimental and theoretical investigations of resonant transfer excitation (RTE) for F6++H2 and Mg9++H2 collisions have been made. For both collision systems good agreement is obtained between the measured cross sections for K-shell x-ray emission coincident with electron-capture and theoretical RTE calculations. For F6+ the present calculations are about 10% lower than previous results of Bhalla and Karim [Phys. Rev. A 39, 6060 (1989); 41, 4097(E) (1990]; the measured cross sections are a factor of 2.3 larger than earlier measurements of Schulz et al. [Phys. Rev. A 38, 5454 (1988)]. The previous disagreement between experiment and theory for F6+ is removed.

  8. [Frailty and its related Factors in Vulnerable Elderly Population by Age Groups].

    PubMed

    Park, Eunok; Yu, Mi

    2016-12-01

    This study aimed to investigate factors affecting frailty by age groups among vulnerable elders in Korea. In this secondary analysis, data were collected from records for 22,868 eldesr registered in the Visiting Health Management program of Publci Health Centers in 2012. Health behaviors, clinically diagnosed disease, frailty, depression and cognitive condition were assessed. Data were analyzed using stepwise regression to determine the associated factors of frailty by age group. Alcohol consumption, physical activity, number of diseases, DM, CVA, arthritis, urinary incontinence, depression and cognitive condition were found to be factors significantly associated with frailty among the elders aged 65~74 (F=135.66, p<.001). Alcohol consumption, physical activity, CVA, arthritis, urinary incontinence, depression and cognitive condition were found to be factors associated with frailty in the elders aged 75~84 (F=245.40, p<.001). Physical activity, CVA, arthritis, depression and cognitive condition were factors associated with frailty in the elders over 85 years of age (F=96.48, p<.001). The findings show that frailty of elders and associated factors were different by age group, and common factors affecting frailty were physical activity, CVA, arthritis, depression and cognitive condition. Thus, these factors should be considered in the development of intervention program for care and prevention of frailty and program should be modified according to age group.

  9. Time varying G and \\varLambda cosmology in f(R,T) gravity theory

    NASA Astrophysics Data System (ADS)

    Tiwari, R. K.; Beesham, A.; Singh, Rameshwar; Tiwari, L. K.

    2017-08-01

    We have studied the time dependence of the gravitational constant G and cosmological constant Λ by taking into account an anisotropic and homogeneous Bianchi type-I space-time in the framework of the modified f(R,T) theory of gravity proposed by Harko et al. (Phys. Rev. D 84:024020, 2011). For a specific choice of f(R,T)=R+2f(T) where f(T)=-λ T, two solutions of the modified gravity field equations have been generated with the help of a variation law between the expansion anisotropy ({σ}/{θ}) and the scale factor (S), together with a general non-linear equation of state. The solution for m≠3 corresponds to singular model of the universe whereas the solution for m=3 represents a non-singular model. We infer that the models entail a constant value of the deceleration parameter. A careful analysis of all the physical parameters of the models has also been carried out.

  10. First experience with early dynamic (18)F-NaF-PET/CT in patients with chronic osteomyelitis.

    PubMed

    Freesmeyer, Martin; Stecker, Franz F; Schierz, Jan-Henning; Hofmann, Gunther O; Winkens, Thomas

    2014-05-01

    This study investigates whether early dynamic positron emission tomography/computed tomography (edPET/CT) using (18)F-sodium fluoride-((18)F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed(18)F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late (18)F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUVmax, edSUVmean, respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late (18)F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed(18)F-NaF -PET offers additional information about early radiotracer distribution to standard (18)F-NaF -PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed(18)F-NaF-PET to a three-phase bone scan.

  11. A new method to measure the virial factors in the reverberation mapping of active galactic nuclei

    NASA Astrophysics Data System (ADS)

    Liu, H. T.; Feng, H. C.; Bai, J. M.

    2017-04-01

    Based on the gravitational red shift, which is a prediction of Einstein's general relativity theory, of broad optical emission lines in active galactic nuclei (AGNs), a new method is proposed to estimate the virial factors f in measuring black hole masses MRM by the reverberation mapping of AGNs. The factors f can be measured based on two physical quantities, I.e. the gravitational red shifts zg and the full widths at half maxima vFWHM of broad lines. In the past, it has been difficult to determine the factors f for individual AGNs. We apply this new method to several reverberation-mapped type 1 Seyfert galaxies. There is a correlation between f and the radius of the broad-line region (BLR) rBLR, f=5.4 r_{BLR}^{0.3}, for the gravitationally red-shifted broad lines He II, He I, Hβ and Hα in the narrow-line type 1 Seyfert galaxy (NLS1) Mrk 110. This correlation results from the influence of the radiation pressure of the accretion disc on the BLR clouds. This influence seems to be more important than usually thought so in AGNs. Mrk 110 has f ≈ 8-16, distinctly larger than the mean <f> ≈ 1 usually used to estimate MRM for vFWHM. NGC 4593 and NLS1 Mrk 486 have f ≈ 3 and f ≈ 9, respectively. Higher f values of several tens are derived for three other NLS1s. There is a correlation between f and accretion rate dot{M}_{f=1}, f=6.8dot{M}^{0.4}_{f=1} for five objects, where dot{M}_{f=1}=dot{M}_{bullet }/L_{Edd}c^{-2} as f = 1 is assumed when estimating MRM used in the Eddington luminosity LEdd, dot{M}_{bullet } is the mass accretion rate, and c is the speed of light. These larger f values will produce higher MRM values and lower Eddington ratios.

  12. Repression of transcriptional activity of C/EBPalpha by E2F-dimerization partner complexes.

    PubMed

    Zaragoza, Katrin; Bégay, Valérie; Schuetz, Anja; Heinemann, Udo; Leutz, Achim

    2010-05-01

    The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, keratinocytes, and cells of the lung and placenta. C/EBPalpha transactivates lineage-specific differentiation genes and inhibits proliferation by repressing E2F-regulated genes. The myeloproliferative C/EBPalpha BRM2 mutant serves as a paradigm for recurrent human C-terminal bZIP C/EBPalpha mutations that are involved in acute myeloid leukemogenesis. BRM2 fails to repress E2F and to induce adipogenesis and granulopoiesis. The data presented here show that, independently of pocket proteins, C/EBPalpha interacts with the dimerization partner (DP) of E2F and that C/EBPalpha-E2F/DP interaction prevents both binding of C/EBPalpha to its cognate sites on DNA and transactivation of C/EBP target genes. The BRM2 mutant, in addition, exhibits enhanced interaction with E2F-DP and reduced affinity toward DNA and yet retains transactivation potential and differentiation competence that becomes exposed when E2F/DP levels are low. Our data suggest a tripartite balance between C/EBPalpha, E2F/DP, and pocket proteins in the control of proliferation, differentiation, and tumorigenesis.

  13. Directionally solidified Eu doped CaF2/Li3AlF6 eutectic scintillator for neutron detection

    NASA Astrophysics Data System (ADS)

    Kamada, Kei; Hishinuma, Kousuke; Kurosawa, Shunsuke; Shoji, Yasuhiro; Pejchal, Jan; Ohashi, Yuji; Yokota, Yuui; Yoshikawa, Akira

    2015-12-01

    Eu doped CaF2/Li3AlF6 eutectics were grown by μ-PD method. The directionally solidified eutectic with well-aligned 600 nm diameter Eu:CaF2 scintillator fibers surrounded with Li3AlF6 was prepared. The grown eutectics showed an emission peak at 422 nm ascribed to Eu2+ 4f-5d transition from Eu:CaF2 scintillation fiber. Li concentration in the Eu:CaF2-Li3AlF6 eutectic is around 0.038 mol/cm3,which is two times higher than that of LiCaAlF6 single crystal (0.016 mol/cm3). The light yield of Eu:CaF2-Li3AlF6 eutectic was around 7000 ph/neutron. The decay time was about 550 ns (89%) and 1450 ns (11%).

