Energy, fine structure, and hyperfine structure of the core-excited states 1s2s2pnp 5P (n = 2-5) and 1s2p2mp 5S (m = 2-5) for Li- ion

International Nuclear Information System (INIS)

Wang, Z.B.; Gou, B.C.; Chen, F.

2006-01-01

The relativistic energies, the oscillator strength, and the lifetimes of high-lying core-excited states 1s2s2pnp 5 P (n=2-5) and 1s2p 2 mp 5 S 0 (m=2-5) of Li - ion are calculated with the saddle-point variational method and restricted variation method. The fine structure and the hyperfine structure of the core-excited states for this system are also explored. The results are compared with other theoretical and experimental data in the literature. The energy obtained in this work are much lower than the others previously published whereas the wavelengths and radiative life-times are in agreement

5-Gb/s 0.18-{mu}m CMOS 2:1 multiplexer with integrated clock extraction

Energy Technology Data Exchange (ETDEWEB)

Zhang Changchun; Wang Zhigong; Shi Si; Miao Peng [Institute of RF- and OE-ICs, Southeast University, Nanjing 210096 (China); Tian Ling, E-mail: zgwang@seu.edu.c [School of Science and Engineering, Southeast University, Nanjing 210096 (China)

2009-09-15

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 {mu}m CMOS technology. The chip area is 670 x 780 {mu}m{sup 2}. At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

Word Frequency Analysis. MOS: 95B. Skill Levels 1 & 2.

Science.gov (United States)

1981-05-01

4 Ll,;- I L ENGT H I Lr- SE~k if I! Scp o 11 LF;’S I LzT -2 LE * -R S------- LEV L 7 Ll ’ ’rIE I L iF I LIFT It L IGHT ? -ifvTL b L IGHTS... OIL ! 126 o -IL iIY I 41NO i P 1NJLkkL I. - 1 fr.fm1lz l’% o 5 𔃾lii 7Ilj E1 I lPPRCPRIATICN I ’I 2OF MT FIED I m Iss ; 4 I M1xTUP E 2 IbCCFL I ~~.I...P AI.,T 3 PC 1:. 3 P? VIS 1Z PA~LM 2 PALMS I1 PAM I PA NyC. * I Ph4"EC 38 P.RA 2 rop!.DE I 1 ARP 3 P..- LL EL I P0;R t-1I L 17AR Y 5 Pi-M. A - AI t

Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

International Nuclear Information System (INIS)

Neuffer, D.B.

1977-05-01

Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

Synthesis optimisation and characterisation of the organic-inorganic layered materials ZnS(m-xylylenediamine){sub 1/2} and ZnS(p-xylylenediamine){sub 1/2}

Energy Technology Data Exchange (ETDEWEB)

Luberda-Durnaś, K. [Institute of Geological Sciences PAS, Research Centre in Krakow, Senacka 1, Krakow 31-002 (Poland); Guillén, A. González [Faculty of Chemistry, Jagiellonian University, Ingardena 3, Krakow 30-060 (Poland); Łasocha, W., E-mail: lasocha@chemia.uj.edu.pl [Jerzy Haber Institute of Catalysis and Surface Chemistry PAS, Niezapominajek 8, Krakow 30-239 (Poland); Faculty of Chemistry, Jagiellonian University, Ingardena 3, Krakow 30-060 (Poland)

2016-06-15

Hybrid organic-inorganic layered materials of the type ZnS(amine){sub 1/2}, where amine=m-xylylenediamine (MXDA) or p-xylylenediamine (PXDA), were synthesised using a simple solvothermal method. Since the samples crystallised in the form of very fine powder, X-ray powder diffraction techniques were used for structural characterisation. The crystal structure studies, involving direct methods, show that both compounds crystallised in the orthorhombic crystal system, but in different space groups: ZnS(MXDA){sub 1/2} in non-centrosymmetric Ccm2{sub 1}, ZnS(PXDA){sub 1/2} in centrosymmetric Pcab. The obtained materials are built according to similar orders: semiconducting monolayers with the formula ZnS, parallel to the (010) plane, are separated by diamines. The organic and inorganic fragments are connected by covalent bonds between metal atoms of the layers and nitrogen atoms of the amino groups. The optical properties of the hybrid materials differ from those of their bulk counterpart. In both compounds a blue-shift of about 0.8 or 0.9 eV was observed with reference to the bulk phase of ZnS. - Highlights: • New hybrid compounds: ZnS(MXDA){sub 1/2} and ZnS(PXDA){sub 1/2} were obtained. • Hybrids were studied using XRD, TG/DSC, XRK, SEM, UV–vis spectroscopy. • Structures of both materials were solved by powder diffraction methods.

EURAMET.M.P-S9: comparison in the negative gauge pressure range -950 to 0 hPa

Science.gov (United States)

Saxholm, S.; Otal, P.; AltintaS, A.; Bermanec, L. G.; Durgut, Y.; Hanrahan, R.; Kocas, I.; Lefkopoulos, A.; Pražák, D.; Sandu, I.; Åetina, J.; Spohr, I.; Steindl, D.; Tammik, K.; Testa, N.

2016-01-01

A comparison in the negative gauge pressure range was arranged in the period 2011 - 2012. A total of 14 laboratories participated in this comparison: BEV (Austria), CMI (Czech Republic), DANIAmet-FORCE (Denmark), EIM (Greece), HMI/FSB-LPM (Croatia), INM (Romania), IPQ (Portugal), LNE (France), MCCAA (Malta), METROSERT (Estonia), MIKES (Finland), MIRS/IMT/LMT (Slovenia), NSAI (Ireland) and UME (Turkey). The project was divided into two loops: Loop1, piloted by MIKES, and Loop2, piloted by LNE. The results of the two loops are reported separately: Loop1 results are presented in this paper. The transfer standard was Beamex MC5 no. 25516865 with internal pressure module INT1C, resolution 0.01 hPa. The nominal pressure range of the INT1C is -1000 hPa to +1000 hPa. The nominal pressure points for the comparison were 0 hPa, -200 hPa, -400 hPa, -600 hPa, -800 hPa and -950 hPa. The reference values and their uncertainties as well as the difference uncertainty between the laboratory results and the reference values were determined from the measurement data by Monte Carlo simulations. Stability uncertainty of the transfer standard was included in the final difference uncertainty. Degrees of equivalences and mutual equivalences between the laboratories were calculated. Each laboratory reported results for all twelve measurement points, which means that there were 168 reported values in total. Some 163 of the 168 values (97 %) agree with the reference values within the expanded uncertainties, with a coverage factor k = 2. Among the laboratories, four different methods were used to determine negative gauge pressure. It is concluded that special attention must be paid to the measurements and methods when measuring negative gauge pressures. There might be a need for a technical guide or a workshop that provides information about details and practices related to the measurements of negative gauge pressure, as well as differences between the different methods. The comparison is

M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

Directory of Open Access Journals (Sweden)

Shoichi Fukui

2018-01-01

Full Text Available ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA.MethodsPeripheral blood mononuclear cells (PBMCs were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55% were anticitrullinated protein antibody (ACPA positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range. There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001. The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028 and significantly greater numbers of OCs in vitro (p = 0.005 than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

5-Gb/s 0.18-μm CMOS 2:1 multiplexer with integrated clock extraction

International Nuclear Information System (INIS)

Zhang Changchun; Wang Zhigong; Shi Si; Miao Peng; Tian Ling

2009-01-01

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 μm CMOS technology. The chip area is 670 x 780 μm 2 . At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

5-Gb/s 0.18-μm CMOS 2:1 multiplexer with integrated clock extraction

Science.gov (United States)

Changchun, Zhang; Zhigong, Wang; Si, Shi; Peng, Miao; Ling, Tian

2009-09-01

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 μm CMOS technology. The chip area is 670 × 780 μm2. At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

Glutathione S-transferase M1 and T1, CYP1A2-2467T/delT ...

African Journals Online (AJOL)

The present study investigated the impact of metabolic gene polymorphisms in modulating lung cancer risk susceptibility. Gene polymorphisms encoding Cytochrome 1A2 (CYP1A2) and Glutathione-S-transferases (GSTT1 and GSTM1) are involved in the bioactivation and detoxification of tobacco carcinogens and may ...

Determination of the 1s2{\\ell }2{{\\ell }}^{\\prime } state production ratios {{}^{4}P}^{o}/{}^{2}P, {}^{2}D/{}^{2}P and {{}^{2}P}_{+}/{{}^{2}P}_{-} from fast (1{s}^{2},1s2s\\,{}^{3}S) mixed-state He-like ion beams in collisions with H2 targets

Science.gov (United States)

Benis, E. P.; Zouros, T. J. M.

2016-12-01

New results are presented on the ratio {R}m={σ }{T2p}( {}4P)/{σ }{T2p}({}2P) concerning the production cross sections of Li-like 1s2s2p quartet and doublet P states formed in energetic ion-atom collisions by single 2p electron transfer to the metastable 1s2s {}3S component of the He-like ion beam. Spin statistics predict a value of R m = 2 independent of the collision system in disagreement with most reported measurements of {R}m≃ 1{--}9. A new experimental approach is presented for the evaluation of R m having some practical advantages over earlier approaches. It also allows for the determination of the separate contributions of ground- and metastable-state beam components to the measured spectra. Applying our technique to zero-degree Auger projectile spectra from 4.5 MeV {{{B}}}3+ (Benis et al 2002 Phys. Rev. A 65 064701) and 25.3 MeV {{{F}}}7+ (Zamkov et al 2002 Phys. Rev. A 65 062706) mixed state (1{s}2 {}1S,1s2s {}3S) He-like ion collisions with H2 targets, we report new values of {R}m=3.5+/- 0.4 for boron and {R}m=1.8+/- 0.3 for fluorine. In addition, the ratios of {}2D/{}2P and {{}2P}+/{{}2P}- populations from either the metastable and/or ground state beam component, also relevant to this analysis, are evaluated and compared to previously reported results for carbon collisions on helium (Strohschein et al 2008 Phys. Rev. A 77 022706) including a critical comparison to theory.

Complementary vapor pressure data for 2-methyl-1-propanol and 3-methyl-1-butanol at a pressure range of (15 to 177) kPa

Energy Technology Data Exchange (ETDEWEB)

Bejarano, Arturo; Quezada, Nathalie [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Avda. Espana 1680, Valparaiso (Chile); Fuente, Juan C. de la [Departamento de Ingenieria Quimica y Ambiental, Universidad Tecnica Federico Santa Maria, Avda. Espana 1680, Valparaiso (Chile)], E-mail: juan.delafuente@usm.cl

2009-09-15

The vapor pressure of pure 2-methyl-1-propanol and 3-methyl-1-butanol, components called congeners that are present in aroma of wine, pisco, and other alcoholic beverages, were measured with a dynamic recirculation apparatus at a pressure range of (15 to 177) kPa with an estimated uncertainty <0.2%. The measurements were performed at temperature ranges of (337 to 392) K for 2-methyl-1-propanol and (358 to 422) K for 3-methyl-1-butanol. Data were correlated using a Wagner-type equation with standard deviations of 0.09 kPa for the vapor pressure of 2-methyl-1-propanol and 0.21 kPa for 3-methyl-1-butanol. The experimental data and correlation were compared with data selected from the literature.

Thermodynamic properties of CuCr/sub 2/S/sub 4/ solid solutions in Cusub(1/2)Msub(1/2) Crsub(2)Ssub(4) (M - Ga, In)

Energy Technology Data Exchange (ETDEWEB)

Titov, V.V.; Kesler, Ya.A.; Shelkotunov, V.A.; Gordeev, I.V.; Tret' yakov, Yu.D.

1985-04-01

By means of an adiabatic calorimeter and quartz dilatometer for CuCr/sub 2/S/sub 4/ in Cusub(1/2)Msub(1/2) Crsub(2)Ssub(4) (M-Ga, In) temperature dependences of heat capacity are determined. The contribution of various components into heat capacity is estimated, thermodynamic parameters of magnetic transformation are calculated.

Energies and E1, M1, E2, and M2 transition rates for states of the 2s{sup 2}2p{sup 3}, 2s2p{sup 4}, and 2p{sup 5} configurations in nitrogen-like ions between F III and Kr XXX

Energy Technology Data Exchange (ETDEWEB)

Rynkun, P., E-mail: pavel.rynkun@gmail.com [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Jönsson, P. [Group for Materials Science and Applied Mathematics, Malmö University, 20506 Malmö (Sweden); Gaigalas, G. [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Vilnius University, Institute of Theoretical Physics and Astronomy, A. Goštauto 12, LT-01108 Vilnius (Lithuania); Froese Fischer, C. [National Institute of Standards and Technology, Gaithersburg, MD 20899-8420 (United States)

2014-03-15

Based on relativistic wavefunctions from multiconfiguration Dirac–Hartree–Fock and configuration interaction calculations, E1, M1, E2, and M2 transition rates, weighted oscillator strengths, and lifetimes are evaluated for the states of the (1s{sup 2})2s{sup 2}2p{sup 3},2s2p{sup 4}, and 2p{sup 5} configurations in all nitrogen-like ions between F III and Kr XXX. The wavefunction expansions include valence, core–valence, and core–core correlation effects through single–double multireference expansions to increasing sets of active orbitals. The computed energies agree very well with experimental values, with differences of only 300–600 cm{sup −1} for the majority of the levels and ions in the sequence. Computed transitions rates are in close agreement with available data from MCHF-BP calculations by Tachiev and Froese Fischer [G.I. Tachiev, C. Froese Fischer, A and A 385 (2002) 716].

Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

Science.gov (United States)

POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

2015-01-01

Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

Lifescience Database Archive (English)

Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

Form factors of descendant operators: reduction to perturbed M(2,2s+1) models

International Nuclear Information System (INIS)

Lashkevich, Michael; Pugai, Yaroslav

2015-01-01

In the framework of the algebraic approach to form factors in two-dimensional integrable models of quantum field theory we consider the reduction of the sine-Gordon model to the Φ 13 -perturbation of minimal conformal models of the M(2,2s+1) series. We find in an algebraic form the condition of compatibility of local operators with the reduction. We propose a construction that make it possible to obtain reduction compatible local operators in terms of screening currents. As an application we obtain exact multiparticle form factors for the compatible with the reduction conserved currents T ±2k , Θ ±(2k−2) , which correspond to the spin ±(2k−1) integrals of motion, for any positive integer k. Furthermore, we obtain all form factors of the operators T 2k T −2l , which generalize the famous TT̄ operator. The construction is analytic in the s parameter and, therefore, makes sense in the sine-Gordon theory.

Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

Science.gov (United States)

Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

2014-01-01

Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

M-theory solutions invariant under D(2,1; γ) + D(2,1;γ)

International Nuclear Information System (INIS)

Bachas, C.; D'Hoker, E.; Estes, J.; Krym, D.

2014-01-01

We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;γ) + D(2,1;γ). Their space-time has the form AdS 3 x S 3 x S 3 warped over a Riemann surface Σ. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (γ, h, G), where γ is the real parameter of the isometry superalgebra, and h and G are functions on Σ whose differential equations and regularity conditions depend only on the sign of γ. The magnitude of γ enters only through the map of h,G onto the supergravity fields, thereby promoting all solutions into families parametrized by vertical stroke γ vertical stroke. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS 3 x S 3 x S 3 x R 2 , modulo discrete identifications of the flat R 2 , and (ii) that solutions with γ 4 /Z 2 or AdS 7 ' regions; highly-curved M5-branes; and a coordinate singularity called the ''cap''. By putting these ''Lego'' pieces together we recover all known global regular solutions with the above symmetry, including the self-dual strings on M5 for γ 0, but now promoted to families parametrized by vertical stroke γ vertical stroke. We also construct exactly new regular solutions which are asymptotic to AdS 4 /Z 2 for γ 0 solutions with highly curved M5-brane regions, which are the formal continuation of the self-dual string solutions across the decompactification point at γ = 0. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Theoretical descriptions of novel triplet germylenes M1-Ge-M2-M3 (M1 = H, Li, Na, K; M2 = Be, Mg, Ca; M3 = H, F, Cl, Br).

Science.gov (United States)

Kassaee, Mohamad Zaman; Ashenagar, Samaneh

2018-02-06

In a quest to identify new ground-state triplet germylenes, the stabilities (singlet-triplet energy differences, ΔE S-T ) of 96 singlet (s) and triplet (t) M 1 -Ge-M 2 -M 3 species were compared and contrasted at the B3LYP/6-311++G**, QCISD(T)/6-311++G**, and CCSD(T)/6-311++G** levels of theory (M 1  = H, Li, Na, K; M 2  = Be, Mg, Ca; M 3  = H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M 3  = F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M 3  = Cl or Br). Triplets with M 1  = K (i.e., the K-Ge-M 2 -M 3 series) seem to be more stable than the corresponding triplets with M 1  = H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M 3  = Cl behave similarly to those with M 3  = Br. Conversely, triplets with M 3  = H show similar stabilities and linearities to those with M 3  = F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M 1 -Ge-M 2 -M 3 become more stable as the electropositivities of the α-substituents (M 1 and M 2 ) and the electronegativity of the β-substituent (M 3 ) increase.

Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

African Journals Online (AJOL)

Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

mTORC1 Targets the Translational Repressor 4E-BP2, but Not S6 Kinase 1/2, to Regulate Neural Stem Cell Self-Renewal In Vivo

Directory of Open Access Journals (Sweden)

Nathaniel W. Hartman

2013-10-01

Full Text Available The mammalian target of rapamycin complex 1 (mTORC1 integrates signals important for cell growth, and its dysregulation in neural stem cells (NSCs is implicated in several neurological disorders associated with abnormal neurogenesis and brain size. However, the function of mTORC1 on NSC self-renewal and the downstream regulatory mechanisms are ill defined. Here, we found that genetically decreasing mTORC1 activity in neonatal NSCs prevented their differentiation, resulting in reduced lineage expansion and aborted neuron production. Constitutive activation of the translational repressor 4E-BP1, which blocked cap-dependent translation, had similar effects and prevented hyperactive mTORC1 induction of NSC differentiation and promoted self-renewal. Although 4E-BP2 knockdown promoted NSC differentiation, p70 S6 kinase 1 and 2 (S6K1/S6K2 knockdown did not affect NSC differentiation but reduced NSC soma size and prevented hyperactive mTORC1-induced increase in soma size. These data demonstrate a crucial role of mTORC1 and 4E-BP for switching on and off cap-dependent translation in NSC differentiation.

Rates of E1, E2, M1, and M2 transitions in Ni II

Science.gov (United States)

Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

2016-03-01

Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

PA-1, a Versatile Anaerobe Obtained in Pure Culture, Catabolizes Benzenoids and Other Compounds in Syntrophy with Hydrogenotrophs, and P-2 plus Wolinella sp. Degrades Benzenoids

Science.gov (United States)

Barik, Sudhakar; Brulla, W. J.; Bryant, M. P.

1985-01-01

Methanogenic enrichments catabolizing 13 mM phenylacetate or 4 mM phenol were established at 37°C, using a 10% inoculum from a municipal anaerobic digester. By using agar roll tubes of the basal medium plus 0.1% yeast extract-25 mM fumarate, a hydrogenotrophic lawn of Wolinella succinogenes and phenol or phenylacetate, strains P-2 and PA-1, respectively, were isolated in coculture with W. succinogenes. With the lawn deleted, PA-1 was isolated in pure culture. Strain P-2 is apparently a new species of anaerobic, motile, gram-negative, spindle-shaped, small rod that as yet has been grown only in coculture with W. succinogenes. It used phenol, hydrocinnamate, benzoate, and phenylacetate as energy sources. Product recovery by the coculture, per mole of phenol and 4.4 mol of fumarate used, included 2.03, 0.12, 0.08, and 3.23 mol, respectively, of acetate, propionate, butyrate, and succinate. Carbon recovery was 75% and H recovery was 80%, although CO2 and a few other possible products were not determined. That P-2 is an obligate proton-reducing acetogen and possible pathways for its degradation of phenol are discussed. Strain PA-1 is apparently a new species of anaerobic, motile, relatively small, gram-negative rod. It utilized compounds such as phenylacetate, hydrocinnamate, benzoate, phenol, resorcinol, gallate, 4-aminophenol, 2-aminobenzoate, pyruvate, Casamino Acids, and aspartate as energy sources in coculture with W. succinogenes. Per mole of phenylacetate and 1.44 mol of fumarate used, 1.04, 0.53, and 0.78 mol of acetate, propionate, and succinate, respectively, were recovered from the coculture. Only about 50% of the carbon and H were recovered. In coculture with Methanospirillum hungatei, 0.96 mol of acetate and 0.25 mol of methane were recovered per mol of pyruvate used; 0.90 mol of acetate and 0.33 mol of methane, per mol of fumarate used; 0.93 mol of acetate and 0.54 mol of methane, per mol of aspartate used; and 1.71 mol of acetate and 0.57 mol of methane

KEY COMPARISON: Final report on APMP.M.P-K6.1 pneumatic key comparison from 20 kPa to 105 kPa in gauge mode

Science.gov (United States)

Hung, Chen-Chuan; Jian, Wu; Changpan, Tawat

2009-01-01

This report describes the key comparison APMP.M.P-K6.1 among the three national metrology institutes, Center for Measurement Standards-ITRI (CMS-ITRI, Taiwan), SPRING Singapore and National Institute of Metrology (NIMT), in the pressure range from 20 kPa to 105 kPa in gas media and gauge mode executed during the period April 2003 to April 2004. This comparison was conducted by CMS-ITRI and was based on the calibration procedure of APMP pneumatic pressure comparison APMP.M.P-K6. We intended to link to the CCM.P-K6 key comparison through the APMP.M.P-K6 key comparison by using the proposed linkage method in the APMP.M.P-K6 key comparison to determine a linking factor that can transform the quantities measured in the APMP.M.P-K6.1 key comparison. All three participating institutes used pneumatic piston gauges as their pressure standards. The Ruska 2465 gas-operated piston-cylinder assembly TL-1409 used as transfer standard offered by CMS-ITRI was calibrated three times by the pilot institute during the comparison period and showed that it was very stable after evaluation. The comparison was conducted on the basis of cross-float experiments to determine the effective area of transfer standards from the national standards of three institutes. The comparison results (as shown in Table 6) were equivalent to the CCM.P-K6 comparison and the relative bilateral degrees of equivalence between two laboratories were smaller than 39.7 × 10-6 from 20 kPa to 105 kPa. These results showed all participating institutes measuring the same quantity in the whole pressure range lay within their expanded uncertainty with confidence level 95%. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

PA-X protein contributes to virulence of triple-reassortant H1N2 influenza virus by suppressing early immune responses in swine.

Science.gov (United States)

Xu, Guanlong; Zhang, Xuxiao; Liu, Qinfang; Bing, Guoxia; Hu, Zhe; Sun, Honglei; Xiong, Xin; Jiang, Ming; He, Qiming; Wang, Yu; Pu, Juan; Guo, Xin; Yang, Hanchun; Liu, Jinhua; Sun, Yipeng

2017-08-01

Previous studies have identified a functional role of PA-X for influenza viruses in mice and avian species; however, its role in swine remains unknown. Toward this, we constructed PA-X deficient virus (Sw-FS) in the background of a Triple-reassortment (TR) H1N2 swine influenza virus (SIV) to assess the impact of PA-X in viral virulence in pigs. Expression of PA-X in TR H1N2 SIV enhanced viral replication and host protein synthesis shutoff, and inhibited the mRNA levels of type I IFNs and proinflammatory cytokines in porcine cells. A delay of proinflammatory responses was observed in lungs of pigs infected by wild type SIV (Sw-WT) compared to Sw-FS. Furthermore, Sw-WT virus replicated and transmitted more efficiently than Sw-FS in pigs. These results highlight the importance of PA-X in the moderation of virulence and immune responses of TR SIV in swine, which indicated that PA-X is a pro-virulence factor in TR SIV in pigs. Copyright © 2017 Elsevier Inc. All rights reserved.

2D numerical comparison between S{sub n} and M{sub 1} radiation transport methods

Energy Technology Data Exchange (ETDEWEB)

Gonzalez, Matthias [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid, calle Jose Gutierrez Abascal 2, 28006 Madrid (Spain)], E-mail: matthias@din.upm.es; Garcia-Fernandez, Carlos [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid, calle Jose Gutierrez Abascal 2, 28006 Madrid (Spain)], E-mail: carlos@din.upm.es; Velarde, Pedro [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid, calle Jose Gutierrez Abascal 2, 28006 Madrid (Spain)], E-mail: velarde@din.upm.es

2009-07-15

In this article we study the accuracy of the M{sub 1} method to solve some relevant radiation transport problems in 2D. We compare two radiation models (S{sub n} and M{sub 1}) with analytical and numerical tests to highlight the strengths and limitations of each method. These methods give comparable results except when sharp geometry effects are present. We have used these methods in a test that mimics, without fluid motion or electron heat conduction, the cone-target interaction relevant to inertial confinement fusion physics. In this case, we show that S{sub n} and M{sub 1} models agree with a quite good accuracy but shows differences in the temperature profiles and heating times inside the target. These results point out that M{sub 1} is a possible alternative candidate for 3D simulations, where full energy transport methods are extremely computer time consuming.

Phase diagram of ZnCr2pA12-2pS(Se)4 and Zn1-pCdpCr2S(Se)4

International Nuclear Information System (INIS)

Afif, K.; Benyoussef, A.; Hamedoun, M.; Hourmatallah, A.

