Electrocatalytic oxidation of formate by [Ni(P(R)2N(R')2)2(CH3CN)]2+ complexes.

PubMed

Galan, Brandon R; Schöffel, Julia; Linehan, John C; Seu, Candace; Appel, Aaron M; Roberts, John A S; Helm, Monte L; Kilgore, Uriah J; Yang, Jenny Y; DuBois, Daniel L; Kubiak, Clifford P

2011-08-17

[Ni(P(R)(2)N(R')(2))(2)(CH(3)CN)](2+) complexes with R = Ph, R' = 4-MeOPh or R = Cy, R' = Ph , and a mixed-ligand [Ni(P(R)(2)N(R')(2))(P(R''(2))N(R'(2)))(CH(3)CN)](2+) with R = Cy, R' = Ph, R'' = Ph, have been synthesized and characterized by single-crystal X-ray crystallography. These and previously reported complexes are shown to be electrocatalysts for the oxidation of formate in solution to produce CO(2), protons, and electrons, with rates that are first-order in catalyst and formate at formate concentrations below ∼0.04 M (34 equiv). At concentrations above ∼0.06 M formate (52 equiv), catalytic rates become nearly independent of formate concentration. For the catalysts studied, maximum observed turnover frequencies vary from <1.1 to 15.8 s(-1) at room temperature, which are the highest rates yet reported for formate oxidation by homogeneous catalysts. These catalysts are the only base-metal electrocatalysts as well as the only homogeneous electrocatalysts reported to date for the oxidation of formate. An acetate complex demonstrating an η(1)-OC(O)CH(3) binding mode to nickel has also been synthesized and characterized by single-crystal X-ray crystallography. Based on this structure and the electrochemical and spectroscopic data, a mechanistic scheme for electrocatalytic formate oxidation is proposed which involves formate binding followed by a rate-limiting proton and two-electron transfer step accompanied by CO(2) liberation. The pendant amines have been demonstrated to be essential for electrocatalysis, as no activity toward formate oxidation was observed for the similar [Ni(depe)(2)](2+) (depe = 1,2-bis(diethylphosphino)ethane) complex.

Turnover of R1 (Type I) and R2 (Type Ii) Retrotransposable Elements in the Ribosomal DNA of Drosophila Melanogaster

PubMed Central

Jakubczak, J. L.; Zenni, M. K.; Woodruff, R. C.; Eickbush, T. H.

1992-01-01

R1 and R2 are distantly related non-long terminal repeat retrotransposable elements each of which inserts into a specific site in the 28S rRNA genes of most insects. We have analyzed aspects of R1 and R2 abundance and sequence variation in 27 geographical isolates of Drosophila melanogaster. The fraction of 28S rRNA genes containing these elements varied greatly between strains, 17-67% for R1 elements and 2-28% for R2 elements. The total percentage of the rDNA repeats inserted ranged from 32 to 77%. The fraction of the rDNA repeats that contained both of these elements suggested that R1 and R2 exhibit neither an inhibition of nor preference for insertion into a 28S gene already containing the other type of element. Based on the conservation of restriction sites in the elements of all strains, and sequence analysis of individual elements from three strains, nucleotide divergence is very low for R1 and R2 elements within or between strains (<0.6%). This sequence uniformity is the expected result of the forces of concerted evolution (unequal crossovers and gene conversion) which act on the rRNA genes themselves. Evidence for the role of retrotransposition in the turnover of R1 and R2 was obtained by using naturally occurring 5' length polymorphisms of the elements as markers for independent transposition events. The pattern of these different length 5' truncations of R1 and R2 was found to be diverse and unique to most strains analyzed. Because recombination can only, with time, amplify or eliminate those length variants already present, the diversity found in each strain suggests that retrotransposition has played a critical role in maintaining these elements in the rDNA repeats of D. melanogaster. PMID:1317313

Electrocatalytic Oxidation of Formate by [Ni(P R 2 N R' 2 ) 2 (CH 3 CN)] 2+ Complexes

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

Galan, Brandon R.; Schöffel, Julia; Linehan, John C.

2011-08-17

New [Ni(P R 2N R` 2) 2+(CH 3CN)] 2+ complexes with R = Ph, R` = 4-MeOPh; R = Cy, R` = Ph and a mixed ligand [Ni(P R 2N R` 2)(P R`` 2N R` 2)] 2+ with R = Cy, R` = Ph, R`` = Ph have been synthesized and characterized by single crystal X-ray crystallography. These complexes are shown to be electrocatalysts for the oxidation of formate in solution to produce CO 2, protons, and electrons with rates which are first order in catalyst and in formate at formate concentrations below approximately 0.05 M. For the catalysts studied,more » maximum observed turnover frequencies vary from <1.1 s -1 to 12.5 s -1 at room temperature, which are the highest rates yet reported for formate oxidation by homogeneous catalysts. A mechanistic scheme is proposed which involves an initial nickel complex bound <1-OC(O)H followed by a rate limiting hydride transfer step. An acetate complex demonstrating the η 1-OC(O)CH 3 binding mode to nickel has also been synthesized and characterized by single crystal X-ray crystallography. The pendant amines have been demonstrated to be essential for this electrocatalytic activity as no activity toward formate was found for the similar [Ni(depe) 2][BF 4] 2+ (depe = diethylphosphinoethane) complex. This work was supported by the US Department of Energy Basic Energy Sciences' Chemical Sciences, Geosciences & Biosciences Division. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.« less

Parallel determination of gut permeability in man with M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol.