  14. Variola virus F1L is a Bcl-2-like protein that unlike its vaccinia virus counterpart inhibits apoptosis independent of Bim

    PubMed Central

    Marshall, B; Puthalakath, H; Caria, S; Chugh, S; Doerflinger, M; Colman, P M; Kvansakul, M

    2015-01-01

    Subversion of host cell apoptosis is an important survival strategy for viruses to ensure their own proliferation and survival. Certain viruses express proteins homologous in sequence, structure and function to mammalian pro-survival B-cell lymphoma 2 (Bcl-2) proteins, which prevent rapid clearance of infected host cells. In vaccinia virus (VV), the virulence factor F1L was shown to be a potent inhibitor of apoptosis that functions primarily be engaging pro-apoptotic Bim. Variola virus (VAR), the causative agent of smallpox, harbors a homolog of F1L of unknown function. We show that VAR F1L is a potent inhibitor of apoptosis, and unlike all other characterized anti-apoptotic Bcl-2 family members lacks affinity for the Bim Bcl-2 homology 3 (BH3) domain. Instead, VAR F1L engages Bid BH3 as well as Bak and Bax BH3 domains. Unlike its VV homolog, variola F1L only protects against Bax-mediated apoptosis in cellular assays. Crystal structures of variola F1L bound to Bid and Bak BH3 domains reveal that variola F1L forms a domain-swapped Bcl-2 fold, which accommodates Bid and Bak BH3 in the canonical Bcl-2-binding groove, in a manner similar to VV F1L. Despite the observed conservation of structure and sequence, variola F1L inhibits apoptosis using a startlingly different mechanism compared with its VV counterpart. Our results suggest that unlike during VV infection, Bim neutralization may not be required during VAR infection. As molecular determinants for the human-specific tropism of VAR remain essentially unknown, identification of a different mechanism of action and utilization of host factors used by a VAR virulence factor compared with its VV homolog suggest that studying VAR directly may be essential to understand its unique tropism. PMID:25766319

  15. Variola virus F1L is a Bcl-2-like protein that unlike its vaccinia virus counterpart inhibits apoptosis independent of Bim.

    PubMed

    Marshall, B; Puthalakath, H; Caria, S; Chugh, S; Doerflinger, M; Colman, P M; Kvansakul, M

    2015-03-12

    Subversion of host cell apoptosis is an important survival strategy for viruses to ensure their own proliferation and survival. Certain viruses express proteins homologous in sequence, structure and function to mammalian pro-survival B-cell lymphoma 2 (Bcl-2) proteins, which prevent rapid clearance of infected host cells. In vaccinia virus (VV), the virulence factor F1L was shown to be a potent inhibitor of apoptosis that functions primarily be engaging pro-apoptotic Bim. Variola virus (VAR), the causative agent of smallpox, harbors a homolog of F1L of unknown function. We show that VAR F1L is a potent inhibitor of apoptosis, and unlike all other characterized anti-apoptotic Bcl-2 family members lacks affinity for the Bim Bcl-2 homology 3 (BH3) domain. Instead, VAR F1L engages Bid BH3 as well as Bak and Bax BH3 domains. Unlike its VV homolog, variola F1L only protects against Bax-mediated apoptosis in cellular assays. Crystal structures of variola F1L bound to Bid and Bak BH3 domains reveal that variola F1L forms a domain-swapped Bcl-2 fold, which accommodates Bid and Bak BH3 in the canonical Bcl-2-binding groove, in a manner similar to VV F1L. Despite the observed conservation of structure and sequence, variola F1L inhibits apoptosis using a startlingly different mechanism compared with its VV counterpart. Our results suggest that unlike during VV infection, Bim neutralization may not be required during VAR infection. As molecular determinants for the human-specific tropism of VAR remain essentially unknown, identification of a different mechanism of action and utilization of host factors used by a VAR virulence factor compared with its VV homolog suggest that studying VAR directly may be essential to understand its unique tropism.

  16. Geraniol suppresses prostate cancer growth through down-regulation of E2F8.

    PubMed

    Lee, Sanghoon; Park, Yu Rang; Kim, Su-Hwa; Park, Eun-Jung; Kang, Min Ji; So, Insuk; Chun, Jung Nyeo; Jeon, Ju-Hong

    2016-10-01

    Geraniol, an acyclic dietary monoterpene, has been found to suppress cancer survival and growth. However, the molecular mechanism underlying the antitumor action of geraniol has not been investigated at the genome-wide level. In this study, we analyzed the microarray data obtained from geraniol-treated prostate cancer cells. Geraniol potently altered a gene expression profile and primarily down-regulated cell cycle-related gene signatures, compared to linalool, another structurally similar monoterpene that induces no apparent phenotypic changes. Master regulator analysis using the prostate cancer-specific regulatory interactome identified that the transcription factor E2F8 as a specific target molecule regulates geraniol-specific cell cycle signatures. Subsequent experiments confirmed that geraniol down-regulated E2F8 expression and the knockdown of E2F8 was sufficient to suppress cell growth by inducing G 2 /M arrest. Epidemiological analysis showed that E2F8 is up-regulated in metastatic prostate cancer and associated with poor prognosis. These results indicate that E2F8 is a crucial transcription regulator controlling cell cycle and survival in prostate cancer cells. Therefore, our study provides insight into the role of E2F8 in prostate cancer biology and therapeutics. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of Mycobacterium tuberculosis MazF Toxins

    PubMed Central

    Nigam, Akanksha; Kumar, Sathish

    2018-01-01

    ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave M. tuberculosis rRNAs. Here we report the in vitro effects of EDFs on the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against M. tuberculosis. PMID:29717013

  18. AMP-activated protein kinase α2 and E2F1 transcription factor mediate doxorubicin-induced cytotoxicity by forming a positive signal loop in mouse embryonic fibroblasts and non-carcinoma cells.

    PubMed

    Yang, Wookyeom; Park, In-Ja; Yun, Hee; Im, Dong-Uk; Ock, Sangmi; Kim, Jaetaek; Seo, Seon-Mi; Shin, Ha-Yeon; Viollet, Benoit; Kang, Insug; Choe, Wonchae; Kim, Sung-Soo; Ha, Joohun

    2014-02-21

    Doxorubicin is one of the most widely used anti-cancer drugs, but its clinical application is compromised by severe adverse effects in different organs including cardiotoxicity. In the present study we explored mechanisms of doxorubicin-induced cytotoxicity by revealing a novel role for the AMP-activated protein kinase α2 (AMPKα2) in mouse embryonic fibroblasts (MEFs). Doxorubicin robustly induced the expression of AMPKα2 in MEFs but slightly reduced AMPKα1 expression. Our data support the previous notion that AMPKα1 harbors survival properties under doxorubicin treatment. In contrast, analyses of Ampkα2(-/-) MEFs, gene knockdown of AMPKα2 by shRNA, and inhibition of AMPKα2 activity with an AMPK inhibitor indicated that AMPKα2 functions as a pro-apoptotic molecule under doxorubicin treatment. Doxorubicin induced AMPKα2 at the transcription level via E2F1, a transcription factor that regulates apoptosis in response to DNA damage. E2F1 directly transactivated the Ampkα2 gene promoter. In turn, AMPKα2 significantly contributed to stabilization and activation of E2F1 by doxorubicin, forming a positive signal amplification loop. AMPKα2 directly interacted with and phosphorylated E2F1. This signal loop was also detected in H9c2, C2C12, and ECV (human epithelial cells) cells as well as mouse liver under doxorubicin treatment. Resveratrol, which has been suggested to attenuate doxorubicin-induced cytotoxicity, significantly blocked induction of AMPKα2 and E2F1 by doxorubicin, leading to protection of these cells. This signal loop appears to be non-carcinoma-specific because AMPKα2 was not induced by doxorubicin in five different tested cancer cell lines. These results suggest that AMPKα2 may serve as a novel target for alleviating the cytotoxicity of doxorubicin.

  19. Pressure-induced photoluminescence in Mn2+-doped BaF2 and SrF2 fluorites

    NASA Astrophysics Data System (ADS)

    Hernández, Ignacio; Rodríguez, Fernando

    2003-01-01

    This work reports an effective way for inducing room temperature photoluminescence (PL) in Mn2+-doped BaF2 and SrF2 using high-pressure techniques. The aim is to understand the surprising PL behavior exhibited by Mn2+ at the cubal site of the fluorite structure. While Mn2+-doped CaF2 shows a green PL with quantum yield close to 1 at room temperature, Mn2+-doped MF2 (M=Ba,Sr) is not PL either at room temperature (SrF2) or at any temperature (BaF2) at ambient pressure. We associate the loss of Mn2+ PL on passing from CaF2 to SrF2 or BaF2 with nonradiative multiphonon relaxation whose thermal activation energy decreases along the series CaF2→SrF2→BaF2. A salient feature of this work deals with the increase of activation energy induced by pressure. It leads to a quantum yield enhancement, which favors PL recovery. Furthermore, the activation energy mainly depends on the crystal volume per molecule irrespective of the crystal structure or the local symmetry around the impurity. In this way, the relevance of the fluorite-to-cotunnite phase transition is analyzed in connection with the PL properties of the investigated compounds. The PL spectrum and the corresponding lifetime are reported for both structural phases as a function of pressure.