1999-06-01

We compute the phase diagram of the nonmetallic compounds ZnCr2 p A1 2-2p S(Se) 4 (I[S,Se]) and Zn 1-p Cd p Cr 2 S(Se) 4 (II[S,Se]). We consider the bond-diluted Ising model on the spinel B site (S.B.S.) lattice with competitive exchange interactions, i.e. the ferromagnetic exchange interaction J 1 between nearest neighbours (n.n.) and the antiferromagnetic superexchange interaction J 2 between next-nearest neighbours' (n.n.n.) (and/or the more distant superexchange interactions J i (i > 1). Dilution and competition are found to be responsible for the spill glass phase and the percolation behaviour. (author)

M-theory solutions invariant under D(2,1; γ) + D(2,1;γ)

Energy Technology Data Exchange (ETDEWEB)

Bachas, C. [Laboratoire de Physique Theorique de l' Ecole Normale Superieure Unite mixte (UMR 8549) du CNRS et de l' ENS, Paris (France); D' Hoker, E. [Department of Physics and Astronomy, University of California, Los Angeles, CA (United States); Estes, J. [Blackett Laboratory, Imperial College, London (United Kingdom); Krym, D. [Physics Department, New York City College of Technology, The City University of New York, Brooklyn, NY (United States)

2014-03-06

We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;γ) + D(2,1;γ). Their space-time has the form AdS{sub 3} x S{sup 3} x S{sup 3} warped over a Riemann surface Σ. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (γ, h, G), where γ is the real parameter of the isometry superalgebra, and h and G are functions on Σ whose differential equations and regularity conditions depend only on the sign of γ. The magnitude of γ enters only through the map of h,G onto the supergravity fields, thereby promoting all solutions into families parametrized by vertical stroke γ vertical stroke. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS{sub 3} x S{sup 3} x S{sup 3} x R {sup 2}, modulo discrete identifications of the flat R {sup 2}, and (ii) that solutions with γ < 0 cannot have more than one asymptotic higher-dimensional AdS region. We classify the allowed singularities of h and G near the boundary of Σ, and identify four local solutions: asymptotic AdS{sub 4}/Z{sub 2} or AdS{sub 7}' regions; highly-curved M5-branes; and a coordinate singularity called the ''cap''. By putting these ''Lego'' pieces together we recover all known global regular solutions with the above symmetry, including the self-dual strings on M5 for γ <0, and the Janus solution for γ > 0, but now promoted to families parametrized by vertical stroke γ vertical stroke. We also construct exactly new regular solutions which are asymptotic to AdS{sub 4}/Z{sub 2} for γ < 0, and conjecture that they are a different superconformal limit of the self-dual string. Finally, we construct exactly γ > 0 solutions with highly curved M5

CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

Directory of Open Access Journals (Sweden)

Paula Mota

2010-01-01

ção T6235C e m2 (transição A4889G, estão associados a uma maior actividade enzimática, tendo sido referidos como factores genéticos de susceptibilidade para o cancro do pulmão.Este trabalho teve como objectivo verificar esta possível associação em 175 doentes com cancro do pulmão e 217 controlos da Região Centro de Portugal, por RFLP (polimorfismo de comprimento de fragmentos de restrição.Foi encontrada a seguinte distribuição para as frequências alélicas: 0.12 e 1.14, para os alelos mutados C e G, respectivamente, na população controlo. Os resultados não revelaram significado estatístico quando comparados com a distribuição encontrada na população de doentes. Relativamente à distribuição genotípica, a situação foi semelhante, não se registando significado estatístico, mesmo quando foram considerados genótipos de alto risco. Tal como noutras populações de diferente origem étnica, parece existir desequilíbrio de ligação para ambos os polimorfimos na população-controlo. Concluímos que nesta amostra de população portuguesa os polimorfismos m1 e m2 de CYP1A1 são particularmente raros, parecendo não existir relevância clínica nem associação à susceptibilidade ao cancro do pulmão. Key-words: Lung cancer, smoking, cytochrome P450, CYP1A1, linkage disequilibrium, Palavras-chave: Cancro do pulmão, tabaco, citocromo p450, CYP1A1, desequilíbrio de ligação

PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

Science.gov (United States)

Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

2013-11-01

We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells. © 2013.

PaTrx1 and PaTrx3, two cytosolic thioredoxins of the filamentous ascomycete Podospora anserina involved in sexual development and cell degeneration.

Science.gov (United States)

Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

2007-12-01

In various organisms, thioredoxins are known to be involved in the reduction of protein disulfide bonds and in protecting the cell from oxidative stress. Genes encoding thioredoxins were found by searching the complete genome sequence of the filamentous ascomycete Podospora anserina. Among them, PaTrx1, PaTrx2, and PaTrx3 are predicted to be canonical cytosolic proteins without additional domains. Targeted disruption of PaTrx1, PaTrx2, and PaTrx3 shows that PaTrx1 is the major thioredoxin involved in sulfur metabolism. Deletions have no effect on peroxide resistance; however, data show that either PaTrx1 or PaTrx3 is necessary for sexual reproduction and for the development of the crippled growth cell degeneration (CG), processes that also required the PaMpk1 mitogen-activated protein kinase (MAPK) pathway. Since PaTrx1 PaTrx3 mutants show not an enhancement but rather an impairment in CG, it seems unlikely that PaTrx1 and PaTrx3 thioredoxins participate in the inhibition of this MAPK pathway. Altogether, these results underscore a role for thioredoxins in fungal development.

H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells.

Science.gov (United States)

Mazel-Sanchez, B; Boal-Carvalho, I; Silva, F; Dijkman, R; Schmolke, M

2018-06-01

Highly pathogenic influenza A viruses (IAV) from avian hosts were first reported to directly infect humans 20 years ago. However, such infections are rare events, and our understanding of factors promoting or restricting zoonotic transmission is still limited. One accessory protein of IAV, PB1-F2, was associated with pathogenicity of pandemic and zoonotic IAV. This short (90-amino-acid) peptide does not harbor an enzymatic function. We thus identified host factors interacting with H5N1 PB1-F2, which could explain its importance for virulence. PB1-F2 binds to HCLS1-associated protein X1 (HAX-1), a recently identified host restriction factor of the PA subunit of IAV polymerase complexes. We demonstrate that the PA of a mammal-adapted H1N1 IAV is resistant to HAX-1 imposed restriction, while the PA of an avian-origin H5N1 IAV remains sensitive. We also showed HAX-1 sensitivity for PAs of A/Brevig Mission/1/1918 (H1N1) and A/Shanghai/1/2013 (H7N9), two avian-origin zoonotic IAV. Inhibition of H5N1 polymerase by HAX-1 can be alleviated by its PB1-F2 through direct competition. Accordingly, replication of PB1-F2-deficient H5N1 IAV is attenuated in the presence of large amounts of HAX-1. Mammal-adapted H1N1 and H3N2 viruses do not display this dependence on PB1-F2 for efficient replication in the presence of HAX-1. We propose that PB1-F2 plays a key role in zoonotic transmission of avian H5N1 IAV into humans. IMPORTANCE Aquatic and shore birds are the natural reservoir of influenza A viruses from which the virus can jump into a variety of bird and mammal host species, including humans. H5N1 influenza viruses are a good model for this process. They pose an ongoing threat to human and animal health due to their high mortality rates. However, it is currently unclear what restricts these interspecies jumps on the host side or what promotes them on the virus side. Here we show that a short viral peptide, PB1-F2, helps H5N1 bird influenza viruses to overcome a human restriction

Enantioselective degradation and unidirectional chiral inversion of 2-phenylbutyric acid, an intermediate from linear alkylbenzene, by Xanthobacter flavus PA1

Energy Technology Data Exchange (ETDEWEB)

Liu, Yishan; Han, Ping [School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Li, Xiao-yan; Shih, Kaimin [Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Gu, Ji-Dong, E-mail: jdgu@hkucc.hku.hk [School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong (China); The Swire Institute of Marine Science, The University of Hong Kong, Shek O, Cape d' Aguilar, Hong Kong (China)

2011-09-15

Highlights: {yields} We isolated a Xanthobacter flavus strain PA1 utilizing the racemic 2-PBA and the single enantiomers as the sole source of carbon and energy. {yields} Both (R) and (S) forms of enantiomers can be degraded in a sequential manner in which the (S) disappeared before the (R) form. {yields} The biochemical degradation pathway involves an initial oxidation of the alkyl side chain before aromatic ring cleavage. - Abstract: Microbial degradation of the chiral 2-phenylbutyric acid (2-PBA), a metabolite of surfactant linear alkylbenzene sulfonates (LAS), was investigated using both racemic and enantiomer-pure compounds together with quantitative stereoselective analyses. A pure culture of bacteria, identified as Xanthobacter flavus strain PA1 isolated from the mangrove sediment of Hong Kong Mai Po Nature Reserve, was able to utilize the racemic 2-PBA as well as the single enantiomers as the sole source of carbon and energy. In the presence of the racemic compounds, X. flavus PA1 degraded both (R) and (S) forms of enantiomers to completion in a sequential manner in which the (S) enantiomer disappeared much faster than the (R) enantiomer. When the single pure enantiomer was supplied as the sole substrate, a unidirectional chiral inversion involving (S) enantiomer to (R) enantiomer was evident. No major difference was observed in the degradation intermediates with either of the individual enantiomers when used as the growth substrate. Two major degradation intermediates were detected and identified as 3-hydroxy-2-phenylbutanoic acid and 4-methyl-3-phenyloxetan-2-one, using a combination of liquid chromatography-mass spectrometry (LC-MS), and {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR) spectroscopy. The biochemical degradation pathway follows an initial oxidation of the alkyl side chain before aromatic ring cleavage. This study reveals new evidence for enantiomeric inversion catalyzed by pure culture of environmental bacteria and emphasizes the

Geniposide activates GSH S-transferase by the induction of GST M1 and GST M2 subunits involving the transcription and phosphorylation of MEK-1 signaling in rat hepatocytes

International Nuclear Information System (INIS)

Kuo, W.-H.; Chou, F.-P.; Young, S.-C.; Chang, Y.-C.; Wang, C.-J.

2005-01-01

Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has biological capabilities of detoxication, antioxidation, and anticarcinogenesis. We have recently found that geniposide possesses a potential for detoxication by inducing GST activity and the expression of GST M1 and GST M2 subunits. In this study, the signaling pathway of geniposide leading to the activation of GSH S-transferase (GST) was investigated. Primary cultured rat hepatocytes were treated with geniposide in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors and examined for GST activity, expression of GST M1 and M2 subunits, and protein levels of MAPK signaling proteins. Western blotting data demonstrated that geniposide induced increased protein levels of GST M1 and GST M2 (∼1.76- and 1.50-fold of control, respectively). The effect of geniposide on the increased protein levels of GST M1 and GST M2 was inhibited by the MEK-1 inhibitor PD98059, but not by other MAPK inhibitors. The GST M1 and GST M2 transcripts as determined by RT-PCR and GST activity were also inhibited concurrently by the MEK-1 inhibitor PD98059. The protein levels of up- and down-stream effectors of the MEK-1, including Ras, Raf, and Erk1/2, and the phosphorylation state of Erk1/2 were found to be induced by geniposide, indicating a two-phase influence of geniposide. The results suggest that geniposide induced GST activity and the expression of GST M1 and GST M2 acting through MEK-1 pathway by activating and increasing expression of Ras/Raf/MEK-1 signaling mediators

Reexamination of M2,3 atomic level widths and L1M2,3 transition energies of elements 69≤Z≤95

Science.gov (United States)

Fennane, K.; Berset, M.; Dousse, J.-Cl.; Hoszowska, J.; Raboud, P.-A.; Campbell, J. L.

2013-11-01

We report on high-resolution measurements of the photoinduced L1M2 and L1M3 x-ray emission lines of 69Tm, 70Yb, 71Lu, 73Ta, 74W, 75Re, 77Ir, 81Tl, 83Bi, and 95Am. From the linewidths of the measured transitions an accurate set of M2 and M3 level widths is determined assuming for the L1 level widths the values reported by Raboud [P.-A. Raboud et al., Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.65.022512 65, 022512 (2002)]. Furthermore, the present experimental M2,3 data set is extended to 80Hg, 90Th, and 92U, using former L1M2,3 high-resolution x-ray emission spectroscopy measurements performed by our group. A detailed comparison of the M2 and M3 level widths determined in the present work with those recommended by Campbell and Papp [J. L. Campbell and T. Papp, At. Data Nucl. Data TablesADNDAT0092-640X10.1006/adnd.2000.0848 77, 1 (2001)] and other available experimental data as well as theoretical predictions is done. The observed abrupt changes of the M2,3 level widths versus atomic number Z can be explained satisfactorily by the cutoffs and onsets of the M2M4N1, respectively M3M4N3,4,5 and M3M5N2,3 Coster-Kronig transitions deduced from the semiempirical (Z+1) approximation. As a spin-off result of this study, precise L1M2 and L1M3 transition energies are obtained for the investigated elements. A very good agreement with transition energies calculated within the many-body perturbation theory is found.

Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1.

Science.gov (United States)

Peng, Wen-Huang; Tien, Yun-Chen; Huang, Chih-Yang; Huang, Tai-Hung; Liao, Jung-Chun; Kuo, Chao-Lin; Lin, Ying-Chih

2010-02-17

To investigate the effect of Fraxinus rhynchophylla ethanol extract (FR(EtOH)) on liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats. Rat hepatic fibrosis was induced by oral administration of CCl(4). Sixty SD rats were divided randomly into 6 groups: control, CCl(4) group, silymarin group and three FR(EtOH)-treated groups. Except for the rats in control group, all rats were administered orally with CCl(4) (20%, 0.2 mL/100g body weight) twice a week for 8 weeks. Rats in FR(EtOH) groups were treated daily with FR(EtOH) (0.1, 0.5 and 1.0 g/kg, p.o.) throughout the whole experimental period. Liver function parameters (such as activities of serum GOT and GPT levels), activities of liver anti-oxidant enzymes (such as catalase, SOD, GPx) and expressions of uPA, tPA, MMP-2, MMP-9 and TIMP-1, -2, -3, -4 in the liver fibrosis pathway were detected. The results showed that FR(EtOH) (0.1, 0.5 and 1.0 g/kg BW) significantly reduced the elevated activities of sGOT and sGPT caused by CCl(4). FR(EtOH) (0.1 and 0.5 g/kg BW) and significantly increased the activities of GSH-Px. The histopathological study showed that FR(EtOH) (0.1 and 0.5 g/kg BW) reduced the incidence of liver lesions, including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization hepatic necrosis and fibrous connective tissue proliferated induced by CCl(4) in rats. In our study it was showed that CCl(4)-treated group significantly increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FR(EtOH) (0.1 and 0.5 g/kg BW) could inhibit the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. Finally, the amount of esculetin in the FR(EtOH) was 33.54 mg/g extract. Oral administration of FR(EtOH) significantly reduces CCl(4)-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular fibrosis by its free radical scavenging ability. FR(EtOH) down-regulated the expressions of uPA, MMP-2 and MMP-9 in CCl(4)-induced liver fibrosis in rats

PaTrx1 and PaTrx3, Two Cytosolic Thioredoxins of the Filamentous Ascomycete Podospora anserina Involved in Sexual Development and Cell Degeneration▿ †

Science.gov (United States)

Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

2007-01-01

In various organisms, thioredoxins are known to be involved in the reduction of protein disulfide bonds and in protecting the cell from oxidative stress. Genes encoding thioredoxins were found by searching the complete genome sequence of the filamentous ascomycete Podospora anserina. Among them, PaTrx1, PaTrx2, and PaTrx3 are predicted to be canonical cytosolic proteins without additional domains. Targeted disruption of PaTrx1, PaTrx2, and PaTrx3 shows that PaTrx1 is the major thioredoxin involved in sulfur metabolism. Deletions have no effect on peroxide resistance; however, data show that either PaTrx1 or PaTrx3 is necessary for sexual reproduction and for the development of the crippled growth cell degeneration (CG), processes that also required the PaMpk1 mitogen-activated protein kinase (MAPK) pathway. Since PaTrx1 PaTrx3 mutants show not an enhancement but rather an impairment in CG, it seems unlikely that PaTrx1 and PaTrx3 thioredoxins participate in the inhibition of this MAPK pathway. Altogether, these results underscore a role for thioredoxins in fungal development. PMID:17933907

Role of polyamines at the G1/S boundary and G2/M phase of the cell cycle.

Science.gov (United States)

Yamashita, Tomoko; Nishimura, Kazuhiro; Saiki, Ryotaro; Okudaira, Hiroyuki; Tome, Mayuko; Higashi, Kyohei; Nakamura, Mizuho; Terui, Yusuke; Fujiwara, Kunio; Kashiwagi, Keiko; Igarashi, Kazuei

2013-06-01

The role of polyamines at the G1/S boundary and in the G2/M phase of the cell cycle was studied using synchronized HeLa cells treated with thymidine or with thymidine and aphidicolin. Synchronized cells were cultured in the absence or presence of α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, plus ethylglyoxal bis(guanylhydrazone) (EGBG), an inhibitor of S-adenosylmethionine decarboxylase. When polyamine content was reduced by treatment with DFMO and EGBG, the transition from G1 to S phase was delayed. In parallel, the level of p27(Kip1) was greatly increased, so its mechanism was studied in detail. Synthesis of p27(Kip1) was stimulated at the level of translation by a decrease in polyamine levels, because of the existence of long 5'-untranslated region (5'-UTR) in p27(Kip1) mRNA. Similarly, the transition from the G2/M to the G1 phase was delayed by a reduction in polyamine levels. In parallel, the number of multinucleate cells increased by 3-fold. This was parallel with the inhibition of cytokinesis due to an unusual distribution of actin and α-tubulin at the M phase. Since an association of polyamines with chromosomes was not observed by immunofluorescence microscopy at the M phase, polyamines may have only a minor role in structural changes of chromosomes at the M phase. In general, the involvement of polyamines at the G2/M phase was smaller than that at the G1/S boundary. Copyright © 2013 Elsevier Ltd. All rights reserved.

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer - correlation with traditional prognostic factors

International Nuclear Information System (INIS)

Lampelj, Maja; Arko, Darja; Cas-Sikosek, Nina; Kavalar, Rajko; Ravnik, Maja; Jezersek-Novakovic, Barbara; Dobnik, Sarah; Dovnik, Nina Fokter; Takac, Iztok

2015-01-01

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman’s rank correlation, Mann Whitney U test and χ 2 test for statistical analysis. Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated

PaTrx1 and PaTrx3, Two Cytosolic Thioredoxins of the Filamentous Ascomycete Podospora anserina Involved in Sexual Development and Cell Degeneration▿ †

OpenAIRE

Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

2007-01-01

In various organisms, thioredoxins are known to be involved in the reduction of protein disulfide bonds and in protecting the cell from oxidative stress. Genes encoding thioredoxins were found by searching the complete genome sequence of the filamentous ascomycete Podospora anserina. Among them, PaTrx1, PaTrx2, and PaTrx3 are predicted to be canonical cytosolic proteins without additional domains. Targeted disruption of PaTrx1, PaTrx2, and PaTrx3 shows that PaTrx1 is the major thioredoxin inv...

Functional Characterization of PaLAX1, a Putative Auxin Permease, in Heterologous Plant Systems1[W][OA

Science.gov (United States)

Hoyerová, Klára; Perry, Lucie; Hand, Paul; Laňková, Martina; Kocábek, Tomáš; May, Sean; Kottová, Jana; Pačes, Jan; Napier, Richard; Zažímalová, Eva

2008-01-01

We have isolated the cDNA of the gene PaLAX1 from a wild cherry tree (Prunus avium). The gene and its product are highly similar in sequences to both the cDNAs and the corresponding protein products of AUX/LAX-type genes, coding for putative auxin influx carriers. We have prepared and characterized transformed Nicotiana tabacum and Arabidopsis thaliana plants carrying the gene PaLAX1. We have proved that constitutive overexpression of PaLAX1 is accompanied by changes in the content and distribution of free indole-3-acetic acid, the major endogenous auxin. The increase in free indole-3-acetic acid content in transgenic plants resulted in various phenotype changes, typical for the auxin-overproducing plants. The uptake of synthetic auxin, 2,4-dichlorophenoxyacetic acid, was 3 times higher in transgenic lines compared to the wild-type lines and the treatment with the auxin uptake inhibitor 1-naphthoxyacetic acid reverted the changes caused by the expression of PaLAX1. Moreover, the agravitropic response could be restored by expression of PaLAX1 in the mutant aux1 plants, which are deficient in auxin influx carrier activity. Based on our data, we have concluded that the product of the gene PaLAX1 promotes the uptake of auxin into cells, and, as a putative auxin influx carrier, it affects the content and distribution of free endogenous auxin in transgenic plants. PMID:18184737

Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development☆

Science.gov (United States)

Neilson, Karen M.; Abbruzzesse, Genevieve; Kenyon, Kristy; Bartolo, Vanessa; Krohn, Patrick; Alfandari, Dominique; Moody, Sally A.

2016-01-01

Mutations in SIX1 and in its co-factor, EYA1, underlie Branchiootorenal Spectrum disorder (BOS), which is characterized by variable branchial arch, otic and kidney malformations. However, mutations in these two genes are identified in only half of patients. We screened for other potential co-factors, and herein characterize one of them, Pa2G4 (aka Ebp1/Plfap). In human embryonic kidney cells, Pa2G4 binds to Six1 and interferes with the Six1-Eya1 complex. In Xenopus embryos, knock-down of Pa2G4 leads to down-regulation of neural border zone, neural crest and cranial placode genes, and concomitant expansion of neural plate genes. Gain-of-function leads to a broader neural border zone, expanded neural crest and altered cranial placode domains. In loss-of-function assays, the later developing otocyst is reduced in size, which impacts gene expression. In contrast, the size of the otocyst in gain-of-function assays is not changed but the expression domains of several otocyst genes are reduced. Together these findings establish an interaction between Pa2G4 and Six1, and demonstrate that it has an important role in the development of tissues affected in BOS. Thereby, we suggest that pa2g4 is a potential candidate gene for BOS. PMID:27940157

Uncleaved ApoM signal peptide is required for formation of large ApoM/sphingosine 1-phosphate (S1P)-enriched HDL particles.

Science.gov (United States)

Liu, Mingxia; Allegood, Jeremy; Zhu, Xuewei; Seo, Jeongmin; Gebre, Abraham K; Boudyguina, Elena; Cheng, Dongmei; Chuang, Chia-Chi; Shelness, Gregory S; Spiegel, Sarah; Parks, John S

2015-03-20

Apolipoprotein M (apoM), a plasma sphingosine 1-phosphate (S1P) carrier, associates with plasma HDL via its uncleaved signal peptide. Hepatocyte-specific apoM overexpression in mice stimulates formation of both larger nascent HDL in hepatocytes and larger mature apoM/S1P-enriched HDL particles in plasma by enhancing hepatic S1P synthesis and secretion. Mutagenesis of apoM glutamine 22 to alanine (apoM(Q22A)) introduces a functional signal peptidase cleavage site. Expression of apoM(Q22A) in ABCA1-expressing HEK293 cells resulted in the formation of smaller nascent HDL particles compared with wild type apoM (apoM(WT)). When apoM(Q22A) was expressed in vivo, using recombinant adenoviruses, smaller plasma HDL particles and decreased plasma S1P and apoM were observed relative to expression of apoM(WT). Hepatocytes isolated from both apoM(WT)- and apoM(Q22A)-expressing mice displayed an equivalent increase in cellular levels of S1P, relative to LacZ controls; however, relative to apoM(WT), apoM(Q22A) hepatocytes displayed more rapid apoM and S1P secretion but minimal apoM(Q22A) bound to nascent lipoproteins. Pharmacologic inhibition of ceramide synthesis increased cellular sphingosine and S1P but not medium S1P in both apoM(WT) and apoM(Q22A) hepatocytes. We conclude that apoM secretion is rate-limiting for hepatocyte S1P secretion and that its uncleaved signal peptide delays apoM trafficking out of the cell, promoting formation of larger nascent apoM- and S1P-enriched HDL particles that are probably precursors of larger apoM/S1P-enriched plasma HDL. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

T-duality of Green-Schwarz superstrings on AdS_d×S"d×M"1"0"−"2"d

International Nuclear Information System (INIS)

Abbott, Michael C.; Murugan, Jeff; Penati, Silvia; Pittelli, Antonio; Sorokin, Dmitri; Sundin, Per; Tarrant, Justine; Wolf, Martin; Wulff, Linus

2015-01-01

We verify the self-duality of Green-Schwarz supercoset sigma models on AdS_d×S"d backgrounds (d=2,3,5) under combined bosonic and fermionic T-dualities without gauge fixing kappa symmetry. We also prove this property for superstrings on AdS_d×S"d×S"d(d=2,3) described by supercoset sigma models with the isometries governed by the exceptional Lie supergroups D(2,1;α) (d=2) and D(2,1;α)×D(2,1;α) (d=3), which requires an additional T-dualisation along one of the spheres. Then, by taking into account the contribution of non-supercoset fermionic modes (up to the second order), we provide evidence for the T-self-duality of the complete type IIA and IIB Green-Schwarz superstring theory on AdS_d×S"d×T"1"0"−"2"d (d=2,3) backgrounds with Ramond-Ramond fluxes. Finally, applying the Buscher-like rules to T-dualising supergravity fields, we prove the T-self-duality of the whole class of the AdS_d×S"d×M"1"0"−"2"d superbackgrounds with Ramond-Ramond fluxes in the context of supergravity.

Expression and biological activity of the cystine knot bioinsecticide PA1b (Pea Albumin 1 Subunit b.

