Sample records for slsf experiment p4

  1. SLSF in-reactor local fault safety experiment P4. Final report

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

    Thompson, D. H.; Holland, J. W.; Braid, T. H.

    The Sodium Loop Safety Facility (SLSF), a major facility in the US fast-reactor safety program, has been used to simulate a variety of sodium-cooled fast reactor accidents. SLSF experiment P4 was conducted to investigate the behavior of a "worse-than-case" local fault configuration. Objectives of this experiment were to eject molten fuel into a 37-pin bundle of full-length Fast-Test-Reactor-type fuel pins form heat-generating fuel canisters, to characterize the severity of any molten fuel-coolant interaction, and to demonstrate that any resulting blockage could either be tolerated during continued power operation or detected by global monitors to prevent fuel failure propagation. The designmore » goal for molten fuel release was 10 to 30 g. Explusion of molten fuel from fuel canisters caused failure of adjacent pins and a partial flow channel blockage in the fuel bundle during full-power operation. Molten fuel and fuel debris also lodged against the inner surface of the test subassembly hex-can wall. The total fuel disruption of 310 g evaluated from posttest examination data was in excellent agreement with results from the SLSF delayed neutron detection system, but exceeded the target molten fuel release by an order of magnitude. This report contains a summary description of the SLSF in-reactor loop and support systems and the experiment operations. results of the detailed macro- and microexamination of disrupted fuel and metal and results from the analysis of the on-line experimental data are described, as are the interpretations and conclusions drawn from the posttest evaluations. 60 refs., 74 figs.« less

  2. FPIN2 posttest analysis of cylindrical canisters in SLSF Experiment P4

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

    Hughes, T H; Kramer, J M

    Results demonstrate that the clad deformation is dominated by the expansion of the fuel when it melts. In our analysis we moved the end space volume and some of the fuel-clad radial gap volume to an artificial central hole. This approximation may affect the details in the early parts of the transient, but clearly did not affect the major cladding deformation. It is also clear that the accuracy of the value of the fuel expansion upon melting is significant as is the dimensional accuracy of the fuel and canisters. The major conclusions from the FPIN2 posttest analysis of the cylindricalmore » canisters in SLSF Experiment P4 are: The maximum melt fractions in the two canisters were about 75%. Both canisters experienced about the same diametral strains of 12% prior to failure. These strains were almost entirely due to the additional volume that must be created inside the canisters to accommodate the expansion of fuel on melting. The mode of cladding failure was plastic instability by necking of the canister walls. The failure time of the 20% CW canister and the nonmechanical failure of the 10% CW canister are consistent with the FPIN2 calculations using the plastic instability failure criteria.« less

  3. Posttest examination of Sodium Loop Safety Facility experiments. [LMFBR

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

    Holland, J.W.

    In-reactor, safety experiments performed in the Sodium Loop Safety Facility (SLSF) rely on comprehensive posttest examinations (PTE) to characterize the postirradiation condition of the cladding, fuel, and other test-subassembly components. PTE information and on-line instrumentation data, are analyzed to identify the sequence of events and the severity of the accident for each experiment. Following in-reactor experimentation, the SLSF loop and test assembly are transported to the Hot Fuel Examination Facility (HFEF) for initial disassembly. Goals of the HFEF-phase of the PTE are to retrieve the fuel bundle by dismantling the loop and withdrawing the test assembly, to assess the macro-conditionmore » of the fuel bundle by nondestructive examination techniques, and to prepare the fuel bundle for shipment to the Alpha-Gamma Hot Cell Facility (AGHCF) at Argonne National Laboratory.« less

  4. Measuring Preferences for a Diabetes Pay-for-Performance for Patient (P4P4P) Program using a Discrete Choice Experiment.

    PubMed

    Chen, Tsung-Tai; Tung, Tao-Hsin; Hsueh, Ya-Seng Arthur; Tsai, Ming-Han; Liang, Hsiu-Mei; Li, Kay-Lun; Chung, Kuo-Piao; Tang, Chao-Hsiun

    2015-07-01

    To elicit a patient's willingness to participate in a diabetes pay-for-performance for patient (P4P4P) program using a discrete choice experiment method. The survey was conducted in March 2013. Our sample was drawn from patients with diabetes at five hospitals in Taiwan (International Classification of Diseases, Ninth Revision, Clinical Modification code 250). The sample size was 838 patients. The discrete choice experiment questionnaire included the attributes monthly cash rewards, exercise time, diet control, and program duration. We estimated a bivariate probit model to derive willingness-to-accept levels after accounting for the characteristics (e.g., severity and comorbidity) of patients with diabetes. The preferred program was a 3-year program involving 30 minutes of exercise per day and flexible diet control. Offering an incentive of approximately US $67 in cash per month appears to increase the likelihood that patients with diabetes will participate in the preferred P4P4P program by approximately 50%. Patients with more disadvantageous characteristics (e.g., elderly, low income, greater comorbidity, and severity) could have less to gain from participating in the program and thus require a higher monetary incentive to compensate for the disutility caused by participating in the program's activities. Our result demonstrates that a modest financial incentive could increase the likelihood of program participation after accounting for the attributes of the P4P4P program and patients' characteristics. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  5. C4'/H4' selective, non-uniformly sampled 4D HC(P)CH experiment for sequential assignments of (13)C-labeled RNAs.

    PubMed

    Saxena, Saurabh; Stanek, Jan; Cevec, Mirko; Plavec, Janez; Koźmiński, Wiktor

    2014-11-01

    A through bond, C4'/H4' selective, "out and stay" type 4D HC(P)CH experiment is introduced which provides sequential connectivity via H4'(i)-C4'(i)-C4'(i-1)-H4'(i-1) correlations. The (31)P dimension (used in the conventional 3D HCP experiment) is replaced with evolution of better dispersed C4' dimension. The experiment fully utilizes (13)C-labeling of RNA by inclusion of two C4' evolution periods. An additional evolution of H4' is included to further enhance peak resolution. Band selective (13)C inversion pulses are used to achieve selectivity and prevent signal dephasing due to the of C4'-C3' and C4'-C5' homonuclear couplings. For reasonable resolution, non-uniform sampling is employed in all indirect dimensions. To reduce sensitivity losses, multiple quantum coherences are preserved during shared-time evolution and coherence transfer delays. In the experiment the intra-nucleotide peaks are suppressed whereas inter-nucleotide peaks are enhanced to reduce the ambiguities. The performance of the experiment is verified on a fully (13)C, (15)N-labeled 34-nt hairpin RNA comprising typical structure elements.

  6. Bacteriophage P2 ogr and P4 delta genes act independently and are essential for P4 multiplication.

    PubMed Central

    Halling, C; Calendar, R

    1990-01-01

    Satellite bacteriophage P4 requires the products of the late genes of a helper phage such as P2 for lytic growth. Expression of the P2 late genes is positively regulated by the P2 ogr gene in a process requiring P2 DNA replication. Transactivation of P2 late gene expression by P4 requires the P4 delta gene product and works even in the absence of P2 DNA replication. We have made null mutants of the P2 ogr and P4 delta genes. In the absence of the P4 delta gene product, P4 multiplication required both the P2 ogr protein and P2 DNA replication. In the absence of the P2 ogr gene product, P4 multiplication required the P4 delta protein. In complementation experiments, we found that the P2 ogr protein was made in the absence of P2 DNA replication but could not function unless P2 DNA replicated. We produced P4 delta protein from a plasmid and found that it complemented the null P4 delta and P2 ogr mutants. Images PMID:2193911

  7. Copper Selenidophosphates Cu4P2Se6, Cu4P3Se4, Cu4P4Se3, and CuP2Se, Featuring Zero-, One-, and Two-Dimensional Anions.

    PubMed

    Kuhn, Alexander; Schoop, Leslie M; Eger, Roland; Moudrakovski, Igor; Schwarzmüller, Stefan; Duppel, Viola; Kremer, Reinhard K; Oeckler, Oliver; Lotsch, Bettina V

    2016-08-15

    Five new compounds in the Cu/P/Se phase diagram have been synthesized, and their crystal structures have been determined. The crystal structures of these compounds comprise four previously unreported zero-, one-, and two-dimensional selenidophosphate anions containing low-valent phosphorus. In addition to two new modifications of Cu4P2Se6 featuring the well-known hexaselenidohypodiphosphate(IV) ion, there are three copper selenidophosphates with low-valent P: Cu4P3Se4 contains two different new anions, (i) a monomeric (zero-dimensional) selenidophosphate anion [P2Se4](4-) and (ii) a one-dimensional selenidophosphate anion [Formula: see text], which is related to the well-known gray-Se-like [Formula: see text] Zintl anion. Cu4P4Se3 contains one-dimensional [Formula: see text] polyanions, whereas CuP2Se contains the 2D selenidophosphate [Formula: see text] polyanion. It consists of charge-neutral CuP2Se layers separated by a van der Waals gap which is very rare for a Zintl-type phase. Hence, besides black P, CuP2Se constitutes a new possible source of 2D oxidized phosphorus containing layers for intercalation or exfoliation experiments. Additionally, the electronic structures and some fundamental physical properties of the new compounds are reported. All compounds are semiconducting with indirect band gaps of the orders of around 1 eV. The phases reported here add to the structural diversity of chalcogenido phosphates. The structural variety of this family of compounds may translate into a variety of tunable physical properties.

  8. Trisomy 4p and deletion 4p- in a family having translocation, t(4p-; 12p+).

    PubMed

    Mortimer, J G; Chewings, W; Miethke, P; Smith, G F

    1978-01-01

    Chromosome studies on a newborn infant with the clinical features of 4p-syndrome revealed a 46,XY,4p-karyotype with deletion of bands distal to 4p14. Investigation of the family revealed normal chromosomes in the mother and a balanced translocation rcp(4;12) (p14;p13) in the father, the paternal grandfather and an uncle. A severely retarded and malformed aunt is a partial trismoy for the short arms of chromosome 4, with the unbalanced karyotype 45,XX,12p+. It appears that monosomy of bands 4p15 and 4p16 leads to the full clinical features of 4p-syndrome, while trisomy of this region causes disabilities consistent with the rather more variable 4p trisomy syndrome. From currently reported cases, a summary is presented of the results of pregnancies of both male and female translocation carriers.

  9. [Pay for performance (P4P). Long-term effects and perspectives].

    PubMed

    Schrappe, M; Gültekin, N

    2011-02-01

    After 10 years of experience and research, a wide array of results on evaluation and long-term effects of pay for performance (P4P) programs have been published. These data do not only give insight into most of the problems of implementation, but also into aspects which, in part, may attenuate the high expectations at the beginning of the discussion. P4P programs exhibit a ceiling effect, some improvements are reversed after incentives are cancelled, and improvements show opportunity costs as absent improvements for indicators, which are not object to financial incentives (in some cases for the same disease). These observations can be explained by the hypothesis that P4P programs have characteristics of fee-for-service reimbursement, if symmetric information is available for insurance and provider. P4P programs are local instruments. While integration of healthcare is considered as an important issue, they should be combined with programs and incentives which foster further vertical and horizontal integration. For Germany, further research in the implementation and effects of P4P programs is necessary.

  10. Electron excitation cross sections for the 2s(2)2p(3)4S(O) -- 2s(2)2p(3)2D(O) (forbidden) and 4S(O) -- 2s2p(4) 4P (resonance) transitions in O II

    NASA Technical Reports Server (NTRS)

    Zuo, M.; Smith, Steven J.; Chutjian, A.; Williams, I. D.; Tayal, S. S.; Mclaughlin, Brendan M.

    1995-01-01

    Experimental and theoretical excitation cross sections are reported for the first forbidden transition 4S(O) -- 2S(2)2p(3) 2D(O) (lambda-lambda 3726, 3729) and the first allowed (resonance) transition 4S(O) -- 2s2p(4) 4P(lambda-833) in O II. Use is made of electron energy loss and merged-beams methods. The electron energy range covered is 3.33 (threshold) to 15 eV for the S -- D transition, and 14.9 (threshold) to 40 eV for the S -- P transition. Care was taken to assess and minimize the metastable fraction of the O II beam. An electron mirror was designed and tested to reflect inelastically backscattered electrons into the forward direction to account for the full range of polar scattering angles. Comparisons are made between present experiments and 11-state R-matrix calculations. Calculations are also presented for the 4S(O) -- 2s(2)2p(3)2P(O) (lambda-2470) transition.

  11. Removal of Covalent Heterogeneity Reveals Simple Folding Behavior for P4-P6 RNA*

    PubMed Central

    Greenfeld, Max; Solomatin, Sergey V.; Herschlag, Daniel

    2011-01-01

    RNA folding landscapes have been described alternately as simple and as complex. The limited diversity of RNA residues and the ability of RNA to form stable secondary structures prior to adoption of a tertiary structure would appear to simplify folding relative to proteins. Nevertheless, there is considerable evidence for long-lived misfolded RNA states, and these observations have suggested rugged energy landscapes. Recently, single molecule fluorescence resonance energy transfer (smFRET) studies have exposed heterogeneity in many RNAs, consistent with deeply furrowed rugged landscapes. We turned to an RNA of intermediate complexity, the P4-P6 domain from the Tetrahymena group I intron, to address basic questions in RNA folding. P4-P6 exhibited long-lived heterogeneity in smFRET experiments, but the inability to observe exchange in the behavior of individual molecules led us to probe whether there was a non-conformational origin to this heterogeneity. We determined that routine protocols in RNA preparation and purification, including UV shadowing and heat annealing, cause covalent modifications that alter folding behavior. By taking measures to avoid these treatments and by purifying away damaged P4-P6 molecules, we obtained a population of P4-P6 that gave near-uniform behavior in single molecule studies. Thus, the folding landscape of P4-P6 lacks multiple deep furrows that would trap different P4-P6 molecules in different conformations and contrasts with the molecular heterogeneity that has been seen in many smFRET studies of structured RNAs. The simplicity of P4-P6 allowed us to reliably determine the thermodynamic and kinetic effects of metal ions on folding and to now begin to build more detailed models for RNA folding behavior. PMID:21478155

  12. S100A4 interacts with p53 in the nucleus and promotes p53 degradation.

    PubMed

    Orre, L M; Panizza, E; Kaminskyy, V O; Vernet, E; Gräslund, T; Zhivotovsky, B; Lehtiö, J

    2013-12-05

    S100A4 is a small calcium-binding protein that is commonly overexpressed in a range of different tumor types, and it is widely accepted that S100A4 has an important role in the process of cancer metastasis. In vitro binding assays has shown that S100A4 interacts with the tumor suppressor protein p53, indicating that S100A4 may have additional roles in tumor development. In the present study, we show that endogenous S100A4 and p53 interact in complex samples, and that the interaction increases after inhibition of MDM2-dependent p53 degradation using Nutlin-3A. Further, using proximity ligation assay, we show that the interaction takes place in the cell nucleus. S100A4 knockdown experiments in two p53 wild-type cell lines, A549 and HeLa, resulted in stabilization of p53 protein, indicating that S100A4 is promoting p53 degradation. Finally, we demonstrate that S100A4 knockdown leads to p53-dependent cell cycle arrest and increased cisplatin-induced apoptosis. Thus, our data add a new layer to the oncogenic properties of S100A4 through its inhibition of p53-dependent processes.

  13. H(C)P and H(P)C triple-resonance experiments at natural abundance employing long-range couplings.

    PubMed

    Malon, Michal; Koshino, Hiroyuki

    2007-09-01

    Modified two-dimensional (2D) triple-resonance H(C)P and H(P)C experiments based on INEPT/HMQC and double-INEPT schemes are applied to the study of organophosphorus compounds at natural abundances. The implementation of effective (1)H--(13)C gradient selection, additional purging pulsed field gradients, spinlock pulses, and improved phase cycling is demonstrated to allow weak correlation signals based on long-range couplings to be readily observed. Through the combination of two heteronuclear long-range coupling constants, (n)J(CH) and (n)J(PC) in H(C)P experiments or (n)J(PH) and (n)J(PC) in H(P)C experiments, protons can be correlated to a second heteronucleus through 4-7 chemical bonds. These experiments thus overcome the inherit limitations of classical (1)H-X HMBC experiments, which require a nonzero value of the heteronuclear coupling constant (n)J(XH). Ultra-broadband inversion composite pulses are successfully employed in the H(P)C INEPT/HMQC and H(P)C double-INEPT pulse sequences to increase the utility of the experiments and the quality of obtained spectra. This work extends and completes a set of 2D phase-sensitive triple-resonance experiments applicable at natural abundances, and also offers insight into the methodology of triple-resonance experiments and the application of pulsed field gradients. A one-dimensional triple-resonance experiment employing carbon detection is suggested for accurate determination of small (n)J(PC).

  14. Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1.

    PubMed

    Midro, Alina T; Zollino, Marcella; Wiland, Ewa; Panasiuk, Barbara; Iwanowski, Piotr S; Murdolo, Marina; Śmigiel, Robert; Sąsiadek, Maria; Pilch, Jacek; Kurpisz, Maciej

    2016-02-01

    The purpose of this study was to compare meiotic segregation in sperm cells from two carriers with t(4;8)(p16;p23.1) reciprocal chromosome translocations (RCTs), differing in localization of the breakpoint positions at the 4p subband-namely, 4p16.3 (carrier 1) and 4p16.1 (carrier 2)-and to compare data of the pedigree analyses performed by direct method. Three-color fluorescent in situ hybridization (FISH) on sperm cells and FISH mapping for the evaluation of the breakpoint positions, data from pedigrees, and direct segregation analysis of the pedigrees were performed. Similar proportions of normal/balanced and unbalanced sperm cells were found in both carriers. The most common was an alternate type of segregation (about 52 % and about 48 %, respectively). Unbalanced adjacent I and adjacent II karyotypes were found in similar proportions about 15 %. The direct segregation analysis (following Stengel-Rutkowski) of the pedigree of carriers of t(4;8)(p16.1;p23.1) was performed and results were compared with the data of the pedigree segregation analysis obtained earlier through the indirect method. The probability of live-born progeny with unbalanced karyotype for carriers of t(4;8)(p16.1;p23.1) was moderately high at 18.8 %-comparable to the value obtained using the indirect method for the same carriership, which was 12 %. This was, however, markedly lower than the value of 41.2 % obtained through the pedigree segregation indirect analysis estimated for carriers of t(4;8)(p16.3;p23.1), perhaps due to the unique composition of genes present within the 4p16.1-4p 16.3 region. Revealed differences in pedigree segregation analysis did not correspond to the very similar profile of meiotic segregation patterns presented by carrier 1 and carrier 2. Most probably, such discordances may be due to differences in embryo survival rates arising from different genetic backgrounds.

  15. P dopants induced ferromagnetism in g-C3N4 nanosheets: Experiments and calculations

    NASA Astrophysics Data System (ADS)

    Liu, Yonggang; Liu, Peitao; Sun, Changqi; Wang, Tongtong; Tao, Kun; Gao, Daqiang

    2017-05-01

    Outstanding magnetic properties are highly desired for two-dimensional (2D) semiconductor nanosheets due to their potential applications in spintronics. Metal-free ferromagnetic 2D materials whose magnetism originated from the pure s/p electron configuration could give a long spin relaxation time, which plays the vital role in spin information transfer. Here, we synthesize 2D g-C3N4 nanosheets with room temperature ferromagnetism induced by P doping. In our case, the Curie temperature of P doped g-C3N4 nanosheets reaches as high as 911 K and the precise control of the P concentration can further adjust the saturation magnetization of the samples. First principles calculation results indicate that the magnetic moment is primarily due to strong hybridization between p bonds of P, N, and C atoms, giving the theoretical evidence of the ferromagnetism. This work opens another door to engineer a future generation of spintronic devices.

  16. Assessing performance enhancing tools: experiences with the open performance review and appraisal system (OPRAS) and expectations towards payment for performance (P4P) in the public health sector in Tanzania.

    PubMed

    Songstad, Nils Gunnar; Lindkvist, Ida; Moland, Karen Marie; Chimhutu, Victor; Blystad, Astrid

    2012-09-10

    Health workers' motivation is a key determinant of the quality of health services, and poor motivation has been found to be an obstacle to service delivery in many low-income countries. In order to increase the quality of service delivery in the public sector in Tanzania, the Open Performance Review and Appraisal System (OPRAS) has been implemented, and a new results-based payment system, Payment for performance (P4P) is introduced in the health sector. This article addresses health workers' experiences with OPRAS, expectations towards P4P and how lessons learned from OPRAS can assist in the implementation of P4P. The broader aim is to generate knowledge on health workers' motivation in low-income contexts. A qualitative study design has been employed to elicit data on health worker motivation at a general level and in relation to OPRAS and P4P in particular. Focus group discussions (FGDs) and in-depth interviews (IDIs) have been conducted with nursing staff, clinicians and administrators in the public health sector in a rural district in Tanzania. The study has an ethnographic backdrop based on earlier long-term fieldwork in Tanzania. Health workers evaluated OPRAS and P4P in terms of the benefits experienced or expected from complying with the tools. The study found a general reluctance towards OPRAS as health workers did not see OPRAS as leading to financial gains nor did it provide feedback on performance. Great expectations were expressed towards P4P due to its prospects of topping up salaries, but the links between the two performance enhancing tools were unclear. Health workers respond to performance enhancing tools based on whether the tools are found appropriate or yield any tangible benefits. The importance placed on salary and allowances forms the setting in which OPRAS operates. The expected addition to the salary through P4P has created a vigorous discourse among health workers attesting to the importance of the salary for motivation. Lessons learned

  17. Assessing performance enhancing tools: experiences with the open performance review and appraisal system (OPRAS) and expectations towards payment for performance (P4P) in the public health sector in Tanzania

    PubMed Central

    2012-01-01

    Background Health workers’ motivation is a key determinant of the quality of health services, and poor motivation has been found to be an obstacle to service delivery in many low-income countries. In order to increase the quality of service delivery in the public sector in Tanzania, the Open Performance Review and Appraisal System (OPRAS) has been implemented, and a new results-based payment system, Payment for performance (P4P) is introduced in the health sector. This article addresses health workers’ experiences with OPRAS, expectations towards P4P and how lessons learned from OPRAS can assist in the implementation of P4P. The broader aim is to generate knowledge on health workers’ motivation in low-income contexts. Methods A qualitative study design has been employed to elicit data on health worker motivation at a general level and in relation to OPRAS and P4P in particular. Focus group discussions (FGDs) and in-depth interviews (IDIs) have been conducted with nursing staff, clinicians and administrators in the public health sector in a rural district in Tanzania. The study has an ethnographic backdrop based on earlier long-term fieldwork in Tanzania. Results Health workers evaluated OPRAS and P4P in terms of the benefits experienced or expected from complying with the tools. The study found a general reluctance towards OPRAS as health workers did not see OPRAS as leading to financial gains nor did it provide feedback on performance. Great expectations were expressed towards P4P due to its prospects of topping up salaries, but the links between the two performance enhancing tools were unclear. Conclusions Health workers respond to performance enhancing tools based on whether the tools are found appropriate or yield any tangible benefits. The importance placed on salary and allowances forms the setting in which OPRAS operates. The expected addition to the salary through P4P has created a vigorous discourse among health workers attesting to the importance of

  18. The response of physician groups to P4P incentives.

    PubMed

    Mehrotra, Ateev; Pearson, Steven D; Coltin, Kathryn L; Kleinman, Ken P; Singer, Janice A; Rabson, Barbra; Schneider, Eric C

    2007-05-01

    Despite substantial enthusiasm among insurers and federal policy makers for pay-for-performance incentives, little is known about the current scope of these incentives or their influence on the delivery of care. To assess the scope and magnitude of pay-for-performance (P4P) incentives among physician groups and to examine whether such incentives are associated with quality improvement initiatives. Structured telephone survey of leaders of physician groups delivering primary care in Massachusetts. ASSESSED METHODS: Prevalence of P4P incentives among physician groups tied to specific measures of quality or utilization and prevalence of physician group quality improvement initiatives. Most group leaders (89%) reported P4P incentives in at least 1 commercial health plan contract. Incentives were tied to performance on Health Employer Data and Information Set (HEDIS) quality measures (89% of all groups), utilization measures (66%), use of information technology (52%), and patient satisfaction (37%). Among the groups with P4P and knowledge of all revenue streams, the incentives accounted for 2.2% (range, 0.3%-8.8%) of revenue. P4P incentives tied to HEDIS quality measures were positively associated with groups' quality improvement initiatives (odds ratio, 1.6; P = .02). Thirty-six percent of group leaders with P4P incentives reported that they were very important or moderately important to the group's financial success. P4P incentives are now common among physician groups in Massachusetts, and these incentives most commonly reward higher clinical quality or lower utilization of care. Although the scope and magnitude of incentives are still modest for many groups, we found an association between P4P incentives and the use of quality improvement initiatives.

  19. The acetylation of transcription factor HBP1 by p300/CBP enhances p16INK4A expression

    PubMed Central

    Wang, Weibin; Pan, Kewu; Chen, Yifan; Huang, Chunyin; Zhang, Xiaowei

    2012-01-01

    HBP1 is a sequence-specific DNA-binding transcription factor with many important biological roles. It activates or represses the expression of some specific genes during cell growth and differentiation. Previous studies have exhibited that HBP1 binds to p16INK4A promoter and activates p16INK4A expression. We found that trichostatin A (TSA), an inhibitor of HDAC (histone deacetylase), induces p16INK4A expression in an HBP1-dependent manner. This result was drawn from a transactivation experiment by measuring relative luciferase activities of p16INK4A promoter with HBP1-binding site in comparison with that of the wild-type p16INK4A promoter by transient cotransfection with HBP1 into HEK293T cells and 2BS cells. HBP1 acetylation after TSA treatment was confirmed by immunoprecipitation assay. Our data showed that HBP1 interacted with histone acetyltransferase p300 and CREB-binding protein (CBP) and also recruited p300/CBP to p16INK4A promoter. HBP1 was acetylated by p300/CBP in two regions: repression domain (K297/305/307) and P domain (K171/419). Acetylation of Repression domain was not required for HBP1 transactivation on p16INK4A. However, luciferase assay and western blotting results indicate that acetylation of P domain, especially K419 acetylation is essential for HBP1 transactivation on p16INK4A. As assayed by SA-beta-gal staining, the acetylation of HBP1 at K419 enhanced HBP1-induced premature senescence in 2BS cells. In addition, HDAC4 repressed HBP1-induced premature senescence through permanently deacetylating HBP1. We conclude that our data suggest that HBP1 acetylation at K419 plays an important role in HBP1-induced p16INK4A expression. PMID:21967847

  20. Characterization of the TIP4P-Ew water model: vapor pressure and boiling point.

    PubMed

    Horn, Hans W; Swope, William C; Pitera, Jed W

    2005-11-15

    The liquid-vapor-phase equilibrium properties of the previously developed TIP4P-Ew water model have been studied using thermodynamic integration free-energy simulation techniques in the temperature range of 274-400 K. We stress that free-energy results from simulations need to be corrected in order to be compared to the experiment. This is due to the fact that the thermodynamic end states accessible through simulations correspond to fictitious substances (classical rigid liquids and classical rigid ideal gases) while experiments operate on real substances (liquids and real gases, with quantum effects). After applying analytical corrections the vapor pressure curve obtained from simulated free-energy changes is in excellent agreement with the experimental vapor pressure curve. The boiling point of TIP4P-Ew water under ambient pressure is found to be at 370.3+/-1.9 K, about 7 K higher than the boiling point of TIP4P water (363.7+/-5.1 K; from simulations that employ finite range treatment of electrostatic and Lennard-Jones interactions). This is in contrast to the approximately +15 K by which the temperature of the density maximum and the melting temperature of TIP4P-Ew are shifted relative to TIP4P, indicating that the temperature range over which the liquid phase of TIP4P-Ew is stable is narrower than that of TIP4P and resembles more that of real water. The quality of the vapor pressure results highlights the success of TIP4P-Ew in describing the energetic and entropic aspects of intermolecular interactions in liquid water.

  1. Collaborative Occupational Therapy: Teachers' Impressions of the Partnering for Change (P4C) Model.

    PubMed

    Wilson, A L; Harris, S R

    2018-05-01

    Occupational therapists (OTs) often face barriers when trying to collaborate with teachers in school-based settings. Partnering for change (P4C), a collaborative practice model designed to support children with developmental coordination disorder, could potentially support all students with special needs. Therefore, the aim of this study was to explore how teachers experience OT services delivered using the P4C model to support children with a variety of special needs. P4C was implemented at one elementary school in Courtenay, British Columbia. Eleven teachers participated in two focus groups and a one-on-one interview to gather descriptive, qualitative data. Grounded theory techniques were used for data analysis. Four themes (collaborating in the thick of it all, learning and taking risks, managing limited time and resources, and appreciating responsive OT support) represented teachers' experiences of P4C. Teachers strongly preferred collaborative OT services based on the P4C model. Students with a variety of special needs were supported within their classrooms as teachers learned new strategies from the OT and found ways to embed these strategies into their daily routines.

  2. Communication: Direct comparison between theory and experiment for correlated angular and product-state distributions of the ground-state and stretching-excited O(3P) + CH4 reactions

    NASA Astrophysics Data System (ADS)

    Czakó, Gábor

    2014-06-01

    Motivated by a recent experiment [H. Pan and K. Liu, J. Chem. Phys. 140, 191101 (2014)], we report a quasiclassical trajectory study of the O(3P) + CH4(vk = 0, 1) → OH + CH3 [k = 1 and 3] reactions on an ab initio potential energy surface. The computed angular distributions and cross sections correlated to the OH(v = 0, 1) + CH3(v = 0) coincident product states can be directly compared to experiment for O + CH4(v3 = 0, 1). Both theory and experiment show that the ground-state reaction is backward scattered, whereas the angular distributions shift toward sideways and forward directions upon antisymmetric stretching (v3) excitation of the reactant. Theory predicts similar behavior for the O + CH4(v1 = 1) reaction. The simulations show that stretching excitation enhances the reaction up to about 15 kcal/mol collision energy, whereas the O + CH4(vk = 1) reactions produce smaller cross sections for OH(v = 1) + CH3(v = 0) than those of O + CH4(v = 0) → OH(v = 0) + CH3(v = 0). The former finding agrees with experiment and the latter awaits for confirmation. The computed cold OH rotational distributions of O + CH4(v = 0) are in good agreement with experiment.

  3. Communication: direct comparison between theory and experiment for correlated angular and product-state distributions of the ground-state and stretching-excited O((3)P) + CH4 reactions.

    PubMed

    Czakó, Gábor

    2014-06-21

    Motivated by a recent experiment [H. Pan and K. Liu, J. Chem. Phys. 140, 191101 (2014)], we report a quasiclassical trajectory study of the O((3)P) + CH4(vk = 0, 1) → OH + CH3 [k = 1 and 3] reactions on an ab initio potential energy surface. The computed angular distributions and cross sections correlated to the OH(v = 0, 1) + CH3(v = 0) coincident product states can be directly compared to experiment for O + CH4(v3 = 0, 1). Both theory and experiment show that the ground-state reaction is backward scattered, whereas the angular distributions shift toward sideways and forward directions upon antisymmetric stretching (v3) excitation of the reactant. Theory predicts similar behavior for the O + CH4(v1 = 1) reaction. The simulations show that stretching excitation enhances the reaction up to about 15 kcal/mol collision energy, whereas the O + CH4(vk = 1) reactions produce smaller cross sections for OH(v = 1) + CH3(v = 0) than those of O + CH4(v = 0) → OH(v = 0) + CH3(v = 0). The former finding agrees with experiment and the latter awaits for confirmation. The computed cold OH rotational distributions of O + CH4(v = 0) are in good agreement with experiment.

  4. Heterozygous Submicroscopic Inversions Involving Olfactory Receptor–Gene Clusters Mediate the Recurrent t(4;8)(p16;p23) Translocation

    PubMed Central

    Giglio, Sabrina; Calvari, Vladimiro; Gregato, Giuliana; Gimelli, Giorgio; Camanini, Silvia; Giorda, Roberto; Ragusa, Angela; Guerneri, Silvana; Selicorni, Angelo; Stumm, Marcus; Tonnies, Holger; Ventura, Mario; Zollino, Marcella; Neri, Giovanni; Barber, John; Wieczorek, Dagmar; Rocchi, Mariano; Zuffardi, Orsetta

    2002-01-01

    The t(4;8)(p16;p23) translocation, in either the balanced form or the unbalanced form, has been reported several times. Taking into consideration the fact that this translocation may be undetected in routine cytogenetics, we find that it may be the most frequent translocation after t(11q;22q), which is the most common reciprocal translocation in humans. Case subjects with der(4) have the Wolf-Hirschhorn syndrome, whereas case subjects with der(8) show a milder spectrum of dysmorphic features. Two pairs of the many olfactory receptor (OR)–gene clusters are located close to each other, on both 4p16 and 8p23. Previously, we demonstrated that an inversion polymorphism of the OR region at 8p23 plays a crucial role in the generation of chromosomal imbalances through unusual meiotic exchanges. These findings prompted us to investigate whether OR-related inversion polymorphisms at 4p16 and 8p23 might also be involved in the origin of the t(4;8)(p16;p23) translocation. In seven case subjects (five of whom both represented de novo cases and were of maternal origin), including individuals with unbalanced and balanced translocations, we demonstrated that the breakpoints fell within the 4p and 8p OR-gene clusters. FISH experiments with appropriate bacterial-artificial-chromosome probes detected heterozygous submicroscopic inversions of both 4p and 8p regions in all the five mothers of the de novo case subjects. Heterozygous inversions on 4p16 and 8p23 were detected in 12.5% and 26% of control subjects, respectively, whereas 2.5% of them were scored as doubly heterozygous. These novel data emphasize the importance of segmental duplications and large-scale genomic polymorphisms in the evolution and pathology of the human genome. PMID:12058347

  5. Novel RepA-MCM proteins encoded in plasmids pTAU4, pORA1 and pTIK4 from Sulfolobus neozealandicus

    PubMed Central

    Greve, Bo; Jensen, Susanne; Phan, Hoa; Brügger, Kim; Zillig, Wolfram; She, Qunxin; Garrett, Roger A.

    2005-01-01

    Three plasmids isolated from the crenarchaeal thermoacidophile Sulfolobus neozealandicus were characterized. Plasmids pTAU4 (7,192 bp), pORA1 (9,689 bp) and pTIK4 (13,638 bp) show unusual properties that distinguish them from previously characterized cryptic plasmids of the genus Sulfolobus. Plasmids pORA1 and pTIK4 encode RepA proteins, only the former of which carries the novel polymerase–primase domain of other known Sulfolobus plasmids. Plasmid pTAU4 encodes a mini-chromosome maintenance protein homolog and no RepA protein; the implications for DNA replication are considered. Plasmid pORA1 is the first Sulfolobus plasmid to be characterized that does not encode the otherwise highly conserved DNA-binding PlrA protein. Another encoded protein appears to be specific for the New Zealand plasmids. The three plasmids should provide useful model systems for functional studies of these important crenarchaeal proteins. PMID:15876565

  6. Effect of pH and Electrolytes on Adsorption of 2,4-D onto Kaolinite

    NASA Astrophysics Data System (ADS)

    Sharma, A.; Kawamoto, K.; Komatsu, T.; Moldrup, P.

    2006-12-01

    The fate and transport of pesticides in soil can be greatly influenced by adsorption onto clay minerals such as kaolinite. The ionic pesticide 2,4-D (2,4-dichlorophenoxyacetic acid) is one of the most commonly used herbicides. The purpose of this study is to investigate the effect of electrolytes and pH on the adsorption of 2,4- D onto kaolinite. The adsorption coefficient (Kd) of 2,4-D on two types of kaolinite was measured in batch experiments using water and 4 different electrolytes (0.005M CaSO4, 0.005M CaCl2, 0.01M KCl, and 0.01M NaCl). The experiments were carried out with 0.5 g kaolinite at a solid:liquid ratio of 1:20 and at different pH (1.9-6.3). The pH of the solution was controlled by addition of 0.2N of HCl. X-ray diffraction analysis of both kaolinite with and without adsorbed 2,4-D was also done to understand the location of 2,4-D adsorption. The effects of pH and electrolytes on Kd were compared and possible adsorption mechanisms were revealed for 2,4-D adsorption onto the two different types of kaolinite. The results implied that 2,4-D adsorption was higher for an electrolyte solution with monovalent cation than with divalent cation for one type of kaolinite, while no such trend was observed for the other kaolinite. The adsorption of 2,4-D increased significantly with decreasing pH for both types of kaolinite.

  7. Calculation of the total electron excitation cross section in the Born approximation using Slater wave functions for the Li (2s yields 2p), Li (2s yields 3p), Na (3s yields 4p), Mg (3p yields 4s), Ca (4s yields 4p) and K (4s yields 4p) excitations. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Simsic, P. L.

    1974-01-01

    Excitation of neutral atoms by inelastic scattering of incident electrons in gaseous nebulae were investigated using Slater Wave functions to describe the initial and final states of the atom. Total cross sections using the Born Approximation are calculated for: Li(2s yields 2p), Na(3s yields 4p), k(4s yields 4p). The intensity of emitted radiation from gaseous nebulae is also calculated, and Maxwell distribution is employed to average the kinetic energy of electrons.

  8. Measurements of the strong-interaction widths of the kaonic 3He and 4He 2p levels

    PubMed Central

    Bazzi, M.; Beer, G.; Bombelli, L.; Bragadireanu, A.M.; Cargnelli, M.; Curceanu (Petrascu), C.; dʼUffizi, A.; Fiorini, C.; Frizzi, T.; Ghio, F.; Guaraldo, C.; Hayano, R.S.; Iliescu, M.; Ishiwatari, T.; Iwasaki, M.; Kienle, P.; Levi Sandri, P.; Longoni, A.; Marton, J.; Okada, S.; Pietreanu, D.; Ponta, T.; Rizzo, A.; Romero Vidal, A.; Sbardella, E.; Scordo, A.; Shi, H.; Sirghi, D.L.; Sirghi, F.; Tatsuno, H.; Tudorache, A.; Tudorache, V.; Vazquez Doce, O.; Wünschek, B.; Widmann, E.; Zmeskal, J.

    2012-01-01

    The kaonic 3He and 4He X-rays emitted in the 3d→2p transitions were measured in the SIDDHARTA experiment. The widths of the kaonic 3He and 4He 2p states were determined to be Γ2p(He3)=6±6(stat.)±7 (syst.) eV, and Γ2p(He4)=14±8 (stat.)±5 (syst.) eV, respectively. Both results are consistent with the theoretical predictions. The width of kaonic 4He is much smaller than the value of 55±34 eV determined by the experiments performed in the 70ʼs and 80ʼs, while the width of kaonic 3He was determined for the first time. PMID:22876000

  9. Theoretical level energies and transition data for 4p64d4, 4p64d34f and 4p54d5 configurations of W34+ ion

    NASA Astrophysics Data System (ADS)

    Karpuškienė, R.; Bogdanovich, P.; Kisielius, R.

    2017-05-01

    The ab initio quasirelativistic approach developed specifically for the calculation of spectral parameters of highly charged ions was used to derive transition data for the tungsten ion W34+. The configuration interaction method was applied to include electron correlation effects. The relativistic effects were taken into account in the Breit-Pauli approximation. The level energies, radiative lifetimes τ, Landé g-factors are determined for the ground configuration 4p64d4 and two excited configurations 4p64d34f and 4p54d5. The radiative transition wavelengths λ and emission transition probabilities A for the electric dipole, electric quadrupole, electric octupole, magnetic dipole, and magnetic quadrupole transitions among the levels of these configurations are produced.

  10. Pilot production of 4 sq cm ITO/InP photovoltaic solar cells

    NASA Technical Reports Server (NTRS)

    Gessert, T. A.; Li, X.; Coutts, T. J.; Tzafaras, N.

    1991-01-01

    Experimental results of a pilot production of 32 4-sq cm indium tin oxide (ITO)InP space solar cells are presented. The discussion includes analysis of the device performance of the best cells produced as well as the performance range of all production cells. The experience gained from the production is discussed, indicating other issues that may be encountered when large-scale productions are initiated. Available data on a 4-sq cm ITO/InP cell that was flown on the UoSAT-5 satellite is reported.

  11. P(4-vinyl pyridine) hydrogel use for the removal of UO(2)(2+) and Th(4+) from aqueous environments.

    PubMed

    Ozay, Ozgur; Ekici, Sema; Aktas, Nahit; Sahiner, Nurettin

    2011-12-01

    4-vinyl pyridine (4-VP) based hydrogels with 2-hydroxyethylmetacrylate (HEMA) and magnetic composites were prepared and tested for use in the removal of UO(2)(2+) and Th(4+) ions from aqueous environments. It was found that the absorption of these metal ions from aqueous environments decreased with an increase in the amount of HEMA contained within p(4-VP-co-HEMA) hydrogels between 0.498 mmol for pure p(4-VP) and 0.027 mmol for pure p(HEMA). The characterization of the hydrogels was determined by swelling experiments, FT-IR and thermal analysis. The effects of initial metal ion concentration, hydrogel amount and the temperature of the medium on absorption of the ions were investigated. Langmuir and Freundlich isotherms were constructed for the absorption of UO(2)(2+) and Th(4+). Both isotherms demonstrated that these metal ions complied with monolayer absorption kinetics. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. WRF4SG: A Scientific Gateway for climate experiment workflows

    NASA Astrophysics Data System (ADS)

    Blanco, Carlos; Cofino, Antonio S.; Fernandez-Quiruelas, Valvanuz

    2013-04-01

    , the user has to select them browsing through LFC Portlet. * Design Experiment workflow: In order to configure the experiment, the user will define the type of experiment (i.e. re-forecast), and its attributes to simulate. In this case the main attributes are: the field of interest (wind, precipitation, ...), the start and end date simulation and the requirements of the experiment. * Monitor workflow: In order to monitor the experiment the user will receive notification messages based on events and also the gateway will display the progress of the experiment. * Data storage: Like Data assimilation case, the user is able to browse and view the output data simulations using LFC Portlet. The objectives of WRF4SG can be described by considering two goals. The first goal is to show how WRF4SG facilitates to execute, monitor and manage climate workflows based on the WRF4G framework. And the second goal of WRF4SG is to help WRF users to execute their experiment workflows concurrently using heterogeneous computing resources such as HPC and Grid. [1] Kacsuk, P.: P-GRADE portal family for grid infrastructures. Concurrency and Computation: Practice and Experience. 23, 235-245 (2011). [2] http://www.meteo.unican.es/software/wrf4g

  13. Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

    PubMed

    Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

    2008-09-14

    PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

  14. Na7Cr4(P2O7)4PO4

    PubMed Central

    Bourguiba Fakhar, Noura; Zid, Mohamed Faouzi; Driss, Ahmed

    2013-01-01

    The title compound, hepta­sodium tetra­chromium(III) tetra­kis­(diphosphate) orthophosphate, was synthesized by solid-state reaction. Its structure is isotypic with that of Na7 M 4(P2O7)4PO4 (M = In, Al) compounds and is made up from a three-dimensional [(CrP2O7)4PO4]7− framework with channels running along [001]. The three Na+ cations are located in the voids of the framework. One of the cations is situated on a general position, one is equally disordered around a twofold rotation axis and one is on a fourfold rotoinversion axis. The isolated PO4 tetra­hedron of the anionic framework is also situated on the -4 axis. Structural relationships between the title compound and different diphosphates containing MP2O11 units (M = Mo, V) are discussed. PMID:23723751

  15. [Pay for performance in dental care: A systematic narrative review of quality P4P models in dental care].

    PubMed

    Chenot, Regine

    2017-11-01

    Pay for performance (P4P) links reimbursement to the achievement of quality objectives. Experiences with P4P instruments and studies on their effects are available for the inpatient sector. A systematic narrative review brings together findings concerning the use and the effects of P4P, especially in dental care. A systematic literature search in PubMed and the Cochrane Library for reimbursement models using quality indicators provided 77 publications. Inclusion criteria were: year of publication not older than 2007, dental sector, models of quality-oriented remuneration, quality of care, quality indicators. 27 publications met the inclusion criteria and were evaluated with regard to the instruments and effects of P4P. The database search was supplemented by a free search on the Internet as well as a search in indicator databases and portals. The results of the included studies were extracted and summarized narratively. 27 studies were included in the review. Performance-oriented remuneration is an instrument of quality competition. In principle, P4P is embedded in an existing remuneration system, i.e., it does not occur in isolation. In the United States, England and Scandinavia, models are currently being tested for quality-oriented remuneration in dental care, based on quality indicators. The studies identified by the literature search are very heterogeneous and do not yield comparable endpoints. Difficulties are seen in the reproducibility of the quality of dental care with regard to certain characteristics which still have to be defined as quality-promoting properties. Risk selection cannot be ruled out, which may have an impact on structural quality (access to care, coordination). There were no long-term effects of P4P on the quality of care. In the short and medium term, adverse effects on the participants' motivation as well as shifting effects towards the private sector are described. A prerequisite for the functioning of P4P is the definition of clear

  16. Pressure-induced transformations in glassy water: A computer simulation study using the TIP4P/2005 model

    NASA Astrophysics Data System (ADS)

    Wong, Jessina; Jahn, David A.; Giovambattista, Nicolas

    2015-08-01

    We study the pressure-induced transformations between low-density amorphous (LDA) and high-density amorphous (HDA) ice by performing out-of-equilibrium molecular dynamics (MD) simulations. We employ the TIP4P/2005 water model and show that this model reproduces qualitatively the LDA-HDA transformations observed experimentally. Specifically, the TIP4P/2005 model reproduces remarkably well the (i) structure (OO, OH, and HH radial distribution functions) and (ii) densities of LDA and HDA at P = 0.1 MPa and T = 80 K, as well as (iii) the qualitative behavior of ρ(P) during compression-induced LDA-to-HDA and decompression-induced HDA-to-LDA transformations. At the rates explored, the HDA-to-LDA transformation is less pronounced than in experiments. By studying the LDA-HDA transformations for a broad range of compression/decompression temperatures, we construct a "P-T phase diagram" for glassy water that is consistent with experiments and remarkably similar to that reported previously for ST2 water. This phase diagram is not inconsistent with the possibility of TIP4P/2005 water exhibiting a liquid-liquid phase transition at low temperatures. A comparison with previous MD simulation studies of SPC/E and ST2 water as well as experiments indicates that, overall, the TIP4P/2005 model performs better than the SPC/E and ST2 models. The effects of cooling and compression rates as well as aging on our MD simulations results are also discussed. The MD results are qualitatively robust under variations of cooling/compression rates (accessible in simulations) and are not affected by aging the hyperquenched glass for at least 1 μs. A byproduct of this work is the calculation of TIP4P/2005 water's diffusion coefficient D(T) at P = 0.1 MPa. It is found that, for T ≥ 210 K, D(T) ≈ (T - TMCT)-γ as predicted by mode coupling theory and in agreement with experiments. For TIP4P/2005 water, TMCT = 209 K and γ = 2.14, very close to the corresponding experimental values TMCT = 221 K

  17. Pressure-induced transformations in glassy water: A computer simulation study using the TIP4P/2005 model.

    PubMed

    Wong, Jessina; Jahn, David A; Giovambattista, Nicolas

    2015-08-21

    We study the pressure-induced transformations between low-density amorphous (LDA) and high-density amorphous (HDA) ice by performing out-of-equilibrium molecular dynamics (MD) simulations. We employ the TIP4P/2005 water model and show that this model reproduces qualitatively the LDA-HDA transformations observed experimentally. Specifically, the TIP4P/2005 model reproduces remarkably well the (i) structure (OO, OH, and HH radial distribution functions) and (ii) densities of LDA and HDA at P = 0.1 MPa and T = 80 K, as well as (iii) the qualitative behavior of ρ(P) during compression-induced LDA-to-HDA and decompression-induced HDA-to-LDA transformations. At the rates explored, the HDA-to-LDA transformation is less pronounced than in experiments. By studying the LDA-HDA transformations for a broad range of compression/decompression temperatures, we construct a "P-T phase diagram" for glassy water that is consistent with experiments and remarkably similar to that reported previously for ST2 water. This phase diagram is not inconsistent with the possibility of TIP4P/2005 water exhibiting a liquid-liquid phase transition at low temperatures. A comparison with previous MD simulation studies of SPC/E and ST2 water as well as experiments indicates that, overall, the TIP4P/2005 model performs better than the SPC/E and ST2 models. The effects of cooling and compression rates as well as aging on our MD simulations results are also discussed. The MD results are qualitatively robust under variations of cooling/compression rates (accessible in simulations) and are not affected by aging the hyperquenched glass for at least 1 μs. A byproduct of this work is the calculation of TIP4P/2005 water's diffusion coefficient D(T) at P = 0.1 MPa. It is found that, for T ≥ 210 K, D(T) ≈ (T - T(MCT))(-γ) as predicted by mode coupling theory and in agreement with experiments. For TIP4P/2005 water, T(MCT) = 209 K and γ = 2.14, very close to the corresponding experimental values T

  18. Quantifying pCO2 in biological ocean acidification experiments: A comparison of four methods.

    PubMed

    Watson, Sue-Ann; Fabricius, Katharina E; Munday, Philip L

    2017-01-01

    Quantifying the amount of carbon dioxide (CO2) in seawater is an essential component of ocean acidification research; however, equipment for measuring CO2 directly can be costly and involve complex, bulky apparatus. Consequently, other parameters of the carbonate system, such as pH and total alkalinity (AT), are often measured and used to calculate the partial pressure of CO2 (pCO2) in seawater, especially in biological CO2-manipulation studies, including large ecological experiments and those conducted at field sites. Here we compare four methods of pCO2 determination that have been used in biological ocean acidification experiments: 1) Versatile INstrument for the Determination of Total inorganic carbon and titration Alkalinity (VINDTA) measurement of dissolved inorganic carbon (CT) and AT, 2) spectrophotometric measurement of pHT and AT, 3) electrode measurement of pHNBS and AT, and 4) the direct measurement of CO2 using a portable CO2 equilibrator with a non-dispersive infrared (NDIR) gas analyser. In this study, we found these four methods can produce very similar pCO2 estimates, and the three methods often suited to field-based application (spectrophotometric pHT, electrode pHNBS and CO2 equilibrator) produced estimated measurement uncertainties of 3.5-4.6% for pCO2. Importantly, we are not advocating the replacement of established methods to measure seawater carbonate chemistry, particularly for high-accuracy quantification of carbonate parameters in seawater such as open ocean chemistry, for real-time measures of ocean change, nor for the measurement of small changes in seawater pCO2. However, for biological CO2-manipulation experiments measuring differences of over 100 μatm pCO2 among treatments, we find the four methods described here can produce similar results with careful use.

  19. Quantifying pCO2 in biological ocean acidification experiments: A comparison of four methods

    PubMed Central

    Fabricius, Katharina E.; Munday, Philip L.

    2017-01-01

    Quantifying the amount of carbon dioxide (CO2) in seawater is an essential component of ocean acidification research; however, equipment for measuring CO2 directly can be costly and involve complex, bulky apparatus. Consequently, other parameters of the carbonate system, such as pH and total alkalinity (AT), are often measured and used to calculate the partial pressure of CO2 (pCO2) in seawater, especially in biological CO2-manipulation studies, including large ecological experiments and those conducted at field sites. Here we compare four methods of pCO2 determination that have been used in biological ocean acidification experiments: 1) Versatile INstrument for the Determination of Total inorganic carbon and titration Alkalinity (VINDTA) measurement of dissolved inorganic carbon (CT) and AT, 2) spectrophotometric measurement of pHT and AT, 3) electrode measurement of pHNBS and AT, and 4) the direct measurement of CO2 using a portable CO2 equilibrator with a non-dispersive infrared (NDIR) gas analyser. In this study, we found these four methods can produce very similar pCO2 estimates, and the three methods often suited to field-based application (spectrophotometric pHT, electrode pHNBS and CO2 equilibrator) produced estimated measurement uncertainties of 3.5–4.6% for pCO2. Importantly, we are not advocating the replacement of established methods to measure seawater carbonate chemistry, particularly for high-accuracy quantification of carbonate parameters in seawater such as open ocean chemistry, for real-time measures of ocean change, nor for the measurement of small changes in seawater pCO2. However, for biological CO2-manipulation experiments measuring differences of over 100 μatm pCO2 among treatments, we find the four methods described here can produce similar results with careful use. PMID:28957378

  20. Solid energy calibration standards for P K-edge XANES: electronic structure analysis of PPh4Br.

    PubMed

    Blake, Anastasia V; Wei, Haochuan; Donahue, Courtney M; Lee, Kyounghoon; Keith, Jason M; Daly, Scott R

    2018-03-01

    P K-edge X-ray absorption near-edge structure (XANES) spectroscopy is a powerful method for analyzing the electronic structure of organic and inorganic phosphorus compounds. Like all XANES experiments, P K-edge XANES requires well defined and readily accessible calibration standards for energy referencing so that spectra collected at different beamlines or under different conditions can be compared. This is especially true for ligand K-edge X-ray absorption spectroscopy, which has well established energy calibration standards for Cl (Cs 2 CuCl 4 ) and S (Na 2 S 2 O 3 ·5H 2 O), but not neighboring P. This paper presents a review of common P K-edge XANES energy calibration standards and analysis of PPh 4 Br as a potential alternative. The P K-edge XANES region of commercially available PPh 4 Br revealed a single, highly resolved pre-edge feature with a maximum at 2146.96 eV. PPh 4 Br also showed no evidence of photodecomposition when repeatedly scanned over the course of several days. In contrast, we found that PPh 3 rapidly decomposes under identical conditions. Density functional theory calculations performed on PPh 3 and PPh 4 + revealed large differences in the molecular orbital energies that were ascribed to differences in the phosphorus oxidation state (III versus V) and molecular charge (neutral versus +1). Time-dependent density functional theory calculations corroborated the experimental data and allowed the spectral features to be assigned. The first pre-edge feature in the P K-edge XANES spectrum of PPh 4 Br was assigned to P 1s → P-C π* transitions, whereas those at higher energy were P 1s → P-C σ*. Overall, the analysis suggests that PPh 4 Br is an excellent alternative to other solid energy calibration standards commonly used in P K-edge XANES experiments.

  1. An inversion inv(4)(p12-p15.3) in autistic siblings implicates the 4p GABA receptor gene cluster.

    PubMed

    Vincent, J B; Horike, S I; Choufani, S; Paterson, A D; Roberts, W; Szatmari, P; Weksberg, R; Fernandez, B; Scherer, S W

    2006-05-01

    We describe the case of two brothers diagnosed with autism who both carry a paracentic inversion of the short arm of chromosome 4 (46,XY, inv(4)(p12-p15.3)). We have determined that this inversion is inherited from an apparently unaffected mother and unaffected maternal grandfather. Methods/ Using fluorescence in situ hybridisation analysis and Southern blot hybridisation we identified the breakpoints. The proximal breakpoint (4p12) maps to a region containing a cluster of gamma-aminobutyric acid A (GABA(A)) receptor genes, and directly interrupts the GABRG1 gene, the distal-most gene of the cluster. We also identified an insertion/deletion polymorphism for a approximately 2 kb LINE1 (L1) element that occurs within intron 7 of GABRG1. Our genotype analysis amongst autism families indicated that the L1 deletion allele did not show increased transmission to affected individuals. No linkage disequilibrium was evident between the L1 and single nucleotide polymorphisms in adjacent GABA(A) receptor genes on 4p, where a recent study has identified significant association with autism. Despite this, the identification of an inversion breakpoint disrupting GABRG1 provides solid support for the genetic involvement of the short arm of chromosome 4 in the genetic aetiology of autism, and for the hypothesis of disrupted GABA neurotransmission in autism.

  2. Methylation of CpG island of p14(ARK), p15(INK4b) and p16(INK4a) genes in coke oven workers.

    PubMed

    Zhang, H; Li, X; Ge, L; Yang, J; Sun, J; Niu, Q

    2015-02-01

    To detect the blood genomic DNA methylation in coke oven workers and find a possible early screening index for occupational lung cancer, 74 coke oven workers as the exposed group and 47 water pump workers as the controls were surveyed, and urine samples and peripheral blood mononuclear cells (PBMCs) were collected. Airborne benzo[a]pyrene (B[a]P) levels in workplace and urinary 1-hydroxypyrene (1-OH-Py) levels were determined by high-performance liquid chromatography. DNA damage of PBMCs and the p14(ARK), p15(INK4b) and p16(INK4a) gene CpG island methylation in the promoter region were detected by comet assay and methylation-specific polymerase chain reaction techniques, respectively. Results show that compared with the controls, concentration of airborne B[a]Ps was elevated in the coke plant, and urinary 1-OH-Py's level and DNA olive tail moment in comet assay were significantly increased in the coke oven workers, and p14(ARK), p15(INK4b) and p16(INK4a) gene methylation rates were also significantly increased. With the working years and urinary 1-OH-Py's level, the rates of p14(ARK) and p16(INK4a) gene methylation were significantly increased while that of p15(INK4b) gene methylation displayed no statistical change. We conclude that PBMCs' p14(ARK) and p16(INK4a) gene methylation may be used for screening and warning lung cancer in coke oven workers. © The Author(s) 2015.

  3. Diadenosine 5', 5'''-P(1),P(4)-tetraphosphate (Ap4A) is synthesized in response to DNA damage and inhibits the initiation of DNA replication.

    PubMed

    Marriott, Andrew S; Copeland, Nikki A; Cunningham, Ryan; Wilkinson, Mark C; McLennan, Alexander G; Jones, Nigel J

    2015-09-01

    The level of intracellular diadenosine 5', 5'''-P(1),P(4)-tetraphosphate (Ap4A) increases several fold in mammalian cells treated with non-cytotoxic doses of interstrand DNA-crosslinking agents such as mitomycin C. It is also increased in cells lacking DNA repair proteins including XRCC1, PARP1, APTX and FANCG, while >50-fold increases (up to around 25 μM) are achieved in repair mutants exposed to mitomycin C. Part of this induced Ap4A is converted into novel derivatives, identified as mono- and di-ADP-ribosylated Ap4A. Gene knockout experiments suggest that DNA ligase III is primarily responsible for the synthesis of damage-induced Ap4A and that PARP1 and PARP2 can both catalyze its ADP-ribosylation. Degradative proteins such as aprataxin may also contribute to the increase. Using a cell-free replication system, Ap4A was found to cause a marked inhibition of the initiation of DNA replicons, while elongation was unaffected. Maximum inhibition of 70-80% was achieved with 20 μM Ap4A. Ap3A, Ap5A, Gp4G and ADP-ribosylated Ap4A were without effect. It is proposed that Ap4A acts as an important inducible ligand in the DNA damage response to prevent the replication of damaged DNA. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Measurement of OH, H2SO4, MSA, and HNO3 Aboard the P-3B Aircraft

    NASA Technical Reports Server (NTRS)

    Eisele, F. L.

    2003-01-01

    This paper addresses the measurement of OH, H2SO4, MSA, and HNO3 aboard the P-3B aircraft under the following headings: 1) Performance Report; 2) Highlights of OH, H2SO4, and MSA Measurements Made Aboard the NASA P-3B During TRACE-P; 3) Development and characteristics of an airborne-based instrument used to measure nitric acid during the NASA TRACE-P field experiment.

  5. [A case of mosaic ring chromosome 4 with subtelomeric 4p deletion].

    PubMed

    Kim, Jeong Hyun; Oh, Phil Soo; Na, Hye Yeon; Kim, Sun-Hee; Cho, Hyoun Chan

    2009-02-01

    Ring chromosome is a structural abnormality that is thought to be the result of fusion and breakage in the short and long arms of chromosome. Wolf-Hirschhorn syndrome (WHS) is a well-known congenital anomaly in the ring chromosome 4 with a partial deletion of the distal short arm. Here we report a 10-month-old male of mosaic ring chromosome 4 with the chief complaint of severe short stature. He showed the height of -4 standard deviation, subtle hypothyroidism and mild atrial septal defect/ventricular septal defect, and also a mild language developmental delay was suspected. Brain magnetic resonance imaging showed multifocal leukomalacia. Chromosomal analysis of the peripheral blood showed the mosaic karyotype with [46,XY,r(4)(p16q35)[84]/45,XY,-4[9]/91,XXYY, dic r(4;4)(p16q35;p16q35)[5]/46,XY,dic r(4;4)(p16q35;p16q35)[2

  6. P4P4P: An Agenda for Research on Pay for Performance for Patients

    PubMed Central

    Volpp, Kevin G.; Pauly, Mark V.; Loewenstein, George; Bangsberg, David

    2012-01-01

    Unhealthy behaviors are a major cause of poor health outcomes and high health care costs. In this Commentary, we describe an agenda for research to guide broader use of patient-targeted financial incentives either in conjunction with provider-targeted financial incentives (P4P) or in clinical contexts where provider-targeted approaches are unlikely to be effective. We discuss evidence of proven effectiveness and limitations of the existing evidence, reasons for underutilization of these approaches, and options for operationalizing wider use. Patient-targeted incentives have great potential, and systematic testing will help determine how they can best be used to improve population health. PMID:19124872

  7. First Principles Investigation of the Geometrical and Electrochemical Properties of Na4P4P2S6

    NASA Astrophysics Data System (ADS)

    Rush, Larry E., Jr.; Holzwarth, N. A. W.

    First principles simulations are used to examine the structural and physical properties of Na4P2S6 in comparison with its Li4P2S6 analog. Four model structures are considered including the C 2 / m structure recently reported by Kuhn and co-workers from their analysis of single crystals of Na4P2S6, and three structures related to the P63 / mcm structure with P site disorder found in 1982 by Mercier and co-workers from their analysis of single crystals of Li4P2S6. The computational results indicate that both Na4P2S6 and Li4P2S6 have the same disordered ground state structures consistent with the P63 / mcm space group, while the optimized C 2 / m structures have higher energies by 0.1 eV and 0.4 eV per formula unit for Na4P2S6 and Li4P2S6, respectively. Simulations of ion migration suggest that Na4P2S6 may have more favorable ionic conductivity compared to Li4P2S6. Supported by NSF Grant DMR-1105485 and DMR-1507942.

  8. 4p- syndrome and 9p tetrasomy mosaicism with cleft lip and palate.

    PubMed

    Kobayashi, J; Kimijima, Y; Yamada, S; Amagasa, T; Saito-Ohara, F

    2000-06-01

    Chromosome 4p- syndrome is a multiple malformation syndrome associated with partial deletion of the short arm of chromosome 4 (4p-). It is characterized by dysmorphic features and retarded development. Cleft lip and/or palate are the major clinical manifestations. Cases of tetrasomy 9p are extremely rare; the principal clinical manifestations of this condition are characteristic craniofacial abnormalities, generalized hypotonia and severe mental retardation. We present the first case of a female infant with 4p deletion and tetrasomy 9p mosaicism, exhibiting a left-sided cleft lip, alveolus and soft palate. Karyotype analysis of lymphocytes cultured from the patient revealed that she was mosaic: 86% of the cells were 46, XX, add (4) (p15.32) and 14% were 47, XX, add (4) (p15.32), +idic (9)(q12). The G-banding pattern appeared consistent with either translocation or partial proximal deletion of 4p. In order to make a definitive cytogenetic diagnosis of isodicentric chromosome 9, fluorescence in situ hybridization (FISH) was applied. At 8 months, when the patient weighed 4.3 kg, her cleft lip was repaired. Before and after surgery there were no seizures, and the postoperative course was uneventful. Copyright 2000 European Association for Cranio-Maxillofacial Surgery.

  9. Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling

    PubMed Central

    Moehring, Francie; Cowie, Ashley M; Menzel, Anthony D; Weyer, Andy D; Grzybowski, Michael; Arzua, Thiago; Geurts, Aron M; Palygin, Oleg

    2018-01-01

    The first point of our body’s contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments. Specific deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and primary afferent mechanical sensitivity, thus positioning keratinocyte-released ATP to sensory neuron P2X4 signaling as a critical component of baseline mammalian tactile sensation. These experiments lay a vital foundation for subsequent studies into the dysfunctional signaling that occurs in cutaneous pain and itch disorders, and ultimately, the development of novel topical therapeutics for these conditions. PMID:29336303

  10. Structural Basis of CDK4 Inhibition by p18INK4

    DTIC Science & Technology

    1999-05-01

    have determined the crystal structure of p 18INK4c to 1.95 A resolution [4] and the atomic coordinates have been deposited in the PDB protein...p 18INK4c function. The results were published [4] (Attached) and the coordinates were deposited in the PDB Protein Structure Database (Accession...Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ŘCurrent address: Institute of Molecular Agrobiology, National University of

  11. Effect of NH4-N/P and Ca/P molar ratios on the reactive crystallization of calcium phosphates for phosphorus recovery from wastewater

    NASA Astrophysics Data System (ADS)

    Vasenko, Liubov; Qu, Haiyan

    2017-02-01

    In this work, the effects of operational parameters, initial phosphorus concentration and molar ratios of Ca/P and NH4-N/P (further in the text N/P), on the nature and purity of precipitated phosphorus products have been investigated in an artificial system that mimics the supernatant in wastewater treatment plants. Metastable zone width was determined for two target phosphorus products: DCPD (dicalcium phosphate dihydrate) and HAp (hydroxyapatite) in the range of pH 4.5 - 7. HAp crystallizes at final pH higher than 6.3 while DCPD crystallizes at the final pH in between 4.7 and 5.7. At the final pH 5.7 - 6.3 and at pH lower than 4.7 the mixtures of DCPD and HAp were obtained. It was observed that N/P ratio affects not only the metastable zone width but also the kinetics of crystal growth for both DCPD and HAp: the higher the N/P ratio, the lower is the growth rate for both P-products. Investigation of the effect of Ca/P and N/P ratios on the nucleation and crystal growth of DCPD in batch crystallization experiment was performed. It showed that at high supersaturation level, crystals with larger median size can be obtained at higher N/P ratio despite the negative effects of N/P ratio on the growth rate of the crystals.

  12. Role of the metabotropic P2Y(4) receptor during hypoglycemia: cross talk with the ionotropic NMDAR1 receptor.

    PubMed

    Cavaliere, Fabio; Amadio, Susanna; Angelini, Daniela F; Sancesario, Giuseppe; Bernardi, Giorgio; Volonté, Cinzia

    2004-10-15

    It is well established that both extracellular ATP and glutamate exert a critical role during metabolic impairment, that several P2 receptor subunits are directly involved in this action and that a strong relationship exists between glutamatergic and purinergic signals. Therefore, here we studied the molecular behavior of the purinergic metabotropic P2Y(4) and the glutamatergic ionotropic NMDAR1 receptors during hypoglycemic cell death. We find that these proteins are oppositely modulated during glucose starvation (P2Y(4) is induced, whereas NMDAR1 is inhibited) and that both P2 and NMDA antagonists can restore basal protein expression levels. Moreover, double immunofluorescence experiments with confocal laser microscopy reveal co-localization at the membrane level between the P2Y(4) and NMDAR1 receptors, in both homologous (cerebellar granule neurons) and heterologous (Hek-293) cellular systems. This is furthermore confirmed by co-immunoprecipitation experiments. Finally, when we express the P2Y(4) receptor in the heterologous SH-SY5Y neuronal cell line, hypoglycemia then causes severe cell death and simultaneous downregulation of the NMDAR1 protein. In summary, our work establishes a potential molecular interplay between P2Y(4) and NMDAR1 receptors during glucose deprivation and the causative role of the P2Y(4) during cell death.

  13. Distortions in 2p4d Partial Fluorescence yield for 4d elements

    NASA Astrophysics Data System (ADS)

    Price, Alexander; de Groot, Frank; Datta, Trinanjan

    2014-03-01

    X-ray absorption spectroscopy (XAS) is a standard tool to determine the electronic structure of molecules and materials. CTM4XAS and CTM4RIXS are semi-empirical programs to analyze transition metal L - and M - edge transitions by evaluating the effects of crystal field and charge transfer parameters on the atomic multiplets. We compute and compare the XAS and the fluorescence yield (FY) XAS, of the 3d and 4d transition metal ions. In the case of 2p edges of 3d elements Auger decay dominates and sets the time scale. The 2p3d X -ray emission spectra (XES) accounts for approximately 80% of the radiative decay. The 2p3d partial FY is distorted and because it dominates the FY, the total FY is also distorted. For the 4d elements the 2p4d XES decay is approximately 10% of 2p3d XES decay, implying that (the energy-constant) core-core XES and Auger channels dominate the decay. The computed 2p4d partial FY -XAS spectra are different from the 2p XAS. Although 2p4d partial FY is distorted, the total FY is not because it is dominated by 2p3d XES. We also find that the 2p3s and 2p4s XES channels contribute less than 1% and can be neglected. Cottrell Research Corporation.

  14. P1,P4-diadenosine tetraphosphate (Ap4A) inhibits proximal tubular reabsorption of sodium in rats.

    PubMed

    Stiepanow-Trzeciak, Anna; Jankowski, Maciej; Angielski, Stefan; Szczepanska-Konkel, Miroslawa

    2007-01-01

    P1,P4-diadenosine tetraphosphate (Ap4A) is a vasoactive dinucleotide possessing natriuretic activity. It is unclear, however, which part of the nephron is the target site of action for Ap4A. We evaluated the tubular sites of Ap4A action using the lithium clearance technique. Ap4A at a priming dose of 2 micromol/kg with subsequent infusion at 20 nmol/kg/min increased fractional water and sodium excretion 2.5- and 5.6-fold, respectively. Moreover, Ap4A increased lithium clearance 1.9-fold and fractional lithium excretion 2.8-fold. Fractional water and sodium excretion from distal nephron segments was not significantly affected by Ap4A. These results suggest that Ap4A induces natriuresis mainly through inhibition of proximal tubular reabsorption of sodium. Copyright 2007 S. Karger AG, Basel.

  15. Synthesis of an allergy inducing tetrasaccharide "4P-X".

    PubMed

    Moriya, Takashi; Nagahata, Naoki; Odaka, Rei; Nakamura, Hirohide; Yoshikawa, Jun; Kurashima, Katsumi; Saito, Tadao

    2017-02-01

    4P-X (β-D-galactopyranosyl-(1 → 4)-β-D-galactopyranosyl-(1 → 6)-[β-D-galactopyranosyl-(1 → 4)]-β-D-glucopyranose) is included in galacto-oligosaccharides (GOSs) produced by β-galactosidase derived from Bacillus circulans. 4P-X has been known to induce particularly strong allergies. High purity 4P-X is essential for use as a standard to quantify the amount of 4P-X in GOSs; however, the isolation of high purity 4P-X has never been reported. In this study, we achieved the synthesis of 4P-X by a combination of organic and enzymatic chemical syntheses in a short time. This is the first report of isolated, high purity 4P-X. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Experimental and first-principles calculation study of the pressure-induced transitions to a metastable phase in GaP O4 and in the solid solution AlP O4-GaP O4

    NASA Astrophysics Data System (ADS)

    Angot, E.; Huang, B.; Levelut, C.; Le Parc, R.; Hermet, P.; Pereira, A. S.; Aquilanti, G.; Frapper, G.; Cambon, O.; Haines, J.

    2017-08-01

    α -Quartz-type gallium phosphate and representative compositions in the AlP O4-GaP O4 solid solution were studied by x-ray powder diffraction and absorption spectroscopy, Raman scattering, and by first-principles calculations up to pressures of close to 30 GPa. A phase transition to a metastable orthorhombic high-pressure phase along with some of the stable orthorhombic C m c m CrV O4 -type material is found to occur beginning at 9 GPa at 320 ∘C in GaP O4 . In the case of the AlP O4-GaP O4 solid solution at room temperature, only the metastable orthorhombic phase was obtained above 10 GPa. The possible crystal structures of the high-pressure forms of GaP O4 were predicted from first-principles calculations and the evolutionary algorithm USPEX. A predicted orthorhombic structure with a P m n 21 space group with the gallium in sixfold and phosphorus in fourfold coordination was found to be in the best agreement with the combined experimental data from x-ray diffraction and absorption and Raman spectroscopy. This method is found to very powerful to better understand competition between different phase transition pathways at high pressure.

  17. Hierarchical CoP/Ni 5 P 4 /CoP microsheet arrays as a robust pH-universal electrocatalyst for efficient hydrogen generation

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

    Mishra, Ishwar Kumar; Zhou, Haiqing; Sun, Jingying

    Exceptional Pt-like electrocatalytic activity was achieved in a sandwich-like catalyst of CoP/Ni 5 P 4 /CoP microsheet arrays for pH-universal hydrogen evolution through simply wrapping Ni 5 P 4 nanosheet arrays in CoP nanoparticles.

  18. Hierarchical CoP/Ni 5 P 4 /CoP microsheet arrays as a robust pH-universal electrocatalyst for efficient hydrogen generation

    DOE PAGES

    Mishra, Ishwar Kumar; Zhou, Haiqing; Sun, Jingying; ...

    2018-01-01

    Exceptional Pt-like electrocatalytic activity was achieved in a sandwich-like catalyst of CoP/Ni 5 P 4 /CoP microsheet arrays for pH-universal hydrogen evolution through simply wrapping Ni 5 P 4 nanosheet arrays in CoP nanoparticles.

  19. Clinical Significance of p53 and p16(ink4a) Status in a Contemporary North American Penile Carcinoma Cohort.

    PubMed

    Zargar-Shoshtari, Kamran; Spiess, Philippe E; Berglund, Anders E; Sharma, Pranav; Powsang, Julio M; Giuliano, Anna; Magliocco, Anthony M; Dhillon, Jasreman

    2016-08-01

    Because of the low incidence of penile carcinoma (PC), the value of p16(ink4a), p53, and human papilloma virus (HPV) infection status in clinical practice remains unclear. Herein, we report our experience with potential clinical utility of these markers in men with PC treated at our institution. Tissue microarrays of 57 cases of invasive penile squamous cell carcinomas were immunohistochemically stained for p16 and p53. HPV in situ hybridization (ISH) for high-risk subtypes was also performed. Association between marker status, nodal disease, overall (OS) and cancer-specific survival (CSS) were assessed. p16 and HPV ISH were positive in 23 (40%) and 24 (42%) of the cohort, respectively. The proportion of warty, basaloid, or mixed warty basaloid tumor subtypes were significantly greater in the p16-positive patients (48% vs. 3%; P < .01). p53 expression was negative in 31 (54%) cases. Only in p16-negative patients, positive p53 status was associated with pN+ disease (odds ratio, 4.4 [95% confidence interval (CI), 1.04-18.6]). In Kaplan-Meier analysis, the unadjusted estimated OS was insignificantly longer in p16-positive patients (median OS, 75 vs. 27 months; P = .27) and median CSS was not reached (P = .16). In a multivariable Cox proportional hazard model, when controlling for pathological nodal status and adjuvant chemotherapy, p16 status was a significant predictor for improved CSS (hazard ratio, 0.36 [95% CI, 0.13-0.99]). The worst CSS was seen in pN+ patients with double negative p16 and p53 expression (8 vs. 34 months; P = .01). In this current cohort, p53 and p16 status showed clinical utility in predicting nodal disease as well as survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Application experiments to trace N-P interactions in forest ecosystems

    NASA Astrophysics Data System (ADS)

    Krüger, Jaane; Niederberger, Jörg; Schulz, Stefanie; Lang, Friederike

    2017-04-01

    Phosphorus is a limited resource and there is increasing debate regarding the principles of tight P recycling. Forest ecosystems show commonly high P use efficiencies but the processes behind this phenomenon are still unresolved. In frame of the priority program "SPP 1685 Ecosystem nutrition - Forest strategies for limited phosphorus resources" around 70 researchers from different disciplines collaborate to unravel these processes. The overall hypothesis to be tested is that the P nutrition strategy of forest ecosystems at sites rich in mineral P is characterized by high P uptake efficiency (acquiring systems). In contrast, the P strategy of forest ecosystems facing low soil P stocks is characterized by highly efficient mechanisms of P recycling. To test this hypothesis, we analyzed five beech forest ecosystems on silicate rock with different parent materials representing a gradient of total P stocks (160 - 900 g P m-2, down to 1m soil depth). In fact, we found evidence confirming our hypothesis, but controls and drivers of P strategies are still unknown as other environmental variables differ. One of those might be the N content, as organisms strive to reach a specific internal N:P ratio. Thus, an additional application of N might also alter P nutrition. To test this, we established a factorial P x N application experiment at three of the study sites. With our presentation we will introduce this experiment and give a review on published P x N experiments discussing different advantages and disadvantages of different basic conditions (e.g. amount and application form, doses, sampling and statistical design, monitoring periods, budget calculation, isotopic tracing). Finally, we want to initiate a common discussion on the standardization of P x N field experiments to enable interdisciplinary and across-compartment comparisons (e.g. different land use, different climate zones, terrestrial and aquatic ecosystems).

  1. The 4d8-(4d74f + 4d76p + 4p54d9) transitions in the spectrum of five times ionized indium (In VI)

    NASA Astrophysics Data System (ADS)

    Ryabtsev, A. N.; Tauheed, A.; Swapnil; Kildiyarova, R. R.; Kononov, E. Ya

    2018-06-01

    The spectrum of five times ionized indium excited in a vacuum spark has been studied in the wavelength region 180-250 Å using a 3 m grazing incidence spectrograph. Transitions from highly excited interacting configurations 4d74f + 4d76p + 4p54d9 to the ground state 4d8 configuration were studied. 165 spectral lines were identified and 81 levels of the excited configurations were found.

  2. 4p16.1-p15.31 duplication and 4p terminal deletion in a 3-years old Chinese girl: Array-CGH, genotype-phenotype and neurological characterization.

    PubMed

    Piccione, Maria; Salzano, Emanuela; Vecchio, Davide; Ferrara, Dante; Malacarne, Michela; Pierluigi, Mauro; Ferrara, Ines; Corsello, Giovanni

    2015-07-01

    Microscopically chromosome rearrangements of the short arm of chromosome 4 include the two known clinical entities: partial trisomy 4p and deletions of the Wolf-Hirschhorn critical regions 1 and 2 (WHSCR-1 and WHSCR-2, respectively), which cause cranio-facial anomalies, congenital malformations and developmental delay/intellectual disability. We report on clinical findings detected in a Chinese patient with a de novo 4p16.1-p15.32 duplication in association with a subtle 4p terminal deletion of 6 Mb in size. This unusual chromosome imbalance resulted in WHS classical phenotype, while clinical manifestations of 4p trisomy were practically absent. This observation suggests the hypothesis that haploinsufficiency of sensitive dosage genes with regulatory function placed in WHS critical region, is more pathogenic than concomitant 4p duplicated segment. Additionally clinical findings in our patient confirm a variable penetrance of major malformations and neurological features in Chinese children despite of WHS critical region's deletion. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. P4 Medicine versus Hippocrates.

    PubMed

    Pulciani, Simonetta; Di Lonardo, Anna; Fagnani, Corrado; Taruscio, Domenica

    2017-01-01

    Hippocrates was the first to raise awareness of medicine as a science. He asserted the body being a unified whole and emphasized the importance of preventive and predictive medicine, spurring physicians to foster patient collaboration. Recent achievements today have permitted a new approach "P4 medicine" - Predictive, Preventive, Personalized and Participatory - with the aim of depicting an individual's health history and molecular profile in determining the best medical intervention in maintaining or restoring wellbeing. There is a link, which brings together Hippocrates and P4 Medicine. This review will elaborate further this statement, considering the scientific achievements that paved the way for recent medical approaches. Emphasis will be given to the social impact of new diagnostic and therapeutic protocols, considering their costs and their success probabilities.

  4. Novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)-binding studies.

    PubMed

    Wright, Michael; Miller, Andrew D

    2006-02-15

    Tandem synthetic-biosynthetic procedures were used to prepare two novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)-binding studies. These compounds (dial-mant-Ap4A and azido-mant-Ap4A) are shown to clearly distinguish known Ap4A-binding proteins from Escherichia coli (LysU and GroEL) and a variety of other control proteins. Successful labelling of chaperonin GroEL appears to be allosteric with respect to the well-characterized adenosine 5'-triphosphate (ATP)-binding site, suggesting that GroEL possesses a distinct Ap4A-binding site.

  5. Binding behaviors of p-sulfonatocalix[4]arene with gemini guests.

    PubMed

    Zhao, Hong-Xia; Guo, Dong-Sheng; Liu, Yu

    2013-02-14

    A dozen of homoditopic cations, possessing different spacer lengths and rigidities, as well as sizes, shapes, and charges of terminal groups, were synthesized as candidate gemini guests for the complexation of p-sulfonatocalix[4]arenes (SC4A). The 12 gemini guests are divided into five species according to the different terminal groups: imidazolium (G1-G3), pyridinium (G4-G6), quinolinium (G7), viologen (G8-G11), and 1,4-diazabicyclo[2.2.2]octane (DBO, G12). Their binding structures and stoichiometries with SC4A were examined by NMR spectroscopy, which is helpful to construct diverse highly ordered assemblies. The obtained results show that the length of the linkers, as well as the charge numbers on the end groups have a pronounced effect on the binding stoichiometry, whereas the size and shape of the terminal groups have no significant influence. Furthermore, both the stability constants and thermodynamic parameters of SC4A with the terminal subunits were determined by the isothermal titration calorimetry experiments, which are valuable to understand the binding behavior, giving quantitatively deep insight.