  20. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort

    PubMed Central

    Schwarz, John; Astermark, Jan; Menius, Erika D.; Carrington, Mary; Donfield, Sharyne M.; Gomperts, Edward D.; Nelson, George W.; Oldenburg, Johannes; Pavlova, Anna; Shapiro, Amy D.; Winkler, Cheryl A.; Berntorp, Erik

    2012-01-01

    Background Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in hemophilia A. It has been suggested that differences in the distribution of factor VIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Design and Methods Data from the HIGS Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1+H2) and inhibitor risk among individuals of genetically-determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and HLA were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Results H3 was associated with higher inhibitor risk among those genetically-identified (N=49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N=223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Conclusion H3 was not an independent predictor of inhibitor risk. Further, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. PMID:22958194

  1. New methods for B meson decay constants and form factors from lattice NRQCD

    DOE PAGES

    Hughes, C.; Davies, C. T.H.; Monahan, C. J.

    2018-03-20

    We determine the normalization of scalar and pseudoscalar current operators made from nonrelativistic b quarks and highly improved staggered light quarks in lattice quantum chromodynamics (QCD) through O(α s) and Λ QCD/m b. We use matrix elements of these operators to extract B meson decay constants and form factors, and then compare to those obtained using the standard vector and axial-vector operators. This provides a test of systematic errors in the lattice QCD determination of the B meson decay constants and form factors. We provide a new value for the B and B s meson decay constants from lattice QCDmore » calculations on ensembles that include u, d, s, and c quarks in the sea and those that have the u/d quark mass going down to its physical value. Our results are f B=0.196(6) GeV, f Bs=0.236(7) GeV, and f Bs/f B=1.207(7), agreeing well with earlier results using the temporal axial current. By combining with these previous results, we provide updated values of f B=0.190(4) GeV, f Bs=0.229(5) GeV, and f Bs/f B=1.206(5).« less

  2. New methods for B meson decay constants and form factors from lattice NRQCD

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

    Hughes, C.; Davies, C. T.H.; Monahan, C. J.

    We determine the normalization of scalar and pseudoscalar current operators made from nonrelativistic b quarks and highly improved staggered light quarks in lattice quantum chromodynamics (QCD) through O(α s) and Λ QCD/m b. We use matrix elements of these operators to extract B meson decay constants and form factors, and then compare to those obtained using the standard vector and axial-vector operators. This provides a test of systematic errors in the lattice QCD determination of the B meson decay constants and form factors. We provide a new value for the B and B s meson decay constants from lattice QCDmore » calculations on ensembles that include u, d, s, and c quarks in the sea and those that have the u/d quark mass going down to its physical value. Our results are f B=0.196(6) GeV, f Bs=0.236(7) GeV, and f Bs/f B=1.207(7), agreeing well with earlier results using the temporal axial current. By combining with these previous results, we provide updated values of f B=0.190(4) GeV, f Bs=0.229(5) GeV, and f Bs/f B=1.206(5).« less

  3. New methods for B meson decay constants and form factors from lattice NRQCD

    NASA Astrophysics Data System (ADS)

    Hughes, C.; Davies, C. T. H.; Monahan, C. J.; Hpqcd Collaboration

    2018-03-01

    We determine the normalization of scalar and pseudoscalar current operators made from nonrelativistic b quarks and highly improved staggered light quarks in lattice quantum chromodynamics (QCD) through O (αs) and ΛQCD/mb. We use matrix elements of these operators to extract B meson decay constants and form factors, and then compare to those obtained using the standard vector and axial-vector operators. This provides a test of systematic errors in the lattice QCD determination of the B meson decay constants and form factors. We provide a new value for the B and Bs meson decay constants from lattice QCD calculations on ensembles that include u , d , s , and c quarks in the sea and those that have the u /d quark mass going down to its physical value. Our results are fB=0.196 (6 ) GeV , fBs=0.236(7 ) GeV , and fB s/fB=1.207 (7 ), agreeing well with earlier results using the temporal axial current. By combining with these previous results, we provide updated values of fB=0.190 (4 ) GeV , fBs=0.229(5 ) GeV , and fB s/fB=1.206 (5 ).

  4. Behaviours and influence factors of radon progeny in three typical dwellings.

    PubMed

    Li, Hongzhao; Zhang, Lei; Guo, Qiuju

    2011-03-01

    To investigate the behaviours and influence factors of radon progeny in rural dwellings in China, site measurements of radon equilibrium factor, unattached fraction and some important indoor environmental factors, such as aerosol concentration, aerosol size distribution and ventilation rate, were carried out in three typical types of dwellings, and a theoretical study was also performed synchronously. Good consistency between the results of site measurements and the theoretical calculation on equilibrium factor F and unattached fraction f(p) was achieved. Lower equilibrium factor and higher unattached fraction in mud or cave houses were found compared to those in brick houses, and it was suggested by the theoretical study that the smaller aerosol size distribution in mud or cave houses might be the main reason for what was observed. The dose conversion factor in the mud houses and the cave houses may be higher than that in brick houses.

  5. OSD’s Obligation and Expenditure Rate Goals: An Examination of the Factors Contributing to the Interference

    DTIC Science & Technology

    2013-07-01

    or other prerequisite events 44% 32% 59% 46% 11% F22 DCAA administrative actions 44% 33% 60% 45% 10% F23 Unplanned congressional adds to PB request...Management Agency (DCMA) administration actions (F36) and Defense Contract Audit Agency (DCAA) administra- tion ( F22 ). Three contract-related factors...of business/finance personnel F31 Programmatic conflicts between government and prime contractor .81 76% Administrative Actions: F36 DCMA & F22 DCAA

  6. Human Parvovirus B19 NS1 Protein Aggravates Liver Injury in NZB/W F1 Mice

    PubMed Central

    Tsai, Chun-Chou; Chiu, Chun-Ching; Hsu, Jeng-Dong; Hsu, Huai-Sheng; Tzang, Bor-Show; Hsu, Tsai-Ching

    2013-01-01

    Human parvovirus B19 (B19) has been associated with a variety of diseases. However, the influence of B19 viral proteins on hepatic injury in SLE is still obscure. To elucidate the effects of B19 viral proteins on livers in SLE, recombinant B19 NS1, VP1u or VP2 proteins were injected subcutaneously into NZB/W F1 mice, respectively. Significant expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected in NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Markedly hepatocyte disarray and lymphocyte infiltration were observed in livers from NZB/WF 1 mice receiving B19 NS1 as compared to those mice receiving PBS. Additionally, significant increases of Tumor Necrosis Factor –α (TNF-α), TNF-α receptor, IκB kinase –α (IKK-α), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB) and nuclear factor-kappa B (NF-κB) were detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Accordingly, significant increases of matrix metalloproteinase-9 (MMP9) and U-plasminogen activator (uPA) were also detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Contrarily, no significant variation on livers from NZB/W F1 mice receiving B19 VP1u or VP2 was observed as compared to those mice receiving PBS. These findings firstly demonstrated the aggravated effects of B19 NS1 but not VP1u or VP2 protein on hepatic injury and provide a clue in understanding the role of B19 NS1 on hepatic injury in SLE. PMID:23555760

  7. Preliminary flight test results of the F100 EMD engine in an F-15 airplane

    NASA Technical Reports Server (NTRS)

    Myers, L. P.; Burcham, F. W., Jr.

    1984-01-01

    A flight evaluation of the F100 Engine Model Derivative (EMD) is conducted. The F100 EMD is an advanced version of the F100 engine that powers the F15 and F16 airplanes. The F100 EMD features a bigger fan, higher temperature turbine, a Digital Electronic Engine Control system (DEEC), and a newly designed 16 segment afterburner, all of which results in a 15 to 20 percent increase in sea level thrust. The flight evaluations consist of investigation of performance (thrust, fuel flow, and airflow) and operability (transient response and airstart) in the F-15 airplane. The performance of the F100 EMD is excellent. Aircraft acceleration time to Mach 2.0 is reduced by 23 percent with two F100 EMD engines. Several anomalies are discovered in the operability evaluations. A software change to the DEEC improved the throttle, and subsequent Cooper Harper ratings of 3 to 4 are obtained. In the extreme upper left hand corner of the flight enveloped, compressor stalls occurr when the throttle is retarded to idle power. These stalls are not predicted by altitude facility tests or stability for the compressor.

  8. Pu 236 ( n , f ) , Pu 237 ( n , f ) , and Pu 238 ( n , f ) cross sections deduced from ( p , t ) , ( p , d ) , and ( p , p ' ) surrogate reactions

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

    Hughes, R. O.; Beausang, C. W.; Ross, T. J.