PubMed

Parlesak, A; Bode, J C; Bode, C

1994-11-01

Polyethylene glycol has been in use for a number of years for the assessment of gut permeability. The methods so far employed are usually limited to polyethylene glycols in the low relative molecular mass range (up to M(r) 1300). We developed a method for the simultaneous determination of gut permeability to M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol, by applying a single oral dose of an appropriate mixture of these polyethylene glycols. After extraction from 24 h-urine, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol were quantified by size exclusion chromatography, while M(r) 400 polyethylene glycol was determined by reversed phase chromatography. The detection limit of polyethylene glycol in the relative molecular mass range between M(r) 1500 and M(r) 10,000 was found to be 0.2 mg/l urine, and the detection limit of M(r) 400 polyethylene glycol 5 mg/l urine. Recovery of the polyethylene glycols (N = 6) were 86.6% (CV: 4.8%) for M(r) 400, 94.1% (CV: 7.2%) for M(r) 1500, 97.1% (CV: 5.5%) for M(r) 4000 and 97.4% (CV: 5.6%) for M(r) 10,000. No significant difference was found between the excretion rates in 24 h-urine of M(r) 400 and M(r) 1500 polyethylene glycols in patients with Crohn's disease (M(r) 400: 34.4 +/- 5.5%; M(r) 1500: 5.22 +/- 2.27%; mean +/- SEM, N = 10) and healthy controls (M(r) 400: 33.6 +/- 3.2%, M(r) 1500: 1.09 +/- 0.26%; N = 21). The excretion rate of M(r) 4000 polyethylene glycol was markedly higher in patients with Crohn's disease (0.462 +/- 0.177%) than in healthy controls (0.049 +/- 0.012%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

R34D1NG W0RD5 W1TH NUMB3R5.

PubMed

Perea, Manuel; Duñabeitia, Jon Andoni; Carreiras, Manuel

2008-02-01

Letter identities and number identities are usually thought to imply different cortical mechanisms. Specifically, the left fusiform gyrus responds more to letters than to digits (T. A. Polk et al., 2002). However, a widely circulated statement on the internet illustrates that it is possible to use numbers (leet digits) as parts of words, 4ND TH3 R35ULT1NG S3NT3NC3 C4N B3 R34D W1TH0UT GR34T 3FF0RT. Two masked priming lexical decision experiments were conducted to determine whether leet digits produce (automatic) lexical activation. Results showed that words are identified substantially faster when they are preceded by a masked leet word (M4T3R14L-MATERIAL) than when they are preceded by a control condition with other letters or digits. In addition, there was only a negligible advantage of the identity condition over the related leet condition. This leet-priming effect is not specific to numbers: A prime in which leet digits are replaced by letter-like symbols (M(Delta symbol)T(euro symbol)R!(Delta symbol)L - MATERIAL) facilitates word processing to the same degree as an identity prime. Therefore, the cognitive system regularizes the shape of the leet digits and letter-like symbols embedded in words with very little cost.

Magnetic and superconducting phase diagrams of single-crystal Er0.8R0.2Ni2B2C (R=Tb,Lu) and ErNi1.9Co0.1B2C: Identification of pair-breaking mechanisms

NASA Astrophysics Data System (ADS)

Takeya, H.; El Massalami, M.

2004-01-01

We investigated the magnetism, superconductivity and their interplay in single crystals Er0.8R0.2Ni2B2C (R=Tb,Lu) and ErNi1.9Co0.1B2C. In contrast to Co substitution, R substitutions induce considerable modifications in the magnetism of Er sublattice: e.g., Tb (Lu) substitution enhances (reduces) TN and critical fields. Both R substitutions introduce size effects and pinning centers; the former modifies the magnon specific heat while the latter hinders the formation of a weak ferromagnetism. The superconductivity, on the other hand, is strongly (weakly) influenced by Tb and Co (Lu) substitution. Taking LuNi2B2C as a nonmagnetic superconducting limit, we analyzed their superconductivities, as well as that of ErNi2B2C, in terms of multiple pair breaking theory on dirty superconductors. Based on this analysis, many of their superconducting features can be explained: The breakdown of de Gennes scaling is due to the presence of multiple pair breakers, the anisotropy of Hc2(T) is related to the magnetic anisotropy, the absence of a structure in Hc2(T) at TN of Lu substitution (TN2(T) of Tb and Co substitutions is in part due to a saturation of antiferromagnetic correlations. For Lu substitution, the strength of magnon mediated pair breaking process(es) is substantially reduced.

Reactivity-worth estimates of the OSMOSE samples in the MINERVE reactor R1-MOX, R2-UO2 and MORGANE/R configurations.