  6. Merging P4P and disease management: how do you know which one is working?

    PubMed

    Smith, Allen L

    2007-03-01

    An intervention movement in managed care, disease management (DM), is a system of coordinated health care interventions and communication for populations with conditions in which patient self-care efforts are significant. Another managed care intervention movement, pay for performance (P4P), involves an incentive component in which payment is defined based on meeting specific, previously agreed-upon process or outcomes targets. To explore the various characteristics of DM and P4P interventions, determine how they differ, and explore the differences in results of programs in current practice. In DM, regular ongoing evaluation of clinical, humanistic, and economic outcomes plays a crucial role in reducing costs and improving quality of care. The goal of improving overall patient health in DM is also accomplished by supporting the physician or practitioner/patient relationship and plan of care. P4P initiatives vary more according to the needs and preferences of local providers and plans than do DM initiatives. While DM programs can be implemented without necessarily changing how providers deliver health care, P4P requires new programs and/or systems within the provider sector to improve patient care quality and/or efficiency. P4P initiatives also typically involve the upside or downside risk by physicians/hospitals. Partners HealthCare, based in Boston, features P4P initiatives for inpatient admissions, diabetes, and radiology that have all been met with success. Both DM and P4P initiatives have been successful in managed care. However, in terms of determining whether DM or P4P initiatives are more effective in improving the quality and efficiency of health care delivery, it is simply too early to tell at this time.

  7. Molecular modeling of cytochrome P450 3A4

    NASA Astrophysics Data System (ADS)

    Szklarz, Grazyna D.; Halpert, James R.

    1997-05-01

    The three-dimensional structure of human cytochrome P450 3A4 was modeled based on crystallographic coordinates of four bacterial P450s: P450 BM-3, P450cam, P450terp, and P450eryF. The P450 3A4 sequence was aligned to those of the known proteins using a structure-based alignment of P450 BM-3, P450cam, P450terp, and P450eryF. The coordinates of the model were then calculated using a consensus strategy, and the final structure was optimized in the presence of water. The P450 3A4 model resembles P450 BM-3 the most, but the B' helix is similar to that of P450eryF, which leads to an enlarged active site when compared with P450 BM-3, P450cam, and P450terp. The 3A4 residues equivalent to known substrate contact residues of the bacterial proteins and key residues of rat P450 2B1 are located in the active site or the substrate access channel. Docking of progesterone into the P450 3A4 model demonstrated that the substrate bound in a 6β-orientation can interact with a number of active site residues, such as 114, 119, 301, 304, 305, 309, 370, 373, and 479, through hydrophobic interactions. The active site of the enzyme can also accommodate erythromycin, which, in addition to the residues listed for progesterone, also contacts residues 101, 104, 105, 214, 215, 217, 218, 374, and 478. The majority of 3A4 residues which interact with progesterone and/or erythromycin possess their equivalents in key residues of P450 2B enzymes, except for residues 297, 480 and 482, which do not contact either substrate in P450 3A4. The results from docking of progesterone and erythromycin into the enzyme model make it possible to pinpoint residues which may be important for 3A4 function and to target them for site-directed mutagenesis.

  8. Clinical manifestations of trisomy 4p syndrome.

    PubMed

    Patel, S V; Dagnew, H; Parekh, A J; Koenig, E; Conte, R A; Macera, M J; Verma, R S

    1995-06-01

    Trisomy 4p syndrome is a distinct clinical entity which was noted almost a quarter century ago by Wilson et al. [71] and later was delineated by Gonzalez and colleagues [29]. The variation in the length of duplicated segment usually associated with monosomy of other genetic material which has resulted in confusion and as a result a so-called 4p syndrome could not be recognized without cytogenetic analysis. We wish to draw the attention of clinicians to this subject by presenting the description of over 75 cases including one from our clinic and stress the point that molecular approaches are imperative to characterize this anomaly. After extensive review, it appears that patients retaining at least the distal two-thirds to the entire short arm share an overlapping phenotypic expression that constitutes pure trisomy 4p syndrome which includes prominent glabella, bulbous nose with flat or depressed nasal bridge, retrognathia, pointed chin, short neck with low hairline, enlarged ears with abnormal helix and antihelix, rocker-bottom feet with prominent heel. Arachnodactyly and camptodactyly. Molecular characterization of 4p is imperative. We have also included an extensive bibliography for clinicians who may find it useful as a single reference source for evaluating their future cases. The 4p-syndrome is a distinct entity but without cytogenetic evaluation, the syndrome can not be recognized.

  9. Ion channel regulation by phosphoinositides analyzed with VSPs—PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility

    PubMed Central

    Rjasanow, Alexandra; Leitner, Michael G.; Thallmair, Veronika; Halaszovich, Christian R.; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs. PMID

  10. MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4

    PubMed Central

    Zhang, Kundong; Cen, Gang; Jiang, Tao; Cao, Jun; Huang, Kejian; Zhao, Qian; Qiu, Zhengjun

    2015-01-01

    Background Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo. Methods By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed. Results Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues. Conclusion MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4. PMID:26019136

  11. Validation of the 4P's Plus screen for substance use in pregnancy validation of the 4P's Plus.

    PubMed

    Chasnoff, I J; Wells, A M; McGourty, R F; Bailey, L K

    2007-12-01

    The purpose of this study is to validate the 4P's Plus screen for substance use in pregnancy. A total of 228 pregnant women enrolled in prenatal care underwent screening with the 4P's Plus and received a follow-up clinical assessment for substance use. Statistical analyses regarding reliability, sensitivity, specificity, and positive and negative predictive validity of the 4Ps Plus were conducted. The overall reliability for the five-item measure was 0.62. Seventy-four (32.5%) of the women had a positive screen. Sensitivity and specificity were very good, at 87 and 76%, respectively. Positive predictive validity was low (36%), but negative predictive validity was quite high (97%). Of the 31 women who had a positive clinical assessment, 45% were using less than 1 day per week. The 4P's Plus reliably and effectively screens pregnant women for risk of substance use, including those women typically missed by other perinatal screening methodologies.

  12. Effects of N and P fertilisation on greenhouse gas (GHG) production in floodplain fen peat: A microcosm fertilisation experiment.

    NASA Astrophysics Data System (ADS)

    Stanley, Kieran; Heppell, Catherine; Belyea, Lisa; Baird, Andrew

    2016-04-01

    Biogeochemical and hydrological cycles are being significantly perturbed by anthropic activities altering atmospheric mole fractions of greenhouse gases (GHG) and increasing global temperatures. With the intensification of the hydrological cycle, lowland areas, such as floodplain fens, may be inundated more frequently. Rivers in agricultural catchments have the potential to pollute floodplain fens with significant amounts of nitrogen (N) and phosphorus (P); however, the effects of short-term (< 15 days) N and P fertilisation via fluvial inundation on GHG emissions from floodplain fens are poorly understood. The aim of this research was to determine how N (51 mg L-1 NO3-N) and P (1.4 mg L-1 PO43--P) additions may alter GHG (CO2, CH4, and N2O) production in floodplain fens of contrasting nutrient status under anaerobic conditions. A five-level (control, glucose (G), N+G, P+G, and N+P+G), fully-factorial microcosm experiment was designed and undertaken in Spring 2013 with peat from two floodplain fens under conservation management with similar vegetation (from Norfolk, United Kingdom). One site receives a higher nutrient load than the other and has a historical legacy of higher N and P contents within the peat. Results from the experiment showed no significant difference in CO2 production between the control and fertilised treatments from 0 to 96 hours, but a significant difference between treatments (ANCOVA, between factors: treatment and site; covariate: time; F4,419 = 11.844, p < 0.001) and site (F1,149 = 5.721, p = 0.017) from 96 hours to in the end of the experiment due to fermentation. N2O production only occurred in samples fertilised with N (N+G and N+P+G) due to denitrification. Rates of N2O production were significantly greater in samples from the lower-nutrient site in comparison to the nutrient-rich site (t12= 6.539, p < 0.001 and t12= 7.273, p < 0.001 for N+G and N+P+G fertilised samples, respectively). Fertilisation with N and P had different effects on

  13. GABARAPs regulate PI4P-dependent autophagosome:lysosome fusion.

    PubMed

    Wang, Hanzhi; Sun, Hui-Qiao; Zhu, Xiaohui; Zhang, Li; Albanesi, Joseph; Levine, Beth; Yin, Helen

    2015-06-02

    The Atg8 autophagy proteins are essential for autophagosome biogenesis and maturation. The γ-aminobutyric acid receptor-associated protein (GABARAP) Atg8 family is much less understood than the LC3 Atg8 family, and the relationship between the GABARAPs' previously identified roles as modulators of transmembrane protein trafficking and autophagy is not known. Here we report that GABARAPs recruit palmitoylated PI4KIIα, a lipid kinase that generates phosphatidylinositol 4-phosphate (PI4P) and binds GABARAPs, from the perinuclear Golgi region to autophagosomes to generate PI4P in situ. Depletion of either GABARAP or PI4KIIα, or overexpression of a dominant-negative kinase-dead PI4KIIα mutant, decreases autophagy flux by blocking autophagsome:lysosome fusion, resulting in the accumulation of abnormally large autophagosomes. The autophagosome defects are rescued by overexpressing PI4KIIα or by restoring intracellular PI4P through "PI4P shuttling." Importantly, PI4KIIα's role in autophagy is distinct from that of PI4KIIIβ and is independent of subsequent phosphatidylinositol 4,5 biphosphate (PIP2) generation. Thus, GABARAPs recruit PI4KIIα to autophagosomes, and PI4P generation on autophagosomes is critically important for fusion with lysosomes. Our results establish that PI4KIIα and PI4P are essential effectors of the GABARAP interactome's fusion machinery.

  14. Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography.

    PubMed

    Elmaleh, D R; Fischman, A J; Tawakol, A; Zhu, A; Shoup, T M; Hoffmann, U; Brownell, A-L; Zamecnik, P C

    2006-10-24

    Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)-monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.

  15. NAIM and site-specific functional group modification analysis of RNase P RNA: magnesium dependent structure within the conserved P1-P4 multihelix junction contributes to catalysis.

    PubMed

    Kaye, Nicholas M; Christian, Eric L; Harris, Michael E

    2002-04-09

    The tRNA processing endonuclease ribonuclease P contains an essential and highly conserved RNA molecule (RNase P RNA) that is the catalytic subunit of the enzyme. To identify and characterize functional groups involved in RNase P RNA catalysis, we applied self-cleaving ribozyme-substrate conjugates, on the basis of the RNase P RNA from Escherichia coli, in nucleotide analogue interference mapping (NAIM) and site-specific modification experiments. At high monovalent ion concentrations (3 M) that facilitate protein-independent substrate binding, we find that the ribozyme is largely insensitive to analogue substitution and that concentrations of Mg2+ (1.25 mM) well below that necessary for optimal catalytic rate (>100 mM) are required to produce interference effects because of modification of nucleotide bases. An examination of the pH dependence of the reaction rate at 1.25 mM Mg2+ indicates that the increased sensitivity to analogue interference is not due to a change in the rate-limiting step. The nucleotide positions detected by NAIM under these conditions are located exclusively in the catalytic domain, consistent with the proposed global structure of the ribozyme, and predominantly occur within the highly conserved P1-P4 multihelix junction. Several sensitive positions in J3/4 and J2/4 are proximal to a previously identified site of divalent metal ion binding in the P1-P4 element. Kinetic analysis of ribozymes with site-specific N7-deazaadenosine and deazaguanosine modifications in J3/4 was, in general, consistent with the interference results and also permitted the analysis of sites not accessible by NAIM. These results show that, in this region only, modification of the N7 positions of A62, A65, and A66 resulted in measurable effects on reaction rate and modification at each position displayed distinct sensitivities to Mg2+ concentration. These results reveal a restricted subset of individual functional groups within the catalytic domain that are particularly

  16. [Recombinant chromosome 4 with partial 4p deletion and 4q duplication inherited from paternal pericentric inversion].

    PubMed

    Mun, Se Jin; Cho, Eun Hae; Chey, Myoung-Jae; Shim, Gyu-Hong; Shin, Bo-Moon; Lee, Rae-Kyung; Ko, Ji-Kyung; Yoo, Soo Jin

    2010-02-01

    Pericentric inversion of chromosome 4 can give rise to 2 alternate recombinant (rec) chromosomesby duplication or deletion of 4p. The deletion of distal 4p manifests as Wolf-Hirschhorn syndrome (WHS). Here, we report the molecular cytogenetic findings and clinical manifestations observed in an infant with 46,XX,rec(4)dup(4q)inv(4)(p16q31.3)pat. The infant was delivered by Cesarean section at the 33rd week of gestation because pleural effusion and polyhydramnios were detected on ultrasonography. At birth, the infant showed no malformation or dysfunction, except for a preauricular skin tag. Array comparative genomic hybridization analysis of neonatal peripheral blood samples showed a gain of 38 Mb on 4q31.3-qter and a loss of 3 Mb on 4p16.3, and these results were consistent with WHS. At the last follow-up at 8 months of age (corrected age, 6 months), the infant had not achieved complete head control.

  17. Skylab experiments. Volume 4: Life sciences

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The life sciences experiments conducted during Skylab missions are discussed. The general categories of the experiments are as follows: (1) mineral and hormonal balance, (2) hematology and immunology, (3) cardiovascular status, (4) energy expenditure, (5) neurophysiology, and (7) biology. Each experiment within the general category is further identified with respect to the scientific objectives, equipment used, performance, and data to be obtained.

  18. Reactive Solute Transport in Streams: 2. Simulation of a pH Modification Experiment

    NASA Astrophysics Data System (ADS)

    Runkel, Robert L.; McKnight, Diane M.; Bencala, Kenneth E.; Chapra, Steven C.

    1996-02-01

    We present an application of an equilibrium-based solute transport model to a pH-modification experiment conducted on the Snake River, an acidic, metal-rich stream located in the Rocky Mountains of Colorado. During the experiment, instream pH decreased from 4.2 to 3.2, causing a marked increase in dissolved iron concentrations. Model application requires specification of several parameters that are estimated using tracer techniques, mass balance calculations, and geochemical data. Two basic questions are addressed through model application: (1) What are the processes responsible for the observed increase in dissolved iron concentrations? (2) Can the identified processes be represented within the equilibrium-based transport model? Simulation results indicate that the increase in iron was due to the dissolution of hydrous iron oxides and the photoreduction of ferric iron. Dissolution from the streambed is represented by considering a trace compartment consisting of freshly precipitated hydrous iron oxide and an abundant compartment consisting of aged precipitates that are less soluble. Spatial variability in the solubility of hydrous iron oxide is attributed to heterogeneity in the streambed sediments, temperature effects, and/or variability in the effects of photoreduction. Solubility products estimated via simulation fall within a narrow range (pKsp from 40.2 to 40.8) relative to the 6 order of magnitude variation reported for laboratory experiments (pKsp from 37.3 to 43.3). Results also support the use of an equilibrium-based transport model as the predominate features of the iron and pH profiles are reproduced. The model provides a valuable tool for quantifying the nature and extent of pH-dependent processes within the context of hydrologic transport.

  19. Quasimolecular emission near the Xe(5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance lines induced by collisions with He atoms

    NASA Astrophysics Data System (ADS)

    Alekseeva, O. S.; Devdariani, A. Z.; Grigorian, G. M.; Lednev, M. G.; Zagrebin, A. L.

    2017-02-01

    This study is devoted to the theoretical investigation of the quasimolecular emission of Xe*-He and Kr*-He collision pairs near the Xe (5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance atomic lines. The potential curves of the quasimolecules Xe(5p 56s) + He and Kr(4p 55s) + He have been obtained with the use of the effective Hamiltonian and pseudopotential methods. Based on these potential curves the processes of quasimolecular emission of Xe*+He and Kr*+He mixtures have been considered and the spectral distributions I(ħΔω) of photons emitted have been obtained in the framework of quasistatic approximation.

  20. Level energies, lifetimes and radiative rates in the 4p44d configurations of bromine-like ions

    NASA Astrophysics Data System (ADS)

    Singh, A. K.; Aggarwal, Sunny; Mohan, Man

    2013-09-01

    Energy levels, lifetimes and wavefunction compositions have been computed for all levels of odd parity 4s24p5 ground configuration as well as 4s4p6 and 4s24p44d even parity excited configurations in Br-like Sr IV, Y V, Zr VI, Nb VII and Mo VIII. Transition probabilities, oscillator strengths and line strengths for the electric dipole (E1) transition from the 4s24p5 configuration have been obtained using the multiconfiguration Dirac-Fock approach. Correlations within the n = 4 complex, Breit and quantum electrodynamics effects have been included. We make a detailed comparison of our results with those of other numerical methods and experiments to assess the quality of our results. Good agreement is observed between our results and those obtained using different approaches confirm the quality of our results. Further, we have also predicted new atomic data that were not available so far and are yet to be observed.

  1. Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels

    PubMed Central

    Dai, Gucan; Yu, Haijie; Traynor-Kaplan, Alexis

    2016-01-01

    Myo-inositol is an important cellular osmolyte in autoregulation of cell volume and fluid balance, particularly for mammalian brain and kidney cells. We find it also regulates excitability. Myo-inositol is the precursor of phosphoinositides, key signaling lipids including phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. However, whether myo-inositol accumulation during osmoregulation affects signaling and excitability has not been fully explored. We found that overexpression of the Na+/myo-inositol cotransporter (SMIT1) and myo-inositol supplementation enlarged intracellular PI(4,5)P2 pools, modulated several PI(4,5)P2-dependent ion channels including KCNQ2/3 channels, and attenuated the action potential firing of superior cervical ganglion neurons. Further experiments using the rapamycin-recruitable phosphatase Sac1 to hydrolyze PI(4)P and the P4M probe to visualize PI(4)P suggested that PI(4)P levels increased after myo-inositol supplementation with SMIT1 expression. Elevated relative levels of PIP and PIP2 were directly confirmed using mass spectrometry. Inositol trisphosphate production and release of calcium from intracellular stores also were augmented after myo-inositol supplementation. Finally, we found that treatment with a hypertonic solution mimicked the effect we observed with SMIT1 overexpression, whereas silencing tonicity-responsive enhancer binding protein prevented these effects. These results show that ion channel function and cellular excitability are under regulation by several “physiological” manipulations that alter the PI(4,5)P2 setpoint. We demonstrate a previously unrecognized linkage between extracellular osmotic changes and the electrical properties of excitable cells. PMID:27217553

  2. Highly selective dry etching of GaP in the presence of AlxGa1–xP with a SiCl4/SF6 plasma

    NASA Astrophysics Data System (ADS)

    Hönl, Simon; Hahn, Herwig; Baumgartner, Yannick; Czornomaz, Lukas; Seidler, Paul

    2018-05-01

    We present an inductively coupled-plasma reactive-ion etching process that simultaneously provides both a high etch rate and unprecedented selectivity for gallium phosphide (GaP) in the presence of aluminum gallium phosphide (AlxGa1–xP). Utilizing mixtures of silicon tetrachloride (SiCl4) and sulfur hexafluoride (SF6), selectivities exceeding 2700:1 are achieved at GaP etch rates above 3000 nm min‑1. A design of experiments has been employed to investigate the influence of the inductively coupled-plasma power, the chamber pressure, the DC bias and the ratio of SiCl4 to SF6. The process enables the use of thin AlxGa1–xP stop layers even at aluminum contents of a few percent.

  3. 4P: fast computing of population genetics statistics from large DNA polymorphism panels

    PubMed Central

    Benazzo, Andrea; Panziera, Alex; Bertorelle, Giorgio

    2015-01-01

    Massive DNA sequencing has significantly increased the amount of data available for population genetics and molecular ecology studies. However, the parallel computation of simple statistics within and between populations from large panels of polymorphic sites is not yet available, making the exploratory analyses of a set or subset of data a very laborious task. Here, we present 4P (parallel processing of polymorphism panels), a stand-alone software program for the rapid computation of genetic variation statistics (including the joint frequency spectrum) from millions of DNA variants in multiple individuals and multiple populations. It handles a standard input file format commonly used to store DNA variation from empirical or simulation experiments. The computational performance of 4P was evaluated using large SNP (single nucleotide polymorphism) datasets from human genomes or obtained by simulations. 4P was faster or much faster than other comparable programs, and the impact of parallel computing using multicore computers or servers was evident. 4P is a useful tool for biologists who need a simple and rapid computer program to run exploratory population genetics analyses in large panels of genomic data. It is also particularly suitable to analyze multiple data sets produced in simulation studies. Unix, Windows, and MacOs versions are provided, as well as the source code for easier pipeline implementations. PMID:25628874

  4. Advanced Plant Experiment, APEX-4

    NASA Image and Video Library

    2017-03-10

    Advanced Plant Experiment, APEX-4, support in the Telescience Support Center at NASA Glenn. APEX-4 continues a highly successful investigation into the effects of microgravity on the development of roots and cells on plant seedlings. After four days of growth, the petri plate will be inserted into the Fluids Integrated Rack (FIR) Light Microscopy Module (LMM) facility for detailed imaging.

  5. Purinergic receptors P2RX4 and P2RX7 in familial multiple sclerosis

    PubMed Central

    Sadovnick, A Dessa; Gu, Ben J; Traboulsee, Anthony L; Bernales, Cecily Q; Encarnacion, Mary; Yee, Irene M; Criscuoli, Maria G; Huang, Xin; Ou, Amber; Milligan, Carol J; Petrou, Steven; Wiley, James S; Vilariño-Güell, Carles

    2017-01-01

    Genetic variants in the purinergic receptors P2RX4 and P2RX7 have been shown to affect susceptibility to multiple sclerosis (MS). In this study we set out to evaluate whether rare coding variants of major effect could also be identified in these purinergic receptors. Sequencing analysis of P2RX4 and P2RX7 in 193 MS patients and 100 controls led to the identification of a rare three variant haplotype (P2RX7 rs140915863:C>T (p.T205M), P2RX7 rs201921967:A>G (p.N361S) and P2RX4 rs765866317:G>A (p.G135S)) segregating with disease in a multi-incident family with six family members diagnosed with MS (LOD=3.07). Functional analysis of this haplotype in HEK293 cells revealed impaired P2X7 surface expression (p<0.01), resulting in over 95% inhibition of ATP-induced pore function (p<0.001) and a marked reduction in phagocytic ability (p<0.05). In addition, transfected cells showed 40% increased peak ATP-induced inward current (p<0.01), and a greater Ca2+ response to the P2X4 135S variant compared to wild type (p<0.0001). Our study nominates rare genetic variants in P2RX4 and P2RX7 as major genetic contributors to disease, further supporting a role for these purinergic receptors in MS and suggesting the disruption of transmembrane cation channels leading to impairment of phagocytosis as the pathological mechanisms of disease. PMID:28326637

  6. 17O NMR studies on 4- and 4'-substituted chalcones and p-substituted β-nitrostyrenes

    NASA Astrophysics Data System (ADS)

    Boykin, D. W.; Baumstark, A. L.; Balakrishnan, P.; Perjéssy, A.; Hrnc˜iar, P.

    The 17O NMR chemical shift data for 17O-enriched 4- and 4'-chalcones in toluene at 90°C and for p-substituted β-nitrostyrenes (natural abundance) in acetonitrile at 70°C are reported. The SCS (substituent chemical shift) range for the 4-chalcones p-CH 3O to p-NO 2 is 16.3 ppm; the range for the 4'-chalcones p-CH 3O to p-NO 2 is 32.4 ppm. The SCS range for the p-substituted-β-nitrostyrenes p-CH 3O to p-NO 2 is 13.2 ppm. The data for the three series gave good correlations with σ + constants, while the Dual Substitutent Parameter treatment only slightly improved the correlations using σ R+ constants. Plots of the 17O chemical shifts for both 4- and 4'-chalcones with 17O data for acetophenones and correlation of 17O chemical shift data for the β-nitrostyrenes with that of nitrobenzenes gave good correlations. Plots of the 17O data for all the three series with their respective functional group stretching frequencies gave fair correlations.

  7. The short arm deletion syndrome of chromosome 4 (4p- syndrome).

    PubMed

    Zellweger, H; Bardach, J; Bordwell, J; Williams, K

    1975-01-01

    Partial deletion of the short arm of chromosome 4 (4p-) represents another (rare) cause of cleft lip and cleft palate. Further characteristic manifestations of the syndrome (also called Wolf or Wolf-Hirschhorn syndrome) are growth failure, microcephaly, prominent glabella, hypertelorism, beaked nose, poorly differentiated and low set ears, cardiac and renal malformation and hypospadias. Life expectancy is often shortened. The 4p- syndrome has many features in common with another deletion syndrome, the cri-du-chat syndrome, and also with the Smith-Lemli-Opitz syndrome. The latter is a hereditary condition with normal karyotype. The cri-du-chat syndrome is characterized by a peculiar high-pitched, mewing cry and can be differentiated from the Wolf syndrome by the different staining characteristics (banding) of chromosomes 4 and 5.

  8. Reactive solute transport in streams: 2. Simulation of a pH modification experiment

    USGS Publications Warehouse

    Runkel, Robert L.; McKnight, Diane M.; Bencala, Kenneth E.; Chapra, Steven C.

    1996-01-01

    We present an application of an equilibrium-based solute transport model to a pH-modification experiment conducted on the Snake River, an acidic, metal-rich stream located in the Rocky Mountains of Colorado. During the experiment, instream pH decreased from 4.2 to 3.2, causing a marked increase in dissolved iron concentrations. Model application requires specification of several parameters that are estimated using tracer techniques, mass balance calculations, and geochemical data. Two basic questions are addressed through model application: (1) What are the processes responsible for the observed increase in dissolved iron concentrations? (2) Can the identified processes be represented within the equilibrium-based transport model? Simulation results indicate that the increase in iron was due to the dissolution of hydrous iron oxides and the photoreduction of ferric iron. Dissolution from the streambed is represented by considering a trace compartment consisting of freshly precipitated hydrous iron oxide and an abundant compartment consisting of aged precipitates that are less soluble. Spatial variability in the solubility of hydrous iron oxide is attributed to heterogeneity in the streambed sediments, temperature effects, and/or variability in the effects of photoreduction. Solubility products estimated via simulation fall within a narrow range (pKsp from 40.2 to 40.8) relative to the 6 order of magnitude variation reported for laboratory experiments (pKsp from 37.3 to 43.3). Results also support the use of an equilibrium-based transport model as the predominate features of the iron and pH profiles are reproduced. The model provides a valuable tool for quantifying the nature and extent of pH-dependent processes within the context of hydrologic transport.

  9. Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma

    PubMed Central

    Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

    2016-01-01

    We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21) [8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA-sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in-frame TBCK-P4HA2 and the reciprocal but out-of-frame P4HA2-TBCK fusion transcripts. The putative TBCK-P4HA2 protein would contain the kinase, the rhodanese-like domain, and the Tre-2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4-hydroxylase. The t(5;8;17)(p15;q13;q21) three-way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in-frame fusions AHRR-NCOA2 and NCOA2-ETV4 as well as an out-of-frame ETV4-AHRR transcript. In the AHRR-NCOA2 protein, the C-terminal part of AHRR is replaced by the C-terminal part of NCOA2 which contains two activation domains. The NCOA2-ETV4 protein would contain the helix-loop-helix, PAS_9 and PAS_11, CITED domains, the SRC-1 domain of NCOA2 and the ETS DNA-binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR-NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor. PMID:27633981

  10. Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma.

    PubMed

    Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

    2016-11-01

    We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21)[8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA‑sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in‑frame TBCK‑P4HA2 and the reciprocal but out‑of‑frame P4HA2‑TBCK fusion transcripts. The putative TBCK‑P4HA2 protein would contain the kinase, the rhodanese‑like domain, and the Tre‑2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4‑hydroxylase. The t(5;8;17)(p15;q13;q21) three‑way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in‑frame fusions AHRR‑NCOA2 and NCOA2‑ETV4 as well as an out‑of‑frame ETV4‑AHRR transcript. In the AHRR‑NCOA2 protein, the C‑terminal part of AHRR is replaced by the C‑terminal part of NCOA2 which contains two activation domains. The NCOA2‑ETV4 protein would contain the helix‑loop‑helix, PAS_9 and PAS_11, CITED domains, the SRC‑1 domain of NCOA2 and the ETS DNA‑binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR‑NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor.

  11. Radiative lifetimes of the 2s2p2(4P) metastable levels of N III

    NASA Technical Reports Server (NTRS)

    Fang, Z.; Kwong, Victor H. S.; Parkinson, W. H.

    1993-01-01

    The radiative decay rates of N III 175 nm intersystem lines were measured in the laboratory by recording the time dependence of photon intensities emitted as the 2s2p2(4P) metastable term of N(2+) ions decay to the 2s22p(2P0) ground term. A cylindrical radio frequency ion trap was used to store the electron impact-produced N(2+) ions. The radiative decay signals were analyzed by multiexponential least-squares fits to the data. The measured radiative decay rates to the ground term are 1019(+/- 64)/s for 4P sub 1/2, 74.5(+/- 5.4)/s for 4P sub 3/2, and 308( +/- 22)/s for 4P sub 5/2. Comparisons of the measured values with theoretical values are presented.

  12. Prenatal Diagnosis of 4p and 4q Subtelomeric Microdeletion in De Novo Ring Chromosome 4

    PubMed Central

    Cine, Naci; Erdemoglu, Mahmut; Atay, Ahmet Engin; Simsek, Selda; Turkyilmaz, Aysegul; Fidanboy, Mehmet

    2013-01-01

    Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH). However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis. PMID:24455347

  13. Prenatal diagnosis of 4p and 4q subtelomeric microdeletion in de novo ring chromosome 4.

    PubMed

    Akbas, Halit; Cine, Naci; Erdemoglu, Mahmut; Atay, Ahmet Engin; Simsek, Selda; Turkyilmaz, Aysegul; Fidanboy, Mehmet

    2013-01-01

    Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH). However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.

  14. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different training...

  15. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different training...

  16. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different training...

  17. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 2 2014-04-01 2014-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... Proficiency examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different...

  18. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different training...

  19. Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4,5)P2 and maintenance of KCNQ2/3 ion channel current

    PubMed Central

    Dickson, Eamonn J.; Jensen, Jill B.; Hille, Bertil

    2014-01-01

    Plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates the activity of many ion channels and other membrane-associated proteins. To determine precursor sources of the PM PI(4,5)P2 pool in tsA-201 cells, we monitored KCNQ2/3 channel currents and translocation of PHPLCδ1 domains as real-time indicators of PM PI(4,5)P2, and translocation of PHOSH2×2, and PHOSH1 domains as indicators of PM and Golgi phosphatidylinositol 4-phosphate [PI(4)P], respectively. We selectively depleted PI(4)P pools at the PM, Golgi, or both using the rapamycin-recruitable lipid 4-phosphatases. Depleting PI(4)P at the PM with a recruitable 4-phosphatase (Sac1) results in a decrease of PI(4,5)P2 measured by electrical or optical indicators. Depleting PI(4)P at the Golgi with the 4-phosphatase or disrupting membrane-transporting motors induces a decline in PM PI(4,5)P2. Depleting PI(4)P simultaneously at both the Golgi and the PM induces a larger decrease of PI(4,5)P2. The decline of PI(4,5)P2 following 4-phosphatase recruitment takes 1–2 min. Recruiting the endoplasmic reticulum (ER) toward the Golgi membranes mimics the effects of depleting PI(4)P at the Golgi, apparently due to the trans actions of endogenous ER Sac1. Thus, maintenance of the PM pool of PI(4,5)P2 appears to depend on precursor pools of PI(4)P both in the PM and in the Golgi. The decrease in PM PI(4,5)P2 when Sac1 is recruited to the Golgi suggests that the Golgi contribution is ongoing and that PI(4,5)P2 production may be coupled to important cell biological processes such as membrane trafficking or lipid transfer activity. PMID:24843134

  20. Instability of isochromosome 4p in a child with pure trisomy 4p syndrome features and entire 4q-arm translocation.

    PubMed

    Pota, Pruthvi; Grammatopoulou, Vasiliki; Torti, Erin; Braddock, Stephen; Batanian, Jacqueline R

    2014-01-01

    Constitutional chromosome instability so far has mainly been associated with ring formation. In addition, isochromosome formation involving the short arm with translocation of the entire long arm is rarely observed. This type of rearrangement has been reported for chromosomes 4, 5, 7, 9, 10, 12, and 20. Here, we present the third patient having an isochromosome 4p with 4q translocation, but showing for the first time chromosome instability detected by FISH following chromosome microarray analysis.

  1. Lanthanide ion (III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (DOTA-4AmP8−) for dual biosensing of pH with CEST (chemical exchange saturation transfer) and BIRDS (biosensor imaging of redundant deviation in shifts)

    PubMed Central

    Huang, Yuegao; Coman, Daniel; Ali, Meser M.; Hyder, Fahmeed

    2014-01-01

    Relaxivity based magnetic resonance of phosphonated ligands chelated with gadolinium (Gd3+) shows promise for pH imaging. However instead of monitoring the paramagnetic effect of lanthanide complexes on the relaxivity of water protons, biosensor (or molecular) imaging with magnetic resonance is also possible by detecting either the non-exchangeable or the exchangeable protons on the lanthanide complexes themselves. The non-exchangeable protons (e.g., –CHx, where 3≥x≥1) are detected using a three-dimensional chemical shift imaging method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), whereas the exchangeable protons (e.g., –OH or –NHy, where 2≥y≥1) are measured with Chemical Exchange Saturation Transfer (CEST) contrast. Here we tested the feasibility of BIRDS and CEST for pH imaging of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (DOTA-4AmP8−) chelated with thulium (Tm3+) and ytterbium (Yb3+). BIRDS and CEST experiments show that both complexes are responsive to pH and temperature changes. Higher pH and temperature sensitivities are obtained with BIRDS for either complex when using the chemical shift difference between two proton resonances vs. using the chemical shift of a single proton resonance, thereby eliminating the need to use water resonance as reference. While CEST contrast for both agents is linearly dependent on pH within a relatively large range (i.e., 6.3-7.9), much stronger CEST contrast is obtained with YbDOTA-4AmP5− than with TmDOTA-4AmP5−. In addition, we demonstrate the prospect of using BIRDS to calibrate CEST as new platform for quantitative pH imaging. PMID:24801742

  2. WARM SPITZER PHOTOMETRY OF THREE HOT JUPITERS: HAT-P-3b, HAT-P-4b AND HAT-P-12b

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

    Todorov, Kamen O.; Deming, Drake; Knutson, Heather A.

    2013-06-20

    We present Warm Spitzer/IRAC secondary eclipse time series photometry of three short-period transiting exoplanets, HAT-P-3b, HAT-P-4b and HAT-P-12b, in both the available 3.6 and 4.5 {mu}m bands. HAT-P-3b and HAT-P-4b are Jupiter-mass objects orbiting an early K and an early G dwarf star, respectively. For HAT-P-3b we find eclipse depths of 0.112%+0.015%-0.030% (3.6 micron) and 0.094%+0.016%-0.009% (4.5 {mu}m). The HAT-P-4b values are 0.142%+0.014%-0.016% (3.6 micron) and 0.122%+0.012%-0.014% 4.5 {mu}m). The two planets' photometry is consistent with inefficient heat redistribution from their day to night sides (and low albedos), but it is inconclusive about possible temperature inversions in their atmospheres. HAT-P-12bmore » is a Saturn-mass planet and is one of the coolest planets ever observed during secondary eclipse, along with the hot Neptune GJ 436b and the hot Saturn WASP-29b. We are able to place 3{sigma} upper limits on the secondary eclipse depth of HAT-P-12b in both wavelengths: <0.042% (3.6 {mu}m) and <0.085% (4.5 {mu}m). We discuss these results in the context of the Spitzer secondary eclipse measurements of GJ 436b and WASP-29b. It is possible that we do not detect the eclipses of HAT-P-12b due to high eccentricity, but find that weak planetary emission in these wavelengths is a more likely explanation. We place 3{sigma} upper limits on the |e cos {omega}| quantity (where e is eccentricity and {omega} is the argument of periapsis) for HAT-P-3b (<0.0081) and HAT-P-4b (<0.0042), based on the secondary eclipse timings.« less

  3. LDEF Experiment P0006 Linear Energy Transfer Spectrum Measurement (LETSME) quick look report

    NASA Technical Reports Server (NTRS)

    1990-01-01

    A preliminary analysis of the various passive radiation detector materials included in the P0006 LETSME experiment flown on LDEF (Long Duration Exposure Facility) is presented. It consists of four tasks: (1) readout and analysis of thermoluminescent detectors (TLD); (2) readout and analysis of fission foil/mica detectors; (3) readout and analysis of (6)LiF/CR-39 detectors; and (4) preliminary processing and readout of CR-39 and polycarbonate plastic nuclear track detectors (PNTD).

  4. Wolf-Hirschhorn (4p-) syndrome: prenatal diagnosis, molecular cytogenetic characterization and association with a 1.2-Mb microduplication at 8p22-p21.3 and a 1.1-Mb microduplication at 10p15.3 in a fetus with an apparently pure 4p deletion.

    PubMed

    Chen, Chih-Ping; Su, Yi-Ning; Chen, Yi-Yung; Su, Jun-Wei; Chern, Schu-Rern; Chen, Yu-Ting; Chen, Wen-Lin; Chen, Li-Feng; Wang, Wayseen

    2011-12-01

    To present prenatal diagnosis and molecular cytogenetic characterization of Wolf-Hirschhorn syndrome (WHS) associated with microduplications at 8p and 10p in a fetus with an apparently pure 4p deletion. A 35-year-old gravida 2, para 1 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Her husband was 38 years of age. There was no family history of congenital malformations. Amniocentesis revealed a karyotype of 46,XY,del(4p16.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 6.5-Mb deletion at 4p16.3-p16.1, a 1.2-Mb microduplication at 8p22-p21.3, and a 1.1-Mb microduplication at 10p15.3, or arr cgh 4p16.3p16.1 (0-6,531,998 bp)×1, 8p22p21.3 (18,705,388-19,940,445 bp)×3, 10p15.3 (0-1,105,065 bp)×3. Polymorphic DNA marker analysis confirmed a paternal origin of 4p deletion. Prenatal ultrasound revealed facial dysmorphism and hypospadias. The aCGH analysis of the parents revealed no genomic imbalance. Fluorescence in situ hybridization study showed an unbalanced reciprocal translocation between chromosomes 4 and 10 at bands 4p16.1 and 10p15.3. The cytogenetic result, thus, was 46,XY,der(4)t(4;10)(p16.1;p15.3),dup(8)(p21.3p22). The parents elected to terminate the pregnancy, and a 470-g malformed fetus was delivered. The present case provides evidence that an apparently pure 4p deletion can be associated with subtle chromosome imbalances in other chromosomes. Copyright © 2011. Published by Elsevier B.V.

  5. PI(4,5)P2-binding effector proteins for vesicle exocytosis

    PubMed Central

    Martin, Thomas F. J.

    2014-01-01

    PI(4,5)P2 participates directly in priming and possibly fusion steps of Ca2+-triggered vesicle exocytosis. High concentration nanodomains of PI(4,5)P2 reside on the plasma membrane of neuroendocrine cells. A subset of vesicles that co-localize with PI(4,5)P2 domains appear to undergo preferential exocytosis in stimulated cells. PI(4,5)P2 directly regulates vesicle exocytosis by recruiting and activating PI(4,5)P2-binding proteins that regulate SNARE protein function including CAPS, Munc13-1/2, synaptotagmin-1, and other C2 domain-containing proteins. These PI(4,5)P2 effector proteins are coincidence detectors that engage in multiple interactions at vesicle exocytic sites. The SNARE protein syntaxin-1 also binds to PI(4,5)P2, which promotes clustering, but an activating role for PI(4,5)P2 in syntaxin-1 function remains to be fully characterized. Similar principles underlie polarized constitutive vesicle fusion mediated in part by the PI(4,5)P2-binding subunits of the exocyst complex (Sec3, Exo70). Overall, focal vesicle exocytosis occurs at sites landmarked by PI(4,5)P2, which serves to recruit and/or activate multifunctional PI(4,5)P2-binding proteins. PMID:25280637

  6. Human Liver Cytochrome P450 3A4 Ubiquitination

    PubMed Central

    Wang, YongQiang; Kim, Sung-Mi; Trnka, Michael J.; Liu, Yi; Burlingame, A. L.; Correia, Maria Almira

    2015-01-01

    CYP3A4 is an abundant and catalytically dominant human liver endoplasmic reticulum-anchored cytochrome P450 enzyme engaged in the biotransformation of endo- and xenobiotics, including >50% of clinically relevant drugs. Alterations of CYP3A4 protein turnover can influence clinically relevant drug metabolism and bioavailability and drug-drug interactions. This CYP3A4 turnover involves endoplasmic reticulum-associated degradation via the ubiquitin (Ub)-dependent 26 S proteasomal system that relies on two highly complementary E2 Ub-conjugating-E3 Ub-ligase (UBC7-gp78 and UbcH5a-C terminus of Hsc70-interacting protein (CHIP)-Hsc70-Hsp40) complexes, as well as protein kinases (PK) A and C. We have documented that CYP3A4 Ser/Thr phosphorylation (Ser(P)/Thr(P)) by PKA and/or PKC accelerates/enhances its Lys ubiquitination by either of these E2-E3 systems. Intriguingly, CYP3A4 Ser(P)/Thr(P) and ubiquitinated Lys residues reside within the cytosol-accessible surface loop and/or conformationally assembled acidic Asp/Glu clusters, leading us to propose that such post-translational Ser/Thr protein phosphorylation primes CYP3A4 for ubiquitination. Herein, this possibility was examined through various complementary approaches, including site-directed mutagenesis, chemical cross-linking, peptide mapping, and LC-MS/MS analyses. Our findings reveal that such CYP3A4 Asp/Glu/Ser(P)/Thr(P) surface clusters are indeed important for its intermolecular electrostatic interactions with each of these E2-E3 subcomponents. By imparting additional negative charge to these Asp/Glu clusters, such Ser/Thr phosphorylation would generate P450 phosphodegrons for molecular recognition by the E2-E3 complexes, thereby controlling the timing of CYP3A4 ubiquitination and endoplasmic reticulum-associated degradation. Although the importance of phosphodegrons in the CHIP targeting of its substrates is known, to our knowledge this is the first example of phosphodegron involvement in gp78-substrate

  7. Homogeneous nucleation of water in argon. Nucleation rate computation from molecular simulations of TIP4P and TIP4P/2005 water model.

    PubMed

    Dumitrescu, Lucia R; Smeulders, David M J; Dam, Jacques A M; Gaastra-Nedea, Silvia V

    2017-02-28

    Molecular dynamics (MD) simulations were conducted to study nucleation of water at 350 K in argon using TIP4P and TIP4P/2005 water models. We found that the stability of any cluster, even if large, strongly depends on the energetic interactions with its vicinity, while the stable clusters change their composition almost entirely during nucleation. Using the threshold method, direct nucleation rates are obtained. Our nucleation rates are found to be 1.08×10 27 cm -3 s -1 for TIP4P and 2.30×10 27 cm -3 s -1 for TIP4P/2005. The latter model prescribes a faster dynamics than the former, with a nucleation rate two times larger due to its higher electrostatic charges. The non-equilibrium water densities derived from simulations and state-of-art equilibrium parameters from Vega and de Miguel [J. Chem. Phys. 126, 154707 (2007)] are used for the classical nucleation theory (CNT) prediction. The CNT overestimates our results for both water models, where TIP4P/2005 shows largest discrepancy. Our results complement earlier data at high nucleation rates and supersaturations in the Hale plot [Phys. Rev. A 33, 4156 (1986)], and are consistent with MD data on the SPC/E and the TIP4P/2005 model.

  8. Semiconducting cubic titanium nitride in the Th 3 P 4 structure

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

    Bhadram, Venkata S.; Liu, Hanyu; Xu, Enshi

    We report the discovery of a long-sought-after phase of titanium nitride with stoichiometry Ti 3 N 4 using diamond anvil cell experiments combined with in situ high-resolution x-ray diffraction and Raman spectroscopy techniques, supported by ab initio calculations. Ti 3 N 4 crystallizes in the cubic Th 3 P 4 structure [space group I ¯ 4 3 d (220)] from a mixture of TiN and N 2 above ≈ 75 GPa and ≈ 2400 K. The density ( ≈ 5.22 g/cc) and bulk modulus ( K 0 = 290 GPa) of cubic- Ti 3 N 4 ( c - Timore » 3 N 4 ) at 1 atm, estimated from the pressure-volume equation of state, are comparable to rocksalt TiN. Ab initio calculations based on the GW approximation and using hybrid functionals indicate that c - Ti 3 N 4 is a semiconductor with a direct band gap between 0.8 and 0.9 eV, which is larger than the previously predicted values. The c - Ti 3 N 4 phase is not recoverable to ambient pressure due to dynamic instabilities, but recovery of Ti 3 N 4 in the defect rocksalt (or related) structure may be feasible.« less

  9. Crystallization of recombinant Haemophilus influenzaee (P4) acid phosphatase

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

    Ou, Zhonghui; Felts, Richard L.; Reilly, Thomas J.

    2006-05-01

    Lipoprotein e (P4) is a class C acid phosphatase and a potential vaccine candidate for nontypeable H. influenzae infections. This paper reports the crystallization of recombinant e (P4) and the acquisition of a 1.7 Å resolution native X-ray diffraction data set. Haemophilus influenzae infects the upper respiratory tract of humans and can cause infections of the middle ear, sinuses and bronchi. The virulence of the pathogen is thought to involve a group of surface-localized macromolecular components that mediate interactions at the host–pathogen interface. One of these components is lipoprotein e (P4), which is a class C acid phosphatase and amore » potential vaccine candidate for nontypeable H. influenzae infections. This paper reports the crystallization of recombinant e (P4) and the acquisition of a 1.7 Å resolution native X-ray diffraction data set. The space group is P4{sub 2}2{sub 1}2, with unit-cell parameters a = 65.6, c = 101.4 Å, one protein molecule per asymmetric unit and 37% solvent content. This is the first report of the crystallization of a class C acid phosphatase.« less

  10. Mapping the involvement of BA 4a and 4p during Motor Imagery.

    PubMed

    Sharma, Nikhil; Jones, P S; Carpenter, T A; Baron, Jean-Claude

    2008-05-15

    Motor Imagery (MI) is an attractive but intriguing means to access the motor network. There are marked inconsistencies in the functional imaging literature regarding the degree, extent and distribution of the primary motor cortex (BA 4) involvement during MI as compared to Executed Movement (EM), which may in part be related to the diverse role of BA 4 and its two subdivisions (i.e., 4a and 4p) in motor processes as well as to methodological issues. Here we used fMRI with monitoring of compliance to show that in healthy volunteers optimally screened for their ability to perform MI the contralateral BA 4 is involved during MI of a finger opposition sequence (2, 3, 4, 5; paced at 1 Hz), albeit less than during EM of the same sequence, and in a location sparing the hand area. Furthermore, both 4a and 4p subdivisions were found to be involved in MI, but the relative involvement of BA 4p appeared more robust and closer to that seen with EM. We suggest that during MI the role of BA 4 and its subdivisions may be non-executive, perhaps related to spatial encoding, though clearly further studies are needed. Finally, we report a similar hemispheric activation balance within BA 4 with both tasks, which extends the commonalities between EM and MI.

  11. Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography

    PubMed Central

    Elmaleh, D. R.; Fischman, A. J.; Tawakol, A.; Zhu, A.; Shoup, T. M.; Hoffmann, U.; Brownell, A.-L.; Zamecnik, P. C.

    2006-01-01

    Diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and its analog P2,P3-monochloromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P2,P3-[18F]monofluoromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate ([18F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [18F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [18F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [18F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [18F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [18F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation. PMID:17038498

  12. Prognostic significance of p16INK4a/p53 in Tunisian patients with breast carcinoma.

    PubMed

    Karray-Chouayekh, Sondes; Baccouche, Sami; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Daoud, Jamel; Frikha, Mounir; Jlidi, Rachid; Gargouri, Ali; Mokdad-Gargouri, Raja

    2011-09-01

    Infiltrating ductal carcinoma (IDC) of the breast is a result of genetic alterations that affect the regulation of the cell cycle check-point and apoptosis. The aim of the present study was analysis using immunohistochemical localization of mouse double minute-2 (mdm2), p16INK4a, p53, bax and bcl-2 markers in Tunisian patients with breast IDC and to determine if there was correlation with the major clinico-pathological parameters and with survival of patients. We showed that the expression of p53, p16INK4a, mdm2, bcl-2, and bax was observed in 46.3%, 20.7%, 38%, 50% and 11.9% of cases, respectively. Statistical analysis revealed that positive expression of mdm2 was associated with larger tumors (P=0.013), whereas bax positivity was more prevalent in younger patients and in tumors of smaller size (P=0.008 and P=0.012 respectively). Furthermore, the expression of p16INK4a correlated with advanced grade (P<0.0001), triple negative tumors (ER-/PR-/HER2-, P=0.001) and mdm2 expression (P=0.017). The absence of nuclear p53 accumulation was predictive of good prognosis as well as when it was associated with negative expression of p16INK4a. Our findings suggest that among the biomarkers tested, p16INK4a might have a useful clinical and prognostic significance in infiltrating ductal carcinoma of the breast. Copyright © 2010 Elsevier GmbH. All rights reserved.

  13. The response of abyssal organisms to low pH conditions during a series of CO2-release experiments simulating deep-sea carbon sequestration

    NASA Astrophysics Data System (ADS)

    Barry, J. P.; Buck, K. R.; Lovera, C.; Brewer, P. G.; Seibel, B. A.; Drazen, J. C.; Tamburri, M. N.; Whaling, P. J.; Kuhnz, L.; Pane, E. F.

    2013-08-01

    The effects of low-pH, high-pCO2 conditions on deep-sea organisms were examined during four deep-sea CO2 release experiments simulating deep-ocean C sequestration by the direct injection of CO2 into the deep sea. We examined the survival of common deep-sea, benthic organisms (microbes; macrofauna, dominated by Polychaeta, Nematoda, Crustacea, Mollusca; megafauna, Echinodermata, Mollusca, Pisces) exposed to low-pH waters emanating as a dissolution plume from pools of liquid carbon dioxide released on the seabed during four abyssal CO2-release experiments. Microbial abundance in deep-sea sediments was unchanged in one experiment, but increased under environmental hypercapnia during another, where the microbial assemblage may have benefited indirectly from the negative impact of low-pH conditions on other taxa. Lower abyssal metazoans exhibited low survival rates near CO2 pools. No urchins or holothurians survived during 30-42 days of exposure to episodic, but severe environmental hypercapnia during one experiment (E1; pH reduced by as much as ca. 1.4 units). These large pH reductions also caused 75% mortality for the deep-sea amphipod, Haploops lodo, near CO2 pools. Survival under smaller pH reductions (ΔpH<0.4 units) in other experiments (E2, E3, E5) was higher for all taxa, including echinoderms. Gastropods, cephalopods, and fish were more tolerant than most other taxa. The gastropod Retimohnia sp. and octopus Benthoctopus sp. survived exposure to pH reductions that episodically reached -0.3 pH units. Ninety percent of abyssal zoarcids (Pachycara bulbiceps) survived exposure to pH changes reaching ca. -0.3 pH units during 30-42 day-long experiments.

  14. Isotope shift of 40,42,44,48Ca in the 4s 2S1/2 → 4p 2P3/2 transition

    NASA Astrophysics Data System (ADS)

    Gorges, C.; Blaum, K.; Frömmgen, N.; Geppert, Ch; Hammen, M.; Kaufmann, S.; Krämer, J.; Krieger, A.; Neugart, R.; Sánchez, R.; Nörtershäuser, W.

    2015-12-01

    We report on improved isotope shift measurements of the isotopes {}{40,42,{44,48}}Ca in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}3/2 (D2) transition using collinear laser spectroscopy. Accurately known isotope shifts in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}1/2(D1) transition were used to calibrate the ion beam energy with an uncertainty of {{Δ }}U≈ +/- 0.25 {{V}}. The accuracy in the D2 transition was improved by a factor of 5-10. A King-plot analysis of the two transitions revealed that the field shift factor in the D2 line is about 1.8(13)% larger than in the D1 transition which is ascribed to relativistic contributions of the 4{{{p}}}1/2 wave function.

  15. Prenatal recognition of 4p- syndrome.

    PubMed Central

    Blunt, S; Berry, A C; Seller, M J; Williams, C A

    1977-01-01

    A fetus with the rare 4p- syndrome was detected by chromosome analysis of amniotic cell culture, and the pregnancy terminated. The fetus showed a number of the physical stigmata of the syndrome. Images PMID:881719

  16. Vba4p, a vacuolar membrane protein, is involved in the drug resistance and vacuolar morphology of Saccharomyces cerevisiae.

    PubMed

    Kawano-Kawada, Miyuki; Pongcharoen, Pongsanat; Kawahara, Rieko; Yasuda, Mayu; Yamasaki, Takashi; Akiyama, Koichi; Sekito, Takayuki; Kakinuma, Yoshimi

    2016-01-01

    In the vacuolar basic amino acid (VBA) transporter family of Saccharomyces cerevisiae, VBA4 encodes a vacuolar membrane protein with 14 putative transmembrane helices. Transport experiments with isolated vacuolar membrane vesicles and estimation of the amino acid contents in vacuoles showed that Vba4p is not likely involved in the transport of amino acids. We found that the vba4Δ cells, as well as vba1Δ and vba2Δ cells, showed increased susceptibility to several drugs, particularly to azoles. Although disruption of the VBA4 gene did not affect the salt tolerance of the cells, vacuolar fragmentation observed under high salt conditions was less prominent in vba4Δ cells than in wild type, vba1Δ, and vba2Δ cells. Vba4p differs from Vba1p and Vba2p as a vacuolar transporter but is important for the drug resistance and vacuolar morphology of S. cerevisiae.

  17. Elevated levels of p-Mnk1, p-eIF4E and p-p70S6K proteins are associated with tumor recurrence and poor prognosis in astrocytomas.

    PubMed

    Fan, Weibing; Wang, Weiyuan; Mao, Xinfa; Chu, Shuzhou; Feng, Juan; Xiao, Desheng; Zhou, Jianhua; Fan, Songqing

    2017-02-01

    Malignant astrocytomas are able to invade neighboring and distant areas of the normal brain. Signaling pathway alterations play important role in the development of astrocytomas. Deregulation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 directly or PI3K/mTOR/S6K pathway indirectly has a critical effect on promoting cellular proliferation, malignant transformation and metastasis. We examined and analyzed the correlation between expression of p-Mnk1, p-eIF4E and p-p70S6K proteins and clinicopathological features in 103 astrocytomas and 54 non-tumorous brain tissues. The results indicated that positive percentage of overexpression of p-Mnk1 and p-eIF4E proteins in astrocytomas were significantly higher than that of in the non-tumorous brain tissues (P < 0.05). Elevated p-Mnk1 and p-eIF4E and co-overexpressed three proteins were associated with tumor recurrence (P = 0.003, P = 0.006, P = 0.007, respectively). Overexpressed p-eIF4E significantly correlated with the tumor size (P = 0.019). In addition, overexpression of p-eIF4E and three proteins common expression were related to the WHO grade of astrocytomas (P = 0.001, P = 0.044 respectively). Spearman's rank correlation test further showed that the expression of p-Mnk1 was strongly positive correlated with the expression of p-eIF4E in astrocytomas (r = 0.294, P = 0.003). Besides, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins were inversely correlated with overall survival rates of astrocytomas. Multivariate Cox regression analysis further identified that the elevated p-eIF4E expression, three proteins common expression were correlated with unfavorable prognosis of astrocytomas regardless of ages and WHO grades. Taken together, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins could be used as novel independent poor prognostic biomarkers for patients

  18. Structural insights into the p97-Ufd1-Npl4 complex

    PubMed Central

    Pye, Valerie E.; Beuron, Fabienne; Keetch, Catherine A.; McKeown, Ciaran; Robinson, Carol V.; Meyer, Hemmo H.; Zhang, Xiaodong; Freemont, Paul S.

    2007-01-01

    p97/VCP (Cdc48 in yeast) is an essential and abundant member of the AAA+ family of ATPases and is involved in a number of diverse cellular pathways through interactions with different adaptor proteins. The two most characterized adaptors for p97 are p47 and the Ufd1 (ubiquitin fusion degradation 1)-Npl4 (nuclear protein localization 4) complex. p47 directs p97 to membrane fusion events and has been shown to be involved in protein degradation. The Ufd1-Npl4 complex directs p97 to an essential role in endoplasmic reticulum-associated degradation and an important role in mitotic spindle disassembly postmitosis. Here we describe the structural features of the Ufd1-Npl4 complex and its interaction with p97 with the aid of EM and other biophysical techniques. The Ufd1-Npl4 heterodimer has an elongated bilobed structure that is ≈80 × 30 Å in dimension. One Ufd1-Npl4 heterodimer is shown to interact with one p97 hexamer to form the p97-Ufd1-Npl4 complex. The Ufd1-Npl4 heterodimer emanates from one region on the periphery of the N-D1 plane of the p97 hexamer. Intriguingly, the p97-p47 and the p97-Ufd1-Npl4 complexes are significantly different in stoichiometry, symmetry, and quaternary arrangement, reflecting their specific actions and their ability to interact with additional cofactors that cooperate with p97 in diverse cellular pathways. PMID:17202270

  19. Differential coexpression of FoxP1, FoxP2, and FoxP4 in the Zebra Finch (Taeniopygia guttata) song system.

    PubMed

    Mendoza, Ezequiel; Tokarev, Kirill; Düring, Daniel N; Retamosa, Eva Camarillo; Weiss, Michael; Arpenik, Nshdejan; Scharff, Constance

    2015-06-15

    Heterozygous disruptions of the Forkhead transcription factor FoxP2 impair acquisition of speech and language. Experimental downregulation in brain region Area X of the avian ortholog FoxP2 disrupts song learning in juvenile male zebra finches. In vitro, transcriptional activity of FoxP2 requires dimerization with itself or with paralogs FoxP1 and FoxP4. Whether this is the case in vivo is unknown. To provide the means for future functional studies we cloned FoxP4 from zebra finches and compared regional and cellular coexpression of FoxP1, FoxP2, and FoxP4 mRNA and protein in brains of juvenile and adult male zebra finches. In the telencephalic song nuclei HVC, RA, and Area X, the three investigated FoxPs were either expressed alone or occurred in specific combinations with each other, as shown by double in situ hybridization and triple immunohistochemistry. FoxP1 and FoxP4 but not FoxP2 were expressed in RA and in the HVCRA and HVCX projection neurons. In Area X and the surrounding striatum the density of neurons expressing all three FoxPs together or FoxP1 and FoxP4 together was significantly higher than the density of neurons expressing other combinations. Interestingly, the proportions of Area X neurons expressing particular combinations of FoxPs remained constant at all ages. In addition, FoxP-expressing neurons in adult Area X express dopamine receptors 1A, 1B, and 2. Together, these data provide the first evidence that Area X neurons can coexpress all avian FoxP subfamily members, thus allowing for a variety of regulatory possibilities via heterodimerization that could impact song behavior in zebra finches. © 2014 Wiley Periodicals, Inc.

  20. Functionalization of P4 through Direct P-C Bond Formation.

    PubMed

    Borger, Jaap E; Ehlers, Andreas W; Slootweg, J Chris; Lammertsma, Koop

    2017-09-04

    Research on chlorine-free conversions of P 4 into organophosphorus compounds (OPCs) has a long track record, but methods that allow desirable, direct P-C bond formations have only recently emerged. These include the use of metal organyls, carbenes, carboradicals, and photochemical approaches. The versatile product scope enables the preparation of both industrially relevant organophosphorus compounds, as well as a broad range of intriguing new compound classes. Herein we provide a concise overview of recent breakthroughs and outline the acquired fundamental insights to aid future developments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Pump-probe photoelectron velocity-map imaging of autoionizing singly excited 4s{sup 1}4p{sup 6}np{sup 1}(n=7,8) and doubly excited 4s{sup 2}4p{sup 4}5s{sup 1}6p{sup 1} resonances in atomic krypton

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

    Doughty, Benjamin; Haber, Louis H.; Leone, Stephen R.

    2011-10-15

    Pump-probe photoelectron velocity-map imaging, using 27-eV high-harmonic excitation and 786-nm ionization, is used to resolve overlapping autoionizing resonances in atomic krypton, obtaining two-photon photoelectron angular distributions (PADs) for singly and doubly excited states. Two features in the photoelectron spectrum are assigned to singly excited 4s{sup 1}4p{sup 6}np{sup 1} (n = 7,8) configurations and four features provide information about double excitation configurations. The anisotropy parameters for the singly excited 7p configuration are measured to be {beta}{sub 2} = 1.61 {+-} 0.06 and {beta}{sub 4} = 1.54 {+-} 0.16 while the 8p configuration gives {beta}{sub 2} = 1.23 {+-} 0.19 and {beta}{submore » 4} = 0.60 {+-} 0.15. These anisotropies most likely represent the sum of overlapping PADs from states of singlet and triplet spin multiplicities. Of the four bands corresponding to ionization of doubly excited states, two are assigned to 4s{sup 2}4p{sup 4}5s{sup 1}6p{sup 1} configurations that are probed to different J-split ion states. The two remaining doubly excited states are attributed to a previously observed, but unassigned, resonance in the vacuum-ultraviolet photoabsorption spectrum. The PADs from each of the double excitation states are also influenced by overlap from neighboring states that are not completely spectrally resolved. The anisotropies of the observed double excitation states are reported, anticipating future theoretical and experimental work to separate the overlapping PADs into the state resolved PADs. The results can be used to test theories of excited state ionization.« less

  2. Toxicological properties of white phosphorus (P{sub 4}): Effect of particle size

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

    Roebuck, B.D.; Nam, S.I.

    1995-12-31

    The ingestion of particles of white phosphorus (P{sub 4}) causes mortality of waterfowl at Eagle River Flats, Alaska. P{sub 4} poisoning results in behaviors that attract predators. To date, the toxic properties of P{sub 4} have been characterized when P{sub 4} is dissolved in various digestible oils. Herein, the authors compare the properties of dissolved P{sub 4} to particulate P{sub 4}. Farm-reared mallards (Anas Platvrhynchos) were gavaged with P{sub 4} (12 mg/kg body weight) dissolved in oil, large particles (1.87 mm mean diameter), or small particles (0.95 mm diameter). Signs of intoxication and times to convulsion were monitored. Individuals weremore » autopsied at the onset of convulsions. P{sub 4} in digestive tracts and body fat was analyzed by gas chromatography. For all 3 treatments, the behaviors of P{sub 4} intoxication were similar to observations of wild ducks. There was no difference between treatments for onset of lethargy, vomiting, poor motor/muscle control, or the first convulsive event. At autopsy, P{sub 4} was found throughout the digestive tracts with residual quantities of approximately 20% or less of the dose. Very little of the dissolved P{sub 4} remained in gizzards; whereas, in the small and large particle groups, the gizzard contents contained 78% and 64%, respectively, of the total P{sub 4} within the digestive tracts. Tissue concentrations of P{sub 4} were small and did not appear to be a significant source of P{sub 4} to predators. In conclusion, intoxication from particles of P{sub 4} is largely not a function of the size of the particles, but rather the dose. Residual P{sub 4} in the digestive tracts represents a risk to secondary receptors. These relative risks of particulate P{sub 4} to tissue P{sub 4} are somewhat similar to poisoning from lead shot.« less

  3. Neurodevelopmental disorders among individuals with duplication of 4p13 to 4p12 containing a GABAA receptor subunit gene cluster

    PubMed Central

    Polan, Michelle B; Pastore, Matthew T; Steingass, Katherine; Hashimoto, Sayaka; Thrush, Devon L; Pyatt, Robert; Reshmi, Shalini; Gastier-Foster, Julie M; Astbury, Caroline; McBride, Kim L

    2014-01-01

    Recent studies have shown that certain copy number variations (CNV) are associated with a wide range of neurodevelopmental disorders, including autism spectrum disorders (ASD), bipolar disorder and intellectual disabilities. Implicated regions and genes have comprised a variety of post synaptic complex proteins and neurotransmitter receptors, including gamma-amino butyric acid A (GABAA). Clusters of GABAA receptor subunit genes are found on chromosomes 4p12, 5q34, 6q15 and 15q11-13. Maternally inherited 15q11-13 duplications among individuals with neurodevelopmental disorders are well described, but few case reports exist for the other regions. We describe a family with a 2.42 Mb duplication at chromosome 4p13 to 4p12, identified in the index case and other family members by oligonucleotide array comparative genomic hybridization, that contains 13 genes including a cluster of four GABAA receptor subunit genes. Fluorescent in-situ hybridization was used to confirm the duplication. The duplication segregates with a variety of neurodevelopmental disorders in this family, including ASD (index case), developmental delay, dyspraxia and ADHD (brother), global developmental delays (brother), learning disabilities (mother) and bipolar disorder (maternal grandmother). In addition, we identified and describe another individual unrelated to this family, with a similar duplication, who was diagnosed with ASD, ADHD and borderline intellectual disability. The 4p13 to 4p12 duplication appears to confer a susceptibility to a variety of neurodevelopmental disorders in these two families. We hypothesize that the duplication acts through a dosage effect of GABAA receptor subunit genes, adding evidence for alterations in the GABAergic system in the etiology of neurodevelopmental disorders. PMID:23695283

  4. Coupled potential energy surface for the F(2P)+CH4→HF+CH3 entrance channel and quantum dynamics of the CH4·F- photodetachment.

    PubMed

    Westermann, Till; Eisfeld, Wolfgang; Manthe, Uwe

    2013-07-07

    An approach to construct vibronically and spin-orbit coupled diabatic potential energy surfaces (PESs) which describe all three relevant electronic states in the entrance channels of the X(P) + CH4 →HX + CH3 reactions (with X=F((2)P), Cl((2)P), or O((3)P)) is introduced. The diabatization relies on the permutational symmetry present in the methane molecule and results in diabatic states which transform as the three p orbitals of the X atom. Spin-orbit coupling is easily and accurately included using the atomic spin-orbit coupling matrix of the isolated X atom. The method is applied to the F + CH4 system obtaining an accurate PES for the entrance channel based on ab initio multi-reference configuration interaction (MRCI) calculations. Comparing the resulting PESs with spin-orbit MRCI calculations, excellent agreement is found for the excited electronic states at all relevant geometries. The photodetachment spectrum of CH4·F(-) is investigated via full-dimensional (12D) quantum dynamics calculations on the coupled PESs using the multi-layer multi-configurational time-dependent Hartree approach. Extending previous work [J. Palma and U. Manthe, J. Chem. Phys. 137, 044306 (2012)], which was restricted to the dynamics on a single adiabatic PES, the contributions of the electronically excited states to the photodetachment spectrum are calculated and compared to experiment. Considering different experimental setups, good agreement between experiment and theory is found. Addressing questions raised in the previous work, the present dynamical calculations show that the main contribution to the second peak in the photodetachment spectrum results from electron detachment into the electronically excited states of the CH4F complex.

  5. Cytochrome P4501A induction, benzo[a]pyrene metabolism, and nucleotide adduct formation in fish hepatoma cells: Effect of preexposure to 3,3',4,4',5-pentachlorobiphenyl

    USGS Publications Warehouse

    Smeets, J.M.W.; Voormolen, A.; Tillitt, D.E.; Everaarts, J.M.; Seinen, W.; Vanden Berg, M.D.

    1999-01-01

    In PLHC-1 hepatoma cells, benzo[a]pyrene (B[a]P) caused a maximum induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O-deethylation (EROD), after 4 to 8 h of exposure, depending on the B[a]P concentration. The decline of EROD activity at longer exposure times was probably caused by the rapid metabolism of B[a]P in this system (57% metabolism within 4 h incubation). In subsequent experiments, PLHC-1 cells were preinduced with PCB 126 for 24 h and then received a dose of 10, 100, or 1,000 nM 3H-B[a]P. A 1-nM concentration of PCB 126 caused an 80-fold induction of CYP1A activity, resulting in an increase in B[a]P metabolism of less than 10%, except at the highest concentration of B[a]P (1,000 nM), where a 50% increase was observed. In another experiment, an 80-fold induction of CYP1A activity caused a 20% increase in the metabolism of B[a]P (100 nM), and RNA adduct formation was increased approximately twofold. These results indicate that, at exposure concentrations up to 100 nM B[a]P, CYP1A activity is not rate limiting for B[a]P metabolism. Furthermore, CYP1A seems to also he specifically involved in B[a]P activation in PLHC-1 cells. However, CYP1A induction causes only a relatively small increase in activation, probably because of the action of other enzymes involved in B[a]P activation and deactivation.

  6. Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p–Rnr4p

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

    Ainsworth, William B.; Hughes, Bridget Todd; Au, Wei Chun

    2013-10-04

    Highlights: •Hug1p overexpression sensitizes wild-type cells to DNA damage and hydroxyurea (HU). •Expression of Hug1p in response to HU treatment is delayed relative to Rnr3p. •MEC1 pathway genes are required for cytoplasmic localization of Hug1p. •Hug1p subcellular compartmentalization to the cytoplasm coincides with Rnr2p–Rnr4p. -- Abstract: The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p–Rnr4p subunits and inactivation of negative regulatorsmore » Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p–Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p–Rnr4p.« less

  7. The effect of varying halogen substituent patterns on the cytochrome P450 catalysed dehalogenation of 4-halogenated anilines to 4-aminophenol metabolites.

    PubMed

    Cnubben, N H; Vervoort, J; Boersma, M G; Rietjens, I M

    1995-05-11

    The cytochrome P450 catalysed biotransformation of 4-halogenated anilines was studied in vitro with special emphasis on the dehalogenation to 4-aminophenol metabolites. The results demonstrated that a fluorine substituent at the C4 position was more easily eliminated from the aromatic ring than a chloro-, bromo- or iodo-substituent. HPLC analysis of in vitro biotransformation patterns revealed that the dehalogenation of the C4-position was accompanied by formation of non-halogenated 4-aminophenol, without formation of NIH-shifted metabolites. Changes in the apparent Vmax for the microsomal oxidative dehalogenation appeared to correlate with the electronegativity of the halogen substituent at C4, the fluorine substituent being the one most easily eliminated. A similar decrease in the rate of dehalogenation from a fluoro- to a chloro- to a bromo- to an iodo-substituent was observed in a system with purified reconstituted cytochrome P450 IIB1, in a tertiair butyl hydroperoxide supported microsomal cytochrome P450 system as well as in a system with microperoxidase 8. This microperoxidase 8 is a haem-based mini-enzyme without a substrate binding site, capable of catalysing cytochrome P450-like reaction chemistry. Together, these results excluded the possibility that the difference in the rate of dehalogenation with a varying C4-halogen substituent arose from a change in the contribution of cytochrome P450 enzymes involved in oxidative dehalogenation with a change in the halogen substituent. Rather, they strongly suggested that the difference was indeed due to an intrinsic electronic parameter of the various C4 halogenated anilines dependent on the type of halogen substituent. Additional in vitro experiments with polyfluorinated anilines demonstrated that elimination of the C4-fluorine substituent became more difficult upon the introduction of additional electron withdrawing fluorine substituents in the aniline-ring. 19F-NMR analysis of the metabolite patterns showed

  8. 5',5'''-P1, P4 diadenosine tetraphosphate (Ap4A): a putative initiator of DNA replication.

    PubMed

    Baril, E F; Coughlin, S A; Zamecnik, P C

    1985-01-01

    The proposal that Ap4A acts as an inducer of DNA replication is based primarily on two pieces of evidence (7). The intracellular levels of Ap4A increase ten- to 1000-fold as cells progress into S phase and the introduction of Ap4A into nonproliferating cells stimulated DNA synthesis. There is also some additional suggestive evidence such as the binding of Ap4A to a protein that is associated with multiprotein forms of the replicative DNA polymerase alpha and the ability of this enzyme to use Ap4A as a primer for DNA synthesis in vitro with single-stranded DNA templates. These observations have stimulated interest in the cellular metabolism of Ap4A. This is well since there is a great need for additional experimentation in order to clearly establish Ap4A as an inducer of DNA replication. Microinjection experiments of Ap4A into quiescent cells are needed in order to ascertain if Ap4A will stimulate DNA replication and possibly cell division in intact cells. Studies of the effects of nonhydrolyzable analogs of Ap4A on DNA replication in intact quiescent cells could also prove valuable. Although Ap4A can function as a primer for in vitro DNA synthesis by DNA polymerase alpha this may not be relevant in regard to its in vivo role in DNA replication. Ap4A in vivo could interact with key protein(s) in DNA replication and in this way act as an effector molecule in the initiation of DNA replication. In this regard the interaction of Ap4A with a protein associated with a multiprotein form of DNA polymerase alpha isolated from S-phase cells is of interest. More experiments are required to determine if there is a specific target protein(s) for Ap4A in vivo and what its role in DNA replication is. The cofractionation of tryptophanyl-tRNA synthetase with the replicative DNA polymerase alpha from animal and plant cells is of interest. The DNA polymerase alpha from synchronized animal cells also interacted with Ap4A. Although the plant cell alpha-like DNA polymerase did not

  9. Regulation of Cell Diameter, For3p Localization, and Cell Symmetry by Fission Yeast Rho-GAP Rga4p

    PubMed Central

    Das, Maitreyi; Wiley, David J.; Medina, Saskia; Vincent, Helen A.; Larrea, Michelle; Oriolo, Andrea

    2007-01-01

    Control of cellular dimensions and cell symmetry are critical for development and differentiation. Here we provide evidence that the putative Rho-GAP Rga4p of Schizosaccharomyces pombe controls cellular dimensions. rga4Δ cells are wider in diameter and shorter in length, whereas Rga4p overexpression leads to reduced diameter of the growing cell tip. Consistent with a negative role in cell growth control, Rga4p protein localizes to the cell sides in a “corset” pattern, and to the nongrowing cell tips. Additionally, rga4Δ cells show an altered growth pattern similar to that observed in mutants of the formin homology protein For3p. Consistent with these observations, Rga4p is required for normal localization of For3p and for normal distribution of the actin cytoskeleton. We show that different domains of the Rga4p protein mediate diverse morphological functions. The C-terminal GAP domain mediates For3p localization to the cell tips and maintains cell diameter. Conversely, overexpression of the N-terminal LIM homology domain of Rga4p promotes actin cable formation in a For3p-dependent manner. Our studies indicate that Rga4p functionally interacts with For3p and has a novel function in the control of cell diameter and cell growth. PMID:17377067

  10. Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-chlorophenyl)imidazole at 2.0-A resolution.

    PubMed

    Gay, Sean C; Shah, Manish B; Talakad, Jyothi C; Maekawa, Keiko; Roberts, Arthur G; Wilderman, P Ross; Sun, Ling; Yang, Jane Y; Huelga, Stephanie C; Hong, Wen-Xu; Zhang, Qinghai; Stout, C David; Halpert, James R

    2010-04-01

    The structure of the K262R genetic variant of human cytochrome P450 2B6 in complex with the inhibitor 4-(4-chlorophenyl)imidazole (4-CPI) has been determined using X-ray crystallography to 2.0-A resolution. Production of diffraction quality crystals was enabled through a combination of protein engineering, chaperone coexpression, modifications to the purification protocol, and the use of unique facial amphiphiles during crystallization. The 2B6-4-CPI complex is virtually identical to the rabbit 2B4 structure bound to the same inhibitor with respect to the arrangement of secondary structural elements and the placement of active site residues. The structure supports prior P450 2B6 homology models based on other mammalian cytochromes P450 and is consistent with the limited site-directed mutagenesis studies on 2B6 and extensive studies on P450 2B4 and 2B1. Although the K262R genetic variant shows unaltered binding of 4-CPI, altered binding affinity, kinetics, and/or product profiles have been previously shown with several other ligands. On the basis of new P450 2B6 crystal structure and previous 2B4 structures, substitutions at residue 262 affect a hydrogen-bonding network connecting the G and H helices, where subtle differences could be transduced to the active site. Docking experiments indicate that the closed protein conformation allows smaller ligands such as ticlopidine to bind to the 2B6 active site in the expected orientation. However, it is unknown whether 2B6 undergoes structural reorganization to accommodate bulkier molecules, as previously inferred from multiple P450 2B4 crystal structures.

  11. 40 CFR 721.10369 - Carbonic acid, diphenyl ester, polymer with diphenyl P-methylphosphonate and 4,4′-(1...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... with diphenyl P-methylphosphonate and 4,4â²-(1-methylethylidene) bis[phenol]. 721.10369 Section 721... Carbonic acid, diphenyl ester, polymer with diphenyl P-methylphosphonate and 4,4′-(1-methylethylidene) bis... identified as carbonic acid, diphenyl ester, polymer with diphenyl P-methylphosphonate and 4,4′-(1...

  12. GEANT4 Tuning For pCT Development

    NASA Astrophysics Data System (ADS)

    Yevseyeva, Olga; de Assis, Joaquim T.; Evseev, Ivan; Schelin, Hugo R.; Paschuk, Sergei A.; Milhoretto, Edney; Setti, João A. P.; Díaz, Katherin S.; Hormaza, Joel M.; Lopes, Ricardo T.

    2011-08-01

    Proton beams in medical applications deal with relatively thick targets like the human head or trunk. Thus, the fidelity of proton computed tomography (pCT) simulations as a tool for proton therapy planning depends in the general case on the accuracy of results obtained for the proton interaction with thick absorbers. GEANT4 simulations of proton energy spectra after passing thick absorbers do not agree well with existing experimental data, as showed previously. Moreover, the spectra simulated for the Bethe-Bloch domain showed an unexpected sensitivity to the choice of low-energy electromagnetic models during the code execution. These observations were done with the GEANT4 version 8.2 during our simulations for pCT. This work describes in more details the simulations of the proton passage through aluminum absorbers with varied thickness. The simulations were done by modifying only the geometry in the Hadrontherapy Example, and for all available choices of the Electromagnetic Physics Models. As the most probable reasons for these effects is some specific feature in the code, or some specific implicit parameters in the GEANT4 manual, we continued our study with version 9.2 of the code. Some improvements in comparison with our previous results were obtained. The simulations were performed considering further applications for pCT development.

  13. 16 CFR 1500.4 - Human experience with hazardous substances.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Human experience with hazardous substances... § 1500.4 Human experience with hazardous substances. (a) Reliable data on human experience with any..., the human experience takes precedence. (b) Experience may show that an article is more or less toxic...

  14. 16 CFR 1500.4 - Human experience with hazardous substances.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Human experience with hazardous substances... § 1500.4 Human experience with hazardous substances. (a) Reliable data on human experience with any..., the human experience takes precedence. (b) Experience may show that an article is more or less toxic...

  15. 16 CFR 1500.4 - Human experience with hazardous substances.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Human experience with hazardous substances... § 1500.4 Human experience with hazardous substances. (a) Reliable data on human experience with any..., the human experience takes precedence. (b) Experience may show that an article is more or less toxic...

  16. 16 CFR 1500.4 - Human experience with hazardous substances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Human experience with hazardous substances... § 1500.4 Human experience with hazardous substances. (a) Reliable data on human experience with any..., the human experience takes precedence. (b) Experience may show that an article is more or less toxic...

  17. Ternary chalcogenides C s 2 Z n 3 S e 4 and C s 2 Z n 3 T e 4 : Potential p -type transparent conducting materials

    DOE PAGES

    Shi, Hongliang; Saparov, Bayrammurad; Singh, David J.; ...

    2014-11-11

    Here we report prediction of two new ternary chalcogenides that can potentially be used as p-type transparent conductors along with experimental synthesis and initial characterization of these previously unknown compounds, Cs 2Zn 3Ch 4 (Ch = Se, Te). In particular, the structures are predicted based on density functional calculations and confirmed by experiments. Phase diagrams, electronic structure, optical properties, and defect properties of Cs 2Zn 3Se 4 and Cs 2Zn 3Te 4 are calculated to assess the viability of these materials as p-type TCMs. Cs 2Zn 3Se 4 and Cs 2Zn 3Te 4, which are stable under ambient air, displaymore » large optical band gaps (calculated to be 3.61 and 2.83 eV, respectively) and have small hole effective masses (0.5-0.77 m e) that compare favorably with other proposed p-type TCMs. Defect calculations show that undoped Cs2Zn3Se4 and Cs2Zn3Te4 are p-type materials. However, the free hole concentration may be limited by low-energy native donor defects, e.g., Zn interstitials. Lastly, non-equilibrium growth techniques should be useful for suppressing the formation of native donor defects, thereby increasing the hole concentration.« less

  18. Oxothiomolybdenum derivatives of the superlacunary crown heteropolyanion {P8W48}: structure of [K4{Mo4O4S4(H2O)3(OH)2}2(WO2)(P8W48O184)]30– and studies in solution.