    2014-07-01

    The Pu 236(n,f), Pu 237(n,f) and Pu 238(n,f) cross sections have been inferred by utilizing the surrogate ratio method. Targets of Pu 239 and U 235 were bombarded with 28.5-MeV protons, and the light ion recoils, as well as fission fragments, were detected using the STARS detector array at the K150 Cyclotron at the Texas A&M cyclotron facility. The (p, tf) reaction on Pu 239 and U 235 targets was used to deduce the σ (Pu 236(n,f))/σ(U 232(n,f)) ratio, and the Pu 236(n,f) cross section was subsequently determined for En=0.5–7.5 MeV. Similarly, the (p,df) reaction on the same two targetsmore » was used to deduce the σ(Pu 237(n,f))/σ(U 233(n,f)) ratio, and the Pu 237(n,f) cross section was extracted in the energy range En=0.5–7 MeV. The Pu 238(n,f) cross section was also deduced by utilizing the (p,p') reaction channel on the same targets. There is good agreement with the recent ENDF/B-VII.1 evaluated cross section data for Pu 238(n,f) in the range En=0.5–10.5 MeV and for Pu 237(n,f) in the range En=0.5–7 MeV; however, the Pu 236(n,f) cross section deduced in the present work is higher than the evaluation between 2 and 7 MeV.« less

  9. Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual-tracer PET/CT study.

    PubMed

    Derlin, Thorsten; Tóth, Zoltán; Papp, László; Wisotzki, Christian; Apostolova, Ivayla; Habermann, Christian R; Mester, Janos; Klutmann, Susanne

    2011-07-01

    Formation and progression of atherosclerotic plaque is a dynamic and complex process involving various pathophysiologic steps including inflammation and calcification. The purpose of this study was to compare macrophage activity as determined by (18)F-FDG PET and ongoing mineral deposition as measured by (18)F-sodium fluoride PET in atherosclerotic plaque and to correlate these findings with calcified plaque burden as assessed by CT. Forty-five patients were examined by whole-body (18)F-FDG PET, (18)F-sodium fluoride PET, and CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio [TBR]). The pattern of tracer uptake in atherosclerotic lesions was compared after color-coded multistudy image fusion of PET and CT studies. The Fisher exact test and the Spearman correlation coefficient r(s) were used for statistical analysis of image-based results and cardiovascular risk factors. Intra- and interrater reproducibility were evaluated using the Cohen κ. (18)F-sodium fluoride uptake was observed at 105 sites in 27 (60%) of the 45 study patients, and mean TBR was 2.3 ± 0.7. (18)F-FDG uptake was seen at 124 sites in 34 (75.6%) patients, and mean TBR was 1.5 ± 0.3. Calcified atherosclerotic lesions were observed at 503 sites in 34 (75.6%) patients. Eighty-one (77.1%) of the 105 lesions with marked (18)F-sodium fluoride uptake and only 18 (14.5%) of the 124 lesions with (18)F-FDG accumulation were colocalized with arterial calcification. Coincident uptake of both (18)F-sodium fluoride and (18)F-FDG was observed in only 14 (6.5%) of the 215 arterial lesions with radiotracer accumulation. PET/CT with (18)F-FDG and (18)F-sodium fluoride may allow evaluation of distinct pathophysiologic processes in atherosclerotic lesions and might provide information on the complex interactions involved in formation and progression of atherosclerotic plaque.

  10. Characterization of the temperature-sensitive reaction of F1-ATPase by using single-molecule manipulation

    PubMed Central

    Watanabe, Rikiya; Noji, Hiroyuki

    2014-01-01

    F1-ATPase (F1) is a rotary motor protein that couples ATP hydrolysis to mechanical rotation with high efficiency. In our recent study, we observed a highly temperature-sensitive (TS) step in the reaction catalyzed by a thermophilic F1 that was characterized by a rate constant remarkably sensitive to temperature and had a Q10 factor of 6–19. Since reactions with high Q10 values are considered to involve large conformational changes, we speculated that the TS reaction plays a key role in the rotation of F1. To clarify the role of the TS reaction, in this study, we conducted a stall and release experiment using magnetic tweezers, and assessed the torque generated during the TS reaction. The results indicate that the TS reaction generates the same amount of rotational torque as does ATP binding, but more than that generated during ATP hydrolysis. Thus, we confirmed that the TS reaction contributes significantly to the rotation of F1. PMID:24825532

  11. Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis

    PubMed Central

    Mori, Munemasa; Hazan, Renin; Danielian, Paul S.; Mahoney, John E.; Li, Huijun; Lu, Jining; Miller, Emily S.; Zhu, Xueliang; Lees, Jacqueline A.; Cardoso, Wellington V.

    2017-01-01

    Abnormal development of multiciliated cells is a hallmark of a variety of human conditions associated with chronic airway diseases, hydrocephalus and infertility. Multiciliogenesis requires both activation of a specialized transcriptional program and assembly of cytoplasmic structures for large-scale centriole amplification that generates basal bodies. It remains unclear, however, what mechanism initiates formation of these multiprotein complexes in epithelial progenitors. Here we show that this is triggered by nucleocytoplasmic translocation of the transcription factor E2f4. After inducing a transcriptional program of centriole biogenesis, E2f4 forms apical cytoplasmic organizing centres for assembly and nucleation of deuterosomes. Using genetically altered mice and E2F4 mutant proteins we demonstrate that centriole amplification is crucially dependent on these organizing centres and that, without cytoplasmic E2f4, deuterosomes are not assembled, halting multiciliogenesis. Thus, E2f4 integrates nuclear and previously unsuspected cytoplasmic events of centriole amplification, providing new perspectives for the understanding of normal ciliogenesis, ciliopathies and cancer. PMID:28675157

  12. 1/ f noise from the laws of thermodynamics for finite-size fluctuations.

    PubMed

    Chamberlin, Ralph V; Nasir, Derek M

    2014-07-01

    Computer simulations of the Ising model exhibit white noise if thermal fluctuations are governed by Boltzmann's factor alone; whereas we find that the same model exhibits 1/f noise if Boltzmann's factor is extended to include local alignment entropy to all orders. We show that this nonlinear correction maintains maximum entropy during equilibrium fluctuations. Indeed, as with the usual way to resolve Gibbs' paradox that avoids entropy reduction during reversible processes, the correction yields the statistics of indistinguishable particles. The correction also ensures conservation of energy if an instantaneous contribution from local entropy is included. Thus, a common mechanism for 1/f noise comes from assuming that finite-size fluctuations strictly obey the laws of thermodynamics, even in small parts of a large system. Empirical evidence for the model comes from its ability to match the measured temperature dependence of the spectral-density exponents in several metals and to show non-Gaussian fluctuations characteristic of nanoscale systems.

  13. Increased risk of recurrent thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation.

    PubMed

    De Stefano, Valerio; Za, Tommaso; Rossi, Elena; Vannucchi, Alessandro M; Ruggeri, Marco; Elli, Elena; Micò, Caterina; Tieghi, Alessia; Cacciola, Rossella R; Santoro, Cristina; Vianelli, Nicola; Guglielmelli, Paola; Pieri, Lisa; Scognamiglio, Francesca; Cacciola, Emma; Rodeghiero, Francesco; Pogliani, Enrico M; Finazzi, Guido; Gugliotta, Luigi; Leone, Giuseppe; Barbui, Tiziano

    2010-02-01

    Evidence suggests that the JAK2 V617F mutation is associated with an increased risk of first thrombosis in patients with essential thrombocythemia (ET). Whether this mutation is also a risk factor for recurrent thrombosis is currently unknown. To investigate the impact of the JAK2 V617F mutation on the risk of recurrent thrombosis in patients with ET, we carried out a multicentre retrospective cohort study. We recruited 143 patients with previous arterial (64.4%) or venous major thrombosis (34.8%) or both (0.8%); 98 of them (68.5%) carried the mutation. Thrombosis recurred in 43 of the patients (30%); overall, after adjustment for sex, age, presence of vascular risk factors, and treatment after the first thrombosis, the presence of the JAK2 mutation did not predict recurrence (multivariable hazard ratio, HR, 0.88, 95% CI 0.46-1.68). Indeed, the individuals homozygous for the JAK2 V617F (allele burden >50%) mutation had an increased risk of recurrence in comparison with wild-type patients (HR 6.15, 95% CI 1.51-24.92). In conclusion, a homozygous JAK2 V617F mutation is an independent risk factor for recurrent thrombosis in patients with ET.

  14. Radiation accumulation of F{sub 2} color centers in LiF crystal

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

    Lisitsyna, L. A.