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

Zhong, Z.; Klann, R. T.; Nuclear Engineering Division

2007-08-03

An initial series of calculations of the reactivity-worth of the OSMOSE samples in the MINERVE reactor with the R2-UO2 and MORGANE/R core configuration were completed. The calculation model was generated using the lattice physics code DRAGON. In addition, an initial comparison of calculated values to experimental measurements was performed based on preliminary results for the R1-MOX configuration.

GESFIDE-PROPELLER approach for simultaneous R2 and R2* measurements in the abdomen.

PubMed

Jin, Ning; Guo, Yang; Zhang, Zhuoli; Zhang, Longjiang; Lu, Guangming; Larson, Andrew C

2013-12-01

To investigate the feasibility of combining GESFIDE with PROPELLER sampling approaches for simultaneous abdominal R2 and R2* mapping. R2 and R2* measurements were performed in 9 healthy volunteers and phantoms using the GESFIDE-PROPELLER and the conventional Cartesian-sampling GESFIDE approaches. Images acquired with the GESFIDE-PROPELLER sequence effectively mitigated the respiratory motion artifacts, which were clearly evident in the images acquired using the conventional GESFIDE approach. There was no significant difference between GESFIDE-PROPELLER and reference MGRE R2* measurements (p=0.162) whereas the Cartesian-sampling based GESFIDE methods significantly overestimated R2* values compared to MGRE measurements (p<0.001). The GESFIDE-PROPELLER sequence provided high quality images and accurate abdominal R2 and R2* maps while avoiding the motion artifacts common to the conventional Cartesian-sampling GESFIDE approaches. © 2013 Elsevier Inc. All rights reserved.

GESFIDE-PROPELLER Approach for Simultaneous R2 and R2* Measurements in the Abdomen

PubMed Central

Jin, Ning; Guo, Yang; Zhang, Zhuoli; Zhang, Longjiang; Lu, Guangming; Larson, Andrew C.

2013-01-01

Purpose To investigate the feasibility of combining GESFIDE with PROPELLER sampling approaches for simultaneous abdominal R2 and R2* mapping. Materials and Methods R2 and R2* measurements were performed in 9 healthy volunteers and phantoms using the GESFIDE-PROPELLER and the conventional Cartesian-sampling GESFIDE approaches. Results Images acquired with the GESFIDE-PROPELLER sequence effectively mitigated the respiratory motion artifacts, which were clearly evident in the images acquired using the conventional GESFIDE approach. There were no significant difference between GESFIDE-PROPELLER and reference MGRE R2* measurements (p = 0.162) whereas the Cartesian-sampling based GESFIDE methods significantly overestimated R2* values compared to MGRE measurements (p < 0.001). Conclusion The GESFIDE-PROPELLER sequence provided high quality images and accurate abdominal R2 and R2* maps while avoiding the motion artifacts common to the conventional Cartesian-sampling GESFIDE approaches. PMID:24041478

Resolution of 1-n-butyl-3-methyl-3-phospholene 1-oxide with TADDOL derivatives and calcium salts of O,O'-Dibenzoyl-(2R,3R)- or O,O'-di-p-toluoyl-(2R,3R)-tartaric acid.

PubMed

Bagi, Péter; Fekete, András; Kállay, Mihály; Hessz, Dóra; Kubinyi, Miklós; Holczbauer, Tamás; Czugler, Mátyás; Fogassy, Elemér; Keglevich, György

2014-03-01

The resolution methods applying (-)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane ("TADDOL"), (-)-(2R,3R)-α,α,α',α'-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol ("spiro-TADDOL"), as well as the acidic and neutral Ca(2+) salts of (-)-O,O'-dibenzoyl- and (-)-O,O'-di-p-toluoyl-(2R,3R)-tartaric acid were extended for the preparation of 1-n-butyl-3-methyl-3-phospholene 1-oxide in optically active form. In one case, the intermediate diastereomeric complex could be identified by single-crystal X-ray analysis. The absolute P-configuration of the enantiomers of the phospholene oxide was also determined by comparing the experimentally obtained and calculated CD spectra. © 2014 Wiley Periodicals, Inc.

Pharmacokinetics and Metabolism of (R,R)-Methoxyfenoterol in Rat

PubMed Central

Siluk, Danuta; Mager, Donald E.; Kim, Hee Seung; Wang, Yan; Furimsky, Anna M.; Ta, Amy; Iyer, Lalitha V.; Green, Carol E.; Wainer, Irving W.