    PubMed

    Korenev, Vladimir S; Floquet, Sébastien; Marrot, Jérôme; Haouas, Mohamed; Mbomekallé, Israël-Martyr; Taulelle, Francis; Sokolov, Maxim N; Fedin, Vladimir P; Cadot, Emmanuel

    2012-02-20

    Reaction of the cyclic lacunary [H(7)P(8)W(48)O(184)](33-) anion (noted P(8)W(48)) with the [Mo(2)S(2)O(2)(H(2)O)(6)](2+) oxothiocation led to two compounds, namely, [K(4){Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(WO(2))(P(8)W(48)O(184))](30-) (denoted 1) and [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) (denoted 2), which were characterized in the solid state and solution. In the solid state, the structure of [K(4){Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(WO(2))(P(8)W(48)O(184))](30-) reveals the presence of two disordered {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) "handles" connected on both sides of the P(8)W(48) ring. Such a disorder is consistent with the presence of two geometrical isomers where the relative disposition of the two {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) handles are arranged in a perpendicular or parallel mode. Such an interpretation is fully supported by (31)P and (183)W NMR solution studies. The relative stability of both geometrical isomers appears to be dependent upon the nature of the internal alkali cations, i.e., Na(+) vs K(+), and increased lability of the two {Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2+) handles, compared to the oxo analogous, was clearly identified by significant broadening of the (31)P and (183)W NMR lines. Solution studies carried out by UV-vis spectroscopy showed that formation of the adduct [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) occurs in the 1.5-4.7 pH range and corresponds to a fast and quantitative condensation process. Furthermore, (31)P NMR titrations in solution reveal formation of the "monohandle" derivative [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(P(8)W(48)O(184))](38-) as an intermediate prior to formation of the "bishandle" derivatives. Furthermore, the electrochemical behavior of [{Mo(4)O(4)S(4)(H(2)O)(3)(OH)(2)}(2)(P(8)W(48)O(184))](36-) was studied in aqueous medium and compared with the parent anion P(8)W(48).

  19. NH4+-NH3 removal from simulated wastewater using UV-TiO2 photocatalysis: effect of co-pollutants and pH.

    PubMed

    Vohra, M S; Selimuzzaman, S M; Al-Suwaiyan, M S

    2010-05-01

    The main objective of the present study was to investigate the efficiency of titanium dioxide (TiO2) assisted photocatalytic degradation (PCD) process for the removal of ammonium-ammonia (NH4(+)-NH3) from the aqueous phase and in the presence of co-pollutants thiosulfate (S2O3(2-)) and p-cresol (C6H4CH3OH) under varying mixed conditions. For the NH4(+)-NH3 only PCD experiments, results showed higher NH4 -NH3 removal at pH 12 compared to pH 7 and 10. For the binary NH4(+)-NH3/S2O3(2-) studies the respective results indicated a significant lowering in NH4(+)-NH3 PCD in the presence of S2O32- at pH 7/12 whereas at pH 10 a marked increase in NH4(+)-NH3 removal transpired. A similar trend was noted for the p-cresol/NH4(+)-NH3 binary system. Comparing findings from the binary (NH4(+)-NH3/S2O3(2-) and p-cresol/NH4(+)-NH3) and tertiary (NH4(+)-NH3/S2O3(2-)/p-cresol) systems, at pH 10, showed fastest NH4(+)-NH3 removal transpiring for the tertiary system as compared to the binary systems, whereas both the binary systems indicated comparable NH4(+)-NH3 removal trends. The respective details have been discussed.

  20. Pay for performance in the inpatient sector: A review of 34 P4P programs in 14 OECD countries.

    PubMed

    Milstein, Ricarda; Schreyoegg, Jonas

    2016-10-01

    Across the member countries of the Organisation for Economic Co-operation and Development (OECD), pay-for-performance (P4P) programs have been implemented in the inpatient sector to improve the quality of care provided by hospitals. This paper provides an overview of 34 existing P4P programs in the inpatient sector in 14 OECD countries based on a structured literature search in five databases to identify relevant sources in Danish, English, French, German, Hebrew, Italian, Japanese, Korean, Norwegian, Spanish, Swedish and Turkish. It assembles information on the design and effects of these P4P systems and discusses whether evaluations of such programs allow preliminary conclusions to be drawn about the effects of P4P. The programs are very heterogeneous in their aim, the selection of indicators and the design of financial rewards. The impact of P4P is unclear and it may be that the moderately positive effects seen for some programs can be attributed to side effects, such as public reporting and increased awareness of data recording. Policy makers must decide whether the potential benefits of introducing a P4P program outweigh the potential risks within their particular national or regional context, and should be aware that P4P programs have yet not lived up to expectations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. GABARAP-mediated targeting of PI4K2A/PI4KIIα to autophagosomes regulates PtdIns4P-dependent autophagosome-lysosome fusion.

    PubMed

    Albanesi, Joseph; Wang, Hanzhi; Sun, Hui-Qiao; Levine, Beth; Yin, Helen

    2015-11-02

    For decades, phosphatidylinositol 4-phosphate (PtdIns4P) was considered primarily as a precursor in the synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P 2 ). More recently, specific functions for PtdIns4P itself have been identified, particularly in the regulation of intracellular membrane trafficking. PI4K2A/PI4KIIα (phosphatidylinositol 4-kinase type 2 α), one of the 4 enzymes that catalyze PtdIns4P production in mammalian cells, promotes vesicle formation from the trans-Golgi network (TGN) and endosomes. We recently identified a novel function for PI4K2A-derived PtdIns4P, as a facilitator of autophagosome-lysosome (A-L) fusion. We further showed that that this function requires the presence of the autophagic adaptor protein GABARAP (GABA[A] receptor-associated protein), which binds to PI4K2A and recruits it to autophagosomes. The mechanism whereby GABARAP-PI4K2A-PtdIns4P promotes A-L fusion remains to be defined. Based on other examples of phosphoinositide involvement in membrane trafficking, we speculate that it acts by recruiting elements of the membrane docking and fusion machinery.

  2. Targeting miR-423-5p Reverses Exercise Training–Induced HCN4 Channel Remodeling and Sinus Bradycardia

    PubMed Central

    D’Souza, Alicia; Pearman, Charles M.; Wang, Yanwen; Nakao, Shu; Logantha, Sunil Jit R.J.; Cox, Charlotte; Bennett, Hayley; Zhang, Yu; Johnsen, Anne Berit; Linscheid, Nora; Poulsen, Pi Camilla; Elliott, Jonathan; Coulson, Jessica; McPhee, Jamie; Robertson, Abigail; da Costa Martins, Paula A.; Kitmitto, Ashraf; Wisløff, Ulrik; Cartwright, Elizabeth J.; Monfredi, Oliver; Lundby, Alicia; Dobrzynski, Halina; Oceandy, Delvac; Morris, Gwilym M.

    2017-01-01

    Rationale: Downregulation of the pacemaking ion channel, HCN4 (hyperpolarization-activated cyclic nucleotide gated channel 4), and the corresponding ionic current, If, underlies exercise training–induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes, and it will be important to understand the underlying processes. Objective: To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of microRNAs (miRs) in the repression of HCN4. Methods and Results: As in rodents, the intrinsic heart rate was significantly lower in human athletes than in nonathletes, and in all subjects, the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes. Next-generation sequencing and quantitative real-time reverse transcription polymerase chain reaction showed remodeling of miRs in the sinus node of swim-trained mice. Computational predictions highlighted a prominent role for miR-423-5p. Interaction between miR-423-5p and HCN4 was confirmed by a dose-dependent reduction in HCN4 3′-untranslated region luciferase reporter activity on cotransfection with precursor miR-423-5p (abolished by mutation of predicted recognition elements). Knockdown of miR-423-5p with anti-miR-423-5p reversed training-induced bradycardia via rescue of HCN4 and If. Further experiments showed that in the sinus node of swim-trained mice, upregulation of miR-423-5p (intronic miR) and its host gene, NSRP1, is driven by an upregulation of the transcription factor Nkx2.5. Conclusions: HCN remodeling likely occurs in human athletes, as well as in rodent models. miR-423-5p contributes to training-induced bradycardia by targeting HCN4. This work presents the first evidence of miR control of HCN4 and heart rate. miR-423-5p could be a therapeutic target for pathological sinus node

  3. Targeting miR-423-5p Reverses Exercise Training-Induced HCN4 Channel Remodeling and Sinus Bradycardia.

    PubMed

    D'Souza, Alicia; Pearman, Charles M; Wang, Yanwen; Nakao, Shu; Logantha, Sunil Jit R J; Cox, Charlotte; Bennett, Hayley; Zhang, Yu; Johnsen, Anne Berit; Linscheid, Nora; Poulsen, Pi Camilla; Elliott, Jonathan; Coulson, Jessica; McPhee, Jamie; Robertson, Abigail; da Costa Martins, Paula A; Kitmitto, Ashraf; Wisløff, Ulrik; Cartwright, Elizabeth J; Monfredi, Oliver; Lundby, Alicia; Dobrzynski, Halina; Oceandy, Delvac; Morris, Gwilym M; Boyett, Mark R

    2017-10-13

    Downregulation of the pacemaking ion channel, HCN4 (hyperpolarization-activated cyclic nucleotide gated channel 4), and the corresponding ionic current, I f , underlies exercise training-induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes, and it will be important to understand the underlying processes. To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of microRNAs (miRs) in the repression of HCN4. As in rodents, the intrinsic heart rate was significantly lower in human athletes than in nonathletes, and in all subjects, the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes. Next-generation sequencing and quantitative real-time reverse transcription polymerase chain reaction showed remodeling of miRs in the sinus node of swim-trained mice. Computational predictions highlighted a prominent role for miR-423-5p. Interaction between miR-423-5p and HCN4 was confirmed by a dose-dependent reduction in HCN4 3'-untranslated region luciferase reporter activity on cotransfection with precursor miR-423-5p (abolished by mutation of predicted recognition elements). Knockdown of miR-423-5p with anti-miR-423-5p reversed training-induced bradycardia via rescue of HCN4 and I f . Further experiments showed that in the sinus node of swim-trained mice, upregulation of miR-423-5p (intronic miR) and its host gene, NSRP1, is driven by an upregulation of the transcription factor Nkx2.5. HCN remodeling likely occurs in human athletes, as well as in rodent models. miR-423-5p contributes to training-induced bradycardia by targeting HCN4. This work presents the first evidence of miR control of HCN4 and heart rate. miR-423-5p could be a therapeutic target for pathological sinus node dysfunction in veteran athletes. © 2017 The Authors.

  4. N-Heterocyclic Carbene Capture by Cytochrome P450 3A4

    PubMed Central

    Jennings, Gareth K.; Ritchie, Caroline M.; Shock, Lisa S.; Lyons, Charles E.

    2016-01-01

    Cytochrome P450 3A4 (CYP3A4) is the dominant P450 enzyme involved in human drug metabolism, and its inhibition may result in adverse interactions or, conversely, favorably reduce the systemic elimination rates of poorly bioavailable drugs. Herein we describe a spectroscopic investigation of the interaction of CYP3A4 with N-methylritonavir, an analog of ritonavir, widely used as a pharmacoenhancer. In contrast to ritonavir, the binding affinity of N-methylritonavir for CYP3A4 is pH-dependent. At pH <7.4, the spectra are definitively type I, whereas at pH ≥7.4 the spectra have split Soret bands, including a red-shifted component characteristic of a P450-carbene complex. Variable-pH UV-visible spectroscopy binding studies with molecular fragments narrows the source of this pH dependence to its N-methylthiazolium fragment. The C2 proton of this group is acidic, and variable-pH resonance Raman spectroscopy tentatively assigns it a pKa of 7.4. Hence, this fragment of N-methylritonavir is expected to be readily deprotonated under physiologic conditions to yield a thiazol-2-ylidene, which is an N-heterocyclic carbene that has high-affinity for and is presumed to be subsequently captured by the heme iron. This mechanism is supported by time-dependent density functional theory with an active site model that accurately reproduces distinguishing features of the experimental UV-visible spectra of N-methylritonavir bound to CYP3A4. Finally, density functional theory calculations support that this novel interaction is as strong as the tightest-binding azaheterocycles found in P450 inhibitors and could offer new avenues for inhibitor development. PMID:27126611

  5. Phenoxyacetic acid degradation by the 2,4-dichlorophenoxyacetic acid (TFD) pathway of plasmid pJP4: mapping and characterization of the TFD regulatory gene, tfdR.

    PubMed Central

    Harker, A R; Olsen, R H; Seidler, R J

    1989-01-01

    Plasmid pJP4 enables Alcaligenes eutrophus JMP134 to degrade 3-chlorobenzoate and 2,4-dichlorophenoxyacetic acid (TFD). Plasmid pRO101 is a derivative of pJP4 obtained by insertion of Tn1721 into a nonessential region of pJP4. Plasmid pRO101 was transferred by conjugation to several Pseudomonas strains and to A. eutrophus AEO106, a cured isolate of JMP134. AEO106(pRO101) and some Pseudomonas transconjugants grew on TFD. Transconjugants with a chromosomally encoded phenol hydroxylase also degraded phenoxyacetic acid (PAA) in the presence of an inducer of the TFD pathway, namely, TFD or 3-chlorobenzoate. A mutant of one such phenol-degrading strain, Pseudomonas putida PPO300(pRO101), grew on PAA as the sole carbon source in the absence of inducer. This isolate carried a mutant plasmid, designated pRO103, derived from pRO101 through the deletion of a 3.9-kilobase DNA fragment. Plasmid pRO103 constitutively expressed the TFD pathway, and this allowed the metabolism of PAA in the absence of the inducer, TFD. Complementation of pRO103 in trans by a DNA fragment corresponding to the fragment deleted in pRO101 indicates that a negative control-regulatory gene (tfdR) is located on the BamHI E fragment of pRO101. Other subcloning experiments resulted in the cloning of the tfdA monooxygenase gene on a 3.5-kilobase fragment derived from pRO101. This subclone, in the absence of other pRO101 DNA, constitutively expressed the tfdA gene and allowed PPO300 to grow on PAA. Preliminary evidence suggests that the monooxygenase activity encoded by this DNA fragment is feedback-inhibited by phenols. Images PMID:2914848

  6. Regulation of the yeast triacylglycerol lipases Tgl4p and Tgl5p by the presence/absence of nonpolar lipids

    PubMed Central

    Klein, Isabella; Klug, Lisa; Schmidt, Claudia; Zandl, Martina; Korber, Martina; Daum, Günther; Athenstaedt, Karin

    2016-01-01

    Tgl3p, Tgl4p, and Tgl5p are the major triacylglycerol lipases of the yeast Saccharomyces cerevisiae. Recently we demonstrated that properties of Tgl3p are regulated by the formation of nonpolar lipids. The present study extends these investigations to the two other yeast triacylglycerol lipases, Tgl4p and Tgl5p. We show that Tgl4p and Tgl5p, which are localized to lipid droplets in wild type, are partially retained in the endoplasmic reticulum in cells lacking triacylglycerols and localize exclusively to the endoplasmic reticulum in a mutant devoid of lipid droplets. In cells lacking steryl esters, the subcellular distribution of Tgl4p and Tgl5p is unaffected, but Tgl5p becomes unstable, whereas the stability of Tgl4p increases. In cells lacking nonpolar lipids, Tgl4p and Tgl5p lose their lipolytic activity but retain their side activity as lysophospholipid acyltransferases. To investigate the regulatory network of yeast triacylglycerol lipases in more detail, we also examined properties of Tgl3p, Tgl4p, and Tgl5p, respectively, in the absence of the other lipases. Surprisingly, lack of two lipases did not affect expression, localization, and stability of the remaining Tgl protein. These results suggest that Tgl3p, Tgl4p, and Tgl5p, although they exhibit similar functions, act as independent entities. PMID:27170177

  7. Ethanol Is a Fast Channel Inhibitor of P2X4 Receptors

    PubMed Central

    Ostrovskaya, Olga; Asatryan, Liana; Wyatt, Letisha; Popova, Maya; Li, Kaixun; Peoples, Robert W.; Alkana, Ronald L.

    2011-01-01

    P2X receptors (P2XRs) are ion channels gated by synaptically released ATP. The P2X4 is the most abundant P2XR subtype expressed in the central nervous system and to date is the most ethanol-sensitive. In addition, genomic findings suggest that P2X4Rs may play a role in alcohol intake/preference. However, little is known regarding how ethanol causes the inhibition of ATP-gated currents in P2X4Rs. We begin to address this issue by investigating the effects of ethanol in wild-type and mutant D331A and M336A P2X4Rs expressed in human embryonic kidney (HEK) 293 cells using whole-cell patch-clamp methods. The results suggest that residues D331 and M336 play a role in P2X4R gating and ethanol inhibits channel functioning via a mechanism different from that in other P2XRs. Key findings from the study include: 1) ethanol inhibits ATP-gated currents in a rapid manner; 2) ethanol inhibition of ATP-gated currents does not depend on voltage and ATP concentration; 3) residues 331 and 336 slow P2X4 current deactivation and regulate the inhibitory effects of ethanol; and 4) ethanol effects are similar in HEK293 cells transfected with P2X4Rs and cultured rat hippocampal neurons transduced with P2X4Rs using a recombinant lentiviral system. Overall, these findings provide key information regarding the mechanism of ethanol action on ATP-gated currents in P2X4Rs and provide new insights into the biophysical properties of P2X4Rs. PMID:21212160

  8. A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations.

    PubMed

    Iype, Thomas; Alakbarzade, Vafa; Iype, Mary; Singh, Royana; Sreekantan-Nair, Ajith; Chioza, Barry A; Mohapatra, Tribhuvan M; Baple, Emma L; Patton, Michael A; Warner, Thomas T; Proukakis, Christos; Kulkarni, Abhi; Crosby, Andrew H

    2015-11-10

    The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance. We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features. We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.

  9. Fabrication and performance analysis of 4-sq cm indium tin oxide/InP photovoltaic solar cells

    NASA Technical Reports Server (NTRS)

    Gessert, T. A.; Li, X.; Phelps, P. W.; Coutts, T. J.; Tzafaras, N.

    1991-01-01

    Large-area photovoltaic solar cells based on direct current magnetron sputter deposition of indium tin oxide (ITO) into single-crystal p-InP substrates demonstrated both the radiation hardness and high performance necessary for extraterrestrial applications. A small-scale production project was initiated in which approximately 50 ITO/InP cells are being produced. The procedures used in this small-scale production of 4-sq cm ITO/InP cells are presented and discussed. The discussion includes analyses of performance range of all available production cells, and device performance data of the best cells thus far produced. Additionally, processing experience gained from the production of these cells is discussed, indicating other issues that may be encountered when large-scale productions are begun.

  10. Two major pathways of penile carcinogenesis: HPV-induced penile cancers overexpress p16ink4a, HPV-negative cancers associated with dermatoses express p53, but lack p16ink4a overexpression.

    PubMed

    Mannweiler, Sebastian; Sygulla, Stephan; Winter, Elke; Regauer, Sigrid

    2013-07-01

    Penile squamous cell carcinomas (SCC) arise either through transforming infections with human papillomavirus (HPV) or independent of HPV, often in the background of lichen sclerosus (LS) and lichen planus (LP). Despite impact on therapy and prognosis, etiologic stratifications are missing in most histological diagnoses and publications about penile cancers/precursors. Classification of penile lesions into HPV-induced or HPV-negative via immunohistochemical demonstration of p16(ink4a) overexpression, a surrogate marker for transforming HPV-high-risk infections, and p53 expression in the absence of p16(ink4a) overexpression. Archival formalin-fixed material of 123 invasive penile cancers and 43 pre-invasive lesions was evaluated for the presence of LS, LP, 28 HPV genotypes, and expression of p53 and p16(ink4a). Seventy-two of 123 SCCs and 33 of 43 pre-invasive lesions showed p16(ink4a) overexpression independent of HPV-HR genotypes involved; 66 of 72 SCCs and 29 of 43 precursor lesions revealed a single HPV-high-risk-genotype (HPV-HR16 in 76% followed by HPV33, HPV31, HPV45, HPV18, HPV56); 5 of 72 SCCs and 4 of 43 precursor lesions revealed multiple HPV-HR-genotypes. One SCC revealed HPV-LR and HR-DNA. Fifty-one of 123 SCCs and 10 precursor lesions were p16(ink4a) negative, but showed nuclear p53 expression in tumor cells and basal keratinocytes. Forty-nine of 51 SCCs and 10 of 10 precursor lesions lacked HPV DNA. Two of 51 SCCs contained HPV18 and HPV45 DNA, respectively, but p16(ink4a) negativity classified them as non-HPV-induced. Twenty-seven of 51 SCCs showed peritumoral LS, 13 of 51 SCCs showed peritumoral LP, and 11 SCCs revealed no peritumoral tissue. Histologically, HPV-negative precursors showed hyperkeratotic, verrucous, atrophic, and basaloid differentiation. This was a retrospective study. p16(ink4a) overexpression identifies HPV-HR-induced penile carcinogenesis independent of HPV-HR genotype. p53 expression along with p16(ink4a) negativity identifies

  11. Dielectric Study of the Phase Transitions in [P(CH3)4]2CuY4 (Y = Cl, Br)

    NASA Astrophysics Data System (ADS)

    Gesi, Kazuo

    2002-05-01

    Phase transitions in [P(CH3)4]2CuY4 (Y = Cl, Br) have been studied by dielectric measurements. In [P(CH3)4]2CuCl4, a slight break and a discontinuous jump on the dielectric constant vs. temperature curve are seen at the normal-incommensurate and the incommensurate-commensurate phase transitions, respectively. A small peak of dielectric constant along the b-direction exists just above the incommensurate-to-commensurate transition temperature. The anisotropic dielectric anomalies of [P(CH3)4]2CuBr4 at phase transitions were measured along the three crystallographic axes. The pressure-temperature phase diagram of [P(CH3)4]2CuCl4 was determined. The initial pressure coefficients of the normal-to-incommensurate and the incommensurate-to-commensurate transition temperatures are 0.19 K/MPa and 0.27 K/MPa, respectively. The incommensurate phase in [P(CH3)4]2CuCl4 disappears at a triple point which exists at 335 MPa and 443 K. The stability and the pressure effects of the incommensurate phases are much different among the four [Z(CH3)4]2CuY4 crystals (Z = N, P; Y = Cl, Br).

  12. TacSat-4 COMMx, Advanced SATCOM Experiment

    DTIC Science & Technology

    2009-01-01

    Schein, M. T. Marley, C. T. Apland, R. E. Lee, B. D . Williams, E. D . Schaefer, S. R. Vernon, P . D . Schwartz , B. L. Kantsiper, E. J. Finnegan;The...Lee, B. D . Williams, E. D . Schaefer, P . D . Schwartz, R. Denissen, B. Kantsiper, E. J. Finnegan; The Johns Hopkins University Applied Physics...Mission Ops Lead, NRL Code 8233 Bob Kuzma, TacSat-4 Payload Controller, NRL Code 8242 Bob Skalitzky, TacSat-4 Power Systems, NRL Code 8244 Doug Bentz

  13. A clinical trial of the accuracy and treatment experience of the Dexcom G4 sensor (Dexcom G4 system) and Enlite sensor (guardian REAL-time system) tested simultaneously in ambulatory patients with type 1 diabetes.

    PubMed

    Matuleviciene, Viktorija; Joseph, Jeffrey I; Andelin, Mervi; Hirsch, Irl B; Attvall, Stig; Pivodic, Aldina; Dahlqvist, Sofia; Klonoff, David; Haraldsson, Börje; Lind, Marcus

    2014-11-01

    Continuous glucose monitoring (CGM) is a tool widely used in the treatment of patients with type 1 diabetes. The purpose of the current study was to evaluate whether accuracy and patient treatment satisfaction differ between the Enlite™ (Medtronic MiniMed, Inc., Northridge, CA) and Dexcom(®) (San Diego, CA) G4 PLATINUM CGM sensors. Thirty-eight ambulatory patients with type 1 diabetes used the Dexcom G4 and Enlite sensors simultaneously for a minimum of 4 and maximum of 6 days. Patients measured capillary glucose levels with a HemoCue(®) (Ängelholm, Sweden) system six to 10 times a day. In addition, two inpatient studies were performed between Days 1-3 and 4-6. The mean absolute relative difference (MARD) in blood glucose for the Dexcom G4 was significantly lower (13.9%) than for the Enlite sensor (17.8%) (P<0.0001). The corresponding MARDs for Days 1-3 were 15.0% versus 19.4% (P=0.0027) and 13.6% versus 15.9% (P=0.026) for Days 4-6. For glucose levels in the hypoglycemic range (<4.0 mmol/L), the MARD for the Dexcom G4 was 20.0% compared with 34.7% for the Enlite (P=0.0041). On a visual analog scale (VAS) (0-100), patients rated the Dexcom G4 more favorably than the Enlite in 12 out of the 13 user experience questions. For example, more patients rated their experience with the Dexcom G4 as positive (VAS, 79.7 vs. 46.6; P<0.0001) and preferred to use it in their daily lives (VAS, 79.1 vs. 42.1; P<0.0001). The Dexcom G4 sensor was associated with greater overall accuracy than the Enlite sensor during initial (Days 1-3) and later (Days 4-6) use and for glucose levels in the hypoglycemic range. Patients reported a significantly more positive experience using the Dexcom G4 than the Enlite.

  14. Phosphoinositides Regulate P2X4 ATP-Gated Channels through Direct Interactions

    PubMed Central

    Bernier, Louis-Philippe; Ase, Ariel R.; Chevallier, Stéphanie; Blais, Dominique; Zhao, Qi; Boué-Grabot, Éric; Logothetis, Diomedes; Séguéla, Philippe

    2008-01-01

    P2X receptors are ATP-gated nonselective cation channels highly permeable to calcium that contribute to nociception and inflammatory responses. The P2X4 subtype, upregulated in activated microglia, is thought to play a critical role in the development of tactile allodynia following peripheral nerve injury. Posttranslational regulation of P2X4 function is crucial to the cellular mechanisms of neuropathic pain, however it remains poorly understood. Here, we show that the phosphoinositides PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3), products of phosphorylation by wortmannin-sensitive phosphatidylinositol 4-kinases and phosphatidylinositol 3-kinases, can modulate the function of native and recombinant P2X4 receptor channels. In BV-2 microglial cells, depleting the intracellular levels of PIP2 and PIP3 with wortmannin significantly decreased P2X4 current amplitude and P2X4-mediated calcium entry measured in patch clamp recordings and ratiometric ion imaging, respectively. Wortmannin-induced depletion of phosphoinositides in Xenopus oocytes decreased the current amplitude of P2X4 responses by converting ATP into a partial agonist. It also decreased their recovery from desensitization and affected their kinetics. Injection of phosphoinositides in wortmannin-treated oocytes reversed these effects and application of PIP2 on excised inside-out macropatches rescued P2X4 currents from rundown. Moreover, we report the direct interaction of phospholipids with the proximal C-terminal domain of P2X4 subunit (Cys360-Val375) using an in vitro binding assay. These results demonstrate novel regulatory roles of the major signaling phosphoinositides PIP2 and PIP3 on P2X4 function through direct channel-lipid interactions. PMID:19036987

  15. 3' Phosphatase activity toward phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] by voltage-sensing phosphatase (VSP).

    PubMed

    Kurokawa, Tatsuki; Takasuga, Shunsuke; Sakata, Souhei; Yamaguchi, Shinji; Horie, Shigeo; Homma, Koichi J; Sasaki, Takehiko; Okamura, Yasushi

    2012-06-19

    Voltage-sensing phosphatases (VSPs) consist of a voltage-sensor domain and a cytoplasmic region with remarkable sequence similarity to phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor phosphatase. VSPs dephosphorylate the 5' position of the inositol ring of both phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] upon voltage depolarization. However, it is unclear whether VSPs also have 3' phosphatase activity. To gain insights into this question, we performed in vitro assays of phosphatase activities of Ciona intestinalis VSP (Ci-VSP) and transmembrane phosphatase with tensin homology (TPTE) and PTEN homologous inositol lipid phosphatase (TPIP; one human ortholog of VSP) with radiolabeled PI(3,4,5)P(3). TLC assay showed that the 3' phosphate of PI(3,4,5)P(3) was not dephosphorylated, whereas that of phosphatidylinositol 3,4-bisphosphate [PI(3,4)P(2)] was removed by VSPs. Monitoring of PI(3,4)P(2) levels with the pleckstrin homology (PH) domain from tandem PH domain-containing protein (TAPP1) fused with GFP (PH(TAPP1)-GFP) by confocal microscopy in amphibian oocytes showed an increase of fluorescence intensity during depolarization to 0 mV, consistent with 5' phosphatase activity of VSP toward PI(3,4,5)P(3). However, depolarization to 60 mV showed a transient increase of GFP fluorescence followed by a decrease, indicating that, after PI(3,4,5)P(3) is dephosphorylated at the 5' position, PI(3,4)P(2) is then dephosphorylated at the 3' position. These results suggest that substrate specificity of the VSP changes with membrane potential.

  16. Distinct subunit contributions to the activation of M-type potassium channels by PI(4,5)P2

    PubMed Central

    Telezhkin, Vsevolod; Brown, David A.

    2012-01-01

    Low-threshold voltage-gated M-type potassium channels (M channels) are tetraheteromers, commonly of two Kv7.2 and two Kv7.3 subunits. Though gated by voltage, the channels have an absolute requirement for binding of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) to open. We have investigated the quantitative relation between the concentration of a water-soluble PI(4,5)P2 analog, dioctanoyl-PI(4,5)P2 (DiC8-PI(4,5)P2), and channel open probability (Popen) by fast application of increasing concentrations of DiC8-PI(4,5)P2 to the inside face of membrane patches excised from Chinese hamster ovary cells expressing M channels as heteromeric Kv7.2/7.3 subunits. The rationale for the experiments is that this will mimic the effect of changes in membrane PI(4,5)P2 concentration. Single-channel conductances from channel current–voltage relations in cell-attached mode were 9.2 ± 0.1 pS with a 2.5-mM pipette [K+]. Plots of Popen against DiC8-PI(4,5)P2 concentration were best fitted using a two-component concentration–Popen relationship with high and low affinity, half-maximal effective concentration (EC50) values of 1.3 ± 0.14 and 75.5 ± 2.5 µM, respectively, and Hill slopes of 1.4 ± 0.06. In contrast, homomeric channels from cells expressing only Kv7.2 or Kv7.3 constructs yielded single-component curves with EC50 values of 76.2 ± 19.9 or 3.6 ± 1.0 µM, respectively. When wild-type (WT) Kv7.2 was coexpressed with a mutated Kv7.3 subunit with >100-fold reduced sensitivity to PI(4,5)P2, the high-affinity component of the activation curve was lost. Fitting the data for WT and mutant channels to an activation mechanism with independent PI(4,5)P2 binding to two Kv7.2 and two Kv7.3 subunits suggests that the two components of the M-channel activation curve correspond to the interaction of PI(4,5)P2 with the Kv7.3 and Kv7.2 subunits, respectively, that channels can open when only the two Kv7.3 subunits have bound DiC8-PI(4,5)P2, and that maximum

  17. Parameterization-based tracking for the P2 experiment

    NASA Astrophysics Data System (ADS)

    Sorokin, Iurii

    2017-08-01

    The P2 experiment in Mainz aims to determine the weak mixing angle θW at low momentum transfer by measuring the parity-violating asymmetry of elastic electronproton scattering. In order to achieve the intended precision of Δ(sin2 θW)/sin2θW = 0:13% within the planned 10 000 hours of running the experiment has to operate at the rate of 1011 detected electrons per second. Although it is not required to measure the kinematic parameters of each individual electron, every attempt is made to achieve the highest possible throughput in the track reconstruction chain. In the present work a parameterization-based track reconstruction method is described. It is a variation of track following, where the results of the computation-heavy steps, namely the propagation of a track to the further detector plane, and the fitting, are pre-calculated, and expressed in terms of parametric analytic functions. This makes the algorithm extremely fast, and well-suited for an implementation on an FPGA. The method also takes implicitly into account the actual phase space distribution of the tracks already at the stage of candidate construction. Compared to a simple algorithm, that does not use such information, this allows reducing the combinatorial background by many orders of magnitude, down to O(1) background candidate per one signal track. The method is developed specifically for the P2 experiment in Mainz, and the presented implementation is tightly coupled to the experimental conditions.

  18. NADPH-cytochrome P450 reductase-mediated denitration reaction of 2,4,6-trinitrotoluene to yield nitrite in mammals.

    PubMed

    Shinkai, Yasuhiro; Nishihara, Yuya; Amamiya, Masahiro; Wakayama, Toshihiko; Li, Song; Kikuchi, Tomohiro; Nakai, Yumi; Shimojo, Nobuhiro; Kumagai, Yoshito

    2016-02-01

    While the biodegradation of 2,4,6-trinitrotoluene (TNT) via the release of nitrite is well established, mechanistic details of the reaction in mammals are unknown. To address this issue, we attempted to identify the enzyme from rat liver responsible for the production of nitrite from TNT. A NADPH-cytochrome P450 reductase (P450R) was isolated and identified from rat liver microsomes as the enzyme responsible for not only the release of nitrite from TNT but also formation of superoxide and 4-hydroxyamino-2,6-dinitrotoluene (4-HADNT) under aerobic conditions. In this context, reactive oxygen species generated during P450R-catalyzed TNT reduction were found to be, at least in part, a mediator for the production of 4-HADNT from TNT via formation of 4-nitroso-2,6-dinitrotoluene. P450R did not catalyze the formation of the hydride-Meisenheimer complex (H(-)-TNT) that is thought to be an intermediate for nitrite release from TNT. Furthermore, in a time-course experiment, 4-HADNT formation reached a plateau level and then declined during the reaction between TNT and P450R with NADPH, while the release of nitrite was subjected to a lag period. Notably, the produced 4-HADNT can react with the parent compound TNT to produce nitrite and dimerized products via formation of a Janovsky complex. Our results demonstrate for the first time that P450R-mediated release of nitrite from TNT results from the process of chemical interaction of TNT and its 4-electron reduction metabolite 4-HADNT. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Tank Pressure Control Experiment: Thermal Phenomena in Microgravity. Video 4 of 4

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The report presents the results of the flight experiment Tank Pressure Control Experiment/Thermal Phenomena (TPCE/TP) performed in the microgravity environment of the space shuttle. TPCE/TP, flown on the Space Transportation System STS-52, was a second flight of the Tank Pressure Control Experiment (TPCE). The experiment used Freon 113 at near saturation conditions. The test tank was filled with liquid to about 83 percent by volume. The experiment consisted of 21 tests. Each test generally started with a heating phase to increase the tank pressure and to develop temperature stratification in the fluid, followed by a fluid mixing phase for the tank pressure reduction and fluid temperature equilibration. The heating phase provided pool boiling data from large (relative to bubble sizes) heating surfaces (0.1046 m by 0.0742 m) at low heat fluxes (0.23 to 1.16 kW/m(exp 2)). The system pressure and the bulk liquid subcooling varied from 39 to 78 kPa and 1 to 3 deg C, respectively. The boiling process during the entire heating period, as well a jet-induced mixing process for the first 2 min. of the mixing period, was also recorded on video. Analyses of data from the two flight experiments (TPCE and TPCE/TP) and their comparison with the results obtained in drop tower experiments suggest that as Bond number approaches zero the flow pattern produced by an axial jet and the mixing time can be predicted by the Weber number. This is video 4 of 4.

  20. Nuclear Magnetic Resonance Structures of GCN4p Are Largely Conserved When Ion Pairs Are Disrupted at Acidic pH but Show a Relaxation of the Coiled Coil Superhelix.

    PubMed

    Kaplan, Anne R; Brady, Megan R; Maciejewski, Mark W; Kammerer, Richard A; Alexandrescu, Andrei T

    2017-03-21

    To understand the roles ion pairs play in stabilizing coiled coils, we determined nuclear magnetic resonance structures of GCN4p at three pH values. At pH 6.6, all acidic residues are fully charged; at pH 4.4, they are half-charged, and at pH 1.5, they are protonated and uncharged. The α-helix monomer and coiled coil structures of GCN4p are largely conserved, except for a loosening of the coiled coil quaternary structure with a decrease in pH. Differences going from neutral to acidic pH include (i) an unwinding of the coiled coil superhelix caused by the loss of interchain ion pair contacts, (ii) a small increase in the separation of the monomers in the dimer, (iii) a loosening of the knobs-into-holes packing motifs, and (iv) an increased separation between oppositely charged residues that participate in ion pairs at neutral pH. Chemical shifts (HN, N, C', Cα, and Cβ) of GCN4p display a seven-residue periodicity that is consistent with α-helical structure and is invariant with pH. By contrast, periodicity in hydrogen exchange rates at neutral pH is lost at acidic pH as the exchange mechanism moves into the EX1 regime. On the basis of 1 H- 15 N nuclear Overhauser effect relaxation measurements, the α-helix monomers experience only small increases in picosecond to nanosecond backbone dynamics at acidic pH. By contrast, 13 C rotating frame T 1 relaxation (T 1ρ ) data evince an increase in picosecond to nanosecond side-chain dynamics at lower pH, particularly for residues that stabilize the coiled coil dimerization interface through ion pairs. The results on the structure and dynamics of GCNp4 over a range of pH values help rationalize why a single structure at neutral pH poorly predicts the pH dependence of the unfolding stability of the coiled coil.

  1. The SHiP experiment at CERN

    NASA Astrophysics Data System (ADS)

    Bonivento, Walter M.

    2017-07-01

    The discovery of the Higgs boson has fully confirmed the Standard Model of particles and fields. Nevertheless, there are still fundamental phenomena, like the existence of dark matter and the baryon asymmetry of the Universe, deserving an explanation that could come from the discovery of new particles. Searches for new physics with accelerators are performed at the LHC, looking for high massive particles coupled to matter with ordinary strength. A new experiment at CERN meant to search for very weakly coupled particles in the few GeV mass domain has been recently proposed. The existence of such particles, foreseen in different theoretical models beyond the Standard Model, is largely unexplored. A beam dump facility using high intensity 400 GeV protons is a copious source of such unknown particles in the GeV mass range. The beam dump is also a copious source of neutrinos and in particular it is an ideal source of tau neutrinos, the less known particle in the Standard Model. The neutrino detector can also search for dark matter through its scattering off the electrons. We report the physics potential of the SHiP experiment.

  2. [The mechanisms of p21WAF1/Cip-1 expression in MOLT-4 cell line induced by TSA].

    PubMed

    Song, Yi; Liu, Mei-Ju; Zhao, Guo-Wei; Qian, Jun-Jie; Dong, Yan; Liu, Hua; Sun, Guo-Jing; Mei, Zhu-Zhong; Liu, Bin; Tian, Bao-Lei; Sun, Zhi-Xian

    2005-04-01

    To investigate the function and molecular mechanism of p21(WAF1/Cip-1) expression in MOLT-4 cells induced by HDAC inhibitor TSA, the expression pattern of p21(WAF1/Cip-1) and the distribution of cell cycle in TSA treated cells were analyzed. The results showed that TSA could effectively induce G(2)/M arrest and apoptosis of MOLT-4 cells. Kinetic experiments demonstrated that p21(WAF1/Cip-1) were upregulated quickly before cell arrested in G(2)/M and began decreasing at the early stage of apoptosis. Meanwhile, the proteasome inhibitor MG-132 could inhibit the decrease of p21(WAF1/Cip-1) at the early stage of apoptosis, which showed that proteasome pathway involved in p21(WAF1/Cip-1) degradation during the TSA induced G(2)/M arrest and apoptosis responses. This study also identified that the protein level of p21(WAF1/Cip-1) was highly associated with the cell cycle change induced by TSA. Compared to cells treated by TSA only, exposure MOLT-4 cells to TSA meanwhile treatment with MG-132 increased the protein level of p21(WAF1/Cip-1) and increased the numbers of cell in G(2)/M-phase, whereas the cell apoptosis were delayed. It is concluded that p21(WAF1/Cip-1) plays a significant role in G(2)/M arrest and apoptosis signaling induced by TSA in MOLT-4 cells.

  3. One-Pot Synthesis of Fe3O4@PS@P(AEMH-FITC) Magnetic Fluorescent Nanocomposites for Bimodal Imaging.

    PubMed

    Wang, Xuandong; Liu, Huiyu; Jun, Ren; Fu, Changhui; Li, Linlin; Li, Tianlong; Tang, Fangqiong; Meng, Xianwei

    2016-03-01

    Magnetic fluorescent nanocomposites have attracted much attention because of their merging magnetic and fluorescent properties for biomedical application. However, the procedure of synthesis of magnetic fluorescent nanocomposites is always complicated. In addition, the properties of fluorescent component could be easily influenced by magnetic component, retaining both of the magnetic and fluorescent properties into one single nanoparticle considered to be a significant challenge. Herein, we report one-pot method to synthesize multifunctional magnetic fluorescent Fe3O4@PS@P(AEMH-FITC) nanocomposites for bimodal imaging. The asprepared Fe3O4@PS@P(AEMH-FITC) nanocomposites with well-define spherical core/shell structure were stable properties. Moreover, the Fe3O4@PS@P(AEMH-FITC) nanocomposites displayed efficient fluorescent and magnetic properties, respectively. Meanwhile, the magnetic resonance imaging (MRI) and HePG2 cancer cell fluorescent images experiment results suggested that Fe3O4@PS@P(AEMH-FITC) nanocomposites could be used as MRI contrast agents and Fluorescence Imaging (FLI) agents for bioimaging application. Our investigation paves a facile avenue for synthesized magnetic fluorescent nanostructures with well biocompatibility for potential bioimaging application in MRI and FLI.

  4. Regulation of the yeast triacylglycerol lipases Tgl4p and Tgl5p by the presence/absence of nonpolar lipids.

    PubMed

    Klein, Isabella; Klug, Lisa; Schmidt, Claudia; Zandl, Martina; Korber, Martina; Daum, Günther; Athenstaedt, Karin

    2016-07-01

    Tgl3p, Tgl4p, and Tgl5p are the major triacylglycerol lipases of the yeast Saccharomyces cerevisiae Recently we demonstrated that properties of Tgl3p are regulated by the formation of nonpolar lipids. The present study extends these investigations to the two other yeast triacylglycerol lipases, Tgl4p and Tgl5p. We show that Tgl4p and Tgl5p, which are localized to lipid droplets in wild type, are partially retained in the endoplasmic reticulum in cells lacking triacylglycerols and localize exclusively to the endoplasmic reticulum in a mutant devoid of lipid droplets. In cells lacking steryl esters, the subcellular distribution of Tgl4p and Tgl5p is unaffected, but Tgl5p becomes unstable, whereas the stability of Tgl4p increases. In cells lacking nonpolar lipids, Tgl4p and Tgl5p lose their lipolytic activity but retain their side activity as lysophospholipid acyltransferases. To investigate the regulatory network of yeast triacylglycerol lipases in more detail, we also examined properties of Tgl3p, Tgl4p, and Tgl5p, respectively, in the absence of the other lipases. Surprisingly, lack of two lipases did not affect expression, localization, and stability of the remaining Tgl protein. These results suggest that Tgl3p, Tgl4p, and Tgl5p, although they exhibit similar functions, act as independent entities. © 2016 Klein, Klug, Schmidt, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  5. p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages

    PubMed Central

    Cudejko, Céline; Wouters, Kristiaan; Fuentes, Lucía; Hannou, Sarah Anissa; Paquet, Charlotte; Bantubungi, Kadiombo; Bouchaert, Emmanuel; Vanhoutte, Jonathan; Fleury, Sébastien; Remy, Patrick; Tailleux, Anne; Chinetti, Giulia; Dombrowicz, David; Staels, Bart; Paumelle, Réjane

    2011-01-01

    The CDKN2A locus, which contains the tumor suppressor gene p16INK4a, is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role. Monocytes can polarize towards classically (CAMφ) or alternatively (AAMφ) activated macrophages. However, the molecular mechanisms underlying the acquisition of these phenotypes are not well defined. Here, we show that p16INK4a-deficiency (p16−/−) modulates the macrophage phenotype. Transcriptome analysis revealed that p16−/− bone marrow-derived macrophages (BMDM) exhibit a phenotype resembling interleukin (IL)-4-induced macrophage polarization. In line with this observation, p16−/− BMDM displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. Furthermore, mice transplanted with p16−/− bone marrow displayed higher hepatic AAMφ marker expression levels upon Schistosoma mansoni infection, an in vivo model of AAMφ phenotype-skewing. Surprisingly, p16−/− BMDM did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and LPS-induced IKKα,β phosphorylation. This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. These findings identify p16INK4a as a modulator of macrophage activation and polarization via the JAK2-STAT1 pathway with possible roles in inflammatory diseases. PMID:21636855

  6. Variation in GABA-A subunit gene copy number in an autistic patient with mosaic 4 p duplication (p12p16).

    PubMed

    Kakinuma, Hiroaki; Ozaki, Mamoru; Sato, Hitoshi; Takahashi, Hiroaki

    2008-09-05

    Autism has been associated with chromosomal aberrations, including duplications at chromosome 4, and the identification of genetic factors contributing to the etiology of this disease is the focus of much research. Here we report a Japanese girl with mosaic of chromosome 4p duplication, mos 46,XX,dup(4)(p12p16)[54]/46,XX[6], who was diagnosed with autism at 3 years of age. Fluorescence in situ hybridization (FISH) with probes covering the region spanning a cluster of the gamma aminobutyric acid A (GABA-A) receptor subunit genes in the proximal short arm of chromosome 4 demonstrated total three signals for the GABRG1, GABRA4, and GABRA2 genes, but only two signals for GABRB1. This suggests that aberrant copy number of the GABA-A receptor subunit genes may contribute to the etiology of autism in this patient. 2007 Wiley-Liss, Inc.

  7. Phosphoinositide 5-phosphatase activities control cell motility in glioblastoma: Two phosphoinositides PI(4,5)P2 and PI(3,4)P2 are involved.

    PubMed

    Ramos, Ana Raquel; Elong Edimo, William's; Erneux, Christophe

    2018-01-01

    Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes. Protein kinase B is one target protein and activation of the kinase will have a major impact on cell proliferation, survival and cell metabolism. Two other PIs, PI(4,5)P2 and PI(3,4)P2, are produced or used as substrates of PI 5-phosphatases (OCRL, INPP5B, SHIP1/2, SYNJ1/2, INPP5K, INPP5J, INPP5E). The inositol lipids may influence many aspects of cytoskeletal organization, lamellipodia formation and F-actin polymerization. PI 5-phosphatases have been reported to control cell migration, adhesion, polarity and cell invasion particularly in cancer cells. In glioblastoma, reducing SHIP2 expression can positively or negatively affect the speed of cell migration depending on the glioblastoma cell type. The two PI 5-phosphatases SHIP2 or SKIP could be localized at the plasma membrane and can reduce either PI(3,4,5)P3 or PI(4,5)P2 abundance. In the glioblastoma 1321 N1 cells, SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Posttest RELAP4 analysis of LOFT experiment L1-4

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

    Grush, W.H.; Holmstrom, H.L.O.

    Results of posttest analysis of LOFT loss-of-coolant experiment L1-4 with the RELAP4 code are presented. The results are compared with the pretest prediction and the test data. Differences between the RELAP4 model used for this analysis and that used for the pretest prediction are in the areas of initial conditions, nodalization, emergency core cooling system, broken loop hot leg, and steam generator secondary. In general, these changes made only minor improvement in the comparison of the analytical results to the data. Also presented are the results of a limited study of LOFT downcomer modeling which compared the performance of themore » conventional single downcomer model with that of the new split downcomer model. A RELAP4 sensitivity calculation with artificially elevated emergency core coolant temperature was performed to highlight the need for an ECC mixing model in RELAP4.« less

  9. The UbL-UBA Ubiquilin4 protein functions as a tumor suppressor in gastric cancer by p53-dependent and p53-independent regulation of p21.

    PubMed

    Huang, Shengkai; Li, Yan; Yuan, Xinghua; Zhao, Mei; Wang, Jia; Li, You; Li, Yuan; Lin, Hong; Zhang, Qiao; Wang, Wenjie; Li, Dongdong; Dong, Xin; Li, Lanfen; Liu, Min; Huang, Weiyan; Huang, Changzhi

    2018-06-13

    Ubiquilin4 (Ubqln4), a member of the UbL-UBA protein family, serves as an adaptor in the degradation of specific substrates via the proteasomal pathway. However, the biological function of Ubqln4 remains largely unknown, especially in cancer. Here, we reported that Ubqln4 was downregulated in gastric cancer tissues and functioned as a tumor suppressor by inhibiting gastric cancer cell proliferation in vivo and in vitro. Overexpression of Ubqln4-induced cellular senescence and G1-S cell cycle arrest in gastric cancer cells and activated the p53/p21 axis. Moreover, Ubqln4 regulated p21 through both p53-dependent and p53-independent manners. Ubqln4 interacted with RNF114, an E3 ubiquitin ligase of p21, and negatively regulated its expression level, which in turn stabilized p21 by attenuating proteasomal degradation of p21. These effects of Ubqln4 were partly abrogated in gastric cancer cells upon silencing of p21. Our findings not only establish the anti-tumor potential of Ubqln4 in gastric cancer but also reveal a role for Ubqln4 in regulation of the cell cycle and cellular senescence via stabilizing p21.

  10. Expression of cdk4 and p16 in Oral Lichen Planus.

    PubMed

    Goel, Sinny; Khurana, Nita; Marwah, Akanksha; Gupta, Sunita

    2015-01-01

    The purpose of this study was to evaluate the expression of cdk4 and p16, the proteins implicated in hyperproliferation and arrest in oral lichen planus and to compare their expression in erosive and non-erosive oral lichen planus and with normal mucosa and oral squamous cell carcinoma. Analysis of cdk4 and p16 expression was done in 43 erosive oral lichen planus (EOLP) and 17 non-erosive oral lichen planus (NOLP) cases, 10 normal mucosa and 10 oral squamous cell carcinoma (OSCC) cases with immunohistochemistry. This study demonstrated a significantly increased expression of cytoplasmic cdk4 (80% cases, cells stained - 19.6%), and cytoplasmic p16 (68.3% cases, cells stained - 16.4%) in oral lichen planus (OLP) compared to normal mucosa. cdk4 was much higher in OSCC in both cytoplasm and nuclei compared to normal mucosa. Also, while comparing OLP with positive control, significant difference was noted for cdk4 and p16, with expression being more in OSCC. While comparing EOLP with NOLP; significant differences were seen for cdk4 cytoplasmic staining only, for number of cases with positive staining as well as number of cells stained. Overexpression of cytoplasmic cdk4 and p16 was registered in oral lichen planus, however considerably lower than in squamous cell carcinoma. Erosive oral lichen planus demonstrated overexpression of cytoplasmic cdk4 and premalignant nature compared to non-erosive lesion. Therefore there is an obvious possibility for cytoplasmic expression of cdk4 and p16 to predict malignant potential of oral lichen planus lesions.

  11. Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response.

    PubMed

    Ceruti, Julieta M; Scassa, María E; Marazita, Mariela C; Carcagno, Abel C; Sirkin, Pablo F; Cánepa, Eduardo T

    2009-06-01

    p19INK4d promotes survival of several cell lines after UV irradiation due to enhanced DNA repair, independently of CDK4 inhibition. To further understand the action of p19INK4d in the cellular response to DNA damage, we aimed to elucidate whether this novel regulator plays a role only in mechanisms triggered by UV or participates in diverse mechanisms initiated by different genotoxics. We found that p19INK4d is induced in cells injured with cisplatin or beta-amyloid peptide as robustly as with UV. The mentioned genotoxics transcriptionally activate p19INK4d expression as demonstrated by run-on assay without influencing its mRNA stability and with partial requirement of protein synthesis. It is not currently known whether DNA damage-inducible genes are turned on by the DNA damage itself or by the consequences of that damage. Experiments carried out in cells transfected with distinct damaged DNA structures revealed that the damage itself is not responsible for the observed up-regulation. It is also not known whether the increased expression of DNA-damage-inducible genes is related to immediate protective responses such as DNA repair or to more delayed responses such as cell cycle arrest or apoptosis. We found that ectopic expression of p19INK4d improves DNA repair ability and protects neuroblastoma cells from apoptosis caused by cisplatin or beta-amyloid peptide. Using clonal cell lines where p19INK4d levels can be modified at will, we show that p19INK4d expression correlates with increased survival and clonogenicity. The results presented here, prompted us to suggest that p19INK4d displays an important role in an early stage of cellular DNA damage response.

  12. Exploring the ϒ (4 S ,5 S ,6 S )→hb(1 P )η hidden-bottom hadronic transitions

    NASA Astrophysics Data System (ADS)

    Zhang, Yawei; Li, Gang

    2018-01-01

    Recently, the Belle Collaboration has reported the measurement of the spin-flipping transition ϒ (4 S )→hb(1 P )η with an unexpectedly large branching ratio: B (ϒ (4 S )→hb(1 P )η )=(2.18 ±0.11 ±0.18 )×10-3 . Such a large branching fraction contradicts with the anticipated suppression for the spin flip. In this work, we examine the effects induced by intermediate bottomed meson loops and point out that these effects are significantly important. Using the effective Lagrangian approach (ELA), we find the experimental data on ϒ (4 S )→hb(1 P )η can be accommodated with the reasonable inputs. We then explore the decays ϒ (5 S ,6 S )→hb(1 P )η and find that these two channels also have sizable branching fractions. We also calculate these processes in the framework of nonrelativistic effective field theory (NREFT). For the decays ϒ (4 S )→hb(1 P )η , the NREFT results are at the same order of magnitude but smaller than the ELA results by a factor of 2 to 5. For the decays ϒ (5 S ,6 S )→hb(1 P )η , the NREFT results are smaller than the ELA results by approximately 1 order of magnitude. We suggest a future experiment Belle-II to search for the ϒ (5 S ,6 S )→hb(1 P )η decays, which will be helpful for understanding the transition mechanism.

  13. Comparison of the solubilizing efficiencies of some pH lowering (sulphur and (NH4)2SO4) amendments on Cd and Zn mobility in soils.

    PubMed

    Amoakwah, Emmanuel; Van Slycken, Stijn; Essumang, David K

    2014-08-01

    The use of conventional methods to clean up the soil is very expensive and destructive to the ecosystem. The concept of phytoextraction has been introduced to safely manage soils contaminated with heavy metals. However, using plants to remediate polluted soils is a lengthy process. This has necessitated the use of amendments to potentially enhance solubilization of metals in order to increase their bioavailability in the soil solution. A pot experiment was conducted to study the effect of some selected pH lowering amendments [elemental sulphur and (NH4)2SO4] on the solubility and availability of Cd and Zn. The application of these amendments resulted in a decrease in the pH of the soil. The decrease in pH significantly enhanced the solubilization and the mobility of Cd and Zn into the soil solution. The CaCl2 extraction protocol was employed to study the effects of the various amendments on the mobility of Cd and Zn.

  14. Polarization effects in the reactions p + 3 He → π+ + 4 He, π+ + 4 He → p + 3 He and quantum character of spin correlations in the final (p, 3 He) system

    NASA Astrophysics Data System (ADS)

    Lyuboshitz, Valery V.; Lyuboshitz, Vladimir L.

    2017-12-01

    The general consequences of T invariance for the direct and inverse binary reactions a + b → c + d, c + d → a + b with spin-1/2 particles a, b and unpolarized particles c, d are considered. Using the formalism of helicity amplitudes, the polarization effects are studied in the reaction p + 3 He → π+ + 4 He and in the inverse process π+ + 4 He → p + 3 He. It is shown that in the reaction π + + 4 He → p + 3 He the spins of the final proton and 3 He nucleus are strongly correlated. A structural expression through helicity amplitudes, corresponding to arbitrary emission angles, is obtained for the correlation tensor. It is established that in the reaction π + + 4 He → p + 3 He one of the “classical” incoherence inequalities of the Bell type for diagonal components of the correlation tensor is necessarily violated and, thus, the spin correlations of the final particles have the strongly pronounced quantum character.

  15. Continuum analyzing power for 4He(p-->,p') at 100 MeV

    NASA Astrophysics Data System (ADS)

    Lawrie, J. J.; Whittal, D. M.; Cowley, A. A.

    1990-08-01

    Distorted-wave impulse approximation calculations of the continuum analyzing power for the inclusive reaction 4He(p-->,p') at an incident energy of 100 MeV are presented. In addition to the quasifree knockout of nucleons, contributions from the knockout of deuteron, triton, and helion clusters are taken into account, together with a breakup component. Whereas nucleon knockout by itself does not account for the experimentally observed analyzing power, the inclusion of clusters has a large effect. Thus a simple knockout model is able to provide a reasonable description of the experimental continuum analyzing power.

  16. The p16INK4alpha/p19ARF gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas.

    PubMed

    Kannan, K; Munirajan, A K; Krishnamurthy, J; Bhuvarahamurthy, V; Mohanprasad, B K; Panishankar, K H; Tsuchida, N; Shanmugam, G

    2000-03-01

    Eighty-seven untreated primary oral squamous cell carcinomas (SCCs) associated with betel quid and tobacco chewing from Indian patients were analysed for the presence of mutations in the commonly shared exon 2 of p16INK4alpha/p19ARF genes. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing analysis were used to detect mutations. SSCP analysis indicated that only 9% (8/87) of the tumours had mutation in p16INK4alpha/p19ARF genes. Seventy-two tumours studied here were previously analysed for p53 mutations and 21% (15/72) of them were found to have mutations in p53 gene. Only one tumour was found to have mutation at both p53 and p16INK4alpha/p19ARF genes. Thus, the mutation rates observed were 21% for p53, 9% for p16INK4alpha/p19ARF, and 1% for both. Sequencing analysis revealed two types of mutations; i) G to C (GCAG to CCAG) transversion type mutation at intron 1-exon 2 splice junction and ii) another C to T transition type mutation resulting in CGA to TGA changing arginine to a termination codon at p16INK4alpha gene codon 80 and the same mutation will alter codon 94 of p19ARF gene from CCG to CTG (proline to leucine). These results suggest that p16INK4alpha/p19ARF mutations are less frequent than p53 mutations in Indian oral SCCs. The p53 and p16INK4alpha/p19ARF mutational events are independent and are mutually exclusive suggesting that mutational inactivation of either p53 or p16INK4alpha/p19ARF may alleviate the need for the inactivation of the other gene.

  17. Biotransformation of 2,4,6-Trinitrotoluene with Phanerochaete chrysosporium in Agitated Cultures at pH 4.5†

    PubMed Central

    Hawari, Jalal; Halasz, Annamaria; Beaudet, Sylvie; Paquet, Louise; Ampleman, Guy; Thiboutot, Sonia

    1999-01-01

    The biotransformation of 2,4,6-trinitrotoluene (TNT) (175 μM) by Phanerochaete chrysosporium with molasses and citric acid at pH 4.5 was studied. In less than 2 weeks, TNT disappeared completely, but mineralization (liberated 14CO2) did not exceed 1%. A time study revealed the presence of several intermediates, marked by the initial formation of two monohydroxylaminodinitrotoluenes (2- and 4-HADNT) followed by their successive transformation to several other products, including monoaminodinitrotoluenes (ADNT). A group of nine acylated intermediates were also detected. They included 2-N-acetylamido-4,6-dinitrotoluene and its p isomer, 2-formylamido-4,6-dinitrotoluene and its p isomer (as acylated ADNT), 4-N-acetylamino-2-amino-6-nitrotoluene and 4-N-formylamido-2-amino-6-nitrotoluene (as acetylated DANT), 4-N-acetylhydroxy-2,6-dinitrotoluene and 4-N-acetoxy-2,6-dinitrotoluene (as acetylated HADNT), and finally 4-N-acetylamido-2-hydroxylamino-6-nitrotoluene. Furthermore, a fraction of HADNTs were found to rearrange to their corresponding phenolamines (Bamberger rearrangement), while another group dimerized to azoxytoluenes which in turn transformed to azo compounds and eventually to the corresponding hydrazo derivatives. After 30 days, all of these metabolites, except traces of 4-ADNT and the hydrazo derivatives, disappeared, but mineralization did not exceed 10% even after the incubation period was increased to 120 days. The biotransformation of TNT was accompanied by the appearance of manganese peroxidase (MnP) and lignin-dependent peroxidase (LiP) activities. MnP activity was observed almost immediately after TNT disappearance, which was the period marked by the appearance of the initial metabolites (HADNT and ADNT), whereas the LiP activity was observed after 8 days of incubation, corresponding to the appearance of the acyl derivatives. Both MnP and LiP activities reached their maximum levels (100 and 10 U/liter, respectively) within 10 to 15 days after

  18. Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4.

    PubMed

    Orlacchio, A; Patrono, C; Gaudiello, F; Rocchi, C; Moschella, V; Floris, R; Bernardi, G; Kawarai, T

    2008-05-20

    To perform a clinical and genetic study of two large Italian families (RM-36 and RM-51) showing the cardinal clinical features of Silver syndrome (SS), a rare dominantly inherited form of hereditary spastic paraplegia (HSP) complicated by amyotrophy of the small hand muscles. Clinical assessment including neurophysiologic, neuropsychological, and neuroimaging evaluations. Genetic studies included linkage and sequence analyses. Using a genome-wide survey in the RM-36 family, a novel locus (SPG38) has been identified and mapped within the 13.1-cM region on chromosome 4p16-p15 between markers D4S432 and D4S1599. The RM-51 family was linked to the SPG4 locus at 2p21-p24 and sequence analysis of SPG4 showed a novel frameshift mutation p.Asp321GlyfsX6. Clinical examination of the affected members carrying the mutation showed high frequency of additional clinical features including decreased vibration sense, pes cavus, temporal lobe epilepsy, and cognitive impairment. This study demonstrates evidence of a novel locus SPG38 for Silver syndrome (SS) and suggests that genetic defects in SPG4 might lead to broad clinical features overlapped with those of SS.

  19. Familial interstitial deletion of the short arm of chromosome 4 (p15.33-p16.3) characterized by molecular cytogenetic analysis.

    PubMed

    Basinko, Audrey; Douet-Guilbert, Nathalie; Parent, Philippe; Blondin, Gilles; Mingam, M; Monot, Françoise; Morel, Frédéric; Le Bris, Marie-Josée; De Braekeleer, Marc

    2008-04-01

    This 15-month boy was expressed at the cytogenetic laboratory because of psychomotor development delay. He was tall and had plagiocephaly, micrognathia, high nasal bridge, anteverted nostrils and pectus excavatum. A 46,XY,del(4)(p16.1p16.3) karyotype was found using high-resolution R-banding technique. FISH studies using the LSI Wolf-Hirschhorn dual color 4p16.3 and the TelVysion 4p probes showed no deletion. Using BACs, the distal breakpoint was located in 4p16.3, between RP11-165K4 and RP11-717M10 and the proximal breakpoint in 4p15.33, between RP11-74M11 and RP11-1J7; therefore, approximately 7.96 Mb of the short arm were deleted. The maternal karyotype showed the same deletion, but in a mosaic status. Two distinct phenotypes have been recognized on the basis of the chromosomal bands involved in 4p deletion: the Wolf-Hirschhorn syndrome (WHS) and a proximal 4p deletion syndrome (4p15.2-p15.32). Our observation confirms that the basic WHS phenotype maps distally to this region. Copyright 2008 Wiley-Liss, Inc.

  20. Spectrophotometric and electrochemical study for metal ion binding of azocalix[4]arene bearing p-ethylester group

    NASA Astrophysics Data System (ADS)

    Kim, Tae Hyun

    2017-05-01

    The complexation behavior of diazophenylcalix[4]arene bearing para-ethylester group (p-EAC) for alkali, alkaline earth, various heavy and transition metal ions (Li+, Na+, K+, Rb+, Cs+, Mg2 +, Ca2 +, Sr2 +, Ba2 +, Cr3 +, Fe2 +, Co2 +, Ni2 +, Cu2 +, Zn2 +, Pb2 +) was investigated by spectrophotometric and electrochemical methods in CH3CN. p-EAC exhibits decreased absorbance at 353 nm in the presence of Cr3 +, Fe2 +, Pb2 +, and Cu2 +. The spectra of p-EAC showed bathochromic shift in absorption maximum on the addition of Cr3 +, Fe2 +, or Pb2 + with decreasing order of absorbance (Cr3 + > Fe2 + > Pb2 +), and on the other hand, hypsochromic shift on the addition of Cu2 +. This leads to the selective coloration from light green to orange and colorless for Cr3 + and Cu2 + that can be detected by the naked eye, respectively. In electrochemistry experiments, p-EAC also showed two different types of voltammetric changes toward Cr3 +, Fe2 +, or Pb2 +, and toward Cu2 +, whereas no significant changes occurred in the presence of the other metal ions. Nonlinear fitting curve procedure was used to determine a logarithmic value of 5.20, 4.92, 3.54 and 4.80 for the stability constants of the complex of p-EAC with Cr3 +, Fe2 +, Pb2 +, and Cu2 +, respectively.

  1. Open-Source Low-Cost Wireless Potentiometric Instrument for pH Determination Experiments

    ERIC Educational Resources Information Center

    Jin, Hao; Qin, Yiheng; Pan, Si; Alam, Arif U.; Dong, Shurong; Ghosh, Raja; Deen, M. Jamal

    2018-01-01

    pH determination is an essential experiment in many chemistry laboratories. It requires a potentiometric instrument with extremely low input bias current to accurately measure the voltage between a pH sensing electrode and a reference electrode. In this technology report, we propose an open-source potentiometric instrument for pH determination…

  2. Evidence for a G protein-coupled diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) receptor binding site in lung membranes from rat.

    PubMed

    Laubinger, W; Reiser, G

    1999-01-29

    Nucleotide receptors are of considerable importance in the treatment of lung diseases, such as cystic fibrosis. Because diadenosine polyphosphates may also be of significance as signalling molecules in lung, as they are in a variety of tissues, in the present work we investigated the binding sites for [3H]diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) in plasma membranes from rat lung and studied their possible coupling to G proteins. We present evidence for a single high-affinity binding site for [3H]Ap4A with similar affinity for other diadenosine polyphosphates ApnA (n = 2 to 6). Displacement studies with different nucleotides revealed that the [3H]Ap4A binding site was different from P2X and P2Y2 receptor binding sites. Pretreatment of lung membranes with GTPgammaS or GTP in the presence of Mg2+ increased the Ki for Ap4A from 91 nM to 5.1 microM, which is indicative of G protein coupling. The putative coupling to G proteins was further confirmed by the enhancement of [35S]GTPgammaS binding (to Galpha proteins) to lung membranes by Ap4A (63% increase over basal) in a concentration-dependent manner. Therefore, our data for the first time provide evidence of a G protein-coupled Ap4A binding site in lung membranes.

  3. Dual doped monolayer and bilayer graphene: The case of 4p and 2p elements

    NASA Astrophysics Data System (ADS)

    Denis, Pablo A.; Iribarne, Federico

    2016-08-01

    4p/2p dual-doped monolayer and bilayer graphene were studied via first principle calculations. Generally, dopants prefer to be agglomerated. A second dopant significantly reduces formation energies. Thus, partially reduced graphene oxide would favor substitutional doping by facilitating the introduction of the 4p dopants. Dual-doping can tune the band gap from 0.1 to 0.8 eV. For bilayer graphene, large atomic radii elements (Gallium and Germanium) form interlayer bonds with the undoped sheet. For some dual-doped graphenes, interlayer GaC and GeC bonds were formed, increasing the chemical reactivity of the undoped layer and affecting its electronic structure, with metallic or semiconducting characters observed.

  4. 16 CFR § 1500.4 - Human experience with hazardous substances.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Human experience with hazardous substances... REGULATIONS § 1500.4 Human experience with hazardous substances. (a) Reliable data on human experience with... data, the human experience takes precedence. (b) Experience may show that an article is more or less...

  5. Synthetic, Infrared, 1Hand 13CNMR Spectral Studies on N-(p-Substituted Phenyl)-p-Substituted Benzenesulphonamides, p-X'C6H4SO2NH- (p-XC6H4), where X' or X = H, CH3, C2H5, F, Cl or Br

    NASA Astrophysics Data System (ADS)

    Gowda, B. Thimme; Jayalakshmi, K. L.; Shetty, Mahesha

    2004-05-01

    Thirty N-(p-substituted phenyl)-p-substituted benzenesulphonamides of the general formula, p-X'C6H4SO2NH(p-XC6H4), where X' or X = H, CH3, C2H5, F, Cl or Br, are synthesised and their infrared spectra in the solid state and 1H and 13C NMR spectra in solution are measured. The N-H stretching vibrational frequencies, νN-H vary in the range 3334 - 3219 cm-1, while the asymmetric and symmetric SO2 vibrations appear in the ranges 1377 - 1311 cm-1 and 1182 - 1151 cm-1, respectively. The compounds exhibit S-N and C-N stretching vibrational absorptions in the ranges 937 - 898 cm-1 and 1310 - 1180 cm-1, respectively. There are no particular trends in the variation of these frequencies on substitution with either electron withdrawing or electron donating groups. The 1H and 13C chemical shifts of N-(p-substituted phenyl)-p-substituted benzenesulphonamides, are assigned to various protons and carbons of the two benzene rings. Further, incremental shifts of the ring protons and carbons due to -SO2NH(p-XC6H4) groups in the compounds of the formula, C6H5SO2NH(p-XC6H4), and p-X'C6H4SO2- and p-X'C6H4SO2NH- groups in the compounds of the formula, p-X'C6H4SO2NH(C6H5) are computed and used to calculate the 1H and 13C chemical shifts of the parallely substituted compounds of the general formula p-X'C6H4SO2NH(p-XC6H4). The computed values agree well with the observed chemical shifts. The above incremental shifts are found to correlate with the Hammett substituent parameters.

  6. Summary and overview of the CYCLOPS P addition Lagrangian experiment in the Eastern Mediterranean

    NASA Astrophysics Data System (ADS)

    Krom, M. D.; Thingstad, T. F.; Brenner, S.; Carbo, P.; Drakopoulos, P.; Fileman, T. W.; Flaten, G. A. F.; Groom, S.; Herut, B.; Kitidis, V.; Kress, N.; Law, C. S.; Liddicoat, M. I.; Mantoura, R. F. C.; Pasternak, A.; Pitta, P.; Polychronaki, T.; Psarra, S.; Rassoulzadegan, F.; Skjoldal, E. F.; Spyres, G.; Tanaka, T.; Tselepides, A.; Wassmann, P.; Wexels Riser, C.; Woodward, E. M. S.; Zodiatis, G.; Zohary, T.

    2005-11-01

    CYCLOPS was a European Framework 5 program to further our understanding of phosphorus cycling in the Eastern Mediterranean. The core of CYCLOPS was a Lagrangian experiment in which buffered phosphoric acid was added to a <4×4 km patch of water together with SF 6 as the inert tracer. The patch was followed for nine days in total. Results obtained prior to the experiment showed that the system was typically ultra-oligotrophic and P-starved with DON:DOP, PON:POP and DIN:DIP all having ratios greatly in excess of 16:1 in surface waters. To our surprise, we found that although the added phosphate was rapidly taken up by the microbial biota, there was a small but significant decrease in chlorophyll a and no increase in primary production, together with an increase in heterotrophic bacterial activity, ciliate numbers and in the gut fullness and egg numbers in the zooplankton community. A microcosm experiment carried out using within-patch and out-of-patch water showed that the phytoplankton community were N and P co-limited while the bacteria and micrograzers were P-limited. Thus this system tends to N and P co-limitation of phytoplankton productivity in summer possibly caused by bioavailable DIN being converted into non-bioavailable forms of DON. On the basis of the data collected within the programme it was concluded that this behavior could be explained by three non-mutually exclusive processes described as (1) trophic by-pass in which the added phosphate gets directly to the grazing part of the predatory food chain from the heterotrophic bacteria bypassing the phytoplankton compartment phosphate, (2) trophic tunnelling in which phosphate is rapidly taken up by both phytoplankton and bacteria via rapid luxury consumption. This causes an immediate change in the phosphorus content but not the abundance of the prey organisms. The added P then "reappears" as responses at the predator level much more rapidly than expected, and (3) mixotrophic by-pass in which inorganic

  7. Understanding causal pathways within health systems policy evaluation through mediation analysis: an application to payment for performance (P4P) in Tanzania.

    PubMed

    Anselmi, Laura; Binyaruka, Peter; Borghi, Josephine

    2017-02-02

    The evaluation of payment for performance (P4P) programmes has focused mainly on understanding contributions to health service coverage, without unpacking causal mechanisms. The overall aim of the paper is to test the causal pathways through which P4P schemes may (or may not) influence maternal care outcomes. We used data from an evaluation of a P4P programme in Tanzania. Data were collected from a sample of 3000 women who delivered in the 12 months prior to interview and 200 health workers at 150 health facilities from seven intervention and four comparison districts in Tanzania in January 2012 and in February 2013. We applied causal mediation analysis using a linear structural equation model to identify direct and indirect effects of P4P on institutional delivery rates and on the uptake of two doses of an antimalarial drug during pregnancy. We first ran a series of linear difference-in-difference regression models to test the effect of P4P on potential mediators, which we then included in a linear difference-in-difference model evaluating the impact of P4P on the outcome. We tested the robustness of our results to unmeasured confounding using semi-parametric methods. P4P reduced the probability of women paying for delivery care (-4.5 percentage points) which mediates the total effect of P4P on institutional deliveries (by 48%) and on deliveries in a public health facility (by 78%). P4P reduced the stock-out rate for some essential drugs, specifically oxytocin (-36 percentage points), which mediated the total effect of P4P on institutional deliveries (by 22%) and deliveries in a public health facility (by 30%). P4P increased kindness at delivery (5 percentage points), which mediated the effect of P4P on institutional deliveries (by 48%) and on deliveries in a public health facility (by 49%). P4P increased the likelihood of supervision visits taking place within the last 90 days (18 percentage points), which mediated 15% of the total P4P effect on the uptake of

  8. The consequence of regional gradients of P-gp and CYP3A4 for drug-drug interactions by P-gp inhibitors and the P-gp/CYP3A4 interplay in the human intestine ex vivo.

    PubMed

    Li, Ming; de Graaf, Inge A M; van de Steeg, Evita; de Jager, Marina H; Groothuis, Geny M M

    2017-04-01

    Intestinal P-gp and CYP3A4 work coordinately to reduce the intracellular concentration of drugs, and drug-drug interactions (DDIs) based on this interplay are of clinical importance and require pre-clinical investigation. Using precision-cut intestinal slices (PCIS) of human jejunum, ileum and colon, we investigated the P-gp/CYP3A4 interplay and related DDIs with P-gp inhibitors at the different regions of the human intestine with quinidine (Qi), dual substrate of P-gp and CYP3A4, as probe. All the P-gp inhibitors increased the intracellular concentrations of Qi by 2.1-2.6 fold in jejunum, 2.6-3.8 fold in ileum but only 1.2-1.3 fold in colon, in line with the different P-gp expression in these intestinal regions. The selective P-gp inhibitors (CP100356 and PSC833) enhanced 3-hydroxy-quinidine (3OH-Qi) in jejunum and ileum, while dual inhibitors of P-gp and CYP3A4 (verapamil and ketoconazole) decreased the 3OH-Qi production, despite of the increased intracellular Qi concentration, due to inhibition of CYP3A4. The outcome of DDIs based on P-gp/CYP3A4 interplay, shown as remarkable changes in the intracellular concentration of both the parent drug and the metabolite, varied among the intestinal regions, probably due to the different expression of P-gp and CYP3A4, and were different from those found in rat PCIS, which may have important implications for the disposition and toxicity of drugs and their metabolites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. P4 medicine approach to obstructive sleep apnoea.

    PubMed

    Lim, Diane C; Sutherland, Kate; Cistulli, Peter A; Pack, Allan I

    2017-07-01

    P4 medicine is an evolving approach to personalized medicine. The four Ps offer a means to: Predict who will develop disease and co-morbidities; Prevent rather than react to disease; Personalize diagnosis and treatment; have patients Participate in their own care. P4 medicine is very applicable to obstructive sleep apnoea (OSA) because each OSA patient has a different pathway to disease and its consequences. OSA has both structural and physiological mechanisms with different clinical subgroups, different molecular profiles and different consequences. This may explain why there are different responses to alternative therapies, such as intraoral devices and hypoglossal nerve stimulation therapy. Currently, technology facilitates patients to participate in their own care from screening for OSA (snoring and apnoea apps) to monitoring response to therapy (sleep monitoring, blood pressure, oxygen saturation and heart rate) as well as monitoring their own continuous positive airway pressure (CPAP) compliance. We present a conceptual framework that provides the basis for a new, P4 medicine approach to OSA and should be considered more in depth: predict and prevent those at high risk for OSA and consequences, personalize the diagnosis and treatment of OSA and build in patient participation to manage OSA. © 2017 Asian Pacific Society of Respirology.

  10. Regulation of p53 Target Gene Expression by Peptidylarginine Deiminase 4 ▿ †

    PubMed Central

    Li, Pingxin; Yao, Hongjie; Zhang, Zhiqiang; Li, Ming; Luo, Yuan; Thompson, Paul R.; Gilmour, David S.; Wang, Yanming

    2008-01-01

    Histone Arg methylation has been correlated with transcriptional activation of p53 target genes. However, whether this modification is reversed to repress the expression of p53 target genes is unclear. Here, we report that peptidylarginine deiminase 4, a histone citrullination enzyme, is involved in the repression of p53 target genes. Inhibition or depletion of PAD4 elevated the expression of a subset of p53 target genes, including p21/CIP1/WAF1, leading to cell cycle arrest and apoptosis. Moreover, the induction of p21, cell cycle arrest, and apoptosis by PAD4 depletion is p53 dependent. Protein-protein interaction studies showed an interaction between p53 and PAD4. Chromatin immunoprecipitation assays showed that PAD4 is recruited to the p21 promoter in a p53-dependent manner. RNA polymerase II (Pol II) activities and the association of PAD4 are dynamically regulated at the p21 promoter during UV irradiation. Paused RNA Pol II and high levels of PAD4 were detected before UV treatment. At early time points after UV treatment, an increase of histone Arg methylation and a decrease of citrullination were correlated with a transient activation of p21. At later times after UV irradiation, a loss of RNA Pol II and an increase of PAD4 were detected at the p21 promoter. The dynamics of RNA Pol II activities after UV treatment were further corroborated by permanganate footprinting. Together, these results suggest a role of PAD4 in the regulation of p53 target gene expression. PMID:18505818

  11. KLF4, p21 and context-dependent opposing forces in cancer.

    PubMed

    Rowland, Benjamin D; Peeper, Daniel S

    2006-01-01

    Krüppel-like factors are transcriptional regulators that influence several cellular functions, including proliferation. Recent studies have shown that one family member, KLF4, can function both as a tumour suppressor and an oncogene. The ability of KLF4 to affect the levels of expression of the cell-cycle regulator p21 seems to be involved, in that this protein might function as a switch that determines the outcome of KLF4 signalling. Is this role of p21 restricted to KLF4, or does p21 represent a nodal point for signals from multiple other factors with opposing functions in cancer?

  12. MiR-129-5p Inhibits Proliferation and Invasion of Chondrosarcoma Cells by Regulating SOX4/Wnt/β-Catenin Signaling Pathway.

    PubMed

    Zhang, Peng; Li, Jifeng; Song, Yuze; Wang, Xiao

    2017-01-01

    Recently, microRNAs (miRNA) have been identified as novel regulators in Chondrosarcoma (CHS). This study was aimed to identify the roles of miR-129-5p-5p in regulation of SOX4 and Wnt/β-catenin signaling pathway, as well as cell proliferation and apoptosis in chondrosarcomas. Tissue samples were obtained from chondrosarcoma patients. Immunohistochemistry, real-time quantitative RT-PCR (RT-qPCR) and western blot analysis were performed to detect the expressions of miR-129-5p and SOX4. Luciferase assay was conducted to confirm that miR-129-5p directly targeted SOX4 mRNA. Manipulations of miR-129-5p and SOX4 expression were achieved through cell transfection. Cell proliferation, migration and apoptosis were evaluated by CCK-8 assay, colony forming assay, wound healing assay and flow cytometry in vitro. For in vivo experiment, the tumor xenograft model was established to evaluate the effects of miR-129-5p and SOX4 on chondrosarcomas. The expression of miR-129-5p was significantly down-regulated in chondrosarcoma tissues as well as cells in comparison with normal ones, while SOX4 was over-activated. Further studies suggested that miR-129-5p suppressed cell proliferation, migration and promoted apoptosis by inhibiting SOX4 and Wnt/β-catenin pathway. MiR-129-5p inhibits the Wnt/β-catenin signaling pathway by targeting SOX4 and further suppresses cell proliferation, migration and promotes apoptosis in chondrosarcomas. © 2017 The Author(s). Published by S. Karger AG, Basel.

  13. 40 CFR 439.4 - General limitation or standard for pH.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false General limitation or standard for pH. 439.4 Section 439.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT... General limitation or standard for pH. The pH must remain within the range 6.0 to 9.0 in any discharge...

  14. 40 CFR 439.4 - General limitation or standard for pH.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 30 2014-07-01 2014-07-01 false General limitation or standard for pH. 439.4 Section 439.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT... General limitation or standard for pH. The pH must remain within the range 6.0 to 9.0 in any discharge...

  15. 40 CFR 439.4 - General limitation or standard for pH.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false General limitation or standard for pH. 439.4 Section 439.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT... General limitation or standard for pH. The pH must remain within the range 6.0 to 9.0 in any discharge...