    2016-01-15

    The paper presents the results of the research of the F{sub 2} centers accumulation dose dependences in the LiF crystals, the kinetics of absorption relaxation initiated by exposure to a single electron pulse in the band maxima of different electron centers obtained by time-resolved spectrometry with nanosecond resolution. An analytical description of the F{sub 2} center accumulation in an absorbed dose range ≤10{sup 3} Gy is provided.

  15. F-14 VSTFE

    NASA Image and Video Library

    1986-04-11

    NASA 834, an F-14 Navy Tomcat, seen here in flight, was used at Dryden in 1986 and 1987 in a program known as the Variable-Sweep Transition Flight Experiment (VSTFE). This program explored laminar flow on variable sweep aircraft at high subsonic speeds. An F-14 aircraft was chosen as the carrier vehicle for the VSTFE program primarily because of its variable-sweep capability, Mach and Reynolds number capability, availability, and favorable wing pressure distribution. The variable sweep outer-panels of the F-14 aircraft were modified with natural laminar flow gloves to provide not only smooth surfaces but also airfoils that can produce a wide range of pressure distributions for which transition location can be determined at various flight conditions and sweep angles. Glove I, seen here installed on the upper surface of the left wing, was a "cleanup" or smoothing of the basic F-14 wing, while Glove II was designed to provide specific pressure distributions at Mach 0.7. Laminar flow research continued at Dryden with a research program on the NASA 848 F-16XL, a laminar flow experiment involving a wing-mounted panel with millions of tiny laser cut holes drawing off turbulent boundary layer air with a suction pump.

  16. Functional polymorphisms of the coagulation factor II gene (F2) and susceptibility to systemic lupus erythematosus.

    PubMed

    Demirci, F Yesim K; Dressen, Amy S; Kammerer, Candace M; Barmada, M Michael; Kao, Amy H; Ramsey-Goldman, Rosalind; Manzi, Susan; Kamboh, M Ilyas

    2011-04-01

    Two F2 functional polymorphisms, rs1799963 (G20210A) and rs3136516 (A19911G), are known to be associated with elevated levels/activity of prothrombin (encoded by F2) and risk of thrombosis. Since patients with systemic lupus erythematosus (SLE) have high risk of thrombosis and accelerated atherosclerosis and also high prevalence of anti-prothrombin antibodies, we hypothesized that these two F2 polymorphisms could affect risk of SLE. We investigated these polymorphisms in 627 women with SLE (84% Caucasian Americans, 16% African Americans) and 657 female controls (78% Caucasian Americans, 22% African Americans). While the rs1799963 A allele was almost absent in African Americans, it was present at ~2% frequency in Caucasian Americans and showed no significant association with SLE. The rs3136516 G allele frequency was significantly higher in Caucasian SLE cases than in controls (48.4% vs 43.7%, respectively) with a covariate-adjusted odds ratio (OR) of 1.22 (95% CI 1.03-1.46, p = 0.023). The association was replicated in African Americans (rs3136516 G allele frequency 91.2% in cases vs 82.2% in controls) with an adjusted OR of 1.96 (95% CI 1.08-3.58, p = 0.022). Stratification of Caucasian SLE patients based on the presence or absence of cardiac and vascular events (CVE) revealed stronger association with the CVE-positive SLE subgroup than the CVE-negative SLE subgroup (OR 1.42 vs 1.20). Prothrombin activity measurements in a subset of SLE cases demonstrated higher activity in the carriers of the rs3136516 G allele. Our results suggest a potential role for prothrombin and the crosstalk between hemostatic and immune/inflammatory systems in SLE and SLE-associated cardiovascular events, which warrants further investigation in independent samples.

  17. $$B\\to Kl^+l^-$$ decay form factors from three-flavor lattice QCD

    DOE PAGES

    Bailey, Jon A.

    2016-01-27

    We compute the form factors for the B → Kl +l - semileptonic decay process in lattice QCD using gauge-field ensembles with 2+1 flavors of sea quark, generated by the MILC Collaboration. The ensembles span lattice spacings from 0.12 to 0.045 fm and have multiple sea-quark masses to help control the chiral extrapolation. The asqtad improved staggered action is used for the light valence and sea quarks, and the clover action with the Fermilab interpretation is used for the heavy b quark. We present results for the form factors f+(q 2), f 0(q 2), and f T(q 2), where q 2more » is the momentum transfer, together with a comprehensive examination of systematic errors. Lattice QCD determines the form factors for a limited range of q 2, and we use the model-independent z expansion to cover the whole kinematically allowed range. We present our final form-factor results as coefficients of the z expansion and the correlations between them, where the errors on the coefficients include statistical and all systematic uncertainties. Lastly, we use this complete description of the form factors to test QCD predictions of the form factors at high and low q 2.« less

  18. Congenital combined deficiency of coagulation factors: a study of seven patients.

    PubMed

    Naderi, Majid; Tabibian, Shadi; Hosseini, Maryam Sadat; Alizadeh, Shaban; Hosseini, Soudabeh; Shamsizadeh, Morteza; Dorgalaleh, Akbar

    2015-01-01

    Combined deficiency of coagulation factors is considered as an extremely rare bleeding disorder (RBD) inherited in an autosomal recessive pattern. This disorder is more likely to occur in regions with a high rate of consanguineous marriages or in restricted communities. Sistan and Baluchistan, a province in southeast of Iran with a high rate of consanguinity, is a clear model of such regions with a very high prevalence of recessively inherited disorders. The aim of this study was to report the frequency of combined factor deficiency in this province. This descriptive study was conducted on 358 patients with RBD. Demographic information and medical history of each patient were recorded, and the patients were examined by a physician. Routine screening tests were carried out for all patients, and further coagulation tests including coagulation factor activity and antigen assays were subsequently performed for all suspected patients. Among 358 patients, four were found to be affected with combined factor (F)V and FVIII deficiency (F5F8D). In addition, one patient with combined deficiency of FVII-FXIII, one with combined FVII-FX and one with combined FVIII-FIX deficiency were identified. In Sistan and Baluchistan Province, coinheritance of recessively inherited disorders like combined coagulation factor deficiencies was surprisingly higher than expected.

  19. Memory Performance and fMRI Signal in Presymptomatic Familial Alzheimer’s Disease

    PubMed Central

    Braskie, Meredith N.; Medina, Luis D.; Rodriguez-Agudelo, Yaneth; Geschwind, Daniel H.; Macias-Islas, Miguel Angel; Thompson, Paul M.; Cummings, Jeffrey L.; Bookheimer, Susan Y.; Ringman, John M.

    2013-01-01

    Rare autosomal dominant mutations result in familial Alzheimer’s disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes. PMID:22806961

  20. Bianchi Type-II String Cosmological Model with Magnetic Field in f ( R, T) Gravity

    NASA Astrophysics Data System (ADS)

    Sharma, N. K.; Singh, J. K.

    2014-09-01

    The spatially homogeneous and totally anisotropic Bianchi type-II cosmological solutions of massive strings have been investigated in the presence of the magnetic field in the framework of f( R, T) gravity proposed by Harko et al. (Phys Rev D 84:024020, 2011). With the help of special law of variation for Hubble's parameter proposed by Berman (Nuovo Cimento B 74:182, 1983) cosmological model is obtained in this theory. We consider f( R, T) model and investigate the modification R+ f( T) in Bianchi type-II cosmology with an appropriate choice of a function f( T)= μ T. We use the power law relation between average Hubble parameter H and average scale factor R to find the solution. The assumption of constant deceleration parameter leads to two models of universe, i.e. power law model and exponential model. Some physical and kinematical properties of the model are also discussed.

  1. Flavor structure in F-theory compactifications

    NASA Astrophysics Data System (ADS)

    Hayashi, Hirotaka; Kawano, Teruhiko; Tsuchiya, Yoichi; Watari, Taizan

    2010-08-01

    F-theory is one of frameworks in string theory where supersymmetric grand unification is accommodated, and all the Yukawa couplings and Majorana masses of righthanded neutrinos are generated. Yukawa couplings of charged fermions are generated at codimension-3 singularities, and a contribution from a given singularity point is known to be approximately rank 1. Thus, the approximate rank of Yukawa matrices in low-energy effective theory of generic F-theory compactifications are minimum of either the number of generations N gen = 3 or the number of singularity points of certain types. If there is a geometry with only one E 6 type point and one D 6 type point over the entire 7-brane for SU(5) gauge fields, F-theory compactified on such a geometry would reproduce approximately rank-1 Yukawa matrices in the real world. We found, however, that there is no such geometry. Thus, it is a problem how to generate hierarchical Yukawa eigenvalues in F-theory compactifications. A solution in the literature so far is to take an appropriate factorization limit. In this article, we propose an alternative solution to the hierarchical structure problem (which requires to tune some parameters) by studying how zero mode wavefunctions depend on complex structure moduli. In this solution, the N gen × N gen CKM matrix is predicted to have only N gen entries of order unity without an extra tuning of parameters, and the lepton flavor anarchy is predicted for the lepton mixing matrix. The hierarchy among the Yukawa eigenvalues of the down-type and charged lepton sector is predicted to be smaller than that of the up-type sector, and the Majorana masses of left-handed neutrinos generated through the see-saw mechanism have small hierarchy. All of these predictions agree with what we observe in the real world. We also obtained a precise description of zero mode wavefunctions near the E 6 type singularity points, where the up-type Yukawa couplings are generated.