2010-01-01

(R,R)-Fenoterol (Fen), a β2-adrenoceptor agonist, is under clinical investigation in the treatment of congestive heart disease. The pharmacokinetics and metabolism of the 4-methoxyphenyl derivative of (R,R)-Fen, (R,R)-MFen, have been determined following intravenous and oral administration to the rat and compared with corresponding results obtained with (R,R)-Fen. Results of the study suggest that (R,R)-MFen can offer pharmacokinetic and metabolic advantages in comparison to an earlier (R,R)-Fen.The oral administration revealed that the net exposure of (R,R)-MFen was about three-fold higher than that of (R,R)-Fen (7.2 versus 2.3 min × nmol ml-1), while intravenous administration proved that the clearance was significantly reduced, 48 versus 146 ml min-1 kg-1, the T1/2 was significantly longer, 152.9 versus 108.9 min and the area under the curve (AUC) was significantly increased, 300 versus 119 min × nmol ml-1.(R,R)-MFen was primarily cleared by glucuronidation associated with significant presystemic glucuronidation of the compound. After intravenous and oral administration of (R,R)-MFen, (R,R)-Fen and (R,R)-Fen-G were detected in the urine samples indicating that (R,R)-MFen was O-demethylated and subsequently conjugated to (R,R)-Fen-G. The total (R,R)-Fen and (R,R)-Fen-G as a percentage of the dose after intravenous administration was 3.6% while after oral administration was 0.3%, indicating that only a small fraction of the drug escaped presystemic glucuronidation and was available for O-demethylation.The glucuronidation pattern was confirmed by the results from in vitro studies where incubation of (R,R)-MFen with rat hepatocytes produced (R,R)-MFen-G, (R,R)-Fen and (R,R)-Fen-G, while incubation with rat intestinal microsomes only resulted in the formation of (R,R)-MFen-G. PMID:20039779

Pharmacokinetics and metabolism of (R,R)-methoxyfenoterol in rat.

PubMed

Siluk, D; Mager, D E; Kim, H S; Wang, Y; Furimsky, A M; Ta, A; Iyer, L V; Green, C E; Wainer, I W

2010-03-01

(R,R)-fenoterol (Fen), a beta(2)-adrenoceptor agonist, is under clinical investigation in the treatment of congestive heart disease. The pharmacokinetics and metabolism of the 4-methoxyphenyl derivative of (R,R)-Fen, (R,R)-MFen, have been determined following intravenous and oral administration to the rat and compared with corresponding results obtained with (R,R)-Fen. Results from the study suggest that (R,R)-MFen can offer pharmacokinetic and metabolic advantages in comparison to an earlier (R,R)-Fen. The oral administration revealed that the net exposure of (R,R)-MFen was about three-fold higher than that of (R,R)-Fen (7.2 versus 2.3 min x nmol ml(-1)), while intravenous administration proved that the clearance was significantly reduced, 48 versus 146 ml min(-1) kg(-1), the T(1/2) was significantly longer, 152.9 versus 108.9 min, and the area under the curve (AUC) was significantly increased, 300 versus 119 min x nmol ml(-1). (R,R)-MFen was primarily cleared by glucuronidation associated with significant presystemic glucuronidation of the compound. After intravenous and oral administration of (R,R)-MFen, (R,R)-Fen and (R,R)-Fen-G were detected in the urine samples indicating that (R,R)-MFen was O-demethylated and subsequently conjugated to (R,R)-Fen-G. The total (R,R)-Fen and (R,R)-Fen-G as a percentage of the dose after intravenous administration was 3.6%, while after oral administration was 0.3%, indicating that only a small fraction of the drug escaped presystemic glucuronidation and was available for O-demethylation. The glucuronidation pattern was confirmed by the results from in vitro studies where incubation of (R,R)-MFen with rat hepatocytes produced (R,R)-MFen-G, (R,R)-Fen and (R,R)-Fen-G, while incubation with rat intestinal microsomes only resulted in the formation of (R,R)-MFen-G.

Crystal structures of the diastereomeric salt pair of the prostaglandin intermediate 1 R, 2 S(+)- cis-2-hydroxycyclopent-4-enylacetic acid with S- and R- 1-phenylethylamine

NASA Astrophysics Data System (ADS)

Czugler, Mátyás; Csöregh, Ingeborg; Kálmán, Alajos; Faigl, Ferenc; Ács, Mária

1989-05-01

Crystal structures of an enantiomeric salt pair formed between 1 R,2 S- cis-2-hydroxycyclopent-4-enylacetic acid ( S-HCA) and R(+)-1-phenylethylamine ( R-PEA) and the corresponding S-PEA salt have been determined by X-ray crystallography. The S-HCA: R-PEA 1:1 salt ( R-HCA-PEA hereafter) is orthorhombic, P2 12 12 1, with the unit-cell parameters a = 5.806(1), b = 9.261(1), c = 27.624(2) Å and R = 0.056 for 1162 reflections at ambient temperature. The S-HCA: S-PEA 1:1 salt ( S-HCAPEA) is also orthorhombic, P2 12 12 1, with the unit-cell data a = 6.034(2), b = 11.840(7), c = 20.198(11) Å at 170 K, R = 0.082 for 1196 data measured at low temperatures (170 K). The R-HCAPEA salt has its two components assembled into an elongated rod-like shape via two-dimensional hydrogen bonding between cations and anions thus forming a well-ordered crystal. In contrast, the cation and anion in the S-HCAPEA salt forms a more globular aggregate and displays orientation disorder in the five-membered ring part of the anion and maintains an essentially one-dimensional hydrogen-bond network, while the total number of hydrogen bonds between cationic and anionic species remains three in both crystals.