Directory of Open Access Journals (Sweden)

Vanessa Eyraud

Full Text Available The PA1b (Pea Albumin 1, subunit b peptide is an entomotoxin extract from Legume seeds with lethal activity on several insect pests, such as mosquitoes, some aphids and cereal weevils. This 37 amino-acid cysteine-rich peptide has been, until now, obtained by biochemical purification or chemical synthesis. In this paper, we present our results for the transient production of the peptide in Nicotiana benthamiana by agro-infiltration, with a yield of about 35 µg/g of fresh leaves and maximum production 8 days after infiltration. PA1b is part of the PA1 gene which, after post-translational modifications, encodes two peptides (PA1b and PA1a. We show that transforming tobacco with the PA1b cDNA alone does not result in production of the toxin and, in fact, the entire cDNA is necessary, raising the question of the role of PA1a. We constructed a PA1-cassette, allowing for the quick "cut/paste" of different PA1b mutants within a conserved PA1 cDNA. This cassette enabled us to produce the six isoforms of PA1b which exist in pea seeds. Biological tests revealed that all the isoforms display similar activity, with the exception of one which is inactive. The lack of activity in this isoform led us to conclude that the amphiphilic nature of the peptide is necessary for activity. The possible applications of this expression system for other cysteine-rich biomolecules are discussed.

PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

Directory of Open Access Journals (Sweden)

Takashi Takeshita

Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

A Shift in ApoM/S1P Between HDL-Particles in Women With Type 1 Diabetes Mellitus Is Associated With Impaired Anti-Inflammatory Effects of the ApoM/S1P Complex.

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Frej, Cecilia; Mendez, Armando J; Ruiz, Mario; Castillo, Melanie; Hughes, Thomas A; Dahlbäck, Björn; Goldberg, Ronald B

2017-06-01

Type 1 diabetes mellitus (T1D) patients have an increased risk of cardiovascular disease despite high levels of high-density lipoproteins (HDL). Apolipoprotein M (apoM) and its ligand sphingosine 1-phospate (S1P) exert many of the anti-inflammatory effects of HDL. We investigated whether apoM and S1P are altered in T1D and whether apoM and S1P are important for HDL functionality in T1D. ApoM and S1P were quantified in plasma from 42 healthy controls and 89 T1D patients. HDL was isolated from plasma and separated into dense, medium-dense, and light HDL by ultracentrifugation. Primary human aortic endothelial cells were challenged with tumor necrosis factor-α in the presence or absence of isolated HDL. Proinflammatory adhesion molecules E-selectin and vascular cellular adhesion molecule-1 were quantified by flow cytometry. Activation of the S1P 1 - receptor was evaluated by analyzing downstream signaling targets and receptor internalization. There were no differences in plasma levels of apoM and S1P between controls and T1D patients, but the apoM/S1P complexes were shifted from dense to light HDL particles in T1D. ApoM/S1P in light HDL particles from women were less efficient in inhibiting expression of vascular cellular adhesion molecule-1 than apoM/S1P in denser particles. The light HDL particles were unable to activate Akt, whereas all HDL subfractions were equally efficient in activating Erk and receptor internalization. ApoM/S1P in light HDL particles were inefficient in inhibiting tumor necrosis factor-α-induced vascular cellular adhesion molecule-1 expression in contrast to apoM/S1P in denser HDL particles. T1D patients have a higher proportion of light particles and hence more dysfunctional HDL, which could contribute to the increased cardiovascular disease risk associated with T1D. © 2017 American Heart Association, Inc.

MIA PaCa-2 and PANC-1 - pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors.

Science.gov (United States)

Gradiz, Rui; Silva, Henriqueta C; Carvalho, Lina; Botelho, Maria Filomena; Mota-Pinto, Anabela

2016-02-17

Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry, and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24(-), CD44(+/++), CD326(-/+) and CD133/1(-), while PANC-1 is CD24(-/+), CD44(+), CD326(-/+) and CD133/1(-). Both cell lines have KRAS and TP53 mutations and homozygous deletions including the first 3 exons of CDKN2A/p16(INK4A), but no SMAD4/DPC4 mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies.

Nicotine can skew the characterization of the macrophage type-1 (M{Phi}1) phenotype differentiated with granulocyte-macrophage colony-stimulating factor to the M{Phi}2 phenotype

Energy Technology Data Exchange (ETDEWEB)

Yanagita, Manabu; Kobayashi, Ryohei [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan); Murakami, Shinya, E-mail: ipshinya@dent.osaka-u.ac.jp [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan)

2009-10-09

Macrophages (M{Phi}s) exhibit functional heterogeneity and plasticity in the local microenvironment. Recently, it was reported that M{Phi}s can be divided into proinflammatory M{Phi}s (M{Phi}1) and anti-inflammatory M{Phi}s (M{Phi}2) based on their polarized functional properties. Here, we report that nicotine, the major ingredient of cigarette smoke, can modulate the characteristics of M{Phi}1. Granulocyte-macrophage colony-stimulating factor-driven M{Phi}1 with nicotine (Ni-M{Phi}1) showed the phenotypic characteristics of M{Phi}2. Like M{Phi}2, Ni-M{Phi}1 exhibited antigen-uptake activities. Ni-M{Phi}1 suppressed IL-12, but maintained IL-10 and produced high amounts of MCP-1 upon lipopolysaccharide stimulation compared with M{Phi}1. Moreover, we observed strong proliferative responses of T cells to lipopolysaccharide-stimulated M{Phi}1, whereas Ni-M{Phi}1 reduced T cell proliferation and inhibited IFN-{gamma} production by T cells. These results suggest that nicotine can change the functional characteristics of M{Phi} and skew the M{Phi}1 phenotype to M{Phi}2. We propose that nicotine is a potent regulator that modulates immune responses in microenvironments.

Data of evolutionary structure change: 1ONAD-1H9PA [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1ONAD-1H9PA 1ONA 1H9P D A ADTIVAVELDTYPNTDIGDPSYPHIGIDIKSVRSKKTAK...WNMQNGKVGTAHIIYNSVDKRLSAVVSYPNADSATVSYDVDLDNVLPEWVRVGLSASTGLYKETNTILSWSFTSKLK--TNALHFMFNQFSKDQKDLILQGDATTGTD...tryChain> 1ONA D 1ONAD

Out-of-equilibrium nanocrystalline R1-s(Fe,M)5+2s alloys (R=Sm,Pr; M=Co,Si,Ga)

International Nuclear Information System (INIS)

Bessais, L.; Djega-Mariadassou, C.

2005-01-01

The out-of-equilibrium hexagonal P6/mmm R 1-s (Fe,M) 5+2s (R=Sm,Pr and M=Co, Si or Ga) intermetallics are obtained by controlled nanocrystallization. A model is presented to explain the structure of the hexagonal phases, which stoichiometry is consistent with Sm(Fe,M) 9 and R(Fe,Ti,Co) 10 . The Curie temperatures increase versus Ga, Si, Co content. The analysis of the Moessbauer spectra leads to monotonous variation of the hyperfine parameters. The refinement of the Moessbauer spectra was performed on the basis of the correlation between Wigner-Seitz cell volumes obtained from X-ray diffraction results and isomer shifts. The abundance of each magnetic site was calculated by the multinomial distribution law. For a given substituting Co, Si, Ga content, the sequence for the isomer shift in the hexagonal cell is 2e>3g>6l. With increasing M content, the isomer shift of the 3g site remains quasi-constant. Those approaches lead to the location of Si, Ga, Co in 3g site, Ti in 6l site. (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Rac1 Regulates the Activity of mTORC1 and mTORC2 and Controls Cellular Size

Science.gov (United States)

Saci, Abdelhafid; Cantley, Lewis C.; Carpenter, Christopher L.

2013-01-01

SUMMARY Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 complex, but regulation of mTORC2 is poorly understood. Here, we report that Rac1, a member of the Rho family of GTPases, is a critical regulator of both mTORC1 and mTORC2 in response to growth-factor stimulation. Deletion of Rac1 in primary cells using an inducible-Cre/Lox approach inhibits basal and growth-factor activation of both mTORC1 and mTORC2. Rac1 appears to bind directly to mTOR and to mediate mTORC1 and mTORC2 localization at specific membranes. Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously. PMID:21474067

Improved wavelengths for the 1s2s3S1-1s2p3P0,2 transitions in helium-like Si12+

International Nuclear Information System (INIS)

Armour, I.A.; Myers, E.G.; Silver, J.D.; Traebert, E.; Oxford Univ.

1979-01-01

The wavelengths of the 1s2s 3 S 1 -1s2p 3 P 0 , 2 transitions in He-like Si 12+ have been remaesured to be 87.86 +- 0.01 nm and 81.48 +- 0.01 nm. The use of Rydberg lines for the calibration of fast beam spectra is discussed. (orig.)

Differential control of MMP and t-PA/PAI-1 expressions by sympathetic and renin-angiotensin systems in rat left ventricle.

Science.gov (United States)

Dab, Houcine; Hachani, Rafik; Hodroj, Wassim; Sakly, Mohsen; Bricca, Giampiero; Kacem, Kamel

2009-10-05

In the present study, we tested the hypothesis that angiotensin II (Ang II) has both direct (via AT1 receptors) and indirect (via sympathostimulator pathway) actions on the synthesis and activity of the enzymes involved in the extracellular matrix degradation in vivo. For this purpose, sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA of the plasminogen activator (t-PA) and its inhibitor (PAI-1), the mRNA, protein and activity of the matrix metalloproteinases MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymographic methods in the left ventricle. t-PA and PAI-1 mRNA were decreased after sympathectomy and remained unchanged after AT1 receptors blockade. mRNA was increased for t-PA and decreased by similar degree for PAI-1 after double treatment. MMPs mRNA and protein levels were decreased either after sympathectomy or AT1 receptors blockade and an additive effect was acquired after double treatment. MMPs activity was decreased by similar degree in the three treated groups. Deducted interpretations from our experimental approach suggest that Ang II inhibits directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) t-PA mRNA synthesis. It seems unable to influence directly PAI-1 mRNA, but stimulates indirectly PAI-1 mRNA synthesis. Ang II stimulates directly (via AT1 receptors) and indirectly (via sympathostimulator pathway) MMPs synthesis at both transcriptional and protein levels. The enzymatic activity of MMPs does not seem to be influenced directly by Ang II but it could be stimulated indirectly (via sympathostimulator pathway).

Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

International Nuclear Information System (INIS)

Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

2005-01-01

The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

Measurement of the 1S-2S frequency in atomic hydrogen

International Nuclear Information System (INIS)

Hildum, E.A.

1986-01-01

A first precise measurement of the 1S-2S energy interval in atomic hydrogen was obtained by observing the 1S-2S transition in an atomic beam by pulsed Doppler-free two-photon spectroscopy and using an interferometrically calibrated line of 130 Te 2 at 486 nm as the references. The measured 1S-2S frequency is 2,466,061 395.6(4.9)MHz. With the calculated 1S Lamb shift, the 1S-2S frequency yields a value for the Rydberg constant, R/sub ∞/ = 109,737.314 92(22) cm -1 , which is not in good agreement with the most recent previously measured value, 109,737.315 44(11) cm -1 , obtained by S.R. Amin et al. It is, however, in good agreement with a previous Rydberg value, 109,737.315 04(32) cm -1 , measured by J.E.M. Goldsmith. If the Rydberg constant is taken as given, the 1S-2S frequency determines a value for the 1S Lamb shift. With Amin's Rydberg, the measured Lamb shift is 8161.0(5.4) MHz, in poor agreement with the theoretical value of 8149.43(8) MHz. With Goldsmith's Rydberg, the measurement Lamb shift is 8151.0(8.7) MHz, in good agreement with theory

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

Science.gov (United States)

Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

2014-05-29

Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA. Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen activator and PAR2 agonists stimulated IL-8 mRNA expression and protein production, which is significantly diminished by PAR2 antagonist

Identification of the 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole inner-shell satellite line in the Ar16+ K-shell x-ray spectrum

Science.gov (United States)

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.

Synthesis and crystal structures of two α-bromoamides, (2'R,1S,2S)-N(2-bromopropanoyl)-2-amino-1-phenylpropane-1,3-diol and (2'S,5S,6S)-N(2-bromopropanoyl)-5-amino-6-phenyl-2-oxo-1,3,2-dioxathiane

International Nuclear Information System (INIS)

English, R.B.; Liddell, R.J.; Whiteley, C.G.

1987-01-01

One pair of diastereomeric bromoamides, (2'R,1S,2S)- and (2'S,1S,2S)-N(2-bromopropanoyl)-2-amino-1-phenylpropane-1,3-diol have been synthesized from ethyl 2-bromopropionate and an optically active amino-diol. The crystal structures of both were determined from single-crystal X-ray analyses. Both compounds are orthorhombic with space group P2 1 2 1 2 1 with Z = 4 in a unit cell of dimensions a 22,124(5),b 12,812(5), and c 4,886(5)A and a 15,510(5), b 9,707(5), and c 9,457(5)A. The proton chemical shifts of the groups attached to the asymmetric centre C(2'), and consequently, the identification of the configuration of the molecules, were resolved with the help of high-resolution nuclear magnetic resonance

Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R.

Science.gov (United States)

Li, Ge; Park, Hyeon U; Liang, Dong; Zhao, Richard Y

2010-07-07

Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R

Directory of Open Access Journals (Sweden)

Liang Dong

2010-07-01

Full Text Available Abstract Background Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. Results To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU and ultraviolet light (UV also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. Conclusions These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function.

Science.gov (United States)

Fatehi, M; Rowan, E G; Harvey, A L

2002-01-01

The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

Synthesis of a novel 'smart' bifunctional chelating agent 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and its Gd(III) complex.

Science.gov (United States)

Wardle, Nick J; Herlihy, Amy H; So, Po-Wah; Bell, Jimmy D; Bligh, S W Annie

2007-07-15

A new synthetic pathway to 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and 1-(2-[beta,D-galactopyranosyloxy]ethyl)-4,7,10-tris(carboxymethyl)-1, 4,7,10-tetraazacyclododecane (Gal-DO3A) chelating agents was developed involving full hydroxyl- and carboxyl-group protection in precursors to product. Two sequences of cyclen-N-functionalisation were subsequently investigated, one successfully, towards synthesis of the novel 'smart' bifunctional Gal-PA-DO3A-NH2 chelate. The longitudinal proton relaxivities of the neutral [Gd-(Gal-PA-DO3A-NH2)] and [Gd-(Gal-DO3A)] complexes were increased by 28% and 37% in the presence of beta-galactosidase, respectively.

Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus

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Sandra Mendoza Elizalde

2016-11-01

Full Text Available The bacterium Helicobacter pylori exhibits great genetic diversity, and the pathogenic roles of its virulence factors have been widely studied. However, the evolutionary dynamics of H. pylori strains during stomach colonization are not well characterized. Here, we analyzed the microevolutionary dynamics of the toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination of both strains in an animal model over time. Meriones unguiculatus were inoculated with the following bacteria: group 1–toxigenic strain vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2–non-toxigenic strain vacAs2m2/ cagA+/ cagE+/ babA2+; ST2901, and group 3–both strains. The gerbils were euthanized at different time points (3, 6, 12 and 18 months. In group 1, genetic alterations were observed at 6 and 12 months. With the combination of both strains, group 3 also exhibited genetic alterations at 3 and 18 months; moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence types (STs were reported in the PubMLST database for H. pylori. Synonymous and non-synonymous mutations were analyzed and associated with alterations in amino acids. Microevolutionary analysis of the STs (PHYLOViZ identified in each group revealed many mutational changes in the toxigenic (vacAs1m1 and non-toxigenic (vacAs2m2 strains. Phylogenetic assessments (eBURST did not reveal clonal complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a combination of toxigenic and non-toxigenic strains acquired genetic material by recombination. The allelic combination, vacAs2m1, displayed the best adaptation in the animal model over time, and a chimera, m1-m2, was also identified, which confirmed previous reports.

QED based on self-energy: The relativistic 2S1/2 → 1S1/2+1γ decay rates of hydrogenlike atoms

International Nuclear Information System (INIS)

Barut, A.O.; Salamin, Y.I.

1989-07-01

Within the framework of the recently advanced formulation of QED based on self-energy, we calculate the relativistic rates of the 2S 1/2 → 1S 1/2 +1γ transition in the hydrogen isoelectronic sequence for values of Z ranging between 1 and 92. We compare our results with those of Johnson (Phys. Rev. Lett. 29, 1123 (1972)) and Parpia and Johnson (Phys. Rev. A 26, 1142 (1982)) and find them to be in good agreement with both. (author). 12 refs, 1 tab

SIRT1 and FOXO1 mRNA expression in PBMC correlates to physical activity in COPD patients

Directory of Open Access Journals (Sweden)

Taka C

2017-11-01

Full Text Available Chihiro Taka, Ryuji Hayashi, Kazuki Shimokawa, Kotaro Tokui, Seisuke Okazawa, Kenta Kambara, Minehiko Inomata, Toru Yamada, Shoko Matsui, Kazuyuki Tobe First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Sugitani, Toyama, Toyama, Japan Background: Physical activity (PA is considered as one of the most important prognostic predictors in chronic obstructive pulmonary disease (COPD patients. Longevity gene, SIRT1, is reported to be involved in the pathogenesis of COPD by regulating the signaling pathways of oxidative stress, inflammation, and aging. We hypothesize that SIRT1 and related genes are also associated with the benefits of PA in COPD patients.Methods: Eighteen COPD outpatients were enrolled in this study, and their PA level was assessed with an accelerometer. We assessed the SIRT1 and related genes mRNA expression levels in the peripheral blood mononuclear cells (PBMCs of the subjects. We carried out respiratory function testing, blood gas analysis, the 6-minute walk test, and measurement of the cross-sectional area of the erector spinae muscles (ESMCSA by chest computed tomography. We analyzed the association of PA with the results of each of the examinations.Results: The mean age was 72±9 years, and the mean forced expiratory volume in 1 second was 1.4±0.56 L (52%±19% predicted. Our findings revealed a correlation between the daily PA and ESMCSA. The SIRT1 and Forkhead box O (FOXO1 mRNA expression levels in PBMCs were positively correlated with moderate-PA time (r=0.60, p=0.008 for SIRT1 and r=0.59, p=0.01 for FOXO1. Keywords: COPD, accelerometer, mRNA, walking, sedentary, moderate

Emergence of multiple clade 2.3.2.1 influenza A (H5N1) virus subgroups in Vietnam and detection of novel reassortants.

Science.gov (United States)

Creanga, Adrian; Thi Nguyen, Diep; Gerloff, Nancy; Thi Do, Hoa; Balish, Amanda; Dang Nguyen, Hoang; Jang, Yunho; Thi Dam, Vui; Thor, Sharmi; Jones, Joyce; Simpson, Natosha; Shu, Bo; Emery, Shannon; Berman, LaShondra; Nguyen, Ha T; Bryant, Juliet E; Lindstrom, Steve; Klimov, Alexander; Donis, Ruben O; Davis, C Todd; Nguyen, Tung

2013-09-01

Phylogenetic analyses of 169 influenza A(H5N1) virus genomes were conducted for samples collected through active surveillance and outbreak responses in Vietnam between September 2010 and September 2012. While clade 1.1 viruses persisted in southern regions, three genetically distinct subgroups of clade 2.3.2.1 were found in northern and central Vietnam. The identification of each subgroup corresponded with detection of novel reassortants, likely due to their overlapping circulation throughout the country. While the previously identified clade 1.1 and A/Hubei/1/2010-like 2.3.2.1 genotypes remained the predominant viruses detected, four viruses were found to be reassortants between A/Hubei/1/2010-like (HA, NA, PB2, PB1, PA, NP) and A/duck/Vietnam/NCVD-885/2010-like (M, NS) viruses and one virus was identified as having A/duck/Vietnam/NCVD-885/2010-like HA, NA, PB1, and NP with A/Hubei/1/2010-like PB2 and PA genes. Additionally, clade 2.3.2.1 A/Hong Kong/6841/2010-like viruses, first detected in mid-2012, were identified as reassortants comprised of A/Hubei/1/2010-like PB2 and PA and A/duck/Vietnam/NCVD-885/2010-like PB1, NP, NA, M, NS genes. Published by Elsevier Inc.

Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal tokamak with circular cross-section

International Nuclear Information System (INIS)

Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.

1977-01-01

A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the tokamak with circular cross-section. The resistive and diamagnetic effects are included in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, a system of two coupled equations is obtained for the harmonic amplitudes. When the shear is finite on q=1 the toroidal coupling is negligible. In the opposite limit, one can explain (a) the experimental behaviour of the (m=1, n=1) mode before the internal disruption, and (b) the simultaneous observation of the modes (m=1, n=1) and (m=2, n=1) before the main disruption. (author)

Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

Science.gov (United States)

He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

2015-01-01

Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio. © International & American Associations for Dental Research 2014.

First Observation of the M1 Transition psi -> gamma eta(c)(2S)

NARCIS (Netherlands)

Ablikim, M.; Achasov, M. N.; Ambrose, D. J.; An, F. F.; An, Q.; An, Z. H.; Bai, J. Z.; Ban, Y.; Becker, J.; Berger, N.; Bertani, M.; Bian, J. M.; Boger, E.; Bondarenko, O.; Boyko, I.; Briere, R. A.; Bytev, V.; Cai, X.; Calcaterra, A.; Cao, G. F.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, Y.; Chen, Y. B.; Cheng, H. P.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; Ding, W. M.; Ding, Y.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Fang, J.; Fang, S. S.; Fava, L.; Feldbauer, F.; Feng, C. Q.; Ferroli, R. B.; Fu, C. D.; Fu, J. L.; Gao, Y.; Geng, C.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y. P.; Han, Y. L.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, M.; He, Z. Y.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, H. M.; Hu, J. F.; Hu, T.; Huang, B.; Huang, G. M.; Huang, J. S.; Huang, X. T.; Huang, Y. P.; Hussain, T.; Ji, C. S.; Ji, Q.; Ji, X. B.; Ji, X. L.; Jia, L. K.; Jiang, L. L.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jing, F. F.; Kalantar-Nayestanaki, N.; Kavatsyuk, M.; Kuehn, W.; Lai, W.; Lange, J. S.; Leung, J. K. C.; Li, C. H.; Li, Cheng; Li, Cui; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, K.; Li, Lei; Li, N. B.; Li, Q. J.; Li, S. L.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, X. R.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Liao, X. T.; Liu, B. J.; Liu, B. J.; Liu, C. L.; Liu, C. X.; Liu, C. Y.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H.; Liu, H. B.; Liu, H. H.; Liu, H. M.; Liu, H. W.; Liu, J. P.; Liu, K. Y.; Liu, Kai; Liu, Kun; Liu, P. L.; Liu, S. B.; Liu, X.; Liu, X. H.; Liu, Y.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H.; Lu, G. R.; Lu, H. J.; Lu, J. G.; Lu, Q. W.; Lu, X. R.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lv, M.; Ma, C. L.; Ma, F. C.; Ma, H. L.; Ma, Q. M.; Ma, S.; Ma, T.; Ma, X. Y.; Ma, Y.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, H.; Mao, Y. J.; Mao, Z. P.; Messchendorp, J. G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Morales, C. Morales; Motzko, C.; Muchnoi, N. Yu.; Nefedov, Y.; Nicholson, C.; Nikolaev, I. B.; Ning, Z.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Park, J. W.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Ping, J. L.; Ping, R. G.; Poling, R.; Prencipe, E.; Pun, C. S. J.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, X. S.; Qin, Y.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Rong, G.; Ruan, X. D.; Sarantsev, A.; Schaefer, B. D.; Schulze, J.; Shao, M.; Shen, C. P.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, X. Y.; Spataro, S.; Spruck, B.; Sun, D. H.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. D.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Thorndike, E. H.; Tian, H. L.; Toth, D.; Ullrich, M.; Varner, G. S.; Wang, B.; Wang, B. Q.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q.; Wang, Q. J.; Wang, S. G.; Wang, X. F.; Wang, X. L.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wei, D. H.; Weidenkaff, P.; Wen, Q. G.; Wen, S. P.; Werner, M.; Wiedner, U.; Wu, L. H.; Wu, N.; Wu, S. X.; Wu, W.; Wu, Z.; Xia, L. G.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, G. M.; Xu, H.; Xu, Q. J.; Xu, X. P.; Xu, Y.; Xu, Z. R.; Xue, F.; Xue, Z.; Yan, L.; Yan, W. B.; Yan, Y. H.; Yang, H. X.; Yang, T.; Yang, Y.; Yang, Y. X.; Ye, H.; Ye, M.; Ye, M. H.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yu, L.; Yu, S. P.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. G.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, L.; Zhang, S. H.; Zhang, T. R.; Zhang, X. J.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. S.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, H. S.; Zhao, J. W.; Zhao, K. X.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, X. H.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, Y. H.; Zheng, Z. P.; Zhong, B.; Zhong, J.; Zhou, L.; Zhou, X. K.; Zhou, X. R.; Zhu, C.; Zhu, K.; Zhu, K. J.; Zhu, S. H.; Zhu, X. L.; Zhu, X. W.; Zhu, Y. M.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Zuo, J. X.

2012-01-01

Using a sample of 106 x 10(6) psi(3686) events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium S-wave spin-triplet and the radially excited S-wave spin-singlet states: psi(3686) -> gamma

Generation of 2.1 m wavelength from degenerate high gray track ...

Indian Academy of Sciences (India)

2014-02-12

Feb 12, 2014 ... Home; Journals; Pramana – Journal of Physics; Volume 82; Issue 2. Generation of 2.1 m wavelength from degenerate high gray track resistant potassium titanyl phosphate optical parametric oscillator. S Verma C Mishra V Kumar M Yadav K C Bahuguna N S Vasan S P Gaba. Contributed Papers Volume ...

O1, P1, N2 models of the global ocean tide on an elastic earth plus surface potential and spherical harmonic decompositions for M2, S2, and K1

Science.gov (United States)

Parke, M. E.