  2. Platypus Pou5f1 reveals the first steps in the evolution of trophectoderm differentiation and pluripotency in mammals.

    PubMed

    Niwa, Hitoshi; Sekita, Yoko; Tsend-Ayush, Enkhjargal; Grützner, Frank

    2008-01-01

    Uterine nourishment of embryos by the placenta is a key feature of mammals. Although a variety of placenta types exist, they are all derived from the trophectoderm (TE) cell layer of the developing embryo. Egg-laying mammals (platypus and echidnas) are distinguished by a very short intrauterine embryo development, in which a simple placenta forms from TE-like cells. The Pou5f1 gene encodes a class V POU family transcription factor Oct3/4. In mice, Oct3/4 together with the highly conserved caudal-related homeobox transcription factor Cdx2, determines TE fate in pre-implantation development. In contrast to Cdx2, Pou5f1 has only been identified in eutherian mammals and marsupials, whereas, in other vertebrates, pou2 is considered to be the Pou5f1 ortholog. Here, we show that platypus and opossum genomes contain a Pou5f1 and pou2 homolog, pou2-related, indicating that these two genes are paralogues and arose by gene duplication in early mammalian evolution. In a complementation assay, we found that platypus or human Pou5f1, but not opossum or zebrafish pou2, restores self-renewal in Pou5f1-null mouse ES cells, showing that platypus possess a fully functional Pou5f1 gene. Interestingly, we discovered that parts of one of the conserved regions (CR4) is missing from the platypus Pou5f1 promoter, suggesting that the autoregulation and reciprocal inhibition between Pou5f1 and Cdx2 evolved after the divergence of monotremes and may be linked to the development of more elaborate placental types in marsupial and eutherian mammals.

  3. Complement Factor H Is Expressed in Adipose Tissue in Association With Insulin Resistance

    PubMed Central

    Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel

    2010-01-01

    OBJECTIVE Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. RESEARCH DESIGN AND METHODS Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. RESULTS Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. CONCLUSIONS Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances. PMID:19833879

  4. Complement factor H is expressed in adipose tissue in association with insulin resistance.

    PubMed

    Moreno-Navarrete, José María; Martínez-Barricarte, Rubén; Catalán, Victoria; Sabater, Mònica; Gómez-Ambrosi, Javier; Ortega, Francisco José; Ricart, Wifredo; Blüher, Mathias; Frühbeck, Gema; Rodríguez de Cordoba, Santiago; Fernández-Real, José Manuel

    2010-01-01

    Activation of the alternative pathway of the complement system, in which factor H (fH; complement fH [CFH]) is a key regulatory component, has been suggested as a link between obesity and metabolic disorders. Our objective was to study the associations between circulating and adipose tissue gene expressions of CFH and complement factor B (fB; CFB) with obesity and insulin resistance. Circulating fH and fB were determined by enzyme-linked immunosorbent assay in 398 subjects. CFH and CFB gene expressions were evaluated in 76 adipose tissue samples, in isolated adipocytes, and in stromovascular cells (SVC) (n = 13). The effects of weight loss and rosiglitazone were investigated in independent cohorts. Both circulating fH and fB were associated positively with BMI, waist circumference, triglycerides, and inflammatory parameters and negatively with insulin sensitivity and HDL cholesterol. For the first time, CFH gene expression was detected in human adipose tissue (significantly increased in subcutaneous compared with omental fat). CFH gene expression in omental fat was significantly associated with insulin resistance. In contrast, CFB gene expression was significantly increased in omental fat but also in association with fasting glucose and triglycerides. The SVC fraction was responsible for these differences, although isolated adipocytes also expressed fB and fH at low levels. Both weight loss and rosiglitazone led to significantly decreased circulating fB and fH levels. Increased circulating fH and fB concentrations in subjects with altered glucose tolerance could reflect increased SVC-induced activation of the alternative pathway of complement in omental adipose tissue linked to insulin resistance and metabolic disturbances.

  5. Detection of race-specific resistance against Puccinia coronata f. sp. avenae in Brachypodium species.

    PubMed

    Omidvar, Vahid; Dugyala, Sheshanka; Li, Feng; Rottschaefer, Susan; Miller, Marisa; Ayliffe, Michael; Moscou, Matthew James; Kianian, Shahryar F; Figueroa, Melania

    2018-06-20

    Oat crown rust caused by Puccinia coronata f. sp. avenae is the most destructive foliar disease of cultivated oat. Characterization of genetic factors controlling resistance responses to Puccinia coronata f. sp. avenae in non-host species could provide new resources for developing disease protection strategies in oat. We examined symptom development and fungal colonization levels of a collection of Brachypodium distachyon and B. hybridum accessions infected with three North American P. coronata f. sp. avenae isolates. Our results demonstrated that colonization phenotypes are dependent on both host and pathogen genotypes, indicating a role for race-specific responses in these interactions. These responses were independent of the accumulation of reactive oxygen species. Expression analysis of several defense-related genes suggested that salicylic acid and ethylene-mediated signaling, but not jasmonic acid are components of resistance reaction to P. coronata f. sp. avenae. Our findings provide the basis to conduct a genetic inheritance study to examine if effector-triggered immunity contributes to non-host resistance to P. coronata f. sp. avenae in Brachypodium species.

  6. 48 CFR 52.247-45 - F.o.b. Origin and/or F.o.b. Destination Evaluation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false F.o.b. Origin and/or F.o.b... Clauses 52.247-45 F.o.b. Origin and/or F.o.b. Destination Evaluation. As prescribed in 47.305-2(b), insert the following provision in solicitations when offers are solicited on the basis of both f.o.b. origin...

  7. YB-1, the E2F Pathway, and Regulation of Tumor Cell Growth

    PubMed Central

    Samuel, Weini; Cao, Helen; Patel, Rachna; Mehta, Reena; Stern, J. Lewis; Reid, Glen; Woolley, Adele G.; Miller, Lance D.; Black, Michael A; Shelling, Andrew N.; Print, Cristin G.; Braithwaite, Antony W.

    2012-01-01

    Background Y-box binding factor 1 (YB-1) has been associated with prognosis in many tumor types. Reduced YB-1 expression inhibits tumor cell growth, but the mechanism is unclear. Methods YB-1 mRNA levels were compared with tumor grade and histology using microarray data from 771 breast cancer patients and with disease-free survival and distant metastasis–free survival using data from 375 of those patients who did not receive adjuvant therapy. Microarrays were further searched for genes that had correlated expression with YB-1 mRNA. Small interfering RNA (siRNA) was used to study the effects of reduced YB-1 expression on growth of three tumor cell lines (MCF-7 breast, HCT116 colon, and A549 lung cancer cells), on tumorigenesis by A549 cells in nude mice, and on global transcription in the three cancer cell lines. Reporter gene assays were used to determine whether YB-1 siRNAs affected the expression of E2F1, and chromatin immunoprecipitation was used to determine whether YB-1 bound to various E2F promoters as well as E2F1-regulated promoters. All P values were from two-sided tests. Results YB-1 levels were elevated in more aggressive tumors and were strongly associated with poor disease-free survival and distant metastasis–free survival. YB-1 expression was often associated with the expression of genes with E2F sites in their promoters. Cells expressing YB-1 siRNA grew substantially more slowly than control cells and formed tumors less readily in nude mice. Transcripts that were altered in cancer cell lines with YB-1 siRNA included 32 genes that are components of prognostic gene expression signatures. YB-1 regulated expression of an E2F1 promoter–reporter construct in A549 cells (eg, relative E2F1 promoter activity with control siRNA = 4.04; with YB-1 siRNA = 1.40, difference= −2.64, 95% confidence interval = −3.57 to −1.71, P < .001) and bound to the promoters of several well-defined E2F1 target genes. Conclusion YB-1 expression is associated with the