Molecular Cloning and Characterization of Two Pig Vasoactive Intestinal Polypeptide Receptors (VPAC1-R and VPAC2-R)

PubMed Central

He, Xiaping; Meng, Fengyan; Wang, Yajun

2014-01-01

We here report the cloning, tissue expression, and functional analyses of the two pig vasoactive intestinal polypeptide (VIP) receptors (pVPAC1-R and pVPAC2-R). The cloned full-length pVPAC1-R and pVPAC2-R share high structural similarity with their mammalian counterparts. Functional assay revealed that the full-length pVPAC1-R and pVPAC2-R-expressed Chinese hamster ovary (CHO) cells could be activated by pVIP and pPACAP38 potently, indicating that pVPAC1-R and pVPAC2-R are capable of binding VIP and pituitary adenylate cyclase-activating polypeptide (PACAP). In addition to the identification of the transcripts encoding the two full-length receptors, multiple splice transcript variants were isolated. Comparison with the pig genome database revealed that pVPAC1-R and pVPAC2-R share a unique gene structure with 14 exons different from other vertebrates. Reverse transcription and polymerase chain reaction (RT-PCR) assays further showed that the transcript encoding the full-length pVPAC2-R is widely expressed in all adult tissues whereas the splice variants of pVPAC1-R are predominantly expressed in all tissues instead of the transcript encoding the full-length receptor, hinting that pVPAC2-R may play more important roles than pVPAC1-R in mediating VIP and PACAP actions. Our present findings help to elucidate the important role of VIP and PACAP and promote to rethink of their species-specific physiological roles including their actions in regulation of phenotypic traits in pigs. PMID:24520933

Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.

PubMed

Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

2014-01-01

From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation.

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs).

PubMed

Mishra, Om P; Simmons, Nicholas; Tyagi, Sonia; Pietrofesa, Ralph; Shuvaev, Vladimir V; Valiulin, Roman A; Heretsch, Philipp; Nicolaou, K C; Christofidou-Solomidou, Melpo

2013-10-01

Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC50=292.17±27.71 μM and 331.94±21.21 μM, respectively), which compared well with that of natural (S,S)-SDG-1 (EC50=275.24±13.15 μM). These values are significantly lower than those of ascorbic acid (EC50=1129.32±88.79 μM) and α-tocopherol (EC50=944.62±148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68±0.27; synthetic (S,S)-SDG-1: 2.09±0.16; synthetic (R,R)-SDG-2: 1.96±0.27], peroxyl [natural (S,S)-SDG-1: 2.55±0.11; synthetic (S,S)-SDG-1: 2.20±0.10; synthetic (R,R)-SDG-2: 3.03±0.04] and DPPH [natural (S,S)-SDG-1: EC50=83.94±2.80 μM; synthetic (S,S)-SDG-1: EC50=157.54±21.30 μM; synthetic (R,R)-SDG-2: EC50=123.63±8.67 μM] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

PubMed Central

Mishra, Om P.; Simmons, Nicholas; Tyagi, Sonia; Pietrofesa, Ralph; Shuvaev, Vladimir V.; Valiulin, Roman A.; Heretsch, Philipp; Nicolaou, K. C.; Christofidou-Solomidou, Melpo

2013-01-01

Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC50 = 292.17 ± 27.71 μM and 331.94 ± 21.21 μM, respectively) which compared well with that of natural (S,S)-SDG-1 (EC50 = 275.24 ± 13.15 μM). These values are significantly lower than those of ascorbic acid (EC50 = 1129.32 ± 88.79 μM) and α-tocopherol (EC50 = 944.62 ± 148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68 ± 0.27; synthetic (S,S)-SDG-1: 2.09 ± 0.16; synthetic (R,R)-SDG-2: 1.96 ± 0.27], peroxyl [natural (S,S)-SDG-1: 2.55 ± 0.11; synthetic (S,S)-SDG-1: 2.20 ± 0.10; synthetic (R,R)-SDG-2: 3.03 ± 0.04] and DPPH [natural (S,S)-SDG-1: EC50 = 83.94 ± 2.80 μM; synthetic (S,S)-SDG-1: EC50 = 157.54 ± 21.30; synthetic (R,R)-SDG-2: EC50 = 123.63 ± 8.67] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use. PMID:23978651

High-Field Magnetization Study of R_{2} {Fe}_{17} {N}_{2} R 2 Fe 17 N 2 ( R = {Ho} R = Ho and Er) Nitrides

NASA Astrophysics Data System (ADS)

Tereshina, I. S.; Tereshina-Chitrova, E. A.; Pelevin, I. A.; Doerr, M.; Law, J. M.; Verbetski, V. N.; Salamova, A. A.

2018-03-01

The structure and magnetic properties of the nitrided compounds R2Fe_{17}N2 (R = Ho and Er) are studied. The type of crystal structure Th2Ni_{17} is preserved upon nitrogenation, and the relative unit cell volume Δ V{/}V increase exceeds 6%. Magnetic studies are performed in fields up to 60 T at 4.2 K on aligned powder samples. Field-induced spin-reorientation (SR) transitions are observed in the M( H) curves of R2Fe_{17}N2. Unlike the parent R2Fe_{17} compounds, where the magnetization increases in steps as the field grows stronger, R2Fe_{17}N2 demonstrate a gradual increase in magnetization. It is indicative of the change of the SR transition from first to the second type. Extrapolation of magnetization curves to the theoretical value of magnetization in the forced ferromagnetic state yields the coefficient of the inter-sublattice R-Fe exchange interaction. The inter-sublattice exchange is found to decrease upon nitrogenation.