  16. 3′ Phosphatase activity toward phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] by voltage-sensing phosphatase (VSP)

    PubMed Central

    Kurokawa, Tatsuki; Takasuga, Shunsuke; Sakata, Souhei; Yamaguchi, Shinji; Horie, Shigeo; Homma, Koichi J.; Sasaki, Takehiko; Okamura, Yasushi

    2012-01-01

    Voltage-sensing phosphatases (VSPs) consist of a voltage-sensor domain and a cytoplasmic region with remarkable sequence similarity to phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor phosphatase. VSPs dephosphorylate the 5′ position of the inositol ring of both phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] upon voltage depolarization. However, it is unclear whether VSPs also have 3′ phosphatase activity. To gain insights into this question, we performed in vitro assays of phosphatase activities of Ciona intestinalis VSP (Ci-VSP) and transmembrane phosphatase with tensin homology (TPTE) and PTEN homologous inositol lipid phosphatase (TPIP; one human ortholog of VSP) with radiolabeled PI(3,4,5)P3. TLC assay showed that the 3′ phosphate of PI(3,4,5)P3 was not dephosphorylated, whereas that of phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] was removed by VSPs. Monitoring of PI(3,4)P2 levels with the pleckstrin homology (PH) domain from tandem PH domain-containing protein (TAPP1) fused with GFP (PHTAPP1-GFP) by confocal microscopy in amphibian oocytes showed an increase of fluorescence intensity during depolarization to 0 mV, consistent with 5′ phosphatase activity of VSP toward PI(3,4,5)P3. However, depolarization to 60 mV showed a transient increase of GFP fluorescence followed by a decrease, indicating that, after PI(3,4,5)P3 is dephosphorylated at the 5′ position, PI(3,4)P2 is then dephosphorylated at the 3′ position. These results suggest that substrate specificity of the VSP changes with membrane potential. PMID:22645351

  17. Periventricular heterotopia in a boy with interstitial deletion of chromosome 4p.

    PubMed

    Gawlik-Kuklinska, Katarzyna; Wierzba, Jolanta; Wozniak, Agnieszka; Iliszko, Mariola; Debiec-Rychter, Maria; Dubaniewicz-Wybieralska, Miroslawa; Limon, Janusz

    2008-01-01

    We report on a 4-year-old boy with a proximal interstitial deletion in the short arm of chromosome 4p with the karyotype 46,XY,del(4)(p14p15.32),inv(9)(p13q13). For a precise delineation of the deleted region, an array-based comparative genomic hybridization (a-CGH) analysis was performed. The proband's phenotype and cytogenetic findings are compared with previously reported cases with proximal 4p deletion syndrome. The syndrome is associated with normal growth, varying degrees of mental retardation, characteristic facial appearance and minor dysmorphic features. Additionally, our patient developed a seizure disorder due to abnormal neuronal migration, i.e., periventricular heterotopia.

  18. A Course-Based Undergraduate Research Experience Investigating p300 Bromodomain Mutations#

    PubMed Central

    Shanle, Erin K.; Tsun, Ian K.; Strahl, Brian D.

    2016-01-01

    Course-based undergraduate research experiences (CUREs) provide an opportunity for students to engage in experiments with outcomes that are unknown to both the instructor and students. These experiences allow students and instructors to collaboratively bridge the research laboratory and classroom, and provide research experiences for a large number of students relative to traditional individual mentored research. Here, we describe a molecular biology CURE investigating the impact of clinically relevant mutations found in the bromodomain of the p300 transcriptional regulator on acetylated histone interaction. In the CURE, students identified missense mutations in the p300 bromo-domain using the Catalogue of Somatic Mutations in Cancer (COSMIC) database and hypothesized the effects of the mutation on the acetyl-binding function of the domain. They cloned and purified the mutated bromodomain and performed peptide pulldown assays to define its potential to bind to acetylated histones. Upon completion of the course, students showed increased confidence performing molecular techniques and reported positively on doing a research project in class. In addition, results generated in the classroom were further validated in the research laboratory setting thereby providing a new model for faculty to engage in both course-based and individual undergraduate research experiences. PMID:26537758

  19. A course-based undergraduate research experience investigating p300 bromodomain mutations.

    PubMed

    Shanle, Erin K; Tsun, Ian K; Strahl, Brian D

    2016-01-01

    Course-based undergraduate research experiences (CUREs) provide an opportunity for students to engage in experiments with outcomes that are unknown to both the instructor and students. These experiences allow students and instructors to collaboratively bridge the research laboratory and classroom, and provide research experiences for a large number of students relative to traditional individual mentored research. Here, we describe a molecular biology CURE investigating the impact of clinically relevant mutations found in the bromodomain of the p300 transcriptional regulator on acetylated histone interaction. In the CURE, students identified missense mutations in the p300 bromodomain using the Catalogue of Somatic Mutations in Cancer (COSMIC) database and hypothesized the effects of the mutation on the acetyl-binding function of the domain. They cloned and purified the mutated bromodomain and performed peptide pulldown assays to define its potential to bind to acetylated histones. Upon completion of the course, students showed increased confidence performing molecular techniques and reported positively on doing a research project in class. In addition, results generated in the classroom were further validated in the research laboratory setting thereby providing a new model for faculty to engage in both course-based and individual undergraduate research experiences. © 2015 The International Union of Biochemistry and Molecular Biology.

  20. The P4 truss is moved to a workstand in the SSPF

    NASA Technical Reports Server (NTRS)

    2000-01-01

    After its move across the Space Station Processing Facility, the International Space Station's P4 truss rests in its workstand. Part of the 10-truss, girder-like structure that will ultimately extend the length of a football field, the P4 is the second port truss segment that will attach to the first port truss segment (P1 truss). The P4 is scheduled for mission 12A in September 2002.

  1. Synthesis and synchrotron X-ray characterization of two 2D Hoffman related compounds [Ni(p-Xylylenediamine)nNi(CN)4] and [Ni(p-tetrafluoroxylylenediamine)nNi(CN)4

    NASA Astrophysics Data System (ADS)

    Wong-Ng, W.; Culp, J. T.; Siderius, D. W.; Chen, Y. S.

    2018-07-01

    Synchrotron X-ray single crystal structure determination of two 2D Hofmann-related compounds, [Ni(p-Xylyenediamine)n-tetracyanonickelate] (abbreviated as Ni-pXdam) and [Ni(tetrafluoro-p-Xylyenediamine)n-tetracyanonickelate] (abbreviated as Ni-pXdamF4), have been conducted. Both the pXdam and pXdamF4 ligands contain two short chains of -CH2NH2 at the para-positions of a phenyl ring. These flexible chains link the 6-fold coordinated Ni2 sites throughout the network. In Ni-pXdam, the closed-2D network of [Ni-(CN-Ni1/4-)4]∞ is broken into 1D chains, leaving the C≡N groups at the trans-positions of the Ni(CN)4 moiety unbridged. The resulting 1D chains [(trans-)-NC-Ni(CN)2-CN-Ni-]∞ runs along the [010] direction of the unit cell. The pXdam ligands bridge in pair between the Ni atoms of the adjacent chains. The catenation structure of [Ni{(pXdam)}]∞ could be referred to as double -1D. In Ni-pXdamF4, the -CH2NH2 ligands connect the neighboring chains via the 6-fold Ni2 site. Surrounding the 4-fold Ni1 site, the two trans terminal C≡N groups were replaced by the Lewis base NH3 during the synthesis process, therefore preventing the propagation of the 2D net to form a 3D network. Computed pore volume of both compounds indicated that there is not sufficient space in the structure to accommodate gas molecules. In both compounds, hydrogen bonds were found, and solvent of crystallization was absent due to the limited free space in the structure.

  2. 40 CFR 439.4 - General limitation or standard for pH.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false General limitation or standard for pH. 439.4 Section 439.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT... limitation or standard for pH. The pH must remain within the range 6.0 to 9.0 in any discharge subject to BPT...

  3. Physics & Preservice Teachers Partnership Project (P4): An interdisciplinary peer learning tool

    NASA Astrophysics Data System (ADS)

    Simmonds, Paul J.; Wenner, Julianne A.

    Physics graduate students (PGs) and teacher candidates (TCs) often graduate with specific weaknesses. PGs frequently lack training in teaching and effective communication. TCs are typically underprepared for teaching science, and physics in particular. In response to these challenges, we created P4 . P4 is an innovative model for peer learning, creating interdisciplinary partnerships that help college physics instructors train their students in the ``soft skills'' prized in both academia and industry, while helping teacher educators infuse more content knowledge into science methods courses. In P4, PGs plan a lesson and deliver physics content to TCs. TCs then use this content to design and execute a 15-minute elementary science lesson. Framed by the concept of peer learning, we expected P4 would help PGs develop their teaching and communication skills, and TCs learn more physics. We studied the affordances and constraints of P4 to inform future iterations. Overall, P4 was successful, with both PGs and TCs reporting benefits. Affordances for PGs included the chance to plan and teach a class; TCs benefitted from working with experts to increase content knowledge. We will share the full findings and implications of our study, and outline next steps for P4.

  4. 40 CFR 721.10369 - Carbonic acid, diphenyl ester, polymer with diphenyl P-methylphosphonate and 4,4′-(1...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Carbonic acid, diphenyl ester, polymer... Carbonic acid, diphenyl ester, polymer with diphenyl P-methylphosphonate and 4,4′-(1-methylethylidene) bis... identified as carbonic acid, diphenyl ester, polymer with diphenyl P-methylphosphonate and 4,4′-(1...

  5. Phosphatidylserine Stimulation of Drs2p·Cdc50p Lipid Translocase Dephosphorylation Is Controlled by Phosphatidylinositol-4-phosphate*

    PubMed Central

    Jacquot, Aurore; Montigny, Cédric; Hennrich, Hanka; Barry, Raphaëlle; le Maire, Marc; Jaxel, Christine; Holthuis, Joost; Champeil, Philippe; Lenoir, Guillaume

    2012-01-01

    Here, Drs2p, a yeast lipid translocase that belongs to the family of P4-type ATPases, was overexpressed in the yeast Saccharomyces cerevisiae together with Cdc50p, its glycosylated partner, as a result of the design of a novel co-expression vector. The resulting high yield allowed us, using crude membranes or detergent-solubilized membranes, to measure the formation from [γ-32P]ATP of a 32P-labeled transient phosphoenzyme at the catalytic site of Drs2p. Formation of this phosphoenzyme could be detected only if Cdc50p was co-expressed with Drs2p but was not dependent on full glycosylation of Cdc50p. It was inhibited by orthovanadate and fluoride compounds. In crude membranes, the phosphoenzyme formed at steady state at 4 °C displayed ADP-insensitive but temperature-sensitive decay. Solubilizing concentrations of dodecyl maltoside left this decay rate almost unaltered, whereas several other detergents accelerated it. Unexpectedly, the dephosphorylation rate for the solubilized Drs2p·Cdc50p complex was inhibited by the addition of phosphatidylserine. Phosphatidylserine exerted its anticipated accelerating effect on the dephosphorylation of Drs2p·Cdc50p complex only in the additional presence of phosphatidylinositol-4-phosphate. These results explain why phosphatidylinositol-4-phosphate tightly controls Drs2p-catalyzed lipid transport and establish the functional relevance of the Drs2p·Cdc50p complex overexpressed here. PMID:22351780

  6. The P4 truss is moved to a workstand in the SSPF

    NASA Technical Reports Server (NTRS)

    2000-01-01

    In the Space Station Processing Facility, workers get ready to lower the International Space Station's P4 truss onto a workstand. Part of the 10-truss, girder-like structure that will ultimately extend the length of a football field, the P4 is the second port truss segment that will attach to the first port truss segment (P1 truss). The P4 is scheduled for mission 12A in September 2002.

  7. Syndrome of proximal interstitial deletion 4p15

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

    Fryns, J.P.

    1995-09-11

    In this journal, Chitayat et al. reported on 2 boys and a girl with interstitial deletion in the short arm of chromosome 4, including p15.2p15.33. All 3 patients had a characteristic face distinct from that of Wolf-Hirschhorn syndrome and multiple minor congenital anomalies. One patient had a congenitally enlarged penis. The authors noted that all had normal growth, and all had moderate psychomotor retardation (patient 1, developmental age of 4-6 years at age 9 years; patient 2, mental age 6 years at age 25 years; and patient 3, global delay with hypotonia, difficulties in both gross and fine motor development,more » and persistent delay in language skills). 5 refs., 1 fig.« less

  8. Combining p-values in replicated single-case experiments with multivariate outcome.

    PubMed

    Solmi, Francesca; Onghena, Patrick

    2014-01-01

    Interest in combining probabilities has a long history in the global statistical community. The first steps in this direction were taken by Ronald Fisher, who introduced the idea of combining p-values of independent tests to provide a global decision rule when multiple aspects of a given problem were of interest. An interesting approach to this idea of combining p-values is the one based on permutation theory. The methods belonging to this particular approach exploit the permutation distributions of the tests to be combined, and use a simple function to combine probabilities. Combining p-values finds a very interesting application in the analysis of replicated single-case experiments. In this field the focus, while comparing different treatments effects, is more articulated than when just looking at the means of the different populations. Moreover, it is often of interest to combine the results obtained on the single patients in order to get more global information about the phenomenon under study. This paper gives an overview of how the concept of combining p-values was conceived, and how it can be easily handled via permutation techniques. Finally, the method of combining p-values is applied to a simulated replicated single-case experiment, and a numerical illustration is presented.

  9. The Top 10 Things I LOVE about p4c Hawai'i

    ERIC Educational Resources Information Center

    Ikeda, Jolyn

    2012-01-01

    In 2001, Dr. Thomas Jackson, or Dr. J as the author and her colleagues affectionately call him, spoke to the faculty at Waikiki Elementary. He described philosophy for children (p4c) Hawai'i and encouraged them to try P4C if something about it "resonated" with them. In the beginning, Dr. J held a p4t (philosophy for teachers)…

  10. Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in Patients with Congenital Anomalies and Developmental Disability.

    PubMed

    Novo-Filho, Gil M; Montenegro, Marília M; Zanardo, Évelin A; Dutra, Roberta L; Dias, Alexandre T; Piazzon, Flavia B; Costa, Taís V M M; Nascimento, Amom M; Honjo, Rachel S; Kim, Chong A; Kulikowski, Leslie D

    2016-01-01

    The most prevalent structural variations in the human genome are copy number variations (CNVs), which appear predominantly in the subtelomeric regions. Variable sizes of 4p/4q CNVs have been associated with several different psychiatric findings and developmental disability (DD). We analyzed 105 patients with congenital anomalies (CA) and developmental and/or intellectual disabilities (DD/ID) using MLPA subtelomeric specific kits (P036 /P070) and 4 of them using microarrays. We found abnormal subtelomeric CNVs in 15 patients (14.3%), including 8 patients with subtelomeric deletions at 4p/4q (53.3%). Additional genomic changes were observed at 1p36, 2q37.3, 5p15.3, 5q35.3, 8p23.3, 13q11, 14q32.3, 15q11.2, and Xq28/Yq12. This indicates the prevalence of independent deletions at 4p/4q, involving PIGG, TRIML2, and FRG1. Furthermore, we identified 15 genes with changes in copy number that contribute to neurological development and/or function, among them CRMP1, SORCS2, SLC25A4, and HELT. Our results highlight the association of genes with changes in copy number at 4p and 4q subtelomeric regions and the DD phenotype. Cytogenomic characterization of additional cases with distal deletions should help clarifying the role of subtelomeric CNVs in neurological diseases. © 2016 S. Karger AG, Basel.

  11. The Microgravity Research Experiments (MICREX) Data Base, Volume 4

    NASA Technical Reports Server (NTRS)

    Winter, C. A.; Jones, J. C.

    1996-01-01

    An electronic data base identifying over 800 fluids and materials processing experiments performed in a low-gravity environment has been created at NASA Marshall Space Flight Center. The compilation, called MICREX (MICrogravity Research Experiments), was designed to document all such experimental efforts performed (1) on U.S. manned space vehicles, (2) on payloads deployed from U.S. manned space vehicles, and (3) on all domestic and international sounding rockets (excluding those of China and the former U.S.S.R.). Data available on most experiments include (1) principal and co-investigators (2) low-gravity mission, (3) processing facility, (4) experimental objectives and results, (5) identifying key words, (6) sample materials, (7) applications of the processed materials/research area, (8) experiment descriptive publications, and (9) contacts for more information concerning the experiment. This technical Memorandum (1) summarizes the historical interest in reduced-gravity fluid dynamics, (2) describes the importance of a low-gravity fluids and materials processing data base, (4) describes the MICREX data base format and computational World Wide Web access procedures, and (5) documents (in hard-copy form) the descriptions of the first 600 fluids and materials processing experiments entered into MICREX.

  12. The P4 truss is moved to a workstand in the SSPF

    NASA Technical Reports Server (NTRS)

    2000-01-01

    In the Space Station Processing Facility, workers oversee the removal of the P4 truss from the truck that transported it from Tulsa, Okla. Part of the 10-truss, girder-like structure that will ultimately extend the length of a football field on the International Space Station, the P4 is the second port truss segment that will attach to the first port truss segment (P1 truss). The P4 is scheduled for mission 12A in September 2002.

  13. Synthesis, characterization, and tuning of the liquid crystal properties of ionic materials based on the cyclic polyoxothiometalate [{Mo4O4S4(H2O)3(OH)2}2(P8W48O184)](36-).

    PubMed

    Watfa, Nancy; Floquet, Sébastien; Terazzi, Emmanuel; Haouas, Mohamed; Salomon, William; Korenev, Vladimir S; Taulelle, Francis; Guénée, Laure; Hijazi, Akram; Naoufal, Daoud; Piguet, Claude; Cadot, Emmanuel

    2015-02-14

    A series of compounds resulting from the ionic association of a nanoscopic inorganic cluster of formula [K2NaxLiy{Mo4O4S4(OH)2(H2O)3}2(HzP8W48O184)]((34-x-y-z)-), 1, with several organic cations such as dimethyldioctadecylammonium DODA(+), trimethylhexadecylammonium TMAC16(+), alkylmethylimidazoliums mimCn(+) (n = 12-20) and alkyl-dimethylimidazoliums dmimCn(+) (n = 12 and 16) was prepared and characterized in the solid state by FT-IR, EDX, Elemental analysis, TGA and solid state NMR. The solid state NMR experiments performed on (1)H, (13)C and (31)P nuclei evidenced the interactions between the cations and 1 as well as the organization of the alkyl chains of the cations within the solid. Polarized optical microscopy, DSC and SA-XRD experiments implicated mesomorphic phases for DODA(+) and mimCn(+) salts of 1. The crystallographic parameters were determined and demonstrated that the inter-lamellar spacing could be controlled upon changing the length of the alkyl chain, a very interesting result if we consider the huge size of the inorganic cluster 1 and the simple nature of the cations.

  14. Mechanism of p-substituted phenol oxidation at a Ti4O7 reactive electrochemical membrane.

    PubMed

    Zaky, Amr M; Chaplin, Brian P

    2014-05-20

    This research investigated the removal mechanisms of p-nitrophenol, p-methoxyphenol, and p-benzoquinone at a porous Ti4O7 reactive electrochemical membrane (REM) under anodic polarization. Cross-flow filtration experiments and density functional theory (DFT) calculations indicated that p-benzoquinone removal was primarily due to reaction with electrochemically formed OH(•), while the dominant removal mechanism of p-nitrophenol and p-methoxyphenol was a function of the anodic potential. At low anodic potentials (1.7-1.8 V/SHE), p-nitrophenol and p-methoxyphenol were removed primarily by an electrochemical adsorption/polymerization mechanism on the REM. Increasing anodic potentials (1.9-3.2 V/SHE) resulted in the electroassisted adsorption mechanism contributing far less to p-methoxyphenol removal compared to p-nitrophenol. DFT calculations indicated that an increase in anodic potential resulted in a shift in p-methoxyphenol removal from a 1e(-) direct electron transfer (DET) reaction that resulted in radical formation and significant adsorption/polymerization, to a 2e(-) DET reaction that formed nonadsorbing products (i.e., p-benzoquinone). However, the anodic potentials were too low for the 2e(-) DET reaction to be thermodynamically favorable for p-nitrophenol. The decreased COD adsorption for p-nitrophenol at higher anodic potentials was attributed to reaction of soluble/adsorbed organics with OH(•). These results provide the first mechanistic explanation for p-substituted phenolic compound removal during advanced electrochemical oxidation processes.

  15. Polarized Exocytosis Induces Compensatory Endocytosis by Sec4p-Regulated Cortical Actin Polymerization

    PubMed Central

    Johansen, Jesper; Alfaro, Gabriel; Beh, Christopher T.

    2016-01-01

    Polarized growth is maintained by both polarized exocytosis, which transports membrane components to specific locations on the cell cortex, and endocytosis, which retrieves these components before they can diffuse away. Despite functional links between these two transport pathways, they are generally considered to be separate events. Using live cell imaging, in vivo and in vitro protein binding assays, and in vitro pyrene-actin polymerization assays, we show that the yeast Rab GTPase Sec4p couples polarized exocytosis with cortical actin polymerization, which induces endocytosis. After polarized exocytosis to the plasma membrane, Sec4p binds Las17/Bee1p (yeast Wiskott—Aldrich Syndrome protein [WASp]) in a complex with Sla1p and Sla2p during actin patch assembly. Mutations that inactivate Sec4p, or its guanine nucleotide exchange factor (GEF) Sec2p, inhibit actin patch formation, whereas the activating sec4-Q79L mutation accelerates patch assembly. In vitro assays of Arp2/3-dependent actin polymerization established that GTPγS-Sec4p overrides Sla1p inhibition of Las17p-dependent actin nucleation. These results support a model in which Sec4p relocates along the plasma membrane from polarized sites of exocytic vesicle fusion to nascent sites of endocytosis. Activated Sec4p then promotes actin polymerization and triggers compensatory endocytosis, which controls surface expansion and kinetically refines cell polarization. PMID:27526190

  16. Investigation of pharmaceutical transport in saturated sandy aquifers using column experiments: the effect of pH

    NASA Astrophysics Data System (ADS)

    Börnick, Hilmar; Boxberger, Norman; Licha, Tobias; Worch, Eckhard

    2010-05-01

    Due to the development of advanced analytical techniques it is increasingly known that a high number of polar organic trace compounds, particularly residues of pharmaceuticals, occur in the aquatic environment. In contrast to the sources and pathways of such compounds, their impact on ecosystems and their fate in different environmental compartments are comparatively less investigated. Because of the spatial extension and time available, the zone between water and natural solids (e.g. sediments or soil in groundwater zones, bank filtration sites and for soil aquifer treatment) plays an important role in the elimination of anthropogenic trace compounds from water phase. Here, degradation and sorption processes mainly influence the content of trace compounds. Correlations, specific for compound groups, between n-octanol-water distribution coefficients, available from experiment or calculations, and sorption coefficients (e.g. KOC) often allow a suitable prognosis of the transport behavior of organic pollutants in an underground passage. In case of polar, ionizable organic compounds such prediction is problematic and often not possible. Here, besides relatively weak non-polar van der Waals attraction, other interaction mechanisms, such as covalent bonding, complex formation, or ion exchange, can dominate. The latter is closely connected with the type of basic and/or acid groups in a molecule. The degree of protonation could be changed in dependence of type and concentration of other ions and of the acidity constants (pKa) and therefore from pH. Laboratory column studies at different pH value (range from 4 to 8) were carried out using natural sandy sediments from aquifers and model water containing selected pharmaceuticals to investigate the influence of degree of protonation on sorption. Eight different pharmaceuticals were chosen for laboratory column experiments. Their selection was based on the presence of basic/acid functional groups, pKa, high production and

  17. Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells.

    PubMed

    Pan, Min-Hsiung; Chen, Wei-Jen; Lin-Shiau, Shoei-Yn; Ho, Chi-Tang; Lin, Jen-Kun

    2002-10-01

    Tangeretin (5,6,7,8,4'-pentamethoxyflavone) is concentrated in the peel of citrus fruits. DNA flow cytometric analysis indicated that tangeretin blocked cell cycle progression at G1 phase in colorectal carcinoma COLO 205 cells. Over a 24 h exposure to tangeretin, the degree of phosphorylation of Rb was decreased after 12 h and G1 arrest developed. The protein expression of cyclins A, D1, and E reduced slightly under the same conditions. Immunocomplex kinase experiments showed that tangeretin inhibited the activities of cyclin-dependent kinases 2 (Cdk2) and 4 (Cdk4) in a dose-dependent manner in the cell-free system. As the cells were exposed to tangeretin (50 microM) over 48 h a gradual loss of both Cdk2 and 4 kinase activities occurred. Tangeretin also increased the content of the Cdk inhibitor p21 protein and this effect correlated with the elevation in p53 levels. In addition, tangeretin also increased the level of the Cdk inhibitor p27 protein within 18 h. These results suggest that tangeretin either exerts its growth-inhibitory effects through modulation of the activities of several key G1 regulatory proteins, such as Cdk2 and Cdk4, or mediates the increase of Cdk inhibitors p21 and p27.

  18. Ab initio computational study on the lattice thermal conductivity of Zintl clathrates [Si19P4] Cl4 and Na4[Al4Si19

    NASA Astrophysics Data System (ADS)

    Härkönen, Ville J.; Karttunen, Antti J.

    2016-08-01

    The lattice thermal conductivity of silicon clathrate framework Si23 and two Zintl clathrates, [Si19P4] Cl4 and Na4[Al4Si19] , is investigated by using an iterative solution of the linearized Boltzmann transport equation in conjunction with ab initio lattice dynamical techniques. At 300 K, the lattice thermal conductivities for Si23, [Si19P4] Cl4 , and Na4[Al4Si19] were found to be 43 W/(m K), 25 W/(m K), and 2 W/(m K), respectively. In the case of Na4[Al4Si19] , the order-of-magnitude reduction in the lattice thermal conductivity was found to be mostly due to relaxation times and group velocities differing from Si23 and [Si19P4] Cl4 . The difference in the relaxation times and group velocities arises primarily due to the phonon spectrum at low frequencies, resulting eventually from the differences in the second-order interatomic force constants (IFCs). The obtained third-order IFCs were rather similar for all materials considered here. The present findings are similar to those obtained earlier for some skutterudites. The predicted lattice thermal conductivity of Na4[Al4Si19] is in line with the experimentally measured thermal conductivity of recently synthesized type-I Zintl clathrate Na8[Al8Si38] (polycrystalline samples).

  19. Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

    PubMed Central

    Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

    2008-01-01

    AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by χ2 test. RESULTS: Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathological features. CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm). PMID:18176968

  20. Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

    PubMed

    Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

    2008-01-07

    To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathological features. By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

  1. Macrophage P2X4 receptors augment bacterial killing and protect against sepsis

    PubMed Central

    Csóka, Balázs; Németh, Zoltán H.; Szabó, Ildikó; Davies, Daryl L.; Varga, Zoltán V.; Pálóczi, János; Falzoni, Simonetta; Di Virgilio, Francesco; Muramatsu, Rieko; Pacher, Pál

    2018-01-01

    The macrophage is a major phagocytic cell type, and its impaired function is a primary cause of immune paralysis, organ injury, and death in sepsis. An incomplete understanding of the endogenous molecules that regulate macrophage bactericidal activity is a major barrier for developing effective therapies for sepsis. Using an in vitro killing assay, we report here that the endogenous purine ATP augments the killing of sepsis-causing bacteria by macrophages through P2X4 receptors (P2X4Rs). Using newly developed transgenic mice expressing a bioluminescent ATP probe on the cell surface, we found that extracellular ATP levels increase during sepsis, indicating that ATP may contribute to bacterial killing in vivo. Studies with P2X4R-deficient mice subjected to sepsis confirm the role of extracellular ATP acting on P2X4Rs in killing bacteria and protecting against organ injury and death. Results with adoptive transfer of macrophages, myeloid-specific P2X4R-deficient mice, and P2rx4 tdTomato reporter mice indicate that macrophages are essential for the antibacterial, antiinflammatory, and organ protective effects of P2X4Rs in sepsis. Pharmacological targeting of P2X4Rs with the allosteric activator ivermectin protects against bacterial dissemination and mortality in sepsis. We propose that P2X4Rs represent a promising target for drug development to control bacterial growth in sepsis and other infections. PMID:29875325

  2. Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion.

    PubMed

    Cao, Qi; Zhong, Xi Zoë; Zou, Yuanjie; Murrell-Lagnado, Ruth; Zhu, Michael X; Dong, Xian-Ping

    2015-06-22

    Intra-endolysosomal Ca(2+) release is required for endolysosomal membrane fusion with intracellular organelles. However, the molecular mechanisms for intra-endolysosomal Ca(2+) release and the downstream Ca(2+) targets involved in the fusion remain elusive. Previously, we demonstrated that endolysosomal P2X4 forms channels activated by luminal adenosine triphosphate in a pH-dependent manner. In this paper, we show that overexpression of P2X4, as well as increasing endolysosomal P2X4 activity by alkalinization of endolysosome lumen, promoted vacuole enlargement in cells and endolysosome fusion in a cell-free assay. These effects were prevented by inhibiting P2X4, expressing a dominant-negative P2X4 mutant, and disrupting the P2X4 gene. We further show that P2X4 and calmodulin (CaM) form a complex at endolysosomal membrane where P2X4 activation recruits CaM to promote fusion and vacuolation in a Ca(2+)-dependent fashion. Moreover, P2X4 activation-triggered fusion and vacuolation were suppressed by inhibiting CaM. Our data thus suggest a new molecular mechanism for endolysosomal membrane fusion involving P2X4-mediated endolysosomal Ca(2+) release and subsequent CaM activation. © 2015 Cao et al.

  3. Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion

    PubMed Central

    Cao, Qi; Zhong, Xi Zoë; Zou, Yuanjie; Murrell-Lagnado, Ruth; Zhu, Michael X.

    2015-01-01

    Intra-endolysosomal Ca2+ release is required for endolysosomal membrane fusion with intracellular organelles. However, the molecular mechanisms for intra-endolysosomal Ca2+ release and the downstream Ca2+ targets involved in the fusion remain elusive. Previously, we demonstrated that endolysosomal P2X4 forms channels activated by luminal adenosine triphosphate in a pH-dependent manner. In this paper, we show that overexpression of P2X4, as well as increasing endolysosomal P2X4 activity by alkalinization of endolysosome lumen, promoted vacuole enlargement in cells and endolysosome fusion in a cell-free assay. These effects were prevented by inhibiting P2X4, expressing a dominant-negative P2X4 mutant, and disrupting the P2X4 gene. We further show that P2X4 and calmodulin (CaM) form a complex at endolysosomal membrane where P2X4 activation recruits CaM to promote fusion and vacuolation in a Ca2+-dependent fashion. Moreover, P2X4 activation-triggered fusion and vacuolation were suppressed by inhibiting CaM. Our data thus suggest a new molecular mechanism for endolysosomal membrane fusion involving P2X4-mediated endolysosomal Ca2+ release and subsequent CaM activation. PMID:26101220

  4. 2,4-D abatement from groundwater samples by photo-Fenton processes at circumneutral pH using naturally iron present. Effect of inorganic ions.

    PubMed

    Gutiérrez-Zapata, Héctor M; Rojas, Karen L; Sanabria, Janeth; Rengifo-Herrera, Julián Andrés

    2017-03-01

    This study evaluated, at laboratory scale, if the using iron naturally present (0.3 mg L -1 ) and adding 10 mg L -1 of hydrogen peroxide was effective to remove 24.3 mgL -1 of 2,4-dichlorophenoxyacetic acid (2,4-D) from groundwater samples by simulated solar irradiation (global intensity = 300 W m -2 ). Under these conditions, the degradation of 2,4-D reached 75.2 % and the apparition of its main oxidation byproduct 2,4-dichlorophenol (DCP) was observed. On the other hand, pH exhibited an increasing from 7.0 to 8.3 during the experiment. Experiments using Milli-Q water at pH 7.0, iron, and H 2 O 2 concentrations of 0.3 and 10 mg L -1 , respectively, were carried out in order to study the effect of ions such as carbonate species, phosphate, and fluoride in typical concentrations often found in groundwater. Ion concentrations were combined by using a factorial experimental design 2 3 . Results showed that carbonates and fluoride did not produce a detrimental effect on the 2,4-D degradation, while phosphate inhibited the process. In this case, the pH increased also from 7.0 to 7.95 and 8.99. Effect of parameters such as pH, iron concentration, and hydrogen peroxide concentration on the 2,4-D degradation by the photo-Fenton process in groundwater was evaluated by using a factorial experimental design 2 3 . Results showed that the pH was the main parameter affecting the process. This study shows for the first time that using the photo-Fenton process at circumneutral pH and iron naturally present seems to be a promising process to remove pesticides from groundwater.

  5. Recruitment of a chromosomally encoded maleylacetate reductase for degradation of 2,4-dichlorophenoxyacetic acid by plasmid pJP4.

    PubMed Central

    Kukor, J J; Olsen, R H; Siak, J S

    1989-01-01

    When Pseudomonas aeruginosa PAO1c or P. putida PPO200 or PPO300 carry plasmid pJP4, which encodes enzymes for the degradation of 2,4-dichlorophenoxyacetic acid (TFD) to 2-chloromaleylacetate, cells do not grow on TFD and UV-absorbing material with spectral characteristics of chloromaleylacetate accumulates in the culture medium. Using plasmid pRO1727, we cloned from the chromosome of a nonfluorescent pseudomonad, Pseudomonas sp. strain PKO1, 6- and 0.5-kilobase BamHI DNA fragments which contain the gene for maleylacetate reductase. When carrying either of the recombinant plasmids, pRO1944 or pRO1945, together with pJP4, cells of P. aeruginosa or P. putida were able to utilize TFD as a sole carbon source for growth. A novel polypeptide with an estimated molecular weight of 18,000 was detected in cell extracts of P. aeruginosa carrying either plasmid pRO1944 or plasmid pRO1945. Maleylacetate reductase activity was induced in cells of P. aeruginosa or P. putida carrying plasmid pRO1945, as well as in cells of Pseudomonas strain PKO1, when grown on L-tyrosine, suggesting that the tyrosine catabolic pathway might be the source from which maleylacetate reductase is recruited for the degradation of TFD in pJP4-bearing cells of Pseudomonas sp. strain PKO1. Images PMID:2722753

  6. Sch9p kinase and the Gcn4p transcription factor regulate glycerol production during winemaking.

    PubMed

    Vallejo, Beatriz; Orozco, Helena; Picazo, Cecilia; Matallana, Emilia; Aranda, Agustín

    2017-01-01

    Grape juice fermentation is a harsh environment with many stressful conditions, and Saccharomyces cerevisiae adapts its metabolism in response to those environmental challenges. Many nutrient-sensing pathways control this feature. The Tor/Sch9p pathway promotes growth and protein synthesis when nutrients are plenty, while the transcription factor Gcn4p is required for the activation of amino acid biosynthetic pathways. We previously showed that Sch9p impact on longevity depends on the nitrogen/carbon ratio. When nitrogen is limiting, SCH9 deletion shortens chronological life span, which is the case under winemaking conditions. Its deletion also increases glycerol during fermentation, so the impact of this pathway on metabolism under winemaking conditions was studied by transcriptomic and metabolomic approaches. SCH9 deletion causes the upregulation of many amino acid biosynthesis pathways. When Gcn4p was overexpressed during winemaking, increased glycerol production was also observed. Therefore, both pathways are related in terms of glycerol production. SCH9 deletion increased the amount of the limiting enzyme in glycerol biosynthesis, glycerol-3-P dehydrogenase Gpd1p at the protein level. The impact on the metabolome of SCH9 deletion and GCN4 overexpression differed, although both showed a downregulation of glycolysis. SCH9 deletion downregulated the amount of most proteinogenic amino acids and increased the amount of lipids, such as ergosterol. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Transition probabilities for the 3s2 3p(2P0)-3s3p2(4P) intersystem lines of Si II

    NASA Technical Reports Server (NTRS)

    Calamai, Anthony G.; Smith, Peter L.; Bergeson, S. D.

    1993-01-01

    Intensity ratios of lines of the spin-changing 'intersystem' multiplet of S II (4P yields 2P0) at 234 nm have been used to determine electron densities and temperatures in a variety of astrophysical environments. However, the accuracy of these diagnostic calculations have been limited by uncertainties associated with the available atomic data. We report the first laboratory measurement, using an ion-trapping technique, of the radiative lifetimes of the three metastable levels of the 3s3p2 4P term of Si II. Our results are 104 +/- 16, 406 +/- 33, and 811 +/- 77 micro-s for lifetimes of the J = 1/2, 5/2, and 3/2 levels, respectively. A-values were derived from our lifetimes by use of measured branching fractions. Our A-values, which differ from calculated values by 30 percent or more, should give better agreement between modeled and observed Si II line ratios.

  8. The P4 truss is moved to a workstand in the SSPF

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Suspended by an overhead crane in the Space Station Processing Facility, the International Space Station's P4 truss moves toward a workstand. Below and behind it on the floor is the Multi- Purpose Logistics Module Raffaello, another segment of the Space Station. Part of the 10-truss, girder-like structure that will ultimately extend the length of a football field, the P4 is the second port truss segment that will attach to the first port truss segment (P1 truss). The P4 is scheduled for mission 12A in September 2002.

  9. Dissociation between the effects of P1, P4-diadenosine tetraphosphate (Ap4A) on renal haemodynamics and tubular function in anaesthetized rats.

    PubMed

    Jankowski, M; Angielski, S; Szczepańska-Konkel, M

    2008-03-01

    Previous studies from our laboratory have reported a marked reduction in glomerular filtration rate (GFR) and sodium reabsorption in renal proximal tubule during intravenous infusion of P(1),P(4)-diadenosine tetraphosphate (Ap(4)A) at dose of 1.0 micromol/kg + 10 nmol/kg/min (i.v., injection followed by infusion) in anaesthetized Wistar rats. In the present study, the changes of GFR and urine sodium excretion were investigated in response to systemic infusion of Ap(4)A at different doses. Ap(4)A at dose of 0.1 micromol/kg + 1.0 nmol/kg/min did not change GFR and sodium urinary excretion whereas 2-fold higher dose produced significant (3.4-fold) increase in sodium excretion without changes in GFR. Significant but transient reduction in GFR by approximately 21% was observed during infusion of Ap(4)A at dose of 0.5 micromol/kg + 5.0 nmol/kg/min. Higher doses of Ap(4)A (1.0 micromol/kg + 10 nmol/kg/min and 2.0 micromol/kg + 20 nmol/kg/min) reduction in GFR and marked natriuresis. Our results suggest that tubular sodium transport systems are more sensitive to Ap(4)A than systems involved in GFR regulation.

  10. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision.

    PubMed

    Battaglia, Agatino; Filippi, Tiziana; Carey, John C

    2008-11-15

    Wolf-Hirschhorn syndrome (WHS) is a well-known multiple congenital anomalies/mental retardation syndrome, firstly described in 1961 by Cooper and Hirschhorn. Its frequency is estimated as 1/50,000-1/20,000 births, with a female predilection of 2:1. The disorder is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3), and is considered a contiguous gene syndrome. No single gene deletions or intragenic mutations have been shown to confer the full WHS phenotype. Since the disorder was brought to the attention of geneticists, many additional cases have been published. Only in 1999, however, were the first data on the natural history brought to the attention of the medical community. The purpose of the present study is to help delineate in more detail and over a longer period of time, the natural history of WHS, in order to establish appropriate health supervision and anticipatory guidance for individuals with this disorder. We have collected information on 87 patients diagnosed with WHS (54 females and 33 males) both in USA and Italy. Age at first observation ranged between newborn and 17 years. Twenty patients have been followed from 4 months to 23 years. The deletion proximal breakpoint varied from 4p15.32 to 4p16.3, and, by FISH, was terminal and included both WHSCR. Deletion was detected by standard cytogenetics in 44/87 (50.5%) patients, whereas FISH was necessary in the other 43 (49.5%). Array-CGH analysis at 1 Mb resolution was performed in 34/87 patients, and, in 15/34 (44%), showed an unbalanced translocation leading to both a 4p monosomy and a partial trisomy for another chromosome arm. Six more patients had been previously shown to have an unbalanced translocation by karyotype analysis or FISH with a WHS-specific probe. Sixty-five of 87 patients had an apparent pure, de novo, terminal deletion; and 1/87 a tandem duplication of 4p16.1p16.3 associated with 4p16.3pter deletion. Age at diagnosis varied between 7

  11. Structural basis for the ligand-binding specificity of fatty acid-binding proteins (pFABP4 and pFABP5) in gentoo penguin.

    PubMed

    Lee, Chang Woo; Kim, Jung Eun; Do, Hackwon; Kim, Ryeo-Ok; Lee, Sung Gu; Park, Hyun Ho; Chang, Jeong Ho; Yim, Joung Han; Park, Hyun; Kim, Il-Chan; Lee, Jun Hyuck

    2015-09-11

    Fatty acid-binding proteins (FABPs) are involved in transporting hydrophobic fatty acids between various aqueous compartments of the cell by directly binding ligands inside their β-barrel cavities. Here, we report the crystal structures of ligand-unbound pFABP4, linoleate-bound pFABP4, and palmitate-bound pFABP5, obtained from gentoo penguin (Pygoscelis papua), at a resolution of 2.1 Å, 2.2 Å, and 2.3 Å, respectively. The pFABP4 and pFABP5 proteins have a canonical β-barrel structure with two short α-helices that form a cap region and fatty acid ligand binding sites in the hydrophobic cavity within the β-barrel structure. Linoleate-bound pFABP4 and palmitate-bound pFABP5 possess different ligand-binding modes and a unique ligand-binding pocket due to several sequence dissimilarities (A76/L78, T30/M32, underlining indicates pFABP4 residues) between the two proteins. Structural comparison revealed significantly different conformational changes in the β3-β4 loop region (residues 57-62) as well as the flipped Phe60 residue of pFABP5 than that in pFABP4 (the corresponding residue is Phe58). A ligand-binding study using fluorophore displacement assays shows that pFABP4 has a relatively strong affinity for linoleate as compared to pFABP5. In contrast, pFABP5 exhibits higher affinity for palmitate than that for pFABP4. In conclusion, our high-resolution structures and ligand-binding studies provide useful insights into the ligand-binding preferences of pFABPs based on key protein-ligand interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Current Results of NEUTRINO-4 Experiment

    NASA Astrophysics Data System (ADS)

    Serebrov, A.; Ivochkin, V.; Samoilov, R.; Fomin, A.; Polyushkin, A.; Zinoviev, V.; Neustroev, P.; Golovtsov, V.; Chernyj, A.; Zherebtsov, O.; Martemyanov, V.; Tarasenkov, V.; Aleshin, V.; Petelin, A.; Izhutov, A.; Tuzov, A.; Sazontov, S.; Ryazanov, D.; Gromov, M.; Afanasiev, V.; Zaytsev, M.; Chaikovskii, M.

    2017-12-01

    The main goal of experiment “Neutrino-4” is to search for the oscillation of reactor antineutrino to a sterile state. Experiment is conducted on SM-3 research reactor (Dimitrovgrad, Russia). Data collection with full-scale detector with liquid scintillator volume of 3m3 was started in June 2016. We present the results of measurements of reactor antineutrino flux dependence on the distance in range 6- 12 meters from the center of the reactor. At that distance range, the fit of experimental dependence has good agreement with the law 1/L2. Which means, at achieved during the data collecting accuracy level oscillations to sterile state are not observed. In addition, the spectrum of prompt signals of neutrino-like events at different distances have been presented.

  13. Interactions of solute (3p, 4p, 5p and 6p) with solute, vacancy and divacancy in bcc Fe

    NASA Astrophysics Data System (ADS)

    You, Yu-Wei; Kong, Xiang-Shan; Wu, Xue-Bang; Liu, Wei; Liu, C. S.; Fang, Q. F.; Chen, J. L.; Luo, G.-N.; Wang, Zhiguang

    2014-12-01

    Solute-vacancy binding energy is a key quantity in understanding solute diffusion kinetics and phase segregation, and may help choice of alloy compositions for future material design. However, the binding energy of solute with vacancy is notoriously difficult to measure and largely unknown in bcc Fe. With first-principles method, we systemically calculate the binding energies of solute (3p, 4p, 5p and 6p alloying solutes are included) with vacancy, divacancy and solute in bcc Fe. The binding energy of Si with vacancy in the present work is in good consistent with experimental value available. All the solutes considered are able to form stable solute-vacancy, solute-divacancy complexes, and the binding strength of solute-divacancy is about two times larger than that of solute-vacancy. Most solutes could not form stable solute-solute complexes except S, Se, In and Tl. The factors controlling the binding energies are analyzed at last.

  14. Diagnostic utility of aP2/FABP4 expression in soft tissue tumours.

    PubMed

    Kashima, T G; Turley, H; Dongre, A; Pezzella, F; Athanasou, N A

    2013-04-01

    Adipocyte P2 (aP2), also known as fatty acid-binding protein 4 (FABP4), is a fatty acid-binding protein found in the cytoplasm of cells of adipocyte differentiation. In this study, we examined a large number of soft tissue tumours with a commercial polyclonal anti-aP2/FABP4 antibody and a newly developed mouse monoclonal antibody raised against this protein to determine the diagnostic utility of aP2/FABP4 as a marker of tumours of adipose differentiation. A mouse monoclonal antibody, clone 175d, was raised against a mixture of synthetic peptides corresponding to the amino acid sequence of residues 10-28 and 121-132 of the human aP2/FABP4 protein. Antigen expression with polyclonal and monoclonal antibodies was immunohistochemically determined in paraffin sections of normal adipose tissue and a wide range of benign and malignant primary soft tissue tumours (n = 200). aP2/FABP4 was expressed around the cytoplasmic lipid vacuole in white and brown fat cells in benign lipomas and hibernomas. Immature fat cells and lipoblasts in spindle cell/pleomorphic lipoma, atypical lipomatous tumour/well-differentiated liposarcoma, myxoid/round cell liposarcoma and pleomorphic liposarcoma also reacted strongly for aP2/FABP4. No specific staining was seen in non-adipose benign and malignant mesenchymal and non-mesenchymal tumours. aP2/FABP4 is expressed by mature and immature fat cells and is a marker of tumours of adipose differentiation. Immunophenotypic aP2/FABP4 expression is useful in identifying lipoblasts, and immunohistochemistry with polyclonal/monoclonal anti-aP2/FABP4 antibodies should be useful in distinguishing liposarcoma from other malignancies, particularly round cell, myxoid and pleomorphic soft tissue sarcomas.

  15. Eya4 Induces Hypertrophy via Regulation of p27kip1.

    PubMed

    Williams, Tatjana; Hundertmark, Moritz; Nordbeck, Peter; Voll, Sabine; Arias-Loza, Paula Anahi; Oppelt, Daniel; Mühlfelder, Melanie; Schraut, Susanna; Elsner, Ines; Czolbe, Martin; Seidlmayer, Lea; Heinze, Britta; Hahner, Stefanie; Heinze, Katrin; Schönberger, Jost; Jakob, Peter; Ritter, Oliver

    2015-12-01

    E193, a heterozygous truncating mutation in the human transcription cofactor Eyes absent 4 (Eya4), causes hearing impairment followed by dilative cardiomyopathy. In this study, we first show Eya4 and E193 alter the expression of p27(kip1) in vitro, suggesting Eya4 is a negative regulator of p27. Next, we generated transgenic mice with cardiac-specific overexpression of Eya4 or E193. Luciferase and chromatin immunoprecipitation assays confirmed Eya4 and E193 bind and regulate p27 expression in a contradictory manner. Activity and phosphorylation status of the downstream molecules casein kinase-2α and histone deacetylase 2 were significantly elevated in Eya4- but significantly reduced in E193-overexpressing animals compared with wild-type littermates. Magnetic resonance imaging and hemodynamic analysis indicate Eya4-overexpression results in an age-dependent development of hypertrophy already under baseline conditions with no obvious functional effects, whereas E193 animals develop onset of dilative cardiomyopathy as seen in human E193 patients. Both cardiac phenotypes were aggravated on pressure overload. Finally, we identified a new heterozygous truncating Eya4 mutation, E215, which leads to similar clinical features of disease and a stable myocardial expression of the mutant protein as seen with E193. Our results implicate Eya4/Six1 regulates normal cardiac function via p27/casein kinase-2α/histone deacetylase 2 and indicate that mutations within this transcriptional complex and signaling cascade lead to the development of cardiomyopathy. © 2015 American Heart Association, Inc.

  16. Measurements of cross section of e + e - → p p ¯ π 0 at center-of-mass energies between 4.008 and 4.600 GeV

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

    Ablikim, M.; Achasov, M. N.; Ahmed, S.

    Based on e +e - annihilation data samples collected with the BESIII detector at the BEPCII collider at 13 center-of-mass energies from 4.008 to 4.600 GeV, measurements of the Born cross section of e +e -→more » $$p\\bar{p}$$π 0 are then performed. No significant resonant structure is observed in the measured energy dependence of the cross section. The upper limit on the Born cross section of e +e -→Y (4260) →$$p\\bar{p}$$π 0 at the 90% C.L. is determined to be 0.01 pb. The upper limit on the ratio of the branching fractions B(Y(4260)→$$p\\bar{p}$$π 0) / B(Y(4260)→π +π - J/ψ) at the 90% C.L. is determined to be 0.02%.« less

  17. Measurements of cross section of e + e - → p p ¯ π 0 at center-of-mass energies between 4.008 and 4.600 GeV

    DOE PAGES

    Ablikim, M.; Achasov, M. N.; Ahmed, S.; ...

    2017-08-10

    Based on e +e - annihilation data samples collected with the BESIII detector at the BEPCII collider at 13 center-of-mass energies from 4.008 to 4.600 GeV, measurements of the Born cross section of e +e -→more » $$p\\bar{p}$$π 0 are then performed. No significant resonant structure is observed in the measured energy dependence of the cross section. The upper limit on the Born cross section of e +e -→Y (4260) →$$p\\bar{p}$$π 0 at the 90% C.L. is determined to be 0.01 pb. The upper limit on the ratio of the branching fractions B(Y(4260)→$$p\\bar{p}$$π 0) / B(Y(4260)→π +π - J/ψ) at the 90% C.L. is determined to be 0.02%.« less

  18. The P2X4 purinergic receptor regulates hepatic myofibroblast activation during liver fibrogenesis.

    PubMed

    Le Guilcher, Camille; Garcin, Isabelle; Dellis, Olivier; Cauchois, Florent; Tebbi, Ali; Doignon, Isabelle; Guettier, Catherine; Julien, Boris; Tordjmann, Thierry

    2018-05-23

    Liver fibrosis is characterized by the accumulation of extracellular matrix produced by hepatic myofibroblasts (hMF), the activation of which is critical to the fibrogenic process. Extracellular adenosine triphosphate, released by dying or stressed cells, and its purinergic receptors, constitute a powerful signaling network after injury. Although the P2X4 purinergic receptor (P2X4) is highly expressed in the liver, its functions in hMF had never been investigated during liver fibrogenesis. In vivo, bile duct ligation (BDL) and methionine- and choline-deficient (MCD) diet were performed in WT and P2X4 knock-out (P2X4-KO) mice. In vitro, hMF were isolated from mouse (WT and P2X4-KO) and human liver. P2X4 pharmacological inhibition (in vitro and in vivo) and P2X4 siRNAs (in vitro) were used. Histological, biochemical and cell culture analysis allowed us to study P2X4 expression and its involvement in the regulation of fibrogenic and fibrolytic factors, as well as of hMF activation markers and properties. P2X4 genetic invalidation or pharmacological inhibition protected mice from liver fibrosis and hMF accumulation after BDL or MCD diet. Human and mouse hMF expressed P2X4, mainly in lysosomes. Invalidation of P2X4 in human and mouse hMF blunted their activation marker expression and their fibrogenic properties. We finally showed that P2X4 regulates calcium entry and lysosomal exocytosis in hMF, with impact on ATP release, pro-fibrogenic secretory profile, and on transcription factor activation. P2X4 expression and activation is critical for hMF to sustain their activated and fibrogenic phenotype. Therefore, the inactivation of P2X4 may be of therapeutic interest during liver fibrotic diseases. During chronic injury, the liver often repairs with fibrotic tissue for which there is currently no treatment. We found that a previously unexplored pathway involving the purinergic receptor "P2X4", can modulate fibrotic liver repair, and could be considered for future

  19. 1D nanostructured Na7V4(P2O7)4(PO4) as high-potential and superior-performance cathode material for sodium-ion batteries.

    PubMed

    Deng, Chao; Zhang, Sen

    2014-06-25

    Tailoring materials into nanostructure offers unprecedented opportunities in the utilization of their functional properties. High-purity Na7V4(P2O7)4(PO4) with 1D nanostructure is prepared as a cathode material for rechargeable Na-ion batteries. An efficient synthetic approach is developed by carefully controlling the crystal growth in the molten sodium phosphate. Based on the XRD, XPS, TG, and morphological characterization, a molten-salt assisted mechanism for nanoarchitecture formation is revealed. The prepared Na7V4(P2O7)4(PO4) nanorod has rectangle sides and preferential [001] growth orientation. GITT evaluation indicates that the sodium de/intercalation of Na7V4(P2O7)4(PO4) nanorod involves V(3+)/V(4+) redox reaction and Na5V(3.5+)4(P2O7)4(PO4) as intermediate phase, which results in two pairs of potential plateaus at the equilibrium potentials of 3.8713 V (V(3+)/V(3.5+)) and 3.8879 V (V(3.5+)/V(4+)), respectively. The unique nanoarchitecture of the phase-pure Na7V4(P2O7)4(PO4) facilitates its reversible sodium de/intercalation, which is beneficial to the high-rate capability and the cycling stability. The Na7V4(P2O7)4(PO4) cathode delivers 80% of the capacity (obtained at C/20) at the 10 C rate and 95% of the initial capacity after 200 cycles. Therefore, it is feasible to design and fabricate an advanced rechargeable sodium-ion battery by employment of 1D nanostructured Na7V4(P2O7)4(PO4) as the cathode material.

  20. Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b: cloning, sequencing, and expression of the tyrosinase gene mepA.

    PubMed Central

    Mercado-Blanco, J; García, F; Fernández-López, M; Olivares, J

    1993-01-01

    Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b (140 MDa). Transfer of this plasmid to GR4-cured derivatives or to Agrobacterium tumefaciens enables these bacteria to produce melanin. Sequence analysis of a 3.5-kb PstI fragment of plasmid pRmeGR4b has revealed the presence of a open reading frame 1,481-bp that codes for a protein whose sequence shows strong homology to two conserved regions involved in copper binding in tyrosinases and hemocyanins. In vitro-coupled transcription-translation experiments showed that this open reading frame codes for a 55-kDa polypeptide. Melanin production in GR4 is not under the control of the RpoN-NifA regulatory system, unlike that in R. leguminosarum bv. phaseoli 8002. The GR4 tyrosinase gene could be expressed in Escherichia coli under the control of the lacZ promoter. For avoiding confusion with mel genes (for melibiose), a change of the name of the previously reported mel genes of R. leguminosarum bv. phaseoli and other organisms to mep genes (for melanin production) is proposed. Images PMID:8366027

  1. Human adenovirus serotypes 4p and 11p are efficiently expressed in cell lines of neural tumour origin.

    PubMed

    Skog, Johan; Mei, Ya-Fang; Wadell, Göran

    2002-06-01

    Most currently used adenovirus vectors are based upon adenovirus serotypes 2 and 5 (Ad2 and Ad5), which have limited efficiencies for gene transfer to human neural cells. Both serotypes bind to the known adenovirus receptor, CAR (coxsackievirus and adenovirus receptor), and have restricted cell tropism. The purpose of this study was to find vector candidates that are superior to Ad5 in infecting human neural tumours. Using flow cytometry, the vector candidates Ad4p, Ad11p and Ad17p were compared to the commonly used adenovirus vector Ad5v for their binding capacity to neural cell lines derived from glioblastoma, medulloblastoma and neuroblastoma cell lines. The production of viral structural proteins and the CAR-binding properties of the different serotypes were also assessed in these cells. Computer-based models of the fibre knobs of Ad4p and Ad17 were created based upon the crystallized fibre knob structure of adenoviruses and analysed for putative receptor-interacting regions that differed from the fibre knob of Ad5. The non CAR-binding vector candidate Ad11p showed clearly the best binding capacity to all of the neural cell lines, binding more than 90% of cells of all of the neural cell lines tested, in contrast to 20% or less for the commonly used vector Ad5v. Ad4p and Ad11p were also internalized and produced viral proteins more successfully than Ad5. Ad4p showed a low binding ability but a very efficient capacity for infection in cell culture. Ad17p virions neither bound or efficiently infected any of the neural cell lines studied.

  2. Inequalities in dental caries experience among 4-year-old New Zealand children.

    PubMed

    Shackleton, Nichola; Broadbent, Jonathan M; Thornley, Simon; Milne, Barry J; Crengle, Sue; Exeter, Daniel J

    2018-06-01

    To investigate ethnic-specific deprivation gradients in early childhood dental caries experience considering different domains of deprivation. We used cross-sectional near whole population-level data on 318 321 four-year-olds attending the "B4 School check," a national health and development check in New Zealand, across 6 fiscal years (2010/2011 to 2015/2016). The "lift the lip" screening tool was used to estimate experience of any caries and severe caries. We investigated deprivation gradients using the Index of Multiple Deprivation (IMD), which measures seven domains of deprivation across 5958 geographical areas ("data zones"). Ethnicity was categorized into five groups: (i) Māori, (ii) Pacific, (iii) Asian, (iv) Middle Eastern, Latin American and African (MELAA) and (v) European & Other (combined). We used a random intercepts model to estimate mutually adjusted associations between deprivation, ethnicity, age, fiscal year, and evidence of any dental caries experience. Reports of any caries experience decreased from 15.8% (95% CI: 15.7; 15.9%) to 14.7% 95% CI: 14.4; 14.8%), while reports of severe caries experience increased from 3.0% (95% CI: 3.0; 3.1%) to 4.4% (95% CI: 4.3; 4.5%) from 2010/2011 to 2015/2016. This varied by ethnicity with larger increases in severe caries for Pacific children from 7.1% (95% CI: 6.8; 7.4%) to 14.1% (95% CI: 13.7; 14.5%). There were deprivation gradients in dental caries experience with considerable variation by ethnicity and by domain of deprivation. The association between deprivation and dental caries experience was weakest for Asian children and was most pronounced for Pacific and Māori children. Socioeconomic gradients in dental caries experience are evident by age 4 years, and these gradients vary by ethnicity and domain of deprivation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Adaptation of Saccharomyces cerevisiae to the Herbicide 2,4-Dichlorophenoxyacetic Acid, Mediated by Msn2p- and Msn4p-Regulated Genes: Important Role of SPI1

    PubMed Central

    Simões, T.; Teixeira, M. C.; Fernandes, A. R.; Sá-Correia, Isabel

    2003-01-01

    The possible roles of 13 Msn2p- and Msn4p-regulated genes in the adaptation of Saccharomyces cerevisiae to the herbicide 2,4-d-dichlorophenoxyacetic acid (2,4-D) were examined. Single deletion of genes involved in defense against oxidizing agents (CTT1, GRX1, and GRX2/TTR1) or encoding chaperones of the HSP70 family (SSA1, SSA4, and SSE2) showed a slight effect. A more significant role was observed for the heat shock genes HSP78, HSP26, HSP104, HSP12, and HSP42, most of which encode molecular chaperones. However, the SPI1 gene, encoding a member of the glycosylphosphatidylinositol-anchored cell wall protein family, emerged as the major determinant of 2,4-D resistance. SPI1 expression reduced the loss of viability of an unadapted yeast population suddenly exposed to the herbicide, allowing earlier growth resumption. Significantly, yeast adaptation to 2,4-D involves the rapid and transient Msn2p- and Msn4p-mediated activation (fivefold) of SPI1 transcription. SPI1 mRNA levels were reduced to values slightly above those in unstressed cells when the adapted population started duplication in the presence of 2,4-D. Since SPI1 deletion leads to the higher β-1,3-glucanase sensitivity of 2,4-D-stressed cells, it was hypothesized that adaptation may involve an Spi1p-mediated increase in the diffusional restriction of the liposoluble acid form of the herbicide across the cell envelope. Such a cell response would avoid a futile cycle due to acid reentry into the cell counteracting the active export of the anionic form, presumably through an inducible plasma membrane transporter(s). Consistent with this concept, the concentration of 14C-labeled 2,4-D in 2,4-D-energized adapted Δspi1 mutant cells and the consequent intracellular acidification are higher than in wild-type cells. PMID:12839777

  4. The solubility of the tetragonal form of hen egg white lysozyme from pH 4.0 to 5.4

    NASA Technical Reports Server (NTRS)

    Cacioppo, Elizabeth; Pusey, Marc L.

    1991-01-01

    Hen egg white lysozyme solubilities in the presence of the tetragonal crystal form have been determined. Conditions investigated cover the pH range 4.0 to 5.4, varying from 2.0 to 7.0 percent NaCl concentrations and from 4 to 25 C. In all instances, the solubilities were found to increase with temperature and decrease with increasing salt concentration. The effects of pH were more complex, showing a decreasing solubility with increasing pH at low salt concentration and an increasing solubility with increasing pH at high salt concentration.

  5. Production and identification of wheat - Agropyron cristatum (1.4P) alien translocation lines.

    PubMed

    Liu, Wei-Hua; Luan, Yang; Wang, Jing-Chang; Wang, Xiao-Guang; Su, Jun-Ji; Zhang, Jin-Peng; Yang, Xin-Ming; Gao, Ai-Nong; Li, Li-Hui

    2010-06-01

    The P genome of Agropyron Gaertn., a wild relative of wheat, contains an abundance of desirable genes that can be utilized as genetic resources to improve wheat. In this study, wheat - Aegilops cylindrica Host gametocidal chromosome 2C addition lines were crossed with wheat - Agropyron cristatum (L.) Gaertn. disomic addition line accession II-21 with alien recombinant chromosome (1.4)P. We successfully induced wheat - A. cristatum alien chromosomal translocations for the first time. The frequency of translocation in the progeny was 3.75%, which was detected by molecular markers and genomic in situ hybridization (GISH). The translocation chromosomes were identified by dual-color GISH /fluorescence in situ hybridization (FISH). The P genomic DNA was used as probe to detect the (1.4)P chromosome fragment, and pHvG39, pAs1, or pSc119.2 repeated sequences were used as probes to identify wheat translocated chromosomes. The results showed that six types of translocations were identified in the three wheat - A. cristatum alien translocation lines, including the whole arm or terminal portion of a (1.4)P chromosome. The (1.4)P chromosome fragments were translocated to wheat chromosomes 1B, 2B, 5B, and 3D. The breakpoints were located at the centromeres of 1B and 2B, the pericentric locations of 5BS, and the terminals of 5BL and 3DS. In addition, we obtained 12 addition-deletion lines that contained alien A. cristatum chromosome (1.4)P in wheat background. All of these wheat - A. cristatum alien translocation lines and addition-deletion lines would be valuable for identifying A. cristatum chromosome (1.4)P-related genes and providing genetic resources and new germplasm accessions for the genetic improvement of wheat. The specific molecular markers of A. cristatum (1.4)P chromosome have been developed and used to track the (1.4)P chromatin.

  6. Two misfolding routes for the prion protein around pH 4.5.

    PubMed

    Garrec, Julian; Tavernelli, Ivano; Rothlisberger, Ursula

    2013-01-01

    Using molecular dynamics simulations, we show that the prion protein (PrP) exhibits a dual behavior, with two possible transition routes, upon protonation of H187 around pH 4.5, which mimics specific conditions encountered in endosomes. Our results suggest a picture in which the protonated imidazole ring of H187 experiences an electrostatic repulsion with the nearby guanidinium group of R136, to which the system responds by pushing either H187 or R136 sidechains away from their native cavities. The regions to which H187 and R136 are linked, namely the C-terminal part of H2 and the loop connecting S1 to H1, respectively, are affected in a different manner depending on which pathway is taken. Specific in vivo or in vitro conditions, such as the presence of molecular chaperones or a particular experimental setup, may favor one transition pathway over the other, which can result in very different [Formula: see text] monomers. This has some possible connections with the observation of various fibril morphologies and the outcome of prion strains. In addition, the finding that the interaction of H187 with R136 is a weak point in mammalian PrP is supported by the absence of the [Formula: see text] residue pair in non-mammalian species that are known to be resistant to prion diseases.

  7. Two Misfolding Routes for the Prion Protein around pH 4.5

    PubMed Central

    Garrec, Julian; Tavernelli, Ivano; Rothlisberger, Ursula

    2013-01-01

    Using molecular dynamics simulations, we show that the prion protein (PrP) exhibits a dual behavior, with two possible transition routes, upon protonation of H187 around pH 4.5, which mimics specific conditions encountered in endosomes. Our results suggest a picture in which the protonated imidazole ring of H187 experiences an electrostatic repulsion with the nearby guanidinium group of R136, to which the system responds by pushing either H187 or R136 sidechains away from their native cavities. The regions to which H187 and R136 are linked, namely the C-terminal part of H2 and the loop connecting S1 to H1, respectively, are affected in a different manner depending on which pathway is taken. Specific in vivo or in vitro conditions, such as the presence of molecular chaperones or a particular experimental setup, may favor one transition pathway over the other, which can result in very different monomers. This has some possible connections with the observation of various fibril morphologies and the outcome of prion strains. In addition, the finding that the interaction of H187 with R136 is a weak point in mammalian PrP is supported by the absence of the residue pair in non-mammalian species that are known to be resistant to prion diseases. PMID:23696721

  8. Selective P4 Activation by a Highly Reduced Cobaltate: Synthesis of Dicobalt Tetraphosphido Complexes.

    PubMed

    Pelties, Stefan; Maier, Thomas; Herrmann, Dirk; de Bruin, Bas; Rebreyend, Christophe; Gärtner, Stefanie; Shenderovich, Ilya G; Wolf, Robert

    2017-05-02

    Although the chemistry of transition metal polyphosphide anions has attracted significant attention, there are few reports of studies in which such species have been synthesized directly from white phosphorus. [K(OEt 2 ) 2 {Co(BIAN)(cod)}] (1, BIAN=1,2-bis(2,6-diisopropylphenylimino)acenaphthene, cod=1,5-cyclooctadiene), which is readily prepared by ligand exchange from [K(thf) x {Co(cod) 2 }], reacts with P 4 to afford [{K(thf)} 2 {(BIAN)Co} 2 (μ-η 44 -P 4 )] (2 a) in 61 % yield (isolated product). [{K(OEt 2 )} 2 {(BIAN)Co} 2 (μ-η 44 -P 4 )] (2 b) and [K([18]crown-6)(MeCN)] 2 [{(BIAN)Co} 2 (μ-η 44 -P 4 )] (2 c) were obtained by recrystallizing 2 a from diethyl ether and acetonitrile (and using [18]crown-6 in case of 2 c). Oxidation of 2 a with [Cp 2 Fe]BAr F 4 (one equivalent) and subsequent recrystallization of the product from different solvents gave [K(OEt 2 ){(BIAN)Co} 2 (μ-η 44 -P 4 )] (3 a) and [K(dme) 4 ][{(BIAN)Co} 2 (μ-η 44 -P 4 )] (3 b; dme=1,2-dimethoxyethane). Neutral [{(BIAN)Co} 2 (μ-η 44 -P 4 )] (4) was obtained in moderate yield by oxidizing 2 a with two equivalents of [Cp 2 Fe]BAr F 4 . The new complexes were characterized by NMR, EPR (in the case of 3 a), and UV/Vis spectroscopy, and elemental analysis. The molecular structures revealed by X-ray crystallography display planar cyclic or open-chain P 4 4- units sandwiched between {(BIAN)Co} fragments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Linewidth studies on the the NI(4S-4P) resonance multiplet. [applicable to analysis of dayglow

    NASA Technical Reports Server (NTRS)

    Erdman, P. W.; Zipf, E. C.

    1983-01-01

    Doppler broadening of the 8691, 8212, and 1200-A multiplet lines of N I is investigated experimentally, and its implications for the interpretation of the earth's 1200-A UV dayglow are considered. A regulated 100-eV, 1-mA electron beam is passed through N2 at 300 K and about 0.0005 torr flowing through a collision chamber within a UHV system, and the radiation emitted is observed with a temperature-stabilized short-focal length monochromator with a bandpass of 0.2 A in the IR and an effective UV resolution (in second-order operation with a 3600-groove/mm plane grating) of about 0.04 A. Both the IR and VUV lines are found to be broadened to about 25 times the thermal Doppler linewidth, with the IR transitions accounting for more than half of the total N(4P) cross section at 100 eV. The kinetic energy of the N(4P) atoms produced by dissociative excitation is such that their 1200-A resonance radiation (2p2 3s4P - 2p3 4SO) would be optically thin in the upper atmosphere, contrary to what has been observed. A need to revise some aspects of current UV-dayglow models is identified.

  10. Evidence that P12, a specific variant of P16{sup INK4A}, plays a suppressive role in human pancreatic carcinogenesis

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

    Poi, Ming J.; Knobloch, Thomas J.; Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH 43210

    2013-06-28

    Highlights: •P12, a variant of P16{sup INK4A}, inhibits the proliferation of pancreatic cancer cells. •P12 is distinct from P16 in function and structure. •Genetic alterations of p12 are prevalent in human pancreatic carcinoma. •P12 represents a potential pancreas-specific tumor suppressor. -- Abstract: The INK4a-ARF locus plays a central role in the development of pancreatic tumors as evidenced by the fact that up to 98% of pancreatic tumor specimens harbored genetic alterations at the INK4a-ARF locus. Interestingly, in addition to the well-known P16{sup INK4A} (P16) and P14ARF tumor suppressors, the INK4a-ARF locus in pancreas encodes another protein, P12, whose structure, function,more » and contributions to pancreatic carcinogenesis remain to be elucidated. In the current study, we demonstrated that over-expression of p12 in human pancreatic cancer cells led to cell arrest at the G1 phase and such cell cycle arrest was related to down-regulation of a number of oncogenes, such as c-Jun, Fos, and SEI1. Furthermore, unlike P16, P12 did not retain any cyclin-dependent kinase 4 (CDK4)-inhibitory activity. Instead, P12 exhibited a transactivating activity not found in P16. We also examined the genetic status of p12 in a cohort of 40 pancreatic tumor specimens and found that p12 alteration was prevalent in pancreatic tumors with an incidence of 70% (28/40). These results support that P12 is a tumor suppressive protein distinct from P16, and its genetic inactivation is associated with pancreatic carcinogenesis.« less

  11. Expression of p16(INK4A) gene in human pituitary tumours.

    PubMed

    Machiavelli, Gloria; Cotignola, Javier; Danilowicz, Karina; Carbonara, Carolina; Paes de Lima, Andrea; Basso, Armando; Bruno, Oscar Domingo; Szijan, Irene

    2008-01-01

    Pituitary adenomas comprise 10-15% of primary intracranial tumours but the mechanisms leading to tumour development are yet to be clearly established. The retinoblastoma pathway, which regulates the progression through the cell cycle, is often deregulated in different types of tumours. We studied the cyclin-dependent kinase inhibitor p16(INK4A) gene expression at mRNA level in human pituitary adenomas. Forty-six tumour specimens of different subtypes, 21 clinically non-functioning, 12 growth hormone-secreting, 6 prolactin-secreting, 6 adrenocorticotropin-secreting, and 1 thyrotropin-secreting tumours were studied. All clinically non-functioning and most of the hormone-secreting tumours were macroadenomas (38/46). The RT-PCR assay and electrophoresis of the PCR-products showed that p16(INK4A) mRNA was undetectable in: 62% of non-functioning, 8% of growth hormone-secreting, 17% of prolactin-secreting and 17% of adrenocorticotropin-secreting adenomas. Forty percent of all macroadenomas and 25% of microadenomas had negative p16(INK4A) mRNA, the latter results suggest that the absence of p16(INK4A) product might be an early event in tumours with no expression of this suppressor gene. Within the non-functioning adenomas 63% were "null cell" and 37% were positive for some hormone, both subgroups showed similar percentage of cases with absence of p16(INK4A) mRNA. Our results show that clinically non-functioning macroadenomas have impaired p16(INK4A) expression in a clearly higher proportion than any other pituitary tumour subtype investigated. Other regulatory pathways may be implicated in the development of tumours with positive p16(INK4A) expression.

  12. Psychometric evaluation of 3-set 4P questionnaire.

    PubMed

    Akerman, Eva; Fridlund, Bengt; Samuelson, Karin; Baigi, Amir; Ersson, Anders

    2013-02-01

    This is a further development of a specific questionnaire, the 3-set 4P, to be used for measuring former ICU patients' physical and psychosocial problems after intensive care and the need for follow-up. The aim was to psychometrically test and evaluate the 3-set 4P questionnaire in a larger population. The questionnaire consists of three sets: "physical", "psychosocial" and "follow-up". The questionnaires were sent by mail to all patients with more than 24-hour length of stay on four ICUs in Sweden. Construct validity was measured with exploratory factor analysis with Varimax rotation. This resulted in three factors for the "physical set", five factors for the "psychosocial set" and four factors for the "follow-up set" with strong factor loadings and a total explained variance of 62-77.5%. Thirteen questions in the SF-36 were used for concurrent validity showing Spearman's r(s) 0.3-0.6 in eight questions and less than 0.2 in five. Test-retest was used for stability reliability. In set follow-up the correlation was strong to moderate and in physical and psychosocial sets the correlations were moderate to fair. This may have been because the physical and psychosocial status changed rapidly during the test period. All three sets had good homogeneity. In conclusion, the 3-set 4P showed overall acceptable results, but it has to be further modified in different cultures before being considered a fully operational instrument for use in clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Liquid film demonstration experiment Skylab SL-4

    NASA Technical Reports Server (NTRS)

    Darbro, W.

    1975-01-01

    The liquid film demonstration experiment performed on Skylab 4 by Astronaut Gerald Carr, which involved the construction of water and soap films by boundary expansion and inertia, is discussed. Results include a 1-ml globule of water expanded into a 7-cm-diameter film as well as complex film structures produced by inertia whose lifetimes are longer in the low-g environment. Also discussed are 1-g acceleration experiments in which the unprovoked rupture of films was photographed and film lifetimes of stationary and rotated soap films were compared. Finally, there is a mathematical discussion regarding minimal surfaces, an isoperimetric problem, and liquid films.

  14. Potential energy landscape of TIP4P/2005 water

    NASA Astrophysics Data System (ADS)

    Handle, Philip H.; Sciortino, Francesco

    2018-04-01

    We report a numerical study of the statistical properties of the potential energy landscape of TIP4P/2005, one of the most accurate rigid water models. We show that, in the region where equilibrated configurations can be generated, a Gaussian landscape description is able to properly describe the model properties. We also find that the volume dependence of the landscape properties is consistent with the existence of a locus of density maxima in the phase diagram. The landscape-based equation of state accurately reproduces the TIP4P/2005 pressure-vs-volume curves, providing a sound extrapolation of the free-energy at low T. A positive-pressure liquid-liquid critical point is predicted by the resulting free-energy.

  15. Experiments in MPEG-4 content authoring, browsing, and streaming

    NASA Astrophysics Data System (ADS)

    Puri, Atul; Schmidt, Robert L.; Basso, Andrea; Civanlar, Mehmet R.

    2000-12-01

    In this paper, within the context of the MPEG-4 standard we report on preliminary experiments in three areas -- authoring of MPEG-4 content, a player/browser for MPEG-4 content, and streaming of MPEG-4 content. MPEG-4 is a new standard for coding of audiovisual objects; the core of MPEG-4 standard is complete while amendments are in various stages of completion. MPEG-4 addresses compression of audio and visual objects, their integration by scene description, and interactivity of users with such objects. MPEG-4 scene description is based on VRML like language for 3D scenes, extended to 2D scenes, and supports integration of 2D and 3D scenes. This scene description language is called BIFS. First, we introduce the basic concepts behind BIFS and then show with an example, textual authoring of different components needed to describe an audiovisual scene in BIFS; the textual BIFS is then saved as compressed binary file/s for storage or transmission. Then, we discuss a high level design of an MPEG-4 player/browser that uses the main components from authoring such as encoded BIFS stream, media files it refers to, and multiplexed object descriptor stream to play an MPEG-4 scene. We also discuss our extensions to such a player/browser. Finally, we present our work in streaming of MPEG-4 -- the payload format, modification to client MPEG-4 player/browser, server-side infrastructure and example content used in our MPEG-4 streaming experiments.

  16. UBE4B targets phosphorylated p53 at serines 15 and 392 for degradation

    PubMed Central

    Du, Cheng; Wu, Hong; Leng, Roger P.

    2016-01-01

    Phosphorylation of p53 is a key mechanism responsible for the activation of its tumor suppressor functions in response to various stresses. In unstressed cells, p53 is rapidly turned over and is maintained at a low basal level. After DNA damage or other forms of cellular stress, the p53 level increases, and the protein becomes metabolically stable. However, the mechanism of phosphorylated p53 regulation is unclear. In this study, we studied the kinetics of UBE4B, Hdm2, Pirh2, Cop1 and CHIP induction in response to p53 activation. We show that UBE4B coimmunoprecipitates with phosphorylated p53 at serines 15 and 392. Notably, the affinity between UBE4B and Hdm2 is greatly decreased after DNA damage. Furthermore, we observe that UBE4B promotes endogenous phospho-p53(S15) and phospho-p53(S392) degradation in response to IR. We demonstrate that UBE4B and Hdm2 repress p53S15A, p53S392A, and p53-2A(S15A, S392A) functions, including p53-dependent transactivation and growth inhibition. Overall, our results reveal that UBE4B plays an important role in regulating phosphorylated p53 following DNA damage. PMID:26673821

  17. Cytochrome P450 3A4 activity after surgical stress.

    PubMed

    Haas, Curtis E; Kaufman, David C; Jones, Carolyn E; Burstein, Aaron H; Reiss, William

    2003-05-01

    To evaluate the relationship between the acute inflammatory response after surgical trauma and changes in hepatic cytochrome P450 3A4 activity, compare changes in cytochrome P450 3A4 activity after procedures with varying degrees of surgical stress, and to explore the time course of any potential drug-cytokine interaction after surgery. Prospective, open-label study with each patient serving as his or her own control. University-affiliated, acute care, general hospital. A total of 16 patients scheduled for elective repair of an abdominal aortic aneurysm (n = 5), complete or partial colectomy (n = 6), or peripheral vascular surgery with graft (n = 5). Cytochrome P450 3A4 activity was estimated using the carbon-14 [14C]erythromycin breath test (ERMBT) before surgery and 24, 48, and 72 hrs after surgery. Abdominal aortic aneurysm and colectomy patients also had an ERMBT performed at discharge. Blood samples were obtained before surgery, immediately after surgery, and 6, 24, 32, 48, and 72 hrs after surgery for determination of plasma concentrations of interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha. Clinical markers of surgical stress that were collected included duration of surgery, estimated blood loss, and volume of fluids administered in the operating room. ERMBT results significantly declined in all three surgical groups, with the lowest value at the time of the 72-hr study in all three groups. There was a trend toward differences in ERMBT results among groups that did not reach statistical significance (p =.06). The nadir ERMBT result was significantly and negatively correlated with both peak interleukin-6 concentration (r(s) = -.541, p =.03) and log interleukin-6 area under the curve from 0 to 72 hrs (r(s) = -.597, p =.014). Subjects with a peak interleukin-6 of >100 pg/mL had a significantly lower nadir ERMBT compared with subjects with a peak interleukin-6 of <100 pg/mL (35.5% +/- 5.2% vs. 74.7% +/- 5.1%, p <.001). Acute inflammation after

  18. Measurements of J/ψ Production and Polarization in p+p and p+Au Collisions at s NN = 200 GeV with the STAR Experiment

    NASA Astrophysics Data System (ADS)

    Liu, Zhen

    We present the measurements of J/ψ production at mid-rapidity via the di-muon decay channel in p+p and p+Au collisions at s NN = 200 GeV by the STAR experiment at RHIC. In p+p collisions, the measured inclusive J/ψ cross section can be qualitatively described by model calculations. The J/ψ polarization parameters, λ𝜃, λϕ as well as the frame-invariant quantity λinv, are presented as a function of transverse momentum in both the helicity and Collins-Soper frames. No significant polarization is observed. In addition, the nuclear modification factor for inclusive J/ψ in p+Au collisions is similar to that measured in d+Au collisions and favors an additional nuclear absorption effect on top of the nuclear PDF effect.

  19. Photoionization of Cl+ from the 3s23p4 3P2,1,0 and the 3s23p4 1D2,1S0 states in the energy range 19-28 eV

    NASA Astrophysics Data System (ADS)

    McLaughlin, Brendan M.

    2017-01-01

    Absolute photoionization cross-sections for the Cl+ ion in its ground and the metastable states, 3s23p4 3P2,1,0 and 3s23p4 1D2,1S0, were measured recently at the Advanced Light Source at Lawrence Berkeley National Laboratory using the merged beams photon-ion technique at a photon energy resolution of 15 meV in the energy range 19-28 eV. These measurements are compared with large-scale Dirac-Coulomb R-matrix calculations in the same energy range. Photoionization of this sulphur-like chlorine ion is characterized by multiple Rydberg series of auto-ionizing resonances superimposed on a direct photoionization continuum. A wealth of resonance features observed in the experimental spectra is spectroscopically assigned, and their resonance parameters are tabulated and compared with the recent measurements. Metastable fractions in the parent ion beam are determined from this study. Theoretical resonance energies and quantum defects of the prominent Rydberg series 3s23p3nd, identified in the spectra as 3p → nd transitions, are compared with the available measurements made on this element. Weaker Rydberg series 3s23p3ns, identified as 3p → ns transitions and window resonances 3s3p4(4P)np features, due to 3s → np transitions, are also found in the spectra.