1982-01-01

The models of M2, S2, and K1 presented in Parke and Hendershott (1980) are supplemented with models of O1, P1, and N2. The models satisfy specified elevation boundary conditions and are generated by fighting a small number of test functions to island data. Maps are presented of the geocentric tide, the induced free space potential, the induced vertical component of the solid earth tide, and the induced vertical component of the gravitational field for each new component. Maps of the tidal potential seen by an observer fixed to the surface of the solid earth are also presented for all six constituents. Spherical harmonic coefficients up to order four and the rms magnitude of the coefficients to order fifteen are presented for each constituent. The rms magnitudes of the P1 and K1 coefficients normalized by their respective equilibrium amplitudes are compared to determine the effect of the diurnal core resonance.

QED based on self-energy: The relativistic 2S1/2→1S1/2+1γ decay rates of hydrogenlike atoms

International Nuclear Information System (INIS)

Barut, A.O.; Salamin, Y.I.

1991-01-01

Within the framework of the recently advanced formulation of QED based on self-energy, we calculate the relativistic rates of the 2S 1/2 →1S 1/2 +1γ transition in the hydrogen isoelectronic sequence for values of Z ranging between 1 and 92. We compare our results with those of Johnson [Phys. Rev. Lett. 29, 1123 (1972)] and Parpia and Johnson [Phys. Rev. A 26, 1142 (1982)], analytically and numerically. Although the two approaches are quite different, the formulas for decay rates are shown to be equivalent

Precision hfs of 126Cs(T1/2=1.63 m) by ABMR

International Nuclear Information System (INIS)

Pinard, J.; Duong, H.T.; Marescaux, D.; Stroke, H.H.; Redi, O.; Gustafsson, M.; Nilsson, T.; Matsuki, S.; Kishimoto, Y.; Kominato, K.; Ogawa, I.; Shibata, M.; Tada, M.; Persson, J.R.; Nojiri, Y.; Momota, S.; Inamura, T.T.; Wakasugi, M.; Juncar, P.; Murayama, T.; Nomura, T.; Koizumi, M.

2005-01-01

The hfs separation Δν of 126 Cs(T1/2=1.63 m) in the 6s S1/22 ground state was obtained in a precision measurement near zero magnetic field by means of atomic beam magnetic resonance with laser optical pumping on-line with the CERN-PSB-ISOLDE mass separator. The result, Δν=3629.514 (0.001) MHz, corrects significantly a previous published value from a high-field experiment. With our result, the precision of the nuclear magnetic moment, μ(Cs126)∼0.776μN, is now limited by the influence of extended nuclear structure on the hfs (the Bohr-Weisskopf effect)

Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury.

Science.gov (United States)

Yang, Xiaodong; Xu, Shaoqing; Qian, Yiwei; Xiao, Qin

2017-08-01

Microglia are the primary cells that exert immune function in the central nervous system (CNS), and accumulating evidence suggests that microglia act as key players in the initiation of neurodegenerative diseases. It is now well recognized that microglia have functional plasticity and dual phenotypes, proinflammatory M1 and anti-inflammatory M2 phenotypes. Inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for the treatment of neuroinflammation-related diseases. Resveratrol has been demonstrated to exert anti-inflammatory effects by suppressing M1 microglia activation. However, the role of resveratrol in regulating microglia polarization and the molecular mechanisms involved have not been fully clarified. In this study, we tested whether resveratrol could suppress microglia activation by promoting microglia polarization toward the M2 phenotype via PGC-1α by measuring M1 and M2 markers in vitro and in vivo. Our study demonstrated that resveratrol reduced inflammatory damage and promoted microglia polarization to the M2 phenotype in LPS-induced neuroinflammation. In addition, resveratrol ameliorated LPS-induced sickness behavior in mice. The promoting effects of resveratrol on M2 polarization were attenuated by knocking down PGC-1α. PGC-1α not only suppressed LPS-evoked M1 marker expression by inhibition of NF-κB activity but also increased M2 marker expression by coactivation of the STAT6 and STAT3 pathways. We propose that overexpression PGC-1α by resveratrol could be a potential therapeutic approach to suppress neuroinflammation by regulating microglia polarization. Copyright © 2017 Elsevier Inc. All rights reserved.

Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

Science.gov (United States)

Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy

2016-01-01

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

Emissions in potassium vapour under 4S1/2-7S1/2 two-photon nsec excitation

International Nuclear Information System (INIS)

Pentaris, D.; Chatzikyriakos, G.; Armyras, A.; Efthimiopoulos, T.

2010-01-01

The two-photon excitation of 4S 1/2 -7S 1/2 transition of potassium atoms is studied. Several coherent emissions and processes are possible, such as parametric four-wave (PFWM), parametric six-wave (PSWM) mixing and competition with the stimulated hyper Raman (SHRS) and the amplified spontaneous emission (ASE). The radiations at the transitions 6P 3/2,1/2 -4S 1/2 , 6S 1/2 -4P 3/2,1/2 and 5P 3/2,1/2 -4S 1/2 are emitted only in the forward direction (indicating a parametric process), while the radiation at the transition 4P 3/2,1/2 -4S 1/2 is emitted in the forward and in the backward direction, indicating an ASE process.

26 CFR 1.401(m)-2 - ACP test.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2 Internal... TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(m)-2 ACP test. (a) Actual contribution percentage (ACP) test—(1) In general—(i) ACP test formula. A plan satisfies the ACP test for a plan year only...

Fatigue 󈨛. Volume 1,

Science.gov (United States)

1987-06-01

277 FATIGUE 87 da/dn (m/ ciclo ) 10 - 07 10 - 08 10 - 0 9 R=0.5 S* • -Long Crack 10-10 e Smax = 195 MPa *Smax = 205 MPa 1Smax = 225 MPa 0.5 1 5 10 AK...MPa/m) Figure 1 Crack growth rate vs stress intensity factor range 10 . da/dn (m/ ciclo ) i0 - ° 09 i0-o -Long crack 10 . ° Smax = 10 Pa 10 Smax...120 NPa Smax = 145 NlPa 0.5 I 10 AKN~~)50 Figure 2 Crack growth rate vs stress intensity factor range 278 FATIGUE 87 da/dn (m/ ciclo ) 10- 10- 0 7 % 10

GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

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Senthilkumar Pitchalu Kasthurinaidu

Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1

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Michael C. Brown

2017-02-01

Full Text Available The mechanistic target of rapamycin (mTOR integrates numerous stimuli and coordinates the adaptive response of many cellular processes. To accomplish this, mTOR associates with distinct co-factors that determine its signaling output. While many of these co-factors are known, in many cases their function and regulation remain opaque. The MAPK-interacting kinase (MNK contributes to rapamycin resistance in cancer cells. Here, we demonstrate that MNK sustains mTORC1 activity following rapamycin treatment and contributes to mTORC1 signaling following T cell activation and growth stimuli in cancer cells. We determine that MNK engages with mTORC1, promotes mTORC1 association with the phosphatidyl inositol 3′ kinase-related kinase (PIKK stabilizer, TELO2, and facilitates mTORC1:substrate binding. Moreover, our data suggest that DEPTOR, the endogenous inhibitor of mTOR, opposes mTORC1:substrate association by preventing TELO2:mTORC1 binding. Thus, MNK orchestrates counterbalancing forces that regulate mTORC1 enzymatic activity.

Diff(S1)/SL(2,R) and Teichmueller space

International Nuclear Information System (INIS)

Nag, S.; Verjovsky, A.

1988-08-01

It is shown that the unique homogeneous Kaehler metric carried by M=Diff(S 1 )/SL(2,R) induces the Weil-Petersson metric on the Teichmueller space. This is via our identification of M as a holomorphic submanifold of universal Teichmueller space T(1). The identification was obtained simply by noting that every diffeomorphism of S 1 is a quasisymmetric homeomorphism. Our computations allow us also to prove that every T(G), G any infinite Fuchsian group, projects out of M transversely. This last assertion is related to the ''fractal'' nature of G-invariant quasicircles. (author). 12 refs

A new series of oxycarbonate superconductors (Cu{sub 0.5}C{sub 0.5}){sub m}Ba{sub m+1}Ca{sub n-1}Cu{sub n}O{sub 2}({sub m+n})+1

Energy Technology Data Exchange (ETDEWEB)

Takayama-Muromachi, E.; Kawashima, T.; Matsui, Y. [National Institute for Research in Inorganic Materials, Ibaraki (Japan)

1994-12-31

We found a new series of oxycarbonate superconductors in the Ba-Ca-Cu-C-O system under high pressure of 5 GPa. Their ideal formula is (Cu{sub 0.5}C{sub 0.5}){sub m}Ba{sub m+1}Ca{sub n-1}Cu{sub n}O{sub 2}({sub m+n})+1 ((Cu,C)-m(m+1)(n-1)n). Thus far, n=3, 4 members of the m=1 series, (Cu,C)-1223 and (Cu,C)-1234, have been prepared in bulk while n=4, 5 members, (Cu,C)-2334 and (Cu,C)-2345, have been prepared for the m=2 series. (Cu,C)-1223 shows superconductivity below 67 K while T{sub c}`s of other compounds are above 110 K. In particular, (Cu,C)=1234 has the highest T{sub c} of 117 K.

Glutathione S-Transferase M1 and T1 Null Genotype Frequency ...

Indian Academy of Sciences (India)

Bluebird

2017-10-25

Oct 25, 2017 ... A comparative analysis with different tribal as well as world ..... T1 and P1) gene polymorphisms with type 2 diabetes mellitus in north .... Houlston R. S. 2000 CYP1A1 polymorphisms and lung cancer risk: a meta-analysis.

The high affinity selectin glycan ligand C2-O-sLex and mRNA transcripts of the core 2 β-1,6-N-acetylglusaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas

International Nuclear Information System (INIS)

St Hill, Catherine A; Farooqui, Mariya; Mitcheltree, Gregory; Gulbahce, H Evin; Jessurun, Jose; Cao, Qing; Walcheck, Bruce

2009-01-01

The metastasis of cancer cells and leukocyte extravasation into inflamed tissues share common features. Specialized carbohydrates modified with sialyl Lewis x (sLe x ) antigens on leukocyte membranes are ligands for selectin adhesion molecules on activated vascular endothelial cells at inflammatory sites. The activity of the enzyme core 2 β1,6 N-acetylglucosaminyltransferase (C2GnT1) in leukocytes greatly increases their ability to bind to endothelial selectins. C2GnT1 is essential for the synthesis of core 2-branched O-linked carbohydrates terminated with sLe x (C2-O-sLe x ). Our goal was to determine the expression profiles of C2-O-sLe x in the malignant progression and metastasis of colorectal adenocarcinomas. The well characterized CHO-131 monoclonal antibody (mAb) specifically recognizes C2-O-sLe x present in human leukocytes and carcinoma cells. Using CHO-131 mAb, we investigated whether C2-O-sLe x was present in 113 human primary colorectal adenocarcinomas, 10 colorectal adenomas, 46 metastatic liver tumors, 28 normal colorectal tissues, and 5 normal liver tissues by immunohistochemistry. We also examined mRNA levels of the enzyme core 2 β1,6-N-acetylglucosaminyltransferase (C2GnT1) in 20 well, 15 moderately, and 2 poorly differentiated colorectal adenocarcinomas, and in 5 normal colorectal tissues by using quantitative real-time polymerase chain reactions (RT-PCR). We observed high reactivity with CHO-131 mAb in approximately 70% of colorectal carcinomas and 87% of metastatic liver tumors but a lack of reactivity in colorectal adenomas and normal colonic and liver tissues. Positive reactivity with CHO-131 mAb was very prominent in neoplastic colorectal glands of well to moderately differentiated adenocarcinomas. The most intense staining with CHO-131 mAb was observed at the advancing edge of tumors with the deepest invasive components. Finally, we analyzed C2GnT1 mRNA levels in 37 colorectal adenocarcinomas and 5 normal colorectal tissues by RT

PGE2-induced colon cancer growth is mediated by mTORC1

International Nuclear Information System (INIS)

Dufour, Marc; Faes, Seraina; Dormond-Meuwly, Anne; Demartines, Nicolas; Dormond, Olivier

2014-01-01

Highlights: • PGE 2 activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE 2 induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE 2 induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E 2 (PGE 2 ) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE 2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE 2 -induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE 2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE 2 EP 4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE 2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE 2 -induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE 2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE 2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth

Spontaneous transition rates for electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2) and magnetic quadrupole (M2) transitions for He-like calcium and sulfur ions

International Nuclear Information System (INIS)

Kingston, A.E.; Norrington, P.H.; Boone, A.W.

2002-01-01

The spontaneous decay rates for the electric dipole (E1), electric quadrupole (E2), magnetic dipole (M1) and magnetic quadrupole (M2) transitions between all of the 1s 2 , 1s2 l and 1s3 l states have been obtained for helium-like calcium and sulfur ions. To assess the accuracy of the calculations, the transition probabilities were calculated using two sets of configuration interaction wavefunctions. One set of wavefunctions was generated using the fully relativistic GRASP code and the other was obtained using CIV3, in which relativistic effects are introduced using the Breit-Pauli approximation. The transition rates, A values, oscillator strengths and line strengths from our two calculations are found to be similar and to compare very well with other recent results for Δn=1 or 2 transitions. For Δn=0 transitions the agreement is much less good; this is mainly due to differences in the calculated excitation energies. (author)

Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

Science.gov (United States)

Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

2012-07-06

In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.

Electron impact excitation-autoionisation of the (2s2)1S, (2p2)1D and (2s2p)1P autoionising states of helium

International Nuclear Information System (INIS)

Samardzic, O.; Hurn, J.A.; Weigold, E.; Brunger, M.J.

1994-01-01

The electron impact excitation of the (2s 2 ) 1 S, (2p 2 ) 1 D and (2s2p) 1 P autoionising states of helium and their subsequent radiationless decay was studied by observation of the ejected electrons. The present work was carried out at an incident energy of 94.6 eV and for ejected electron scattering angles in the range 25-135 deg C. The lineshapes observed in the present ejected electron spectra are analysed using the Shore-Balashov parametrisation. As part of the analysis procedure, numerically rigorous confidence limits were determined for the derived parameters. No previous experimental or theoretical work has been undertaken at the incident energy of the present investigation but, where possible, the resulting parameters are qualitatively compared against the 80 eV results of other experiments and theory. 37 refs., 4 figs

Phosphorylation of Human Metapneumovirus M2-1 Protein Upregulates Viral Replication and Pathogenesis.

Science.gov (United States)

Cai, Hui; Zhang, Yu; Lu, Mijia; Liang, Xueya; Jennings, Ryan; Niewiesk, Stefan; Li, Jianrong

2016-08-15

Human metapneumovirus (hMPV) is a major causative agent of upper- and lower-respiratory-tract infections in infants, the elderly, and immunocompromised individuals worldwide. Like all pneumoviruses, hMPV encodes the zinc binding protein M2-1, which plays important regulatory roles in RNA synthesis. The M2-1 protein is phosphorylated, but the specific role(s) of the phosphorylation in viral replication and pathogenesis remains unknown. In this study, we found that hMPV M2-1 is phosphorylated at amino acid residues S57 and S60. Subsequent mutagenesis found that phosphorylation is not essential for zinc binding activity and oligomerization, whereas inhibition of zinc binding activity abolished the phosphorylation and oligomerization of the M2-1 protein. Using a reverse genetics system, recombinant hMPVs (rhMPVs) lacking either one or both phosphorylation sites in the M2-1 protein were recovered. These recombinant viruses had a significant decrease in both genomic RNA replication and mRNA transcription. In addition, these recombinant viruses were highly attenuated in cell culture and cotton rats. Importantly, rhMPVs lacking phosphorylation in the M2-1 protein triggered high levels of neutralizing antibody and provided complete protection against challenge with wild-type hMPV. Collectively, these data demonstrated that phosphorylation of the M2-1 protein upregulates hMPV RNA synthesis, replication, and pathogenesis in vivo The pneumoviruses include many important human and animal pathogens, such as human respiratory syncytial virus (hRSV), hMPV, bovine RSV, and avian metapneumovirus (aMPV). Among these viruses, hRSV and hMPV are the leading causes of acute respiratory tract infection in infants and children. Currently, there is no antiviral or vaccine to combat these diseases. All known pneumoviruses encode a zinc binding protein, M2-1, which is a transcriptional antitermination factor. In this work, we found that phosphorylation of M2-1 is essential for virus

The Р60-S6K1 isoform of ribosomal protein S6 kinase 1 is a product of alternative mRNA translation

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I. V. Zaiets

2018-07-01

Full Text Available Ribosomal protein S6 kinase 1 (S6K1 is a well-known downstream effector of mTORC1 (mechanistic target of rapamycin complex 1 participating primarily in the regulation of cell growth and metabolism. Deregulation of mTOR/S6K1 signaling can promote numerous human pathologies, including cancer, neurodegeneration, cardiovascular disease, and metabolic disorders. As existing data suggest, the S6K1 gene encodes several protein isoforms, including p85-S6K1, p70-S6K1, and p60-S6K1. The two of these isoforms, p85-S6K1 and p70-S6K1, were extensively studied to date. The origin and functional significance of the p60-S6K1 isoform remains a mystery, however, it was suggested that the isoform could be a product of alternative S6K1 mRNA translation. Herein we report the generation of HEK-293 cells exclusively expressing p60-S6K1 as a result of CRISPR/Cas9-mediated inactivation of p85/p70-S6K1 translation. Moreover, the generated modified cells displayed the elevated level of p60-S6K1 expression compared to that in wild-type HEK-293 cells. Our data confirm an assumption that p60-S6K1 is alternatively translated, most probably, from the common for both p70- and p85-S6K1 mRNA transcript and reveal a link between p60-S6K1 expression and such cellular processes as cell proliferation and motility. In addition, our findings indicate that the p60-S6K1 isoform of S6K1 may undergo a mode of regulation distinct from p70- and p85-S6K1 due to the absence of mTOR-regulated p60-S6K1 phosphorylation at T389 that is important for S6K1 activation.

Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

Directory of Open Access Journals (Sweden)

Marija G Matic

Full Text Available OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS AND METHODS: A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR with corresponding 95% confidence interval (95%CI was calculated. RESULTS: The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067. CONCLUSION: Null or low-activity genotypes of the

Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal Tokomak with circular cross sections

International Nuclear Information System (INIS)

Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.

1976-01-01

A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the Tokomak with circular cross sections. One includes the resistive and diamagnetic effects in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, one obtains a system of two coupled equations for the harmonic amplitudes. When the shear is finite on q=1, the toroidal coupling is negligible. In the opposite limit, one can explain: the experimental behaviour of the (m=1, n=1) mode before the internal disruption; the simultaneous observation of the modes (m=1, n=1) and [de

Electron Excitation Rate Coefficients for Transitions from the IS21S Ground State to the 1S2S1,3S and 1S2P1,3P0 Excited States of Helium

Science.gov (United States)

Aggarwal, K. M.; Kingston, A. E.; McDowell, M. R. C.

1984-03-01

The available experimental and theoretical electron impact excitation cross section data for the transitions from the 1s2 1S ground state to the 1s2s 1,3S and 1s2p 1,3P0 excited states of helium are assessed. Based on this assessed data, excitation rate coefficients are calculated over a wide electron temperature range below 3.0×106K. A comparison with other published results suggests that the rates used should be lower by a factor of 2 or more.

The Armys M-1 Abrams, M-2/M-3 Bradley, and M-1126 Stryker: Background and Issues for Congress

Science.gov (United States)

2016-04-05

the Army John McHugh , urging instead the limited production of 70 M-1A2SEPv2 tanks per year from FY2013 to FY2017. 32 Congress subsequently decided...House Members sent a letter to Secretary of the Army McHugh expressing concern over the Army’s failure to fund production of the M-1A2. Congress...John McHugh by Rep. Sander Levin and Rep. Mike Rogers, May 6, 2011. 33 See CRS Reports: CRS Report R43323, Defense: FY2014 Authorization and

The transcriptional response to the inactivation of the PaMpk1 and PaMpk2 MAP kinase pathways in Podospora anserina.

Science.gov (United States)

Bidard, Frédérique; Coppin, Evelyne; Silar, Philippe

2012-08-01

Transcription pattern during mycelium growth of Podospora anserina was assayed by microarray analysis in wild type and in mutants affected in the MAP kinase genes PaMpk1 and PaMpk2 and in the NADPH oxidase gene PaNox1. 15% of the genes have their expression modified by a factor two or more as growth proceeds in wild type. The genes whose expression is modified during growth in P. anserina are either not conserved or differently regulated in Neurospora crassa and Aspergillus niger, two fungi for which transcriptome data during growth are available. The P. anserina mutants display a similar alteration of their transcriptome profile, with nearly 1000 genes affected similarly in the three mutants, accounting for their similar growth phenotypes. Yet, each mutant has its specific set of modified transcripts, in line with particular phenotypes exhibited by each mutant. Again, there is limited conservation during evolution of the genes regulated at the transcription level by MAP kinases, as indicated by the comparison the P. anserina data, with those of Aspergillus fumigatus and N. crassa, two fungi for which gene expression data are available for mutants of the MAPK pathways. Among the genes regulated in wild type and affected in the mutants, those involved in carbohydrate and secondary metabolisms appear prominent. The vast majority of the genes differentially expressed are of unknown function. Availability of their transcription profile at various stages of development should help to decipher their role in fungal physiology and development. Copyright © 2012 Elsevier Inc. All rights reserved.

El día más blanco o el país de la memoria de Raúl Zurita

Directory of Open Access Journals (Sweden)

María Luisa Fischer

2014-06-01

Full Text Available Estudio la adscripción genérica de El día más blanco del poeta chileno Raúl Zurita, así como la significación de los epígrafes, otra forma de enmarcación del volumen. Entre la novela y la autobiografía, el libro se propone cubrir la grieta que existe entre la memoria personal y la memoria traumática del país. Describo la especial calidad visual de las imágenes del texto y su relación con las dificultades de construir una versión de la historia subjetiva y personal que se aúne a la historia del país, cuando ambas están quebradas.

Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

Science.gov (United States)

Yang, Weiwei; Li, Qinghua; Pan, Zhifang

2014-01-01

Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

Vapour pressures for 1-(butoxymethoxy)butane (dibutoxymethane) and 1,1,1,2,2,3,3,4,4-nonafluoro-4-methoxybutane (methyl nonafluorobutyl ether) over the pressure range of (15–80) kPa

International Nuclear Information System (INIS)

Gárate, María P.; Bejarano, Arturo; Fuente, Juan C. de la

2016-01-01

Highlights: • Vapour pressures of two pure potential dry-cleaning solvent were measured. • Measurements were made over the temperature range of (294.6–442.7) K. • Three commonly used vapour pressure equations were fitted to the experimental data. • The parameters of Antoine and Wagner type equations were estimated. • The relative deviations (rmsd) from the three vapour-pressure equations were <0.6%. - Abstract: Saturated pressures of 1-(butoxymethoxy)butane (dibutoxymethane) and 1,1,1,2,2,3,3,4,4-nonafluoro-4-methoxybutane (methyl nonafluorobutyl ether), new potential solvents for dry-cleaning processes, were measured with a dynamic recirculation apparatus at a pressure range of (15–80) kPa, at temperatures of (390.4–442.7) K for dibutoxymethane and (294.6–322.4) K for methyl nonafluorobutyl ether. The vapour pressures were represented using the correlations of Antoine, extended Antoine and Wagner with relative root mean square deviations of, 1%, 6% and 0.6% for dibutoxymethane, and, 1%, 2% and 0.6% for methyl nonafluorobutyl ether, respectively. The experimental data of dibutoxymethane was compared with those available in literature, the result showed consistency between both data sets.

LTV1 raidījuma „Aizliegtais paņēmiens” ētiskie aspekti

OpenAIRE

Zeikate, Ieva

2015-01-01

Bakalaura darba tēma ir LTV1 Raidījuma „Aizliegtais paľēmiens” ētiskie aspekti. Darba mērķis ir izpētīt raidījuma saturu, noskaidrot, vai tajā tiek ievēroti ţurnālistikas ētikas principi un vērtības, noteikt raidījuma mērķus un izmantotos līdzekļus, kā arī to saskaľotību, veicot raidījuma izpēti aptuveni gada garumā. Teorija balstīta par televīziju, pētnieciskās ţurnālistikas teorētisko raksturojumu, ētiku un ţurnālistikas ētikas pamatprincipiem. Izvēlētās pētniecības metodes i...

Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

Directory of Open Access Journals (Sweden)

Shweta Joshi

Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1.

Science.gov (United States)

Basso, Daniela; Bozzato, Dania; Padoan, Andrea; Moz, Stefania; Zambon, Carlo-Federico; Fogar, Paola; Greco, Eliana; Scorzeto, Michele; Simonato, Francesca; Navaglia, Filippo; Fassan, Matteo; Pelloso, Michela; Dupont, Sirio; Pedrazzoli, Sergio; Fassina, Ambrogio; Plebani, Mario

2014-03-26

In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-κB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines. NT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-κB, Akt and mTOR signaling with S100A8, but mainly with TGFβ1. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-κB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-κB and Akt in the presence of an intact TGFβ1 canonical signaling pathway. TGFβ1 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGFβ1 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGFβ1 (MALDI-TOF/MS and co-immuno-precipitation). The effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGFβ1 on cell signaling, and the formation of complexes between TGFβ1 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT.

Berberine diminishes side population and down-regulates stem cell-associated genes in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2.