Unprecedented genomic diversity of AhR1 and AhR2 genes in Atlantic salmon (Salmo salar L.).

PubMed

Hansson, Maria C; Wittzell, Håkan; Persson, Kerstin; von Schantz, Torbjörn

2004-06-24

Aryl hydrocarbon receptor (AhR) genes encode proteins involved in mediating the toxic responses induced by several environmental pollutants. Here, we describe the identification of the first two AhR1 (alpha and beta) genes and two additional AhR2 (alpha and beta) genes in the tetraploid species Atlantic salmon (Salmo salar L.) from a cosmid library screening. Cosmid clones containing genomic salmon AhR sequences were isolated using a cDNA clone containing the coding region of the Atlantic salmon AhR2gamma as a probe. Screening revealed 14 positive clones, from which four were chosen for further analyses. One of the cosmids contained genomic AhR sequences that were highly similar to the rainbow trout (Oncorhynchus mykiss) AhR2alpha and beta genes. SMART RACE amplified two complete, highly similar but not identical AhR type 2 sequences from salmon cDNA, which from phylogenetic analyses were determined as the rainbow trout AhR2alpha and beta orthologs. The salmon AhR2alpha and beta encode proteins of 1071 and 1058 residues, respectively, and encompass characteristic AhR sequence elements like a basic-helix-loop-helix (bHLH) and two PER-ARNT-SIM (PAS) domains. Both genes are transcribed in liver, spleen and muscle tissues of adult salmon. A second cosmid contained partial sequences, which were identical to the previously characterized AhR2gamma gene. The last two cosmids contained partial genomic AhR sequences, which were more similar to other AhR type 1 fish genes than the four characterized salmon AhR2 genes. However, attempts to amplify the corresponding complete cDNA sequences of the inserts proved very difficult, suggesting that these genes are non-functional or very weakly transcribed in the examined tissues. Phylogenetic analyses of the conserved regions did, however, clearly indicate that these two AhRs belong to the AhR type 1 clade and have been assigned as the Atlantic salmon AhR1alpha and AhR1beta genes. Taken together, these findings demonstrate that

Transport and thermoelectric properties of Sr{sub 3}(Ti{sub 0.95}R{sub 0.05}){sub 2}O{sub 7} (R = Ta, Nb, W) oxides

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

Sun, R. R.; Qin, X. Y.; Li, L. L.

2012-12-15

The Sr{sub 3}(Ti{sub 0.95}R{sub 0.05}){sub 2}O{sub 7} (R = Ta, Nb, W) polycrystalline compounds were fabricated, and their transport and thermoelectric properties were investigated. The results indicate that at T > 300 K electrical resistivity {rho} for all the doped compounds increases monotonically with temperature, and basically can be described by a relation {rho}{proportional_to}T{sup M} at T > {approx}650 K, with M = 1.39, 1.66, and 1.77 for R = Ta, Nb, and W, respectively, implying that at the high temperatures the acoustic phonon scattering dominates the scattering process. Although the resistivity {rho} of Sr{sub 3}(Ti{sub 0.95}Ta{sub 0.05}){sub 2}O{sub 7}more » exhibits a metallic-like behavior at the temperature as low as 5 K, a transition from metallic state (d{rho}/dT > 0) to semiconductor-like state (d{rho}/dT < 0) was observed at a critical low temperature {approx}41 K and {approx}79 K for R = Nb and W, respectively. At T < {approx}22 K, {approx}57 K, and {approx}80 K, a relation of {sigma}{proportional_to}T{sup 1/2} (here conductivity {sigma} = 1/{rho}) holds for the doped compounds with R = Nb, Ta, and W, respectively, suggesting that at the low temperatures the main transport mechanism is electron-electron interaction due to the presence of disorder induced by the dopants. The thermoelectric figure of merit (ZT) for Ta-doped compound increases more steeply with increasing temperature among the three compounds and reaches 0.066 at 1000 K.« less

Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

PubMed

Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

2016-10-11

The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca 2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca 2+ -ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

Electrochemical sensing of modified ABO3 perovskite: LaFe0.8 R0.2O3(R= Cr, Co, Al)

NASA Astrophysics Data System (ADS)

Vidya Rajan, N.; Alexander, L. K.

2017-06-01

Perovskite LaFeO3 with orthorhombic structure has been synthesized by citric acid mediated solution method. The effectiveness of ionic radii and Oxidation state of the doping material on ionic conductivity of the host matrix was evaluated by B-site (Fe) doping on LaFeO3 with Cr, Co and Al, resulting LaFe0.8 R0.2O3 (R = Cr, Co, Al). XRD with Rietveld refinement and Raman spectroscopic analysis demonstrate successful synthesis. The effect of the 20% B site doping on electrochemical activity is reported. The doped materials exhibit a decrease in sensing activity towards the non enzymatic detection of H2O2.

Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients.

PubMed

Meng, Xiaodan; Joosse, Simon A; Müller, Volkmar; Trillsch, Fabian; Milde-Langosch, Karin; Mahner, Sven; Geffken, Maria; Pantel, Klaus; Schwarzenbach, Heidi

2015-11-03

Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC. Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines. Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I-II and III-IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III-IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III-IV (P=0.02). Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.

Cross-reactivity of anti-PLA2R1 autoantibodies to rabbit and mouse PLA2R1 antigens and development of two novel ELISAs with different diagnostic performances in idiopathic membranous nephropathy.

PubMed

Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Tomas, Nicola M; Lochouarn, Marine; Jeammet, Louise; Mariat, Christophe; Krummel, Thierry; Burtey, Stéphane; Courivaud, Cécile; Schlumberger, Wolfgang; Zorzi, Kévin; Benzaken, Sylvia; Bernard, Ghislaine; Esnault, Vincent L M; Lambeau, Gérard

2015-11-01

About 70% of patients with idiopathic membranous nephropathy (iMN) have autoantibodies to the phospholipase A2 receptor PLA2R1. We screened sera from iMN patients for their cross-reactivity to human (h), rabbit (rb) and mouse (m) PLA2R1 by western blot (WB) and antigen-specific ELISAs. All iMN patients recognized hPLA2R1 and rbPLA2R1 by WB, and a rbPLA2R1 ELISA was as sensitive as the standardized hPLA2R1 ELISA to monitor anti-PLA2R1 in patients with active disease or in drug-induced remission. In contrast, only 51% of patients were reactive to mPLA2R1 by WB, and a maximum of 78% were weakly to highly positive in the mPLA2R1 ELISA, suggesting that iMN patients exhibit different subsets of anti-PLA2R1 autoantibodies against epitopes that are shared or not among PLA2R1 orthologs. In a cohort of 41 patients with a mean follow-up of 42 months from anti-PLA2R1 assay, the detection of anti-mPLA2R1 autoantibodies was an independent predictor of clinical outcome in multivariate analysis (p = 0.009), and a ROC curve analysis identified a threshold of 605 RU/mL above which 100% of patients (12 patients) had a poor renal outcome (p < 0.001). A similar threshold could not be defined in hPLA2R1 and rbPLA2R1 ELISAs. We conclude that rbPLA2R1 is an alternative antigen to hPLA2R1 to measure anti-PLA2R1 in active disease while mPLA2R1 is a unique antigen that can detect a subset of anti-PLA2R1 autoantibodies present at high levels (>605 RU/mL) only in iMN patients at risk of poor prognosis, and is thus useful to predict iMN outcome. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Dependences of the density of M 1- x R x F2 + x and R 1- y M y F3- y single crystals ( M = Ca, Sr, Ba, Cd, Pb; R means rare earth elements) on composition

NASA Astrophysics Data System (ADS)

Sorokin, N. I.; Krivandina, E. A.; Zhmurova, Z. I.

2013-11-01

The density of single crystals of nonstoichiometric phases Ba1 - x La x F2 + x (0 ≤ x ≤ 0.5) and Sr0.8La0.2 - x Lu x F2.2 (0 ≤ x ≤ 0.2) with the fluorite (CaF2) structure type and R 1 - y Sr y F3 - y ( R = Pr, Nd; 0 ≤ y ≤ 0.15) with the tysonite (LaF3) structure type has been measured. Single crystals were grown from a melt by the Bridgman method. The measured concentration dependences of single crystal density are linear. The interstitial and vacancy models of defect formation in the fluorite and tysonite phases, respectively, are confirmed. To implement the composition control of single crystals of superionic conductors M 1 - x R x F2 + x and R 1 - y M y F3 - y in practice, calibration graphs of X-ray density in the MF2- RF3 systems ( M = Ca, Sr, Ba, Cd, Pb; R = La-Lu, Y) are plotted.

The mGlu(2/3) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate, is anti- and proconvulsant in DBA/2 mice.

PubMed

Moldrich, R X; Talebi, A; Beart, P M; Chapman, A G; Meldrum, B S

2001-02-16

The anticonvulsant activity of the selective group II metabotropic glutamate receptor (mGlu) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been evaluated in chemoconvulsant and sound-induced models of epileptic seizures in DBA/2 mice. 2R,4R-APDC (> or =10 nmol, intracerebroventricularly (i.c.v.), -15 min) transiently reduced sound-induced seizure activity including clonic seizures to 40% of vehicle at 20 nmol (i.c.v.) and 30% of vehicle at 100 mg/kg (intraperitoneally (i.p.), -15 min). 2R,4R-APDC inhibited clonic seizures induced by the group III mGlu antagonist (R,S)-alpha-methylserine-O-phosphate (2.5 micromol, i.c.v.) when co-injected at 20-40 nmol and inhibited limbic seizure activity induced by the mGlu(1/5) agonist (R,S)-3,5-dihydroxyphenylglycine (1.5 micromol, i.c.v.) when co-injected at 10-40 nmol. A reversal of the anticonvulsant activity of 2R,4R-APDC was observed at (>20 nmol) in each of the chemoconvulsant and sound-induced models of epileptic seizures. 2R,4R-APDC (0.1-1 micromol, i.c.v.) induced stimulus-independent, rapid and dose-dependent clonic seizures. Selective mGlu(2/3) agonists represent a novel class of potential anti-epileptic drugs, however due to the proconvulsant activity observed here, 2R,4R-APDC is obviously limited in this regard.