  20. Methylation of p15INK4b and Expression of ANRIL on Chromosome 9p21 Are Associated with Coronary Artery Disease

    PubMed Central

    Zhuang, Jianhui; Peng, Wenhui; Li, Hailing; Wang, Wei; Wei, Yidong; Li, Weiming; Xu, Yawei

    2012-01-01

    Background Genome-wide association studies have identified that multiple single nucleiotide polymorphisms on chromosome 9p21 are tightly associated with coronary artery disease (CAD). However, the mechanism linking this risk locus to CAD remains unclear. Methodology/Principal Findings The methylation status of six candidate genes (BAX, BCL-2, TIMP3, p14ARF, p15INK4b and p16INK4a) in 205 patients and controls who underwent coronary angiography were analyzed by quantitative MethyLight assay. Rs10757274 was genotyped and expression of INK4/ARF and antisense non-coding RNA in the INK4 locus (ANRIL) was determined by real-time RT-PCR. Compared with controls, DNA methylation levels at p15INK4b significantly increased in CAD patients (p = 0.006). To validate and dissect the methylation percentage of each target CpG site at p15INK4b, pyrosequencing was performed, finding CpG +314 and +332 remarkably hypermethylated in CAD patients. Further investigation determined that p15INK4b hypermethylation prevalently emerged in lymphocytes of CAD patients (p = 0.013). The rs10757274 genotype was significantly associated with CAD (p = 0.003) and GG genotype carriers had a higher level of ANRIL exon 1–5 expression compared among three genotypes (p = 0.009). There was a stepwise increase in p15INK4b and p16INK4a methylation as ANRIL exon 1–5 expression elevated (r = 0.23, p = 0.001 and r = 0.24, p = 0.001, respectively), although neither of two loci methylation was directly linked to rs10757274 genotype. Conclusions/Significance p15INK4b methylation is associated with CAD and ANRIL expression. The epigenetic changes in p15INK4b methylation and ANRIL expression may involve in the mechanisms of chromosome 9p21 on CAD development. PMID:23091611

  1. Distributions and Seasonal Variations of Tropospheric Ethene (C2H4) from Atmospheric Chemistry Experiment (ACE-FTS) Solar Occultation Spectra

    NASA Technical Reports Server (NTRS)

    Herbin, H.; Hurtmans, D.; Clarisse, L.; Turquety, S.; Clerbaux, C.; Rinsland, Curtis P.; Boone, C.; Bernath, P. F.; Coheur, P.-F.

    2009-01-01

    This work reports the first measurements of ethene (C2H4) distributions in the upper troposphere. These are obtained by retrieving vertical profiles from 5 to 20 km from infrared solar occultation spectra recorded in 2005 and 2006 by the Atmospheric Chemistry Experiment-Fourier Transform Spectrometer (ACE-FTS). Background volume mixin^ ratios (vmrs) ranging from a few to about 50 pptv (10(exp -1) are measured at the different altitudes, while for certain occultations, vmrs as high as 200 pptv are observed. Zonal distributions and vertically resolved latitudinal distributions are derived for the two year period analyzed, highlighting spatial - including a North-South gradient - as well as seasonal variations. We show the latter to be more pronounced at the highest latitudes, presumably as a result of less active photochemistry during winter. The observation of C2H4 enhancements in remote Arctic regions at high latitudes is consistent with the occurrence of fast transport processes of gaseous pollution from the continents leading to Arctic haze. Citation: Herbin, H., D. Hurtmans, L. Clarisse, S. Turquety, C. Clerbaux, C. P. Rinsland, C. Boone, P. F. Bernath, and P.-F. Colieur (2009), Distributions and seasonal variations of tropospheric ethene (C2H4) from Atmospheric Chemistry Experiment (ACE-FTS) solar occultation spectra,

  2. One step beyond the electric dipole approximation: An experiment to observe the 5p → 6p forbidden transition in atomic rubidium

    NASA Astrophysics Data System (ADS)

    Ponciano-Ojeda, F.; Hernández-Gómez, S.; Mojica-Casique, C.; Ruiz-Martínez, E.; López-Hernández, O.; Colín-Rodríguez, R.; Ramírez-Martínez, F.; Flores-Mijangos, J.; Sahagún, D.; Jáuregui, R.; Jiménez-Mier, J.

    2018-01-01

    An advanced undergraduate experiment to study the 5 P 3 / 2 → 6 P 3 / 2 electric quadrupole transition in rubidium atoms is presented. The experiment uses two external cavity diode lasers, one operating at the D2 rubidium resonance line and the other built with commercial parts to emit at 911 nm. The lasers produce the 5 s → 5 p → 6 p excitation sequence in which the second step is the forbidden transition. Production of atoms in the 6 P 3 / 2 state is observed by detection of the 420 nm fluorescence that results from electric dipole decay into the ground state. Lines whose widths are significantly narrower than the Doppler width are used to study the hyperfine structure of the 6 P 3 / 2 state in rubidium. The spectra illustrate characteristics unique to electric dipole forbidden transitions, like the electric quadrupole selection rules; they are also used to show general aspects of two-color laser spectroscopy such as velocity selection and hyperfine pumping.

  3. Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol.

    PubMed

    Fili, S; Valmas, A; Norrman, M; Schluckebier, G; Beckers, D; Degen, T; Wright, J; Fitch, A; Gozzo, F; Giannopoulou, A E; Karavassili, F; Margiolaki, I

    2015-09-01

    This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50-8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs.

  4. Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol

    PubMed Central

    Fili, S.; Valmas, A.; Norrman, M.; Schluckebier, G.; Beckers, D.; Degen, T.; Wright, J.; Fitch, A.; Gozzo, F.; Giannopoulou, A. E.; Karavassili, F.; Margiolaki, I.

    2015-01-01

    This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50–8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs. PMID:26306195

  5. PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K.

    PubMed

    Malek, Mouhannad; Kielkowska, Anna; Chessa, Tamara; Anderson, Karen E; Barneda, David; Pir, Pınar; Nakanishi, Hiroki; Eguchi, Satoshi; Koizumi, Atsushi; Sasaki, Junko; Juvin, Véronique; Kiselev, Vladimir Y; Niewczas, Izabella; Gray, Alexander; Valayer, Alexandre; Spensberger, Dominik; Imbert, Marine; Felisbino, Sergio; Habuchi, Tomonori; Beinke, Soren; Cosulich, Sabina; Le Novère, Nicolas; Sasaki, Takehiko; Clark, Jonathan; Hawkins, Phillip T; Stephens, Len R

    2017-11-02

    The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P 3 . PI(3,4,5)P 3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P 2 . The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P 3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P 2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P 2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P 2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P 2 , which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P 2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P 2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P 2 in the phenotype caused by loss-of-function mutations or deletions in PTEN. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. The active muon shield in the SHiP experiment

    NASA Astrophysics Data System (ADS)

    Akmete, A.; Alexandrov, A.; Anokhina, A.; Aoki, S.; Atkin, E.; Azorskiy, N.; Back, J. J.; Bagulya, A.; Baranov, A.; Barker, G. J.; Bay, A.; Bayliss, V.; Bencivenni, G.; Berdnikov, A. Y.; Berdnikov, Y. A.; Bertani, M.; Betancourt, C.; Bezshyiko, I.; Bezshyyko, O.; Bick, D.; Bieschke, S.; Blanco, A.; Boehm, J.; Bogomilov, M.; Bondarenko, K.; Bonivento, W. M.; Boyarsky, A.; Brenner, R.; Breton, D.; Brundler, R.; Bruschi, M.; Büscher, V.; Buonaura, A.; Buontempo, S.; Cadeddu, S.; Calcaterra, A.; Campanelli, M.; Chauveau, J.; Chepurnov, A.; Chernyavsky, M.; Choi, K.-Y.; Chumakov, A.; Ciambrone, P.; Dallavalle, G. M.; D'Ambrosio, N.; D'Appollonio, G.; De Lellis, G.; De Roeck, A.; De Serio, M.; Dedenko, L.; Di Crescenzo, A.; Di Marco, N.; Dib, C.; Dijkstra, H.; Dmitrenko, V.; Domenici, D.; Donskov, S.; Dubreuil, A.; Ebert, J.; Enik, T.; Etenko, A.; Fabbri, F.; Fabbri, L.; Fedin, O.; Fedorova, G.; Felici, G.; Ferro-Luzzi, M.; Fini, R. A.; Fonte, P.; Franco, C.; Fukuda, T.; Galati, G.; Gavrilov, G.; Gerlach, S.; Golinka-Bezshyyko, L.; Golubkov, D.; Golutvin, A.; Gorbunov, D.; Gorbunov, S.; Gorkavenko, V.; Gornushkin, Y.; Gorshenkov, M.; Grachev, V.; Graverini, E.; Grichine, V.; Guler, A. M.; Guz, Yu.; Hagner, C.; Hakobyan, H.; van Herwijnen, E.; Hollnagel, A.; Hosseini, B.; Hushchyn, M.; Iaselli, G.; Iuliano, A.; Jacobsson, R.; Jonker, M.; Kadenko, I.; Kamiscioglu, C.; Kamiscioglu, M.; Khabibullin, M.; Khaustov, G.; Khotyantsev, A.; Kim, S. H.; Kim, V.; Kim, Y. G.; Kitagawa, N.; Ko, J.-W.; Kodama, K.; Kolesnikov, A.; Kolev, D. I.; Kolosov, V.; Komatsu, M.; Konovalova, N.; Korkmaz, M. A.; Korol, I.; Korol'ko, I.; Korzenev, A.; Kovalenko, S.; Krasilnikova, I.; Krivova, K.; Kudenko, Y.; Kurochka, V.; Kuznetsova, E.; Lacker, H. M.; Lai, A.; Lanfranchi, G.; Lantwin, O.; Lauria, A.; Lebbolo, H.; Lee, K. Y.; Lévy, J.-M.; Lopes, L.; Lyubovitskij, V.; Maalmi, J.; Magnan, A.; Maleev, V.; Malinin, A.; Mefodev, A.; Mermod, P.; Mikado, S.; Mikhaylov, Yu.; Milstead, D. A.; Mineev, O.; Montanari, A.; Montesi, M. C.; Morishima, K.; Movchan, S.; Naganawa, N.; Nakamura, M.; Nakano, T.; Novikov, A.; Obinyakov, B.; Ogawa, S.; Okateva, N.; Owen, P. H.; Paoloni, A.; Park, B. D.; Paparella, L.; Pastore, A.; Patel, M.; Pereyma, D.; Petrenko, D.; Petridis, K.; Podgrudkov, D.; Poliakov, V.; Polukhina, N.; Prokudin, M.; Prota, A.; Rademakers, A.; Ratnikov, F.; Rawlings, T.; Razeti, M.; Redi, F.; Ricciardi, S.; Roganova, T.; Rogozhnikov, A.; Rokujo, H.; Rosa, G.; Rovelli, T.; Ruchayskiy, O.; Ruf, T.; Samoylenko, V.; Saputi, A.; Sato, O.; Savchenko, E. S.; Schmidt-Parzefall, W.; Serra, N.; Shakin, A.; Shaposhnikov, M.; Shatalov, P.; Shchedrina, T.; Shchutska, L.; Shevchenko, V.; Shibuya, H.; Shustov, A.; Silverstein, S. B.; Simone, S.; Skorokhvatov, M.; Smirnov, S.; Sohn, J. Y.; Sokolenko, A.; Starkov, N.; Storaci, B.; Strolin, P.; Takahashi, S.; Timiryasov, I.; Tioukov, V.; Tosi, N.; Treille, D.; Tsenov, R.; Ulin, S.; Ustyuzhanin, A.; Uteshev, Z.; Vankova-Kirilova, G.; Vannucci, F.; Venkova, P.; Vilchinski, S.; Villa, M.; Vlasik, K.; Volkov, A.; Voronkov, R.; Wanke, R.; Woo, J.-K.; Wurm, M.; Xella, S.; Yilmaz, D.; Yilmazer, A. U.; Yoon, C. S.; Zaytsev, Yu.

    2017-05-01

    The SHiP experiment is designed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. An essential task for the experiment is to keep the Standard Model background level to less than 0.1 event after 2× 1020 protons on target. In the beam dump, around 1011 muons will be produced per second. The muon rate in the spectrometer has to be reduced by at least four orders of magnitude to avoid muon-induced combinatorial background. A novel active muon shield is used to magnetically deflect the muons out of the acceptance of the spectrometer. This paper describes the basic principle of such a shield, its optimization and its performance.

  7. Allosteric Modulation of Ca2+ flux in Ligand-gated Cation Channel (P2X4) by Actions on Lateral Portals*

    PubMed Central

    Samways, Damien S. K.; Khakh, Baljit S.; Egan, Terrance M.

    2012-01-01

    Human P2X receptors are a family of seven ATP-gated ion channels that transport Na+, K+, and Ca2+ across cell surface membranes. The P2X4 receptor is unique among family members in its sensitivity to the macrocyclic lactone, ivermectin, which allosterically modulates both ion conduction and channel gating. In this paper we show that removing the fixed negative charge of a single acidic amino acid (Glu51) in the lateral entrance to the transmembrane pore markedly attenuates the effect of ivermectin on Ca2+ current and channel gating. Ca2+ entry through P2X4 receptors is known to trigger downstream signaling pathways in microglia. Our experiments show that the lateral portals could present a novel target for drugs in the treatment of microglia-associated disease including neuropathic pain. PMID:22219189

  8. Characterization of Al-coated and Uncoated Steel Slags in Flow-through Experiments: An Approach to Evaluate the Potential Efficiency of P Sorption Materials in P Removal Structures

    NASA Astrophysics Data System (ADS)

    Chagas, I. S. P.; Penn, C. J.; Huang, C. H.

    2017-12-01

    Excessive phosphorus (P) in surface waters is one of the key drivers of eutrophication. P removal structures are an emerging technology developed to reduce excessive dissolved P in runoff and drainage water, preventing or mitigating P delivery to water systems. One of the determining factors for the success of these structures is the type of P sorption material (PSM) being used. Steel slag, a residue of the steel industry, is an example of PSM proven to be efficient in sequestering dissolved P from water. However, its P sorption capacity can significantly vary, mostly because different steel-making processes generate this PSM. Aluminum-coating is a technology aiming to improve the P sorptive qualities of steel slag. In this study, we characterized eighteen different slag samples from different plants and steel-making processes. Safety, i.e., presence of trace metals, as well as chemical and physical properties were evaluated through digestions, metal-extractions and general chemical and physical characterization (e.g.: pH, buffer index, bulk density). We conducted flow-through experiments, a dynamic sorption approach, on coated and uncoated slag samples in order to evaluate differences in P removal efficiency and the effects of Al-coating. For the Al-coating, a solution of Al2(SO4)3 at two concentrations (94.5 or 66.2 g L-1) was used to coat the slag samples. After 48 hours in contact with the solution, flow-through experiments were performed. All samples were tested with an incoming P concentration of 0.5 mg L-1. Hydraulic residence time was regulated for each steel slag sample, alternating between 9.85 minutes or 0.28 minutes. This study will provide essential information about intrinsic differences in steel slag composition and its efficiency in sequestering P from flowing waters. Moreover, we explore the effects of the Al-coating technique, which can in turn enhance P removal structures efficacy and broaden its adoption.

  9. CREG1 enhances p16INK4a-induced cellular senescence

    PubMed Central

    Moolmuang, Benchamart

    2011-01-01

    Cellular senescence is an irreversible growth arrest that is activated in normal cells upon shortening of telomere and other cellular stresses. Bypassing cellular senescence is a necessary step for cells to become immortal during oncogenic transformation. During the spontaneous immortalization of Li-Fraumeni Syndrome (LFS) fibroblasts, we found that CREG1 (Cellular Repressor of E1A-stimulated Genes 1) expression was decreased during immortalization and increased in senescence. Moreover, we found that repression of CREG1 expression occurs via an epigenetic mechanism, promoter DNA methylation. Ectopic expression of CREG1 in the immortal LFS cell lines decreases cell proliferation but does not directly induce senescence. We confirmed this in osteosarcoma and fibrosarcoma cancer cell lines, cancers commonly seen in Li-Fraumeni Syndrome. In addition, we found that p16INK4a is also downregulated in immortal cells and that coexpression of CREG1 and p16INK4a, an inhibitor of CDK4/6 and Rb phosphorylation, has a greater effect than either CREG1 and p16INK4a alone to reduce cell growth, induce cell cycle arrest and cellular senescence in immortal LFS fibroblasts, osteosarcoma and fibrosarcoma cell lines. Moreover, cooperation of CREG1 and p16INK4a inhibits the expression of cyclin A and cyclin B by inhibiting promoter activity, thereby decreasing mRNA and protein levels; these proteins are required for S-phase entry and G2/M transition. In conclusion, this is the first evidence to demonstrate that CREG1 enhances p16INK4a-induced senescence by transcriptional repression of cell cycle-regulated genes. PMID:21263217

  10. Whole-genome analyses of DS-1-like human G2P[4] and G8P[4] rotavirus strains from Eastern, Western and Southern Africa

    PubMed Central

    Nyaga, Martin M.; Stucker, Karla M.; Esona, Mathew D.; Jere, Khuzwayo C.; Mwinyi, Bakari; Shonhai, Annie; Tsolenyanu, Enyonam; Mulindwa, Augustine; Chibumbya, Julia N.; Adolfine, Hokororo; Halpin, Rebecca A.; Roy, Sunando; Stockwell, Timothy B.; Berejena, Chipo; Seheri, Mapaseka L.; Mwenda, Jason M.; Steele, A. Duncan; Wentworth, David E.

    2018-01-01

    Group A rotaviruses (RVAs) with distinct G and P genotype combinations have been reported globally. We report the genome composition and possible origin of seven G8P[4] and five G2P[4] human RVA strains based on the genetic evolution of all 11 genome segments at the nucleotide level. Twelve RVA ELISA positive stool samples collected in the representative countries of Eastern, Southern and West Africa during the 2007–2012 surveillance seasons were subjected to sequencing using the Ion Torrent PGM and Illumina MiSeq platforms. A reference-based assembly was performed using CLC Bio’s clc_ref_assemble_long program, and full-genome consensus sequences were obtained. With the exception of the neutralising antigen, VP7, all study strains exhibited the DS-1-like genome constellation (P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2) and clustered phylogenetically with reference strains having a DS-1-like genetic backbone. Comparison of the nucleotide and amino acid sequences with selected global cognate genome segments revealed nucleotide and amino acid sequence identities of 81.7–100 % and 90.6–100 %, respectively, with NSP4 gene segment showing the most diversity among the strains. Bayesian analyses of all gene sequences to estimate the time of divergence of the lineage indicated that divergence times ranged from 16 to 44 years, except for the NSP4 gene where the lineage seemed to arise in the more distant past at an estimated 203 years ago. However, the long-term effects of changes found within the NSP4 genome segment should be further explored, and thus we recommend continued whole-genome analyses from larger sample sets to determine the evolutionary mechanisms of the DS-1-like strains collected in Africa. PMID:24952422

  11. 40 CFR 180.437 - Methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-p-toluate and methyl 6-(4-isopropyl-4...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific... for the combined residues of the herbicide methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-p...

  12. Development of Novel p16INK4a Mimetics as Anticancer Therapy

    DTIC Science & Technology

    2015-10-01

    peptide (or substituted peptide) or the crystal structure of the relevant sequence from p16INK4 ( PDB 1BI7) was used as the starting structure . Model...small peptides that interact with CDK4/6. The specific aims are as follows. (1) Determine structure -function relationships of overlapping peptides...Determine structure -function relationships of overlapping peptides derived from p16 INK4a that inhibit the activity of CDK4/6 and identify stabilized

  13. WARM SPITZER OBSERVATIONS OF THREE HOT EXOPLANETS: XO-4b, HAT-P-6b, AND HAT-P-8b

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

    Todorov, Kamen O.; Deming, Drake; Knutson, Heather A.

    2012-02-10

    We analyze Warm Spitzer/Infrared Array Camera observations of the secondary eclipses of three planets, XO-4b, HAT-P-6b, and HAT-P-8b. We measure secondary eclipse amplitudes at 3.6 {mu}m and 4.5 {mu}m for each target. XO-4b exhibits a stronger eclipse depth at 4.5 {mu}m than at 3.6 {mu}m, which is consistent with the presence of a temperature inversion. HAT-P-8b shows a stronger eclipse amplitude at 3.6 {mu}m and is best described by models without a temperature inversion. The eclipse depths of HAT-P-6b can be fitted with models with a small or no temperature inversion. We consider our results in the context of amore » postulated relationship between stellar activity and temperature inversion and a relationship between irradiation level and planet dayside temperature, as discussed by Knutson et al. and Cowan and Agol, respectively. Our results are consistent with these hypotheses, but do not significantly strengthen them. To measure accurate secondary eclipse central phases, we require accurate ephemerides. We obtain primary transit observations and supplement them with publicly available observations to update the orbital ephemerides of the three planets. Based on the secondary eclipse timing, we set upper boundaries for ecos ({omega}) for HAT-P-6b, HAT-P-8b, and XO-4b and find that the values are consistent with circular orbits.« less

  14. Human rotavirus strains circulating in Venezuela after vaccine introduction: predominance of G2P[4] and reemergence of G1P[8].

    PubMed

    Vizzi, Esmeralda; Piñeros, Oscar A; Oropeza, M Daniela; Naranjo, Laura; Suárez, José A; Fernández, Rixio; Zambrano, José L; Celis, Argelia; Liprandi, Ferdinando

    2017-03-21

    Rotavirus (RV) is the most common cause of severe childhood diarrhea worldwide. Despite Venezuela was among the first developing countries to introduce RV vaccines into their national immunization schedules, RV is still contributing to the burden of diarrhea. Concerns exist about the selective pressure that RV vaccines could exert on the predominant types and/or emergence of new strains. To assess the impact of RV vaccines on the genotype distribution 1 year after the vaccination was implemented, a total of 912 fecal specimens, collected from children with acute gastroenteritis in Caracas from February 2007 to April 2008, were screened, of which 169 (18.5%) were confirmed to be RV positive by PAGE. Rotavirus-associated diarrhea occurred all year-round, although prevailed during the coolest and driest months among unvaccinated children under 24 months old. Of 165 RV strains genotyped for G (VP7) and P (VP4) by seminested multiplex RT-PCR, 77 (46.7%) were G2P[4] and 63 (38.2%) G1P[8]. G9P[8], G3P[8] and G2P[6] were found in a lower proportion (7.3%). Remarkable was also the detection of <5% of uncommon combinations (G8P[14], G8P[4], G1P[4] and G4P[4]) and 3.6% of mixed infections. A changing pattern of G/P-type distribution was observed during the season studied, with complete predominance of G2P[4] from February to June 2007 followed by its gradual decline and the reemergence of G1P[8], predominant since January 2008. Phylogenetic analysis of VP7 and VP4 genes revealed a high similarity among G2P[4] and global strains belonging to G2-II and P[4]-V lineages. The amino acid substitution 96D → N, related with reemergence of the G2 genotype elsewhere, was observed. The G1P[8] strains from Caracas were grouped into the lineages G1-I and P[8]-III, along with geographically remote G1P[8] rotaviruses, but they were rather distant from Rotarix ® vaccine and pre-vaccine strains. Unique amino acid substitutions observed on neutralization domains of the VP7 sequence from

  15. The MVMp P4 promoter is a host cell-type range determinant in vivo.

    PubMed

    Meir, Chen; Mincberg, Michal; Rostovsky, Irina; Tal, Saar; Vollmers, Ellen M; Levi, Adi; Tattersall, Peter; Davis, Claytus

    2017-06-01

    The protoparvovirus early promoters, e.g. P4 of Minute Virus of Mice (MVM), play a critical role during infection. Initial P4 activity depends on the host transcription machinery only. Since this is cell-type dependent, it is hypothesized that P4 is a host cell-type range determinant. Yet host range determinants have mapped mostly to capsid, never P4. Here we test the hypothesis using the mouse embryo as a model system. Disruption of the CRE element of P4 drastically decreased infection levels without altering range. However, when we swapped promoter elements of MVM P4 with those from equivalent regions of the closely related H1 virus, we observed elimination of infection in fibroblasts and chondrocytes and the acquisition of infection in skeletal muscle. We conclude that P4 is a host range determinant and a target for modifying the productive infection potential of the virus - an important consideration in adapting these viruses for oncotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Strategies to re-express epigenetically silenced p15(INK4b) and p21(WAF1) genes in acute myeloid leukemia.

    PubMed

    Geyer, C Ronald

    2010-01-01

    p15(INK4B) and p21(WAF1) are TGF-β targets that are silenced in leukemia by epigenetic mechanisms involving DNA methylation and/or histone modifications. Mechanisms for establishing and maintaining epigenetic silencing of p15(INK4B) and p21(WAF1) are not well established. The reversible nature of epigenetic modifications has lead to the development of drugs that target DNA methyltransferases, histone deacetylases, and histone methyltransferases, which have been used to re-express aberrantly silenced genes in leukemia. Recently, non-coding RNA, referred to as natural antisense transcripts (NATs), have been implicated in the regulation of epigenetic modifications. Here, we review epigenetic mechanisms for silencing p15(INK4B) and p21(WAF1) and the role of NATs in this process. We also review epigenetic drugs and drug combinations used to re-express p15(INK4B) and p21(WAF1). Lastly, we discuss the potential use of NATs to target the activity of epigenetic drugs to specific genes and to permanently re-express epigenetically silenced genes.

  17. Binding of the cyclic AMP receptor protein of Escherichia coli and DNA bending at the P4 promoter of pBR322.

    PubMed Central

    Brierley, I; Hoggett, J G

    1992-01-01

    The binding of the Escherichia coli cyclic AMP receptor protein (CRP) to its specific site on the P4 promoter of pBR322 has been studied by gel electrophoresis. Binding to the P4 site was about 40-50-fold weaker than to the principal CRP site on the lactose promoter at both low (0.01 M) and high (0.1 M) ionic strengths. CRP-induced bending at the P4 site was investigated from the mobilities of CRP bound to circularly permuted P4 fragments. The estimated bending angle, based on comparison with Zinkel & Crothers [(1990) Biopolymers 29, 29-38] A-tract bending standards, was found to be approximately 96 degrees, similar to that found for binding to the lac site. These observations suggest that there is not a simple relationship between strength of CRP binding and the extent of induced bending for different CRP sites. The apparent centre of bending in P4 is displaced about 6-8 bp away from the conserved TGTGA sequence and the P4 transcription start site. Images Fig. 1. Fig. 3. Fig. 4. PMID:1322129

  18. pH homeostasis during coral calcification in a free ocean CO2 enrichment (FOCE) experiment, Heron Island reef flat, Great Barrier Reef

    PubMed Central

    Georgiou, Lucy; Falter, James; Trotter, Julie; Kline, David I.; Holcomb, Michael; Dove, Sophie G.; Hoegh-Guldberg, Ove; McCulloch, Malcolm

    2015-01-01

    Geochemical analyses (δ11B and Sr/Ca) are reported for the coral Porites cylindrica grown within a free ocean carbon enrichment (FOCE) experiment, conducted on the Heron Island reef flat (Great Barrier Reef) for a 6-mo period from June to early December 2010. The FOCE experiment was designed to simulate the effects of CO2-driven acidification predicted to occur by the end of this century (scenario RCP4.5) while simultaneously maintaining the exposure of corals to natural variations in their environment under in situ conditions. Analyses of skeletal growth (measured from extension rates and skeletal density) showed no systematic differences between low-pH FOCE treatments (ΔpH = ∼−0.05 to −0.25 units below ambient) and present day controls (ΔpH = 0) for calcification rates or the pH of the calcifying fluid (pHcf); the latter was derived from boron isotopic compositions (δ11B) of the coral skeleton. Furthermore, individual nubbins exhibited near constant δ11B compositions along their primary apical growth axes (±0.02 pHcf units) regardless of the season or treatment. Thus, under the highly dynamic conditions of the Heron Island reef flat, P. cylindrica up-regulated the pH of its calcifying fluid (pHcf ∼8.4–8.6), with each nubbin having near-constant pHcf values independent of the large natural seasonal fluctuations of the reef flat waters (pH ∼7.7 to ∼8.3) or the superimposed FOCE treatments. This newly discovered phenomenon of pH homeostasis during calcification indicates that coral living in highly dynamic environments exert strong physiological controls on the carbonate chemistry of their calcifying fluid, implying a high degree of resilience to ocean acidification within the investigated ranges. PMID:26438833

  19. pH homeostasis during coral calcification in a free ocean CO2 enrichment (FOCE) experiment, Heron Island reef flat, Great Barrier Reef.

    PubMed

    Georgiou, Lucy; Falter, James; Trotter, Julie; Kline, David I; Holcomb, Michael; Dove, Sophie G; Hoegh-Guldberg, Ove; McCulloch, Malcolm

    2015-10-27

    Geochemical analyses (δ(11)B and Sr/Ca) are reported for the coral Porites cylindrica grown within a free ocean carbon enrichment (FOCE) experiment, conducted on the Heron Island reef flat (Great Barrier Reef) for a 6-mo period from June to early December 2010. The FOCE experiment was designed to simulate the effects of CO2-driven acidification predicted to occur by the end of this century (scenario RCP4.5) while simultaneously maintaining the exposure of corals to natural variations in their environment under in situ conditions. Analyses of skeletal growth (measured from extension rates and skeletal density) showed no systematic differences between low-pH FOCE treatments (ΔpH = ∼-0.05 to -0.25 units below ambient) and present day controls (ΔpH = 0) for calcification rates or the pH of the calcifying fluid (pHcf); the latter was derived from boron isotopic compositions (δ(11)B) of the coral skeleton. Furthermore, individual nubbins exhibited near constant δ(11)B compositions along their primary apical growth axes (±0.02 pHcf units) regardless of the season or treatment. Thus, under the highly dynamic conditions of the Heron Island reef flat, P. cylindrica up-regulated the pH of its calcifying fluid (pHcf ∼8.4-8.6), with each nubbin having near-constant pHcf values independent of the large natural seasonal fluctuations of the reef flat waters (pH ∼7.7 to ∼8.3) or the superimposed FOCE treatments. This newly discovered phenomenon of pH homeostasis during calcification indicates that coral living in highly dynamic environments exert strong physiological controls on the carbonate chemistry of their calcifying fluid, implying a high degree of resilience to ocean acidification within the investigated ranges.

  20. Aromatic organic contaminant removal from an aqueous environment by p(4-VP)-based materials.

    PubMed

    Sahiner, Nurettin; Ozay, Ozgur; Aktas, Nahit

    2011-10-01

    p(4-vinylpyridine) (p(4-VP)) hydrogels were prepared in bulk (macro, 5 × 6 mm) and in nanosizes (370 nm) dimensions. The prepared hydrogels were used to remove organic aromatic contaminates such as 4-nitrophenol (4-NP), 2-nitrophenol (2-NP), phenol (Ph) and nitrobenzene (NB) from an aqueous environment. Important parameters affecting the absorption phenomena, such as the initial concentration of the organic species and the absorbent, absorption rate, absorption capacity, pH and the temperature of the medium, were evaluated for both hydrogel sizes. The absorption capacity of bulk and microgels were found to be 4-NP>2-NP>Ph>NB. Furthermore, p(4-VP) microgels were embedded in poly(acrylamide) (p(AAm)) bulk hydrogel as a microgel-hydrogel interpenetrating polymer network and proved to be very practical in overcoming the difficulty of using the microgels in real applications. Moreover, it was demonstrated that separately prepared magnetic ferrite particles inserted inside p(4-VP) microgels during synthesis allowed for trouble-free removal of p(4-VP)-magnetic composite microgels from the aqueous environment by an externally applied magnetic field upon completion of their task. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Binding of the cyclic AMP receptor protein of Escherichia coli and DNA bending at the P4 promoter of pBR322.

    PubMed

    Brierley, I; Hoggett, J G

    1992-07-01

    The binding of the Escherichia coli cyclic AMP receptor protein (CRP) to its specific site on the P4 promoter of pBR322 has been studied by gel electrophoresis. Binding to the P4 site was about 40-50-fold weaker than to the principal CRP site on the lactose promoter at both low (0.01 M) and high (0.1 M) ionic strengths. CRP-induced bending at the P4 site was investigated from the mobilities of CRP bound to circularly permuted P4 fragments. The estimated bending angle, based on comparison with Zinkel & Crothers [(1990) Biopolymers 29, 29-38] A-tract bending standards, was found to be approximately 96 degrees, similar to that found for binding to the lac site. These observations suggest that there is not a simple relationship between strength of CRP binding and the extent of induced bending for different CRP sites. The apparent centre of bending in P4 is displaced about 6-8 bp away from the conserved TGTGA sequence and the P4 transcription start site.

  2. Identification of the interleukin 4 receptor alpha gene as a direct target for p73.

    PubMed

    Sasaki, Yasushi; Mita, Hiroaki; Toyota, Minoru; Ishida, Setsuko; Morimoto, Ichiro; Yamashita, Toshiharu; Tanaka, Toshihiro; Imai, Kohzoh; Nakamura, Yusuke; Tokino, Takashi

    2003-12-01

    p73 has a high degree of structural homology to p53 and can activate transcription of p53-responsive genes. However, analysis of p73-deficient mice revealed a marked divergence in the physiological activities of p53 family genes and distinguishes p73 from p53. Mice deficient for p73 exhibit profound defects, including hippocampal dysgenesis, chronic infection, and inflammation, as well as abnormalities in pheromone sensory pathways. p73 plays important roles in neurogenesis, sensory pathways, and homeostatic regulation. Here, we found that the interleukin 4 receptor alpha (IL-4Ralpha) gene is up-regulated by p73 but not significantly by p53 in several human cancer cell lines. IL-4Ralphatranscription is also activated in response to cisplatin, a DNA-damaging agent known to induce p73. By using small interference RNA designed to target p73, we demonstrated that silencing endogenous p73 abrogates the induction of the IL-4Ralpha gene after cisplatin treatment. Furthermore, we identified a p73-binding site in the first intron of the IL-4Ralpha gene that can directly interact with the p73 protein in vivo. This p73-binding site consists of eight copies of a 10-bp consensus p53-binding motif and is a functional response element that is relatively specific for p73 among the p53 family. p73beta promoted localized nucleosomal acetylation through recruitment of coactivator p300, indicating that p73 regulates transcription of IL-4Ralpha through the unique p73-binding site. We also found that p73beta-transfected tumor cells are sensitive to IL-4-mediated apoptosis. Our data suggest that IL-4Ralpha could mediate, in part, certain immune responses and p73-dependent cell death.

  3. Synthesis of Fe3O4@P4VP@ZIF-8 core-shell microspheres and their application in a Knoevenagel condensation reaction

    NASA Astrophysics Data System (ADS)

    Miao, Zongcheng; Yang, Fengxia; Luan, Yi; Shu, Xin; Ramella, Daniele

    2017-12-01

    In this work, a core-shell magnetic composite Fe3O4@P4VP@ZIF-8 microspheres were successfully designed and synthesized. A polymerization approach on the surface of pre-made Fe3O4 microspheres was employed for the synthesis of Fe3O4@P4VP. The zinc-derived Zeolite Imidazolate Framework (ZIF) shell was introduced through a layer-by-layer strategy. The obtained Fe3O4@P4VP@ZIF-8 core-shell structure was employed as an efficient Knoevenagel condensation catalyst for a variety of aldehydes. Furthermore, the inner P4VP layer also served as a basic additive in the condensation reaction process, while much less homogeneous basic additive was used. High catalytic reaction efficiency was achieved when the P4VP layer was utilized in combination with a Lewis acidity bearing ZIF-8 layer. The Fe3O4@P4VP@ZIF-8 catalyst was tested for recyclability and no drop in the catalytic activity was observed after more than five cycles.

  4. Molecular Determinants of Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2) Binding to Transient Receptor Potential V1 (TRPV1) Channels*

    PubMed Central

    Poblete, Horacio; Oyarzún, Ingrid; Olivero, Pablo; Comer, Jeffrey; Zuñiga, Matías; Sepulveda, Romina V.; Báez-Nieto, David; González Leon, Carlos; González-Nilo, Fernando; Latorre, Ramón

    2015-01-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been recognized as an important activator of certain transient receptor potential (TRP) channels. More specifically, TRPV1 is a pain receptor activated by a wide range of stimuli. However, whether or not PI(4,5)P2 is a TRPV1 agonist remains open to debate. Utilizing a combined approach of mutagenesis and molecular modeling, we identified a PI(4,5)P2 binding site located between the TRP box and the S4-S5 linker. At this site, PI(4,5)P2 interacts with the amino acid residues Arg-575 and Arg-579 in the S4-S5 linker and with Lys-694 in the TRP box. We confirmed that PI(4,5)P2 behaves as a channel agonist and found that Arg-575, Arg-579, and Lys-694 mutations to alanine reduce PI(4,5)P2 binding affinity. Additionally, in silico mutations R575A, R579A, and K694A showed that the reduction in binding affinity results from the delocalization of PI(4,5)P2 in the binding pocket. Molecular dynamics simulations indicate that PI(4,5)P2 binding induces conformational rearrangements of the structure formed by S6 and the TRP domain, which cause an opening of the lower TRPV1 channel gate. PMID:25425643

  5. Inactivation of Cytochrome P450 (P450) 3A4 but not P450 3A5 by OSI-930, a Thiophene-Containing Anticancer DrugS⃞

    PubMed Central

    Lin, Hsia-lien; Zhang, Haoming; Medower, Christine; Johnson, William W.

    2011-01-01

    An investigational anticancer agent that contains a thiophene moiety, 3-[(quinolin-4-ylmethyl)-amino]-N-[4-trifluoromethox)phenyl] thiophene-2-carboxamide (OSI-930), was tested to investigate its ability to modulate the activities of several cytochrome P450 enzymes. Results showed that OSI-930 inactivated purified, recombinant cytochrome P450 (P450) 3A4 in the reconstituted system in a mechanism-based manner. The inactivation was dependent on cytochrome b5 and required NADPH. Catalase did not protect against the inactivation. No inactivation was observed in studies with human 2B6, 2D6, or 3A5 either in the presence or in the absence of b5. The inactivation of 3A4 by OSI-930 was time- and concentration-dependent. The inactivation of the 7-benzyloxy-4-(trifluoromethyl)coumarin catalytic activity of 3A4 was characterized by a KI of 24 μM and a kinact of 0.04 min−1. This KI is significantly greater than the clinical OSI-930 Cmax of 1.7 μM at the maximum tolerated dose, indicating that clinical drug interactions of OSI-930 via this pathway are not likely. Spectral analysis of the inactivated protein indicated that the decrease in the reduced CO spectrum at 450 nm was comparable to the amount of inactivation, thereby suggesting that the inactivation was primarily due to modification of the heme. High-pressure liquid chromatography (HPLC) analysis with detection at 400 nm showed a loss of heme comparable to the activity loss, but a modified heme was not detected. This result suggests either that the heme must have been modified enough so as not to be observed in a HPLC chromatograph or, possibly, that it was destroyed. The partition ratio for the inactivation of P450 3A4 was approximately 23, suggesting that this P450 3A4-mediated pathway occurs with approximately 4% frequency during the metabolism of OSI-930. Modeling studies on the binding of OSI-930 to the active site of the P450 3A4 indicated that OSI-930 would be oriented properly in the active site for oxidation

  6. Chemical Reactivity of Formaldehyde in FeAlP0{sub 4} Sieve

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

    Yeom, Young-Hoon; Ulagappan, Nagappan; Frei, Heinz

    2001-03-12

    Formaldehyde gas loaded into framework Fe aluminophosphate sieve (FeAlP O4-5) at 250 K was found to react with adsorbed H2O, CH3OH, H2O2, or lattice OH groups to yield the corresponding addition product, namely CH2(OH)2, CH3OCH2OH, HO 2CH2OH, or POCH2OH, respectively. Reactions were monitored in situ by static FT-IR spectroscopy, and assignments are based on experiments with CD2=0 and CD3OD. Most efficient was the reaction with H2O2 as indicated by the fact that HO2CH2OH was formed at the exclusion of CH2(OH)2 and POCH2OH when adsorbing formaldehyde onto a sieve loaded with H2O2 and H2O. Methoxymethanol, methanediol, and POCH2OH were stable atmore » 250 K, but dissociated above 0 degrees C under release of formaldehyde. Hydromethyl hydroperoxide disproportionates to formic acid and water. Under 355 nm irradiation in FeAlPO4 sieve, HO2CH2OH was found to undergo efficient photofragmentation.« less

  7. 1,2,3,4-Tetrahydroisoquinolines as inhibitors of HIV-1 integrase and human LEDGF/p75 interaction.

    PubMed

    George, Anu; Gopi Krishna Reddy, Alavala; Satyanarayana, Gedu; Raghavendra, Nidhanapati K

    2018-06-01

    Alkaloids are a class of organic compounds with a wide range of biological properties, including anti-HIV activity. The 1,2,3,4-tetrahydroisoquinoline is a ubiquitous structural motif of many alkaloids. Using a short and an efficient route for synthesis, a series of 1,2,3,4-tetrahydroisoquinolines/isoquinolines was developed. These compounds have been analysed for their ability to inhibit an important interaction between HIV-1 integrase enzyme (IN) and human LEDGF/p75 protein (p75) which assists in the viral integration into the active genes. A lead compound 6d is found to inhibit the LEDGF/p75-IN interaction in vitro with an IC 50 of ~10 μm. Molecular docking analysis of the isoquinoline 6d reveals its interactions with the LEDGF/p75-binding residues of IN. Based on an order of addition experiment, the binding of 6d or LEDGF/p75 to IN is shown to be mutually exclusive. Also, the activity of 6d in vitro is found to be unaffected by the presence of a non-specific DNA. As reported earlier for the inhibitors of LEDGF/p75-IN interaction, 6d exhibits a potent inhibition of both the early and late stages of HIV-1 replication. Compound 6d differing from the known inhibitors in the chemical moieties and interactions with CCD could potentially be explored further for developing small molecule inhibitors of LEDGF/p75-IN interaction having a higher potency. © 2018 John Wiley & Sons A/S.

  8. Kinetics of PTEN-mediated PI(3,4,5)P3 hydrolysis on solid supported membranes

    PubMed Central

    Liu, Chun; Deb, Sanghamitra; Ferreira, Vinicius S.; Xu, Eric; Baumgart, Tobias

    2018-01-01

    Phosphatidylinositides play important roles in cellular signaling and migration. Phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) is an important phosphatidylinositide because it acts as a secondary messenger to trigger cell movement and proliferation. A high level of PI(3,4,5)P3 at the plasma membrane is known to contribute to tumorigenesis. One key enzyme that regulates PI(3,4,5)P3 levels at the plasma membrane is phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which dephosphorylates PI(3,4,5)P3 through hydrolysis to form phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). It has been reported that PI(4,5)P2 is involved in positive feedback in the PI(3,4,5)P3 hydrolysis by PTEN. However, how PI(3,4,5)P3 dephosphorylation by PTEN is regulated, is still under debate. How other PI(3,4,5)P3-binding proteins affect the dephosphorylation kinetics catalyzed by PTEN also remains unclear. Here, we develop a fluorescent-protein biosensor approach to study how PI(3,4,5)P3 dephosphorylation is regulated by PTEN as well as its membrane-mediated feedback mechanisms. Our observation of sigmoidal kinetics of the PI(3,4,5)P3 hydrolysis reaction supports the notion of autocatalysis in PTEN function. We developed a kinetic model to describe the observed reaction kinetics, which allowed us to i) distinguish between membrane-recruitment and allosteric activation of PTEN by PI(4,5)P2, ii) account for the influence of the biosensor on the observed reaction kinetics, and iii) demonstrate that all of these mechanisms contribute to the kinetics of PTEN-mediated catalysis. PMID:29447222

  9. Kinetics of PTEN-mediated PI(3,4,5)P3 hydrolysis on solid supported membranes.

    PubMed

    Liu, Chun; Deb, Sanghamitra; Ferreira, Vinicius S; Xu, Eric; Baumgart, Tobias

    2018-01-01

    Phosphatidylinositides play important roles in cellular signaling and migration. Phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) is an important phosphatidylinositide because it acts as a secondary messenger to trigger cell movement and proliferation. A high level of PI(3,4,5)P3 at the plasma membrane is known to contribute to tumorigenesis. One key enzyme that regulates PI(3,4,5)P3 levels at the plasma membrane is phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which dephosphorylates PI(3,4,5)P3 through hydrolysis to form phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). It has been reported that PI(4,5)P2 is involved in positive feedback in the PI(3,4,5)P3 hydrolysis by PTEN. However, how PI(3,4,5)P3 dephosphorylation by PTEN is regulated, is still under debate. How other PI(3,4,5)P3-binding proteins affect the dephosphorylation kinetics catalyzed by PTEN also remains unclear. Here, we develop a fluorescent-protein biosensor approach to study how PI(3,4,5)P3 dephosphorylation is regulated by PTEN as well as its membrane-mediated feedback mechanisms. Our observation of sigmoidal kinetics of the PI(3,4,5)P3 hydrolysis reaction supports the notion of autocatalysis in PTEN function. We developed a kinetic model to describe the observed reaction kinetics, which allowed us to i) distinguish between membrane-recruitment and allosteric activation of PTEN by PI(4,5)P2, ii) account for the influence of the biosensor on the observed reaction kinetics, and iii) demonstrate that all of these mechanisms contribute to the kinetics of PTEN-mediated catalysis.

  10. Intra-genotypic Diversity of Archival G4P[8] Human Rotaviruses from Washington, DC

    PubMed Central

    McDonald, Sarah M.; Davis, Kristin; McAllen, John K.; Spiro, David J.; Patton, John T.

    2011-01-01

    Group A human rotaviruses (RVs) remain the most frequently detected viral agents associated with acute gastroenteritis in infants and young children. Despite their medical importance, relatively few complete genome sequences have been determined for commonly circulating G/P-type strains (i.e., G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]). In the current study, we sequenced the genomes of 11 G4P[8] isolates from stool specimens that were collected in Washington, DC during the years of 1974-1991. We found that the VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6-encoding genes of all 11 G4P[8] RVs have the genotypes of G4-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. By constructing phylogenetic trees for each gene, extensive intra-genotypic diversity was revealed among the G4P[8] RVs, and new sub-genotype gene alleles were identified. Several of these alleles are nearly identical to those of G3P[8] isolates previously sequenced from this same Washington, DC collection, strongly suggesting that the RVs underwent gene reassortment. On the other hand, we observed that some G4P[8] RVs exhibit completely different allele-based genome constellations, despite being collected during the same epidemic season; there was no evidence of gene reassortment between these strains. This observation extends our previous findings and supports the notion that stable, genetically-distinct clades of human RVs with the same G/P-type can co-circulate in a community. Interestingly, the sub-genotype gene alleles found in some of the DC RVs share a close evolutionary relationship with genes of more contemporary human strains. Thus, archival human RVs sequenced in this study might represent evolutionary precursors to modern-day strains. PMID:21712102

  11. Energy dependence of π, p and p¯ transverse momentum spectra for Au+Au collisions at s=62.4 and 200 GeV

    NASA Astrophysics Data System (ADS)

    STAR Collaboration; Abelev, B. I.; Aggarwal, M. M.; Ahammed, Z.; Anderson, B. D.; Arkhipkin, D.; Averichev, G. S.; Bai, Y.; Balewski, J.; Barannikova, O.; Barnby, L. S.; Baumgart, S.; Belaga, V. V.; Bellingeri-Laurikainen, A.; Bellwied, R.; Benedosso, F.; Betts, R. R.; Bharadwaj, S.; Bhasin, A.; Bhati, A. K.; Bichsel, H.; Bielcik, J.; Bielcikova, J.; Billmeier, A.; Bland, L. C.; Blyth, S.-L.; Bombara, M.; Bonner, B. E.; Botje, M.; Bouchet, J.; Brandin, A. V.; Bravar, A.; Burton, T. P.; Bystersky, M.; Cadman, R. V.; Cai, X. Z.; Caines, H.; Calderón de La Barca Sánchez, M.; Callner, J.; Catu, O.; Cebra, D.; Chajecki, Z.; Chaloupka, P.; Chattopadhyay, S.; Chen, H. F.; Chen, J. H.; Chen, J. Y.; Cheng, J.; Cherney, M.; Chikanian, A.; Choi, H. A.; Christie, W.; Chung, S. U.; Coffin, J. P.; Cormier, T. M.; Cosentino, M. R.; Cramer, J. G.; Crawford, H. J.; Das, D.; Dash, S.; Daugherity, M.; de Moura, M. M.; Dedovich, T. G.; Dephillips, M.; Derevschikov, A. A.; Didenko, L.; Dietel, T.; Djawotho, P.; Dogra, S. M.; Dong, X.; Drachenberg, J. L.; Draper, J. E.; Du, F.; Dunin, V. B.; Dunlop, J. C.; Dutta Mazumdar, M. R.; Eckardt, V.; Edwards, W. R.; Efimov, L. G.; Emelianov, V.; Engelage, J.; Eppley, G.; Erazmus, B.; Estienne, M.; Fachini, P.; Fatemi, R.; Fedorisin, J.; Feng, A.; Filip, P.; Finch, E.; Fine, V.; Fisyak, Y.; Fornazier, K. S. F.; Fu, J.; Gagliardi, C. A.; Gaillard, L.; Ganti, M. S.; Garcia-Solis, E.; Ghazikhanian, V.; Ghosh, P.; Gorbunov, Y. G.; Gos, H.; Grebenyuk, O.; Grosnick, D.; Guertin, S. M.; Guimaraes, K. S. F. F.; Gupta, N.; Haag, B.; Hallman, T. J.; Hamed, A.; Harris, J. W.; He, W.; Heinz, M.; Henry, T. W.; Hepplemann, S.; Hippolyte, B.; Hirsch, A.; Hjort, E.; Hoffman, A. M.; Hoffmann, G. W.; Hofman, D.; Hollis, R.; Horner, M. J.; Huang, H. Z.; Hughes, E. W.; Humanic, T. J.; Igo, G.; Iordanova, A.; Jacobs, P.; Jacobs, W. W.; Jakl, P.; Jia, F.; Jiang, H.; Jones, P. G.; Judd, E. G.; Kabana, S.; Kang, K.; Kapitan, J.; Kaplan, M.; Keane, D.; Kechechyan, A.; Kettler, D.; Khodyrev, V. Yu.; Kim, B. C.; Kiryluk, J.; Kisiel, A.; Kislov, E. M.; Klein, S. R.; Knospe, A. G.; Kocoloski, A.; Koetke, D. D.; Kollegger, T.; Kopytine, M.; Kotchenda, L.; Kouchpil, V.; Kowalik, K. L.; Kramer, M.; Kravtsov, P.; Kravtsov, V. I.; Krueger, K.; Kuhn, C.; Kulikov, A. I.; Kumar, A.; Kurnadi, P.; Kuznetsov, A. A.; Lamont, M. A. C.; Landgraf, J. M.; Lange, S.; Lapointe, S.; Laue, F.; Lauret, J.; Lebedev, A.; Lednicky, R.; Lee, C.-H.; Lehocka, S.; Levine, M. J.; Li, C.; Li, Q.; Li, Y.; Lin, G.; Lin, X.; Lindenbaum, S. J.; Lisa, M. A.; Liu, F.; Liu, H.; Liu, J.; Liu, L.; Ljubicic, T.; Llope, W. J.; Long, H.; Longacre, R. S.; Lopez-Noriega, M.; Love, W. A.; Lu, Y.; Ludlam, T.; Lynn, D.; Ma, G. L.; Ma, J. G.; Ma, Y. G.; Mahapatra, D. P.; Majka, R.; Mangotra, L. K.; Manweiler, R.; Margetis, S.; Markert, C.; Martin, L.; Matis, H. S.; Matulenko, Yu. A.; McClain, C. J.; McShane, T. S.; Melnick, Yu.; Meschanin, A.; Millane, J.; Miller, M. L.; Minaev, N. G.; Mioduszewski, S.; Mironov, C.; Mischke, A.; Mitchell, J.; Mohanty, B.; Molnar, L.; Morozov, D. A.; Munhoz, M. G.; Nandi, B. K.; Nattrass, C.; Nayak, T. K.; Nelson, J. M.; Nepali, C.; Netrakanti, P. K.; Nikitin, V. A.; Nogach, L. V.; Nurushev, S. B.; Odyniec, G.; Ogawa, A.; Okorokov, V.; Oldenburg, M.; Olson, D.; Pachr, M.; Pal, S. K.; Panebratsev, Y.; Panitkin, S. Y.; Pavlinov, A. I.; Pawlak, T.; Peitzmann, T.; Perevoztchikov, V.; Perkins, C.; Peryt, W.; Phatak, S. C.; Planinic, M.; Pluta, J.; Poljak, N.; Porile, N.; Poskanzer, A. M.; Potekhin, M.; Potrebenikova, E.; Potukuchi, B. V. K. S.; Prindle, D.; Pruneau, C.; Putschke, J.; Qattan, I. A.; Raniwala, R.; Raniwala, S.; Ray, R. L.; Razin, S. V.; Reinnarth, J.; Relyea, D.; Ridiger, A.; Ritter, H. G.; Roberts, J. B.; Rogachevskiy, O. V.; Romero, J. L.; Rose, A.; Roy, C.; Ruan, L.; Russcher, M. J.; Sahoo, R.; Sakrejda, I.; Sakuma, T.; Salur, S.; Sandweiss, J.; Sarsour, M.; Savin, I.; Sazhin, P. S.; Schambach, J.; Scharenberg, R. P.; Schmitz, N.; Seger, J.; Selyuzhenkov, I.; Seyboth, P.; Shabetai, A.; Shahaliev, E.; Shao, M.; Sharma, M.; Shen, W. Q.; Shimanskiy, S. S.; Sichtermann, E.; Simon, F.; Singaraju, R. N.; Smirnov, N.; Snellings, R.; Sorensen, P.; Sowinski, J.; Speltz, J.; Spinka, H. M.; Srivastava, B.; Stadnik, A.; Stanislaus, T. D. S.; Stock, R.; Strikhanov, M.; Stringfellow, B.; Suaide, A. A. P.; Suarez, M. C.; Subba, N. L.; Sumbera, M.; Sun, X. M.; Sun, Z.; Surrow, B.; Symons, T. J. M.; Szanto de Toledo, A.; Takahashi, J.; Tang, A. H.; Tarnowsky, T.; Thomas, J. H.; Timmins, A. R.; Timoshenko, S.; Tokarev, M.; Trainor, T. A.; Trentalange, S.; Tribble, R. E.; Tsai, O. D.; Ulery, J.; Ullrich, T.; Underwood, D. G.; van Buren, G.; van der Kolk, N.; van Leeuwen, M.; Vander Molen, A. M.; Varma, R.; Vasilevski, I. M.; Vasiliev, A. N.; Vernet, R.; Vigdor, S. E.; Viyogi, Y. P.; Vokal, S.; Voloshin, S. A.; Waggoner, W. T.; Wang, F.; Wang, G.; Wang, J. S.; Wang, X. L.; Wang, Y.; Watson, J. W.; Webb, J. C.; Westfall, G. D.; Wetzler, A.; Whitten, C., Jr.; Wieman, H.; Wissink, S. W.; Witt, R.; Wu, J.; Wu, J.; Xu, N.; Xu, Q. H.; Xu, Z.; Yepes, P.; Yoo, I.-K.; Yue, Q.; Yurevich, V. I.; Zhan, W.; Zhang, H.; Zhang, W. M.; Zhang, Y.; Zhang, Z. P.; Zhao, Y.; Zhong, C.; Zoulkarneev, R.; Zoulkarneeva, Y.; Zubarev, A. N.; Zuo, J. X.

    2007-11-01

    We study the energy dependence of the transverse momentum (p) spectra for charged pions, protons and anti-protons for Au+Au collisions at s=62.4 and 200 GeV. Data are presented at mid-rapidity (|y|<0.5) for 0.2<p<12GeV/c. In the intermediate p region (2<p<6GeV/c), the nuclear modification factor is higher at 62.4 GeV than at 200 GeV, while at higher p (p>7GeV/c) the modification is similar for both energies. The p/π and p¯/π ratios for central collisions at s=62.4GeV peak at p≃2GeV/c. In the p range where recombination is expected to dominate, the p/π ratios at 62.4 GeV are larger than at 200 GeV, while the p¯/π ratios are smaller. For p>2GeV/c, the p¯/π ratios at the two beam energies are independent of p and centrality indicating that the dependence of the p¯/π ratio on p does not change between 62.4 and 200 GeV. These findings challenge various models incorporating jet quenching and/or constituent quark coalescence.

  12. Hyperfine induced transition probabilities from 4{f}^{14}5s5p{}^{3}{{\\rm{P}}}_{0,2}^{o} states in Sm-like ions

    NASA Astrophysics Data System (ADS)

    Zhou, Fuyang; Li, Jiguang; Qu, Yizhi; Wang, Jianguo

    2017-11-01

    The hyperfine induced 4{f}145s5p{}3{{{P}}}0,2o-4{f}145{s}2{}1{{{S}}}0 transition probabilities for highly charged Sm-like ions are calculated within the framework of the multiconfiguration Dirac-Hartree-Fock method. Electron correlation, the Breit interaction and quantum electrodynamical effects are taken into account. For ions ranging from Z = 79 to Z=94,4{f}145s5p{}3{{{P}}}0o is the first excited state, and the hyperfine induced transition (HIT) is a dominant decay channel. For the 4{f}145s5p{}3{{{P}}}2o state, the HIT rates of Sm-like ions with Z=82-94 are reported as well as the magnetic dipole (M1) {}3{{{P}}}2o-{}3{{{P}}}1o, the electric quadrupole (E2) {}3{{{P}}}2o-{}3{{{P}}}0,1o, and the magnetic quadrupole (M2) {}3{{{P}}}2o-{}1{{{S}}}0 transition probabilities. It is found that M1 transition from the 4{f}145s5p{}3{{{P}}}2o state is the most important decay channel in this range on Z≥slant 82.

  13. Alterations of cyclin-dependent kinase 4 inhibitor (p16INK4A/MTS1) gene structure and expression in acute lymphoblastic leukemias.

    PubMed

    Delmer, A; Tang, R; Senamaud-Beaufort, C; Paterlini, P; Brechot, C; Zittoun, R

    1995-07-01

    The cyclin-dependent kinase 4 (cdk4) inhibitor (p16INK4/MTS1/CDKN2) gene has been recently identified as a putative tumor suppressor gene because of the high frequency of homozygous deletion observed in numerous human tumor cell lines, including leukemias. However, results obtained from uncultured tumor samples have led to discussion of the relevance of these findings. Using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis, we have investigated p16INK4A gene at both RNA and genomic levels in various types of leukemias: acute myeloid leukemia (AML) (n = 23); acute lymphocytic leukemia (ALL) (n = 22) and B cell chronic lymphoproliferative disorders (CLPD) (n = 33). p16INK4A mRNA expression was not found in only 1/20 AML and 2/23 CLPD samples. Conversely, p16INK4A mRNA was not detected in 5/17 ALL cases, and intensity of PCR products were barely detectable in seven additional cases, possibly related to the contamination by normal cells in some cases. By Southern blotting, a homozygous deletion of p16INK4A gene was found in 6/17 ALL cases (35%) among which 4/6 were negative or weakly positive by RT-PCR assay. None of the five AML and 20 CLL samples studied had p16INK4A deletion. Sequence analysis of p16INK4A exon 2 did not show point mutation in two of these cases lacking mRNA expression. Our data provide further evidence that among hematological malignancies, ALL are the most likely to be associated with p16INK4A inactivation, mainly by homozygous gene deletion. Since most hematological malignancies-except ALL-are infrequently associated with p16INK4A and retinoblastoma (Rb) gene alteration it seems worthwhile to explore cdk4 and cdk6 expression to determine whether or not the disruption of the p16INK4A/Rb/cdk4/cdk6 regulatory loop might play a role in their pathogenesis.

  14. Vascular Endothelial Growth Factor (VEGF) mRNA Isoforms are Altered in Bovine Granulosa Cells (GC) by Circulating Progestin Concentrations (P4) and May Indicate Follicle Status and Oocyte Competence

    USDA-ARS?s Scientific Manuscript database

    Previously, Melengestrol Acetate (MGA) fed for 14 d (0.5mg/cow/d; < 1 ng/ml P4) resulted in persistent follicles with increased size, decreased number of GC/follicular fluid (FF) volume, and less fertile oocytes. An experiment was conducted to determine effects of circulating P4 on amount of mRNA fo...

  15. Kinetic evidence for interaction of TMPyP4 with two different G-quadruplex conformations of human telomeric DNA.

    PubMed

    Pérez-Arnaiz, Cristina; Busto, Natalia; Santolaya, Javier; Leal, José M; Barone, Giampaolo; García, Begoña

    2018-03-01

    Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in >80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence. UV-Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics. TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na + or K + . T-Jump kinetic experiments show that the rates of formation and dissociation of these complexes in the ms time scale differ by one order of magnitude. MD simulations reveal that, in K + buffer, "hybrid 1" conformation yields kinetic constants on interaction with TMPyP4 one order lower than "hybrid 2". The binding involves π-π stacking with external loop bases. For the first time we show that for a particular buffer TMPyP4 interacts in a kinetically different way with the two Tel22 conformations even if the complexes formed are thermodynamically indistinguishable. G-quadruplexes, endowed with technological applications and potential impact on regulation mechanisms, define a new research field. The possibility of building different conformations from same sequence is a complex issue that confers G-quadruplexes very interesting features. The obtaining of reliable kinetic data constitutes an efficient tool to determine reaction mechanisms between conformations and small molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Ranitidine is unable to maintain gastric pH levels above 4 in septic patients.

    PubMed

    Terzi Coelho, Cristina B; Dragosavac, Desanka; Coelho Neto, João S; Montes, Ciro G; Guerrazzi, Fábio; Andreollo, Nelson Adami

    2009-12-01

    The study aimed to evaluate whether ranitidine and pantoprazole are able to maintain gastric pH >or=4 in septic patients. Twenty intensive care unit patients from a university teaching hospital with sepsis were included in this study. Ten patients received ranitidine (50 mg as an intermittent bolus 3 times a day) and 10 received pantoprazole (40 mg as an intermittent bolus twice a day). Gastric pH was measured continuously for 48 hours. Endoscopy of the upper digestive tract, gastric biopsy, and investigation for Helicobacter pylori were carried out before and at the end of the study. pH values >or=4 were maintained for 46.27% +/- 38.21% and 81.57% +/- 19.65% of study time in the ranitidine and pantoprazole groups, respectively (P = .04). Intravenous ranitidine was unable to maintain gastric pH above 4 in septic patients. All cases in the ranitidine group in whom pH remained above 4 had gastric hypotrophy or atrophy. Pantoprazole successfully maintained pH levels above 4.

  17. Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

    PubMed

    Sengul, Gulgun; Puchalski, Ralph B; Watson, Charles

    2012-05-01

    Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord. Copyright © 2012 Wiley Periodicals, Inc.

  18. SHiP: a new multipurpose beam-dump experiment at the SPS

    NASA Astrophysics Data System (ADS)

    Dijkstra, H. B.

    2016-11-01

    SHiP is an experiment to look for very weakly interacting particles at a new to be constructed beam-dump facility at the CERN SPS. The SHiP Technical Proposal has been submitted to the CERN SPS Committee in April 2015. The 400 GeV/c proton beam extracted from the SPS will be dumped on a heavy target with the aim of integrating 2 × 1020 proton on target in five years. A detector located downstream of the target, based on a long vacuum tank followed by a spectrometer and particle identification detectors, will allow probing a variety of models with light long-lived exotic particles and masses below a few GeV/c2. The main focus will be the physics of the so-called Hidden Portals, i.e. search for Dark Photons, Light scalars and pseudo-scalars, and Heavy Neutral Leptons (HNL). The sensitivity to HNL will allow for the first time to probe, in the mass range between the kaon and the charm meson mass, a coupling range for which Baryogenesis and active neutrino masses could also be explained. Integrated in SHiP is an Emulsion Cloud Chamber, already used in the OPERA experiment, which will allow to study active neutrino cross-sections and angular distributions. In particular SHiP can distinguish between vτ and v¯τ, and their deep inelastic scattering cross sections will be measured with statistics three orders of magnitude larger than currently available.

  19. Diving into Science. Hands-On Water-Related Experiments. Grades 2-4.

    ERIC Educational Resources Information Center

    Perdue, Peggy K.

    This book contains hands-on ocean-related laboratory activities. Major chapter hearings are: (1) "Water Experiments" (dealing with the physical nature of water and listing 10 activities); (2) "Ocean-Going Vessels" (studying the principles of boats, with three experiments); (3) "Experiments Using Shells" (containing four activities); (4) "Sand…

  20. AGC-4 Experiment Irradiation Monitoring Data Qualification Interim Report

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

    Hull, Laurence Charles

    2016-08-01

    The Graphite Technology Development Program is running a series of six experiments to quantify the effects of irradiation on nuclear grade graphite. The fourth experiment, Advanced Graphite Creep 4 (AGC 4), began with Advanced Test Reactor (ATR) cycle 157D on May 30, 2015, and has been irradiated for two cycles. The capsule was removed from the reactor after ATR cycle 158A, which ended on January 2, 2016, due to interference with another experiment. Irradiation will resume when the interfering experiment is removed from the reactor. This report documents qualification of AGC 4 experiment irradiation monitoring data for use by themore » Advanced Reactor Technologies (ART) Technology Development Office (TDO) Program for research and development activities required to design and license the first HTR nuclear plant. Qualified data meet the requirements for use as described in the experiment planning and quality assurance documents. Failed data do not meet the requirements and provide no useable information. Trend data may not meet all requirements, but still provide some useable information. Use of Trend data requires assessment of how any deficiencies affect a particular use of the data. All thermocouples (TCs) have functioned throughout the AGC-4 experiment. All temperature data are Qualified for use by the ART TDO Program. Argon, helium, and total gas flow data were within expected ranges and are Qualified for use by the ART TDO Program. Discharge gas line moisture values were consistently low during cycle 157D. At the start of cycle 158A, gas moisture briefly spiked to over 600 ppmv and then declined throughout the cycle. Moisture values are within the measurement range of the instrument and are Qualified for use by the ART TDO Program. Graphite creep specimens were subjected to one of three loads, 393, 491, or 589 lbf. For a brief period during cycle 157D between 12:19 on June 2, 2015 and 08:23 on June 11, 2015 the load cells were wired incorrectly resulting in

  1. Complete genomic sequences for hepatitis C virus subtypes 4b, 4c, 4d, 4g, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r and 4t.

    PubMed

    Li, Chunhua; Lu, Ling; Wu, Xianghong; Wang, Chuanxi; Bennett, Phil; Lu, Teng; Murphy, Donald

    2009-08-01

    In this study, we characterized the full-length genomic sequences of 13 distinct hepatitis C virus (HCV) genotype 4 isolates/subtypes: QC264/4b, QC381/4c, QC382/4d, QC193/4g, QC383/4k, QC274/4l, QC249/4m, QC97/4n, QC93/4o, QC139/4p, QC262/4q, QC384/4r and QC155/4t. These were amplified, using RT-PCR, from the sera of patients now residing in Canada, 11 of which were African immigrants. The resulting genomes varied between 9421 and 9475 nt in length and each contains a single ORF of 9018-9069 nt. The sequences showed nucleotide similarities of 77.3-84.3 % in comparison with subtypes 4a (GenBank accession no. Y11604) and 4f (EF589160) and 70.6-72.8 % in comparison with genotype 1 (M62321/1a, M58335/1b, D14853/1c, and 1?/AJ851228) reference sequences. These similarities were often higher than those currently defined by HCV classification criteria for subtype (75.0-80.0 %) and genotype (67.0-70.0 %) division, respectively. Further analyses of the complete and partial E1 and partial NS5B sequences confirmed these 13 'provisionally assigned subtypes'.

  2. Deletion of the pH sensor GPR4 decreases renal acid excretion.

    PubMed

    Sun, Xuming; Yang, Li V; Tiegs, Brian C; Arend, Lois J; McGraw, Dennis W; Penn, Raymond B; Petrovic, Snezana

    2010-10-01

    Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

  3. Low-temperature high-density magneto-optical trapping of potassium using the open 4S{yields}5P transition at 405 nm

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

    McKay, D. C.; Jervis, D.; Fine, D. J.

    2011-12-15

    We report the laser cooling and trapping of neutral potassium on an open transition. Fermionic {sup 40}K is captured using a magneto-optical trap (MOT) on the closed 4S{sub 1/2}{yields}4P{sub 3/2} transition at 767 nm and then transferred, with high efficiency, to a MOT on the open 4S{sub 1/2}{yields}5P{sub 3/2} transition at 405 nm. Because the 5P{sub 3/2} state has a smaller linewidth than the 4P{sub 3/2} state, the Doppler limit is reduced from 145 {mu}K to 24 {mu}K, and we observe temperatures as low as 63(6) {mu}K. The density of trapped atoms also increases, due to reduced temperature and reducedmore » expulsive light forces. We measure a two-body loss coefficient of {beta}=1.4(1)x10{sup -10} cm{sup 3}/s near saturation intensity, and estimate an upper bound of 8x10{sup -18} cm{sup 2} for the ionization cross section of the 5P state at 405 nm. The combined temperature and density improvement in the 405 nm MOT is a twenty-fold increase in phase-space density over our 767 nm MOT, showing enhanced precooling for quantum gas experiments. A qualitatively similar enhancement is observed in a 405 nm MOT of bosonic {sup 41}K.« less

  4. 40 CFR 439.4 - General limitation or standard for pH.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false General limitation or standard for pH. 439.4 Section 439.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY General § 439.4 General...

  5. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

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

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin

    2014-03-28

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined themore » impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21.« less

  6. P21-activated kinase 4--not just one of the PAK.

    PubMed

    Dart, Anna E; Wells, Claire M

    2013-01-01

    P21-activated kinase 4 (PAK4) is a member of the p21-activated kinase (PAK) family. Historically much of the attention has been directed towards founding family member PAK1 but the focus is now shifting towards PAK4. It is a pluripotent serine/threonine kinase traditionally recognised as a downstream effector of the Rho-family GTPases. However, emerging research over the last few years has revealed that this kinase is much more than that. New findings have shed light on the molecular mechanism of PAK4 activation and how this kinase is critical for early development. Moreover, the number of PAK4 substrates and binding partners is rapidly expanding highlighting the increasing amount of cellular functions controlled by PAK4. We propose that PAK4 should be considered a signalling integrator regulating numerous fundamental cellular processes, including actin cytoskeletal dynamics, cell morphology and motility, cell survival, embryonic development, immune defence and oncogenic transformation. This review will outline our current understanding of PAK4 biology. Copyright © 2013 Elsevier GmbH. All rights reserved.

  7. Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor.

    PubMed

    Onuma, Takashi; Tanabe, Kumiko; Kito, Yuko; Tsujimoto, Masanori; Uematsu, Kodai; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Doi, Tomoaki; Nagase, Kiyoshi; Akamatsu, Shigeru; Tokuda, Haruhiko; Ogura, Shinji; Iwama, Toru; Kozawa, Osamu; Iida, Hiroki

    2017-08-01

    Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gαi and GTP-bound Gα13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Plasmid-mediated bioaugmentation of sequencing batch reactors for enhancement of 2,4-dichlorophenoxyacetic acid removal in wastewater using plasmid pJP4.

    PubMed

    Tsutsui, Hirofumi; Anami, Yasutaka; Matsuda, Masami; Hashimoto, Kurumi; Inoue, Daisuke; Sei, Kazunari; Soda, Satoshi; Ike, Michihiko

    2013-06-01

    Plasmid-mediated bioaugmentation was demonstrated using sequencing batch reactors (SBRs) for enhancing 2,4-dichlorophenoxyacetic acid (2,4-D) removal by introducing Cupriavidus necator JMP134 and Escherichia coli HB101 harboring 2,4-D-degrading plasmid pJP4. C. necator JMP134(pJP4) can mineralize and grow on 2,4-D, while E. coli HB101(pJP4) cannot assimilate 2,4-D because it lacks the chromosomal genes to degrade the intermediates. The SBR with C. necator JMP134(pJP4) showed 100 % removal against 200 mg/l of 2,4-D just after its introduction, after which 2,4-D removal dropped to 0 % on day 7 with the decline in viability of the introduced strain. The SBR with E. coli HB101(pJP4) showed low 2,4-D removal, i.e., below 10 %, until day 7. Transconjugant strains of Pseudomonas and Achromobacter isolated on day 7 could not grow on 2,4-D. Both SBRs started removing 2,4-D at 100 % after day 16 with the appearance of 2,4-D-degrading transconjugants belonging to Achromobacter, Burkholderia, Cupriavidus, and Pandoraea. After the influent 2,4-D concentration was increased to 500 mg/l on day 65, the SBR with E. coli HB101(pJP4) maintained stable 2,4-D removal of more than 95 %. Although the SBR with C. necator JMP134(pJP4) showed a temporal depression of 2,4-D removal of 65 % on day 76, almost 100 % removal was achieved thereafter. During this period, transconjugants isolated from both SBRs were mainly Achromobacter with high 2,4-D-degrading capability. In conclusion, plasmid-mediated bioaugmentation can enhance the degradation capability of activated sludge regardless of the survival of introduced strains and their 2,4-D degradation capacity.

  9. HIVR4P 2016, Partnering for Prevention: Conference Summary and Highlights

    PubMed Central

    Shacklett, Barbara L.; Derdeyn, Cynthia A.; Folayan, Morenike Oluwatoyin; Landovitz, Raphael J.; Anthony, Colin; Behrens, Anna-Janina; Hope, Thomas J.; Landais, Elise; Leal, Lorna; Marrazzo, Jeanne M.; Morris, Lynn; Mugo, Nelly; Ngure, Kenneth; Noseda, Veronica; Ranasinghe, Srinika; Tully, Damien C.; Voronin, Yegor; Warren, Mitchell; Wibmer, Constantinos Kurt; Xie, Irene Y.; Scarlatti, Gabriella

    2017-01-01

    Abstract HIV Research for Prevention: AIDS Vaccine, Microbicide, and ARV-based Prevention Science (HIVR4P) was built on a growing consensus that effective HIV prevention requires a combination of approaches and that understanding, analyzing, and debating the cross-cutting issues that impact prevention research are all essential to combat the global HIV/AIDS epidemic. To that end, the biennial HIVR4P conference is dedicated to all biomedical HIV prevention research approaches, including HIV vaccines, microbicides, pre-exposure prophylaxis, and treatment as prevention. The HIVR4P 2016 conference was held in Chicago, Illinois (USA), on October 17–21, and included more than 700 scientific presentations and 21 satellite sessions covering the latest and most promising advances across the HIV prevention research field. The theme “Partnering for Prevention” represented the conference's commitment to breaking down silos between research disciplines as well as between researchers, program developers, care providers, advocates, communities, and funders. Delegates spanning 42 countries attended the conference. One-third of those in attendance were early career investigators, which reflects a firm commitment to emerging researchers and ultimately to the goal of developing a sustainable scientific enterprise well into the future. This article presents a concise summary of highlights from the conference. For a more detailed account, one may find full abstracts, daily summaries, and webcasts on the conference website at hivr4p.org. PMID:28649869

  10. HIVR4P 2016, Partnering for Prevention: Conference Summary and Highlights.

    PubMed

    Shacklett, Barbara L; Derdeyn, Cynthia A; Folayan, Morenike Oluwatoyin; Landovitz, Raphael J; Anthony, Colin; Behrens, Anna-Janina; Hope, Thomas J; Landais, Elise; Leal, Lorna; Marrazzo, Jeanne M; Morris, Lynn; Mugo, Nelly; Ngure, Kenneth; Noseda, Veronica; Ranasinghe, Srinika; Tully, Damien C; Voronin, Yegor; Warren, Mitchell; Wibmer, Constantinos Kurt; Xie, Irene Y; Scarlatti, Gabriella; Thyagarajan, Bargavi

    2017-08-01

    HIV Research for Prevention: AIDS Vaccine, Microbicide, and ARV-based Prevention Science (HIVR4P) was built on a growing consensus that effective HIV prevention requires a combination of approaches and that understanding, analyzing, and debating the cross-cutting issues that impact prevention research are all essential to combat the global HIV/AIDS epidemic. To that end, the biennial HIVR4P conference is dedicated to all biomedical HIV prevention research approaches, including HIV vaccines, microbicides, pre-exposure prophylaxis, and treatment as prevention. The HIVR4P 2016 conference was held in Chicago, Illinois (USA), on October 17-21, and included more than 700 scientific presentations and 21 satellite sessions covering the latest and most promising advances across the HIV prevention research field. The theme "Partnering for Prevention" represented the conference's commitment to breaking down silos between research disciplines as well as between researchers, program developers, care providers, advocates, communities, and funders. Delegates spanning 42 countries attended the conference. One-third of those in attendance were early career investigators, which reflects a firm commitment to emerging researchers and ultimately to the goal of developing a sustainable scientific enterprise well into the future. This article presents a concise summary of highlights from the conference. For a more detailed account, one may find full abstracts, daily summaries, and webcasts on the conference website at hivr4p.org.

  11. Prenatal diagnosis of trisomy 4p: a new locus for holoprosencephaly?

    PubMed

    Karmous-Benailly, Houda; Tabet, Anne-Claude; Thaly, Adeline; Dupuy, Olivier; Huten, Yolène; Luton, Dominique; Baumann, Clarisse; Delezoide, Anne-Lise

    2005-03-01

    Trisomy of the short arm of chromosome 4 is a well-known syndrome, and several observations have been made in the last 30 years. Herein, we report a new observation of trisomy 4p in a fetus with a semi-lobar holoprosencephaly (HPE), dysmorphic features and multiple malformations. The diagnosis of HPE was made, at 33 weeks' gestation, on the fetus of a healthy G1P0 woman. Amniocentesis was performed for chromosome analysis and additional material was found on a chromosome 22. The couple elected to terminate the pregnancy and fetal examination was realized. Conventional and molecular cytogenetic studies were performed on the fetus and the parents, which showed that the additional material found on one chromosome 22 corresponded to the short arm of chromosome 4 and therefore led us to establish a diagnosis of trisomy 4p inherited from the malsegregation of a paternal translocation t(4;22)(q12;q11.1). The etiology of HPE is very heterogeneous; it includes non-genetic factors such as maternal diabetes and genetic causes. HPE cases have been described in association with many chromosomal anomalies, trisomy 13 being the most frequent. However, to our knowledge, HPE has never been previously reported in association with a trisomy involving solely the short arm of chromosome 4. Copyright 2005 John Wiley & Sons, Ltd.

  12. Association between BMP4 rs17563 polymorphism and NSCL/P risk: a meta-analysis.

    PubMed

    Hu, Yuan-Yuan; Qin, Chuan-Qi; Deng, Mo-Hong; Niu, Yu-Ming; Long, Xing

    2015-01-01

    To investigate the association between bone morphogenetic protein 4 (BMP4) rs17563 polymorphism and nonsyndromic cleft lip with or without palate (NSCL/P) risk. Four online databases were researched and the related publications were collected. Odds ratio (OR) with 95% confidence interval (CI) was applied to assess the relationship; publication bias, metaregression, and sensitivity analysis were conducted to guarantee the strength of results. Six published case-control studies were collected. Overall, no significant association between BMP4 rs17563 polymorphism and NSCL/P risk was found. It was notable that significant susceptibility on different ethnicity was observed in the stratified analysis. For Chinese population, the BMP4 rs17563 polymorphism was a significantly increased risk for NSCL/P (C versus T: OR = 1.52, 95% CI = 1.28-1.82, P < 0.01, I (2) = 0%; CC versus TT: OR = 2.58, 95% CI = 1.74-3.82, P < 0.01, I (2) = 0%; TC + CC versus TT: OR = 1.45, 95% CI = 1.14-1.84, P < 0.01, I (2) = 0%; CC versus TT + TC: OR=2.46, 95% CI = 1.46-4.14, P < 0.01, I(2) = 47.0%). On the contrary, significantly protective effects were found in Brazilian population (C versus T: OR = 0.69, 95% CI = 0.50-0.96, P = 0.03, I(2) = 68.5%; TC versus TT: OR = 0.52, 95% CI = 0.40-0.68, P < 0.01, I(2) = 0%; TC + CC versus TT: OR = 0.52, 95% CI = 0.35-0.78, P < 0.010, I(2) = 54.4%). This meta-analysis indicated that BMP4 rs17563 polymorphism could play a different role during the development of NSCL/P based on ethnicity diversity.