  8. Combined Raman and SEM study on CaF2 formed on/in enamel by APF treatments.

    PubMed

    Tsuda, H; Jongebloed, W L; Stokroos, I; Arends, J

    1993-01-01

    Raman spectra containing the distinct band at 322 cm-1 due to CaF2 or CaF2-like material formed in/on fluoridated bovine enamel were recorded using a micro-Raman spectrograph. Due to increasing levels of background fluorescence with increasing thickness of enamel, the Raman measurements were carried out on thin regions of wedged enamel sections. The distribution of the CaF2 or CaF2-like material was estimated using a simple model. The results indicate that 1/3 of the total CaF2 was concentrated within the narrow depth < 2 microns with high CaF2 concentrations (> 10 wt%), and that the majority of the CaF2 was distributed over the depths up to 26 microns (1 wt% CaF2). SEM observations on fractured fluoridated enamel confirmed that morphological changes were present in the depth range comparable to that of the high CaF2 concentration region expected from the Raman analysis. In deeper regions where lower concentration (< 10%) but a large amount of CaF2 was still expected, the SEM images failed to distinguish between the normal and fluoridated enamel. After KOH treatment, the Raman spectra did not show evidence of the CaF2 peak and the SEM micrographs also confirmed the removal of globules. The peak position of the Raman band of the CaF2 formed by the fluoridation was identical to that of pure CaF2. However, the linewidth was 23 cm-1 (FWHM) and a factor of 2 broader than that of pure CaF2 (12 cm-1). This implies that the lattice dynamics of the CaF2 formed by fluoridation is different from of pure CaF2, and that the material formed is 'CaF2-like' or 'disordered CaF2'.

  9. Beauty, charm, and F{sub L} at HERA: New data vs. Early predictions

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

    Nikolaev, N. N.; Zoller, V. R., E-mail: zoller@itep.r

    One of the well-known effects of the asymptotic freedom is splitting of the leading-log BFKL pomeron into a series of isolated poles in complex angular momentum plane. Following our earlier works we explore the phenomenological consequences of the emerging BFKL-Regge factorized expansion for the small-x charm (F{sub 2}{sup c}) and beauty (F{sub 2}{sup b}) structure functions of the proton. As we found earlier, the colordipole approach to the BFKL dynamics predicts uniquely decoupling of subleading hard BFKL exchanges from F{sub 2}{sup c} at moderately large Q{sup 2}. We predicted precocious BFKL asymptotics of F{sub 2}{sup c} (x,Q{sup 2}) with interceptmore » of the rightmost BFKL pole {alpha}{sub P}(0) - 1 = {Delta}{sub P} {approx} 0.4. High-energy open beauty photo- and electroproduction probes the vacuum exchange at much smaller distances and detects significant corrections to the BFKL asymptotics coming from the subleading vacuum poles. In view of the accumulation of the experimental data on small -xF{sub 2}{sup c} and F{sub 2}{sup b} we extended our early predictions to the kinematical domain covered by new HERA measurements. Our structure functions obtained in 1999 agree well with the determination of both F{sub 2}{sup c} and F{sub 2}{sup b} by the H1 published in 2006 but contradict very recent (2008, preliminary)H1 results on F{sub 2}{sup b}. We present also comparison of our early predictions for the longitudinal structure function F{sub L} with recent H1 data (2008) taken at very low Bjorken x. We comment on the electromagnetic corrections to the Okun-Pomeranchuk theorem.« less

  10. The F-111D Retention Issue.

    DTIC Science & Technology

    1986-06-06

    Washington D.C.: Office of Air Force History, 1978), pp. 234, 241, 254, ?59. 3 Knaack, Post- Worl -g War 11 Fighters, p. 254. 7 CHAPTER 2 HISTORICAL...The F-IlIA in Southeast Asia: 19 Second Deployment The F-I11B 22 The F-111C 25 The F-1111 25 The F-1IE 30 The F-1I1F 33 iv...Sortie 98 3-13 Maintenance Plan / Scheduling Effectiveness 99 3-14 War Readiness Spares Kit (WRSK) Fill Rate 99 3-15 WRSK / BLSS Withdrawals 100 3-16

  11. Syntactic Computation in the Human Brain: The Degree of Merger as a Key Factor

    PubMed Central

    Ohta, Shinri; Fukui, Naoki; Sakai, Kuniyoshi L.

    2013-01-01

    Our goal of this study is to characterize the functions of language areas in most precise terms. Previous neuroimaging studies have reported that more complex sentences elicit larger activations in the left inferior frontal gyrus (L. F3op/F3t), although the most critical factor still remains to be identified. We hypothesize that pseudowords with grammatical particles and morphosyntactic information alone impose a construction of syntactic structures, just like normal sentences, and that “the Degree of Merger” (DoM) in recursively merged sentences parametrically modulates neural activations. Using jabberwocky sentences with distinct constructions, we fitted various parametric models of syntactic, other linguistic, and nonlinguistic factors to activations measured with functional magnetic resonance imaging. We demonstrated that the models of DoM and “DoM+number of Search (searching syntactic features)” were the best to explain activations in the L. F3op/F3t and supramarginal gyrus (L. SMG), respectively. We further introduced letter strings, which had neither lexical associations nor grammatical particles, but retained both matching orders and symbol orders of sentences. By directly contrasting jabberwocky sentences with letter strings, localized activations in L. F3op/F3t and L. SMG were indeed independent of matching orders and symbol orders. Moreover, by using dynamic causal modeling, we found that the model with a inhibitory modulatory effect for the bottom-up connectivity from L. SMG to L. F3op/F3t was the best one. For this best model, the top-down connection from L. F3op/F3t to L. SMG was significantly positive. By using diffusion-tensor imaging, we confirmed that the left dorsal pathway of the superior longitudinal and arcuate fasciculi consistently connected these regions. Lastly, we established that nonlinguistic order-related and error-related factors significantly activated the right (R.) lateral premotor cortex and R. F3op/F3t, respectively

  12. Difluorophosphoryl nitrene F2P(O)N: matrix isolation and unexpected rearrangement to F2PNO.

    PubMed

    Zeng, Xiaoqing; Beckers, Helmut; Willner, Helge; Neuhaus, Patrik; Grote, Dirk; Sander, Wolfram

    2009-12-14

    Triplet difluorophosphoryl nitrene F(2)P(O)N (X(3)A'') was generated on ArF excimer laser irradiation (lambda=193 nm) of F(2)P(O)N(3) in solid argon matrix at 16 K, and characterized by its matrix IR, UV/Vis, and EPR spectra, in combination with DFT and CBS-QB3 calculations. On visible light irradiation (lambda>420 nm) at 16 K F(2)P(O)N reacts with molecular nitrogen and some of the azide is regenerated. UV irradiation (lambda=255 nm) of F(2)P(O)N (X(3)A'') induced a Curtius-type rearrangement, but instead of a 1,3-fluorine shift, nitrogen migration to give F(2)PON is proposed to be the first step of the photoisomerization of F(2)P(O)N into F(2)PNO (difluoronitrosophosphine). Formation of novel F(2)PNO was confirmed with (15)N- and (18)O-enriched isotopomers by IR spectroscopy and DFT calculations. Theoretical calculations predict a rather long P-N bond of 1.922 A [B3LYP/6-311+G(3df)] and low bond-dissociation energy of 76.3 kJ mol(-1) (CBS-QB3) for F(2)PNO.

  13. 11. Historic American Buildings Survey S.F. Chronicle Library Collection, S.F. ...

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

    11. Historic American Buildings Survey S.F. Chronicle Library Collection, S.F. WALLS AND TOWER AFTER DISASTER OF 1906 - St. Mary's Church, 660 California Street, San Francisco, San Francisco County, CA

  14. Algebraic cycles and local anomalies in F-theory

    NASA Astrophysics Data System (ADS)

    Bies, Martin; Mayrhofer, Christoph; Weigand, Timo

    2017-11-01

    We introduce a set of identities in the cohomology ring of elliptic fibrations which are equivalent to the cancellation of gauge and mixed gauge-gravitational anomalies in F-theory compactifications to four and six dimensions. The identities consist in (co)homological relations between complex codimension-two cycles. The same set of relations, once evaluated on elliptic Calabi-Yau three-folds and four-folds, is shown to universally govern the structure of anomalies and their Green-Schwarz cancellation in six- and four-dimensional F-theory vacua, respectively. We furthermore conjecture that these relations hold not only within the cohomology ring, but even at the level of the Chow ring, i.e. as relations among codimension-two cycles modulo rational equivalence. We verify this conjecture in non-trivial examples with Abelian and non-Abelian gauge groups factors. Apart from governing the structure of local anomalies, the identities in the Chow ring relate different types of gauge backgrounds on elliptically fibred Calabi-Yau four-folds.