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Park, S H; Sung, J H; Chung, N

2014-09-01

Cancer stem cells play an important role in metastasis and the relapse of drug resistant cancers. Side-population (SP) cells are capable of effluxing Hoechst 33342 dye and are referred to as cancer stem cells. We investigated the effect of berberine on pancreatic cancer stem cells of PANC-1 and MIA PaCa-2. For both cell lines, the proportions of SP cells in the presence of berberine were investigated and compared to the proportions in the presence of gemcitabine, a standard pancreatic anti-cancer drug. The proportions of SP cells in the PANC-1 and MIA PaCa-2 cell lines were about 9 and PANC-1 decreased to 5.7 ± 2.0 and 6.8 ± 0.8%, respectively, which compares to the control proportion of (9.7 ± 1.7). After berberine and gemcitabine treatment of PANC-1, of the four stem cell-associated genes (SOX2, POU5F1, NANOG, and NOTCH1), all but NOTCH1 were down-regulated. Unfortunately, the effect of berberine and gemcitabine treatments on MIA PaCa-2 SP cells could not be clearly observed because SP cells represented only a very small proportion of MIA PaCa-2 cells. However, SOX2, POU5F1, and NANOG genes were shown to be effectively down-regulated in the MIA PaCa-2 cell line as a whole. Taken together, these results indicate that berberine is as effective at targeting pancreatic cancer cell lines as gemcitabine. Therefore, we believe that POU5F1, SOX2, and NANOG can serve as potential markers, and berberine may be an effective anti-cancer agent when targeting human pancreatic cancer cells and/or their cancer stem cells.

Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

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Mário Henrique M Barros

Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

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Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

2013-01-01

Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression.

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Dlugolenski, Daniel; Jones, Les; Howerth, Elizabeth; Wentworth, David; Tompkins, S Mark; Tripp, Ralph A

2015-05-01

Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment

Infinitely many N=1 dualities from m+1−m=1

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Agarwal, Prarit; Intriligator, Kenneth; Song, Jaewon [Department of Physics, University of California,San Diego, La Jolla, CA 92093 (United States)

2015-10-06

We discuss two infinite classes of 4d supersymmetric theories, T{sub N}{sup (m)} and U{sub N}{sup (m)}, labelled by an arbitrary non-negative integer, m. The T{sub N}{sup (m)} theory arises from the 6d, A{sub N−1} type N=(2,0) theory reduced on a 3-punctured sphere, with normal bundle given by line bundles of degree (m+1,−m); the m=0 case is the N=2 supersymmetric T{sub N} theory. The novelty is the negative-degree line bundle. The U{sub N}{sup (m)} theories likewise arise from the 6d N=(2,0) theory on a 4-punctured sphere, and can be regarded as gluing together two (partially Higgsed) T{sub N}{sup (m)} theories. The T{sub N}{sup (m)} and U{sub N}{sup (m)} theories can be represented, in various duality frames, as quiver gauge theories, built from T{sub N} components via gauging and nilpotent Higgsing. We analyze the RG flow of the U{sub N}{sup (m)} theories, and find that, for all integer m>0, they end up at the same IR SCFT as SU(N) SQCD with 2N flavors and quartic superpotential. The U{sub N}{sup (m)} theories can thus be regarded as an infinite set of UV completions, dual to SQCD with N{sub f}=2N{sub c}. The U{sub N}{sup (m)} duals have different duality frame quiver representations, with 2m+1 gauge nodes.

M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

International Nuclear Information System (INIS)

Genin, Marie; Clement, Francois; Fattaccioli, Antoine; Raes, Martine; Michiels, Carine

2015-01-01

Tumor associated macrophages (TAMs) are present in high density in solid tumors. TAMs share many characteristics with alternatively activated macrophages, also called M2. They have been shown to favor tumor development and a role in chemoresistance has also been suggested. Here, we investigated the effects of M2 in comparison to M1 macrophages on cancer cell sensitivity to etoposide. We set up a model of macrophage polarization, starting from THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate). Once differentiated (M0 macrophages), they were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). To mimic the communication between cancer cells and TAMs, M0, M1 or M2 macrophages and HepG2 or A549 cancer cells were co-cultured during respectively 16 (HepG2) or 24 (A549) hours, before etoposide exposure for 24 (HepG2) or 16 (A549) hours. After the incubation, the impact of etoposide on macrophage polarization was studied and cancer cell apoptosis was assessed by western-blot for cleaved caspase-3 and cleaved PARP-1 protein, caspase activity assay and FACS analysis of Annexin V and PI staining. mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages, which provide a new, easy and well-characterized model of polarized human macrophages. Etoposide-induced cancer cell apoptosis was markedly reduced in the presence of THP-1 M2 macrophages, while apoptosis was increased in cells co-cultured with M1 macrophages. On the other hand, etoposide did not influence M1 or M2 polarization. These results evidence for the first time a clear protective effect of M2 on the contrary to M1 macrophages on etoposide-induced cancer cell apoptosis

Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

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Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

2016-08-01

Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice. Copyright © 2016 the American Physiological Society.

Proyección de trabajo en el interior del país y factores asociados en médicos recién colegiados de Lima, Perú 2010 Labor projection in the countryside and associated factors in newly collegiated physicians in Lima, Peru 2010

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Percy Mayta-Tristán

2011-06-01

Full Text Available Objetivos. Estimar la prevalencia y factores asociados con la proyección de trabajo en el interior del país de médicos de Lima. Materiales y métodos. Se realizó un estudio de corte transversal en 782 médicos quienes fueron encuestados durante su proceso de colegiatura entre los meses de marzo y abril del 2010. Se definió como proyección de trabajo en el interior del país si respondieron "interior del país" a la pregunta ¿dónde planea estar laborando en los próximos cinco años?. Se usó la regresión logística múltiple para encontrar los factores asociados. Resultados. La edad media de los participantes fue de 25 años, 54% fueron mujeres y 73% son de universidades privadas. Sólo 7,0% refirió proyectarse trabajar en el interior del país y el 0,5% en zonas rurales. No se encontró asociación con el género, lugar de nacimiento, tener familiares médicos, tipo de universidad, dominio del inglés, haber residido por más de un año en provincias y el año de realización del internado. En el análisis multivariado se encontró asociación con haber realizado el internado en un hospital del interior del país (OR:3,1; IC95%:1,5-6,3, comunicarse en quechua (OR: 2,9; IC:1,4-6,1, que ambos padres nacieran en el interior del país (OR:2,8; IC:1,4-5,6; mientras que la proyección de un sueldo mensual superior a 5000 nuevos soles (OR:0,4; IC:0,2-0,8 y vivir con su familia nuclear o pareja (OR:0,3; IC:0,1-0,5 se asociaron en forma negativa. Conclusiones. Es baja la proyección de trabajo en el interior del país en los médicos colegiados en Lima. Algunos de los factores encontrados pueden ayudar a diseñar estrategias para revertir esta situación.Objectives. To estimate the prevalence and associated factors with the labor porjection in the countryside of physicians from Lima. Materials and methods. We conducted a cross-sectional study of 782 physicians who were surveyed during their affiliation at Peruvian Medical College during March

Structure-based drug discovery for combating influenza virus by targeting the PA-PB1 interaction.

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Watanabe, Ken; Ishikawa, Takeshi; Otaki, Hiroki; Mizuta, Satoshi; Hamada, Tsuyoshi; Nakagaki, Takehiro; Ishibashi, Daisuke; Urata, Shuzo; Yasuda, Jiro; Tanaka, Yoshimasa; Nishida, Noriyuki

2017-08-25

Influenza virus infections are serious public health concerns throughout the world. The development of compounds with novel mechanisms of action is urgently required due to the emergence of viruses with resistance to the currently-approved anti-influenza viral drugs. We performed in silico screening using a structure-based drug discovery algorithm called Nagasaki University Docking Engine (NUDE), which is optimised for a GPU-based supercomputer (DEstination for Gpu Intensive MAchine; DEGIMA), by targeting influenza viral PA protein. The compounds selected by NUDE were tested for anti-influenza virus activity using a cell-based assay. The most potent compound, designated as PA-49, is a medium-sized quinolinone derivative bearing a tetrazole moiety, and it inhibited the replication of influenza virus A/WSN/33 at a half maximal inhibitory concentration of 0.47 μM. PA-49 has the ability to bind PA and its anti-influenza activity was promising against various influenza strains, including a clinical isolate of A(H1N1)pdm09 and type B viruses. The docking simulation suggested that PA-49 interrupts the PA-PB1 interface where important amino acids are mostly conserved in the virus strains tested, suggesting the strain independent utility. Because our NUDE/DEGIMA system is rapid and efficient, it may help effective drug discovery against the influenza virus and other emerging viruses.

PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation*

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Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C.; Simons, S. Stoney

2013-01-01

Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (Amax), the potency of agonists (EC50), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses Amax, increases the EC50, and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC50, and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene. PMID:23161582

PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation.

Science.gov (United States)

Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C; Simons, S Stoney

2013-01-04

Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (A(max)), the potency of agonists (EC(50)), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene.

Heterologous Coproduction of Enterocin A and Pediocin PA-1 by Lactococcus lactis: Detection by Specific Peptide-Directed Antibodies

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Martínez, José M.; Kok, Jan; Sanders, Jan W.; Hernández, Pablo E.

2000-01-01

Antibodies against enterocin A were obtained by immunization of rabbits with synthetic peptides PH4 and PH5 designed, respectively, on the N- and C-terminal amino acid sequences of enterocin A and conjugated to the carrier protein KLH. Anti-PH4-KLH antibodies not only recognized enterocin A but also pediocin PA-1, enterocin P, and sakacin A, three bacteriocins which share the N-terminal class IIa consensus motif (YGNGVXC) that is contained in the sequence of the peptide PH4. In contrast, anti-PH5-KLH antibodies only reacted with enterocin A because the amino acid sequences of the C-terminal parts of class IIa bacteriocins are highly variable. Enterocin A and/or pediocin PA-1 structural and immunity genes were introduced in Lactococcus lactis IL1403 to achieve (co)production of the bacteriocins. The level of production of the two bacteriocins was significantly lower than that obtained by the wild-type producers, a fact that suggests a low efficiency of transport and/or maturation of these bacteriocins by the chromosomally encoded bacteriocin translocation machinery of IL1403. Despite the low production levels, both bacteriocins could be specifically detected and quantified with the anti-PH5-KLH (anti-enterocin A) antibodies isolated in this study and the anti-PH2-KLH (anti-pediocin PA-1) antibodies previously generated (J. M. Martínez, M. I. Martínez, A. M. Suárez, C. Herranz, P. Casaus, L. M. Cintas, J. M. Rodríguez, and P. E. Hernández, Appl. Environ. Microbiol. 64:4536–4545, 1998). In this work, the availability of antibodies for the specific detection and quantification of enterocin A and pediocin PA-1 was crucial to demonstrate coproduction of both bacteriocins by L. lactis IL1403(pJM04), because indicator strains that are selectively inhibited by each bacteriocin are not available. PMID:10919819

Crystal structures of (RS-N-[(1R,2S-2-benzyloxy-1-(2,6-dimethylphenylpropyl]-2-methylpropane-2-sulfinamide and (RS-N-[(1S,2R-2-benzyloxy-1-(2,4,6-trimethylphenylpropyl]-2-methylpropane-2-sulfinamide: two related protected 1,2-amino alcohols

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Matthew R. Carbone

2014-11-01

Full Text Available The title compounds, C22H31NO2S, (1, and C23H33NO2S, (2, are related protected 1,2-amino alcohols. They differ in the substituents on the benzene ring, viz. 2,6-dimethylphenyl in (1 and 2,4,6-trimethylphenyl in (2. The plane of the phenyl ring is inclined to that of the benzene ring by 28.52 (7° in (1 and by 44.65 (19° in (2. In the crystal of (1, N—H...O=S and C—H...O=S hydrogen bonds link molecules, forming chains along [100], while in (2, similar hydrogen bonds link molecules into chains along [010]. The absolute structures of both compounds were determined by resonance scattering.

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice.

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Joseph, Lauren; Thomsen, Morgane

2017-06-30

Muscarinic M 1 /M 4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (S D ) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M 1 , M 2 , or M 4 receptors (M 1 -/- , M 2 -/- , M 4 -/- ), as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity (scopolamine), or preferential affinity at the M 1 , M 2 , or M 4 subtype (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested alone and in combination with cocaine. In intact animals, antagonists with high affinity at M 1 /M 4 receptors partially substituted for cocaine and increased the S D effect of cocaine, while M 2 -preferring antagonists did not substitute, and reduced the S D effect of cocaine. The cocaine-like effects of scopolamine were absent in M 1 -/- mice. The cocaine S D attenuating effects of methoctramine were absent in M 2 -/- mice and almost absent in M 1 -/- mice. The findings indicate that the cocaine-like S D effects of muscarinic antagonists are primarily mediated through M 1 receptors, with a minor contribution of M 4 receptors. The data also support our previous findings that stimulation of M 1 receptors and M 4 receptors can each attenuate the S D effect of cocaine, and show that this can also be achieved by blocking M 2 autoreceptors, likely via increased acetylcholine release. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si, and "1"1"3In(n,γ)"1"1"4"mIn reactions

International Nuclear Information System (INIS)

Zolotarev, K.I.

2014-10-01

Cross section data for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions are needed for solving a wide spectrum of scientific and technical tasks. The excitation function of "2"8Si(n,p)"2"8Al reaction refers to the nuclear data involved in fusion reactor design calculations. The "2"8Si(n,p)"2"8Al reaction is interesting also as the monitor reaction for measurements at fusion facilities. Activation detectors on the basis of the 31P(n,p)31Si reaction are commonly used in the reactor dosimetry. The "1"1"3In(n,γ)"1"1"4"mIn reaction is promising regarding reactor dosimetry application for two reasons. First, due to the "1"1"4"mIn decay parameters which are rather suitable for activation measurements. Half-life of "1"1"4"mIn is equal to T_1/_2 = (49.51 ± 0.01) days and gamma spectrum accompanying decay has only one line with energy 190.27 keV and intensity (15.56 ± 0.15)%. Second, the "1"1"3In(n,γ)"1"1"4"mIn reaction rate may be measured by using one activation detector simultaneously with the "1"1"5In(n,γ)"1"1"6"mIn reaction. Preliminary analysis of existing evaluated excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions show that new evaluations are needed for all above mentioned reactions. This report is devoted to the preparation of the new evaluations of cross sections data and related covariance matrixes of uncertainties for the "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions.

Supplementary data Fig. S1 Fig. S1. FE-SEM images of the ...

Indian Academy of Sciences (India)

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Fig. S3. Cycling behavior of V2O5 nanomaterials recorded by CV at 20 mV·s-1 scan rate. Page 4. 4. Fig. S4. Fig. S4. Cycling behavior of V2O5 nanomaterials electrodes of galvanostatic charge and discharge profiles recorded by GCD at a current density of 1 A·g-1. Page 5. 5. Fig. S5. Fig. S5. Cycling behavior of V2O5 ...

The September 2017 M=8.1 Chiapas and M=7.1 Puebla, Mexico, earthquakes: Chain reaction or coincidence?

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Toda, S.; Stein, R. S.

2017-12-01

The M=8.1 and M=7.1 events struck 12 days and 600 km apart, both with an independent probability of occurrence of 0.5% per year, based on the GEAR model [Bird et al., 2015]. Are they related? First, we calculated the static stress imparted by the M=8.1 shock to the fault that ruptured in the M=7.1, and find a tiny push that would favor rupture. But the stress increase (0.2 kPa) is less than the fault would experience from the tidal stresses, and so it should be inconsequential. We next used the México Servicio Sismológico Nacional (UNAM) online catalog to look at the quakes in the month before the M=8.1 and in the 13 days since. We calculate the completeness to be M≥4.0. There are virtually no remote aftershocks from the Chiapas rupture that extend within 250 km of the M=7.1 shock during the first week after the M=8.1. So, if anything, the M=8.1 turned off for a week or more the region that ruptured in the M=7.1. Events started turning on about 2-3 days before the M=7.1, but none of those struck within 40 km of the future M=7.1 mainshock. The seismic surface waves unleashed by great earthquakes envelop the globe in just 160 minutes, and yet triggering of remote large aftershocks during these 2-3 hours is either very rare [Pollitz et al., Nature 2012] or in dispute [Fan & Shearer, 2016 vs. Yue et al., 2017]. So, the waves must trigger tiny shocks that cascade into larger shocks after some delay. Or, perhaps the stresses conveyed by the waves pump pockets of fluids that slowly diffuse into nearby fault zones, lubricating them to the point of failure [Parsons at al., 2017]. In the cases where great earthquakes are indisputably seen to trigger aftershocks at great distances or even globally, they to do so within several days, or a week at most. Since Puebla struck 12 days later, this seems to us too long a period to be explained by dynamic triggering. Even though neither quake on their own is rare, what's the chance of independent M=8.1 and M=7.1 events just 12

Detection of Panulirus argus Virus 1 (PaV1) in exported frozen tails of subadult-adult Caribbean spiny lobsters Panulirus argus.

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Huchin-Mian, Juan Pablo; Briones-Fourzán, Patricia; Simá-Alvarez, Raúl; Cruz-Quintana, Yanis; Pérez-Vega, Juan Antonio; Lozano-Alvarez, Enrique; Pascual-Jiménez, Cristina; Rodríguez-Canul, Rossanna

2009-09-23

The Caribbean spiny lobster Panulirus argus is a valuable fishing resource and the trade in frozen lobster tails is an important industry. However, the presence of the pathogenic virus Panulirus argus Virus 1 (PaV1), which causes systemic infection in P. argus and is particularly lethal to juvenile individuals, has not been previously examined in imported/exported lobster products. We used PCR assays to determine the presence of PaV1 in abdominal muscle tissue of 22 frozen P. argus tails exported from Belize to Mexico. Based on their size, the tails belonged to subadult-adult lobsters. Using specific primers targeted for PaV1 resulted in 11 tails showing a specific 499 bp band. The sequence of positive amplified fragments showed a high similarity to PaV1 (95% identity with GenBank accession no. EF206313.1). Although the pathogenicity of PaV1 was not evaluated in the present study, our results provide the first evidence of PaV1 in frozen lobster tails exported in the seafood industry as well as the first molecular evidence of PaV1 in adult lobsters.

Overexpression of KAI1 induces autophagy and increases MiaPaCa-2 cell survival through the phosphorylation of extracellular signal-regulated kinases

International Nuclear Information System (INIS)

Wu, Chun-Yan; Yan, Jun; Yang, Yue-Feng; Xiao, Feng-Jun; Li, Qing-Fang; Zhang, Qun-Wei; Wang, Li-Sheng; Guo, Xiao-Zhong; Wang, Hua

2011-01-01

Research highlights: → We first investigate the effects of KAI1 on autophagy in MiaPaCa-2 cells. → Our findings demonstrate that KAI1 induces autophagy, which in turn inhibits KAI1-induced apoptosis. → This study also supplies a possible novel therapeutic method for the treatment of pancreatic cancer using autophagy inhibitors. -- Abstract: KAI1, a metastasis-suppressor gene belonging to the tetraspanin family, is known to inhibit cancer metastasis without affecting the primary tumorigenicity by inhibiting the epidermal growth factor (EGF) signaling pathway. Recent studies have shown that hypoxic conditions of solid tumors induce high-level autophagy and KAI1 expression. However, the relationship between autophagy and KAI1 remains unclear. By using transmission electron microscopy, confocal microscopy, and Western blotting, we found that KAI1 can induce autophagy in a dose- and time-dependent manner in the human pancreatic cell line MiaPaCa-2. KAI1-induced autophagy was confirmed by the expression of autophagy-related proteins LC3 and Beclin 1. KAI1 induces autophagy through phosphorylation of extracellular signal-related kinases rather than that of AKT. KAI1-induced autophagy protects MiaPaCa-2 cells from apoptosis and proliferation inhibition partially through the downregulation of poly [adenosine diphosphate (ADP)-ribose] polymerase (PARP) cleavage and caspase-3 activation.

mPGES-1-derived prostaglandin E2 stimulates Stat3 to promote podocyte apoptosis.

Science.gov (United States)

Yu, Jing; Wu, Yimei; Wang, Lu; Zhang, Wen; Xu, Man; Song, Jiayu; Fu, Yu; Cui, Yiyun; Gong, Wei; Li, Shuzhen; Xia, Weiwei; Huang, Songming; Zhang, Aihua; Jia, Zhanjun

2017-11-01

We previously reported that microsomal prostaglandin E synthase-1 (mPGES-1) contributed to adriamycin (Adr)-induced podocyte apoptosis. However, the molecular mechanism remains unclear. Here we studied the role of mPGES-1/PGE2 cascade in activating Stat3 signaling and the contribution of Stat3 in PGE2- and Adr-induced podocyte apoptosis. In murine podocytes, PGE2 dose- and time-dependently increased the phosphorylation of Stat3 in line with the enhanced cell apoptosis and reduced podocyte protein podocin. In agreement with the increased Stat3 phosphorylation, Stat3-derived cytokines including IL-6, IL-17, MCP-1, and ICAM-1 were significantly upregulated following PGE2 treatment. By application of a specific Stat3 inhibitor S3I-201, PGE2-induced podocyte apoptosis was largely abolished in parallel with a blockade of podocin reduction. Next, we observed that Adr treatment also enhanced p-Stat3 and activated mPGES-1/PGE2 cascade. Blockade of Stat3 by S3I-201 significantly ameliorated Adr-induced cell apoptosis and podocin reduction. More interestingly, silencing mPGES-1 in podocytes by mPGES-1 siRNA blocked Adr-induced increments of Stat-3 phosphorylation, PGE2 production, and Stat3-derived inflammatory cytokines. Taken together, this study suggested that mPGES-1-derived PGE2 could activate Stat3 signaling to promote podocyte apoptosis. Targeting mPGES-1/PGE2/Stat3 signaling might be a potential strategy for the treatment of podocytopathy.

The PaAlr1 magnesium transporter is required for ascospore development in Podospora anserina.

Science.gov (United States)

Grognet, Pierre; Lalucque, Hervé; Silar, Philippe

2012-10-01

The PaAlr1 gene encoding a putative plasma membrane magnesium (Mg) transporter in Podospora anserina was inactivated. The PaAlr1(Δ) mutants showed sensitivity to deprivation and excess Mg(2+) and Ca(2+). They also exhibited an autonomous ascospore maturation defect. Mutant ascospores were arrested at an early stage when they contained two nuclei. These data emphasize the role of Mg ions during sexual development in a filamentous fungus. Copyright © 2012 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Radiative rates for E1, E2, M1, and M2 transitions in the Br-like ions Sr IV, Y V, Zr VI, Nb VII, and Mo VIII

International Nuclear Information System (INIS)

Aggarwal, Kanti M.; Keenan, Francis P.

2015-01-01

Energies and lifetimes are reported for the lowest 375 levels of five Br-like ions, namely Sr IV, Y V, Zr VI, Nb VII, and Mo VIII, mostly belonging to the 4s 2 4p 5 , 4s 2 4p 4 4ℓ, 4s4p 6 , 4s 2 4p 4 5ℓ, 4s 2 4p 3 4d 2 , 4s4p 5 4ℓ, and 4s4p 5 5ℓ configurations. Extensive configuration interaction has been included and the general-purpose relativistic atomic structure package (GRASP) has been adopted for the calculations. Additionally, radiative rates are listed among these levels for all E1, E2, M1, and M2 transitions. From a comparison with the measurements, the majority of our energy levels are assessed to be accurate to better than 2%, although discrepancies between theory and experiment for a few are up to 6%. An accuracy assessment of the calculated radiative rates (and lifetimes) is more difficult, because no prior results exist for these ions

Weak mixing angle and the SU(3)CxSU(3) model on M4xS1/(Z2xZ'2)

International Nuclear Information System (INIS)

Li Tianjun; Wei Liao

2002-05-01

We show that the desirable weak mixing angle sin 2 θ W =0.2312 at m Z scale can be generated naturally in the SU(3) C xSU(3) model on M 4 xS 1 /(Z 2 x Z 2 ') where the gauge symmetry SU(3) is broken down to SU(2) L xU(1) Y by orbifold projection. For a supersymmetric model with a TeV scale extra dimension, the SU(3) unification scale is about hundreds of TeVs at which the gauge couplings for SU(3) C and SU(3) can also be equal in the mean time. For the non-supersymmetric model, SU(2) L xU(1) Y are unified at order of 10 TeV. These models may serve as good candidates for physics beyond the SM or MSSM. (author)

Prevalence of Panulirus argus Virus 1 (PaV1) and habitation patterns of healthy and diseased Caribbean spiny lobsters in shelter-limited habitats.

Science.gov (United States)

Lozano-Alvarez, Enrique; Briones-Fourzán, Patricia; Ramírez-Estévez, Aurora; Placencia-Sánchez, David; Huchin-Mian, Juan Pablo; Rodríguez-Canul, Rossana

2008-07-07

Caribbean spiny lobsters Panulirus argus are socially gregarious, preferring shelters harboring conspecifics over empty shelters. In laboratory trials, however, healthy lobsters strongly avoided shelters harboring lobsters infected with the highly pathogenic Panulirus argus Virus 1 (PaV1). Because PaV1 is transmitted by contact, this behavior may thwart its spread in wild lobsters. In a field experiment conducted from 1998 to 2002 in a shelter-poor reef lagoon (Puerto Morelos, Mexico), densities of juvenile P. argus increased significantly on sites enhanced with artificial shelters (casitas) but not on control sites. Because PaV1 emerged in this location during 2000, we reexamined these data to assess whether casitas could potentially increase transmission of PaV1. In 2001, PaV1 prevalence was 2.5% and the cohabitation level (percentage of healthy lobsters cohabiting with diseased lobsters) was similar between natural shelters (3.5%) and casitas (2.4 %). The relative lobster densities in casita sites and control sites did not change significantly before (1998-1999) or after (2001-2002) the disease emergence. In late 2006, data from casita sites showed a significant increase in prevalence (10.9%) and cohabitation level (29.4%), but no significant changes in lobster density. In May 2006, casitas were deployed on shelter-poor sites within Chinchorro Bank, 260 km south of Puerto Morelos. In late 2006, prevalence and cohabitation level were 7.4 and 21.7%, respectively. Our results are inconclusive as to whether or not casitas increase PaV1 transmission, but suggest that across shelter-poor habitats, lobsters make a trade-off between avoiding diseased conspecifics and avoiding predation risk.