  13. Simple, Scalable, Script-Based Science Processor (S4P)

    NASA Technical Reports Server (NTRS)

    Lynnes, Christopher; Vollmer, Bruce; Berrick, Stephen; Mack, Robert; Pham, Long; Zhou, Bryan; Wharton, Stephen W. (Technical Monitor)

    2001-01-01

    The development and deployment of data processing systems to process Earth Observing System (EOS) data has proven to be costly and prone to technical and schedule risk. Integration of science algorithms into a robust operational system has been difficult. The core processing system, based on commercial tools, has demonstrated limitations at the rates needed to produce the several terabytes per day for EOS, primarily due to job management overhead. This has motivated an evolution in the EOS Data Information System toward a more distributed one incorporating Science Investigator-led Processing Systems (SIPS). As part of this evolution, the Goddard Earth Sciences Distributed Active Archive Center (GES DAAC) has developed a simplified processing system to accommodate the increased load expected with the advent of reprocessing and launch of a second satellite. This system, the Simple, Scalable, Script-based Science Processor (S42) may also serve as a resource for future SIPS. The current EOSDIS Core System was designed to be general, resulting in a large, complex mix of commercial and custom software. In contrast, many simpler systems, such as the EROS Data Center AVHRR IKM system, rely on a simple directory structure to drive processing, with directories representing different stages of production. The system passes input data to a directory, and the output data is placed in a "downstream" directory. The GES DAAC's Simple Scalable Script-based Science Processing System is based on the latter concept, but with modifications to allow varied science algorithms and improve portability. It uses a factory assembly-line paradigm: when work orders arrive at a station, an executable is run, and output work orders are sent to downstream stations. The stations are implemented as UNIX directories, while work orders are simple ASCII files. The core S4P infrastructure consists of a Perl program called stationmaster, which detects newly arrived work orders and forks a job to run the

  14. Energetic and entropic components of the Tolman length for mW and TIP4P/2005 water nanodroplets

    NASA Astrophysics Data System (ADS)

    Joswiak, Mark N.; Do, Ryan; Doherty, Michael F.; Peters, Baron

    2016-11-01

    The surface free energy of a droplet is approximately γ ( R ) = γ ( ∞ ) ( 1 - 2 δ / R ) , with R being the droplet radius and δ being the Tolman length. Here we use the mitosis method to compute δ = - 0.56 ± 0.1 Å at 300 K for mW water, indicating that γ ( R ) increases as the droplet size decreases. The computed Tolman length agrees quite well with a previous study of TIP4P/2005 water. We also decompose the size-dependent surface free energy into energetic and entropic contributions for the mW and TIP4P/2005 force fields. Despite having similar Tolman lengths, the energy-entropy decompositions are very different for the two force fields. We discuss critical assumptions which lead to these findings and their relation to experiments on the nucleation of water droplets. We also discuss surface broken bonds and structural correlations as possible explanations for the energetic and entropic contributions.

  15. XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice

    PubMed Central

    Yan, Catherine T.; Kaushal, Dhruv; Murphy, Michael; Zhang, Yu; Datta, Abhishek; Chen, Changzhong; Monroe, Brianna; Mostoslavsky, Gustavo; Coakley, Kristen; Gao, Yijie; Mills, Kevin D.; Fazeli, Alex P.; Tepsuporn, Suprawee; Hall, Giles; Mulligan, Richard; Fox, Edward; Bronson, Roderick; De Girolami, Umberto; Lee, Charles; Alt, Frederick W.

    2006-01-01

    Inactivation of the XRCC4 nonhomologous end-joining factor in the mouse germ line leads to embryonic lethality, in association with apoptosis of newly generated, postmitotic neurons. We now show that conditional inactivation of the XRCC4 in nestin-expressing neuronal progenitor cells, although leading to no obvious phenotype in a WT background, leads to early onset of neuronally differentiated medulloblastomas (MBs) in a p53-deficient background. A substantial proportion of the XRCC4/p53-deficient MBs have high-level N-myc gene amplification, often intrachromosomally in the context of complex translocations or other alterations of chromosome 12, on which N-myc resides, or extrachromosomally within double minutes. In addition, most XRCC4/p53-deficient MBs harbor clonal translocations of chromosome 13, which frequently involve chromosome 6 as a partner. One copy of the patched gene (Ptc), which lies on chromosome 13, was deleted in all tested XRCC4/p53-deficient MBs in the context of translocations or interstitial deletions. In addition, Cyclin D2, a chromosome 6 gene, was amplified in a subset of tumors. Notably, amplification of Myc-family or Cyclin D2 genes and deletion of Ptc also have been observed in human MBs. We therefore conclude that, in neuronal cells of mice, the nonhomologous end-joining pathway plays a critical role in suppressing genomic instability that, in a p53-deficient background, routinely contributes to genesis of MBs with recurrent chromosomal alterations. PMID:16670198

  16. Pentose Phosphate Pathway Function Affects Tolerance to the G-Quadruplex Binder TMPyP4

    PubMed Central

    Andrew, Elizabeth J.; Merchan, Stephanie; Lawless, Conor; Banks, A. Peter; Wilkinson, Darren J.; Lydall, David

    2013-01-01

    G-quadruplexes form in guanine-rich regions of DNA and the presence of these structures at telomeres prevents the activity of telomerase in vitro. Ligands such as the cationic porphyrin TMPyP4 stabilise G-quadruplexes and are therefore under investigation for their potential use as anti-cancer drugs. In order to investigate the mechanism of action of TMPyP4 in vivo, we carried out a genome-wide screen in the budding yeast Saccharomyces cerevisiae. We found that deletion of key pentose phosphate pathway (PPP) genes increased the sensitivity of yeast to the presence of TMPyP4. The PPP plays an important role in the oxidative stress response and sensitivity to TMPyP4 also increased when genes involved in the oxidative stress response, CCS1 and YAP1, were deleted. For comparison we also report genome wide-screens using hydrogen peroxide, which causes oxidative stress, RHPS4, another G-quadruplex binder and hydroxyurea, an S phase poison. We found that a number of TMPyP4-sensitive strains are also sensitive to hydrogen peroxide in a genome-wide screen. Overall our results suggest that treatment with TMPyP4 results in light-dependent oxidative stress response in budding yeast, and that this, rather than G-quadruplex binding, is the major route to cytotoxicity. Our results have implications for the usefulness and mechanism of action of TMPyP4. PMID:23776642

  17. Synthesis and Characterization of Chitosan-p-t-Butylcalix[4]arene acid

    NASA Astrophysics Data System (ADS)

    Handayani, D. S.; Frimadasi, W.; Kusumaningsih, T.; Pranoto

    2018-03-01

    The synthesis of chitosan-p-t-butylcalix[4]arene acid was done with DIC (N, N’-diisopropylcarbodiimide) as the coupling agent. The structural analysis of the chitosan-p-t-butylcalix[4]arene acid was conducted by spectrophotometer Fourier Transform Infra Red (FTIR) and X-Ray Diffraction (XRD). Meanwhile, the surface area was investigated by Surface Area Analysis, the Scanning Electrone Microscope (SEM) analysed the surface morphology, and also the melting point temperature was determined. FTIR analysis on Chitosan-p-t-butylcalix[4]arene provides an overlapped absorption of -OH and -NH groups at 3438.26 cm-1. Meanwhile, a C = C aromatic bond present at 1480.43 cm-1. XRD analysis shows some broaden peaks due to the amorphous phase of the prepared material. The prepared material is a brownish yellow solid, odorless and porous. The melting point, surface area, and the average pore radius are above 300 °C, 9.42 m2 / g, and 52.5938 Å, respectively.

  18. Immunogenicity and Safety of Three Doses of a Bivalent (B:4:P1.19,15 and B:4:P1.7-2,4) Meningococcal Outer Membrane Vesicle Vaccine in Healthy Adolescents▿

    PubMed Central

    Boutriau, Dominique; Poolman, Jan; Borrow, Ray; Findlow, Jamie; Domingo, Javier Diez; Puig-Barbera, Joan; Baldó, José María; Planelles, Victoria; Jubert, Angels; Colomer, Julia; Gil, Angel; Levie, Karin; Kervyn, Anne-Diane; Weynants, Vincent; Dominguez, Francisco; Barberá, Ramon; Sotolongo, Franklin

    2007-01-01

    An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection. PMID:17065257

  19. Culturing on Wharton's jelly extract delays mesenchymal stem cell senescence through p53 and p16INK4a/pRb pathways.

    PubMed

    Hao, Haojie; Chen, Guanghui; Liu, Jiejie; Ti, Dongdong; Zhao, Yali; Xu, Shenjun; Fu, Xiaobing; Han, Weidong

    2013-01-01

    Mesenchymal stem cells (MSCs) hold great therapeutic potential. However, MSCs undergo replication senescence during the in vitro expansion process. Wharton's jelly from the human umbilical cord harbors a large number of MSCs. In this study, we hypothesized that Wharton's jelly would be beneficial for in vitro expansion of MSCs. Wharton's jelly extract (WJEs), which is mainly composed of extracellular matrix and cytokines, was prepared as coating substrate. Human MSCs were isolated and cultured on WJE-coated plates. Although the proliferation capacity of cells was not augmented by WJE in early phase culture, adynamic growth in late-phase culture was clearly reduced, suggesting that the replicative senescence of MSCs was efficiently slowed by WJE. This was confirmed by β-galactosidase staining and telomere length measurements of MSCs in late-phase culture. In addition, the decreased differentiation ability of MSCs after long-term culture was largely ameliorated by WJE. Reactive oxygen species (ROS), p53, and p16INK4a/pRb expression increased with passaging. Analysis at the molecular level revealed that WJE-based culture efficiently suppressed the enhancement of intracellular ROS, p53, and p16INK4a/pRb in MSCs. These data demonstrated that WJE provided an ideal microenvironment for MSCs culture expansion in vitro preserved MSC properties by delaying MSCs senescence, and allowed large numbers of MSCs to be obtained for basic research and clinical therapies.

  20. Comparative study of electronic structure and microscopic model of SrMn3P4O14 and Sr3Cu3(PO4)4

    NASA Astrophysics Data System (ADS)

    Khanam, Dilruba; Rahaman, Badiur

    2018-05-01

    We present the first principle density functional calculations to figure out the comparative study of the underlying spin model SrMn3P4O14 and Sr3Cu3(PO4)4. We explicitly discuss the nature of the exchange paths and provide quantitative estimates of magnetic exchange couplings for both compounds. A microscopic modeling based on analysis of the electronic structure of both systems puts them in the interesting class of weakly coupled trimer units, which makes chains S=5/2 for SrMn3P4O14 and S=1/2 for Sr3Cu3(PO4)4 that are in turn weakly coupled to each other.

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

    PubMed Central

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

    2015-01-01

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

  2. TiF(4) and NaF at pH 1.2 but not at pH 3.5 are able to reduce dentin erosion.

    PubMed

    Wiegand, Annette; Magalhães, Ana Carolina; Sener, Beatrice; Waldheim, Elena; Attin, Thomas

    2009-08-01

    This study aimed to analyse and compare the protective effect of buffered (pH 3.5) and native (pH 1.2) TiF(4) in comparison to NaF solutions of same pH on dentin erosion. Bovine samples were pretreated with 1.50% TiF(4) or 2.02% NaF (both 0.48M F) solutions, each with a pH of 1.2 and 3.5. The control group received no fluoride pretreatment. Ten samples in each group were eroded with HCl (pH 2.6) for 10x60s. Erosion was analysed by determination of calcium release into the acid. Additionally, the surface and the elemental surface composition were examined by scanning electron microscopy (two samples in each group) and X-ray energy-dispersive spectroscopy in fluoridated but not eroded samples (six samples in each group). Cumulative calcium release (nmol/mm(2)) was statistically analysed by repeated measures ANOVA and one-way ANOVA at t=10min. TiF(4) and NaF at pH 1.2 decreased calcium release significantly, while TiF(4) and NaF at pH 3.5 were not effective. Samples treated with TiF(4) at pH 1.2 showed a significant increase of Ti, while NaF pretreatment increased F concentration significantly. TiF(4) at pH 1.2 led to the formation of globular precipitates occluding dentinal tubules, which could not be observed on samples treated with TiF(4) at pH 3.5. NaF at pH 1.2 but not at pH 3.5 induced the formation of surface precipitates covering dentinal tubules. Dentin erosion can be significantly reduced by TiF(4) and NaF at pH 1.2, but not at pH 3.5.

  3. p38 MAP kinase inhibitors. Part 3: SAR on 3,4-dihydropyrimido[4,5-d]pyrimidin-2-ones and 3,4-dihydropyrido[4,3-d]pyrimidin-2-ones.

    PubMed

    Natarajan, Swaminathan R; Wisnoski, David D; Thompson, James E; O'Neill, Edward A; O'Keefe, Stephen J

    2006-08-15

    p38 inhibitors based on 3,4-dihydropyrimido[4,5-d]pyrimidin-2-one and 3,4-dihydropyrido[4,3-d]pyrimidin-2-one platforms were synthesized and preliminary SAR explored. Among the pyrimido-pyrimidones the emergence of two sub-types of analogs-C7-amino-pyrimidines such as 24 and C7-amino-piperidines such as 42-characterized with good p38 inhibition and better off-target profiles in terms of ion channel activities was significant. Representative compound 54 in the pyrido-pyrimidone class was found to be equipotent with corresponding analog in the quinazolinone series.

  4. 1,4-Naphthoquinones potently inhibiting P2X7 receptor activity.

    PubMed

    Faria, R X; Oliveira, F H; Salles, J P; Oliveira, A S; von Ranke, N L; Bello, M L; Rodrigues, C R; Castro, H C; Louvis, A R; Martins, D L; Ferreira, V F

    2018-01-01

    P2X7 receptor (P2X7R) is an ATP-gated ion-channel with potential therapeutic applications. In this study, we prepared and searched a series of 1,4-naphthoquinones derivatives to evaluate their antagonistic effect on both human and murine P2X7 receptors. We explored the structure-activity relationship and binding mode of the most active compounds using a molecular modeling approach. Biological analysis of this series (eight analogues and two compounds) revealed significant in vitro inhibition against both human and murine P2X7R. Further characterization revealed that AN-03 and AN-04 had greater potency than BBG and A740003 in inhibiting dye uptake, IL-1β release, and carrageenan-induced paw edema in vivo. Moreover, we used electrophysiology and molecular docking analysis for characterizing AN-03 and AN-04 action mechanism. These results suggest 1,4-napthoquinones, mainly AN-04, as potential leads to design new P2X7R blockers and anti-inflammatory drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Utilization Chitosan-p-t-Butylcalix[4]Arene for Red MX 8B Adsorbent

    NASA Astrophysics Data System (ADS)

    Handayani, D. S.; Kusumaningsih, T.; Hak, L. A.

    2017-02-01

    Adsorption of Procion Red MX 8B using chitosan dan chitosan-linked p-t-butylcalix[4]arene has been done. The research aimed to understand the adsorption of Procion Red MX 8B using chitosan p-t-butylcalix[4]arene compared to ordinary chitosan. The research was conducted in a batch process varying in pH, contact time and initial concentration of the Procion Red MX 8B. The amount of dye adsorbed was determined using UV-Vis spectrophotometer and the adsorben was characterized using FTIR and SEM-EDX spectrophotometer. The result showed that the optimum condition was achieved when the pH was set at 4, contact time 135 minutes and initial concentration at 200 ppm. The kinetic analysis showed that the adsorption followed Ho kinetic model and pseudo second order with the adsorption rate constant was 3.69×10-3 g/mg.minute and 2.03×10-3 g/mg.minute. The isotherm analysis showed that the adsorption process tend to occur following the Langmuir model with maximum capacity for chitosan and chitosan-linked p-t-butylcalix[4]arene 136.09 mg/g and 147.35 mg/g respectively. The adsorption energy of chitosan and chitosan-linked p-t-butylcalix[4]arene at 30.53 kJ/mole and 33.65 kJ/mole.

  6. Photochemistry of bromoacetylene - Formation of HBr and quenching of excited Br/4 2P 0 1/2/

    NASA Technical Reports Server (NTRS)

    Laufer, A. H.

    1979-01-01

    The photolysis of bromacetylene is examined by means of vacuum ultraviolet flash photolysis-kinetic spectroscopy, with attention given to the production of Br atoms in the 2P 0 3/2 and 2P 0 1/2 states, the production of HBr, and UV absorption attributable to the ethynyl radical. Although Br(2P 0 1/2) and Br(2P 0 3/2) were both directly observed at the shortest delay time after the flash, strongly indicating the presence of the ethynyl radical, transient absorption by C2H was not detected in the range 125 to 180 nm. Quenching rate constants for the decay of the 2P 0 1/2 state of Br, which is observed to form concurrently with the ground state, are derived for quenching by He, CH2Br, CF4, and D2 from the pseudo-first-order decay rates. HBr was observed as a secondary photolysis product, and a model of its formation by the exothermic reaction of ground-state atoms with C2HBR, coupled with the secondary production of Br atoms, is found to agree well with the experiment.

  7. The dynamics of plasma membrane PtdIns(4,5)P(2) at fertilization of mouse eggs.

    PubMed

    Halet, Guillaume; Tunwell, Richard; Balla, Tamas; Swann, Karl; Carroll, John

    2002-05-15

    A series of intracellular Ca2+ oscillations are responsible for triggering egg activation and cortical granule exocytosis at fertilization in mammals. These Ca2+ oscillations are generated by an increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)], which results from the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)]. Using confocal imaging to simultaneously monitor Ca2+ and plasma membrane PtdIns(4,5)P(2) in single living mouse eggs we have sought to establish the relationship between the kinetics of PtdIns(4,5)P(2) metabolism and the Ca2+ oscillations at fertilization. We report that there is no detectable net loss of plasma membrane PtdIns(4,5)P(2) either during the latent period or during the subsequent Ca2+ oscillations. When phosphatidylinositol 4-kinase is inhibited with micromolar wortmannin a limited decrease in plasma membrane PtdIns(4,5)P(2) is detected in half the eggs studied. Although we were unable to detect a widespread loss of PtdIns(4,5)P(2), we found that fertilization triggers a net increase in plasma membrane PtdIns(4,5)P(2) that is localized to the vegetal cortex. The fertilization-induced increase in PtdIns(4,5)P(2) follows the increase in Ca2+, is blocked by Ca2+ buffers and can be mimicked, albeit with slower kinetics, by photoreleasing Ins(1,4,5)P(3). Inhibition of Ca2+-dependent exocytosis of cortical granules, without interfering with Ca2+ transients, inhibits the PtdIns(4,5)P(2) increase. The increase appears to be due to de novo synthesis since it is inhibited by micromolar wortmannin. Finally, there is no increase in PtdIns(4,5)P(2) in immature oocytes that are not competent to extrude cortical granules. These studies suggest that fertilization does not deplete plasma membrane PtdIns(4,5)P(2) and that one of the pathways for increasing PtdIns(4,5)P(2) at fertilization is invoked by exocytosis of cortical granules.

  8. Synthesis of Bi2S3/BiVO4 Heterojunction with a One-Step Hydrothermal Method Based on pH Control and the Evaluation of Visible-Light Photocatalytic Performance

    PubMed Central

    Zhao, Deqiang; Wang, Wenwen; Zong, Wenjuan; Xiong, Shimin; Zhang, Qian; Ji, Fangying; Xu, Xuan

    2017-01-01

    The band gaps of bismuth vanadate (BiVO4) and bismuth sulfide (Bi2S3) are about 2.40 eV and 1.30 eV, respectively. Although both BiVO4 and Bi2S3 are capable of strong visible light absorption, electron–hole recombination occurs easily. To solve this problem, we designed a one-step hydrothermal method for synthesizing a Bismuth sulfide (Bi2S3)/Bismuth vanadate (BiVO4) heterojunction using polyvinylpyrrolidone K-30 (PVP) as a structure-directing agent, and 2-Amino-3-mercaptopropanoic acid (l-cysteine) as a sulfur source. The pH of the reaction solution was regulated to yield different products: when the pH was 7.5, only monoclinic BiVO4 was produced (sample 7.5); when the pH was 8.0 or 8.5, both Bi2S3 and BiVO4 were produced (samples 8.0 and 8.5); and when the pH was 9.0, only Bi2S3 was produced (sample 9.0). In sample 8.0, Bi2S3 and BiVO4 were closely integrated with each other, with Bi2S3 particles formed on the surface of concentric BiVO4 layers, but the two compounds grew separately in a pH solution of 8.5. Visible-light photocatalytic degradation experiments demonstrated that the degradation efficiency of the Bi2S3/BiVO4 heterojunction was highest when prepared under a pH of 8.0. The initial rhodamine B in the solution (5 mg/L) was completely degraded within three hours. Recycling experiments verified the high stability of Bi2S3/BiVO4. The synthesis method proposed in this paper is expected to enable large-scale and practical use of Bi2S3/BiVO4. PMID:28767085

  9. The Cytoprotective Effects of E-α-(4-Methoxyphenyl)-2’,3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC)—A Novel and Non-Cytotoxic HO-1 Inducer

    PubMed Central

    Kaufmann, Kai B.; Al-Rifai, Nafisah; Ulbrich, Felix; Schallner, Nils; Rücker, Hannelore; Enzinger, Monika; Petkes, Hermina; Pitzl, Sebastian

    2015-01-01

    Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1), is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2’,3,4,4’-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS) production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2’-hydroxychalcone, calythropsin and 2’-hydroxy-3,4,4’-trimethoxychalcone) prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl)-2’,3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC) demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264

  10. The Cobalt cyclo‐P4 Sandwich Complex and Its Role in the Formation of Polyphosphorus Compounds

    PubMed Central

    Dielmann, Fabian; Timoshkin, Alexey; Piesch, Martin; Balázs, Gábor

    2017-01-01

    Abstract A synthetic approach to the sandwich complex [Cp′′′Co(η4P4)] (2) containing a cyclo‐P4 ligand as an end‐deck was developed. Complex 2 is the missing homologue in the series of first‐row cyclo‐Pn sandwich complexes, and shows a unique tendency to dimerize in solution to form two isomeric P8 complexes [(Cp′′′Co)2(μ,η4:η2:η1‐P8)] (3 and 4). Reactivity studies indicate that 2 and 3 react with further [Cp′′′Co] fragments to give [(Cp′′′Co)2(μ,η2:η2‐P2)2] (5) and [(Cp′′′Co)3P8] (6), respectively. Furthermore, complexes 2, 3, and 4 thermally decompose forming 5, 6, and the P12 complex [(Cp′′′Co)3P12] (7). DFT calculations on the P4 activation process suggest a η3‐P4 Co complex as the key intermediate in the synthesis of 2 as well as in the formation of larger polyphosphorus complexes via a unique oligomerization pathway. PMID:28078794

  11. Developmental toxicity of p,p'-dichlorodiphenyltrichloroethane, 2,4,6-trinitrotoluene, their metabolites, and benzo[a]pyrene in Xenopus laevis embryos.

    PubMed

    Saka, Masahiro

    2004-04-01

    Since 1995, high incidences of deformed frogs have been documented in Kitakyushu, Japan. In this area, relatively high concentrations of DDT, trinitrotoluene (TNT), their metabolites (p,p'-dichlorodiphenyldichloroethylene [DDE], p,p'-dichlorodiphenyldichloroethane [DDD], 2-amino-4,6-dinitrotoluene [2ADNT], and 4-amino-2,6-dinitrotoluene [4ADNT]), and benzo[a]pyrene [BaP]) have been identified from field samples. I used a standardized assay with Xenopus laevis embryos (frog embryo teratogenesis assay--Xenopus, FETAX) to examine the developmental toxicity of these compounds. Both DDE and BaP were considered nearly nontoxic in embryonic development because they induced low (< 10%) mortality and malformation incidence even at the highest concentrations tested (DDE, 393 microM; BaP, 13.2 microM). The DDD (96-h median lethal concentration [LC50] = 44.1 microM, 96-h median effective concentration [EC50] for malformation = 14.9 microM) was more lethal and teratogenic than its parent compound, DDT (96-h LC50 = 101 microM, 96-h EC50 = 41.5 microM). Predominant symptoms observed were axial malformations (DDT and DDD) and irregular gut coiling (DDT). However, DDT and DDD should not act as major lethal or teratogenic toxicants in the aquatic environment within a short-term exposure via water because their 96-h LC50 and 96-h EC50 values were extremely high, considering their low solubility in water. The TNT (96-h LC50 = 16.7 microM) was more lethal than 2ADNT (96-h LC50 = 166 microM) or 4ADNT (96-h LC50 = 115 microM). Although 4ADNT (96-h EC50 = 85.8 microM) induced various tadpole malformations, it was a weak teratogen compared with TNT (96-h EC50 = 9.78 microM) and 2ADNT (96-h EC50 = 16.9 microM). The most typical malformations observed were axial malformations, eye abnormalities (TNT), edema, and irregular gut coiling (2ADNT and 4ADNT). The 96-h LC50 and 96-h EC50 values of TNT, 2ADNT, and 4ADNT were lower than their saturated concentrations in water. Therefore, these

  12. Inactivation of p16INK4a, with retention of pRB and p53/p21cip1 function, in human MRC5 fibroblasts that overcome a telomere-independent crisis during immortalization.

    PubMed

    Taylor, Lisa M; James, Alexander; Schuller, Christine E; Brce, Jesena; Lock, Richard B; Mackenzie, Karen L

    2004-10-15

    Recent investigations, including our own, have shown that specific strains of fibroblasts expressing telomerase reverse transcriptase (hTERT) have an extended lifespan, but are not immortal. We previously demonstrated that hTERT-transduced MRC5 fetal lung fibroblasts (MRC5hTERTs) bypassed senescence but eventually succumbed to a second mortality barrier (crisis). In the present study, 67 MRC5hTERT clones were established by limiting dilution of a mass culture. Whereas 39/67 clones had an extended lifespan, all 39 extended lifespan clones underwent crisis. 11 of 39 clones escaped crisis and were immortalized. There was no apparent relationship between the fate of clones at crisis and the level of telomerase activity. Telomeres were hyperextended in the majority of the clones analyzed. There was no difference in telomere length of pre-crisis compared with post-crisis and immortal clones, indicating that hyperextended telomeres were conducive for immortalization and confirming that crisis was independent of telomere length. Immortalization of MRC5hTERT cells was associated with repression of the cyclin-dependent kinase inhibitor p16INK4a and up-regulation of pRB. However, the regulation of pRB phosphorylation and the response of the p53/p21cip1/waf1 pathway were normal in immortal cells subject to genotoxic stress. Overexpression of oncogenic ras failed to de-repress p16INK4a in immortal cells. Furthermore, expression of ras enforced senescent-like growth arrest in p16INK4a-positive, but not p16INK4a-negative MRC5hTERT cells. Immortal cells expressing ras formed small, infrequent colonies in soft agarose, but were non-tumorigenic. Overall, these results implicate the inactivation of p16INK4a as a critical event for overcoming telomere-independent crisis, immortalizing MRC5 fibroblasts and overcoming ras-induced premature senescence.

  13. Dielectronic recombination of the 4p and 4d open sub-shell tungsten ions

    NASA Astrophysics Data System (ADS)

    Li, M. J.; Fu, Y. B.; Zhang, G. D.; Zhang, Y. Z.; Dong, C. Z.; Koike, F.

    2014-04-01

    Dielectronic recombination rate coefficients are given theoretically for several highly charged tungsten ions. As 4p open sub-shell ions, Ga-, Ge-, As-, Br-, Kr-like ions are considered. Rb-like ion is further considered as a 4d open sub-shell ion. Theoretical calculations are carried out using a relativistic atomic code FAC. The effect of configuration interaction is taking into account. Inner-shell electron excitations play a significant role for the dielectronic recombination process. Simple analytical formulae are given for the total rate coefficients by fitting to the presently obtained numerical results.

  14. Mir-338-3p Mediates Tnf-A-Induced Hepatic Insulin Resistance by Targeting PP4r1 to Regulate PP4 Expression.

    PubMed

    Dou, Lin; Wang, Shuyue; Sun, Libo; Huang, Xiuqing; Zhang, Yang; Shen, Tao; Guo, Jun; Man, Yong; Tang, Weiqing; Li, Jian

    2017-01-01

    Insulin resistance is a critical factor contributing to the pathogenesis of type 2 diabetes and other metabolic diseases. Recent studies have indicated that miR-338-3p plays an important role in cancer. Here, we investigated whether miR-338-3p mediates tumour necrosis factor-α (TNF-α)-induced hepatic insulin resistance. The activation of the insulin signalling pathway and the level of glycogenesis were examined in the livers of the db/db and high fat diet (HFD)-fed mice and in HEP1-6 cells transfected with miR-338-3p mimic or inhibitor. Computational prediction of microRNA target, luciferase assay and Western blot were used to assess the miR-338-3p target. Chromatin immunoprecipitation (ChIP) assay was used to determine the transcriptional regulator of miR-338-3p. miR-338-3p was down-regulated in the livers of the db/db, HFD-fed and TNF-α-treated C57BL/6J mice, as well as in mouse HEP1-6 hepatocytes treated with TNF-α. Importantly the down-regulation of miR-338-3p induced insulin resistance, as indicated by impaired glucose tolerance and insulin tolerance. Further research showed that the down-regulated miR-338-3p resulted in the impaired AKT/ glycogen synthase kinase 3 beta (GSl·Gβ) signalling pathway and glycogen synthesis. In contrast, hepatic over-expression of miR-338-3p rescued the TNF-α-induced insulin resistance. Moreover, protein phosphatase 4 regulator subunit 1 (PP4R1) was identified as a direct target of miR-338-3p that mediated hepatic insulin signalling by regulating protein phosphatase 4 (PP4). Finally we identified hepatic nuclear factor 4 alpha (HNF-4α) as the transcriptional regulator of miRNA-338-3p. Our studies provide novel insight into the critical role and molecular mechanism by which miR-338-3p is involved in TNF-α-induced hepatic insulin resistance. miR-338-3p might mediate TNF-α-induced hepatic insulin resistance by targeting PP4R1 to regulate PP4 expression. © 2017 The Author(s). Published by S. Karger AG, Basel.

  15. Spectral Line Polarisation Atlases for 53 Cam (A4p) and alpha 2 CVn (A0p)

    NASA Astrophysics Data System (ADS)

    Wade, G. A.

    2002-08-01

    Wade, Donati & Landstreet (2000) presented a atlas of the R=35,000 Stokes IQUV spectrum of the cool magnetic Ap star beta CrB in the spectral range 450-660 nm. In this report we present analogous atlases for the well-studied magnetic Ap stars 53 Cam (HD 65339, A4p) and alpha 2 CVn (HD 112413, A0p).

  16. Phosphate solubilization and promotion of maize growth by Penicillium oxalicum P4 and Aspergillus niger P85 in a calcareous soil.

    PubMed

    Yin, Zhongwei; Shi, Fachao; Jiang, Hongmei; Roberts, Daniel P; Chen, Sanfeng; Fan, Bingquan

    2015-12-01

    Alternative tactics for improving phosphorus nutrition in crop production are needed in China and elsewhere, as the overapplication of phosphatic fertilizers can adversely impact agricultural sustainability. Penicillium oxalicum P4 and Aspergillus niger P85 were isolated from a calcareous soil in China that had been exposed to excessive application of phosphatic fertilizer for decades. Each isolate excreted a number of organic acids into, acidified, and solubilized phosphorus in a synthetic broth containing insoluble tricalcium phosphate or rock phosphate. Isolate P4, applied as a seed treatment, increased maize fresh mass per plant when rock phosphate was added to the calcareous soil in greenhouse pot studies. Isolate P85 did not increase maize fresh mass per plant but did significantly increase total phosphorus per plant when rock phosphate was added. Significant increases in 7 and 4 organic acids were detected in soil in association with isolates P4 and P85, respectively, relative to the soil-only control. The quantity and (or) number of organic acids produced by these isolates increased when rock phosphate was added to the soil. Both isolates also significantly increased available phosphorus in soil in the presence of added rock phosphate and effectively colonized the maize rhizosphere. Studies reported here indicate that isolate P4 is adapted to and capable of promoting maize growth in a calcareous soil. Plant-growth promotion by this isolate is likely due, at least in part, to increased phosphorus availability resulting from the excretion of organic acids into, and the resulting acidification of, this soil.

  17. Tributyltin potentiates 3,3',4,4',5-pentachlorobiphenyl-induced cytochrome P-4501A-related activity.

    PubMed

    DeLong, G T; Rice, C D

    1997-06-06

    Induction of cytochrome P-4501A protein and induction of related enzyme activity are hallmark physiological responses following exposure to planar halogenated aromatic hydrocarbons (HAHs) such as 3,3',4,4',5-pentachlorobiphenyl (PCB 126; PeCB). Environments contaminated by HAHs are often contaminated by mixtures of anthropogenic contaminants, including organometallic compounds. Both HAHs and organometallics easily bioconcentrate and bioaccumulate in aquatic food chains that may ultimately be linked to humans through seafood consumption. Tributyltin (TBT), a marine biocide, has been detected in many aquatic environments due to its primary use as a marine antifoulant agent. Exposure to TBT, as well as several PCBs, has been associated with immunotoxicity, neurotoxicity, and endocrine disruption. Recently TBT has been shown to inhibit cytochrome P-4501A activity in vitro, but information concerning these effects in vivo and in combination with classical inducers of P-4501A, such PeCB, is lacking. We exposed female B6C3F1 mice to 0.01, 0.1, and 1.0 mg/kg PeCB, TBT, or both in combination, with corn oil (CO) serving as a carrier control. Cytochrome P-4501A protein levels and related benzo[a]pyrene hydroxylation (BaP-OHase) activity were measured following a single acute intraperitoneal (ip) dose or seven daily injections. Body, thymus, and liver weights were used to monitor general physiological responses following exposure. P-4501A levels and BaP-OHase activity were significantly elevated in mice exposed to PeCB alone. This effect was enhanced by coexposure to low levels of TBT; PeCB-induced P-4501A-related activity was potentiated at the low range of each. The highest dose of TBT, however, inhibited these activities when given in combination with PeCB. Thymic atrophy was evident only in mice exposed daily to 0:1 and 1.0 mg/kg PeCB alone, or to a combination of the lowest and highest dose of PeCB and TBT, respectively. Because environmental levels of TBT are not

  18. Oscillator strengths and branching fractions of 4d75p-4d75s Rh II transitions

    NASA Astrophysics Data System (ADS)

    Bouazza, Safa

    2017-01-01

    This work reports semi-empirical determination of oscillator strengths, transition probabilities and branching fractions for Rh II 4d75p-4d75s transitions in a wide wavelength range. The angular coefficients of the transition matrix, beforehand obtained in pure SL coupling with help of Racah algebra are transformed into intermediate coupling using eigenvector amplitudes of these two configuration levels determined for this purpose; The transition integral was treated as free parameter in the least squares fit to experimental oscillator strength (gf) values found in literature. The extracted value: <4d75s|r1|4d75p> =2.7426 ± 0.0007 is slightly smaller than that computed by means of ab-initio method. Subsequently to oscillator strength evaluations, transition probabilities and branching fractions were deduced and compared to those obtained experimentally or through another approach like pseudo-relativistic Hartree-Fock model including core-polarization effects.

  19. Simulation of Different Truncated p16INK4a Forms and In Silico Study of Interaction with Cdk4

    PubMed Central

    Fahham, Najmeh; Ghahremani, Mohammad Hossein; Sardari, Soroush; Vaziri, Behrouz; Ostad, Seyed Nasser

    2008-01-01

    Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4), a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point and p16INK4a, a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy. PMID:19352455

  20. A novel tandem repeat sequence located on human chromosome 4p: isolation and characterization.

    PubMed

    Kogi, M; Fukushige, S; Lefevre, C; Hadano, S; Ikeda, J E

    1997-06-01

    In an effort to analyze the genomic region of the distal half of human chromosome 4p, to where Huntington disease and other diseases have been mapped, we have isolated the cosmid clone (CRS447) that was likely to contain a region with specific repeat sequences. Clone CRS447 was subjected to detailed analysis, including chromosome mapping, restriction mapping, and DNA sequencing. Chromosome mapping by both a human-CHO hybrid cell panel and FISH revealed that CRS447 was predominantly located in the 4p15.1-15.3 region. CRS447 was shown to consist of tandem repeats of 4.7-kb units present on chromosome 4p. A single EcoRI unit was subcloned (pRS447), and the complete sequence was determined as 4752 nucleotides. When pRS447 was used as a probe, the number of copies of this repeat per haploid genome was estimated to be 50-70. Sequence analysis revealed that it contained two internal CA repeats and one putative ORF. Database search established that this sequence was unreported. However, two homologous STS markers were found in the database. We concluded that CRS447/pRS447 is a novel tandem repeat sequence that is mainly specific to human chromosome 4p.

  1. Initiation of Anaerobic Degradation of p-Cresol by Formation of 4-Hydroxybenzylsuccinate in Desulfobacterium cetonicum

    PubMed Central

    Müller, Jochen A.; Galushko, Alexander S.; Kappler, Andreas; Schink, Bernhard

    2001-01-01

    The anaerobic bacterium Desulfobacterium cetonicum oxidized p-cresol completely to CO2 with sulfate as the electron acceptor. During growth, 4-hydroxybenzylsuccinate accumulated in the medium. This finding indicated that the methyl group of p-cresol is activated by addition to fumarate, analogous to anaerobic toluene, m-xylene, and m-cresol degradation. In cell extracts, the formation of 4-hydroxybenzylsuccinate from p-cresol and fumarate was detected at an initial rate of 0.57 nmol min−1 (mg of protein)−1. This activity was specific for extracts of p-cresol-grown cells. 4-Hydroxybenzylsuccinate was degraded further to 4-hydroxybenzoyl-coenzyme A (CoA), most likely via β-oxidation. 4-Hydroxybenzoyl-CoA was reductively dehydroxylated to benzoyl-CoA. There was no evidence of degradation of p-cresol via methyl group oxidation by p-cresol-methylhydroxylase in this bacterium. PMID:11133971

  2. 4. Historic American Buildings Survey (Fed.) Stanley P. Mixon, Photographer ...

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

    4. Historic American Buildings Survey (Fed.) Stanley P. Mixon, Photographer Sept. 16, 1940 (A) EXTERIOR, GENERAL VIEW FROM SOUTH WEST - Watson-Bancroft House, Main Street, East Windsor Hill, Hartford County, CT

  3. P-REx: The Piston Reconstruction Experiment for infrared interferometry

    NASA Astrophysics Data System (ADS)

    Widmann, Felix; Pott, Jörg-Uwe; Velasco, Sergio

    2018-03-01

    For sensitive infrared interferometry, it is crucial to control the differential piston evolution between the used telescopes. This is classically done by the use of a fringe tracker. In this work, we develop a new method to reconstruct the temporal piston variation from the atmosphere, by using real-time data from adaptive optics (AO) wavefront sensing: the Piston Reconstruction Experiment (P-REx). In order to understand the principle performance of the system in a realistic multilayer atmosphere, it is first extensively tested in simulations. The gained insights are then used to apply P-REx to real data, in order to demonstrate the benefit of using P-REx as an auxiliary system in a real interferometer. All tests show positive results, which encourages further research and eventually a real implementation. Especially, the tests on on-sky data showed that the atmosphere is, under decent observing conditions, sufficiently well structured and stable, in order to apply P-REx. It was possible to conveniently reconstruct the piston evolution in two-thirds of the data sets from good observing conditions (r0 ˜ 30 cm). The main conclusion is that applying the piston reconstruction in a real system would reduce the piston variation from around 10 μm down to 1-2 μm over time-scales of up to two seconds. This suggests an application for mid-infrared interferometry, for example for MATISSE at the very large telescope interferometer or the large binocular telescope interferometer. P-REx therefore provides the possibility to improve interferometric measurements without the need for more complex AO systems than already in regular use at 8-m-class telescopes.

  4. Analysis of the OPERA 15-pin experiment with SABRE-2P. [LMFBR

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

    Rose, S.D.; Carbajo, J.J.

    The OPERA (Out-of-Pile Expulsion and Reentry Apparatus) experiment simulates the initial phase of a pump coastdown without scram of a liquid-metal fast breeder reactor, specifically the Fast Flux Test Facility. The test section is a 15-pin 60/sup 0/ triangular sector designed to simulate a full-size 61-pin hexagonal bundle. A previous study indicates this to be an adequate simulation. In this paper, experimental results from the OPERA 15-pin experiment performed at ANL in 1982 are compared to analytical calculations obtained with the SABRE-2P code at ORNL.

  5. Identification and characterization of a selective allosteric antagonist of human P2X4 receptor channels.

    PubMed

    Ase, Ariel R; Honson, Nicolette S; Zaghdane, Helmi; Pfeifer, Tom A; Séguéla, Philippe

    2015-04-01

    P2X4 is an ATP-gated nonselective cation channel highly permeable to calcium. There is increasing evidence that this homomeric purinoceptor, which is expressed in several neuronal and immune cell types, is involved in chronic pain and inflammation. The current paucity of unambiguous pharmacological tools available to interrogate or modulate P2X4 function led us to pursue the search for selective antagonists. In the high-throughput screen of a compound library, we identified the phenylurea BX430 (1-(2,6-dibromo-4-isopropyl-phenyl)-3-(3-pyridyl)urea, molecular weight = 413), with antagonist properties on human P2X4-mediated calcium uptake. Patch-clamp electrophysiology confirmed direct inhibition of P2X4 currents by extracellular BX430, with submicromolar potency (IC50 = 0.54 µM). BX430 is highly selective, having virtually no functional impact on all other P2X subtypes, namely, P2X1-P2X3, P2X5, and P2X7, at 10-100 times its IC50. Unexpected species differences were noticed, as BX430 is a potent antagonist of zebrafish P2X4 but has no effect on rat and mouse P2X4 orthologs. The concentration-response curve for ATP on human P2X4 in the presence of BX430 shows an insurmountable blockade, indicating a noncompetitive allosteric mechanism of action. Using a fluorescent dye uptake assay, we observed that BX430 also effectively suppresses ATP-evoked and ivermectin-potentiated membrane permeabilization induced by P2X4 pore dilation. Finally, in single-cell calcium imaging, we validated its selective inhibitory effects on native P2X4 channels at the surface of human THP-1 cells that were differentiated into macrophages. In summary, this ligand provides a novel molecular probe to assess the specific role of P2X4 in inflammatory and neuropathic conditions, where ATP signaling has been shown to be dysfunctional. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Deregulated expression of p16INK4a and p53 pathway members in benign and malignant myoepithelial tumours of the salivary glands.

    PubMed

    Vékony, H; Röser, K; Löning, T; Raaphorst, F M; Leemans, C R; Van der Waal, I; Bloemena, E

    2008-12-01

    Myoepithelial salivary gland tumours are uncommon and follow an unpredictable biological course. The aim was to examine their molecular background to acquire a better understanding of their clinical behaviour. Expression of protein (E2F1, p16(INK4a), p53, cyclin D1, Ki67 and Polycomb group proteins BMI-1, MEL-18 and EZH2) was investigated in 49 benign and 30 primary malignant myoepithelial tumours and five histologically benign recurrences by immunohistochemistry and the findings correlated with histopathological characteristics. Benign tumours showed a higher percentage of cells with expression of p16(INK4a) pathway members [p16(INK4a) and E2F1 (both P < 0.001), and cyclin D1, P = 0.002] compared with normal salivary gland. Furthermore, malignant tumours expressed p53 (P = 0.003) and EZH2 (P = 0.09) in a higher percentage. Recurrences displayed more p53 + tumour cells (P = 0.02) than benign primaries. Amongst the benign tumours, the clear cell type had the highest proliferation fraction (P = 0.05) and a higher percentage of EZH2 was detected in the plasmacytoid cell type (P = 0.002). This study is the first to demonstrate that deregulation of the p16(INK4a) senescence pathway is involved in the development of myoepithelial tumours. We propose that additional inactivation of p53 in malignant primaries and benign recurrences contributes to myoepithelial neoplastic transformation and aggressive tumour growth.

  7. P2P-Based Data System for the EAST Experiment

    NASA Astrophysics Data System (ADS)

    Shu, Yantai; Zhang, Liang; Zhao, Weifeng; Chen, Haiming; Luo, Jiarong

    2006-06-01

    A peer-to-peer (P2P)-based EAST Data System is being designed to provide data acquisition and analysis support for the EAST superconducting tokamak. Instead of transferring data to the servers, all collected data are stored in the data acquisition subsystems locally and the PC clients can access the raw data directly using the P2P architecture. Both online and offline systems are based on Napster-like P2P architecture. This allows the peer (PC) to act both as a client and as a server. A simulation-based method and a steady-state operational analysis technique are used for performance evaluation. These analyses show that the P2P technique can significantly reduce the completion time of raw data display and real-time processing on the online system, and raise the workload capacity and reduce the delay on the offline system.

  8. Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the K2P background K+ channel TASK-2

    PubMed Central

    Niemeyer, María Isabel; Cid, L. Pablo; Paulais, Marc; Teulon, Jacques; Sepúlveda, Francisco V.

    2017-01-01

    Two-pore domain K2P K+ channels responsible for the background K+ conductance and the resting membrane potential, are also finely regulated by a variety of chemical, physical and physiological stimuli. Hormones and transmitters acting through Gq protein-coupled receptors (GqPCRs) modulate the activity of various K2P channels but the signalling involved has remained elusive, in particular whether dynamic regulation by membrane PI(4,5)P2, common among other classes of K+ channels, affects K2P channels is controversial. Here we show that K2P K+ channel TASK-2 requires PI(4,5)P2 for activity, a dependence that accounts for its run down in the absence of intracellular ATP and its full recovery by addition of exogenous PI(4,5)P2, its inhibition by low concentrations of polycation PI scavengers, and inhibition by PI(4,5)P2 depletion from the membrane. Comprehensive mutagenesis suggests that PI(4,5)P2 interaction with TASK-2 takes place at C-terminus where three basic aminoacids are identified as being part of a putative binding site. PMID:28358046

  9. Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the K2P background K+ channel TASK-2.

    PubMed

    Niemeyer, María Isabel; Cid, L Pablo; Paulais, Marc; Teulon, Jacques; Sepúlveda, Francisco V

    2017-03-30

    Two-pore domain K 2P K + channels responsible for the background K + conductance and the resting membrane potential, are also finely regulated by a variety of chemical, physical and physiological stimuli. Hormones and transmitters acting through Gq protein-coupled receptors (GqPCRs) modulate the activity of various K 2P channels but the signalling involved has remained elusive, in particular whether dynamic regulation by membrane PI(4,5)P 2 , common among other classes of K + channels, affects K 2P channels is controversial. Here we show that K 2P K + channel TASK-2 requires PI(4,5)P 2 for activity, a dependence that accounts for its run down in the absence of intracellular ATP and its full recovery by addition of exogenous PI(4,5)P 2 , its inhibition by low concentrations of polycation PI scavengers, and inhibition by PI(4,5)P 2 depletion from the membrane. Comprehensive mutagenesis suggests that PI(4,5)P 2 interaction with TASK-2 takes place at C-terminus where three basic aminoacids are identified as being part of a putative binding site.

  10. Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in Severe Sepsis.

    PubMed

    Morton, Ben; Mitsi, Elena; Pennington, Shaun H; Reiné, Jesús; Wright, Angela D; Parker, Robert; Welters, Ingeborg D; Blakey, John D; Rajam, Gowrisankar; Ades, Edwin W; Ferreira, Daniela M; Wang, Duolao; Kadioglu, Aras; Gordon, Stephen B

    2016-12-01

    Antimicrobial resistance threatens to undermine treatment of severe infection; new therapeutic strategies are urgently needed. Preclinical work shows that augmented passive immunotherapy with P4 peptide increases phagocytic activity and shows promise as a novel therapeutic strategy. Our aim was to determine ex vivo P4 activity in a target population of patients admitted to critical care with severe infection. We prospectively recruited UK critical care unit patients with severe sepsis and observed clinical course (≥3 months postdischarge). Blood samples were taken in early (≤48 h postdiagnosis, n = 54), latent (7 days postdiagnosis, n = 39), and convalescent (3-6 months postdiagnosis, n = 18) phases of disease. The primary outcome measure was killing of opsonized Streptococcus pneumoniae by neutrophils with and without P4 peptide stimulation. We also used a flow cytometric whole blood phagocytosis assay to determine phagocyte association and oxidation of intraphagosomal reporter beads. P4 peptide increased neutrophil killing of opsonized pneumococci by 8.6% (confidence interval 6.35-10.76, P < 0.001) in all phases of sepsis, independent of infection source and microbiological status. This represented a 54.9% increase in bacterial killing compared with unstimulated neutrophils (15.6%) in early phase samples. Similarly, P4 peptide treatment significantly increased neutrophil and monocyte intraphagosomal reporter bead association and oxidation, independent of infection source. We have extended preclinical work to demonstrate that P4 peptide significantly increases phagocytosis and bacterial killing in samples from a target patient population with severe sepsis. This study supports the rationale for augmented passive immunotherapy as a therapeutic strategy in severe sepsis.

  11. High resolution emission Fourier transform infrared spectra of the 4p-5s and 5p-6s bands of ArH.

    PubMed

    Baskakov, O I; Civis, S; Kawaguchi, K

    2005-03-15

    In the 2500-8500 cm(-1) region several strong emission bands of (40)ArH were observed by Fourier transform spectroscopy through a dc glow discharge in a mixture of argon and hydrogen. Rotational-electronic transitions of the two previously unstudied 4p-5s and 5p-6s,v = 0-0, bands of (40)ArH were measured and assigned in the 6060 and 3770 cm(-1) regions, respectively. A simultaneous fit of the emission transitions of the 4p-5s and 5p-6s bands and an extended set of transitions of the 6s-4p band observed by Dabrowski, Tokaryk, and Watson [J. Mol. Spectrosc. 189, 95 (1998)] and remeasured in the present work yielded consistent values of the spectroscopic parameters of the electronic states under investigation. In the branch of the 4p-5s band with transitions of type (Q)Q(f(3)e) we observed a narrowing in the linewidths with increasing rotational quantum number N. The rotational dependence of the linewidth is caused by predissociation of the 5s state by the repulsive ground 4s state through homogeneous coupling and changes in overlap integrals of the vibrational wave functions with the rotational level. Analysis was based on the Fermi's golden rule approximation model. In the 4p-5s band region a vibrational sequence ofv(')-v(")=1-1, 2-2, and 3-3 were recorded and a number of transitions belonging to the strongest (Q)Q(f(3)e) form branch of the 1-1 band were analyzed.

  12. pH Control Enables Simultaneous Enhancement of Nitrogen Retention and N2O Reduction in Shewanella loihica Strain PV-4.

    PubMed

    Kim, Hayeon; Park, Doyoung; Yoon, Sukhwan

    2017-01-01

    pH has been recognized as one of the key environmental parameters with significant impacts on the nitrogen cycle in the environment. In this study, the effects of pH on NO 3 - /NO 2 - fate and N 2 O emission were examined with Shewanella loihica strain PV-4, an organism with complete denitrification and respiratory ammonification pathways. Strain PV-4 was incubated at varying pH with lactate as the electron donor and NO 3 - /NO 2 - and N 2 O as the electron acceptors. When incubated with NO 3 - and N 2 O at pH 6.0, transient accumulation of N 2 O was observed and no significant NH 4 + production was observed. At pH 7.0 and 8.0, strain PV-4 served as a N 2 O sink, as N 2 O concentration decreased consistently without accumulation. Respiratory ammonification was upregulated in the experiments performed at these higher pH values. When NO 2 - was used in place of NO 3 - , neither growth nor NO 2 - reduction was observed at pH 6.0. NH 4 + was the exclusive product from NO 2 - reduction at both pH 7.0 and 8.0 and neither production nor consumption of N 2 O was observed, suggesting that NO 2 - regulation superseded pH effects on the nitrogen-oxide dissimilation reactions. When NO 3 - was the electron acceptor, nirK transcription was significantly upregulated upon cultivation at pH 6.0, while nrfA transcription was significantly upregulated at pH 8.0. The highest level of nosZ transcription was observed at pH 6.0 and the lowest at pH 8.0. With NO 2 - as the electron acceptor, transcription profiles of nirK, nrfA , and nosZ were statistically indistinguishable between pH 7.0 and 8.0. The transcriptions of nirK and nosZ were severely downregulated regardless of pH. These observations suggested that the kinetic imbalance between N 2 O production and consumption, but neither decrease in expression nor activity of NosZ, was the major cause of N 2 O accumulation at pH 6.0. The findings also suggest that simultaneous enhancement of nitrogen retention and N 2 O emission reduction

  13. Five years experience on 3,4-diaminopyridine phosphate in Lambert–Eaton syndrome

    PubMed Central

    Portaro, Simona; Brizzi, Teresa; Sinicropi, Stefano; Cacciola, Alberto; De Cola, Maria Cristina; Bramanti, Alessia; Milardi, Demetrio; Lupica, Antonino; Bramanti, Placido; Toscano, Antonio; Rodolico, Carmelo

    2017-01-01

    Abstract Rationale: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert–Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. Patient concerns: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation. Outcomes: Five out of 7 patients presented a clinical improvement persisting at last 5-year follow-up; 2 out of them improved taking only 3,4-DAPP at the maximal dosage, whereas the remaining received concomitant medications, such as prednisone and azathioprine. However, the clinical amelioration was not statistically significant. No one of the patients reported severe adverse events, except one, complaining of transient chin and perioral paresthesias. A significant association between QMG and the type of pharmacological drugs therapy (P = .028) emerged. Indeed, we observed an improvement of the clinical condition in all 3 subjects treated with 3,4-DAPP and prednisone. Conclusions: In this study, we confirm 3,4-DAPP treatment efficacy on muscle strength, but minor evidence of drug effectiveness have been demonstrated on the autonomic nervous system involvement and on the deep tendon reflexes reappearance, a part from patients who received 3,4-DAPP associated to prednisone. PMID:28930822

  14. Crystal growth and characterization of third order nonlinear optical piperazinium bis(4-hydroxybenzenesulphonate) (P4HBS) single crystal

    NASA Astrophysics Data System (ADS)

    Pichan, Karuppasamy; Muthu, Senthil Pandian; Perumalsamy, Ramasamy

    2017-09-01

    The organic single crystal of piperazinium bis(4-hydroxybenzenesulphonate) (P4HBS) was grown by slow evaporation solution technique (SEST) at room temperature. The lattice parameters of the grown crystal were confirmed by single crystal X-ray diffraction analysis. Functional groups of P4HBS crystal were confirmed by FTIR spectrum analysis. The optical quality of the grown crystal was identified by the UV-Vis NIR spectrum analysis. The grown crystal has good optical transmittance in the range of 410-1100 nm. In photoluminescence spectrum, sharp emission peaks are observed, which indicates the ultraviolet (UV) emission. The photoconductivity study reveals that the grown crystal has negative photoconductive nature. The thermal behaviour of the P4HBS crystal was investigated by thermogravimetric and differential thermal analysis (TG-DTA). The mechanical stability of grown crystal was analyzed and the indentation size effect (ISE) was explained by Hays-Kendall's (HK) approach and proportional specimen resistance model (PSRM). Chemical etching study was carried out and the etch pit density (EPD) was calculated. The dielectric constant (ε‧) and dielectric loss (tan δ) as a function of frequency were measured for the grown crystal. The solid state parameters such as valence electron, plasma energy, Penn gap and Fermi energy were evaluated theoretically for the P4HBS using the empirical relation. The estimated values are used to calculate the electronic polarizability. The third-order nonlinear optical properties such as nonlinear refractive index (n2), absorption co-efficient (β) and susceptibility (χ(3)) were studied by Z-scan technique at 632.8 nm using He-Ne laser.

  15. The use of reactive material for limiting P-leaching from green roof substrate.

    PubMed

    Bus, Agnieszka; Karczmarczyk, Agnieszka; Baryła, Anna

    2016-01-01

    The aim of the study is to assess the influence of drainage layer made of reactive material Polonite(®) on the water retention and P-PO(4) concentration in runoff. A column experiment was performed for extensive substrate underlined by 2 cm of Polonite(®) layer (SP) and the same substrate without supporting layer as a reference (S). The leakage phosphorus concentration ranged from 0.001 to 0.082 mg P-PO(4)·L(-1), with average value 0.025 P-PO(4)·L(-1) of S experiment and 0.000-0.004 P-PO(4)·L(-1) and 0.001 P-PO(4)·L(-1) of SP experiment, respectively. The 2 cm layer of Polonite(®) was efficient in reducing P outflow from green roof substrate by 96%. The average effluent volumes from S and SP experiments amounted 61.1 mL (5.8-543.3 mL) and 46.4 mL (3.3-473.3 mL) with the average irrigation rate of 175.5 mL (6.3-758.0 mL). The substrate retention ability of S and SP experiments was 65% and 74%, respectively. Provided with reactive materials, green roof layers implemented in urban areas for rain water retention and delaying runoff also work for protection of water quality.

  16. PI(4)P Promotes Phosphorylation and Conformational Change of Smoothened through Interaction with Its C-terminal Tail

    PubMed Central

    Zhang, Jie; Li, Xiang-An; Evers, B. Mark; Zhu, Haining; Jia, Jianhang

    2016-01-01

    In Hedgehog (Hh) signaling, binding of Hh to the Patched-Interference Hh (Ptc-Ihog) receptor complex relieves Ptc inhibition on Smoothened (Smo). A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation. In this study, we found that Hh elevates production of phosphatidylinositol 4-phosphate (PI(4)P). Increased levels of PI(4)P promote, whereas decreased levels of PI(4)P inhibit, Hh signaling activity. We further found that PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. Moreover, we identified the pleckstrin homology (PH) domain of G protein-coupled receptor kinase 2 (Gprk2) as an essential component for enriching PI(4)P and facilitating Smo activation. PI(4)P also binds mouse Smo (mSmo) and promotes its phosphorylation and ciliary accumulation. Finally, Hh treatment increases the interaction between Smo and PI(4)P but decreases the interaction between Ptc and PI(4)P, indicating that, in addition to promoting PI(4)P production, Hh regulates the pool of PI(4)P associated with Ptc and Smo. PMID:26863604

  17. The energy structure and decay channels of the 4p6-shell excited states in Sr

    NASA Astrophysics Data System (ADS)

    Kupliauskienė, A.; Kerevičius, G.; Borovik, V.; Shafranyosh, I.; Borovik, A.

    2017-11-01

    The ejected-electron spectra arising from the decay of the 4p{}5{{nln}}{\\prime }{l}{\\prime }{n}{\\prime\\prime }{l}{\\prime\\prime } autoionizing states in Sr atoms have been studied precisely at the incident-electron energies close to excitation and ionization thresholds of the 4{{{p}}}6 subshell. The excitation behaviors for 58 lines observed between 12 and 21 eV ejected-electron kinetic energy have been investigated. Also, the ab initio calculations of excitation energies, autoionization probabilities and electron-impact excitation cross sections of the states 4p{}5{{nln}}{\\prime }{l}{\\prime }{n}{\\prime\\prime }{l}{\\prime\\prime } (nl = 4d, 5s, 5p; {n}{\\prime }{l}{\\prime } = 4d, 5s, 5p; {n}{\\prime\\prime }{l}{\\prime\\prime } = 5s, 6s, 7s, 8s, 9s, 5p, 6p, 5d, 6d, 7d, 8d, 4f, 5g) have been performed by employing the large-scale configuration-interaction method in the basis of the solutions of Dirac-Fock-Slater equations. The obtained experimental and theoretical data have been used for the accurate identification of the 60 lines in ejected-electron spectra and the 68 lines observed earlier in photoabsorption spectra. The excitation and decay processes for 105 classified states in the 4p55s{}2{nl}, 4p54d{}2{nl} and 4p55s{{nln}}{\\prime }{l}{\\prime } configurations have been considered in detail. In particular, most of the states lying below the ionization threshold of the 4p6 subshell at 26.92 eV possess up to four decay channels with formation of Sr+ in 5s{}1/2, 4d{}3/{2,5/2} and 5p{}1/{2,3/2} states. Two-step autoionization and two-electron Auger transitions with formation of Sr2+ in the 4p6 {}1{{{S}}}0 ground state are the main decay paths for high-lying autoionizing states. The excitation threshold of the 4{{{p}}}6 subshell in Sr has been established at 20.98 ± 0.05 eV.

  18. The Luteovirus P4 Movement Protein Is a Suppressor of Systemic RNA Silencing

    PubMed Central

    Fusaro, Adriana F.; Barton, Deborah A.; Nakasugi, Kenlee; Jackson, Craig; Kalischuk, Melanie L.; Kawchuk, Lawrence M.; Vaslin, Maite F. S.; Waterhouse, Peter M.

    2017-01-01

    The plant viral family Luteoviridae is divided into three genera: Luteovirus, Polerovirus and Enamovirus. Without assistance from another virus, members of the family are confined to the cells of the host plant’s vascular system. The first open reading frame (ORF) of poleroviruses and enamoviruses encodes P0 proteins which act as silencing suppressor proteins (VSRs) against the plant’s viral defense-mediating RNA silencing machinery. Luteoviruses, such as barley yellow dwarf virus-PAV (BYDV-PAV), however, have no P0 to carry out the VSR role, so we investigated whether other proteins or RNAs encoded by BYDV-PAV confer protection against the plant’s silencing machinery. Deep-sequencing of small RNAs from plants infected with BYDV-PAV revealed that the virus is subjected to RNA silencing in the phloem tissues and there was no evidence of protection afforded by a possible decoy effect of the highly abundant subgenomic RNA3. However, analysis of VSR activity among the BYDV-PAV ORFs revealed systemic silencing suppression by the P4 movement protein, and a similar, but weaker, activity by P6. The closely related BYDV-PAS P4, but not the polerovirus potato leafroll virus P4, also displayed systemic VSR activity. Both luteovirus and the polerovirus P4 proteins also showed transient, weak local silencing suppression. This suggests that systemic silencing suppression is the principal mechanism by which the luteoviruses BYDV-PAV and BYDV-PAS minimize the effects of the plant’s anti-viral defense. PMID:28994713

  19. The Luteovirus P4 Movement Protein Is a Suppressor of Systemic RNA Silencing.

    PubMed

    Fusaro, Adriana F; Barton, Deborah A; Nakasugi, Kenlee; Jackson, Craig; Kalischuk, Melanie L; Kawchuk, Lawrence M; Vaslin, Maite F S; Correa, Regis L; Waterhouse, Peter M

    2017-10-10

    The plant viral family Luteoviridae is divided into three genera: Luteovirus , Polerovirus and Enamovirus . Without assistance from another virus, members of the family are confined to the cells of the host plant's vascular system. The first open reading frame (ORF) of poleroviruses and enamoviruses encodes P0 proteins which act as silencing suppressor proteins (VSRs) against the plant's viral defense-mediating RNA silencing machinery. Luteoviruses, such as barley yellow dwarf virus-PAV (BYDV-PAV), however, have no P0 to carry out the VSR role, so we investigated whether other proteins or RNAs encoded by BYDV-PAV confer protection against the plant's silencing machinery. Deep-sequencing of small RNAs from plants infected with BYDV-PAV revealed that the virus is subjected to RNA silencing in the phloem tissues and there was no evidence of protection afforded by a possible decoy effect of the highly abundant subgenomic RNA3. However, analysis of VSR activity among the BYDV-PAV ORFs revealed systemic silencing suppression by the P4 movement protein, and a similar, but weaker, activity by P6. The closely related BYDV-PAS P4, but not the polerovirus potato leafroll virus P4, also displayed systemic VSR activity. Both luteovirus and the polerovirus P4 proteins also showed transient, weak local silencing suppression. This suggests that systemic silencing suppression is the principal mechanism by which the luteoviruses BYDV-PAV and BYDV-PAS minimize the effects of the plant's anti-viral defense.

  20. Substance P increases Sympathetic Activity during Combined Angiotensin Converting Enzyme and Dipeptidyl Peptidase-4 Inhibition

    PubMed Central

    Devin, Jessica K.; Pretorius, Mias; Nian, Hui; Yu, Chang; Billings, Frederic T.; Brown, Nancy J.

    2014-01-01

    Dipeptidyl peptidase-4 inhibitors prevent the degradation of incretin hormones and reduce post-prandial hyperglycemia in patients with type 2 diabetes mellitus. Dipeptidyl peptidase-4 degrades other peptides with a penultimate proline or alanine, including bradykinin and substance P, which are also substrates of angiotensin-converting enzyme. During angiotensin-converting enzyme inhibition, substance P is inactivated primarily by dipeptidyl peptidase-4, while bradykinin is first inactivated by aminopeptidase P. This study tested the hypothesis that dipeptidyl peptidase-4 inhibition potentiates vasodilator and fibrinolytic responses to substance P when angiotensin-converting enzyme is inhibited. Twelve healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received sitagliptin 200 mg p.o. or placebo. Substance P and bradykinin were infused via brachial artery before and during intra-arterial enalaprilat. Sitagliptin and enalaprilat each reduced forearm vascular resistance and increased forearm blood flow without affecting mean arterial pressure, but there was no interactive effect of the inhibitors. Enalaprilat increased bradykinin-stimulated vasodilation and tissue plasminogen activator release; sitagliptin did not affect these responses to bradykinin. The vasodilator response to substance P was unaffected by sitagliptin and enalaprilat, however, substance P increased heart rate and vascular release of norepinephrine during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition. In women, sitagliptin diminished tissue plasminogen activator release in response to substance P both alone and during enalaprilat. Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition. PMID:24516103

  1. Pregnane X receptor-dependent induction of the CYP3A4 gene by o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane.

    PubMed

    Medina-Díaz, Irma M; Arteaga-Illán, Georgina; de León, Mario Bermudez; Cisneros, Bulmaro; Sierra-Santoyo, Adolfo; Vega, Libia; Gonzalez, Frank J; Elizondo, Guillermo

    2007-01-01

    CYP3A4, the predominant cytochrome P450 (P450) expressed in human liver and intestine, contributes to the metabolism of approximately half the drugs in clinical use today. CYP3A4 catalyzes the 6beta-hydroxylation of a number of steroid hormones and is involved in the bioactivation of environmental procarcinogens. The expression of CYP3A4 is affected by several stimuli, including environmental factors such as insecticides and pesticides. The o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane (DDT) isomer of DDT comprises approximately 20% of technical grade DDT, which is an organochloride pesticide. We have recently shown that o,p'-DDT exposure increases CYP3A4 mRNA levels in HepG2 cells. To determine the mechanism by which o,p'-DDT induces CYP3A4 expression, transactivation and electrophoretic mobility shift assays were carried out, revealing that o,p'-DDT activates the CYP3A4 gene promoter through the pregnane X receptor (PXR). CYP3A4 gene promoter activation resulted in both an increase in CYP3A4 mRNA levels and an increase in the total CYP3A4 activity in HepG2 cells. We also observed induction of CYP3A4 and mouse Cyp3a11 mRNA in the intestine of CYP3A4-transgenic mice after exposure to 1 mg/kg o,p'-DDT. At higher doses, a decrease of CYP3A4 inducibility was observed together with an increase in levels of interleukin 6 mRNA, a proinflammatory cytokine that strongly represses CYP3A4 transcription. The present study indicates that regulation of other genes under PXR control may be altered by o,p'-DDT exposure.

  2. Synthesis, crystal structures and ionic conductivities of Bi{sub 14}P{sub 4}O{sub 31} and Bi{sub 50}V{sub 4}O{sub 85}. Two members of the series Bi{sub 18-4m}M{sub 4m}O{sub 27+4m} (M=P, V) related to the fluorite-type structure

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

    Mauvy, F.; Launay, J.C.; Darriet, J.

    2005-06-15

    The two hitherto unknown compounds Bi{sub 14}P{sub 4}O{sub 31} and Bi{sub 50}V{sub 4}O{sub 85} were prepared by the direct solid-state reaction of Bi{sub 2}O{sub 3} and (NH{sub 4})H{sub 2}PO{sub 4} or V{sub 2}O{sub 5}, respectively. Bi{sub 14}P{sub 4}O{sub 31} crystallizes in a C-centred monoclinic symmetry (C2/c space group) with the unit-cell parameters: a=19.2745(2)A, b=11.3698(1)A, c=52.4082(2)A and {beta}=93.63(1){sup o} (Z=16). The symmetry of Bi{sub 50}V{sub 4}O{sub 85} is also monoclinic (I2/m space group) with lattice parameters of a=11.8123(3)A, b=11.7425(2)A, c=16.5396(2)A and {beta}=90.14(1){sup o} (Z=2). Both structures correspond to a fluorite-type superstructure where the Bi and P or V atoms are orderedmore » in the framework. An idealized structural model is proposed where the structures result of the stacking of mixed atomic layers of composition [Bi{sub 14}M{sub 4}O{sub 31}] and [Bi{sub 18}O{sub 27}] respectively. This new family can be formulated Bi{sub 18-4m}M{sub 4m}O{sub 27+4m} with M=P, V and where the parameter m (0=4}O{sub 31}] layers to the total number of layers in the sequence. Bi{sub 14}P{sub 4}O{sub 31} corresponds to m=1 when Bi{sub 50}V{sub 8}O{sub 85} corresponds to m=1/3. In this last case, the structural sequence is simply one [Bi{sub 14}V{sub 4}O{sub 31}] layer to two [Bi{sub 18}O{sub 27}] layers. As predicted by the proposed structural building principle, Bi{sub 14}P{sub 4}O{sub 31} is not a good ionic conductor. The conductivity at 650 deg. C is 4 orders of magnitude lower from those found in Bi{sub 46}M{sub 8}O{sub 89} (M=P, V) (m=2/3) and Bi{sub 50}V{sub 4}O{sub 85} (m=1/3)« less

  3. Dynamically polarized target for the g {2/ p } and G {/E p } experiments at Jefferson Lab

    NASA Astrophysics Data System (ADS)

    Pierce, J.; Maxwell, J.; Keith, C.

    2014-01-01

    Recently, two experiments were concluded in Hall A at Jefferson Lab which utilized a newly assembled, solid, polarized hydrogen target. The primary components of the target are a new, high cooling power 4He evaporation refrigerator, and a re-purposed, superconducting split-coil magnet. It has been used to polarize protons in irradiated NH3 at a temperature of 1 K and at fields of 2.5 and 5.0 tesla. Maximum polarizations of 55% and 95% were obtained at those fields, respectively. To satisfy the requirements of both experiments, the magnet had to be routinely rotated between angles of 0°, 6°, and 90° with respect to the incident electron beam.

  4. Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II.

    PubMed

    Hong, Seung-Keun; Cha, Mee-Kyung; Choi, Yong-Soo; Kim, Won-Cheol; Kim, Il-Han

    2002-04-05

    We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells.

  5. Deployed P4 Radiator during STS-115 EVA during Joint Operations

    NASA Image and Video Library

    2006-09-15

    S115-E-06143 (15 Sept. 2006) --- Backdropped by a blue and white Earth, the newly installed P3/P4 truss and the Canadarm2 of the International Space Station are featured in this image photographed by a STS-115 crewmember while the Space Shuttle Atlantis was docked with the International Space Station.

  6. Partial monosomy Xq(Xq23 --> qter) and trisomy 4p(4p15.33 --> pter) in a woman with intractable focal epilepsy, borderline intellectual functioning, and dysmorphic features.

    PubMed

    Bartocci, Arnaldo; Striano, Pasquale; Mancardi, Maria Margherita; Fichera, Marco; Castiglia, Lucia; Galesi, Ornella; Michelucci, Roberto; Elia, Maurizio

    2008-06-01

    Studies of epilepsy associated with chromosomal abnormalities may provide information about clinical and EEG phenotypes and possibly to identify new epilepsy genes. We describe a female patient with intractable focal epilepsy, borderline intellectual functioning, and facial dysmorphisms, in whom genetic study (i.e., karyotype and array-CGH analysis) revealed a distal trisomy 4p and distal monosomy Xq. Although any genetic hypothesis remains speculative, several genes are located in the 4p chromosome segment involved in the rearrangement, some of which may be related to epilepsy.

  7. Factors Related to the Developmental Experiences of Youth Serving as 4-H Camp Counselors

    ERIC Educational Resources Information Center

    Carter, David N.; Kotrlik, Joe W.

    2008-01-01

    The purpose of this study was to investigate the developmental experiences of high-school-aged 4-H youth volunteering as counselors at Louisiana 4-H summer camps. A total of 288 counselors from 10 different camping sessions participated in the study. The Youth Experiences Survey 2.0 and the Developmental Experience Survey measured the personal…

  8. 4p terminal deletion and 11p subtelomeric duplication detected by genomic microarray in a patient with Wolf-Hirschhorn syndrome and an atypical phenotype.

    PubMed

    Stevenson, David A; Carey, John C; Cowley, Brett C; Bayrak-Toydemir, Pinar; Mao, Rong; Brothman, Arthur R

    2004-12-01

    We report a de novo cryptic 11p duplication found by genomic microarray with a cytogenetically detected 4p deletion. Terminal 4p deletions cause Wolf-Hirschhorn syndrome, but the phenotype probably was modified by the paternally derived 11p duplication. This emphasizes the clinical utility of genomic microarray.

  9. Mechanistic study of lead desorption during the leaching process of ion-absorbed rare earths: pH effect and the column experiment.

    PubMed

    Tang, Jie; Xue, Qiang; Chen, Honghan; Li, Wenting

    2017-05-01

    High concentrations of ammonium sulfate, often used in the in situ mining process, can result in a decrease of pH in the environment and dissolution of rare earth metals. Ammonium sulfate can also cause desorption of toxic heavy metals, leading to environmental and human health implications. In this study, the desorption behavior and fraction changes of lead in the ion-absorbed rare earth ore were studied using batch desorption experiments and column leaching tests. Results from batch desorption experiments showed that the desorption process of lead included fast and slow stages and followed an Elovich model well. The desorption rate and the proportion of lead content in the solution to the total lead in the soil were observed to increase with a decrease in the initial pH of the ammonium sulfate solution. The lead in soil included an acid-extractable fraction, reducible fraction, oxidizable fraction, and a residual fraction, with the predominant fractions being the reducible and acid-extractable fractions. Ninety-six percent of the extractable fraction in soil was desorbed into solution at pH = 3.0, and the content of the reducible fraction was observed to initially increase (when pH >4.0) and then decrease (when pH <4.0) with a decrease in pH. Column leaching tests indicated that the content of lead in the different fractions of soil followed the trend of reducible fraction > oxidizable fraction > acid-extractable fraction > residual fraction after the simulating leaching mining process. The change in pH was also found to have a larger influence on the acid-extractable and reducible fractions than the other two fractions. The proportion of the extractable fraction being leached was ca. 86%, and the reducible fraction was enriched along the migration direction of the leaching liquid. These results suggest that certain lead fractions may desorb again and contaminate the environment via acid rain, which provides significant information for environmental assessment

  10. Mechanistic study of lead desorption during the leaching process of ion-absorbed rare earths: pH effect and the column experiment

    NASA Astrophysics Data System (ADS)

    Xue, Q.; Tang, J., Sr.; Chen, H.

    2017-12-01

    High concentrations of ammonium sulfate, often used in the in-situ mining process, can result in a decrease of pH in the environment and dissolution of rare earth metals. Ammonium sulfate can also cause desorption of toxic heavy metals, leading to environmental and human health implications. In this study, the desorption behavior and fraction changes of lead in the ion-absorbed rare earth ore were studied using batch desorption experiments and column leaching tests. Results from batch desorption experiments showed that the desorption process of lead included fast and slow stages, and followed an Elovich model well. The desorption rate and the proportion of lead content in the solution to the total lead in the soil were observed to increase with a decrease in the initial pH of the ammonium sulfate solution. The lead in soil included an acid extractable fraction, reducible fraction, oxidizable fraction, and a residual fraction, with the predominant fractions being the reducible and acid extractable fractions. 96% of the extractable fraction in soil were desorbed into solution at pH=3.0, and the content of the reducible fraction was observed to initially increase (when pH>4.0) and then decrease (when pH<4.0) with a decrease in pH. Column leaching tests indicated that the content of lead in the different fractions of soil followed the trend of reducible fraction > oxidizable fraction > acid extractable fraction > residual fraction after the simulating leaching mining process. The change in pH was also found to have a larger influence on the acid extractable and reducible fractions than the other two fractions. The proportion of the extractable fraction being leached was ca. 86%, and the reducible fraction was enriched along the migration direction of the leaching liquid. These results suggest that certain lead fractions may desorb again and contaminate the environment via acid rain, which provides significant information for environmental assessment and remediation

  11. MiR-30e suppresses proliferation of hepatoma cells via targeting prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA

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

    Feng, Guoxing; Shi, Hui; Li, Jiong

    Aberrant microRNA expression has been shown to be characteristic of many cancers. It has been reported that the expression levels of miR-30e are decreased in liver cancer tissues. However, the role of miR-30e in hepatocellular carcinoma remains poorly understood. In the present study, we investigated the significance of miR-30e in hepatocarcinogenesis. Bioinformatics analysis reveals a putative target site of miR-30e in the 3′-untranslated region (3′UTR) of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA. Moreover, luciferase reporter gene assays verified that miR-30e directly targeted 3′UTR of P4HA1 mRNA. Then, we demonstrated that miR-30e was able to reduce the expression of P4HA1 atmore » the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blot analysis. Enforced expression of miR-30e suppressed proliferation of HepG2 cells by 5-ethynyl-2-deoxyuridine (EdU) assay and reduced colony formation of these cells by colony formation analysis. Conversely, anti-miR-30e enhanced the proliferation of hepatoma cells in vitro. Interestingly, the ectopic expression of P4HA1 could efficiently rescue the inhibition of cell proliferation mediated by miR-30e in HepG2 cells. Meanwhile, silencing of P4HA1 abolished the anti-miR-30e-induced proliferation of cells. Clinically, quantitative real-time PCR showed that miR-30e was down-regulated in liver tumor tissues relative to their peritumor tissues. The expression levels of miR-30e were negatively correlated to those of P4HA1 mRNA in clinical liver tumor tissues. Thus, we conclude that miR-30e suppresses proliferation of hepatoma cells through targeting P4HA1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. - Highlights: • P4HA1 is a novel target gene of miR-30e. • P4HA1 is increased in clinical HCC tissues. • MiR-30e is negatively correlated with P4HA1 in clinical HCC tissues. • MiR-30e suppresses the proliferation of HCC cells

  12. PEO-b-P4VP/Yttrium Hydroxide Hybrid Nanotubes as Supporter for Catalyst Gold Nanoparticles

    NASA Astrophysics Data System (ADS)

    Yang, Qian; Chen, Dao-yong

    2012-06-01

    The adsorption of poly (ethylene oxide)-b-poly(4-vinylpyridine)(PEO-b-P4VP) micelles onto the surface of yttrium hydroxide nanotubes (YNTs) resulted in the hybrid nanotubes with a dense P4VP inner layer and a stretched PEO outer layer surrounding YNTs. The dense P4VP layer was further stabilized by the crosslinking using 1,4-dibromobutane as the crosslinker. Then, the crosslinked hybrid nanotubes (CHNTs) were used as a novel nano supporter for loading the catalyst gold nanoparticles (GNPs) within the crosslinked P4VP layer. The resultant GNPs/CHNTs (GNTs loaded on CHNTs) were applied to catalyze the reduction reaction of p-nitrophenol. The results indicate that this novel nano supporter has advantages such as good dispersity in the suspension, high capacity in loading GNPs (0.87 mmol/g), high catalytic activity of the loaded GNPs (12.9 μmol-1min-1), and good reusability of GNTs/CHNTs.

  13. Novel Gal3 proteins showing altered Gal80p binding cause constitutive transcription of Gal4p-activated genes in Saccharomyces cerevisiae.

    PubMed Central

    Blank, T E; Woods, M P; Lebo, C M; Xin, P; Hopper, J E

    1997-01-01

    Gal4p-mediated activation of galactose gene expression in Saccharomyces cerevisiae normally requires both galactose and the activity of Gal3p. Recent evidence suggests that in cells exposed to galactose, Gal3p binds to and inhibits Ga180p, an inhibitor of the transcriptional activator Gal4p. Here, we report on the isolation and characterization of novel mutant forms of Gal3p that can induce Gal4p activity independently of galactose. Five mutant GAL3(c) alleles were isolated by using a selection demanding constitutive expression of a GAL1 promoter-driven HIS3 gene. This constitutive effect is not due to overproduction of Gal3p. The level of constitutive GAL gene expression in cells bearing different GAL3(c) alleles varies over more than a fourfold range and increases in response to galactose. Utilizing glutathione S-transferase-Gal3p fusions, we determined that the mutant Gal3p proteins show altered Gal80p-binding characteristics. The Gal3p mutant proteins differ in their requirements for galactose and ATP for their Gal80p-binding ability. The behavior of the novel Gal3p proteins provides strong support for a model wherein galactose causes an alteration in Gal3p that increases either its ability to bind to Gal80p or its access to Gal80p. With the Gal3p-Gal80p interaction being a critical step in the induction process, the Gal3p proteins constitute an important new reagent for studying the induction mechanism through both in vivo and in vitro methods. PMID:9111326

  14. Proteomic Analysis Reveals a Novel Function of the Kinase Sat4p in Saccharomyces cerevisiae Mitochondria

    PubMed Central

    Gey, Uta; Czupalla, Cornelia; Hoflack, Bernard; Krause, Udo; Rödel, Gerhard

    2014-01-01

    The Saccharomyces cerevisiae kinase Sat4p has been originally identified as a protein involved in salt tolerance and stabilization of plasma membrane transporters, implicating a cytoplasmic localization. Our study revealed an additional mitochondrial (mt) localization, suggesting a dual function for Sat4p. While no mt related phenotype was observed in the absence of Sat4p, its overexpression resulted in significant changes of a specific mitochondrial subproteome. As shown by a comparative two dimensional difference gel electrophoresis (2D-DIGE) approach combined with mass spectrometry, particularly two groups of proteins were affected: the iron-sulfur containing aconitase-type proteins (Aco1p, Lys4p) and the lipoamide-containing subproteome (Lat1p, Kgd2p and Gcv3p). The lipoylation sites of all three proteins could be assigned by nanoLC-MS/MS to Lys75 (Lat1p), Lys114 (Kgd2p) and Lys102 (Gcv3p), respectively. Sat4p overexpression resulted in accumulation of the delipoylated protein variants and in reduced levels of aconitase-type proteins, accompanied by a decrease in the activities of the respective enzyme complexes. We propose a regulatory role of Sat4p in the late steps of the maturation of a specific subset of mitochondrial iron-sulfur cluster proteins, including Aco1p and lipoate synthase Lip5p. Impairment of the latter enzyme may account for the observed lipoylation defects. PMID:25117470

  15. Influence of pH and ionic strength (NaCl/Na2SO4) on the reaction HO Cl/ClO- + NO2-

    NASA Astrophysics Data System (ADS)

    Marcellos da Rosa, M.; Zetzsch, C.