  15. f1: a code to compute Appell's F1 hypergeometric function

    NASA Astrophysics Data System (ADS)

    Colavecchia, F. D.; Gasaneo, G.

    2004-02-01

    In this work we present the FORTRAN code to compute the hypergeometric function F1( α, β1, β2, γ, x, y) of Appell. The program can compute the F1 function for real values of the variables { x, y}, and complex values of the parameters { α, β1, β2, γ}. The code uses different strategies to calculate the function according to the ideas outlined in [F.D. Colavecchia et al., Comput. Phys. Comm. 138 (1) (2001) 29]. Program summaryTitle of the program: f1 Catalogue identifier: ADSJ Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADSJ Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Licensing provisions: none Computers: PC compatibles, SGI Origin2∗ Operating system under which the program has been tested: Linux, IRIX Programming language used: Fortran 90 Memory required to execute with typical data: 4 kbytes No. of bits in a word: 32 No. of bytes in distributed program, including test data, etc.: 52 325 Distribution format: tar gzip file External subprograms used: Numerical Recipes hypgeo [W.H. Press et al., Numerical Recipes in Fortran 77, Cambridge Univ. Press, 1996] or chyp routine of R.C. Forrey [J. Comput. Phys. 137 (1997) 79], rkf45 [L.F. Shampine and H.H. Watts, Rep. SAND76-0585, 1976]. Keywords: Numerical methods, special functions, hypergeometric functions, Appell functions, Gauss function Nature of the physical problem: Computing the Appell F1 function is relevant in atomic collisions and elementary particle physics. It is usually the result of multidimensional integrals involving Coulomb continuum states. Method of solution: The F1 function has a convergent-series definition for | x|<1 and | y|<1, and several analytic continuations for other regions of the variable space. The code tests the values of the variables and selects one of the precedent cases. In the convergence region the program uses the series definition near the origin of coordinates, and a numerical integration of the third-order differential

  16. Radiation damage and sensitization effects on thermoluminescence of LiF:Mg,Ti (TLD-700)

    NASA Astrophysics Data System (ADS)

    Farag, M. A.; Sadek, A. M.; Shousha, Hany. A.; El-Hagg, A. A.; Atta, M. R.; Kitis, G.

    2017-09-01

    The radiation damage effects and enhancement the thermoluminescence (TL) efficiency of LiF:Mg,Ti (TLD-700)dosimeters via sensitization method were discussed. Attempts to eliminate the effects of damage and sensitization were made using different types of annealing processes. The results showed that after irradiating the dosimeters with dose > 250 Gy of 60Co gamma source, damage effects were observed. The sensitivity of the total area under the curve was decreased by a factor of ∼0.5 after irradiation at a pre-test dose of 2 kGy. However, the effects of radiation damage on each glow-peak are different. The glow-peak 2 was the only peak that was not affected by the high-dose irradiation. It has been shown that the degree of the radiation damage effect is related to the maximum dose-response function, f(D)max of the glow-peak. In general, significant radiation damage effects were observed for the glow-peaks of high f(D)max . Post-irradiation anneal at 280 °C for 30 min causes dramatic effects on the shape of the glow-curve and as well as on the sensitivity of the dosimeters. An increasing by a factor of ∼35 in the sensitivity of the total area under the curve was observed at a pre-test dose of 2 kGy. Improving the sensitivity of peak 7 by a factor of∼22 was the dominant factor in increasing the sensitivity of the dosimeters. On the other hand, an increasing by factors of ∼2.5 and ∼4 was found for peaks 2 and 5 respectively. On the other hand, a decreasing by a factor ∼0.5 was observed for peaks 3 and 4. At pre-test dose levels >250 Gy, a very strange and high intensity tail was observed in the high-temperature region of the glow-curves. The readout anneal was not enough to remove this tail. While, the furnace anneal could eliminate the sensitization effects but not the radiation damage effects on the sensitivity of the dosimeters.

  17. Status of development of LCOS projection displays for F-22A, F/A-18E/F, and JSF cockpits

    NASA Astrophysics Data System (ADS)

    Kalmanash, Michael H.

    2001-09-01

    Projection display technology has been found to be an attractive alternative to direct view flat panel displays in many avionics applications. The projection approach permits compact high performance systems to be tailored to specific platform needs while using a complement of commercial off the shelf (COTS) components, including liquid crystal on silicon (LCOS) microdisplay imagers. A common projection engine used on multiple platforms enables improved performance, lower cost and shorter development cycles. This paper provides a status update for projection displays under development for the F-22A, the F/A-18E/F and the Lockheed Joint Strike Fighter (JSF) aircraft.

  18. The effect of renal failure on 18F-FDG uptake: a theoretic assessment.

    PubMed

    Laffon, Eric; Cazeau, Anne-Laure; Monet, Antoine; de Clermont, Henri; Fernandez, Philippe; Marthan, Roger; Ducassou, Dominique

    2008-12-01

    This work addresses the issue of using (18)F-FDG PET in patients with renal failure. A model analysis has been developed to compare tissue (18)F-FDG uptake in a patient who has normal renal function with uptake in a theoretic limiting case that assumes tracer plasma decay is tracer physical decay and is trapped irreversibly. This comparison has allowed us to propose, in the limiting case, that the usually injected activity be lowered by a factor of 3. We also proposed that the PET static acquisition be obtained at about 160 min after tracer injection. These 2 proposals were aimed at obtaining a similar patient radiation dose and similar tissue (18)F-FDG uptake. In patients with arbitrary renal failure (i.e., between the 2 extremes of normal function and the theoretic limiting case), we propose that the injected activity be lowered (without exceeding a factor of 3) and that the acquisition be started between 45 and 160 min after tracer injection, depending on the severity of renal failure. Furthermore, the model also shows that the more severe the renal failure is, the more overestimated is the standardized uptake value, unless the renal failure indirectly impairs tissue sensitivity to insulin and hence glucose metabolism.

  19. Laser cooling of BaF

    NASA Astrophysics Data System (ADS)

    Bo, Yan; Bu, Wenhao; Chen, Tao; Lv, Guitao

    2017-04-01

    In this poster, we report our recently experimental progresses in laser cooling of BaF molecule. Our theoretic calculation shows BaF is a good candidate for laser cooling: quasi-cycling transitions, good wavelengths (around 900nm) for the main transitions. We have built a 4K cryogenic machine, laser ablate the target to make BaF molecules. The precise spectroscopy of BaF is measured and the laser cooling related transitions are identified. The collision between BaF and 4K He is carefully characterized. The quasi-cycling transition is demonstrated. And laser cooling experiment is going on.

  20. Uncertainties in estimates of fAPAR for photosynthesis (fAPARPSN) in tropical, Arctic/boreal, coastal, and wetland-dominant regions when approximated with fAPARcanopy and NDVI

    NASA Astrophysics Data System (ADS)

    Zhang, Q.; Yao, T.

    2016-12-01

    The climate is affected by the land surface through regulating the exchange of mass and energy with the atmosphere. The energy that reaches the land surface has three pathways: (1) reflected into atmosphere; (2) absorbed for photosynthesis; and (3) discarded as latent and sensible heat or emitted as fluorescence. Vegetation removes CO2 from the atmosphere during the process of photosynthesis, but also releases CO2 back into the atmosphere through the process of respiration. The complex set of vegetation-soil-atmosphere interactions requires that a realistic land-surface parameterization be included in any climate model or general circulation model (GCM) to accurately simulate canopy photosynthesis and stomatal conductance.We retrieve fraction of PAR absorbed by chlorophyll (fAPARchl) with an advanced canopy-leaf-soil-snow-water coupled radiative transfer model. Most ecological models and land-surface models that simulate vegetation GPP with remote sensing data utilize fraction of PAR absorbed by the whole canopy (fAPARcanopy). However, only the PAR absorbed by chlorophyll is potentially available for photosynthesis since the PAR absorbed by non-photosynthetic vegetation section (NPV) of the canopy is not used for photosynthesis. Therefore, fAPARchl (rather than fAPARcanopy) should be utilized to estimate fAPAR for photosynthesis (fAPARPSN), and thus in GPP simulation. Globally selected sites include those sites in tropical, Arctic/boreal, coastal, and wetland-dominant regions. The fAPARchl and fAPARcanopy products for a surrounding area 50 km x 50 km of each site are mapped. The fAPARchl is utilized to estimate GPP, and compared to tower flux GPP for validation. The GPP estimation performance with fAPARchl is also compared with the GPP estimation performance with MOD15A2 FPAR. The fAPARchl product is further implemented into ecological models and land-surface models to simulate vegetation GPP. NDVI is the other proxy of fAPARPSN in GPP estimation. We quantify the