Figure S1 Figure S2

Indian Academy of Sciences (India)

WINTEC

6.8. 7.0. 7.2. 7.4. 7.6. 7.8. 8.0. 8.2. 8.4. 8.6. 8.8 ppm. 0.0. 1.8. 9.7. 5.4. 6.9. 8.1. 9.0. 10.8. 3.2. 10.3. Figure S3. NMR titration of DAN-Ia acid with NDI at 30% MeOH in CDCl3. The numbers represent the mole ratios of the DAN-acid to the repeat unit.

Molecular Characterization of the Llamas (Lama glama) Casein Cluster Genes Transcripts (CSN1S1, CSN2, CSN1S2, CSN3) and Regulatory Regions

Science.gov (United States)

Pauciullo, Alfredo; Erhardt, Georg

2015-01-01

In the present paper, we report for the first time the characterization of llama (Lama glama) caseins at transcriptomic and genetic level. A total of 288 casein clones transcripts were analysed from two lactating llamas. The most represented mRNA populations were those correctly assembled (85.07%) and they encoded for mature proteins of 215, 217, 187 and 162 amino acids respectively for the CSN1S1, CSN2, CSN1S2 and CSN3 genes. The exonic subdivision evidenced a structure made of 21, 9, 17 and 6 exons for the αs1-, β-, αs2- and κ-casein genes respectively. Exon skipping and duplication events were evidenced. Two variants A and B were identified in the αs1-casein gene as result of the alternative out-splicing of the exon 18. An additional exon coding for a novel esapeptide was found to be cryptic in the κ-casein gene, whereas one extra exon was found in the αs2-casein gene by the comparison with the Camelus dromedaries sequence. A total of 28 putative phosphorylated motifs highlighted a complex heterogeneity and a potential variable degree of post-translational modifications. Ninety-six polymorphic sites were found through the comparison of the lama casein cDNAs with the homologous camel sequences, whereas the first description and characterization of the 5’- and 3’-regulatory regions allowed to identify the main putative consensus sequences involved in the casein genes expression, thus opening the way to new investigations -so far- never achieved in this species. PMID:25923814

Molecular Characterization of the Llamas (Lama glama) Casein Cluster Genes Transcripts (CSN1S1, CSN2, CSN1S2, CSN3) and Regulatory Regions.

Science.gov (United States)

Pauciullo, Alfredo; Erhardt, Georg

2015-01-01

In the present paper, we report for the first time the characterization of llama (Lama glama) caseins at transcriptomic and genetic level. A total of 288 casein clones transcripts were analysed from two lactating llamas. The most represented mRNA populations were those correctly assembled (85.07%) and they encoded for mature proteins of 215, 217, 187 and 162 amino acids respectively for the CSN1S1, CSN2, CSN1S2 and CSN3 genes. The exonic subdivision evidenced a structure made of 21, 9, 17 and 6 exons for the αs1-, β-, αs2- and κ-casein genes respectively. Exon skipping and duplication events were evidenced. Two variants A and B were identified in the αs1-casein gene as result of the alternative out-splicing of the exon 18. An additional exon coding for a novel esapeptide was found to be cryptic in the κ-casein gene, whereas one extra exon was found in the αs2-casein gene by the comparison with the Camelus dromedaries sequence. A total of 28 putative phosphorylated motifs highlighted a complex heterogeneity and a potential variable degree of post-translational modifications. Ninety-six polymorphic sites were found through the comparison of the lama casein cDNAs with the homologous camel sequences, whereas the first description and characterization of the 5'- and 3'-regulatory regions allowed to identify the main putative consensus sequences involved in the casein genes expression, thus opening the way to new investigations -so far- never achieved in this species.

Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program).

Science.gov (United States)

Leontieva, Olga V; Demidenko, Zoya N; Blagosklonny, Mikhail V

2015-09-15

In proliferating cells, mTOR is active and promotes cell growth. When the cell cycle is arrested, then mTOR converts reversible arrest to senescence (geroconversion). Rapamycin and other rapalogs suppress geroconversion, maintaining quiescence instead. Here we showed that ATP-competitive kinase inhibitors (Torin1 and PP242), which inhibit both mTORC1 and TORC2, also suppressed geroconversion. Despite inhibition of proliferation (in proliferating cells), mTOR inhibitors preserved re-proliferative potential (RP) in arrested cells. In p21-arrested cells, Torin 1 and PP242 detectably suppressed geroconversion at concentrations as low as 1-3 nM and 10-30 nM, reaching maximal gerosuppression at 30 nM and 300 nM, respectively. Near-maximal gerosuppression coincided with inhibition of p-S6K(T389) and p-S6(S235/236). Dual mTOR inhibitors prevented senescent morphology and hypertrophy. Our study warrants investigation into whether low doses of dual mTOR inhibitors will prolong animal life span and delay age-related diseases. A new class of potential anti-aging drugs can be envisioned.

Physiological and immunological characterization of Caribbean spiny lobsters Panulirus argus naturally infected with Panulirus argus Virus 1 (PaV1).

Science.gov (United States)

Pascual Jiménez, Cristina; Huchin-Mian, Juan Pablo; Simões, Nuno; Briones-Fourzán, Patricia; Lozano-Álvarez, Enrique; Sánchez Arteaga, Ariadna; Pérez-Vega, Juan Antonio; Simá-Álvarez, Raúl; Rosas Vazquez, Carlos; Rodríguez-Canul, Rossanna

2012-08-27

The present study compares 13 physiological and immunological variables between a group of healthy Panulirus argus lobsters and a group of lobsters naturally infected with Panulirus argus Virus 1 (PaV1). Viral infection was determined through histopathology and PCR. Ten of the 13 variables differed significantly between the 2 groups. Using these variables, a principal component analysis yielded 2 separate clusters: one corresponding to the healthy group and the other corresponding to the infected group. In particular, infected lobsters exhibited significantly lower levels of osmotic pressure, total hemocyte counts, plasmatic proteins, and total phenoloxidase (PO) activity in plasma, as well as significantly higher levels of cholesterol and acylglycerides. These features are consistent with metabolic wasting, hyperlipidemia, and presumed immune suppression. Infection with PaV1 appears to increase the susceptibility of lobsters to some other opportunistic pathogens, as 61.1% of infected lobsters presented infestations of ciliate epibionts (Epystilis and Zoothamniun) in the gill chamber compared with 11.5% lobsters in the healthy group. Infected lobsters also showed significantly higher levels of total PO activity in degranulated hemocytes and trypsin inhibitor activity, potentially indicating activation of immune response by the PO system during the systemic infection with PaV1.

PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

Energy Technology Data Exchange (ETDEWEB)

Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch; Demartines, Nicolas, E-mail: Demartines@chuv.ch; Dormond, Olivier, E-mail: Olivier.dormond@chuv.ch

2014-09-05

Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 2} directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 2} increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 2} increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

S = -1 and S = -2 few-body hypernuclei

International Nuclear Information System (INIS)

Gibson, B.F.

1997-01-01

The S = -1 and S = -2 few-body bound states are the focus of this discussion. Implications for the understanding of the baryon-baryon interaction are examined. Octet-octet coupling effects not found in conventional, non-strange nuclei are highlighted. TJNAF wave function tests for the S = -1 sector are noted. The need to identify S = -2 hypernuclei to explore the S = -2 strong interaction and to test model predictions is emphasized

Study on the Υ(1S)→B_cM Weak Decays

International Nuclear Information System (INIS)

Huang, Jinshu; Chang, Qin; Wang, Na; Chen, Lili; Sun, Junfeng; Yang, Yueling

2015-01-01

Motivated by the prospects of the potential Υ(1S) particle at high-luminosity heavy-flavor experiments, we studied the Υ(1S)→B_cM weak decays, where M = π, ρ, K"("∗"). The nonfactorizable contributions to hadronic matrix elements are taken into consideration with the QCDF approach. It is found that the CKM-favored Υ(1S)→B_cρ decay has branching ratio of O(10"-"1"0), which might be measured promisingly by the future experiments.

Dysprosium-doped PbGa2S4 laser generating at 4.3 μm directly pumped by 1.7 μm laser diode.

Science.gov (United States)

Jelínková, Helena; Doroshenko, Maxim E; Jelínek, Michal; Sulc, Jan; Osiko, Vyacheslav V; Badikov, Valerii V; Badikov, Dmitrii V

2013-08-15

In this Letter, we demonstrate the pulsed and CW operation of the Dy:PbGa(2)S(4) laser directly pumped by the 1.7 μm laser diode. In the pulsed regime (pulse duration 5 ms; repetition rate 20 Hz), the maximum mean output power of 9.5 mW was obtained with the slope efficiency of 9.3% with respect to the absorbed pump power. The generated wavelength was 4.32 μm, and the laser beam cross section was approximately Gaussian on both axes. Stable CW laser generation was also successfully obtained with the maximum output power of 67 mW and the slope efficiency of 8%. Depopulation of the lower laser level by 1.7 μm pump radiation absorption followed by 1.3 μm upconversion fluorescence was demonstrated. These results show the possibility of construction of the compact diode-pumped solid-state pulsed or CW laser generating at 4.3 μm in the power level of tens mW operating at room temperature.

β-adrenergic-stimulated macrophages: Comprehensive localization in the M1–M2 spectrum

Science.gov (United States)

Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.

2016-01-01

β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1–M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1–M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1–M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1–M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1–M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

Critical Parameters and Critical-Region (p,ρ ,T) Data of trans-1,1,1,3-Tetrafluorobut-2-ene [HFO-1354mzy(E)

Science.gov (United States)

Kimura, Takeru; Kayukawa, Yohei; Miyamoto, Hiroyuki; Saito, Kiyoshi

2017-08-01

This study presents the experimental measurement of the pρ T properties and critical parameters of a low GWP type refrigerant, trans-1,1,1,3-Tetrafluorobut-2-ene (HFO-1354mzy(E)). The sample purity of the substance was 99 area %. p ρ T property measurements and visual observations of the meniscus of HFO-1354mzy(E) were carried out using a metal-bellows volumometer with an optical cell. The critical temperature was determined by observation of the critical opalescence. The critical pressure and critical density were determined as the inflection point of the isothermal p ρ T property data at the critical temperature. For more precise clarification of the thermodynamic surface in the vicinity of the critical point, additional p ρ T property measurements were carried out on three isotherms in the supercritical region. The expanded uncertainties (k = 2) in the temperature, pressure, and density measurements were estimated to be less than 3 mK, 1.2 kPa, and 0.32 \\hbox {kg} \\cdot \\hbox {m}^{-3}, respectively. The expanded uncertainties of the critical parameters were estimated to be less than 13 mK, 1.4 kPa, and 2.3 \\hbox {kg} \\cdot \\hbox {m}^{-3}, respectively. These values are the first reported for HFO-1354mzy(E) and are necessary for the development of its equation of state in the near future.

1.2V, 24mW/ch, 10bit, 80MSample/s Pipelined A/D Converters

Science.gov (United States)

Ueno, Takeshi; Ito, Tomohiko; Kurose, Daisuke; Yamaji, Takafumi; Itakura, Tetsuro

This paper describes 10-bit, 80-MSample/s pipelined A/D converters for wireless-communication terminals. To reduce power consumption, we employed the I/Q amplifier sharing technique [1] in which an amplifier is used for both I and Q channels. In addition, common-source, pseudo-differential (PD) amplifiers are used in all the conversion stages for further power reduction. Common-mode disturbances are removed by the proposed common-mode feedforward (CMFF) technique without using fully differential (FD) amplifiers. The converter was implemented in a 90-nm CMOS technology, and it consumes only 24mW/ch from a 1.2V power supply. The measured SNR and SNDR are 58.6dB and 52.2dB, respectively.

Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

Science.gov (United States)

Patmanathan, Sathya Narayanan; Johnson, Steven P; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R; Herr, Deron R; Murray, Paul G; Yap, Lee Fah; Paterson, Ian C

2016-05-10

Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.

Light-emitting diodes based on two-dimensional PA2(CsPbBr3)n-1PbBr4 layered perovskites%基于PA2(CsPbBr3)n-1PbBr4二维层状钙钛矿的电致发光二极管

Institute of Scientific and Technical Information of China (English)

孟妍; 牛连斌; 许龙; 林春燕; 熊自阳; 熊祖洪; 陈平

2018-01-01

进一步提高全无机卤铅钙钛矿材料CsPbBr3的发光效率,对制备高效率、高稳定性的电致发光二极管(PeLED)具有重要意义.制备纳米级的钙钛矿量子点,一方面有助于提高激子的束缚能和钙钛矿晶体的荧光效率,另一方面也有利于形成连续、致密的二维层状钙钛矿薄膜.本文采用“原位生长”的策略,将一种具有长链结构的丙基溴化胺(CH3CH2CH2NH3Br,PABr)作为添加剂,与CsPbBr3的前驱体溶液进行共混,得到PA2(CsPbBr3)n-1PbBr4钙钛矿量子点.形成的二维层状钙钛矿薄膜均匀致密,在光致发光条件下,呈现出明亮的蓝绿光发射(发光峰位于506 nm).在电致发光方面,基于PA2(CsPbBr3)n-1PbBr4的PeLED启亮电压为～4.2 V,最大亮度为～2370 cd/m2,最高电流效率为～1.06 cd/A,最高EQE为～0.57％.相较于传统方法,本工作在制作工艺、成膜质量以及PeLED的发光效率有了显著的提升,为将来进一步探索低成本、高效率的蓝光PeLEDs提供了一种可行的思路.%Solution-processed organometal halide perovskites (formulated as ABX3,where A is the methylammonium (CH3NH3+)(MA) or metal cesium cation (Cs+),B is the lead cation (Pb2+) and X is the halide anion (Br-,I-,Cl-)) are promising candidates for next generation light-emitting materials owing to their unique optoelectronic properties.These properties mainly include extremely high photoluminescence quantum yield (PLQY),easily tunable band gap and narrow emission characteristics.During the past two years,impressive progresses have been made in perovskite light-emitting diodes (PeLED) with hybrid organic-inorganic perovskite materials (i.e.,CH3NH3PbBr3).So far,the best external quantum efficiency (EQE) of CH3NH3PbBr3-based PeLED was reaching up to ～8.53％ which was close to the results of organic light-emitting diodes (OLED).Despite the remarkable performance of the devices demonstrated,the stability of organic-inorganic hybrid perovskites

Hydrogen sulfide upregulated mRNA expressions of sodium bicarbonate cotransporter1, trefoil factor1 and trefoil factor2 in gastric mucosa in rats.

Science.gov (United States)

Cheraghi, Parisa; Mard, Seyyed Ali; Nagi, Tahereh

2016-01-01

Hydrogen sulfide (H 2 S) has been shown to protect the gastric mucosa through several protective mechanisms but till now its effect on mRNA expression of sodium bicarbonate cotransporter 1 (NBC1), trefoil factor1 (TFF1) and trefoil factor2 (TFF2) was not investigated. This study was aimed to evaluate the effect of H 2 S on mRNA expression of NBC1, TFF1 and TFF2 in rat gastric mucosa in response to gastric distention. Thirty two rats were randomly assigned into four equal groups. They were control (C), distention (D), propargylglycine (PAG)-, and NaHS-treated groups. To evaluate the effect of exogenous and endogenous H 2 S on gene expression of NBC1, TFF1 and TFF2, two groups of rats were received H 2 S donor, intra-peritoneal NaHS (80 µg Kg -1 ), and PAG (50 mg kg -1 ), accompanied to stimulate the gastric acid secretion, respectively. Under general anesthesia and laparotomy, a catheter was inserted into the stomach through duodenum for instillation of isotonic saline for gastric distention. Ninety min after beginning the experiment, animals were sacrificed and the gastric mucosa was collected to determine total acid content of gastric effluents and to quantify the mRNA expression of studied genes by quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that A) gastric distention increased the level of mRNA expressions of NBC1, TFF1 and TFF2; B) these levels in NaHS-treated rats were significantly higher than those in Distention group; and C) PAG decreased the expression levels of NBC1 and TFF1. The Findings showed H 2 S upregulated gene expression of NBC1, TFF1 and TFF2 in gastric mucosa.

Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

Science.gov (United States)

Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

2013-07-18

The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

Impact of fgd1 and ddn Diversity in Mycobacterium tuberculosis Complex on In Vitro Susceptibility to PA-824

KAUST Repository

Feuerriegel, S.

2011-09-19

PA-824 is a promising drug candidate for the treatment of tuberculosis (TB). It is in phase II clinical trials as part of the first newly designed regimen containing multiple novel antituberculosis drugs (PA-824 in combination with moxifloxacin and pyrazinamide). However, given that the genes involved in resistance against PA-824 are not fully conserved in the Mycobacterium tuberculosis complex (MTBC), this regimen might not be equally effective against different MTBC genotypes. To investigate this question, we sequenced two PA-824 resistance genes (fgd1 [Rv0407] and ddn [Rv3547]) in 65 MTBC strains representing major phylogenetic lineages. The MICs of representative strains were determined using the modified proportion method in the Bactec MGIT 960 system. Our analysis revealed single-nucleotide polymorphisms in both genes that were specific either for several genotypes or for individual strains, yet none of these mutations significantly affected the PA-824 MICs (≤0.25 μg/ml). These results were supported by in silico modeling of the mutations identified in Fgd1. In contrast, “Mycobacterium canettii” strains displayed a higher MIC of 8 μg/ml. In conclusion, we found a large genetic diversity in PA-824 resistance genes that did not lead to elevated PA-824 MICs. In contrast, M. canettii strains had MICs that were above the plasma concentrations of PA-824 documented so far in clinical trials. As M. canettii is also intrinsically resistant against pyrazinamide, new regimens containing PA-824 and pyrazinamide might not be effective in treating M. canettii infections. This finding has implications for the design of multiple ongoing clinical trials.

Crystal structures of the 2:2 complex of 1,1′-(1,2-phenylenebis(3-m-tolylurea and tetrabutylammonium chloride or bromide

Directory of Open Access Journals (Sweden)

Chao Huang

2017-09-01

Full Text Available The title compounds, tetrabutylammonium chloride–1,1′-(1,2-phenylenebis(3-m-tolylurea (1/1, C16H36N+·Cl−·C22H22N4O2 or [(n-Bu4N+·Cl−(C22H22N4O2] (I and tetrabutylammonium bromide–1,1′-(1,2-phenylenebis(3-m-tolylurea (1/1, C16H36N+·Br−·C22H22N4O2 or [(n-Bu4N+·Br−(C22H22N4O2] (II, both comprise a tetrabutylammonium cation, a halide anion and an ortho-phenylene bis-urea molecule. Each halide ion shows four N—H...X (X = Cl or Br interactions with two urea receptor sites of different bis-urea moieties. A crystallographic inversion centre leads to the formation of a 2:2 arrangement of two halide anions and two bis-urea molecules. In the crystals, the dihedral angle between the two urea groups of the bis-urea molecule in (I [defined by the four N atoms, 165.4 (2°] is slightly smaller than that in (II [167.4 (2°], which is probably due to the smaller ionic radius of chloride compared to bromide.

Partial molar volume of paracetamol in water, 0.1 M HCl and 0.154 M NaCl at T = (298.15, 303.15, 308.15 and 310.65) K and at 101.325 kPa

Energy Technology Data Exchange (ETDEWEB)

Iqbal, Muhammad Javed [Department of Chemistry, Quaid-i-Azam University, Islamabad, Capital 54320 (Pakistan)]. E-mail: mjiqauchem@yahoo.com; Malik, Qaisar Mahmood [Department of Chemistry, Quaid-i-Azam University, Islamabad, Capital 54320 (Pakistan)]. E-mail: qaisar_@hotmail.com

2005-12-15

The apparent molar volume of paracetamol (4-acetamidophenol) in water, 0.1 M HCl and 0.154 M NaCl as solvents at (298.15, 303.15, 308.15 and 310.65) K temperatures and at a pressure of 101.325 kPa were determined from the density data obtained with the help of a vibrating-tube Anton Paar DMA-48 densimeter. The partial molar volume, V {sub m}, of paracetamol in these solvents at different temperatures was evaluated by extrapolating the apparent molar volume versus molality plots to m = 0. In addition, the partial molar expansivity, E {sup .}, the isobaric coefficient of thermal expansion, {alpha} {sub p}, and the interaction coefficient, S {sub v}, have also been computed. The expansivity data show dependence of E {sup .} values on the structure of the solute molecules.

Partial molar volume of paracetamol in water, 0.1 M HCl and 0.154 M NaCl at T = (298.15, 303.15, 308.15 and 310.65) K and at 101.325 kPa

International Nuclear Information System (INIS)

Iqbal, Muhammad Javed; Malik, Qaisar Mahmood

2005-01-01

The apparent molar volume of paracetamol (4-acetamidophenol) in water, 0.1 M HCl and 0.154 M NaCl as solvents at (298.15, 303.15, 308.15 and 310.65) K temperatures and at a pressure of 101.325 kPa were determined from the density data obtained with the help of a vibrating-tube Anton Paar DMA-48 densimeter. The partial molar volume, V m , of paracetamol in these solvents at different temperatures was evaluated by extrapolating the apparent molar volume versus molality plots to m = 0. In addition, the partial molar expansivity, E . , the isobaric coefficient of thermal expansion, α p , and the interaction coefficient, S v , have also been computed. The expansivity data show dependence of E . values on the structure of the solute molecules

Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages.

Science.gov (United States)

Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan

2017-09-01

Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC 50 value of 1.04μM. Results from NPOI further showed that the K on and K off of PUN-PTP1B complex were 3.38e2M -1 s -1 and 4.13e-3s -1 , respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Localization on AdS{sub 2}×S{sup 1}

Energy Technology Data Exchange (ETDEWEB)

David, Justin R. [Centre for High Energy Physics, Indian Institute of Science,C.V. Raman Avenue, Bangalore, 560012 (India); Gava, Edi [INFN, Sezione di Trieste,Strada Costiera 11, Trieste (Italy); Gupta, Rajesh Kumar; Narain, Kumar [ICTP,Strada Costiera 11, Trieste, 34151 (Italy)

2017-03-09

Conformal symmetry relates the metric on AdS{sub 2}×S{sup 1} to that of S{sup 3}. This implies that under a suitable choice of boundary conditions for fields on AdS{sub 2} the partition function of conformal field theories on these spaces must agree which makes AdS{sub 2}×S{sup 1} a good testing ground to study localization on non-compact spaces. We study supersymmetry on AdS{sub 2}×S{sup 1} and determine the localizing Lagrangian for N=2 supersymmetric Chern-Simons theory on AdS{sub 2}×S{sup 1}. We evaluate the partition function of N=2 supersymmetric Chern-Simons theory on AdS{sub 2}×S{sup 1} using localization, where the radius of S{sup 1} is q times that of AdS{sub 2}. With boundary conditions on AdS{sub 2}×S{sup 1} which ensure that all the physical fields are normalizable and lie in the space of square integrable wave functions in AdS{sub 2}, the result for the partition function precisely agrees with that of the theory on the q-fold covering of S{sup 3}.

Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma.

Science.gov (United States)

Oricchio, Elisa; Katanayeva, Natalya; Donaldson, Maria Christine; Sungalee, Stephanie; Pasion, Joyce P; Béguelin, Wendy; Battistello, Elena; Sanghvi, Viraj R; Jiang, Man; Jiang, Yanwen; Teater, Matt; Parmigiani, Anita; Budanov, Andrei V; Chan, Fong Chun; Shah, Sohrab P; Kridel, Robert; Melnick, Ari M; Ciriello, Giovanni; Wendel, Hans-Guido

2017-06-28

Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation ( EZH2 Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. SESTRIN1 loss represents an alternative to RRAGC mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, EZH2 Y641X mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Homoleptic diphosphacyclobutadiene complexes [M(η(4)-P2C2R2)2]x- (M = Fe, Co; x = 0, 1).

Science.gov (United States)

Wolf, Robert; Ehlers, Andreas W; Khusniyarov, Marat M; Hartl, František; de Bruin, Bas; Long, Gary J; Grandjean, Fernande; Schappacher, Falko M; Pöttgen, Rainer; Slootweg, J Chris; Lutz, Martin; Spek, Anthony L; Lammertsma, Koop

2010-12-27

The preparation and comprehensive characterization of a series of homoleptic sandwich complexes containing diphosphacyclobutadiene ligands are reported. Compounds [K([18]crown-6)(thf)(2)][Fe(η(4)-P(2)C(2)tBu(2))(2)] (K1), [K([18]crown-6)(thf)(2)][Co(η(4)-P(2)C(2)tBu(2))(2)] (K2), and [K([18]crown-6)(thf)(2)][Co(η(4)-P(2)C(2)Ad(2))(2)] (K3, Ad = adamantyl) were obtained from reactions of [K([18]crown-6)(thf)(2)][M(η(4)-C(14)H(10))(2)] (M = Fe, Co) with tBuC[triple bond]P (1, 2), or with AdC[triple bond]P (3). Neutral sandwiches [M(η(4)-P(2)C(2)tBu(2))(2)] (4: M = Fe 5: M = Co) were obtained by oxidizing 1 and 2 with [Cp(2)Fe]PF(6). Cyclic voltammetry and spectro-electrochemistry indicate that the two [M(η(4)-P(2)C(2)tBu(2))(2)](-)/[M(η(4)-P(2)C(2)tBu(2))(2)] moieties can be reversibly interconverted by one electron oxidation and reduction, respectively. Complexes 1-5 were characterized by multinuclear NMR, EPR (1 and 5), UV/Vis, and Mössbauer spectroscopies (1 and 4), mass spectrometry (4 and 5), and microanalysis (1-3). The molecular structures of 1-5 were determined by using X-ray crystallography. Essentially D(2d)-symmetric structures were found for all five complexes, which show the two 1,3-diphosphacyclobutadiene rings in a staggered orientation. Density functional theory calculations revealed the importance of covalent metal-ligand π bonding in 1-5. Possible oxidation state assignments for the metal ions are discussed.