    2003-04-01

    Equilibria such as HOCl + NO_2^- leftrightarrow ClNO_2 + OH^- and ClNO_2 + H_2O leftrightarrow NO_3^- + 2H^+ + Cl^- play an important role in halogen activation in the troposphere. We studied the oxidation of NO_2^- by HOCl/ClO^- in aqueous phase by stopped-flow measurements at different ionic strengths (bidestilled water, 0.1M NaCl, 1.0M NaCl and 1.0M Na_2SO^4) at various pH values (4.0, 5.5, 6.2 and 10.0) at 293K. The experiments were performed using a SX.18MV Applied Photophysics spectrophotometer, observing the exponential decay of HOCl/ClO^- at λ = 290nm between 10ms and 100s. HOCl (pK_a= 7.50) was obtained by bubbling N_2 with 1% Cl_2 through bidestilled water. The pH of the aqueous solutions of HOCl was determined by a pH meter (CG820, Schott) with a glass electrode N6180 (calibrated with standard buffer solutions at pH = 3.0, 4.0, 7.0 and 10.0), and the pH values were adjusted by dropwise addition of HClO_4 or NaOH. The concentrations of HOCl (ɛHOCl (230nm) = 100M-1cm-1) ([HOCl] = 1.3mM - 10mM) and ClO- (ɛClO- (292nm) = 350 M-1cm-1) ([ClO^-] = 1.3mM - 5mM) were determined by UV spectrometry (Kontron UVIKON 860) at a resolution of 2 nm in 1 cm cells at various pH values. The concentration range of NO_2^- was between 5mM and 50mM. The following second-order rate constant kII were obtained at 293K at various pH values (in units of M-1s-1) in H_2O: pH 4.0, (5.6±0.3)\\cdot 10^3; pH 5.5, (5.0±0.4)\\cdot 10^3; pH 10.0, 3.9±0.4; in 0.1M NaCl: pH 5.5, (4.3±0.4)\\cdot 10^3; pH 10.0, 2.6±0.4; in 1.0M NaCl: pH 5.5, (4.0±0.3); pH 10.0, 0.7±0.2 and in 1.0M Na_2SO_4: pH 5.5, (3.0±0.3)\\cdot 10^3; pH 10.0, 1.9±0.4. There is a strong effect of the pH on the reaction HOCl/ClO^- + NO_2^-, as reflected in the ratio kII_a(pH 5.5, HOCl)/kII_b(pH 10.0, ClO^-): in H_2O (kII_a ˜ 1200 \\cdot kII_b), in 0.1M NaCl (kII_a ˜ 1900 \\cdot kII_b), in 1.0M NaCl (kII_a ˜ 5700 \\cdot kII_b) and in 1.0 M Na_2SO_4 (kII_a ˜ 1500 \\cdot kII_b). A mechanism for the oxidation of NO

  16. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1. [T.D. 9445, 74 FR 6830, Feb. 11, 2009] ...

  17. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1. [T.D. 9445, 74 FR 6830, Feb. 11, 2009] ...

  18. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1. [T.D. 9445, 74 FR 6830, Feb. 11, 2009] ...

  19. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1. [T.D. 9445, 74 FR 6830, Feb. 11, 2009] ...

  20. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1. [T.D. 9445, 74 FR 6830, Feb. 11, 2009] ...

  1. Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition.

    PubMed

    Devin, Jessica K; Pretorius, Mias; Nian, Hui; Yu, Chang; Billings, Frederic T; Brown, Nancy J

    2014-05-01

    Dipeptidyl peptidase-4 inhibitors prevent the degradation of incretin hormones and reduce postprandial hyperglycemia in patients with type 2 diabetes mellitus. Dipeptidyl peptidase-4 degrades other peptides with a penultimate proline or alanine, including bradykinin and substance P, which are also substrates of angiotensin-converting enzyme (ACE). During ACE inhibition, substance P is inactivated primarily by dipeptidyl peptidase-4, whereas bradykinin is first inactivated by aminopeptidase P. This study tested the hypothesis that dipeptidyl peptidase-4 inhibition potentiates vasodilator and fibrinolytic responses to substance P when ACE is inhibited. Twelve healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received sitagliptin 200 mg by mouth or placebo. Substance P and bradykinin were infused via brachial artery before and during intra-arterial enalaprilat. Sitagliptin and enalaprilat each reduced forearm vascular resistance and increased forearm blood flow without affecting mean arterial pressure, but there was no interactive effect of the inhibitors. Enalaprilat increased bradykinin-stimulated vasodilation and tissue plasminogen activator release; sitagliptin did not affect these responses to bradykinin. The vasodilator response to substance P was unaffected by sitagliptin and enalaprilat; however, substance P increased heart rate and vascular release of norepinephrine during combined ACE and dipeptidyl peptidase-4 inhibition. In women, sitagliptin diminished tissue plasminogen activator release in response to substance P both alone and during enalaprilat. Substance P increases sympathetic activity during combined ACE and dipeptidyl peptidase-4 inhibition. - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01413542.

  2. Superaerophobic P-doped Ni(OH)2/NiMoO4 hierarchical nanosheet arrays grown on Ni foam for electrocatalytic overall water splitting.

    PubMed

    Xi, Wenguang; Yan, Gang; Tan, Huaqiao; Xiao, Liguang; Cheng, Sihang; Khan, Shifa Ullah; Wang, Yonghui; Li, Yangguang

    2018-06-19

    Transition metal (TM) oxides and hydroxides are one of the important candidates for the development of durable and low-cost electrocatalysts towards water splitting. The key issue is exploring effective methods to improve their electrocatalytic activity. Herein, we report a new type of P-doped Ni(OH)2/NiMoO4 hierarchical nanosheet array (abbr. P-Ni(OH)2/NiMoO4) grown on Ni foam (NF), which can act as a highly efficient electrocatalyst towards overall water splitting. Such a composite was obtained by a three-step preparation process. In the first two hydrothermal reactions, the crystalline Ni(OH)2 hierarchical nanosheet arrays were grown on NF and then the low crystallinity NiMoO4 was grafted on the Ni(OH)2 nanosheets. In the third phosphorization step, P element was doped into the composite Ni(OH)2/NiMoO4. Electrocatalytic experiments show that P-Ni(OH)2/NiMoO4 possesses a smaller overpotential (60 mV) and lower Tafel slope (130 mV dec-1) toward HER in 1 M KOH. When it was employed as an integrated water splitting catalyst, only a potential of 1.55 V was required to achieve a current density of 10 mA cm-2. This catalytic activity is even better than those of electrolyzers constructed with noble metals Pt/C∥IrO2. The superior electrocatalytic performance of P-Ni(OH)2/NiMoO4 can be attributed to the high quality of crystalline Ni(OH)2 nanosheet arrays grown on NF, which dramatically improve the conductivity. Furthermore, the hierarchical structure not only increases the surface area and exposes more catalytically active sites, but also provides a superaerophobic surface, which helps to accelerate the release of generated bubbles. Moreover, the synergistic effects between P-Ni(OH)2 and P-NiMoO4 efficiently promote the HER and OER processes also. This work may suggest new a way to explore TM oxide/hydroxide-based durable electrocatalysts with highly efficient electrocatalytic activities towards overall water splitting.

  3. Detection of minority carrier traps in p-type 4H-SiC

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

    Alfieri, G.; Kimoto, T.

    2014-03-03

    Contrarily to the case of n-type 4H-SiC, very little is known about the presence of minority carrier traps in p-type epilayers. In this study, we performed the electrical characterization of as-grown, electron irradiated, and thermally oxidized p-type 4H-SiC, by using minority carrier transient spectroscopy. Four minority carrier traps are reported in 1.6–2.3 eV energy range above the valence band edge (E{sub V}). Particular emphasis is given to the mid-gap minority carrier trap (EH{sub 6∕7}) and to its correlation to an energetically close mid-gap majority carrier trap (HK4)

  4. DIRECT MODULATION OF P2X1 RECEPTOR-CHANNELS BY THE LIPID PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE

    PubMed Central

    Bernier, Louis-Philippe; Ase, Ariel R.; Tong, Xinkang; Hamel, Edith; Blais, Dominique; Zhao, Qi; Logothetis, Diomedes E.; Séguéla, Philippe

    2012-01-01

    The P2X1 receptor-channels activated by extracellular ATP contribute to the neurogenic component of smooth muscle contraction in vascular beds and genito-urinary tracts of rodents and humans. In the present study, we investigated the interactions of plasma membrane phosphoinositides with P2X1 ATP receptors and their physiological consequences. In an isolated rat mesenteric artery preparation, we observed a strong inhibition of P2X1-mediated constrictive responses by depletion of PI(4,5)P2 with the PI4-kinase inhibitor wortmannin. Using the Xenopus oocyte expression system, we provided electrophysiological evidence that lowering PI(4,5)P2 levels with wortmannin significantly decreases P2X1 currents amplitude and recovery. Previously reported modulation of recovery of desensitized P2X1 currents by phospholipase C-coupled 5-HT2A metabotropic receptors was also found wortmannin-sensitive. Treatment with wortmannin alters the kinetics of P2X1 activation and inactivation without changing its sensitivity to ATP. The functional impact of wortmannin on P2X1 currents could be reversed by addition of intracellular PI(4,5)P2, but not PI(3,4,5)P3. and direct application of PI(4,5)P2 to excised inside-out macropatches rescued P2X1 currents from rundown. We showed that the proximal region of the intracellular C-terminus of P2X1 subunit directly binds to PI(4,5)P2 and other anionic phospholipids, and we identified the basic residue K364 as a critical determinant for phospholipid binding and sensitivity to wortmannin. Overall, these results indicate that PI(4,5)P2 plays a key role in the expression of full native and heterologous P2X1 function by regulating the amplitude, recovery and kinetics of ionotropic ATP responses through direct receptor-lipid interactions. PMID:18523136

  5. Solubility of Anhydrite (CaSO4) in NaCl-H2O Fluids at High T and P

    NASA Astrophysics Data System (ADS)

    Newton, R. C.; Manning, C. E.

    2003-12-01

    Weight losses of single crystals of a very pure natural anhydrite exposed to NaCl solutions of 0-0.3 mol fraction were measured at 600-800 \\deg C and 6-14 kbar. Experimental charges were contained in welded Pt capsules in 1.91 cm-diameter piston-cylinder apparatus with NaCl pressure medium for 5-72 hr. Measurements in initially pure H2O were made with HM, NNO, and MnO2 buffers, as well as without buffering. At 800 \\deg C and 10 kbar, CaSO4 molalities are: MnO2, 0.014 mol/kg H2O; HM, 0.017; NNO, 0.148; and unbuffered, 0.026. Variation in oxygen fugacity thus has a large effect on CaSO4 solubility, increasing with H2S/SO2 in the fluid. Unbuffered (self-buffered) charges gave solubilities much closer to HM than NNO. Melting occurred in the NNO experiment at this P and T. NaCl increases CaSO4 solubility enormously, with m(CaSO4) reaching 5.4, or 23.5 wt. %, at 800 \\deg C, 10 kbar and X(NaCl)=0.3. There is also a very large increase with temperature. Regression of all the data give: log(m-mo) = -1.533 + 0.00291T + (1.441 + 0.00016T)logX(NaCl) + 0.0413(P-10) where mo is molality in pure H2O, P is in kbar, and T is in Kelvins. The very large carrying capacity for sulfate in even mildly saline fluids at high P and T, together with the high oxygen potential generated when these solutions react with FeO in rocks to yield pyrrhotite, indicates that such fluids should be considered as principal agents in S-rich, highly oxidizing processes such as Pinatubo-type volcanic eruptions, certain deep-crustal granulite facies metamorphism, as in Bamble, Norway and Shevaroy Hills, S. India, and the anhydrite-related, oxidized Au ore deposits like Abitibi, Ontario, and Kalgoorlie, Australia.

  6. Activation of p38-MAPK by CXCL4/CXCR3 axis contributes to p53-dependent intestinal apoptosis initiated by 5-fluorouracil.

    PubMed

    Gao, Jing; Gao, Jin; Qian, Lan; Wang, Xia; Wu, Mingyuan; Zhang, Yang; Ye, Hao; Zhu, Shunying; Yu, Yan; Han, Wei

    2014-08-01

    Chemotherapy-induced mucositis (CIM) is a major does limiting side-effect of chemoagents such as 5-fluorouracil (5-FU). Molecules involved in this disease process are still not fully understood. We proposed that the homeostatically regulated genes during CIM may participate in the disease. A cluster of such genes were previously identified by expression gene-array from the mouse jejunum in 5-FU-induced mucositis model. Here, we report that CXCL4 is such a homeostatically regulated gene and serves as a new target for the antibody treatment of CIM. CXCL4 and its receptor CXCR3 were confirmed at both the gene and protein levels to be homeostatically regulated during 5-FU-induced mucositis. Using of CXCL4 neutralizing monoclonal antibody (CXCL4mab) decreased the incidence, severity, and duration of the chemotherapy-induced diarrhea, the major symptom of CIM, in a 5-FU mouse CIM model. Mechanistically, CXCL4mab reduced the apoptosis of the crypt epithelia by suppression of the 5-FU-induced expression of p53 and Bax through its receptor CXCR3. The downstream signaling pathway of CXCL4 in activation of the epithelial apoptosis was identified in an intestinal epithelial cell line (IEC-6). CXCL4 activated the phosphorylation of p38 MAPK, which mediated the stimulated expression of p53 and Bax, and resulted in the ultimate activation of Caspase-8, -9, and -3. Taken together, activation of CXCL4 expression by 5-FU in mice participates in 5-FU-induced intestinal mucositis through upregulation of p53 via activation of p38-MAPK, and CXCL4mab is potentially beneficial in preventing CIM in the intestinal tract.

  7. Activation of p38-MAPK by CXCL4/CXCR3 axis contributes to p53-dependent intestinal apoptosis initiated by 5-fluorouracil

    PubMed Central

    Gao, Jing; Gao, Jin; Qian, Lan; Wang, Xia; Wu, Mingyuan; Zhang, Yang; Ye, Hao; Zhu, Shunying; Yu, Yan; Han, Wei

    2014-01-01

    Chemotherapy-induced mucositis (CIM) is a major does limiting side-effect of chemoagents such as 5-fluorouracil (5-FU). Molecules involved in this disease process are still not fully understood. We proposed that the homeostatically regulated genes during CIM may participate in the disease. A cluster of such genes were previously identified by expression gene-array from the mouse jejunum in 5-FU-induced mucositis model. Here, we report that CXCL4 is such a homeostatically regulated gene and serves as a new target for the antibody treatment of CIM. CXCL4 and its receptor CXCR3 were confirmed at both the gene and protein levels to be homeostatically regulated during 5-FU-induced mucositis. Using of CXCL4 neutralizing monoclonal antibody (CXCL4mab) decreased the incidence, severity, and duration of the chemotherapy-induced diarrhea, the major symptom of CIM, in a 5-FU mouse CIM model. Mechanistically, CXCL4mab reduced the apoptosis of the crypt epithelia by suppression of the 5-FU-induced expression of p53 and Bax through its receptor CXCR3. The downstream signaling pathway of CXCL4 in activation of the epithelial apoptosis was identified in an intestinal epithelial cell line (IEC-6). CXCL4 activated the phosphorylation of p38 MAPK, which mediated the stimulated expression of p53 and Bax, and resulted in the ultimate activation of Caspase-8, -9, and -3. Taken together, activation of CXCL4 expression by 5-FU in mice participates in 5-FU-induced intestinal mucositis through upregulation of p53 via activation of p38-MAPK, and CXCL4mab is potentially beneficial in preventing CIM in the intestinal tract. PMID:24800927

  8. Low external pH replaces 2,4-D in maintaining and multiplying 2,4-D-initiated embryogenic cells of carrot

    NASA Technical Reports Server (NTRS)

    Smith, D. L.; Krikorian, A. D.

    1990-01-01

    A mixed culture comprised of both embryonic globules and nonembryogenic callus was derived from seedling hypocotyls of Daucus carota cv. Scarlet Nantes on 2,4-D- containing medium using well-established methods. Then the mixed cultures were transferred to, and serially subcultured on, a hormone-free medium near pH 4. The medium contained 1 mM NH4+ as the sole nitrogen source. When cultured in this way, embryonic globules were able to multiply without development into later embryo stages. Nonembryogenic callus did not survive. Continuous culture of embryonic globules on this low pH hormone-free medium yielded cultures consisting entirely of preglobular stage proembryos (PGSPs). PGSP cultures have been maintained as such with continuous multiplication for nearly 2 years without loss of embryogenic potential. These hormone-free-maintained PGSPs continue their development to later embryo stages when cultured on the same hormone-free medium buffered at pH 5.8. We show that hormone-free medium near pH 4 can replace 2,4-D in its ability to sustain multiplication of 2,4-D-initiated embryogenic cells of carrot at an acceptable growth rate without their development into later embryo stages. This procedure provides selective conditions that do not permit the growth of non-embryogenic cells while providing an adequate environment for embryogenic cell proliferation and should prove invaluable in studying habituation.

  9. Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization.

    PubMed

    Forst, Anna-Lena; Olteanu, Vlad Sorin; Mollet, Géraldine; Wlodkowski, Tanja; Schaefer, Franz; Dietrich, Alexander; Reiser, Jochen; Gudermann, Thomas; Mederos y Schnitzler, Michael; Storch, Ursula

    2016-03-01

    Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X4) blocker 5-BDBD. Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X4 channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X4 channels as mechanotransducers in podocytes. Copyright © 2016 by the American Society of Nephrology.

  10. Phosphatidylinositol 4,5-Bisphosphate (PtdIns(4,5)P2) Specifically Induces Membrane Penetration and Deformation by Bin/Amphiphysin/Rvs (BAR) Domains*

    PubMed Central

    Yoon, Youngdae; Zhang, Xiuqi; Cho, Wonhwa

    2012-01-01

    Cellular proteins containing Bin/amphiphysin/Rvs (BAR) domains play a key role in clathrin-mediated endocytosis. Despite extensive structural and functional studies of BAR domains, it is still unknown how exactly these domains interact with the plasma membrane containing phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and whether they function by a universal mechanism or by different mechanisms. Here we report that PtdIns(4,5)P2 specifically induces partial membrane penetration of the N-terminal amphiphilic α-helix (H0) of two representative N-BAR domains from Drosophila amphiphysin (dAmp-BAR) and rat endophilin A1 (EndoA1-BAR). Our quantitative fluorescence imaging analysis shows that PtdIns(4,5)P2-dependent membrane penetration of H0 is important for self-association of membrane-bound dAmp-BAR and EndoA1-BAR and their membrane deformation activity. EndoA1-BAR behaves differently from dAmp-BAR because the former has an additional amphiphilic α-helix that penetrates the membrane in a PtdIns(4,5)P2-independent manner. Depletion of PtdIns(4,5)P2 from the plasma membrane of HEK293 cells abrogated the membrane deforming activity of EndoA1-BAR and dAmp-BAR. Collectively, these studies suggest that the local PtdIns(4,5)P2 concentration in the plasma membrane may regulate the membrane interaction and deformation by N-BAR domain-containing proteins during clathrin-mediated endocytosis. PMID:22888025

  11. Effects of gaseous ammonia on intracellular pH values in leaves of C 3- and C 4-plants

    NASA Astrophysics Data System (ADS)

    Yin, Zu-Hua; Kaiser, Werner; Heber, Ulrich; Raven, John A.

    Responses of cytosolic and vacuolar pH to different concentrations (1.3-5.4 μmol NH 3 mol -1 gas or 0.940-3.825 mg NH 3 m -3 gas) of gaseous NH 3 were studied in experiments of 3 h duration by recording changes in fluorescence of pyranine and esculin in leaves of C 3 and C 4 plants. After a lag phase of 0.5-4 min, the uptake of NH 3 at 50-200 nmol m -2 leaf area s -1 increased pyranine fluorescence, indicating cytosolic alkalinization in leaves of Pelargonium zonale L. (C 3) and Amaranthus caudatus L. (C 4). A smaller increase in esculin fluorescence induced by NH 3 indicated some vacuolar alkalization in a Spinacia oleracea L. leaf. Photosynthesis and transpiration remained unchanged during exposure of illuminated leaves to NH 3 for up to 30 min (the maximum tested). CO 2 concentrations influenced the extent of cytosolic alkalinization. 500 μmol CO 2 mol -1 gas suppressed the NH 3-induced cytosolic alkalinization relative to that found in 16 μmol CO 2 mol -1 gas. The suppressing effect of CO 2 on NH 3-induced alkalization was larger in illuminated leaves of the C 4Amaranthus than the C 3Pelargonium. These results indicate that the alkaline pH shift caused by solution and protonation of NH 3 in aqueous leaf compartments is affected by assimilation of NH 3.

  12. Foam Experiment Hardware are Flown on Microgravity Rocket MAXUS 4

    NASA Astrophysics Data System (ADS)

    Lockowandt, C.; Löth, K.; Jansson, O.; Holm, P.; Lundin, M.; Schneider, H.; Larsson, B.

    2002-01-01

    The Foam module was developed by Swedish Space Corporation and was used for performing foam experiments on the sounding rocket MAXUS 4 launched from Esrange 29 April 2001. The development and launch of the module has been financed by ESA. Four different foam experiments were performed, two aqueous foams by Doctor Michele Adler from LPMDI, University of Marne la Vallée, Paris and two non aqueous foams by Doctor Bengt Kronberg from YKI, Institute for Surface Chemistry, Stockholm. The foam was generated in four separate foam systems and monitored in microgravity with CCD cameras. The purpose of the experiment was to generate and study the foam in microgravity. Due to loss of gravity there is no drainage in the foam and the reactions in the foam can be studied without drainage. Four solutions with various stabilities were investigated. The aqueous solutions contained water, SDS (Sodium Dodecyl Sulphate) and dodecanol. The organic solutions contained ethylene glycol a cationic surfactant, cetyl trimethyl ammonium bromide (CTAB) and decanol. Carbon dioxide was used to generate the aqueous foam and nitrogen was used to generate the organic foam. The experiment system comprised four complete independent systems with injection unit, experiment chamber and gas system. The main part in the experiment system is the experiment chamber where the foam is generated and monitored. The chamber inner dimensions are 50x50x50 mm and it has front and back wall made of glass. The front window is used for monitoring the foam and the back window is used for back illumination. The front glass has etched crosses on the inside as reference points. In the bottom of the cell is a glass frit and at the top is a gas in/outlet. The foam was generated by injecting the experiment liquid in a glass frit in the bottom of the experiment chamber. Simultaneously gas was blown through the glass frit and a small amount of foam was generated. This procedure was performed at 10 bar. Then the pressure was

  13. Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy

    PubMed Central

    Bebeacua, Cecilia; Förster, Andreas; McKeown, Ciarán; Meyer, Hemmo H.; Zhang, Xiaodong; Freemont, Paul S.

    2012-01-01

    p97 is a key regulator of numerous cellular pathways and associates with ubiquitin-binding adaptors to remodel ubiquitin-modified substrate proteins. How adaptor binding to p97 is coordinated and how adaptors contribute to substrate remodeling is unclear. Here we present the 3D electron cryomicroscopy reconstructions of the major Ufd1-Npl4 adaptor in complex with p97. Our reconstructions show that p97-Ufd1-Npl4 is highly dynamic and that Ufd1-Npl4 assumes distinct positions relative to the p97 ring upon addition of nucleotide. Our results suggest a model for substrate remodeling by p97 and also explains how p97-Ufd1-Npl4 could form other complexes in a hierarchical model of p97-cofactor assembly. PMID:22232657

  14. Mobilization and acquisition of sparingly soluble P-Sources by Brassica cultivars under P-starved environment II. Rhizospheric pH changes, redesigned root architecture and pi-uptake kinetics.

    PubMed

    Akhtar, Muhammad Shahbaz; Oki, Yoko; Adachi, Tadashi

    2009-11-01

    Non-mycorrhizal Brassica does not produce specialized root structures such as cluster or dauciform roots but is an effective user of P compared with other crops. In addition to P-uptake, utilization and remobilization activity, acquisition of orthophosphate (Pi) from extracellular sparingly P-sources or unavailable bound P-forms can be enhanced by biochemical rescue mechanisms such copious H(+)-efflux and/or carboxylates exudation into rhizosphere by roots via plasmalemma H(+) ATPase and anion channels triggered by P-starvation. To visualize the dissolution of sparingly soluble Ca-phosphate (Ca-P), newly formed Ca-P was suspended in agar containing other essential nutrients. With NH(4)(+) applied as the N source, the precipitate dissolved in the root vicinity can be ascribed to rhizosphere acidification, whereas no dissolution occurred with nitrate nutrition. To observe in situ rhizospheric pH changes, images were recorded after embedding the roots in agar containing bromocresol purple as a pH indicator. P-tolerant cultivar showed a greater decrease in pH than the sensitive cultivar in the culture media (the appearance of typical patterns of various colors of pH indicator in the root vicinity), and at stress P-level this acidification was more prominent. In experiment 2, low P-tolerant class-I cultivars (Oscar and Con-II) showed a greater decrease in solution media pH than low P-sensitive class-II (Gold Rush and RL-18) cultivars, and P-contents of the cultivars was inversely related to decrease in culture media pH. To elucidate P-stress-induced remodeling and redesigning in a root architectural system, cultivars were grown in rhizoboxes in experiment 3. The elongation rates of primary roots increased as P-supply increased, but the elongation rates of the branched zones of primary roots decreased. The length of the lateral roots and topological index values increased when cultivars were exposed to a P-stress environment. To elucidate Pi-uptake kinetics, parameters

  15. Degradative pathways for p-toluenecarboxylate and p-toluenesulfonate and their multicomponent oxygenases in Comamonas testosteroni strains PSB-4 and T-2.

    PubMed

    Junker, F; Saller, E; Schläfli Oppenberg, H R; Kroneck, P M; Leisinger, T; Cook, A M

    1996-09-01

    Three multicomponent oxygenases involved in the degradation of p-toluenesulfonate and p-toluenecarboxylate and the regulation of their synthesis have been examined in three strains (T-2, PSB-4 and TER-1) of Comamonas testosteroni. Strain T-2 utilizes p-toluenesulfonate as a source of carbon and energy for growth via p-sulfobenzoate and protocatechuate, and p-toluenecarboxylate via terephthalate and protocatechuate, and has the unusual property of requiring the reductase (TsaB) of the toluenesulfonate methyl monooxygenase system (TsaMB) in an incompletely expressed sulfobenzoate dioxygenase system (PsbAC) [Schläfli Oppenberg, H.R., Chen, G., Leisinger, T. & Cook, A. M. (1995). Microbiology 141, 1891-1899]. The independently isolated C. testosteroni PSB-4 utilized only sulfobenzoate and terephthalate via protocatechuate. Mutant TER-1, derived from strain T-2, utilized only terephthalate via protocatechuate. We detected no enzymes of the pathway from toluenesulfonate to sulfobenzoate in strains PSB-4 and TER-1, and confirmed by PCR and Southern blot analysis that the genes (tsaMB) encoding toluenesulfonate monooxygenase were absent. We concluded that, in strain PSB-4, the regulatory unit encoding the genes for the conversion of toluenesulfonate to sulfobenzoate was missing, and that generation of mutant TER-1 involved deletion of this regulatory unit and of the regulatory unit encoding desulfonation of sulfobenzoate. The degradation of sulfobenzoate in strain PSB-4 was catalysed by a fully inducible sulfobenzoate dioxygenase system (PsbACPSB-4), which, after purification of the oxygenase component (PsbAPSB-4), turned out to be indistinguishable from the corresponding component from strain T-2 (PsbAT-2). Reductase PsbCPSB-4, which we could separate but not purify, was active with oxygenase PsbAPSB-4 and PsbAT-2. Oxygenase PsbAPSB-4 was shown by electron paramagnetic resonance spectroscopy to contain a Rieske [2Fe-2S] centre. The enzyme system oxygenating terephthalate

  16. 4. Historic American Buildings Survey (Fed.) Stanley P. Mixon, Photographer ...

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

    4. Historic American Buildings Survey (Fed.) Stanley P. Mixon, Photographer May 16, 1940 (A) EXTERIOR, GENERAL VIEW EAST (TOWER) END AND SOUTH SIDE. (Belfry & Spire have been rebuilt since Hurricane of Sept 21, 1938) - Unitarian Church, Brooklyn, Windham County, CT

  17. The SHiP experiment at CERN SPS

    NASA Astrophysics Data System (ADS)

    Di Crescenzo, A.; SHiP Collaboration

    2016-01-01

    SHiP is a new general purpose fixed target facility, whose Technical Proposal has been recently submitted to the CERN SPS Committee. In its initial phase, the 400GeV proton beam extracted from the SPS will be dumped on a heavy target with the aim of integrating 2×1020 pot in 5years. A dedicated detector located downstream of the target, based on a long vacuum tank followed by a spectrometer and particle identification detectors, will allow probing a variety of models with light long-lived exotic particles and masses below a few GeV/c2. The beam dump is also an ideal source of tau neutrinos, the less known particle in the Standard Model. Another dedicated detector, based on the Emulsion Cloud Chamber technology already used in the OPERA experiment, will allow to perform for the first time measurements of the tau neutrino deep inelastic scattering cross section. Tau neutrinos will be distinguished from tau anti-neutrinos, thus providing the first observation of the tau anti-neutrino.

  18. The Completely Sequenced Plasmid pEST4011 Contains a Novel IncP1 Backbone and a Catabolic Transposon Harboring tfd Genes for 2,4-Dichlorophenoxyacetic Acid Degradation

    PubMed Central

    Vedler, Eve; Vahter, Merle; Heinaru, Ain

    2004-01-01

    The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacterium Achromobacter xylosoxidans subsp. denitrificans strain EST4002 contains plasmid pEST4011. This plasmid ensures its host a stable 2,4-D+ phenotype. We determined the complete 76,958-bp nucleotide sequence of pEST4011. This plasmid is a deletion and duplication derivative of pD2M4, the 95-kb highly unstable laboratory ancestor of pEST4011, and was self-generated during different laboratory manipulations performed to increase the stability of the 2,4-D+ phenotype of the original strain, strain D2M4(pD2M4). The 47,935-bp catabolic region of pEST4011 forms a transposon-like structure with identical copies of the hybrid insertion element IS1071::IS1471 at the two ends. The catabolic regions of pEST4011 and pJP4, the best-studied 2,4-D-degradative plasmid, both contain homologous, tfd-like genes for complete 2,4-D degradation, but they have little sequence similarity other than that. The backbone genes of pEST4011 are most similar to the corresponding genes of broad-host-range self-transmissible IncP1 plasmids. The backbones of the other three IncP1 catabolic plasmids that have been sequenced (the 2,4-D-degradative plasmid pJP4, the haloacetate-catabolic plasmid pUO1, and the atrazine-catabolic plasmid pADP-1) are nearly identical to the backbone of R751, the archetype plasmid of the IncP1 β subgroup. We show that despite the overall similarity in plasmid organization, the pEST4011 backbone is sufficiently different (51 to 86% amino acid sequence identity between individual backbone genes) from the backbones of members of the three IncP1 subgroups (the α, β, and γ subgroups) that it belongs to a new IncP1subgroup, the δ subgroup. This conclusion was also supported by a phylogenetic analysis of the trfA2, korA, and traG gene products of different IncP1 plasmids. PMID:15489427

  19. 4,4,4-trifluoro-3-(indole-3-)butyric acid promotes root elongation in Lactuca sativa independent of ethylene synthesis and pH

    NASA Technical Reports Server (NTRS)

    Zhang, Nenggang; Hasenstein, Karl H.

    2002-01-01

    We studied the mode of action of 4,4,4-trifluoro-3- (indole-3-) butyric acid (TFIBA), a recently described root growth stimulator, on primary root growth of Lactuca sativa L. seedlings. TFIBA (100 micromoles) promoted elongation of primary roots by 40% in 72 h but inhibited hypocotyl growth by 35%. TFIBA induced root growth was independent of pH. TFIBA did not affect ethylene production, but reduced the inhibitory effect of ethylene on root elongation. TFIBA promoted root growth even in the presence of the ethylene biosynthesis inhibitor L-alpha-(2-aminoethoxyvinyl)glycine. TFIBA and the ethylene-binding inhibitor silver thiosulphate (STS) had a similar effect on root elongation. The results indicate that TFIBA-stimulated root elongation was neither pH-dependent nor related to inhibition of ethylene synthesis, but was possibly related to ethylene action.

  20. When incentives work too well: locally implemented pay for performance (P4P) and adverse sanctions towards home birth in Tanzania - a qualitative study

    PubMed Central

    2014-01-01

    Background Despite limited evidence of its effectiveness, performance-based payments (P4P) are seen by leading policymakers as a potential solution to the slow progress in reaching Millennium Development Goal 5: improved maternal health. This paper offers insights into two of the aspects that are lacking in the current literature on P4P, namely what strategies health workers employ to reach set targets, and how the intervention plays out when implemented by local government as part of a national programme that does not receive donor funding. Methods A total of 28 in-depth interviews (IDIs) with 25 individuals were conducted in Mvomero district over a period of 15 months in 2010 and 2011, both before and after P4P payments. Seven facilities, including six dispensaries and one health centre, were covered. Informants included 17 nurses, three clinical officers, two medical attendants, one lab technician and two district health administrators. Results Health workers reported a number of strategies to increase the number of deliveries at their facility, including health education and cooperation with traditional health providers. The staff at all facilities also reported that they had told the women that they would be sanctioned if they gave birth at home, such as being fined or denied clinical cards and/or vaccinations for their babies. There is a great uncertainty in relation to the potential health impacts of the behavioural changes that have come with P4P, as the reported strategies may increase the numbers, but not necessarily the quality. Contrary to the design of the P4P programme, payments were not based on performance. We argue that this was due in part to a lack of resources within the District Administration, and in part as a result of egalitarian fairness principles. Conclusions Our results suggest that particular attention should be paid to adverse effects when using external rewards for improved health outcomes, and secondly, that P4P may take on a

  1. Measured solubilities and speciations from oversaturation experiments of neptunium, plutonium, and americium in UE-25p No. 1 well water from the Yucca Mountain region: Milestone report 3329-WBS1.2.3.4.1.3.1

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

    Nitsche, H.; Roberts, K.; Prussin, T.

    1994-04-01

    Solubility and speciation are important in understanding aqueous radionuclide transport through the geosphere. They define the source term for transport retardation processes such as sorption and colloid formation. Solubility and speciation data are useful in verifying the validity of geochemical codes that are a part of predictive transport models. Results are presented from solubility and speciation experiments of {sup 237}NpO{sub 2}{sup +}, {sup 239}Pu{sup 4+}, and {sup 241}Am{sup 3+}/Nd{sup 3+} in a modified UE-25p No. 1 groundwater (from the Yucca Mountain region, Nevada, which is being investigated as a potential high-level nuclear waste disposal site) at two different temperatures (25{degree}more » and 60{degree}C) and three pH values (6.0, 7.0, 8.5). The solubility-controlling steady-state solids were identified and the speciation and/or oxidation states present in the supernatant solutions were determined. The neptunium solubility decreased with increasing temperature and pH. Plutonium concentrations significantly decreased with increasing temperature at pH 6 and 7. The concentration at pH 8.5 hardly decreased at all with increasing temperature. At both temperatures the concentrations were highest at pH 8.5, lowest at pH 7, and in between at pH 6. For the americium/neodymium solutions, the solubility decreased significantly with increasing temperature and increased somewhat with increasing pH.« less

  2. Electron Excitation Cross Sections for the 2s(sup 2)2p(sup 3) (sup 4)S -> 2s(sup 2)2p(sup 3) (sup 2d) ->2s2p(sup 4) (sup 4p) (Resonance) Transitions in Oil

    NASA Technical Reports Server (NTRS)

    Zuo, M.; Smith, S.; Chutjian, A.; Williams, I.; Tayal, S.; McLaughlin, B.

    1994-01-01

    Experimental and theoretical excitation cross sections are reported for the first forbidden transition xxx and the first allowed (resonance) transition xxx in OII. Use is made of electron-energy loss and merged beams methods. The electron energy range covered is 3.33 eV (threshold) to 15 eV for the S->D transition, and 14.9 eV (threshold) to 40 eV for the S->P transition. Care was taken to assess and minimize the metastable fraction of the OII beam. An electron mirror was designed and tested to reflect inelastically back-scattered electrons into the forward direction to account for the full range of polar scattering angles. Comparisons are made between present experiments and 11-state R-Matrix calculations. Calculations are also presented for the xxx transition.

  3. Overview of the Micro Vertex Detector for the P bar ANDA experiment

    NASA Astrophysics Data System (ADS)

    Calvo, Daniela; P¯ANDA MVD Group

    2017-02-01

    The P bar ANDA experiment is devoted to study interactions between cooled antiproton beams and a fixed target (the interaction rate is of about 107 events/s), hydrogen or heavier nuclei. The innermost tracker of P bar ANDA is the Micro Vertex Detector (MVD), specially designed to ensure the secondary vertex resolution for the discrimination of short-lived charmonium states. Hybrid epitaxial silicon pixels and double-sided silicon microstrips will equip four barrels, arranged around the interaction point, and six forward disks. The experiment features a triggerless architecture with a master clock of 160 MHz, therefore the MVD has to run with a continuous data transmission where the hits need precise timestamps. The energy loss of the particles in the sensor will be measured as well. The challenging request of a triggerless readout suggested to develop custom readout chips for both pixel (ToPix) and microstrip (PASTA) devices. To validate components and the triggerless readout architecture, prototypes have been built and tested. After an overview of the MVD, the technological aspects and performances of some prototypes will be reported.

  4. CCHCR1 interacts with EDC4, suggesting its localization in P-bodies

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

    Ling, Y.H.; Wong, C.C.; Li, K.W.

    2014-09-10

    Coiled‐coil alpha‐helical rod protein 1 (CCHCR1) is suggested as a candidate biomarker for psoriasis for more than a decade but its function remains poorly understood because of the inconsistent findings in the literature. CCHCR1 protein is suggested to be localized in the cytoplasm, nucleus, mitochondria, or centrosome and to regulate various cellular functions, including steroidogenesis, proliferation, differentiation, and cytoskeleton organization. In this study, we attempted to find a consensus between these findings by identifying the interaction partners of CCHCR1 using co-immunoprecipiation with a stable cell line expressing EGFP-tagged CCHCR1. Out of more than 100 co-immunoprecipitants identified by liquid chromatography-tandem massmore » spectrometry (LC-MS/MS), the enhancer of mRNA-decapping protein 4 (EDC4), which is a processing body (P-body) component, was particularly found to be the major interacting partner of CCHCR1. Confocal imaging confirmed the localization of CCHCR1 in P-bodies and its N-terminus is required for this subcellular localization, suggesting that CCHCR1 is a novel P-body component. As P-bodies are the site for mRNA metabolism, our findings provide a molecular basis for the function of CCHCR1, any disruption of which may affect the transcriptome of the cell, and causing abnormal cell functions. - Highlights: • We identified CCHCR1 as a novel P-body component. • We identified EDC4 as the major interacting partner of CCHCR1. • N-terminus of CCHCR1 protein is required for its P-bodies localization.« less

  5. Analysis of the methylation patterns of the p16 INK4A, p15 INK4B, and APC genes in gastric adenocarcinoma patients from a Brazilian population.

    PubMed

    do Nascimento Borges, Bárbara; Burbano, Rommel Mario Rodriguez; Harada, Maria Lúcia

    2013-08-01

    Gastric cancer is a major public health problem in Pará state, where studies suggest complex genetic and epigenetic profiles of the population, indicating the need for the identification of molecular markers for this tumor type. In the present study, the methylation patterns of three genes [p16 (INK4A), p15 (INK4B), and adenomatous polyposis coli (APC)] were assessed in patients with gastric adenocarcinoma from Pará state in order to identify possible molecular markers of gastric carcinogenesis. DNA samples from tumoral and non-tumoral gastric tissues were modified with sodium bisulfite. A fragment of the promoter region of each gene was amplified and sequenced, and samples with more than 20 % of methylated CpG sites were considered hypermethylated. The correlation between the methylation pattern of the selected genes and the MTHFR C677T polymorphism, as well as the relationship between APC and CDH1 methylation, were evaluated. The results suggest that APC hypermethylation is an age-specific marker of gastric carcinogenesis, and the concordance of this event with CDH1 hypermethylation suggests that the Wnt pathway has an important role in gastric carcinogenesis. While the hypermethylation pattern of p15 (INK4B) seems to be an earlier event in this type of tumor, the hypomethylated status of this gene seems to be correlated to the C677T MTHFR TT genotype. On the other hand, the observed pattern of p16 (INK4A) hypermethylation suggests that this event is a good marker for the gastric cancer pathway in the Pará state population.

  6. P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer.

    PubMed

    Sharma, Shivani; Nagpal, Neha; Ghosh, Prahlad C; Kulshreshtha, Ritu

    2017-08-01

    miRNAs have emerged as key participants of p53 signaling pathways because they regulate or are regulated by p53. Here, we provide the first study demonstrating direct regulation of an oncogenic miRNA, miR-191-5p, by p53 and existence of a regulatory feedback loop. Using a combination of qRT-PCR, promoter-luciferase, and chromatin-immunoprecipitation assays, we show that p53 brings about down-regulation of miR-191-5p in breast cancer. miR-191-5p overexpression brought about inhibition of apoptosis in breast cancer cell lines (MCF7 and ZR-75) as demonstrated by reduction in annexin-V stained cells and caspase 3/7 activity, whereas miR-191-5p down-regulation showed the opposite. We further unveiled that SOX4 was a direct target of miR-191-5p. SOX4 overexpression was shown to increase p53 protein levels in MCF7 cells. miR-191-5p overexpression brought about down-regulation of SOX4 and thus p53 levels, suggesting the existence of a regulatory feedback loop. Breast cancer treatment by doxorubicin, an anti-cancer drug, involves induction of apoptosis by p53; we thus wanted to check whether miR-191-5p affects doxorubicin sensitivity. Interestingly, Anti-miR-191 treatment significantly decreased the IC50 of the doxorubicin drug and thus sensitized breast cancer cells to doxorubicin treatment by promoting apoptosis. Overall, this work highlights the importance of the p53-miR-191- SOX4 axis in the regulation of apoptosis and drug resistance in breast cancer and offers a preclinical proof-of-concept for use of an Anti-miR-191 and doxorubicin combination as a rational approach to pursue for better breast cancer treatment. © 2017 Sharma et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  7. Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice

    PubMed Central

    Wyatt, Letisha R.; Finn, Deborah A.; Khoja, Sheraz; Yardley, Megan M; Asatryan, Liana; Alkana, Ronald L.; Davies, Daryl L.

    2014-01-01

    P2X receptors (P2XRs) are a family of cation-permeable ligand-gated ion channels activated by synaptically released extracellular ATP. The P2X4 subtype is abundantly expressed in the CNS and is sensitive to low intoxicating ethanol concentrations. Genetic meta-analyses identified the p2rx4 gene as a candidate gene for innate alcohol intake and/or preference. The current study used mice lacking the p2rx4 gene (knockout, KO) and wildtype (WT) C57BL/6 controls to test the hypothesis that P2X4Rs contribute to ethanol intake. The early acquisition and early maintenance phases of ethanol intake were measured with three different drinking procedures. Further, we tested the effects of ivermectin (IVM), a drug previously shown to reduce ethanol’s effects on P2X4Rs and to reduce ethanol intake and preference, for its ability to differentially alter stable ethanol intake in KO and WT mice. Depending on the procedure and the concentration of the ethanol solution, ethanol intake was transiently increased in P2X4R KO versus WT mice during the acquisition of 24-hr and limited access ethanol intake. IVM significantly reduced ethanol intake in P2X4R KO and WT mice, but the degree of reduction was 50% less in the P2X4R KO mice. Western blot analysis identified significant changes in -γ aminobutyric acidA receptor (GABAAR) α1 subunit expression in brain regions associated with the regulation of ethanol behaviors in P2X4R KO mice. These findings add to evidence that P2X4Rs contribute to ethanol intake and indicate that there is a complex interaction between P2X4Rs, ethanol, and other neurotransmitter receptor systems. PMID:24671605

  8. NAD(P)H:Flavin Mononucleotide Oxidoreductase Inactivation during 2,4,6-Trinitrotoluene Reduction

    PubMed Central

    Riefler, R. Guy; Smets, Barth F.

    2002-01-01

    Bacteria readily transform 2,4,6-trinitrotoluene (TNT), a contaminant frequently found at military bases and munitions production facilities, by reduction of the nitro group substituents. In this work, the kinetics of nitroreduction were investigated by using a model nitroreductase, NAD(P)H:flavin mononucleotide (FMN) oxidoreductase. Under mediation by NAD(P)H:FMN oxidoreductase, TNT rapidly reacted with NADH to form 2-hydroxylamino-4,6-dinitrotoluene and 4-hydroxylamino-2,6-dinitrotoluene, whereas 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene were not produced. Progressive loss of activity was observed during TNT reduction, indicating inactivation of the enzyme during transformation. It is likely that a nitrosodinitrotoluene intermediate reacted with the NAD(P)H:FMN oxidoreductase, leading to enzyme inactivation. A half-maximum constant with respect to NADH, KN, of 394 μM was measured, indicating possible NADH limitation under typical cellular conditions. A mathematical model that describes the inactivation process and NADH limitation provided a good fit to TNT reduction profiles. This work represents the first step in developing a comprehensive enzyme level understanding of nitroarene biotransformation. PMID:11916686

  9. Involvement of Bmi-1 gene in the development of gastrointestinal stromal tumor by regulating p16Ink4A/p14ARF gene expressions: An in vivo and in vitro study.

    PubMed

    Wang, Jiang-Li; Wu, Jiang-Hong; Hong, Cai; Wang, Ya-Nong; Zhou, Ye; Long, Zi-Wen; Zhou, Ying; Qin, Hai-Shu

    2017-12-01

    This study was conducted in order to explore the role that Bmi-1 plays during the development of a gastrointestinal stromal tumor (GIST) by regulation of the p16 Ink4A and p14 ARF expressions. Eighty-six patients diagnosed with GIST were selected to take part in this experiment. The Bmi-1 protein expressions in GIST and adjacent normal tissues were detected using immunohistochemistry and further analyzed by using photodensitometry. To monitor and track the progression of the GIST, a 3-year follow-up was conducted for all affected patients. After cell transfection, the GIST cells were assigned into the control group (without transfection), the negative control (NC) group (transfected with Bmi-1-Scramble plasmid), and the Bmi-1 shRNA group (transfected with the pcDNA3.1-Bmi-1 shRNA plasmid). Protein and mRNA expressions collected from Bmi-1, p16 lnk4A , P14 ARF , cyclin D1, and CDK4 were measured using both the RT-qPCR and western blotting methods Cell senescence was assessed and obtained by using the β-Galactosidase (β-Gal) activity assay. The use of a Soft agar colony formation assay and CCK-8 assay were performed in order to detect the cell growth and subsequent proliferation. Cell invasion and migration were analyzed using the Transwell assay and scratch test. Bmi-1 in the GIST tissues was found to be significantly higher and the p16 lnk4A and P14 ARF expressions were lower than those in the adjacent normal tissues. Bmi-1 was negatively correlated with p16 lnk4A and P14 ARF expressions according to the correlation analysis. Bmi-1 expression was associated with the TNM stage, postoperative recurrence, metastasis, tumor size, and the 5-year survival rate. Area under ROC curve was calculated at 0.884, and sensitivity, specificity, and accuracy of Bmi-1 predicting the GIST were 67.44%, 97.67%, and 65.12%, respectively. Patients exhibiting a high Bmi-1 expression in the GIST tissues had lower survival rates than those with low Bmi-1 expression. In comparison with

  10. Nonstructural proteins nsP3 and nsP4 of Ross River and O'Nyong-nyong viruses: sequence and comparison with those of other alphaviruses.

    PubMed

    Strauss, E G; Levinson, R; Rice, C M; Dalrymple, J; Strauss, J H

    1988-05-01

    We have sequenced the nsP3 and nsP4 region of two alphaviruses, Ross River virus and O'Nyong-nyong virus, in order to examine these viruses for the presence or absence of an opal termination codon present between nsP3 and nsP4 in many alphaviruses. We found that Ross River virus possesses an in-phase opal termination codon between nsP3 and nsP4, whereas in O'Nyong-nyong virus this termination codon is replaced by an arginine codon. Previous studies have shown that two other alphaviruses, Sindbis virus and Middelburg virus, possess an opal termination codon separating nsP3 and nsP4 [E.G. Strauss, C.M. Rice, and J.H. Strauss (1983), Proc. Natl. Acad. Sci. USA 80, 5271-5275], whereas Semliki Forest virus possesses an arginine codon in lieu of the opal codon [K. Takkinen (1986), Nucleic Acids Res. 14, 5667-5682]. Thus, of the five alphaviruses examined to date, three possess the opal codon and two do not. Production of nsP4 requires readthrough of the opal codon in those alphaviruses that possess this termination codon and the function of the termination codon may be to regulate the amount of nsP4 produced. It is an open question then as to whether alphaviruses with no termination codon use other mechanisms to regulate the activity of this gene. The nsP4s of these five alphaviruses are highly conserved, sharing 71-76% amino acid sequence similarity, and all five contain the Gly-Asp-Asp motif found in many RNA virus replicases. The nsP3s are somewhat less conserved, sharing 52-73% amino acid sequence similarity throughout most of the protein, but each possesses a nonconserved C-terminal domain of 134 to 246 amino acids of unknown function.

  11. Interactions between Cytochromes P450 2B4 (CYP2B4) and 1A2 (CYP1A2) Lead to Alterations in Toluene Disposition and P450 Uncoupling

    PubMed Central

    Reed, James R.; Cawley, George F.; Backes, Wayne L.

    2013-01-01

    The goal of this study was to characterize the effects of CYP1A2•CYP2B4 complex formation on the rates and efficiency of toluene metabolism by comparing the results from simple reconstituted systems containing P450 reductase (CPR) and a single P450 to those using a mixed system containing CPR and both P450s. In the mixed system, the rates of formation of CYP2B4-specific benzyl alcohol and p-cresol were inhibited, whereas that of CYP1A2-specific o-cresol was increased, results consistent with the formation of a CYP1A2•CYP2B4 complex where the CYP1A2 moiety has higher affinity for CPR binding. Comparison of the rates of NADPH oxidation and production of hydrogen peroxide and excess water by the simple and mixed systems indicated that excess water formed at a much lower rate in the mixed system. The commensurate increase in the rate of CYP1A2-specific product formation suggested the P450•P450 interaction increased the putative rate-limiting step of CYP1A2 catalysis, abstraction of a hydrogen radical from the substrate. Cumene hydroperoxide-supported metabolism was measured to determine whether the effects of the P450•P450 interaction required the presence of CPR. Peroxidative metabolism was not affected by the interaction of the two P450s, even with CPR present. However, CPR did stimulate peroxidative metabolism by the simple system containing CYP1A2. These results suggest the major functional effects of the P450•P450 interaction are mediated by changes in the relative abilities of the P450s to receive electrons from CPR. Furthermore, CPR may play an effector role by causing a conformation change in CYP1A2 that makes its metabolism more efficient. PMID:23675771

  12. Lack of P4H-TM in mice results in age-related retinal and renal alterations.

    PubMed

    Leinonen, Henri; Rossi, Maarit; Salo, Antti M; Tiainen, Päivi; Hyvärinen, Jaana; Pitkänen, Marja; Sormunen, Raija; Miinalainen, Ilkka; Zhang, Chi; Soininen, Raija; Kivirikko, Kari I; Koskelainen, Ari; Tanila, Heikki; Myllyharju, Johanna; Koivunen, Peppi

    2016-09-01

    Age-related macular degeneration (AMD), affecting the retinal pigment epithelium (RPE), is the leading cause of blindness in middle-aged and older people in developed countries. Genetic and environmental risk factors have been identified, but no effective cure exists. Using a mouse model we show that a transmembrane prolyl 4-hydroxylase (P4H-TM), which participates in the oxygen-dependent regulation of the hypoxia-inducible factor (HIF), is a potential novel candidate gene for AMD. We show that P4h-tm had its highest expression levels in the mouse RPE and brain, heart, lung, skeletal muscle and kidney. P4h-tm -/- mice were fertile and had a normal life span. Lack of P4h-tm stabilized HIF-1α in cortical neurons under normoxia, while in hypoxia it increased the expression of certain HIF target genes in tissues with high endogenous P4h-tm expression levels more than in wild-type mice. Renal erythropoietin levels increased in P4h-tm -/- mice with aging, but the resulting ∼2-fold increase in erythropoietin serum levels did not lead to erythrocytosis. Instead, accumulation of lipid-containing lamellar bodies in renal tubuli was detected in P4h-tm -/- mice with aging, resulting in inflammation and fibrosis, and later glomerular sclerosis and albuminuria. Lack of P4h-tm was associated with retinal thinning, rosette-like infoldings and drusen-like structure accumulation in RPE with aging, as is characteristic of AMD. Photoreceptor recycling was compromised, and electroretinograms revealed functional impairment of the cone pathway in adult P4h-tm -/- mice and cone and rod deficiency in middle-aged mice. P4H-TM is therefore imperative for normal vision, and potentially a novel candidate for age-induced diseases, such as AMD. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Endothelial cell dysfunction and cytoskeletal changes associated with repression of p16INK4a during immortalization

    PubMed Central

    Kan, C-Y; Wen, V W; Pasquier, E; Jankowski, K; Chang, M; Richards, L A; Kavallaris, M; MacKenzie, K L

    2012-01-01

    The immortalization process is a fundamental step in the development of most (if not all) human cancers, including the aggressive endothelial cell (EC)-derived malignancy angiosarcoma. Inactivation of the tumor suppressor p16INK4a and the development of multiple chromosomal abnormalities are features of angiosarcoma that are recapitulated during telomerase-mediated immortalization of human ECs in vitro. The present study used a panel of telomerase-immortalized bone marrow EC (BMEC) lines to define the consequences of inactivation of p16INK4a on EC function and to identify molecular changes associated with repression of p16INK4a. In a comparison of two immortalized BMEC mass cultures and six clones, the cell lines that repressed p16INK4a showed a higher rate of proliferation and an impaired ability to undergo morphogenic differentiation and form vessel-like structures in vitro. Proteomic comparison of a p16INK4a-negative and a p16INK4a-positive BMEC mass culture at early- and late-passage time points following transduction with telomerase reverse transcriptase (hTERT) revealed altered expression of cytoskeletal proteins, including vimentin and α-tropomyosin (αTm), in the immortal cells. Immunoblot analyses of a panel of 11 immortal clones showed that cells that lacked p16INK4a expression tended to accumulate more dramatic changes in these cytoskeletal proteins than cells that retained p16INK4a expression. This corresponded with aberrant cytoskeletal architectures among p16INK4a-negative clones, which featured thicker actin stress fibers and less fluid membrane ruffles than p16INK4a-positive cells. A direct link between p16INK4a repression and defective EC function was confirmed by analysis of normal cells transfected with small interfering RNA (siRNA) targeting p16INK4a. siRNA-mediated repression of p16INK4a significantly impaired random motility and vessel formation in vitro. This report is the first to demonstrate that ECs that repress the expression of p16INK4a

  14. Membrane Order Is a Key Regulator of Divalent Cation-Induced Clustering of PI(3,5)P2 and PI(4,5)P2.

    PubMed

    Sarmento, Maria J; Coutinho, Ana; Fedorov, Aleksander; Prieto, Manuel; Fernandes, Fábio

    2017-10-31

    Although the evidence for the presence of functionally important nanosized phosphorylated phosphoinositide (PIP)-rich domains within cellular membranes has accumulated, very limited information is available regarding the structural determinants for compartmentalization of these phospholipids. Here, we used a combination of fluorescence spectroscopy and microscopy techniques to characterize differences in divalent cation-induced clustering of PI(4,5)P 2 and PI(3,5)P 2 . Through these methodologies we were able to detect differences in divalent cation-induced clustering efficiency and cluster size. Ca 2+ -induced PI(4,5)P 2 clusters are shown to be significantly larger than the ones observed for PI(3,5)P 2 . Clustering of PI(4,5)P 2 is also detected at physiological concentrations of Mg 2+ , suggesting that in cellular membranes, these molecules are constitutively driven to clustering by the high intracellular concentration of divalent cations. Importantly, it is shown that lipid membrane order is a key factor in the regulation of clustering for both PIP isoforms, with a major impact on cluster sizes. Clustered PI(4,5)P 2 and PI(3,5)P 2 are observed to present considerably higher affinity for more ordered lipid phases than the monomeric species or than PI(4)P, possibly reflecting a more general tendency of clustered lipids for insertion into ordered domains. These results support a model for the description of the lateral organization of PIPs in cellular membranes, where both divalent cation interaction and membrane order are key modulators defining the lateral organization of these lipids.

  15. Optimising the Active Muon Shield for the SHiP Experiment at CERN

    NASA Astrophysics Data System (ADS)

    Baranov, A.; Burnaev, E.; Derkach, D.; Filatov, A.; Klyuchnikov, N.; Lantwin, O.; Ratnikov, F.; Ustyuzhanin, A.; Zaitsev, A.

    2017-12-01

    The SHiP experiment is designed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. The critical challenge for this experiment is to keep the Standard Model background level negligible. In the beam dump, around 1011 muons will be produced per second. The muon rate in the spectrometer has to be reduced by at least four orders of magnitude to avoid muoninduced backgrounds. It is demonstrated that new improved active muon shield may be used to magnetically deflect the muons out of the acceptance of the spectrometer.

  16. Semiconducting cubic titanium nitride in the Th 3 P 4 structure

    DOE PAGES

    Bhadram, Venkata S.; Liu, Hanyu; Xu, Enshi; ...

    2018-01-22

    We report the discovery of a long-sought-after phase of titanium nitride with stoichiometry Ti3N4 using diamond anvil cell experiments combined with in situ high-resolution x-ray diffraction and Raman spectroscopy techniques, supported by ab initio calculations.

  17. Deployment of the P4 Truss SAW during Expedition 13 / STS-115 Joint Operations

    NASA Image and Video Library

    2006-09-15

    S115-E-06184 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m. (CDT). The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Sept. 12 and the deployment of the arrays set the stage for future expansion of the station.

  18. Deployment of the P4 Truss SAW during Expedition 13 / STS-115 Joint Operations

    NASA Image and Video Library

    2006-09-15

    S115-E-06186 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m. (CDT). The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Sept. 12 and the deployment of the arrays set the stage for future expansion of the station.

  19. P4 Truss FWD SAW during Expedition 13 and STS-115 EVA Joint Operations

    NASA Image and Video Library

    2006-09-14

    S115-E-05999 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m CDT. The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Tuesday, and the deployment of the arrays set the stage for future expansion of the station.

  20. Cooperation of p27Kip1 and p18INK4c in Progestin-Mediated Cell Cycle Arrest in T-47D Breast Cancer Cells

    PubMed Central

    Swarbrick, Alexander; Lee, Christine S. L.; Sutherland, Robert L.; Musgrove, Elizabeth A.

    2000-01-01

    The steroid hormone progesterone regulates proliferation and differentiation in the mammary gland and uterus by cell cycle phase-specific actions. The long-term effect of progestins on T-47D breast cancer cells is inhibition of cellular proliferation. This is accompanied by decreased G1 cyclin-dependent kinase (CDK) activities, redistribution of the CDK inhibitor p27Kip1 among these CDK complexes, and alterations in the elution profile of cyclin E-Cdk2 upon gel filtration chromatography, such that high-molecular-weight complexes predominate. This study aimed to determine the relative contribution of CDK inhibitors to these events. Following progestin treatment, the majority of cyclin E- and D-CDK complexes were bound to p27Kip1 and few were bound to p21Cip1. In vitro, recombinant His6-p27 could quantitatively reproduce the effects on cyclin E-Cdk2 kinase activity and the shift in molecular weight observed following progestin treatment. In contrast, cyclin D-Cdk4 was not inhibited by His6-p27 in vitro or p27Kip1 in vivo. However, an increase in the expression of the Cdk4/6 inhibitor p18INK4c and its extensive association with Cdk4 and Cdk6 were apparent following progestin treatment. Recombinant p18INK4c led to the reassortment of cyclin-CDK-CDK inhibitor complexes in vitro, with consequent decrease in cyclin E-Cdk2 activity. These results suggest a concerted model of progestin action whereby p27Kip1 and p18INK4c cooperate to inhibit cyclin E-Cdk2 and Cdk4. Since similar models have been developed for growth inhibition by transforming growth factor β and during adipogenesis, interaction between the Cip/Kip and INK4 families of inhibitors may be a common theme in physiological growth arrest and differentiation. PMID:10713180

  1. Cytochrome P450 induction by rifampicin in healthy subjects: determination using the Karolinska cocktail and the endogenous CYP3A4 marker 4beta-hydroxycholesterol.

    PubMed

    Kanebratt, K P; Diczfalusy, U; Bäckström, T; Sparve, E; Bredberg, E; Böttiger, Y; Andersson, T B; Bertilsson, L

    2008-11-01

    The Karolinska cocktail, comprising caffeine, losartan, omeprazole, and quinine, was given before and after administration of rifampicin (20, 100, or 500 mg daily) to measure induction of cytochrome P450 (P450) enzymes. Rifampicin was given for 14 days to eight healthy subjects (all of whom possessed at least one wild-type CYP2C9 and one wild-type CYP2C19 gene) in each dose group. 4beta-hydroxycholesterol was assessed as an endogenous marker of CYP3A4 induction. A fourfold induction of CYP3A4 was seen at the highest dose by both quinine:3'-hydroxyquinine and 4beta-hydroxycholesterol measurements (P < 0.001). CYP3A4 was also induced at the two lower doses of rifampicin when measured by these two markers (P < 0.01 or P < 0.001). CYP1A2, CYP2C9, and CYP2C19 were induced after 500 mg rifampicin daily (1.2-fold, P < 0.05; 1.4-fold, P < 0.05; and 4.2-fold, P < 0.01, respectively). In conclusion, we have shown that the Karolinska cocktail and 4beta-hydroxycholesterol can be used for an initial screening of the induction properties of a drug candidate.

  2. INDUCTION AND POST-TRANSCRIPTIONAL SUPPRESSION OF HEPATIC CYTOCHROME P450 1A1 BY 3,3',4,4'-TETRACHLOROBIPHENYL. (R827102)

    EPA Science Inventory

    Abstract

    <p>3,3',4,4'-Tetrachlorobiphenyl (TCB) can induce and inhibit cytochrome P450 1A1 (CYP1A1) in vertebrates. TCB may also suppress CYP1A1 protein levels, but the mechanism is unknown. This study examined transcriptional and translational aspects of hepatic ...

  3. DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo.

    PubMed

    Wallace, Lindsay M; Garwick, Sara E; Mei, Wenyan; Belayew, Alexandra; Coppee, Frederique; Ladner, Katherine J; Guttridge, Denis; Yang, Jing; Harper, Scott Q

    2011-03-01

    Facioscapulohumeral muscular dystrophy (FSHD) is associated with D4Z4 repeat contraction on human chromosome 4q35. This genetic lesion does not result in complete loss or mutation of any gene. Consequently, the pathogenic mechanisms underlying FSHD have been difficult to discern. In leading FSHD pathogenesis models, D4Z4 contractions are proposed to cause epigenetic changes, which ultimately increase expression of genes with myopathic potential. Although no gene has been conclusively linked to FSHD development, recent evidence supports a role for the D4Z4-encoded DUX4 gene in FSHD. In this study, our objective was to test the in vivo myopathic potential of DUX4. We delivered DUX4 to zebrafish and mouse muscle by transposon-mediated transgenesis and adeno-associated viral vectors, respectively. Overexpression of DUX4, which encodes a transcription factor, caused abnormalities associated with muscular dystrophy in zebrafish and mice. This toxicity required DNA binding, because a DUX4 DNA binding domain mutant produced no abnormalities. Importantly, we found the myopathic effects of DUX4 were p53 dependent, as p53 inhibition mitigated DUX4 toxicity in vitro, and muscles from p53 null mice were resistant to DUX4-induced damage. Our work demonstrates the myopathic potential of DUX4 in animal muscle. Considering previous studies showed DUX4 was elevated in FSHD patient muscles, our data support the hypothesis that DUX4 overexpression contributes to FSHD development. Moreover, we provide a p53-dependent mechanism for DUX4 toxicity that is consistent with previous studies showing p53 pathway activation in FSHD muscles. Our work justifies further investigation of DUX4 and the p53 pathway in FSHD pathogenesis. Copyright © 2010 American Neurological Association.

  4. DUX4, a Candidate Gene for Facioscapulohumeral Muscular Dystrophy, Causes p53-Dependent Myopathy In Vivo

    PubMed Central

    Wallace, Lindsay M.; Garwick, Sara E.; Mei, Wenyan; Belayew, Alexandra; Coppee, Frederique; Ladner, Katherine J.; Guttridge, Denis; Yang, Jing; Harper, Scott Q.

    2014-01-01

    Objective Facioscapulohumeral muscular dystrophy (FSHD) is associated with D4Z4 repeat contraction on human chromosome 4q35. This genetic lesion does not result in complete loss or mutation of any gene. Consequently, the pathogenic mechanisms underlying FSHD have been difficult to discern. In leading FSHD pathogenesis models, D4Z4 contractions are proposed to cause epigenetic changes, which ultimately increase expression of genes with myopathic potential. Although no gene has been conclusively linked to FSHD development, recent evidence supports a role for the D4Z4-encoded DUX4 gene in FSHD. In this study, our objective was to test the in vivo myopathic potential of DUX4. Methods We delivered DUX4 to zebrafish and mouse muscle by transposon-mediated transgenesis and adeno-associated viral vectors, respectively. Results Overexpression of DUX4, which encodes a transcription factor, caused abnormalities associated with muscular dystrophy in zebrafish and mice. This toxicity required DNA binding, because a DUX4 DNA binding domain mutant produced no abnormalities. Importantly, we found the myopathic effects of DUX4 were p53 dependent, as p53 inhibition mitigated DUX4 toxicity in vitro, and muscles from p53 null mice were resistant to DUX4-induced damage. Interpretation Our work demonstrates the myopathic potential of DUX4 in animal muscle. Considering previous studies showed DUX4 was elevated in FSHD patient muscles, our data support the hypothesis that DUX4 overexpression contributes to FSHD development. Moreover, we provide a p53-dependent mechanism for DUX4 toxicity that is consistent with previous studies showing p53 pathway activation in FSHD muscles. Our work justifies further investigation of DUX4 and the p53 pathway in FSHD pathogenesis. PMID:21446026

  5. Lanthanide ion (III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate for dual biosensing of pH with chemical exchange saturation transfer (CEST) and biosensor imaging of redundant deviation in shifts (BIRDS).

    PubMed

    Huang, Yuegao; Coman, Daniel; Ali, Meser M; Hyder, Fahmeed

    2015-01-01

    Relaxivity-based magnetic resonance of phosphonated ligands chelated with gadolinium (Gd(3+)) shows promise for pH imaging. However instead of monitoring the paramagnetic effect of lanthanide complexes on the relaxivity of water protons, biosensor (or molecular) imaging with magnetic resonance is also possible by detecting either the nonexchangeable or the exchangeable protons on the lanthanide complexes themselves. The nonexchangeable protons (e.g. -CHx, where 3 ≥ x ≥ 1) are detected using a three-dimensional chemical shift imaging method called biosensor imaging of redundant deviation in shifts (BIRDS), whereas the exchangeable protons (e.g. -OH or -NHy , where 2 ≥ y ≥ 1) are measured with chemical exchange saturation transfer (CEST) contrast. Here we tested the feasibility of BIRDS and CEST for pH imaging of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (DOTA-4AmP(8-)) chelated with thulium (Tm(3+) ) and ytterbium (Yb(3+)). BIRDS and CEST experiments show that both complexes are responsive to pH and temperature changes. Higher pH and temperature sensitivities are obtained with BIRDS for either complex when using the chemical shift difference between two proton resonances vs using the chemical shift of a single proton resonance, thereby eliminating the need to use water resonance as reference. While CEST contrast for both agents is linearly dependent on pH within a relatively large range (i.e. 6.3-7.9), much stronger CEST contrast is obtained with YbDOTA-4AmP(5-) than with TmDOTA-4AmP(5-). In addition, we demonstrate the prospect of using BIRDS to calibrate CEST as new platform for quantitative pH imaging. Copyright © 2014 John Wiley & Sons, Ltd.

  6. The role of loop ZA and Pro371 in the function of yeast Gcn5p bromodomain revealed through molecular dynamics and experiment.

    PubMed

    Pizzitutti, Francesco; Giansanti, Andrea; Ballario, Paola; Ornaghi, Prisca; Torreri, Paola; Ciccotti, Giovanni; Filetici, Patrizia

    2006-01-01

    Biological experiments were combined with molecular dynamics simulations to understand the importance of amino acidic residues present in the bromodomain of the yeast histone acetyltransferase Gcn5p. It was found that residue Pro371 plays an important role in the molecular recognition of the acetylated histone H4 tail by Gcn5p bromodomain. Crystallographic analysis of the complex showed that this residue does not directly interact with the histone substrate. It has been demonstrated that a double mutation Pro371Thr and Met372Ala in the Gcn5p bromodomain impairs chromatin remodeling activity. It is demonstrated here that, in this double mutant and in the fully deleted bromodomain strain, there is lower growth under amino acid deprivation conditions. By in vitro surface plasmon resonance (Biacore) experiments it is shown that the binding affinity of the double mutation to acetyl lysine 16 histone H4 peptide decreases. Molecular dynamics simulations were used to explain this loss in acetyl lysine-Gcn5p bromodomain affinity, in the double mutant. By comparing nanosecond molecular dynamics trajectories of the native as well as the single and doubly mutated bromodomain, it is concluded that the presence of Pro371 is important to the functionality of the Gcn5p bromodomain. In the simulation a point mutation involving this highly conserved residue induced an increase in the flexibility of the ZA loop, which in turn modulated the exposure of the binding pocket to the acetyl lysine. The combined double mutations (Pro371Thr-Met372Ala) not only markedly perturb the motion of the ZA loop but also destabilize the entire structure of the bromodomain. Copyright 2005 John Wiley & Sons, Ltd.

  7. Cadmium resistance mechanism in Escherichia coli P4 and its potential use to bioremediate environmental cadmium.

    PubMed

    Khan, Zaman; Nisar, Muhammad Atif; Hussain, Syed Zajif; Arshad, Muhammad Nauman; Rehman, Abdul

    2015-12-01

    A cadmium-resistant bacterium was isolated from industrial wastewater and identified as Escherichia coli (dubbed as P4) on the basis of morphological, biochemical tests and 16S rRNA ribotyping. It showed optimum growth at 30 °C and pH 7. E. coli P4 found to resist Cd(+2) (10.6 mM) as well as Zn(+2) (4.4 mM), Pb(+2) (17 mM), Cu(+2) (3.5 mM), Cr(+6) (4.4 mM), As(+2) (10.6 mM), and Hg(+2) (0.53 mM). It could remove 18.8, 37, and 56 % Cd(+2) from aqueous medium after 48, 96, and 144 h, respectively. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and Energy-dispersive X-ray (EDX) analysis also confirmed the biosorption of Cd(+2) by E. coli P4. However, temperature and pH were found to be the most critical factors in biosorption of Cd(+2) by E. coli P4. Cd(+2) stress altered E. coli P4 cell physiology analyzed by measuring glutathione (GSH) and non-protein thiol (cysteine) levels which were increased up to 130 and 48 %, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) showed alteration in the expression levels of ftsZ, mutS, clpB, ef-tu, and dnaK genes in the presence of Cd(+2). Total protein profiles of E. coli P4 in the absence and presence of Cd(+2) were compared by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), which showed remarkable difference in the banding pattern. czcB gene, a component of czcCBA operon, was amplified from genomic DNA which suggested the chromosomal-borne Cd(+2) resistance in E. coli P4. Furthermore, it harbors smtAB gene which plays a significant role in Cd(+2) resistance.

  8. The retinoblastoma protein/p16 INK4A pathway but not p53 is disrupted by human papillomavirus in penile squamous cell carcinoma.

    PubMed

    Stankiewicz, Elzbieta; Prowse, David M; Ktori, Elena; Cuzick, Jack; Ambroisine, Laurence; Zhang, Xiaoxi; Kudahetti, Sakunthala; Watkin, Nicholas; Corbishley, Catherine; Berney, Daniel M

    2011-02-01

    The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood. Human papillomavirus (HPV) may be involved in carcinogenesis, but few studies have compared cell-cycle protein expression in HPV positive and negative cancers. The aim was to determine the extent of HPV infection in different histological subtypes of PSCC and its impact on the expression of key cell-cycle proteins: p53, p21, p16(INK4A) and retinoblastoma (RB) protein. One hundred and forty-eight PSCC samples were examined immunohistochemically for RB, p16(INK4A) , p53 and p21 protein expression. One hundred and two cases were typed for HPV by PCR. HPV DNA was detected in 56% of tumours, with HPV16 present in 81%. Basaloid tumours were related strongly to HPV infection (10 of 13), while verrucous were not (three of 13). Fifty-nine per cent (38 of 64) of usual type SCCs had HPV infection. RB protein correlated negatively (P<0.0001) and p16(INK4A) (P<0.0001) and p21 (P=0.0002) correlated positively with HPV infection. p53 did not correlate with HPV infection. HPV infection is present in more than half of penile cancers and it is responsible for RB pathway disruption. However, no link between HPV and p53 immunodetection was found. Only basaloid and half of usual-type PSSCs correlate with HPV infection, confirming possible separate aetiologies for those tumours. © 2011 Blackwell Publishing Limited.

  9. [Dynamics of upland field P pool under a long-term application of fertilizer P in yellow soil area and their effects on P concentration in runoff].

    PubMed

    Liu, Fang; Huang, Changyong; He, Tengbin; Qian, Xiaogang; Liu, Yuansheng; Luo, Haibo

    2003-02-01

    Studies on the dynamics of upland field P pool under a long-term application of fertilizer P in yellow soil area and their effects on P concentration in runoff showed that the contents of A1-P, Fe-P and Ca-P in soil cultivated layer increased greatly, and Olsen-P and algae-available P also accumulated obviously. The correlation coefficients of algae-available P content in the high-P soils (Olsen-P > 25 mg.kg-1) with the quantities of A1-P, Fe-P and Ca-P were 0.859**, 0.903** and 0.650*, respectively, of which, Fe-P was the most important. By a 30-min rainfall simulation experiment with a constant rainfall rate of 63.2 mm.h-1, the concentrations of dissolved reactive P and bio-available P in runoff from low-P upland fields (Olsen-P 4.62-15.9 mg.kg-1) were 2.81-4.17 micrograms.L-1 and 0.723-0.876 mg.L-1, respectively, whereas their concentrations in runoff from high-P upland fields (Olsen-P 29.4-59.2 mg.kg-1) were 0.026-0.714 mg.L-1 and 0.996-1.281 mg.L-1, respectively. Therefore, runoff from high-P upland fields could accelerate water eutrophication.

  10. Tumor suppressor p16 INK4a: Downregulation of galectin-3, an endogenous competitor of the pro-anoikis effector galectin-1, in a pancreatic carcinoma model.

    PubMed

    Sanchez-Ruderisch, Hugo; Fischer, Christian; Detjen, Katharina M; Welzel, Martina; Wimmel, Anja; Manning, Joachim C; André, Sabine; Gabius, Hans-Joachim

    2010-09-01

    The tumor suppressor p16(INK4a) has functions beyond cell-cycle control via cyclin-dependent kinases. A coordinated remodeling of N- and O-glycosylation, and an increase in the presentation of the endogenous lectin galectin-1 sensing these changes on the surface of p16(INK4a)-expressing pancreatic carcinoma cells (Capan-1), lead to potent pro-anoikis signals. We show that the p16(INK4a)-dependent impact on growth-regulatory lectins is not limited to galectin-1, but also concerns galectin-3. By monitoring its expression in relation to p16(INK4a) status, as well as running anoikis assays with galectin-3 and cell transfectants with up- or downregulated lectin expression, a negative correlation between anoikis and the presence of this lectin was established. Nuclear run-off and northern blotting experiments revealed an effect of the presence of p16(INK4a) on steady-state levels of galectin-3-specific mRNA that differed from decreasing the transcriptional rate. On the cell surface, galectin-3 interferes with galectin-1, which initiates signaling toward its pro-anoikis activity via caspase-8 activation. The detected opposite effects of p16(INK4a) at the levels of growth-regulatory galectins-1 and -3 shift the status markedly towards the galectin-1-dependent pro-anoikis activity. A previously undescribed orchestrated fine-tuning of this effector system by a tumor suppressor is discovered.

  11. Performance of in silico tools for the evaluation of p16INK4a (CDKN2A) variants in CAGI.

    PubMed

    Carraro, Marco; Minervini, Giovanni; Giollo, Manuel; Bromberg, Yana; Capriotti, Emidio; Casadio, Rita; Dunbrack, Roland; Elefanti, Lisa; Fariselli, Pietro; Ferrari, Carlo; Gough, Julian; Katsonis, Panagiotis; Leonardi, Emanuela; Lichtarge, Olivier; Menin, Chiara; Martelli, Pier Luigi; Niroula, Abhishek; Pal, Lipika R; Repo, Susanna; Scaini, Maria Chiara; Vihinen, Mauno; Wei, Qiong; Xu, Qifang; Yang, Yuedong; Yin, Yizhou; Zaucha, Jan; Zhao, Huiying; Zhou, Yaoqi; Brenner, Steven E; Moult, John; Tosatto, Silvio C E

    2017-09-01

    Correct phenotypic interpretation of variants of unknown significance for cancer-associated genes is a diagnostic challenge as genetic screenings gain in popularity in the next-generation sequencing era. The Critical Assessment of Genome Interpretation (CAGI) experiment aims to test and define the state of the art of genotype-phenotype interpretation. Here, we present the assessment of the CAGI p16INK4a challenge. Participants were asked to predict the effect on cellular proliferation of 10 variants for the p16INK4a tumor suppressor, a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene. Twenty-two pathogenicity predictors were assessed with a variety of accuracy measures for reliability in a medical context. Different assessment measures were combined in an overall ranking to provide more robust results. The R scripts used for assessment are publicly available from a GitHub repository for future use in similar assessment exercises. Despite a limited test-set size, our findings show a variety of results, with some methods performing significantly better. Methods combining different strategies frequently outperform simpler approaches. The best predictor, Yang&Zhou lab, uses a machine learning method combining an empirical energy function measuring protein stability with an evolutionary conservation term. The p16INK4a challenge highlights how subtle structural effects can neutralize otherwise deleterious variants. © 2017 Wiley Periodicals, Inc.

  12. Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition

    PubMed Central

    Naruse, Mie; Ono, Ryuichi; Irie, Masahito; Nakamura, Kenji; Furuse, Tamio; Hino, Toshiaki; Oda, Kanako; Kashimura, Misho; Yamada, Ikuko; Wakana, Shigeharu; Yokoyama, Minesuke; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2014-01-01

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function. PMID:25468940

  13. Remedial Investigations Report, Phase 2. Volume 4. Appendices Sites P11/P13 and A12/P36/P37, Fort Devens Sudbury Training Annex, Maynard, Massachusetts

    DTIC Science & Technology

    1995-12-01

    Geotechnical Data D Geophysical Surveys E Analysis of QA/QC Program F Aquifer Hydraulic Characterization (Slug Testing) G Groundwater Model Report H...M " f ; Soil/Rock ~ Dataii~ 2!Desc~lpliOn ccl - -GR OUND SURFACE- -~~ MMJrb OMOE U)IF ’G gm~ * t -iG O p& 11 i 1 ’ w //* I M E - F .51"’/j H5As o4 2-e...o fS A D 11tL IN SNE,7f ’(;v ,* , F * It~ .-. 4 1I4O WLD ~*’h4,Ft , T6.r,17,L ’DIULLe8ING NOTa 4 14.6@AO 0w- IUL W 33s - reyce pae A-, 7 1= amd n 01r0r

  14. Resolution of the diadenosine 5',5"'-P1,P4-tetraphosphate binding subunit from a multiprotein form of HeLa cell DNA polymerase alpha.