IDC1, a pezizomycotina-specific gene that belongs to the PaMpk1 MAP kinase transduction cascade of the filamentous fungus Podospora anserina.

Science.gov (United States)

Jamet-Vierny, Corinne; Debuchy, Robert; Prigent, Magali; Silar, Philippe

2007-12-01

Components involved in the activation of the MAPK cascades in filamentous fungi are not well known. Here, we provide evidence that IDC1, a pezizomycotina-specific gene is involved along with the PaNox1 NADPH oxidase in the nuclear localization of the PaMpk1 MAP kinase, a prerequisite for MAPK activity. Mutants of IDC1 display the same phenotypes as mutants in PaNox1 and PaMpk1, i.e., lack of pigment and of aerial hyphae, female sterility, impairment in hyphal interference and inability to develop Crippled Growth cell degeneration. As observed for the PaNox1 mutant, IDC1 mutants are hypostatic to PaMpk1 mutants. IDC1 seems to play a key role in sexual reproduction. Indeed, fertility is diminished in strains with lower level of IDC1. In strains over-expressing IDC1, protoperithecia reach a later stage of development towards perithecia without fertilization; however, upon fertilization maturation of fertile perithecia is diminished and delayed. In addition, heterokaryon construction shows that IDC1 is necessary together with PaNox1 in the perithecial envelope but not in the dikaryon resulting from fertilization.

Positronium formation and hydrated positron reactions in H2O, D2O, 1.74 M PPS/H2O and 1.74 M PPS/D2O solutions of Cl−, Br− and I−

DEFF Research Database (Denmark)

Mogensen, O. E.; Pedersen, Niels Jørgen

1986-01-01

Angular correlation of annihilation photons were measured for H2O, D2O, 1.74 M PPS/H2O and 1.74 M PPS/D2O solutions of Cl−, Br− and I−. The three components of the angular correlation spectra for D2O and H2O were nearly identical in shape. The positronium (Ps) yields for the H2O and D2O solutions...... before annihilation (lifetime 400 ps) was determined for the three halides in the four solvents. Simple kinetic equations (“trapping model”) with time dependent rate constant, solved analytically, could explain the [X−, e+] formation in H2O fairly well for concentrations below 0.03 M X−, if a diffusion...... controlled reaction with positron diffusion constant D = 5 × 10−5 cm2/s and reaction radius R = 1 nm were assumed. The three halides gave roughly identical [X−, e+] formation below 0.03 M X−. The difference between the four solutions could be explained partly only in terms of viscosity change for the model...

MoS2 @HKUST-1 Flower-Like Nanohybrids for Efficient Hydrogen Evolution Reactions.

Science.gov (United States)

Wang, Chengli; Su, Yingchun; Zhao, Xiaole; Tong, Shanshan; Han, Xiaojun

2018-01-24

A novel MoS 2 -based flower-like nanohybrid for hydrogen evolution was fabricated through coating the Cu-containing metal-organic framework (HKUST-1) onto MoS 2 nanosheets. It is the first time that MoS 2 @HKUST-1 nanohybrids have been reported for the enhanced electrochemical performance of HER. The morphologies and components of the MoS 2 @HKUST-1 flower-like nanohybrids were characterized by scanning electron microscopy, X-ray diffraction analysis and Fourier transform infrared spectroscopy. Compared with pure MoS 2 , the MoS 2 @HKUST-1 hybrids exhibit enhanced performance on hydrogen evolution reaction with an onset potential of -99 mV, a smaller Tafel slope of 69 mV dec -1 , and a Faradaic efficiency of nearly 100 %. The MoS 2 @HKUST-1 flower-like nanohybrids exhibit excellent stability in acidic media. This design opens new possibilities to effectively synthesize non-noble metal catalysts with high performance for the hydrogen evolution reaction (HER). © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

mPGES-1-derived PGE2 mediates dehydration natriuresis

Science.gov (United States)

Jia, Zhanjun; Liu, Gang; Sun, Ying; Kakizoe, Yutaka; Guan, Guangju; Zhang, Aihua; Zhou, Shu-Feng

2013-01-01

PGE2 is a natriuretic factor whose production is elevated after water deprivation (WD) but its role in dehydration natriuresis is not well-defined. The goal of the present study was to investigate the role of microsomal prostaglandin E synthase-1 (mPGES-1) in dehydration natriuresis. After 24-h WD, wild-type (WT) mice exhibited a significant increase in 24-h urinary Na+ excretion accompanied with normal plasma Na+ concentration and osmolality. In contrast, WD-induced elevation of urinary Na+ excretion was completely abolished in mPGES-1 knockout (KO) mice in parallel with increased plasma Na+ concentration and a trend increase in plasma osmolality. WD induced a 1.8-fold increase in urinary PGE2 output and a 1.6-fold increase in PGE2 content in the renal medulla of WT mice, both of which were completely abolished by mPGES-1 deletion. Similar patterns of changes were observed for urinary nitrate/nitrite and cGMP. The natriuresis in dehydrated WT mice was associated with a significant downregulation of renal medullary epithelial Na channel-α mRNA and protein, contrasting to unaltered expressions in dehydrated KO mice. By quantitative RT-PCR, WD increased the endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS expressions in the renal medulla of WT mice by 3.9-, 1.48-, and 2.6-fold, respectively, all of which were significantly blocked in mPGES-1 KO mice. The regulation of eNOS expression was further confirmed by immunoblotting. Taken together, our results suggest that mPGES-1-derived PGE2 contributes to dehydration natriuresis likely via NO/cGMP. PMID:23171554

M2-F1 in flight over lakebed on tow line

Science.gov (United States)

1963-01-01

the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47 aircraft and released. These initial car-tow tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. A small solid landing rocket, referred to as the 'instant L/D rocket,' was installed in the rear base of the M2-F1. This rocket, which could be ignited by the pilot, provided about 250 pounds of thrust for about 10 seconds. The rocket could be used to extend the flight time near landing if needed. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers--the M2-F2 and the HL-10, both built by the Northrop Corporation, and the U.S. Air Force's X-24 program, with an X-24A and -B built by Martin. The Lifting Body program also heavily influenced the Space Shuttle program. The M2-F1 program demonstrated the feasibility of the lifting body concept for horizontal landings of atmospheric entry vehicles. It also demonstrated a procurement and management concept for prototype flight test vehicles that produced rapid results at very low cost (approximately $50,000, excluding salaries of government employees assigned to the project).

Raman Spectroscopy evidence of 1:1:1 complex formation during dissolution of WO3 : K2SO4 in a melt of K2S2O7

DEFF Research Database (Denmark)

Berg, Rolf W.; Maijó Ferré, Irene

2005-01-01

The dissolution reaction of solid WO3 into a melt consisting of a 1:1 molar mixture of K2S2O7 and K2SO4 was studied by Raman spectroscopy. It was found that a new compound was formed, dimeric K8[(WO2)2(m-SO4)2(SO4)4]. The assigned Raman spectrum is given. Extended abstract of Poster presented...

Observation of the hadronic transitions χb1,2(2P)→ωΥ(1S)

International Nuclear Information System (INIS)

Cronin-Hennessy, D.; Park, C.S.; Park, W.; Thayer, J.B.; Thorndike, E.H.; Coan, T.E.; Gao, Y.S.; Liu, F.; Stroynowski, R.; Artuso, M.; Boulahouache, C.; Blusk, S.; Dambasuren, E.; Dorjkhaidav, O.; Mountain, R.; Muramatsu, H.; Nandakumar, R.; Skwarnicki, T.; Stone, S.; Wang, J.C.

2004-01-01

The CLEO Collaboration has made the first observations of hadronic transitions among bottomonium (bb-bar) states other than the dipion transitions among Υ(nS) states. In our study of Υ(3S) decays, we find a significant signal for Υ(3S)→γωΥ(1S) that is consistent with radiative decays Υ(3S)→γχ b1,2 (2P), followed by χ b1,2 (2P)→ωΥ(1S). The branching ratios we obtain are B[χ b1 (2P)→ωΥ(1S)]=(1.63 -0.31-0.15 +0.35+0.16 )% and B[χ b2 (2P)→ωΥ(1S)]=(1.10 -0.28-0.10 +0.32+0.11 )%, in which the first error is statistical and the second is systematic.

Aspergillus niger PA2: a novel strain for extracellular biotransformation of L-tyrosine into L-DOPA.

Science.gov (United States)

Agarwal, Pragati; Pareek, Nidhi; Dubey, Swati; Singh, Jyoti; Singh, R P

2016-05-01

L-DOPA (3,4-dihydroxyphenyl-L-alanine), an amino acid derivative is the most widely used drug of choice for the treatment of Parkinson's disease and other neurologic injuries. The present study deals with the elevated biochemical transformation of L-tyrosine to L-DOPA by Aspergillus niger PA2, a potent tyrosinase producer, isolated from decomposed food wastes. This appears to be the first report on A. niger as a notable extracellular tyrosinase producer. The extracellular tyrosinase activity produced remarkably higher levels of L-DOPA, i.e. 2.44 mg mL(-1) when the media was supplemented with 5 mg mL(-1) L-tyrosine. The optimum pH for tyrosinase production was 6.0, with the maximal L-DOPA production at the same pH. The product thus produced was analyzed by thin-layer chromatography, UV spectroscopy, high-performance liquid chromatography and Fourier transform infrared spectroscopy, that had denoted this to be L-DOPA. Kinetic parameters viz. Y p/s, Q s and Q p had further indicated the notable levels of production. Thus, Aspergillus niger PA2 could be a promising resource and may be further exploited for large-scale production of L-DOPA.

Inflammation induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation.

Science.gov (United States)

Banerjee, Dipanjan; Sinha, Archana; Saikia, Sudeshna; Gogoi, Bhaskarjyoti; Rathore, Arvind K; Das, Anindhya Sundar; Pal, Durba; Buragohain, Alak K; Dasgupta, Suman

2018-06-05

The transformation of macrophages into lipid loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying molecular mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activating mTORC2 induces Akt phosphorylation at serine 473 and that aggravate mTORC1 dependent scavenger receptors expression and consequent lipid accumulation in THP-1 macrophages. Inhibition of mTORC2 either by silencing Rictor expression or inhibiting its association with mTOR notably prevents LPS induced Akt activation, scavenger receptors expression and macrophage lipid accumulation. Although suppression of mTORC1 expression by genetic knockdown of Raptor did not produce any significant change in Akt S473 phosphorylation, however, incubation with Akt activator in Rictor silenced cells failed to promote scavenger receptors expression and macrophage foam cell formation. Thus, present research explored the signaling pathway involved in inflammation induced macrophage foam cells formation and therefore, targeting this pathway might be useful for preventing macrophage foam cell formation. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

M2-F1 lifting body and Paresev 1B on ramp

Science.gov (United States)

1963-01-01

near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47 aircraft and released. These initial car-tow tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. A small solid landing rocket, referred to as the 'instant L/D rocket,' was installed in the rear base of the M2-F1. This rocket, which could be ignited by the pilot, provided about 250 pounds of thrust for about 10 seconds. The rocket could be used to extend the flight time near landing if needed. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers--the M2-F2 and the HL-10, both built by the Northrop Corporation, and the U.S. Air Force's X-24 program, with an X-24A and -B built by Martin. The Lifting Body program also heavily influenced the Space Shuttle program. The M2-F1 program demonstrated the feasibility of the lifting body concept for horizontal landings of atmospheric entry vehicles. It also demonstrated a procurement and management concept for prototype flight test vehicles that produced rapid results at very low cost (approximately $50,000, excluding salaries of government employees assigned to the project). The Paresev (Paraglider Rescue Vehicle) was an indirect outgrowth of kite

FeS2-doped MoS2 nanoflower with the dominant 1T-MoS2 phase as an excellent electrocatalyst for high-performance hydrogen evolution

International Nuclear Information System (INIS)

Zhao, Xue; Ma, Xiao; Lu, Qingqing; Li, Qun; Han, Ce; Xing, Zhicai; Yang, Xiurong

2017-01-01

Well-established methods to improve the hydrogen evolution reaction (HER) performances include, but are not limited to, tailoring the morphology and electronic structure of transition metal dichalcogenides (TMDs), and doping of earth abundant chemicals such as iron pyrite FeS 2 into existing TMDs. In this work, MoS 2 nanoflowers with the majority being octahedral MoS 2 (1T-MoS 2 ) and doped with FeS 2 were prepared and applied to HER. The as-prepared catalysts were characterized by X-ray absorption fine structure at the K-edge of Mo, S, and Fe to probe the local electronic structures. The resulting nanomaterial was identified to be FeS 2 doped MoS 2 nanoflower (denoted as Fe-MoS 2 NF) with 66% 1T-MoS 2 which was the metallic phase and could drastically boost the HER properties. The Fe-MoS 2 NF exhibited high HER performance with a Tafel slope of 82 mV dec −1 and it needs 136 mV to achieve a current density of 10 mA cm −2 . The synthesis of Fe-MoS 2 NF with refined morphology and active electronic structure is expected to open a new era for improving the catalytic activity and stability of MoS 2 .

Novel deletion alleles carrying CYP21A1P/A2 chimeric genes in Brazilian patients with 21-hydroxylase deficiency

Directory of Open Access Journals (Sweden)

Guerra-Júnior Gil

2010-06-01

Full Text Available Abstract Background Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in CYP21A2 gene. The human gene is located at 6p21.3 within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module. The CYP21 extra copy is a pseudogene (CYP21A1P. In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric CYP21A1P/A2 genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular C4/CYP21 locus. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency. Methods We used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of CYP21A1P/A2 chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with C4/CYP21 30-kb deletion were included in the study. Results An allele carrying a CYP21A1P/A2 chimeric gene was found unusually associated to a C4B/C4A Taq I 6.4-kb fragment, generally associated to C4B and CYP21A1P deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in CYP21A1P of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different

M2-F1 in flight being towed by a C-47

Science.gov (United States)

1964-01-01

Langley research centers--the M2-F2 and the HL-10, both built by the Northrop Corporation, and the U.S. Air Force's X-24 program. The Lifting Body program also heavily influenced the Space Shuttle program. The M2-F1 program demonstrated the feasibility of the lifting body concept for horizontal landings of atmospheric entry vehicles. It also demonstrated a procurement and management concept for prototype flight test vehicles that produced rapid results at very low cost (approximately $50,000, excluding salaries of government employees assigned to the project).

Model and experimental investigation of frequency conversion in AgGaGexS2(1+x) (x = 0, 1) crystals

International Nuclear Information System (INIS)

Wang Tiejun; Kang Zhihui; Zhang Hongzhi; Feng Zhishu; Jiang Yun; Gao Jinyue; Andreev, Yury M; Lanskii, Gregory V; Shaiduko, Anna V

2007-01-01

Analysis of available and developed data on phase matching in AgGaGe x S 2(1+x) (x = 0, 1) crystals is carried out. Nanosecond AgGaS 2 type I optical parametric oscillator with a continuously tunable range 2.65-5.29 μm is demonstrated pumped by a Q-switched Nd : YAG laser. An output pulse energy of up to 0.56 mJ at 4 μm is recorded. Phase matching of second harmonic generation in both crystals is represented. Best sets of Sellmeier equations for two crystals are determined

Transport and activation of S-(1,2-dichlorovinyl)-L-cysteine and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine in rat kidney proximal tubules

International Nuclear Information System (INIS)

Zhang, G.H.; Stevens, J.L.

1989-01-01

An important step in understanding the mechanism underlying the tubular specificity of the nephrotoxicity of toxic cysteine conjugates is to identify the rate-limiting steps in their activation. The rate-limiting steps in the activation of toxic cysteine conjugates were characterized using isolated proximal tubules from the rat and 35S-labeled S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAC-DCVC) as model compounds. The accumulation by tubules of 35S radiolabel from both DCVC and NAC-DCVC was time and temperature dependent and was mediated by both Na+-dependent and independent processes. Kinetic studies with DCVC in the presence of sodium revealed the presence of two components with apparent Km and Vmax values of (1) 46 microM and 0.21 nmol/mg min and (2) 2080 microM and 7.3 nmol/mg.min. NAC-DVVC uptake was via a single system with apparent Km and Vmax values of 157 microM and 0.65 nmol/mg.min, respectively. Probenecid, an inhibitor of the renal organic anion transport system, inhibited accumulation of radiolabel from NAC-DCVC, but not from DCVC. The covalent binding of 35S label to cellular macromolecules was much greater from [35S]DCVC than from NAC-[35S]DCVC. Analysis of metabolites showed that a substantial amount of the cellular NAC-[35S]DCVC was unmetabolized while [35S]DCVC was rapidly metabolized to bound 35S-labeled material and unidentified products. The data suggest that DCVC is rapidly metabolized following transport, but that activation of NAC-DCVC depends on a slower rate of deacetylation. The results are discussed with regard to the segment specificity of cysteine conjugate toxicity and the role of disposition in vivo in the nephrotoxicity of glutathione conjugates

Production and identification of an isomeric state in 217Pa and the new isotope 218Pa

International Nuclear Information System (INIS)

Schmidt, K.H.; Faust, W.; Muenzenberg, G.; Ewald, H.; Guettner, K.; Clerc, H.G.; Lang, W.; Wohlfarth, H.; Pielenz, K.

1977-02-01

Evaporation residues produced in the reaction 40Ar(176 MeV) + 181Ta were separated from the primary beam by the velocity filter SHIP and detected by a ΔE-E counter telescope. The technique of delayed coincidences was applied to individually identify the reaction products implanted into a Si-surface barrier detector by their subsequent alpha decays. The previously unknown nucleus 218Pa was identified by its known daughter decays. 218Pa was found to decay with Esub(α) = (9.614 +- 0.015) MeV, T(1/2) = (140 +- 50) μs and probably also with Esub(α) = (9.535 +- 0.020) MeV, T(1/2) = (150 + 100 - 50) μs. The half-life of the 8.33 MeV alpha decay of 217Pa was determined to be (o.2 +- 0.4) ms. Anew isomer in 217 Pa was found which decays with Esub(α) = (10.16 +- 0.02) MeV and T(1/2) = (1.8 +- 0.5) ms. (orig./BJ) [de

M2-F1 in flight during low-speed car tow

Science.gov (United States)

1963-01-01

seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47 aircraft and released. These initial car-tow tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. A small solid landing rocket, referred to as the 'instant L/D rocket,' was installed in the rear base of the M2-F1. This rocket, which could be ignited by the pilot, provided about 250 pounds of thrust for about 10 seconds. The rocket could be used to extend the flight time near landing if needed. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers--the M2-F2 and the HL-10, both built by the Northrop Corporation, and the U.S. Air Force's X-24 program, with an X-24A and -B built by Martin. The Lifting Body program also heavily influenced the Space Shuttle program. The M2-F1 program demonstrated the feasibility of the lifting body concept for horizontal landings of atmospheric entry vehicles. It also demonstrated a procurement and management concept for prototype flight test vehicles that produced rapid results at very low cost (approximately $50,000, excluding salaries of government employees assigned to the project).

The sphingosine 1-phosphate receptor S1P(2) triggers hepatic wound healing

NARCIS (Netherlands)

Serriere-Lanneau, Valerie; Teixeira-Clerc, Fatima; Li, Liying; Schippers, Marlies; de Wries, Willie; Julien, Boris; Tran-Van-Nhieu, Jeanne; Manin, Sylvie; Poelstra, Klaas; Chun, Jerold; Carpentier, Stephane; Levade, Thierry; Mallat, Ariane; Lotersztajn, Sophie

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK1 and 2). We previously showed that S1P receptors (S1P(1), S1P(2), and S1P(3)) are expressed in hepatic myofibroblasts (hMF), a population of cells that triggers matrix remodeling during liver injury. Here

Ranked solutions of the matric equation A1X1=A2X2

Directory of Open Access Journals (Sweden)

A. Duane Porter

1980-01-01

Full Text Available Let GF(pz denote the finite field of pz elements. Let A1 be s×m of rank r1 and A2 be s×n of rank r2 with elements from GF(pz. In this paper, formulas are given for finding the number of X1,X2 over GF(pz which satisfy the matric equation A1X1=A2X2, where X1 is m×t of rank k1, and X2 is n×t of rank k2. These results are then used to find the number of solutions X1,…,Xn, Y1,…,Ym, m,n>1, of the matric equation A1X1…Xn=A2Y1…Ym.

Experiment data report for semiscale Mod-1 Test S-06-2 (LOFT counterpart test)

International Nuclear Information System (INIS)

Patton, M.L. Jr.; Collins, B.L.; Sackett, K.E.

1977-08-01

Recorded test data are presented for Test S-06-2 of the Semiscale Mod-1 LOFT counterpart test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying an hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-06-2 was conducted from initial conditions of 15 513 kPa and 563 K to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the broken loop cold leg piping. During the test, cooling water was injected into the cold leg of the intact loop to simulate emergency core coolant injection in a PWR. The heater rods in the electrically heated core were operated at an axial peak power density which was 50% of the maximum peak power density

Cardiac mTORC1 Dysregulation Impacts Stress Adaptation and Survival in Huntington’s Disease

Directory of Open Access Journals (Sweden)

Daniel D. Child

2018-04-01

Full Text Available Summary: Huntington’s disease (HD is a dominantly inherited neurological disorder caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT. But in addition to the neurological disease, mutant HTT (mHTT, which is ubiquitously expressed, impairs other organ systems. Indeed, epidemiological and animal model studies suggest higher incidence of and mortality from heart disease in HD. Here, we show that the protein complex mTORC1 is dysregulated in two HD mouse models through a mechanism that requires intrinsic mHTT expression. Moreover, restoring cardiac mTORC1 activity with constitutively active Rheb prevents mortality and relieves the mHTT-induced block to hypertrophic adaptation to cardiac stress. Finally, we show that chronic mTORC1 dysregulation is due in part to mislocalization of endogenous Rheb. These data provide insight into the increased cardiac-related mortality of HD patients, with cardiac mHTT expression inhibiting mTORC1 activity, limiting heart growth, and decreasing the heart’s ability to compensate to chronic stress. : Child et al. demonstrate that mTORC1 dysregulation is a key molecular mechanism in the Huntington’s disease (HD heart phenotype. Impaired cardiac mTORC1 activity in HD mouse models requires intrinsic mHTT expression and explains the limited adaptation to cardiac stress. Keywords: Huntington’s disease, heart, mTOR, Rheb

Sestrin2 inhibits mTORC1 through modulation of GATOR complexes

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeong Sig; Ro, Seung-Hyun; Kim, Myungjin; Park, Hwan-Woo; Semple, Ian A.; Park, Haeli; Cho, Uhn-Soo; Wang, Wei; Guan, Kun-Liang; Karin, Michael; Lee, Jun Hee (Michigan); (UCSD)

2015-03-30

Sestrins are stress-inducible metabolic regulators that suppress a wide range of age- and obesity-associated pathologies, many of which are due to mTORC1 overactivation. Upon various stresses, the Sestrins inhibit mTORC1 activity through an indirect mechanism that is still unclear. GATORs are recently identified protein complexes that regulate the activity of RagB, a small GTPase essential for mTORC1 activation. GATOR1 is a GTPase activating protein (GAP) for RagB whereas GATOR2 functions as an inhibitor of GATOR1. However, how the GATORs are physiologically regulated is unknown. Here we show that Sestrin2 binds to GATOR2, and liberates GATOR1 from GATOR2-mediated inhibition. Released GATOR1 subsequently binds to and inactivates RagB, ultimately resulting in mTORC1 suppression. Consistent with this biochemical mechanism, genetic ablation of GATOR1 nullifies the mTORC1-inhibiting effect of Sestrin2 in both cell culture and Drosophila models. Collectively, we elucidate a new signaling cascade composed of Sestrin2-GATOR2-GATOR1-RagB that mediates stress-dependent suppression of mTORC1 activity.

Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

Science.gov (United States)

Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

2017-10-01

Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

BaO-Nd2O3-CuOx subsolidus equilibria under carbonate-free conditions at pO2=100 Pa and at pO2=21 kPa

International Nuclear Information System (INIS)

Wong-Ng, W.; Cook, L.P.; Suh, J.; Coutts, R.; Stalick, J.K.; Levin, I.; Huang, Q.

2003-01-01

Subsolidus phase equilibria of the BaO-Nd 2 O 3 -CuO x system at pO 2 =100 Pa (0.1% O 2 volume fraction, 810 deg. C) and at pO 2 =21 kPa (21% O 2 volume fraction, 930 deg. C) have been investigated by applying controlled-atmosphere methods to minimize the presence of carbonate and CO 2 and H 2 O contamination. Under carbonate-free conditions, the BaO-Nd 2 O 3 -CuO x phase diagrams at pO 2 =100 Pa and at pO 2 =21 kPa are similar to one another except for differences in the extent of the solid solutions. Apart from the limiting binary phases, the ternary system consists of three solid solutions and one stoichiometric ternary compound. The first solid solution is the high T c series, Ba 2-x Nd 1+x Cu 3 O 6+z (0.3≥x≥0 at pO 2 =100 Pa; 0.95≥x≥ 0 at pO 2 =21 kPa). At pO 2 =21 kPa, a compositionally dependent phase change was detected, from tetragonal (0.7>x≥0) to orthorhombic (0.95≥x≥0.7). The second solid solution series, the 'brown-phase' Ba 1+x Nd 2-x CuO z , has a narrow homogeneity region (0.10>x≥0 at pO 2 =100 Pa; 0.15>x≥0 at pO 2 =21 kPa). In the high BaO part of the phase diagram, a third solid solution (Ba 2-x Nd x )CuO 3+z (x=0 to ∼ 0.3 at pO 2 =100 Pa; x=0-0.45 at pO 2 =21 kPa) was confirmed, as well as a nominally stoichiometric phase, Ba 4 Nd 2 Cu 2 O z . The latter phase is an insulator, with a structure comprised of unusual CuO 5 linear chains. A significant difference in tie line distribution involving the Ba 2-x Nd 1+x Cu 3 O 6+z superconductor was found under carbonate-free conditions relative to literature studies completed in air. Instead of the BaCuO 2+x -Ba 2+x Nd 4-x Cu 2 O z tie line normally encountered in air, a Ba 2-x Nd 1+x Cu 3 O 6+z -(Ba,Nd) 2 CuO 3+x tie line was established. This tie line substantially expands the field of stability of the Ba 2-x Nd 1+x Cu 3 O 6+z superconductor phase into the BaO-rich region of the phase diagram. Implications for the processing of materials based on the Ba 2-x Nd 1+x Cu 3 O 6+z

Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer

DEFF Research Database (Denmark)

Winther, Stine Braendegaard; Österlund, Pia; Berglund, Åke

2017-01-01

to select which older patients should receive therapy. Methods: The NORDIC 9 trial is a Nordic multicenter randomized phase II study comparing full dose monotherapy (S-1 30 mg/m2 twice daily days 1-14 every 3 weeks, followed by second line irinotecan 250-350 mg/m2 iv day 1 every 3 weeks or 180-250 mg/m2 iv...... day 1 every 2 weeks) with reduced dose combination therapy (S-1 20 mg/m2 days 1-14 + oxaliplatin 100 mg/m2 iv day 1 every 3 weeks, followed by second line S-1 20 mg/m2 days 1-14 + irinotecan 180 mg/m2 day 1 every 3 week) for older patients (≥70 years) with mCRC who are not candidates for full...... chance for tailored treatment strategies in these patients. Trial registration: EU Clinical Trial Register, EudraCT no. 2014-000394-39. Registered 05 May 2014....

Charge Transfer Effects in Naturally Occurring van der Waals Heterostructures (PbSe )1.16(TiSe2 )m (m =1 , 2)

Science.gov (United States)

Yao, Q.; Shen, D. W.; Wen, C. H. P.; Hua, C. Q.; Zhang, L. Q.; Wang, N. Z.; Niu, X. H.; Chen, Q. Y.; Dudin, P.; Lu, Y. H.; Zheng, Y.; Chen, X. H.; Wan, X. G.; Feng, D. L.

2018-03-01

van der Waals heterostructures (VDWHs) exhibit rich properties and thus has potential for applications, and charge transfer between different layers in a heterostructure often dominates its properties and device performance. It is thus critical to reveal and understand the charge transfer effects in VDWHs, for which electronic structure measurements have proven to be effective. Using angle-resolved photoemission spectroscopy, we studied the electronic structures of (PbSe )1.16(TiSe2 )m (m =1 , 2), which are naturally occurring VDWHs, and discovered several striking charge transfer effects. When the thickness of the TiSe2 layers is halved from m =2 to m =1 , the amount of charge transferred increases unexpectedly by more than 250%. This is accompanied by a dramatic drop in the electron-phonon interaction strength far beyond the prediction by first-principles calculations and, consequently, superconductivity only exists in the m =2 compound with strong electron-phonon interaction, albeit with lower carrier density. Furthermore, we found that the amount of charge transferred in both compounds is nearly halved when warmed from below 10 K to room temperature, due to the different thermal expansion coefficients of the constituent layers of these misfit compounds. These unprecedentedly large charge transfer effects might widely exist in VDWHs composed of metal-semiconductor contacts; thus, our results provide important insights for further understanding and applications of VDWHs.

Th1/M1 conversion to Th2/M2 responses in models of inflammation lacking cell death stimulates maturation of monocyte precursors to fibroblasts

Directory of Open Access Journals (Sweden)

JoAnn eTrial

2013-09-01

Full Text Available We have demonstrated that cardiac fibrosis arises from the differentiation of monocyte-derived fibroblasts. We present here evidence that this process requires sequential Th1 and Th2 induction promoting analogous M1 (classically activated and M2 (alternatively activated macrophage polarity. Our models are 1 mice subjected to daily repetitive ischemia reperfusion (I/R without infarction and 2 the in vitro transmigration of human mononuclear leukocytes through human cardiac microvascular endothelium. In the mouse heart, leukocytes entered after I/R in response to monocyte chemoattractant protein-1 (MCP-1 which is the major cytokine induced by this protocol. Monocytes within the heart then differentiated into fibroblasts making collagen while bearing the markers of M2 macrophages. T cells were seen in these hearts as well as in the human heart with cardiomyopathy. In the in vitro model, transmigration of the leukocytes was likewise induced by MCP-1 and some monocytes matured into fibroblasts bearing M2 markers. In this model, the MCP-1 stimulus induced a transient Th1 and M1 response that developed into a predominately Th2 and M2 response. An increase in the Th2 product IL-13 was present in both the human and the mouse models, consistent with its known role in fibrosis. In these simplified models, in which there is no cell death to stimulate an anti-inflammatory response, there is nonetheless a resolution of inflammation enabling a profibrotic environment. This induces the maturation of monocyte precursors into fibroblasts.

The elusive 2s3s1S level in B II

International Nuclear Information System (INIS)

Martinson, I; Awaya, Y; Ekberg, J O; Kink, I; Mannervik, S; Ryabtsev, A N

2003-01-01

It has been known for nearly 30 years that the theoretical and experimental values for the energy of the 2s3s 1 S level in singly ionized boron, B II, differ strongly. Since there is much better agreement for other B II levels, it has been concluded that the experimental value for 2s3s 1 S must be revised. Despite a number of recordings over the years of sliding-spark, hollow cathode and beam-foil spectra, this level has not been located. We have now performed another beam-foil experiment, using higher resolution and sensitivity than in most previous studies. By combining these new data with previous results, we have identified transitions from the 2s4p, 2s5p and 2p3s 1 P levels to 2s3s 1 S, the excitation energy (137 622 ± 3 cm -1 ) of which is now well established and in excellent agreement with theoretical predictions

Replication-independent chromatin loading of Dnmt1 during G2 and M phases

Science.gov (United States)

Easwaran, Hariharan P; Schermelleh, Lothar; Leonhardt, Heinrich; Cardoso, M Cristina

2004-01-01

The major DNA methyltransferase, Dnmt1, associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand. In view of the slow kinetics of Dnmt1 in vitro versus the fast progression of the replication fork, we have tested whether Dnmt1 associates with chromatin beyond S phase. Using time-lapse microscopy of mammalian cells expressing green-fluorescent-protein-tagged Dnmt1 and DsRed-tagged DNA Ligase I as a cell cycle progression marker, we have found that Dnmt1 associates with chromatin during G2 and M. This association is mediated by a specific targeting sequence, shows strong preference for constitutive but not facultative heterochromatin and is independent of heterochromatin-specific histone H3 Lys 9 trimethylation, SUV39H and HP1. Moreover, photobleaching analyses showed that Dnmt1 is continuously loaded onto chromatin throughout G2 and M, indicating a replication-independent role of Dnmt1 that could represent a novel and separate pathway to maintain DNA methylation. PMID:15550930

A Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels

Directory of Open Access Journals (Sweden)

Cerrone Cabanos

2017-08-01

Full Text Available Lipid regulation of ion channels by low-abundance signaling lipids phosphatidylinositol 4,5-bisphosphate (PIP2 and phosphatidic acid (PA has emerged as a central cellular mechanism for controlling ion channels and the excitability of nerves. A lack of robust assays suitable for facile detection of a lipid bound to a channel has hampered the probing of the lipid binding sites and measuring the pharmacology of putative lipid agonists for ion channels. Here, we show a fluorescent PIP2 competition assay for detergent-purified potassium channels, including TWIK-1-related K+-channel (TREK-1. Anionic lipids PA and phosphatidylglycerol (PG bind dose dependently (9.1 and 96 μM, respectively and agonize the channel. Our assay shows PIP2 binds with high affinity (0.87 μM but surprisingly can directly antagonize TREK-1 in liposomes. We propose a model for TREK-1 lipid regulation where PIP2 can compete with PA and PG agonism based on the affinity of the lipid for a site within the channel.

Selective mGAT2 (BGT-1) GABA Uptake Inhibitor

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Jørgensen, Lars; Madsen, Karsten Kirkegaard

2013-01-01

β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compou...... 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors....

Experiment data report for semiscale Mod-1 test S-28-2 (steam generator tube rupture test)

International Nuclear Information System (INIS)

Patton, M.L.; Sackett, K.E.

1977-10-01

Recorded test data are presented for Test S-28-2 of the Semiscale Mod-1 steam generator tube rupture test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-28-2 was conducted from initial conditions of 15 936 kPa and 558 K to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the broken loop cold leg piping. During the test, cooling water was injected into the cold leg of the intact and broken loops to simulate emergency core coolant injection in a PWR. For Test S-28-2, accumulator injection into the intact loop hot leg was provided to simulate simulate the rupture of six steam generator tubes

Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

International Nuclear Information System (INIS)

Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.

1982-01-01

The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells

International Nuclear Information System (INIS)

Bu, Youquan; Suenaga, Yusuke; Okoshi, Rintaro; Sang, Meixiang; Kubo, Natsumi; Song, Fangzhou; Nakagawara, Akira; Ozaki, Toshinori

2010-01-01

NFBD1/MDC1 is a large nuclear protein involved in the early cellular response to DNA damage. Upon DNA damage, NFBD1 has an ability to facilitate the efficient DNA repair. In the present study, we have found that, in addition to DNA damage response, NFBD1 plays a critical role in the regulation of G2/M transition. Expression study using synchronized HeLa cells demonstrated that, like the mitotic kinase Plk1, NFBD1 expression level is maximal in G2/M-phase of the cell cycle. siRNA-mediated knockdown of NFBD1 resulted in G2/M arrest as well as simultaneous apoptosis in association with a significant increase in the amounts of γH2AX and pro-apoptotic p73. Since a remarkable down-regulation of mitotic phospho-histone H3 was detectable in NFBD1-knocked down cells, it is likely that knocking down of NFBD1 inhibits G2/M transition. Taken together, our present findings suggest that NFBD1 has a pivotal role in the regulation of proper mitotic entry.

Vite et bien 1 A1/A2 : méthode rapide pour adultes

CERN Document Server

Miquel, Claire

2009-01-01

Vite et bien s'adresse à des adultes pressés et impatients de communiquer avec succès en français ! Le vocabulaire est simple et usuel et les thèmes, variés, pour faire face, efficacement, à toutes les situations de la vie quotidienne et professionnelle. Livre + CD audio et corrigés inclus. La méthode rapide Vite et bien 1 permet à la fois d'apprendre le français et de découvrir la réalité de la vie en France, les différences culturelles, le langage de la vie quotidienne, le tout en un temps record. En effet, le premier volume couvre, en vingt unités, les niveaux A1 et A2 du Cadre Européen de référence (CECR). Ainsi, en 100 à 120 heures de cours selon les publics, il sera possible d'acquérir une bonne base de grammaire et de vocabulaire, claire, simple, fonctionnelle, et de se sentir à l'aise dans la communication orale et écrite. L'ouvrage s'adresse aux vrais et et aux faux débutants, constituant donc un outil d'apprentissage et/ou de rafraîchissement des connaissances. Chacune des v...

Influencia del eslogan y el logotipo de la marca país en el posicionamiento de los países

Directory of Open Access Journals (Sweden)

Gina Pipoli de Azambuja

2010-10-01

Full Text Available Para construir la imagen de un país en la mente de los consumidores, los países aplican estrategias demárketing que parten del desarrollo de su marca país, de la misma forma en que las empresas aplican elmárketing a sus productos y servicios. El desarrollo del logotipo y el eslogan que se utilizará en la estrategiade comunicación, constituyen dos elementos fundamentales de su éxito en el proceso de construcción de lamarca país (Keller 2008. Es así que el objetivo de la presente investigación es el de conocer la importanciade la utilización del logotipo y el eslogan en las estrategias de márketing internacional de los países. Paraello, esta investigación analiza el uso de estos dos elementos, logotipo y eslogan, en las estrategias demarca país de aquellos países que han ocupado los primeros lugares en el Country Brand Index (2009 de Future Brand.

The oxygen sensitivity of a multipoint antimony electrode for tissue pH measurements. A study of the sensitivity for in vivo PO2 variations below 6 kPa.

Science.gov (United States)

Sjöberg, F; Edwall, G; Lund, N

1987-02-01

Monocrystalline micro antimony electrodes in a multipoint arrangement as described by Lund et al. were placed on the skeletal muscle surface of the rabbit. Tissue oxygen levels were measured simultaneously with the MDO (Mehrdraht Dortmund Oberfläche) oxygen electrode. The sensitivity for variations in tissue PO2 (PO2(t)) was evaluated for the antimony metal-metal oxide sensor. The sensitivity (delta E/delta log10 PO2)+/- SE was found to be 21.8 +/- 1.2 mV in the interval between 0.1 kPa and 1 kPa and 53 +/- 5 mV in the interval between 1 kPa and 6 kPa. These results are not consistent with the oxygen sensitivity of monocrystalline antimony described in vitro, but are in agreement with the findings of Nilsson & Edwall. A plausible explanation for the S-shaped oxygen sensitivity curve of antimony at oxygen levels below 10 kPa could be an interaction, at the electrode surface, between the dissolved oxygen and the oxygen bound to haemoglobin. If this is the case, the use of an antimony electrode would make possible the determination of the dissociation of oxyhaemoglobin in tissues.

Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.

Science.gov (United States)

Tsai, Hsing-Chuan; Han, May H

2016-07-01

Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.

PA0148 from Pseudomonas aeruginosa Catalyzes the Deamination of Adenine

Energy Technology Data Exchange (ETDEWEB)

Goble, A.M.; Swaminathan, S.; Zhang, Z.; Sauder, J. M.; Burley, S. K.; Raushel, F. M.

2011-08-02

Four proteins from NCBI cog1816, previously annotated as adenosine deaminases, have been subjected to structural and functional characterization. Pa0148 (Pseudomonas aeruginosa PAO1), AAur1117 (Arthrobacter aurescens TC1), Sgx9403e, and Sgx9403g have been purified and their substrate profiles determined. Adenosine is not a substrate for any of these enzymes. All of these proteins will deaminate adenine to produce hypoxanthine with k{sub cat}/K{sub m} values that exceed 10{sup 5} M{sup -1} s{sup -1}. These enzymes will also accept 6-chloropurine, 6-methoxypurine, N-6-methyladenine, and 2,6-diaminopurine as alternate substrates. X-ray structures of Pa0148 and AAur1117 have been determined and reveal nearly identical distorted ({beta}/{alpha}){sub 8} barrels with a single zinc ion that is characteristic of members of the amidohydrolase superfamily. Structures of Pa0148 with adenine, 6-chloropurine, and hypoxanthine were also determined, thereby permitting identification of the residues responsible for coordinating the substrate and product.

M2, S2, K1 models of the global ocean tide

Science.gov (United States)

Parke, M. E.; Hendershott, M. C.

1979-01-01

Ocean tidal signals appear in many geophysical measurements. Geophysicists need realistic tidal models to aid in interpretation of their data. Because of the closeness to resonance of dissipationless ocean tides, it is difficult for numerical models to correctly represent the actual open ocean tide. As an approximate solution to this problem, test functions derived by solving Laplace's Tidal Equations with ocean loading and self gravitation are used as a basis for least squares dynamic interpolation of coastal and island tidal data for the constituents M2, S2, and Kl. The resulting representations of the global tide are stable over at least a ?5% variation in the mean depth of the model basin, and they conserve mass. Maps of the geocentric tide, the induced free space potential, the induced vertical component of the solid earth tide, and the induced vertical component of the gravitational field for each contituent are presented.

Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

Science.gov (United States)

Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

2015-06-01

Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

vacA s1m1 genotype and cagA EPIYA-ABC pattern are predominant among Helicobacter pylori strains isolated from Mexican patients with chronic gastritis.

Science.gov (United States)

Atrisco-Morales, Josefina; Martínez-Santos, Verónica I; Román-Román, Adolfo; Alarcón-Millán, Judit; De Sampedro-Reyes, José; Cruz-Del Carmen, Iván; Martínez-Carrillo, Dinorah N; Fernández-Tilapa, Gloria

2018-03-01

Virulent genotypes of Helicobacter pylori vacA s1m1/cagA + /babA2 + have been associated with severe gastric diseases. VacA, CagA and BabA are polymorphic proteins, and their association with the disease is allele-dependent. The aims of this work were: (i) to determine the prevalence of H. pylori by type of chronic gastritis; (ii) to describe the frequency of cagA, babA2 and vacA genotypes in strains from patients with different types of chronic gastritis; (iii) to characterize the variable region of cagA alleles. A total of 164 patients with chronic gastritis were studied. Altogether, 50 H. pylori strains were isolated, and the status of cagA, babA2 and vacA genotypes was examined by PCR. cagA EPIYA segment identification was performed using PCR and sequencing of cagA fragments of six randomly selected strains.Results/Key findings. The overall prevalence of H. pylori was 30.5 %. Eighty percent of the isolated strains were vacA s1m1, and the cagA and babA2 genes were detected in 74 and 32 % of the strains, respectively. The most frequent genotypes were vacA s1m1/cagA + /babA2 - and vacA s1m1/cagA + /babA2 + , with 40 % (20/50) and 28 % (14/50), respectively. In cagA + , the most frequent EPIYA motif was -ABC (78.4 %), and EPIYA-ABCC and -ABCCC motifs were found in 10.8 % of the strains. A modified EPIYT-B motif was found in 66.6 % of the sequenced strains. H. pylori strains carrying vacA s1m1, cagA + and babA2 - genotypes were the most prevalent in patients with chronic gastritis from the south of Mexico. In the cagA + strains, the EPIYA-ABC motif was the most common.

An Investigation on the He−(1s2s2 2S Resonance in Debye Plasmas

Directory of Open Access Journals (Sweden)

Arijit Ghoshal

2017-01-01

Full Text Available The effect of Debye plasma on the 1 s 2 s 2 2 S resonance states in the scattering of electron from helium atom has been investigated within the framework of the stabilization method. The interactions among the charged particles in Debye plasma have been modelled by Debye–Huckel potential. The 1 s 2 s excited state of the helium atom has been treated as consisting of a H e + ionic core plus an electron moving around. The interaction between the core and the electron has then been modelled by a model potential. It has been found that the background plasma environment significantly affects the resonance states. To the best of our knowledge, such an investigation of 1 s 2 s 2 2 S resonance states of the electron–helium system embedded in Debye plasma environment is the first reported in the literature.

Bioproduction of L-Aspartic Acid and Cinnamic Acid by L-Aspartate Ammonia Lyase from Pseudomonas aeruginosa PAO1.

Science.gov (United States)

Patel, Arti T; Akhani, Rekha C; Patel, Manisha J; Dedania, Samir R; Patel, Darshan H

2017-06-01

Aspartase (L-aspartate ammonia lyase, EC 4.3.1.1) catalyses the reversible amination and deamination of L-aspartic acid to fumaric acid which can be used to produce important biochemical. In this study, we have explored the characteristics of aspartase from Pseudomonas aeruginosa PAO1 (PA-AspA). To overproduce PA-AspA, the 1425-bp gene was introduced in Escherichia coli BL21 and purified. A 51.0-kDa protein was observed as a homogenous purified protein on SDS-PAGE. The enzyme was optimally active at pH 8.0 and 35 °C. PA-AspA has retained 56% activity after 7 days of incubation at 35 °C, which displays the hyperthermostablility characteristics of the enzyme. PA-AspA is activated in the presence of metal ions and Mg2+ is found to be most effective. Among the substrates tested for specificity of PA-AspA, L-phenylalanine (38.35 ± 2.68) showed the highest specific activity followed by L-aspartic acid (31.21 ± 3.31) and fumarate (5.42 ± 2.94). K m values for L-phenylalanine, L-aspartic acid and fumarate were 1.71 mM, 0.346 μM and 2 M, respectively. The catalytic efficiency (k cat /K m ) for L-aspartic acid (14.18 s -1  mM -1 ) was higher than that for L-phenylalanine (4.65 s -1  mM -1 ). For bioconversion, from an initial concentration of 1000 mM of fumarate and 30 mM of L-phenylalanine, PA-AspA was found to convert 395.31 μM L-aspartic acid and 3.47 mM cinnamic acid, respectively.

Rugged Ozone Sterilization System Model M1 (ROSS M1)

Science.gov (United States)

2017-07-13

13. SUPPLEMENTARY NOTES Cleared, 88PA, Case # 2017-3765, 1 Aug 2017. 14. ABSTRACT Contaminated surgical instruments may result in secondary...surgical instruments are free of contamination and that critical surgeries can be performed in a timely manner. Special Operations Surgical Teams...literature, predicate technology, Food and Drug Administration (FDA) guidance, and industry standards provided a plan for design verification, validation

On the simultaneous Pell equations x 2 - (4m 2 - 1)y 2 = y 2 - pz 2 ...

African Journals Online (AJOL)

Let m be a positive integer, and let p be an odd prime. By using certain properties of Pell and quartic diophantine equations with some elementary number theory methods, we prove that the system of equations x2 - (4m2 - 1)y2 = 1 and y2 - pz2 = 1 has positive integer solutions (x, y, z) if and only if p ≡ 7(mod 8) and m = 1/4 ...

Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC)

DEFF Research Database (Denmark)

Winther, Stine Braendegaard; Zubcevic, Kanita; Qvortrup, Camilla

2016-01-01

BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate...... of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx......) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44...

Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence.

Science.gov (United States)

Uranbileg, Baasanjav; Ikeda, Hitoshi; Kurano, Makoto; Enooku, Kenichiro; Sato, Masaya; Saigusa, Daisuke; Aoki, Junken; Ishizawa, Takeaki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

2016-01-01

Although sphingosine 1-phosphate (S1P) has been reported to play an important role in cancer pathophysiology, little is known about S1P and hepatocellular carcinoma (HCC). To clarify the relationship between S1P and HCC, 77 patients with HCC who underwent surgical treatment were consecutively enrolled in this study. In addition, S1P and its metabolites were quantitated by LC-MS/MS. The mRNA levels of sphingosine kinases (SKs), which phosphorylate sphingosine to generate S1P, were increased in HCC tissues compared with adjacent non-HCC tissues. Higher mRNA levels of SKs in HCC were associated with poorer differentiation and microvascular invasion, whereas a higher level of SK2 mRNA was a risk factor for intra- and extra-hepatic recurrence. S1P levels, however, were unexpectedly reduced in HCC compared with non-HCC tissues, and increased mRNA levels of S1P lyase (SPL), which degrades S1P, were observed in HCC compared with non-HCC tissues. Higher SPL mRNA levels in HCC were associated with poorer differentiation. Finally, in HCC cell lines, inhibition of the expression of SKs or SPL by siRNA led to reduced proliferation, invasion and migration, whereas overexpression of SKs or SPL enhanced proliferation. In conclusion, increased SK and SPL mRNA expression along with reduced S1P levels were more commonly observed in HCC tissues compared with adjacent non-HCC tissues and were associated with poor differentiation and early recurrence. SPL as well as SKs may be therapeutic targets for HCC treatment.

N,N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) suppresses the proliferation of PANC-1 pancreatic cancer cells via apoptosis and G2/M cell cycle arrest.

Science.gov (United States)

Chen, Su-Feng; Xia, Jun; Lv, Ya-Ping; Liu, Jin-Lin; Li, Wan-Xiang; Yu, Xi-Ping; Hu, Wei-Xiao; Zhou, Yong-Lie

2015-04-01

Pancreatic cancer is one of the human gastrointestinal malignancies with a high mortality and poor prognosis. Approximately eighty percent of patients are diagnosed with unresectable or metastatic disease. Thus, development of novel chemicals in the treatment of pancreatic cancer is imperative. This study aimed to investigate the anticancer effects of N,N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1), a new tetrazine derivative, on the PANC-1 pancreatic cancer cell line and clarify the underlying molecular mechanism. Using an MTT assay, we found that ZGDHu-1 significantly suppressed the proliferation of PANC-1 cells in a time- and dose-dependent manner. Moreover, according to the morphological and flow cytometric analysis, the results indicated that ZGDHu-1 induced PANC-1 cell apoptosis and G2/M cell cycle arrest in a dose-dependent manner. In the western blot analysis, expression of the pro-apoptotic Bax gene was upregulated while the anti-apoptotic Bcl-2 gene was downregulated following treatment with ZGDHu-1. ZGDHu-1 also activated pro-caspase-3 and PARP and increased the expression of NF-κB inhibitor IκB. Furthermore, the expression levels of G2/M regulatory molecules such as cyclin B1 and cdc2 were decreased while that of Chk1 was increased. These results suggested that ZGDHu-1 suppressed the proliferation of pancreatic cancer cells, rendering it a potential therapeutic drug for the treatment of pancreatic cancer.