    PubMed Central

    Baril, E; Bonin, P; Burstein, D; Mara, K; Zamecnik, P

    1983-01-01

    A diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) binding subunit has been resolved from a high molecular weight (640,000) multiprotein form of DNA polymerase alpha [deoxynucleoside triphosphate:DNA nucleotidyltransferase (DNA-directed), EC 2.7.7.7] from HeLa cells [DNA polymerase alpha 2 of Lamothe, P., Baril, B., Chi, A., Lee, L. & Baril, E. (1981) Proc. Natl. Acad. Sci. USA 78, 4723-4727]. The Ap4A binding activity copurifies with the DNA polymerizing activity during the course of purification. Hydrophobic chromatography on butylagarose resolves the Ap4A binding activity from the DNA polymerase. The Ap4A binding activity is protein in nature since the binding of Ap4A is abolished by treatment of the isolated binding activity with proteinase K but is insensitive to treatment with DNase or RNase. The molecular weight of the Ap4A binding protein, as determined by polyacrylamide gel electrophoresis under nondenaturing conditions or by NaDodSO4/polyacrylamide gel electrophoresis after photoaffinity labeling of the protein with [32P]Ap4A is 92,000 or 47,000. The binding activity of this protein is highly specific for Ap4A. Images PMID:6576366

  15. Simulations in support of the T4B experiment

    NASA Astrophysics Data System (ADS)

    Qerushi, Artan; Ross, Patrick; Lohff, Chriss; Raymond, Anthony; Montecalvo, Niccolo

    2017-10-01

    Simulations in support of the T4B experiment are presented. These include a Grad-Shafranov equilibrium solver and equilibrium reconstruction from flux-loop measurements, collision radiative models for plasma spectroscopy (determination of electron density and temperature from line ratios) and fast ion test particle codes for neutral beam - plasma coupling. ©2017 Lockheed Martin Corporation. All Rights Reserved.

  16. Identification of the 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole inner-shell satellite line in the Ar16+ K-shell x-ray spectrum

    NASA Astrophysics Data System (ADS)

    Beiersdorfer, P.; Bitter, M.; Hey, D.; Reed, K. J.

    2002-09-01

    We have identified the dipole-forbidden 1s2s2p 4P5/2-->1s22s 2S1/2 transition in lithiumlike Ar15+ in high-resolution K-shell x-ray emission spectra recorded at the Livermore EBIT-II electron-beam ion trap and the Princeton National Spherical Tokamak Experiment. Unlike other Ar15+ satellite lines, which can be excited by dielectronic recombination, the line is exclusively excited by electron-impact excitation. Its predicted radiative rate is comparable to that of the well-known 1s2p 3P1-->1s2 1S0 magnetic quadrupole transition in heliumlike Ar16+. As a result, it can also only be observed in low-density plasma. We present calculations of the electron-impact excitation cross sections of the innershell excited Ar15+ satellite lines, including the magnetic sublevels needed for calculating the linear line polarization. We compare these calculations to the relative magnitudes of the observed 1s2s2p-->1s22s transitions and find good agreement, confirming the identification of the lithiumlike 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole line.

  17. Microsatellite DNA assays reveal an allelic imbalance in p16(Ink4), GALT, p53, and APOA2 loci in patients with endometriosis.

    PubMed

    Goumenou, A G; Arvanitis, D A; Matalliotakis, I M; Koumantakis, E E; Spandidos, D A

    2001-01-01

    To detect allelic imbalance on specific genetic loci occurring in endometriosis. Microsatellite analysis. Paraffin-embedded tissues histologically confirmed as endometriotic or normal endometrium. Premenopausal women undergoing laparoscopy for suspected endometriosis. Laparoscopic excision of specimens. Allelic imbalance and alterations of intensity of microsatellite alleles. Five of 17 microsatellite DNA markers (29.4%) showed allelic imbalance. Eight samples (36.4%) showed allelic imbalance in at least one locus. Loci 9p21, 1q21, and 17p13.1 exhibited imbalance in 27.3%, 4.5%, and 4.5%, respectively. A 3-fold increase of the fractional allelic loss was observed from disease stage II to III and IV, whereas only 1.3-fold was found between patients of 41-50 and 20-40 years. We found that loss of heterozygosity on p16(Ink4), GALT, and p53, as well as on APOA2, a region frequently lost in ovarian cancer, occurs in endometriosis, even in stage II of the disease. The occurrence of such genomic alterations may represent important events in the development of endometriosis. The 9p21 locus may contain a gene associated with the pathogenesis of the disease, and therefore its loss may be a prognostic marker of the disease.

  18. Outcomes of a Seven Practice Pilot in a Pay For Performance (P4P)-Based Program in Pennsylvania

    PubMed Central

    Johnson, Rhonda M.; Johnson, Twyla; Zimmerman, Sarah D.; Marsh, Gary M.; Garcia-Dominic, Oralia

    2014-01-01

    Objectives To examine how a targeted six-month interventions impacted Best Practice/Patient Outcomes for minority patients receiving primary care in physician practices participating in a pay-for-performance (P4P) program. Methods P4P Practices were invited to participate in a pilot intervention study designed to improve care for minority patients with hypertension, diabetes or pediatric asthma. Patient medical records were reviewed to assess how the interventions impacted (n=7 practices): Body mass index, diet and exercise, smoking, compliance with visits as recommended, blood pressure, sodium intake and weight management counseling, medication reconciliation, HbA1c testing, annual lipid profile, and anti-inflammatory medications. Results Significant improvements in various clinical quality measures were observed in all seven practices. Of the 19 specified interventions, 13 were statistically significant at α=0.05 level and 14 met the target proportion. This suggests that the best practice intervention had a significant impact on some of the health care processes in the physician practices. Conclusions The most impactful interventions were those related to face-to-face educational discussions, patient medical chart documentations rather than those pertaining to medication adherence. Improvements in measuring reporting and recording of data at post-intervention were also observed. PMID:25893158

  19. The cytochrome P450 CYP6P4 is responsible for the high pyrethroid resistance in knockdown resistance-free Anopheles arabiensis

    PubMed Central

    Ibrahim, Sulaiman S.; Riveron, Jacob M.; Stott, Robert; Irving, Helen; Wondji, Charles S.

    2016-01-01

    Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, resistance in major vectors such as Anopheles arabiensis is posing a serious challenge to the success of malaria control. Herein, we elucidated the molecular and biochemical basis of pyrethroid resistance in a knockdown resistance-free Anopheles arabiensis population from Chad, Central Africa. Using heterologous expression of P450s in Escherichia coli coupled with metabolism assays we established that the over-expressed P450 CYP6P4, located in the major pyrethroid resistance (rp1) quantitative trait locus (QTL), is responsible for resistance to Type I and Type II pyrethroid insecticides, with the exception of deltamethrin, in correlation with field resistance profile. However, CYP6P4 exhibited no metabolic activity towards non-pyrethroid insecticides, including DDT, bendiocarb, propoxur and malathion. Combining fluorescent probes inhibition assays with molecular docking simulation, we established that CYP6P4 can bind deltamethrin but cannot metabolise it. This is possibly due to steric hindrance because of the large vdW radius of bromine atoms of the dihalovinyl group of deltamethrin which docks into the heme catalytic centre. The establishment of CYP6P4 as a partial pyrethroid resistance gene explained the observed field resistance to permethrin, and its inability to metabolise deltamethrin probably explained the high mortality from deltamethrin exposure in the field populations of this Sudano-Sahelian An. arabiensis. These findings describe the heterogeneity in resistance towards insecticides, even from the same class, highlighting the need to thoroughly understand the molecular basis of resistance before implementing resistance management/control tools. PMID:26548743

  20. Relevance of P-glycoprotein on CXCR4+ B cells to organ manifestation in highly active rheumatoid arthritis.

    PubMed

    Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Kawabe, Akio; Tanaka, Yoshiya

    2018-03-01

    In rheumatoid arthritis (RA), P-glycoprotein (P-gp) expression on activated B cells is associated with active efflux of intracellular drugs, resulting in drug resistance. CXCR4 is associated with migration of B cells. This study was designed to elucidate the relevance of P-gp expression on CXCR4 + B cells to clinical manifestations in refractory RA. CD19 + B cells were analyzed using flow cytometry and immunohistochemistry. P-gp was highly expressed especially on CXCR4 + CD19 + B cells in RA. The proportion of P-gp-expressing CXCR4 + B cells correlated with disease activity, estimated by Simplified Disease Activity Index (SDAI), and showed marked expansion in RA patients with high SDAI and extra-articular involvement. In highly active RA, massive infiltration of P-gp + CXCR4 + CD19 + B cells was noted in CXCL12-expressing inflammatory lesions of RA synovitis and RA-associated interstitial pneumonitis. In RA patient with active extra-articular involvement, intracellular dexamethasone level (IDL) in lymphocytes diminished with expansion of P-gp + CXCR4 + CD19 + B cells. Adalimumab reduced P-gp + CXCR4 + CD19 + B cells, increased IDL in lymphocytes, and improved the clinical manifestation and allowed tapering of concomitant medications. Expansion of P-gp + CXCR4 + B cells seems to be associated with drug resistance, disease activity and progressive destructive arthritis with extra-articular involvement in RA.

  1. 4. Historic American Buildings Survey, John P. O'Neill, Photographer February ...

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

    4. Historic American Buildings Survey, John P. O'Neill, Photographer February 20, 1937 DETAIL OF DOOR ON NORTH SIDE NEAR WEST END. - Mormon Tabernacle, Temple Square, Salt Lake City, Salt Lake County, UT

  2. Genome expression analysis in yeast reveals novel transcriptional regulation by inositol and choline and new regulatory functions for Opi1p, Ino2p, and Ino4p.

    PubMed

    Santiago, Teresa C; Mamoun, Choukri Ben

    2003-10-03

    In Saccharomyces cerevisiae, genes encoding phospholipid-synthesizing enzymes are regulated by inositol and choline (IC). The current model suggests that when these precursors become limiting, the transcriptional complex Ino2p-Ino4p activates the expression of these genes, whereas repression requires Opi1p and occurs when IC are available. In this study, microarray-based expression analysis was performed to assess the global transcriptional response to IC in a wild-type strain and in the opi1delta, ino2delta, and ino4delta null mutant strains. Fifty genes were either activated or repressed by IC in the wild-type strain, including three already known IC-repressed genes. We demonstrated that the IC response was not limited to genes involved in membrane biogenesis, but encompassed various metabolic pathways such as biotin synthesis, one-carbon compound metabolism, nitrogen-containing compound transport and degradation, cell wall organization and biogenesis, and acetyl-CoA metabolism. The expression of a large number of IC-regulated genes did not change in the opi1delta, ino2delta, and ino4delta strains, thus implicating new regulatory elements in the IC response. Our studies revealed that Opi1p, Ino2p, and Ino4p have dual regulatory activities, acting in both positive and negative transcriptional regulation of a large number of genes, most of which are not regulated by IC and only a subset of which is involved in membrane biogenesis. These data provide the first global response profile of yeast to IC and reveal novel regulatory mechanisms by these precursors.

  3. JENDL-4.0/HE Benchmark Test with Concrete and Iron Shielding Experiments at JAEA/TIARA

    NASA Astrophysics Data System (ADS)

    Konno, Chikara; Matsuda, Norihiro; Kwon, Saerom; Ohta, Masayuki; Sato, Satoshi

    2017-09-01

    As a benchmark test of JENDL-4.0/HE released in 2015, we have analyzed the concrete and iron shielding experiments with the quasi mono-energetic 40 and 65 MeV neutron sources at TIARA in JAEA by using MCNP5 and ACE files processed from JENDL-4.0/HE with NJOY2012. As a result, it was found out that the calculation results with JENDL-4.0/HE agreed with the measured ones in the concrete experiment well, while they underestimated the measured ones in the iron experiment with 65 MeV neutrons more for the thicker assemblies. We examined the 56Fe data of JENDL-4.0/HE in detail and it was considered that the larger non-elastic scattering cross sections of 56Fe caused the underestimation in the calculation with JENDL-4.0/HE for the iron experiment with 65 MeV neutrons.

  4. PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels

    PubMed Central

    Itsuki, Kyohei; Imai, Yuko; Hase, Hideharu; Okamura, Yasushi; Inoue, Ryuji

    2014-01-01

    Transient receptor potential classical (or canonical) (TRPC)3, TRPC6, and TRPC7 are a subfamily of TRPC channels activated by diacylglycerol (DAG) produced through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) by phospholipase C (PLC). PI(4,5)P2 depletion by a heterologously expressed phosphatase inhibits TRPC3, TRPC6, and TRPC7 activity independently of DAG; however, the physiological role of PI(4,5)P2 reduction on channel activity remains unclear. We used Förster resonance energy transfer (FRET) to measure PI(4,5)P2 or DAG dynamics concurrently with TRPC6 or TRPC7 currents after agonist stimulation of receptors that couple to Gq and thereby activate PLC. Measurements made at different levels of receptor activation revealed a correlation between the kinetics of PI(4,5)P2 reduction and those of receptor-operated TRPC6 and TRPC7 current activation and inactivation. In contrast, DAG production correlated with channel activation but not inactivation; moreover, the time course of channel inactivation was unchanged in protein kinase C–insensitive mutants. These results suggest that inactivation of receptor-operated TRPC currents is primarily mediated by the dissociation of PI(4,5)P2. We determined the functional dissociation constant of PI(4,5)P2 to TRPC channels using FRET of the PLCδ Pleckstrin homology domain (PHd), which binds PI(4,5)P2, and used this constant to fit our experimental data to a model in which channel gating is controlled by PI(4,5)P2 and DAG. This model predicted similar FRET dynamics of the PHd to measured FRET in either human embryonic kidney cells or smooth muscle cells, whereas a model lacking PI(4,5)P2 regulation failed to reproduce the experimental data, confirming the inhibitory role of PI(4,5)P2 depletion on TRPC currents. Our model also explains various PLC-dependent characteristics of channel activity, including limitation of maximum open probability, shortening of the peak time, and the bell-shaped response of

  5. Co3O4/CoP composite hollow polyhedron: A superior catalyst with dramatic efficiency and stability for the room temperature reduction of 4-nitrophenol

    NASA Astrophysics Data System (ADS)

    Liu, Xing; Li, Xiangqing; Qin, Lixia; Mu, Jin; Kang, Shi-Zhao

    2018-03-01

    In the present work, Co3O4/CoP composite hollow polyhedrons were prepared and characterized with X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and N2 adsorption-desorption isotherms. Then, the catalytic activity of the as-prepared Co3O4/CoP hollow polyhedrons was evaluated for the borohydride-assisted reduction of 4-nitrophenol at room temperature. The results indicate that the as-prepared Co3O4/CoP hollow polyhedrons are an efficient recyclable catalyst for the reduction of 4-nitrophenol. When the 4-nitrophenol initial concentration is 1.0 × 10-4 mol L-1 (100 mL), almost 100% 4-nitrophenol can be reduced within 3 min in the presence of the Co3O4/CoP hollow polyhedrons. The apparent rate constant of the 4-nitrophenol reduction is 1.61 min-1 at room temperature, and the activity factor is about 5.37 × 104 mL min-1 g-1, which is almost two times higher than that over Ag nanoparticles. Finally, the catalytic mechanism was preliminarily discussed. It is found that CoP plays an important role in the catalytic process. Here, CoP serves as active sites, which leads to efficient formation of hydrogen atoms from BH4- and fast electron transfer.

  6. Understanding and controlling morphology formation in Langmuir-Blodgett block copolymer films using PS-P4VP and PS-P4VP/PDP.

    PubMed

    Perepichka, Iryna I; Lu, Qing; Badia, Antonella; Bazuin, C Geraldine

    2013-04-09

    This contribution offers a comprehensive understanding of the factors that govern the morphologies of Langmuir-Blodgett (LB) monolayers of amphiphilic diblock copolymers (BCs). This is achieved by a detailed investigation of a wide range of polystyrene-poly(4-vinyl pyridine) (PS-P4VP) block copolymers, in contrast to much more limited ranges in previous studies. Parameters that are varied include the block ratios (mainly for similar total molecular weights, occasionally other total molecular weights), the presence or not of 3-n-pentadecylphenol (PDP, usually equimolar with VP, with which it hydrogen bonds), the spreading solution concentration ("low" and "high"), and the LB technique (standard vs "solvent-assisted"). Our observations are compared with previously published results on other amphiphilic diblock copolymers, which had given rise to contradictory interpretations of morphology formation. Based on the accumulated results, we re-establish early literature conclusions that three main categories of LB block copolymer morphologies are obtained depending on the block ratio, termed planar, strand, and dot regimes. The block composition boundaries in terms of mol % block content are shown to be similar for all BCs having alkyl chain substituents on the hydrophilic block (such as PS-P4VP/PDP) and are shifted to higher values for BCs with no alkyl chain substituents (such as PS-P4VP). This is attributed to the higher surface area per repeat unit of the hydrophilic block monolayer on the water surface for the former, as supported by the onset and limiting areas of the Langmuir isotherms for the BCs in the dot regime. 2D phase diagrams are discussed in terms of relative effective surface areas of the two blocks. We identify and discuss how kinetic effects on morphology formation, which have been highlighted in more recent literature, are superposed on the compositional effects. The kinetic effects are shown to depend on the morphology regime, most strongly

  7. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4.

    PubMed

    Cheng, Dantong; Zhao, Senlin; Tang, Huamei; Zhang, Dongyuan; Sun, Hongcheng; Yu, Fudong; Jiang, Weiliang; Yue, Ben; Wang, Jingtao; Zhang, Meng; Yu, Yang; Liu, Xisheng; Sun, Xiaofeng; Zhou, Zongguang; Qin, Xuebin; Zhang, Xin; Yan, Dongwang; Wen, Yugang; Peng, Zhihai

    2016-07-19

    Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. miR-20a-5p negatively regulated Smad4 by directly targeting its 3'UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients' clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.

  8. Nqrs Data for C24H76BLiN12O4P4 (Subst. No. 1593)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume B 'Substances Containing C10H16 … Zn' of Volume 48 'Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains an extract of Section '3.2 Data tables' of the Chapter '3 Nuclear quadrupole resonance data' providing the NQRS data for C24H76BLiN12O4P4 (Subst. No. 1593)

  9. Magnetoelectricity in CoFe2O4 nanocrystal-P(VDF-HFP) thin films

    PubMed Central

    2013-01-01

    Transition metal ferrites such as CoFe2O4, possessing a large magnetostriction coefficient and high Curie temperature (Tc > 600 K), are excellent candidates for creating magnetic order at the nanoscale and provide a pathway to the fabrication of uniform particle-matrix films with optimized potential for magnetoelectric coupling. Here, a series of 0–3 type nanocomposite thin films composed of ferrimagnetic cobalt ferrite nanocrystals (8 to 18 nm) and a ferroelectric/piezoelectric polymer poly(vinylidene fluoride-co-hexafluoropropene), P(VDF-HFP), were prepared by multiple spin coating and cast coating over a thickness range of 200 nm to 1.6 μm. We describe the synthesis and structural characterization of the nanocrystals and composite films by XRD, TEM, HRTEM, STEM, and SEM, as well as dielectric and magnetic properties, in order to identify evidence of cooperative interactions between the two phases. The CoFe2O4 polymer nanocomposite thin films exhibit composition-dependent effective permittivity, loss tangent, and specific saturation magnetization (Ms). An enhancement of the effective permittivity and saturation magnetization of the CoFe2O4-P(VDF-HFP) films was observed and directly compared with CoFe2O4-polyvinylpyrrolidone, a non-ferroelectric polymer-based nanocomposite prepared by the same method. The comparison provided evidence for the observation of a magnetoelectric effect in the case of CoFe2O4-P(VDF-HFP), attributed to a magnetostrictive/piezoelectric interaction. An enhancement of Ms up to +20.7% was observed at room temperature in the case of the 10 wt.% CoFe2O4-P(VDF-HFP) sample. PMID:24004499

  10. Imidazole as a pH Probe: An NMR Experiment for the General Chemistry Laboratory

    ERIC Educational Resources Information Center

    Hagan, William J., Jr.; Edie, Dennis L.; Cooley, Linda B.

    2007-01-01

    The analysis describes an NMR experiment for the general chemistry laboratory, which employs an unknown imidazole solution to measure the pH values. The described mechanism can also be used for measuring the acidity within the isolated cells.

  11. SPRUCE Deep Peat Microbial Diversity, CO2 and CH4 Production in Response to Nutrient, Temperature, and pH Treatments during Incubation Studies.

    DOE Data Explorer

    A., Kluber Laurel [Oak Ridge National Laboratory, U.S. Department of Energy, Oak Ridge, Tennessee, U.S.A.; Allen, Samantha A. [Oak Ridge National Laboratory, U.S. Department of Energy, Oak Ridge, Tennessee, U.S.A.; Hendershot, Nicholas [Oak Ridge National Laboratory, U.S. Department of Energy, Oak Ridge, Tennessee, U.S.A.; Hanson, Paul J. [Oak Ridge National Laboratory, U.S. Department of Energy, Oak Ridge, Tennessee, U.S.A.; Schadt, Christopher W. [Oak Ridge National Laboratory, U.S. Department of Energy, Oak Ridge, Tennessee, U.S.A.

    2014-09-01

    This data set contains the results of a microcosm incubation study on deep peat collected from the SPRUCE experimental site in the S1 Bog in September 2014. Microcosms were monitored for CO2 and CH4 production, and microbial community dynamics were assessed using qPCR and amplicon sequencing.The experiment was designed with a full factorial design with elevated temperature, nitrogen (N), (P), and pH treatments was used with samples from each transect serving replicates. In all, 96 microcosms were constructed to account for the 16 treatment combinations (N x P x pH x temperature), 2 time points, and 3 replicates. Temperature treatments were 6 °C, to mimic the SPRUCE ambient plot temperatures, and 15 °C to mimic the SPRUCE +9 °C treatment.

  12. When the C in C P does not matter: Anatomy of order-4 C P eigenstates and their Yukawa interactions

    NASA Astrophysics Data System (ADS)

    Aranda, Alfredo; Ivanov, Igor P.; Jiménez, Enrique

    2017-03-01

    We explore the origin and Yukawa interactions of the scalars with peculiar C P properties which were recently found in a multi-Higgs model based on an order-4 C P symmetry. We relate the existence of such scalars to the enhanced freedom of defining C P , even beyond the well-known generalized C P symmetries, which arises in models with several zero-charge scalar fields. We also show that despite possessing exotic C P quantum numbers, these scalars do not have to be inert: they can have C P -conserving Yukawa interactions provided the C P acts on fermions by also mixing generations. This paper focuses on formal aspects—exposed in a pedagogical manner—and includes a brief discussion of possible phenomenological consequences.

  13. The cytochrome P450 CYP6P4 is responsible for the high pyrethroid resistance in knockdown resistance-free Anopheles arabiensis.

    PubMed

    Ibrahim, Sulaiman S; Riveron, Jacob M; Stott, Robert; Irving, Helen; Wondji, Charles S

    2016-01-01

    Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, resistance in major vectors such as Anopheles arabiensis is posing a serious challenge to the success of malaria control. Herein, we elucidated the molecular and biochemical basis of pyrethroid resistance in a knockdown resistance-free Anopheles arabiensis population from Chad, Central Africa. Using heterologous expression of P450s in Escherichia coli coupled with metabolism assays we established that the over-expressed P450 CYP6P4, located in the major pyrethroid resistance (rp1) quantitative trait locus (QTL), is responsible for resistance to Type I and Type II pyrethroid insecticides, with the exception of deltamethrin, in correlation with field resistance profile. However, CYP6P4 exhibited no metabolic activity towards non-pyrethroid insecticides, including DDT, bendiocarb, propoxur and malathion. Combining fluorescent probes inhibition assays with molecular docking simulation, we established that CYP6P4 can bind deltamethrin but cannot metabolise it. This is possibly due to steric hindrance because of the large vdW radius of bromine atoms of the dihalovinyl group of deltamethrin which docks into the heme catalytic centre. The establishment of CYP6P4 as a partial pyrethroid resistance gene explained the observed field resistance to permethrin, and its inability to metabolise deltamethrin probably explained the high mortality from deltamethrin exposure in the field populations of this Sudano-Sahelian An. arabiensis. These findings describe the heterogeneity in resistance towards insecticides, even from the same class, highlighting the need to thoroughly understand the molecular basis of resistance before implementing resistance management/control tools. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Homeostatic Regulation of the PI(4,5)P2-Ca2+ Signaling System at ER-PM Junctions

    PubMed Central

    Chang, Chi-Lun; Liou, Jen

    2016-01-01

    The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca2+ signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca2+ from the endoplasmic reticulum (ER) store to the cytosol to activate Ca2+-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca2+ must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca2+. Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca2+ influx across the PM is required to refill the ER Ca2+ store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca2+ signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca2+ signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca2+ signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occurs, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca2+ signaling, including the ER Ca2+ sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This review is part of a Special Issue entitled The Cellular Lipid Landscape. PMID:26924250

  15. Conversion of 2-chloro-cis,cis-muconate and its metabolites 2-chloro- and 5-chloromuconolactone by chloromuconate cycloisomerases of pJP4 and pAC27.

    PubMed Central

    Vollmer, M D; Schlömann, M

    1995-01-01

    2-Chloro-cis,cis-muconate, the product of ortho-cleavage of 3-chlorocatechol, was converted by purified preparations of the pJP4- and pAC27-encoded chloromuconate cycloisomerases (EC 5.5.1.7) to trans-dienelactone (trans-4-carboxymethylenebut-2-en-4-olide). The same compound was also formed when (+)-2-chloro- and (+)-5-chloromuconolactone were substrates of these enzyme preparations. Thus, the pJP4- and pAC27-encoded chloromuconate cycloisomerases are able to catalyze chloride elimination from (+)-5-chloromuconolactone. The ability to convert (+)-2-chloromuconolactone differentiates these enzymes from other groups of cycloisomerases. PMID:7751312

  16. HTV-4 approach

    NASA Image and Video Library

    2013-08-09

    ISS036-E-030064 (9 Aug. 2013) --- The unpiloted Japanese "Kounotori" H2 Transfer Vehicle-4 (HTV-4) approaches the International Space Station. The HTV, a 33-foot-long, 13-foot-diameter unmanned cargo transfer spacecraft, is delivering 3.6 tons of science experiments, equipment and supplies to the orbiting complex. HTV-4 launched from the Tanegashima Space Center in southern Japan on Aug.3 at 3:48 p.m. (Aug. 4 at 4:48 a.m., Japan time).

  17. HTV-4 approach

    NASA Image and Video Library

    2013-08-09

    ISS036-E-029969 (9 Aug. 2013) --- The unpiloted Japanese "Kounotori" H2 Transfer Vehicle-4 (HTV-4) approaches the International Space Station. The HTV, a 33-foot-long, 13-foot-diameter unmanned cargo transfer spacecraft, is delivering 3.6 tons of science experiments, equipment and supplies to the orbiting complex. HTV-4 launched from the Tanegashima Space Center in southern Japan on Aug.3 at 3:48 p.m. (Aug. 4 at 4:48 a.m., Japan time).

  18. HTV-4 approach

    NASA Image and Video Library

    2013-08-09

    ISS036-E-029963 (9 Aug. 2013) --- The unpiloted Japanese "Kounotori" H2 Transfer Vehicle-4 (HTV-4) approaches the International Space Station. The HTV, a 33-foot-long, 13-foot-diameter unmanned cargo transfer spacecraft, is delivering 3.6 tons of science experiments, equipment and supplies to the orbiting complex. HTV-4 launched from the Tanegashima Space Center in southern Japan on Aug.3 at 3:48 p.m. (Aug. 4 at 4:48 a.m., Japan time).

  19. HTV-4 approach

    NASA Image and Video Library

    2013-08-09

    ISS036-E-030067 (9 Aug. 2013) --- The unpiloted Japanese "Kounotori" H2 Transfer Vehicle-4 (HTV-4) approaches the International Space Station. The HTV, a 33-foot-long, 13-foot-diameter unmanned cargo transfer spacecraft, is delivering 3.6 tons of science experiments, equipment and supplies to the orbiting complex. HTV-4 launched from the Tanegashima Space Center in southern Japan on Aug.3 at 3:48 p.m. (Aug. 4 at 4:48 a.m., Japan time).

  20. Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity.

    PubMed

    Slobodin, Gleb; Ahmad, Mohammad Sheikh; Rosner, Itzhak; Peri, Regina; Rozenbaum, Michael; Kessel, Aharon; Toubi, Elias; Odeh, Majed

    2010-01-01

    The role and function of T regulatory (Treg) cells have not been fully investigated in patients with systemic sclerosis (SSc). Ten patients with SSc donated 20ml of peripheral blood. Activity (Valentini) and severity (Medsger) scores for SSc were calculated for all patients. Healthy volunteers (controls) were matched to each patient by gender and age. CD4(+) cells were separated using the MACS system. The numbers of Treg cells were estimated by flow cytometry after staining for CD4, CD25, and FoxP3 and calculated as patient-to-control ratio separately for each experiment. Correlations with activity and severity indices of the disease were performed. Twenty-four-hour production of TGF-beta and IL-10 by activated CD4(+) cells was measured by ELISA in culture supernatants. The numbers of Treg cells, expressed as patient-to-control ratio, correlated significantly with both activity and severity indices (r=0.71, p=0.034 and r=0.67, p=0.044, respectively). ELISA-measured production of TGF-beta and IL-10 by CD4(+) cells was similar in patients and controls. Increased numbers of Treg cells are present in patients with SSc, correlating with activity and severity of the disease. This expansion of Treg cells was not accompanied, however, by heightened TGF-beta or IL-10 production. Further studies to elaborate the causes and functional significance of Treg cell expansion in SSc are needed. 2010 Elsevier Inc. All rights reserved.

  1. Investigation of p16(INK4a) as a prognostic biomarker in oral epithelial dysplasia.

    PubMed

    Nankivell, Paul; Williams, Hazel; Webster, Keith; Pearson, David; High, Alec; MacLennan, Kenneth; Senguven, Burcu; McConkey, Christopher; Rabbitts, Pamela; Mehanna, Hisham

    2014-04-01

    Human papilloma virus is a risk factor for oropharyngeal cancer. Evidence for a similar aetiological role in the development of oral dysplasia or its transformation to oral cancer is not as clear. Meta-analyses estimate the prevalence of high-risk human papilloma virus (HPV) serotypes to be three times higher in pre-malignant lesions and cancer than in normal oral mucosa. However, this does not imply a causal relationship. Conflicting results are reported from the few studies examining the prognostic significance of HPV positivity in the development of oral cancer. We aimed to examine the ability of p16(INK4a) protein expression, a surrogate marker of HPV infection, to predict malignant progression in a large cohort of oral dysplasia patients. One hundred forty eight oral dysplasia cases underwent immunohistochemical analysis using a monoclonal antibody against p16(INK4a) . Clinical factors were also collated on each case. Slides were double scored independently by two trained observers. Univariate analyses using both logistic and Cox regression models were performed. Thirty nine of 148 cases progressed to cancer. Ten of 148 cases (7%) were p16(INK4a) positive. High grade of dysplasia (P = 0.0002) and lesion morphology (P = 0.03) were found to be prognostic of malignant progression. p16(INK4a) score was not prognostic in this cohort (P = 0.29). This did not change with a time to event analysis (P = 0.24). Few studies have assessed the aetiological role of HPV in cancer development from dysplastic lesions. Our study, using one of the largest cohorts of oral dysplasia, demonstrated a low rate of p16(INK4a) positivity and was unable to confirm a prognostic ability for this biomarker. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Attosecond relative delay among xenon 5p, 5s, and 4d photoionization

    NASA Astrophysics Data System (ADS)

    Magrakvelidze, Maia; Madjet, Mohamed; Chakraborty, Himadri

    2017-04-01

    Attosecond Wigner-Smith (WS) time delays of the photoemissions of Xe valence 5p, 5s, and core 4d electrons are investigated in details using the time-dependent local density approximation (TDLDA). Electron correlations determine the energy-dependent structures in ionization phases of the dipole channels and in the resulting WS delays at various shape resonances, induced by the collective motion of 4d electrons, and at various Cooper minima. We find that our calculation closely agrees with the streaking measurement for the delay of 4d relative to 5s, and predicts accelerated emission of 5p with respect to 4d as was experimentally observed at similar photon energies for Xe atoms adsorbed on the tungsten surface. This work was supported by the U.S. National Science Foundation.

  3. Polarization Transfer in the Reaction 4He($$\\vec{v}$$,e'$$\\vec{p}$$) 3H in the Quasielastic Scattering Region

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

    Dieterich, Sonja

    2002-05-01

    There has been a longstanding issue concerning possible nucleon modifications in a (dense) nuclear medium. Polarization transfer data for exclusive quasielastic electron scattering are a sensitive to the ratio of the electric and magnetic nucleon form factors in the medium. Although proper interpretation of the results requires accounting for such effects as final state interactions and meson exchange currents, their effect on polarization transfer is predicted to be small. Studies of model dependencies, e.g., the off-shell current operator and spinor distortions, have been done. Final results of a measurement of polarization transfer in the 4He(more » $$\\vec{v}$$,e'$$\\vec{p}$$) 3H reaction will be discussed. The experiments were carried out at MAMI, Mainz at a Q 2 of 0.4 GeV 2 and at the Thomas Jefferson Lab, Newport News, Virginia at the Q 2 values 0.5, 1.0, 1.6 and 2.6 GeV 2. Measured values of the transferred and induced polarization are compared with various theoretical calculations. The experiment showed a difference between the fully relativistic model with may indicate medium modifications of the form factor.« less

  4. A de novo 11p12-p15.4 duplication in a patient with pharmacoresistant epilepsy, mental retardation, and dysmorphisms.

    PubMed

    Coppola, Antonietta; Striano, Pasquale; Gimelli, Stefania; Ciampa, Clotilde; Santulli, Lia; Caranci, Ferdinando; Zuffardi, Orsetta; Gimelli, Giorgio; Striano, Salvatore; Zara, Federico

    2010-03-01

    We report a 22-year-old male patient with pharmacoresistant epilepsy, mental retardation and dysmorphisms. Standard cytogenetic analysis revealed a de novo interstitial duplication of the short arm of chromosome 11 (11p). High density array-CGH analysis showed that the rearrangement spans about 35Mb on chromosome 11p12-p15.4. Duplications of 11p are rare and usually involve the distal part of the chromosome arm (11p15), being not associated with epilepsy, whereas our patient showed a unique epileptic phenotype associated with mental retardation and dysmorphic features. The role of some rearranged genes in epilepsy pathogenesis in this patient is also discussed.

  5. The induction of H3K9 methylation by PIWIL4 at the p16{sup Ink4a} locus

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

    Sugimoto, Keiki; Kage, Hidenori; Aki, Naomi

    The field of epigenetics has made progress by the identification of the small RNA-mediated epigenetic modification. However, little is known about the key proteins. Here, we report that the human PIWI-like family is a candidate protein that is involved in the pathway responsible for chromatin remodeling. The PIWI-like family proteins, expressed as the Flag-fusion proteins, formed a bulky body and localized to the nuclear periphery. Transient transfection of PIWI-like 4 (PIWIL4), only member of the PIWI-like family that was ubiquitously expressed in human tissues, induced histone H3 lysine 9 methylation at the p16{sup Ink4a} (CDKN2A) locus. The elevated level ofmore » histone methylation resulted in the downregulation of the p16{sup Ink4a} gene. These results suggest PIWIL4 plays important roles in the chromatin-modifying pathway in human somatic cells.« less

  6. Outer membrane protein P4 is not required for virulence in the human challenge model of Haemophilus ducreyi infection.

    PubMed

    Janowicz, Diane M; Zwickl, Beth W; Fortney, Kate R; Katz, Barry P; Bauer, Margaret E

    2014-06-24

    Bacterial lipoproteins often play important roles in pathogenesis and can stimulate protective immune responses. Such lipoproteins are viable vaccine candidates. Haemophilus ducreyi, which causes the sexually transmitted disease chancroid, expresses a number of lipoproteins during human infection. One such lipoprotein, OmpP4, is homologous to the outer membrane lipoprotein e (P4) of H. influenzae. In H. influenzae, e (P4) stimulates production of bactericidal and protective antibodies and contributes to pathogenesis by facilitating acquisition of the essential nutrients heme and nicotinamide adenine dinucleotide (NAD). Here, we tested the hypothesis that, like its homolog, H. ducreyi OmpP4 contributes to virulence and stimulates production of bactericidal antibodies. We determined that OmpP4 is broadly conserved among clinical isolates of H. ducreyi. We next constructed and characterized an isogenic ompP4 mutant, designated 35000HPompP4, in H. ducreyi strain 35000HP. To test whether OmpP4 was necessary for virulence in humans, eight healthy adults were experimentally infected. Each subject was inoculated with a fixed dose of 35000HP on one arm and three doses of 35000HPompP4 on the other arm. The overall parent and mutant pustule formation rates were 52.4% and 47.6%, respectively (P = 0.74). These results indicate that expression of OmpP4 in not necessary for H. ducreyi to initiate disease or progress to pustule formation in humans. Hyperimmune mouse serum raised against purified, recombinant OmpP4 did not promote bactericidal killing of 35000HP or phagocytosis by J774A.1 mouse macrophages in serum bactericidal and phagocytosis assays, respectively. Our data suggest that, unlike e (P4), H. ducreyi OmpP4 is not a suitable vaccine candidate. OmpP4 may be dispensable for virulence because of redundant mechanisms in H. ducreyi for heme acquisition and NAD utilization.

  7. FABP4/aP2 Regulates Macrophage Redox Signaling and Inflammasome Activation via Control of UCP2.

    PubMed

    Steen, Kaylee A; Xu, Hongliang; Bernlohr, David A

    2017-01-15

    Obesity-linked metabolic disease is mechanistically associated with the accumulation of proinflammatory macrophages in adipose tissue, leading to increased reactive oxygen species (ROS) production and chronic low-grade inflammation. Previous work has demonstrated that deletion of the adipocyte fatty acid-binding protein (FABP4/aP2) uncouples obesity from inflammation via upregulation of the uncoupling protein 2 (UCP2). Here, we demonstrate that ablation of FABP4/aP2 regulates systemic redox capacity and reduces cellular protein sulfhydryl oxidation and, in particular, oxidation of mitochondrial protein cysteine residues. Coincident with the loss of FABP4/aP2 is the upregulation of the antioxidants superoxide dismutase (SOD2), catalase, methionine sulfoxide reductase A, and the 20S proteasome subunits PSMB5 and αβ. Reduced mitochondrial protein oxidation in FABP4/aP2 -/- macrophages attenuates the mitochondrial unfolded-protein response (mtUPR) as measured by expression of heat shock protein 60, Clp protease, and Lon peptidase 1. Consistent with a diminished mtUPR, FABP4/aP2 -/- macrophages exhibit reduced expression of cleaved caspase-1 and NLRP3. Secretion of interleukin 1β (IL-1β), in response to inflammasome activation, is ablated in FABP4/aP2 -/- macrophages, as well as in FABP4/aP2 inhibitor-treated cells, but partially rescued in FABP4/aP2-null macrophages when UCP2 is silenced. Collectively, these data offer a novel pathway whereby FABP4/aP2 regulates macrophage redox signaling and inflammasome activation via control of UCP2 expression. Copyright © 2017 American Society for Microbiology.

  8. Versatile assembly of p-carboxylatocalix[4]arene-O-alkyl ethers

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

    Kennedy, Stuart; Teat, Simon J.; Dalgarno, Scott J.

    Crystallisation of lower-rim tetra-O-alkylated p-carboxylatocalix[4]arenes from pyridine results in the formation of both bi-layer and pillar type supramolecular motifs. Full alkylation at the calixarene lower rim has significant influence over the supramolecular self-assembly motif, including preclusion of pyridine guest molecules from the calixarene cavity in the solid state.

  9. Palmitate induces VSMC apoptosis via toll like receptor (TLR)4/ROS/p53 pathway.

    PubMed

    Zhang, Yuanjun; Xia, Guanghao; Zhang, Yaqiong; Liu, Juxiang; Liu, Xiaowei; Li, Weihua; Lv, Yaya; Wei, Suhong; Liu, Jing; Quan, Jinxing

    2017-08-01

    Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4

    PubMed Central

    Zhang, Dongyuan; Sun, Hongcheng; Yu, Fudong; Yue, Ben; Wang, Jingtao; Zhang, Meng; Yu, Yang; Liu, Xisheng; Sun, Xiaofeng; Zhou, Zongguang; Qin, Xuebin; Zhang, Xin; Yan, Dongwang; Wen, Yugang; Peng, Zhihai

    2016-01-01

    Background Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. Results miR-20a-5p negatively regulated Smad4 by directly targeting its 3′UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients’ clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Methods Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan–Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. Conclusions miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer. PMID:27286257

  11. Precision Laser Spectroscopic Measurement of Helium -4(1S2S S(3) to 1S2P P(3)) Lamb Shift and Fine Structure

    NASA Astrophysics Data System (ADS)

    Dixson, Ronald Gene

    This thesis is a presentation of the results of a precise measurement of the absolute wavelength and fine structure splitting of the 1s2s ^3S to 1s2p ^3P transition of the ^4He atom. The experiment described in this thesis is the first one in which laser spectroscopy has been done on the 2 ^3S to 2^3 P transition in a metastable atomic beam. The energy interval between the 2^3S and the 2^3P state is precisely determined by comparison of the absolute wavelength of the transition with our standard laser (an iodine stabilized He-Ne laser with an accuracy of 1.6 parts in 10^{10 }) in a Fabry-Perot interferometer. The experimental Lamb shift of the transition is determined by subtracting from the measured frequency the precisely known non-quantum electrodynamic contributions to the theoretical value of the interval. From our measurements of the absolute wavelength, the following weighted (2J + 1) average for the 2^3S to 2^3P transition frequency and experimental Lamb Shift are obtained:eqalign{& rm f_{2S{-}2P} = 276 736 495.59 (5) rm MHz.cr& {bf L}[ 2^3Sto2 ^3P] = 5311.26 (5) rm MHz.cr} Our value for the Lamb Shift is in agreement with the best previous measurement but a factor of 60 more precise. It is also two orders of magnitude more precise than the present theoretical calculation, presenting quite a challenge to theorists. Nevertheless, this work is very timely since it is anticipated (DRA94) (MOR94) that the theory will reach this level in the near future. The measured fine structure splittings of the 2^3P level are: eqalign{rm 2^3P_0to rm2^3P_2 &: 31908.135 (3) rm MHzcrrm 2^3P_1to rm2^3P_2 &: sk{5}2291.173 (3) rm MHz}These results are more precise than previous microwave measurements and in significant disagreement with them, a situation which is especially timely and interesting since new theoretical calculations of these fine structure intervals (DRA94) at this level of precision are nearing completion.

  12. C P -invariance violation at short-baseline experiments in 3 +1 neutrino scenarios

    NASA Astrophysics Data System (ADS)

    de Gouvêa, André; Kelly, Kevin J.; Kobach, Andrew

    2015-03-01

    New neutrino degrees of freedom allow for more sources of charge parity- (C P ) invariance violation (CPV). We explore the requirements for accessing C P -odd mixing parameters in the so-called 3 +1 scenario, where one assumes the existence of one extra, mostly sterile neutrino degree of freedom, heavier than the other three mass eigenstates. As a first step, we concentrate on the νe→νμ appearance channel in a hypothetical, upgraded version of the ν STORM proposal. We establish that the optimal baseline for CPV studies depends strongly on the value of Δ m142—the new mass-squared difference—and that the ability to observe CPV depends significantly on whether the experiment is performed at the optimal baseline. Even at the optimal baseline, it is very challenging to see CPV in 3 +1 scenarios if one considers only one appearance channel. Full exploration of CPV in short-baseline experiments will require precision measurements of tau appearance, a challenge significantly beyond what is currently being explored by the experimental neutrino community.

  13. TMPYP4 exerted antitumor effects in human cervical cancer cells through activation of p38 mitogen-activated protein kinase.

    PubMed

    Cheng, Ming-Jun; Cao, Yun-Gui

    2017-07-03

    The aim of the present study was to investigate the potential effects of the 5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of human cervical cancer cells and the underlying mechanisms by which TMPyP4 exerted its actions. After human cervical cancer cells were treated with different doses of TMPyP4, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, the apoptosis was observed by flow cytometry (FCM), and the expression of p38 mitogen-activated protein kinase (MAPK), phosphated p38 MAPK (p-p38 MAPK), capase-3, MAPKAPK2 (MK-2) and poly ADP-ribose polymerase (PARP) was measured by Western blot analysis. The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of human cervical cancer cells in a dose-dependent manner. In addition, the up-regulation of p-p38 MAPK expression levels was detected in TMPyP4-treated human cervical cancer cells. However, followed by the block of p38 MAPK signaling pathway using the inhibitor SB203580, the effects of TMPyP4 on proliferation and apoptosis of human cervical cancer cells were significantly changed. It was indicated that TMPyP4-inhibited proliferation and -induced apoptosis in human cervical cancer cells was accompanied by activating the p38 MAPK signaling pathway. Taken together, our study demonstrates that TMPyP4 may represent a potential therapeutic method for the treatment of cervical carcinoma.

  14. Gene transfer of Alcaligenes eutrophus JMP134 plasmid pJP4 to indigenous soil recipients.

    PubMed Central

    DiGiovanni, G D; Neilson, J W; Pepper, I L; Sinclair, N A

    1996-01-01

    This study evaluated the potential for gene transfer of a large catabolic plasmid from an introduced organism to indigenous soil recipients. The donor organism Alcaligenes eutrophus JMP134 contained the 80-kb plasmid pJP4, which contains genes that code for mercury resistance. Genes on this plasmid plus chromosomal genes also allow degradation of 2,4-dichloruphenoxyacetic acid (2,4-D). When JMP134 was inoculated into a nonsterile soil microcosm amended with 1,000 micrograms of 2,4-D g-1, significant (10(6) g of soil-1) populations of indigenous recipients or transconjugants arose. These transconjugants all contained an 80-kb plasmid similar in size to pJP4, and all degraded 2,4-D. In addition, all transconjugants were resistant to mercury and contained the tfdB gene of pJP4 as detected by PCR. No mercury-resistant, 2,4-D-degrading organisms with large plasmids or the tfdB gene were found in the 2,4-D-amended but uninoculated control microcosm. These data clearly show that the plasmid pJP4 was transferred to indigenous soil recipients. Even more striking is the fact that not only did the indigenous transconjugant population survive and proliferate but also enhanced rates of 2,4-D degradation occurred relative to microcosms in which no such gene transfer occurred. Overall, these data indicate that gene transfer from introduced organisms is an effective means of bioaugmentation and that survival of the introduced organism is not a prerequisite for biodegradation that utilizes introduced biodegradative genes. PMID:8779592

  15. Status of the TRIGA-LASER experiment

    NASA Astrophysics Data System (ADS)

    Gorges, C.; Kaufmann, S.; Geppert, Ch.; Krämer, J.; Sánchez, R.; Nörtershäuser, W.

    2017-11-01

    We report on the newly developed control system called TRITON and the new data acquisition called TILDA as well as on improved isotope shift measurements of the isotopes 40,42,44,48Ca in the 4 s 2S1/2 → 4 p 2P3/2 (D2) transition at the TRIGA-LASER experiment in Mainz using collinear laser spectroscopy. Well known isotope shift measurements in the 4 s 2S1/2 → 4 p 2P1/2 (D1) transition act as calibration points to reduce the uncertainties in the D2-line to provide reference values for the determination of nuclear charge radii and quadrupole moments of neutron rich calcium isotopes at COLLAPS.

  16. Linkage of Wolfram syndrome to chromosome 4p16.1 and evidence for heterogeneity

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

    Collier, D.A.; Curtis, D.; Arranz, M.J.

    1996-10-01

    Wolfram syndrome (DIDMOAD syndrome; MIM 222300) is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and bilateral optic atrophy. Previous linkage analysis of multiply affected families indicated that the gene for Wolfram syndrome is on chromosome 4p, and it produced no evidence for locus heterogeneity. We have investigated 12 U.K. families with Wolfram syndrome, and we report confirmation of linkage to chromosome 4p, with a maximum two-point LOD score of 4.6 with DRD5, assuming homogeneity, and of 5.1, assuming heterogeneity. Overlapping multipoint analysis using six markers at a time produced definite evidence for locus heterogeneity: the maximum multipointmore » LOD score under homogeneity was <2, whereas when heterogeneity was allowed for an admixture a LOD of 6.2 was obtained in the interval between D4S432 and D4S431, with the peak close to the marker D4S3023. One family with an atypical phenotype was definitely unlinked to the region. Haplotype inspection of the remaining 11 families, which appear linked to chromosome 4p and had typical phenotypes, revealed crossover events during meiosis, which also placed the gene in the interval D4S432 and D4S431. In these families no recombinants were detected with the marker D4S3023, which maps within the same interval. 22 refs., 3 figs., 2 tabs.« less

  17. RNA packaging device of double-stranded RNA bacteriophages, possibly as simple as hexamer of P4 protein.

    PubMed

    Kainov, Denis E; Pirttimaa, Markus; Tuma, Roman; Butcher, Sarah J; Thomas, George J; Bamford, Dennis H; Makeyev, Eugene V

    2003-11-28

    Genomes of complex viruses have been demonstrated, in many cases, to be packaged into preformed empty capsids (procapsids). This reaction is performed by molecular motors translocating nucleic acid against the concentration gradient at the expense of NTP hydrolysis. At present, the molecular mechanisms of packaging remain elusive due to the complex nature of packaging motors. In the case of the double-stranded RNA bacteriophage phi 6 from the Cystoviridae family, packaging of single-stranded genomic precursors requires a hexameric NTPase, P4. In the present study, the purified P4 proteins from two other cystoviruses, phi 8 and phi 13, were characterized and compared with phi 6 P4. All three proteins are hexameric, single-stranded RNA-stimulated NTPases with alpha/beta folds. Using a direct motor assay, we found that phi 8 and phi 13 P4 hexamers translocate 5' to 3' along ssRNA, whereas the analogous activity of phi 6 P4 requires association with the procapsid. This difference is explained by the intrinsically high affinity of phi 8 and phi 13 P4s for nucleic acids. The unidirectional translocation results in RNA helicase activity. Thus, P4 proteins of Cystoviridae exhibit extensive similarity to hexameric helicases and are simple models for studying viral packaging motor mechanisms.

  18. The Regulatory Mechanisms of Tumor Suppressor P16INK4A and Relevance to Cancer†

    PubMed Central

    Li, Junan; Poi, Ming Jye; Tsai, Ming-Daw

    2011-01-01

    P16INK4A (also known as P16 and MTS1), a protein consisting exclusively of four ankyrin repeats, is recognized as a tumor suppressor mainly due to the prevalence of genetic inactivation of the p16INK4A (or CDKN2A) gene in virtually all types of human cancers. However, it has also been shown that elevated expression (up-regulation) of P16 is involved in cellular senescence, aging, and cancer progression, indicating that the regulation of P16 is critical for its function. Here, we discuss the regulatory mechanisms of P16 function at the DNA level, the transcription level, and the posttranscriptional level, as well as their implications in the structure-function relationship of P16 and in human cancers. PMID:21619050

  19. Two Cases of Partial Trisomy 4p and Partial Trisomy 14q

    PubMed Central

    Kim, Yeo-Hyang; Kim, Heung-Sik; Ryoo, Nam-Hee

    2013-01-01

    We present clinical and cytogenetic data on 2 cases of partial trisomy 4p and partial trisomy 14q. Both patients had an extra der(14)t(4;14)(p15.31;q12) chromosome due to a 3:1 segregation from a balanced translocation carrier mother. Array analyses indicated that their chromosomal breakpoints were similar, but there was no relationship between the 2 families. Both patients showed prominent growth retardation and psychomotor developmental delay. Other phenotypic manifestations were generally mild and variable; for example, patient 1 had a short palpebral fissure and low-set ears whereas patient 2 had a round face, asymmetric eyes, small ears, a short neck, finger/toe abnormalities, and behavioral problems. PMID:23301226

  20. Polyoxometal cations within polyoxometalate anions. Seven-coordinate uranium and zirconium heteroatom groups in [(UO2)12(μ3-O)4(μ2-H2O)12(P2W15O56)4]32- and [Zr4(μ3-O)2(μ2-OH)2(H2O)4 (P2W16O59)2]14-

    NASA Astrophysics Data System (ADS)

    Gaunt, Andrew J.; May, Iain; Collison, David; Travis Holman, K.; Pope, Michael T.

    2003-08-01

    Two new composite polyoxotungstate anions with unprecedented structural features, [(UO2)12(μ3-O)4(μ2-H2O)12(P2W15O56)4]32- (1) and [Zr4(μ3-O)2(μ2-OH)2(H2O)4 (P2W16O59)2]14- (2) contain polyoxo-uranium and -zirconium clusters as bridging units. The anions are synthesized by reaction of Na12[P2W15O56] with solutions of UO2(NO3)2 and ZrCl4. The structure of 1 in the sodium salt contains four [P2W15O56]12- anions assembled into an overall tetrahedral cluster by means of trigonal bridging groups formed by three equatorial-edge-shared UO7 pentagonal bipyramids. The structure of anion 2 consists of a centrosymmetric assembly of two [P2W16O59]12- anions linked by a {Zr4O2(OH)2(H2O)4}10+ cluster. Both complexes in solution yield the expected two-line 31P-NMR spectra with chemical shifts of -2.95, -13.58 and -6.45, -13.69 ppm, respectively.

  1. Management of HPV-related cervical disease: role of p16INK4a immunochemistry. Review of the literature.

    PubMed

    Savone, Delia; Carrone, Angela; Riganelli, Lucia; Merlino, Lucia; Mancino, Pasquale; Benedetti Panici, Pierluigi

    2016-10-13

    This systematic review of 43 studies aims to evaluate the absolute and relative sensitivity and specificity of p16INK4a with regard to uterine cervix lesions, describing innovations and techniques for the detection of high-grade cervical dysplasia and allowing correct treatment. Studies were identified in the PubMed database up to March 2015. The keywords hrHPV, p16INK4a gene, and uterine cervical disease (MeSH terms) were used. Only English-language articles were included. We considered retrospective and prospective studies that assessed p16INK4a or p16INK4a/Ki67 staining, with or without HPV-DNA testing (HC2/PCR) as a comparator test, in cytological/histological specimens for which the diagnosis of ASCUS, LSIL or HSIL was verified with a reference standard. The primary outcome for cervical lesions was evaluation of the absolute p16INK4a immunoreactivity; the secondary outcome was evaluation of the relative p16INK4a immunoreactivity versus HPV testing in those studies where comparator tests were available. p16INK4a was more specific than HPV-DNA test (median values of 56.1% vs. 52.25% in CIN grade ≥2 lesions; 82.5% vs. 53% in negative and CIN grade ≥1 lesions). The main limitation of this study is linked to both qualitative and quantitative p16INK4a levels of expression, while the second limitation is the lack of standardized scales. p16INK4a and HPV-DNA used together increased the sensitivity and negative predictive value for CIN detection. p16INK4a can be considered a biomarker of CIN2 or CIN3, indicating a high risk of relapse or evolution to invasive carcinoma. Also p16INK4a-negative CIN should be considered and further research should be performed.

  2. Phosphate solubilization and promotion of maize growth in a calcareous soil by penicillium oxalicum P4 and aspergillus niger P85

    USDA-ARS?s Scientific Manuscript database

    Alternative tactics for improving phosphorus nutrition in crop production are needed in China and elsewhere as the over-application of phosphatic fertilizers can adversely impact agricultural sustainability. Penicillium oxalicum P4 and Aspergillus niger P85 were isolated from a calcareous soil in C...

  3. Dynamically polarized target for the g p 2 and G p E experiments at Jefferson Lab

    DOE PAGES

    Pierce, J.; Maxwell, J.; Badman, T.; ...

    2013-12-16

    We describe a dynamically polarized target that has been utilized for two electron scattering experiments in Hall A at Jefferson Lab. The primary components of the target are a new, high cooling power 4 He evaporation refrigerator, and a re-purposed, superconducting split-coil magnet. It has been used to polarize protons in irradiated NH 3 at a temperature of 1 K and at fields of 2.5 and 5.0 Tesla. The performance of the target material in the electron beam under these conditions will be discussed. The maximum polarizations of 28% and 95% were obtained at those fields, respectively. To satisfy themore » requirements of both experiments, the magnet had to be routinely rotated between angles of 0, 6, and 90 degrees with respect to the incident electron beam. This was accomplished using a new rotating vacuum seal which permits rotations to be performed in only a few minutes.« less

  4. Nuclear translocation of p19INK4d in response to oxidative DNA damage promotes chromatin relaxation.

    PubMed

    Sonzogni, Silvina V; Ogara, María F; Castillo, Daniela S; Sirkin, Pablo F; Radicella, J Pablo; Cánepa, Eduardo T

    2015-01-01

    DNA is continuously exposed to damaging agents that can lead to changes in the genetic information with adverse consequences. Nonetheless, eukaryotic cells have mechanisms such as the DNA damage response (DDR) to prevent genomic instability. The DNA of eukaryotic cells is packaged into nucleosomes, which fold the genome into highly condensed chromatin, but relatively little is known about the role of chromatin accessibility in DNA repair. p19INK4d, a cyclin-dependent kinase inhibitor, plays an important role in cell cycle regulation and cellular DDR. Extensive data indicate that p19INK4d is a critical factor in the maintenance of genomic integrity and cell survival. p19INK4d is upregulated by various genotoxics, improving the repair efficiency for a variety of DNA lesions. The evidence of p19INK4d translocation into the nucleus and its low sequence specificity in its interaction with DNA prompted us to hypothesize that p19INK4d plays a role at an early stage of cellular DDR. In the present study, we demonstrate that upon oxidative DNA damage, p19INK4d strongly binds to and relaxes chromatin. Furthermore, in vitro accessibility assays show that DNA is more accessible to a restriction enzyme when a chromatinized plasmid is incubated in the presence of a protein extract with high levels of p19INK4d. Nuclear protein extracts from cells overexpressing p19INK4d are better able to repair a chromatinized and damaged plasmid. These observations support the notion that p19INK4d would act as a chromatin accessibility factor that allows the access of the repair machinery to the DNA damage site.

  5. Crystal field parameters in UCI 4: Experiment versus theory

    NASA Astrophysics Data System (ADS)

    Zolnierek, Z.; Gajek, Z.; Malek, Ch. Khan

    1984-08-01

    Crystal field effect on U 4+ ion with the 3H 4 ground term in tetragonal ligand field of UCl 4 has been studied in detail. Crystal field parameters determined experimentally from optical spectroscopy and magnetic susceptibility are in good agreement with CFP sets derived from the modified point charge model and the ab initio method. Theoretical calculations lead to overestimating the A44< r4> and lowering the A02< r2> values in comparison to those found in the experiments. The discrepancies are, however, within an accuracy of calculations. A large reduction of expectation values of the magnetic moment operator for the eigenvectors of lowest CF levels (17.8%), determined from magnetic susceptibility, cannot be attributed to the overlap and covalency effects only. The detailed calculations have shown that the latter effects provide about 4.6% reduction of respective matrix elements, and the applied J-J mixing procedure increases this factor up to 6.5%. Since similar, as in UCl 4, reduction factor(≈15%) has already been observed in a number of different uranium compounds, it seems likely that this feature is involved in the intrinsic properties of the U 4+ ion. We endeavor to explain this effect in terms of configuration interaction mechanisms.

  6. P2X4 Receptor in Silico and Electrophysiological Approaches Reveal Insights of Ivermectin and Zinc Allosteric Modulation

    PubMed Central

    Latapiat, Verónica; Rodríguez, Felipe E.; Godoy, Francisca; Montenegro, Felipe A.; Barrera, Nelson P.; Huidobro-Toro, Juan P.

    2017-01-01

    Protein allosteric modulation is a pillar of metabolic regulatory mechanisms; this concept has been extended to include ion channel regulation. P2XRs are ligand-gated channels activated by extracellular ATP, sensitive to trace metals and other chemicals. By combining in silico calculations with electrophysiological recordings, we investigated the molecular basis of P2X4R modulation by Zn(II) and ivermectin, an antiparasite drug currently used in veterinary medicine. To this aim, docking studies, molecular dynamics simulations and non-bonded energy calculations for the P2X4R in the apo and holo states or in the presence of ivermectin and/or Zn(II) were accomplished. Based on the crystallized Danio rerio P2X4R, the rat P2X4R, P2X2R, and P2X7R structures were modeled, to determine ivermectin binding localization. Calculations revealed that its allosteric site is restricted to transmembrane domains of the P2X4R; the role of Y42 and W46 plus S341 and non-polar residues were revealed as essential, and are not present in the homologous P2X2R or P2X7R transmembrane domains. This finding was confirmed by preferential binding conformations and electrophysiological data, revealing P2X4R modulator specificity. Zn(II) acts in the P2X4R extracellular domain neighboring the SS3 bridge. Molecular dynamics in the different P2X4R states revealed allosterism-induced stability. Pore and lateral fenestration measurements of the P2X4R showed conformational changes in the presence of both modulators compatible with a larger opening of the extracellular vestibule. Electrophysiological studies demonstrated additive effects in the ATP-gated currents by joint applications of ivermectin plus Zn(II). The C132A P2X4R mutant was insensitive to Zn(II); but IVM caused a 4.9 ± 0.7-fold increase in the ATP-evoked currents. Likewise, the simultaneous application of both modulators elicited a 7.1 ± 1.7-fold increase in the ATP-gated current. Moreover, the C126A P2X4R mutant evoked similar ATP

  7. Evidence for 4-chlorobenzoic acid dehalogenation mediated by plasmids related to pSS50.

    PubMed Central

    Layton, A C; Sanseverino, J; Wallace, W; Corcoran, C; Sayler, G S

    1992-01-01

    The biodegradation of 4-chlorobiphenyl usually proceeds through the intermediate 4-chlorobenzoate. Few bacterial strains can degrade 4-chlorobiphenyl to 4-chlorobenzoate and 4-chlorobenzoate to CO2. This study demonstrates that the 4-chlorobiphenyl-degrading Alcaligenes sp. strain ALP83 can degrade 4-chlorobenzoate to 4-hydroxybenzoate. The dehalogenase activity is correlated with a 10-kb fragment carried on plasmid pSS70. Images PMID:1539985

  8. Evaluation of buffers toxicity in tobacco cells: Homopiperazine-1,4-bis (2-ethanesulfonic acid) is a suitable buffer for plant cells studies at low pH.

    PubMed

    Borgo, Lucélia

    2017-06-01

    Low pH is an important environmental stressor of plant root cells. Understanding the mechanisms of stress and tolerance to acidity is critical; however, there is no widely accepted pH buffer for studies of plant cells at low pH. Such a buffer might also benefit studies of Al toxicity, in which buffering at low pH is also important. The challenge is to find a buffer with minimal cellular effects. We examined the cytotoxicity and possible metabolic disturbances of four buffers that have adequate pK a values and potential use for studies in the pH range of 4.0-5.0. These were homopipes (homopiperazine-1,4-bis (2-ethanesulfonic acid); pK a1 4.4), 3,3-dimethylglutaric acid (pK a1 3.73), β-alanine (pK a1 3.70) and potassium biphthalate (pK a1 2.95; pK a2 5.41). First, tobacco BY-2 cells were grown in a rich medium containing 10 mM of each buffer or MES (2-(N-morpholino) ethanesulfonic acid) as a control, with the pH initially adjusted to 5.7. β-alanine was clearly toxic and dimethylgluturate and biphthalate were found to be cytostatic, in which no culture growth occurred but cell viability was either unaffected or decreased only after 5 days. Only homopipes allowed normal culture growth and cell viability. Homopipes (10 mM) was then tested in cell cultures with an initial pH of 4.3 ± 0.17 in minimal medium to examine whether its undissociated species (H 2 A) displayed any cellular effects and no cytotoxic effects were observed. It is possible to conclude that among tested buffers, homopipes is the most suitable for studies at low pH, and may be especially useful for aluminum toxicity experiments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Expression of p16Ink4a in mixed squamous cell and glandular papilloma of the lung.

    PubMed

    Miyoshi, Ryo; Menju, Toshi; Yoshizawa, Akihiko; Date, Hiroshi

    2017-06-01

    Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is an extremely rare neoplasm, with only 21 cases reported in the English literature. Although the expression of p16 Ink4a has been analyzed in only two cases of mixed papilloma, they were negative for p16 Ink4a . Therefore, the significance of p16 Ink4a overexpression in mixed papilloma remains unclear. This is the first case of mixed papilloma with positive p16 Ink4a expression in a 72-year-old male smoker. The 20 mm sized tumor was histologically diagnosed as mixed papilloma following right upper lobectomy. Immunohistochemically, cytokeratin 5 and p40 positivity was predominant in basal cells of the glandular component and squamous cells, while thyroid transcription factor-1, p53, and Ki-67 were focally positive. Both glandular and squamous components were diffusely positive for p16 Ink4a . This finding could be important to clarify the pathogenesis and biology of mixed papilloma. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  10. 4C-ker: A Method to Reproducibly Identify Genome-Wide Interactions Captured by 4C-Seq Experiments.

    PubMed

    Raviram, Ramya; Rocha, Pedro P; Müller, Christian L; Miraldi, Emily R; Badri, Sana; Fu, Yi; Swanzey, Emily; Proudhon, Charlotte; Snetkova, Valentina; Bonneau, Richard; Skok, Jane A

    2016-03-01

    4C-Seq has proven to be a powerful technique to identify genome-wide interactions with a single locus of interest (or "bait") that can be important for gene regulation. However, analysis of 4C-Seq data is complicated by the many biases inherent to the technique. An important consideration when dealing with 4C-Seq data is the differences in resolution of signal across the genome that result from differences in 3D distance separation from the bait. This leads to the highest signal in the region immediately surrounding the bait and increasingly lower signals in far-cis and trans. Another important aspect of 4C-Seq experiments is the resolution, which is greatly influenced by the choice of restriction enzyme and the frequency at which it can cut the genome. Thus, it is important that a 4C-Seq analysis method is flexible enough to analyze data generated using different enzymes and to identify interactions across the entire genome. Current methods for 4C-Seq analysis only identify interactions in regions near the bait or in regions located in far-cis and trans, but no method comprehensively analyzes 4C signals of different length scales. In addition, some methods also fail in experiments where chromatin fragments are generated using frequent cutter restriction enzymes. Here, we describe 4C-ker, a Hidden-Markov Model based pipeline that identifies regions throughout the genome that interact with the 4C bait locus. In addition, we incorporate methods for the identification of differential interactions in multiple 4C-seq datasets collected from different genotypes or experimental conditions. Adaptive window sizes are used to correct for differences in signal coverage in near-bait regions, far-cis and trans chromosomes. Using several datasets, we demonstrate that 4C-ker outperforms all existing 4C-Seq pipelines in its ability to reproducibly identify interaction domains at all genomic ranges with different resolution enzymes.

  11. 4C-ker: A Method to Reproducibly Identify Genome-Wide Interactions Captured by 4C-Seq Experiments

    PubMed Central

    Raviram, Ramya; Rocha, Pedro P.; Müller, Christian L.; Miraldi, Emily R.; Badri, Sana; Fu, Yi; Swanzey, Emily; Proudhon, Charlotte; Snetkova, Valentina

    2016-01-01

    4C-Seq has proven to be a powerful technique to identify genome-wide interactions with a single locus of interest (or “bait”) that can be important for gene regulation. However, analysis of 4C-Seq data is complicated by the many biases inherent to the technique. An important consideration when dealing with 4C-Seq data is the differences in resolution of signal across the genome that result from differences in 3D distance separation from the bait. This leads to the highest signal in the region immediately surrounding the bait and increasingly lower signals in far-cis and trans. Another important aspect of 4C-Seq experiments is the resolution, which is greatly influenced by the choice of restriction enzyme and the frequency at which it can cut the genome. Thus, it is important that a 4C-Seq analysis method is flexible enough to analyze data generated using different enzymes and to identify interactions across the entire genome. Current methods for 4C-Seq analysis only identify interactions in regions near the bait or in regions located in far-cis and trans, but no method comprehensively analyzes 4C signals of different length scales. In addition, some methods also fail in experiments where chromatin fragments are generated using frequent cutter restriction enzymes. Here, we describe 4C-ker, a Hidden-Markov Model based pipeline that identifies regions throughout the genome that interact with the 4C bait locus. In addition, we incorporate methods for the identification of differential interactions in multiple 4C-seq datasets collected from different genotypes or experimental conditions. Adaptive window sizes are used to correct for differences in signal coverage in near-bait regions, far-cis and trans chromosomes. Using several datasets, we demonstrate that 4C-ker outperforms all existing 4C-Seq pipelines in its ability to reproducibly identify interaction domains at all genomic ranges with different resolution enzymes. PMID:26938081

  12. Complete Genome Sequence of the p-Nitrophenol-Degrading Bacterium Pseudomonas putida DLL-E4

    PubMed Central

    Hu, Xiaojun; Wang, Jue; Wang, Fei; Chen, Qiongzhen; Huang, Yan

    2014-01-01

    The first complete genome sequence of a p-nitrophenol (PNP)-degrading bacterium is reported here. Pseudomonas putida DLL-E4, a Gram-negative bacterium isolated from methyl-parathion-polluted soil, can utilize PNP as the sole carbon and nitrogen source. P. putida DLL-E4 has a 6,484,062 bp circular chromosome that contains 5,894 genes, with a G+C content of 62.46%. PMID:24948765

  13. Faithful chromosome transmission requires Spt4p, a putative regulator of chromatin structure in Saccharomyces cerevisiae.

    PubMed Central

    Basrai, M A; Kingsbury, J; Koshland, D; Spencer, F; Hieter, P

    1996-01-01

    A chromosome transmission fidelity (ctf) mutant, s138, of Saccharomyces cerevisiae was identified by its centromere (CEN) transcriptional readthrough phenotype, suggesting perturbed kinetochore integrity in vivo. The gene complementing the s138 mutation was found to be identical to the S. cerevisiae SPT4 gene. The s138 mutation is a missense mutation in the second of four conserved cysteine residues positioned similarly to those of zinc finger proteins, and we henceforth refer to the mutation of spt4-138. Both spt4-138 and spt4 delta strains missegregate a chromosome fragment at the permissive temperature, are temperature sensitive for growth at 37 degrees C, and upon a shift to the nonpermissive temperature show an accumulation of large budded cells, each with a nucleus. Previous studies suggest that Spt4p functions in a complex with Spt5p and Spt6p, and we determined that spt6-140 also causes missegregation of a chromosome fragment. Double mutants carrying spt4 delta 2::HIS3 and kinetochore mutation ndc10-42 or ctf13-30 show a synthetic conditional phenotype. Both spt4-138 and spt4 delta strains exhibit synergistic chromosome instability in combination with CEN DNA mutations and show in vitro defects in microtubule binding to minichromosomes. These results indicate that Spt4p plays a role in chromosome segregation. The results of in vivo genetic interactions with mutations in kinetochore proteins and CEN DNA and of in vitro biochemical assays suggest that Spt4p is important for kinetochore function. PMID:8649393

  14. CXCL4L1 and CXCL4 signaling in human lymphatic and microvascular endothelial cells and activated lymphocytes: involvement of mitogen-activated protein (MAP) kinases, Src and p70S6 kinase.

    PubMed

    Van Raemdonck, Katrien; Gouwy, Mieke; Lepers, Stefanie Antoinette; Van Damme, Jo; Struyf, Sofie

    2014-07-01

    CXC chemokines influence a variety of biological processes, such as angiogenesis, both in a physiological and pathological context. Platelet factor-4 (PF-4)/CXCL4 and its variant PF-4var/CXCL4L1 are known to favor angiostasis by inhibiting endothelial cell proliferation and chemotaxis. CXCL4L1 in particular is a potent inhibitor of angiogenesis with anti-tumoral characteristics, both through regulation of neovascularization and through attraction of activated lymphocytes. However, its underlying signaling pathways remain to be elucidated. Here, we have identified various intracellular pathways activated by CXCL4L1 in comparison with other CXCR3 ligands, including CXCL4 and interferon-γ-induced protein 10/CXCL10. Signaling experiments show involvement of the mitogen-activated protein kinase (MAPK) family in CXCR3A-transfected cells, activated lymphocytes and human microvascular endothelial cells (HMVEC). In CXCR3A transfectants, CXCL4 and CXCL4L1 activated p38 MAPK, as well as Src kinase within 30 and 5 min, respectively. Extracellular signal-regulated kinase (ERK) phosphorylation occurred in activated lymphocytes, yet was inhibited in microvascular and lymphatic endothelial cells. CXCL4L1 and CXCL4 counterbalanced the angiogenic chemokine stromal cell-derived factor-1/CXCL12 in both endothelial cell types. Notably, inhibition of ERK signaling by CXCL4L1 and CXCL4 in lymphatic endothelial cells implies that these chemokines might also regulate lymphangiogenesis. Furthermore, CXCL4, CXCL4L1 and CXCL10 slightly enhanced forskolin-stimulated cAMP production in HMVEC. Finally, CXCL4, but not CXCL4L1, induced activation of p70S6 kinase within 5 min in HMVEC. Our findings confirm that the angiostatic chemokines CXCL4L1 and CXCL4 activate both CXCR3A and CXCR3B and bring new insights into the complexity of their signaling cascades.

  15. Synthesis of 1,4,7-triphenyl-1,4,7-triphosphacyclononane: the first metal-free synthesis of a [9]-aneP(3)R(3) ring.

    PubMed

    Lowry, Daniel J; Helm, Monte L

    2010-06-07

    The 1,4,7-triphenyl-1,4,7-triphosphacyclononane ([9]-aneP(3)Ph(3)) macrocycle was synthesized through the reaction of lithium bis(2-phenylphosphidoethyl)phenylphosphine with 1,2-dichloroethane. [9]-aneP(3)Ph(3) was subsequently coordinated to a Mo(0) metal center and isolated as the fac-Mo([9]-aneP(3)Ph(3))(CO)(3) metal complex.

  16. Mutant Kras- and p16-regulated NOX4 activation overcomes metabolic checkpoints in development of pancreatic ductal adenocarcinoma

    PubMed Central

    Ju, Huai-Qiang; Ying, Haoqiang; Tian, Tian; Ling, Jianhua; Fu, Jie; Lu, Yu; Wu, Min; Yang, Lifeng; Achreja, Abhinav; Chen, Gang; Zhuang, Zhuonan; Wang, Huamin; Nagrath, Deepak; Yao, Jun; Hung, Mien-Chie; DePinho, Ronald A.; Huang, Peng; Xu, Rui-Hua; Chiao, Paul J.

    2017-01-01

    Kras activation and p16 inactivation are required to develop pancreatic ductal adenocarcinoma (PDAC). However, the biochemical mechanisms underlying these double alterations remain unclear. Here we discover that NAD(P)H oxidase 4 (NOX4), an enzyme known to catalyse the oxidation of NAD(P)H, is upregulated when p16 is inactivated by looking at gene expression profiling studies. Activation of NOX4 requires catalytic subunit p22phox, which is upregulated following Kras activation. Both alterations are also detectable in PDAC cell lines and patient specimens. Furthermore, we show that elevated NOX4 activity accelerates oxidation of NADH and supports increased glycolysis by generating NAD+, a substrate for GAPDH-mediated glycolytic reaction, promoting PDAC cell growth. Mechanistically, NOX4 was induced through p16-Rb-regulated E2F and p22phox was induced by KrasG12V-activated NF-κB. In conclusion, we provide a biochemical explanation for the cooperation between p16 inactivation and Kras activation in PDAC development and suggest that NOX4 is a potential therapeutic target for PDAC. PMID:28232723

  17. The gene for cherubism maps to chromosome 4p16.

    PubMed Central

    Tiziani, V; Reichenberger, E; Buzzo, C L; Niazi, S; Fukai, N; Stiller, M; Peters, H; Salzano, F M; Raposo do Amaral, C M; Olsen, B R

    1999-01-01

    Cherubism is an autosomal dominant disorder that may be related to tooth development and eruption. It is a disorder of age-related bone remodeling, mostly limited to the maxilla and the mandible, with loss of bone in the jaws and its replacement with large amounts of fibrous tissue. We have used a genomewide search with a three-generation family and have established linkage to chromosome 4p16. Three other families affected with cherubism were also genotyped and were mapped to the same locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus spans an interval of approximately 22 cM. PMID:10364528

  18. Frustration of square cupola in Sr(TiO)Cu4(PO4)4

    NASA Astrophysics Data System (ADS)

    Islam, S. S.; Ranjith, K. M.; Baenitz, M.; Skourski, Y.; Tsirlin, A. A.; Nath, R.

    2018-05-01

    The structural and magnetic properties of the square-cupola antiferromagnet Sr (TiO ) Cu4(PO4)4 are investigated via x-ray diffraction, magnetization, heat capacity, and 31P nuclear magnetic resonance experiments on polycrystalline samples, as well as density-functional band-structure calculations. The temperature-dependent unit-cell volume could be described well using the Debye approximation with a Debye temperature of θD≃ 550 K. Magnetic response reveals a pronounced two-dimensionality with a magnetic long-range order below TN≃6.2 K. High-field magnetization exhibits a kink at about 1 /3 of the saturation magnetization. Asymmetric 31P NMR spectra clearly suggest strong in-plane anisotropy in the magnetic susceptibility, as anticipated from the crystal structure. From the 31P NMR shift versus bulk susceptibility plot, the isotropic and axial parts of the hyperfine coupling between the 31P nuclei and the Cu2 + spins are calculated to be Ahfiso≃6539 and Ahfax≃952 Oe/μB, respectively. The low-temperature and low-field 31P NMR spectra indicate a commensurate antiferromagnetic ordering. The frustrated nature of the compound is inferred from the temperature-dependent 31P NMR spin-lattice relaxation rate and confirmed by our microscopic analysis, which reveals strong frustration of the square cupola by next-nearest-neighbor exchange couplings.

  19. Fluorescent LaVO4:Eu(3+) micro/nanocrystals: pH-tuned shape and phase evolution and investigation of the mechanism of detection of Fe(3+) ions.

    PubMed

    Zhu, Yaqiong; Ni, Yonghong; Sheng, Enhong

    2016-06-07

    LaVO4:Eu(3+) micro/nanocrystals with various shapes were hydrothermally synthesized by adjusting the pH of the system at 180 °C for 12 h in the presence of ethylenediaminetetraacetic acid (EDTA). The shape and phase of the final product were characterized by field emission scanning electron microscopy (FESEM) and X-ray powder diffraction (XRD). Experiments showed that when the other conditions were kept unchanged, the shape of the final product changed from hollow microspheres constructed by nanorods to long nanorods, to short nanorods and finally to grains with microscale sizes with the pH increase from 4.0, 7.0, 11.0 to 13.0 in the system. Meanwhile, the t-LaVO4 phase was always obtained from the system at pH below 13.0 and the m-LaVO4 phase was formed at pH 13.0. It was found that the final product with various shapes presented different luminescence performances. LaVO4:Eu(3+) nanorods obtained from the system at pH 11.0 displayed the strongest luminescence and good fluorescence stability in water. Also, the above strong PL spectrum could be quenched by Fe(3+) ions without the interference of other ions, indicating that the present product could be used as an efficient fluorescent probe for highly selective detection of Fe(3+) ions in water systems. The fluorescence quenching mechanism was investigated simultaneously.

  20. The structure of the Myo4p globular tail and its function in ASH1 mRNA localization.

    PubMed

    Heuck, Alexander; Fetka, Ingrid; Brewer, Daniel N; Hüls, Daniela; Munson, Mary; Jansen, Ralf-Peter; Niessing, Dierk

    2010-05-03

    Type V myosin (MyoV)-dependent transport of cargo is an essential process in eukaryotes. Studies on yeast and vertebrate MyoV showed that their globular tails mediate binding to the cargo complexes. In Saccharomyces cerevisiae, the MyoV motor Myo4p interacts with She3p to localize asymmetric synthesis of HO 1 (ASH1) mRNA into the bud of dividing cells. A recent study showed that localization of GFP-MS2-tethered ASH1 particles does not require the Myo4p globular tail, challenging the supposed role of this domain. We assessed ASH1 mRNA and Myo4p distribution more directly and found that their localization is impaired in cells expressing globular tail-lacking Myo4p. In vitro studies further show that the globular tail together with a more N-terminal linker region is required for efficient She3p binding. We also determined the x-ray structure of the Myo4p globular tail and identify a conserved surface patch important for She3p binding. The structure shows pronounced similarities to membrane-tethering complexes and indicates that Myo4p may not undergo auto-inhibition of its motor domain.