The Odorant ( R)-Citronellal Attenuates Caffeine Bitterness by Inhibiting the Bitter Receptors TAS2R43 and TAS2R46.

PubMed

Suess, Barbara; Brockhoff, Anne; Meyerhof, Wolfgang; Hofmann, Thomas

2018-03-14

Sensory studies showed the volatile fraction of lemon grass and its main constituent, the odor-active citronellal, to significantly decrease the perceived bitterness of a black tea infusion as well as caffeine solutions. Seven citronellal-related derivatives were synthesized and shown to inhibit the perceived bitterness of caffeine in a structure-dependent manner. The aldehyde function at carbon 1, the ( R)-configuration of the methyl-branched carbon 3, and a hydrophobic carbon chain were found to favor the bitter inhibitory activity of citronellal; for example, even low concentrations of 25 ppm were observed to reduce bitterness perception of caffeine solution (6 mmol/L) by 32%, whereas ( R)-citronellic acid (100 pm) showed a reduction of only 21% and ( R)-citronellol (100 pm) was completely inactive. Cell-based functional experiments, conducted with the human bitter taste receptors TAS2R7, TAS2R10, TAS2R14, TAS2R43, and TAS2R46 reported to be sensitive to caffeine, revealed ( R)-citronellal to completely block caffeine-induced calcium signals in TAS2R43-expressing cells, and, to a lesser extent, in TAS2R46-expressing cells. Stimulation of TAS2R43-expressing cells with structurally different bitter agonists identified ( R)-citronellal as a general allosteric inhibitor of TAS2R43. Further structure/activity studies indicated 3-methyl-branched aliphatic aldehydes with a carbon chain of ≥4 C atoms as best TAS2R43 antagonists. Whereas odor-taste interactions have been mainly interpreted in the literature to be caused by a central neuronal integration of odors and tastes, rather than by peripheral events at the level of reception, the findings of this study open up a new dimension regarding the interaction of the two chemical senses.

Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507

PubMed Central

Fleuren, Emmy D.G.; Versleijen-Jonkers, Yvonne M.H.; van de Luijtgaarden, Addy C.M.; Molkenboer-Kuenen, Janneke D.M.; Heskamp, Sandra; Roeffen, Melissa H.S.; van Laarhoven, Hanneke W.M.; Houghton, Peter J.; Oyen, Wim J.G.; Boerman, Otto C.; van der Graaf, Winette T.A.

2011-01-01

Purpose To investigate whether 111In-R1507 immuno-SPECT, a novel non-invasive, in vivo screening method to visualize membranous Insulin-like Growth Factor 1 Receptor (IGF-1R) expression and accessibility, can be used to predict IGF-1R treatment (R1507) responsein bone sarcomas. Experimental design BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human bone sarcoma xenografts (OS-1, EW-5 and EW-8) which demonstrated high, modest or no response, respectively, to R1507, a monoclonal antibody targeting the extracellular domain of IGF-1R. An IGF-1R-negative tumor (OS-33), unresponsive to IGF-1R inhibitors, was examined as well. Mice were injected with indium-111 labeled R1507 (111In-R1507). Biodistribution and immuno-SPECT/CT imaging studies were performed 1, 3 and 7 days p.i. in mice with OS-1 and EW-5 xenografts and 3 days p.i. in mice with EW-8 and OS-33 xenografts. Results Biodistribution studies showed specific accumulation of 111In-R1507 in OS-1 and EW-5 xenografts (27.5±6.5%ID/g and 14.0±2.8%ID/g, 3 days p.i., respectively). Most importantly, 111In-R1507 uptake in IGF-1R-positive, but unresponsive, EW-8 xenografts (6.5±1.5%ID/g, 3 days p.i.) was similar to that of the IGF-1R-negative OS-33 tumor (5.5±0.6%ID/g, 3 days p.i.). Uptake in normal tissues was low and non-specific. Corresponding immuno-SPECT images clearly discriminated between high, modest and non-responding tumors by demonstrating a homogeneous (OS-1), heterogeneous (EW-5) or non-specific (EW-8 and OS-33)tumor uptake of 111In-R1507. Conclusions 111In-R1507 immuno-SPECT is an excellent method to visualize membranous IGF-1R expression and target accessibility in vivo in human bone sarcoma xenografts and may serve as an independent marker to predict IGF-1R therapy (R1507) responsein bone sarcoma patients. PMID:22038993

40 CFR Table 1 to Subpart R of... - General Provisions Applicability to Subpart R

Code of Federal Regulations, 2012 CFR

2012-07-01

... Subpart R 1 Table 1 to Subpart R of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Pipeline Breakout Stations) Pt. 63, Subpt. R, Table 1 Table 1 to Subpart R of Part 63—General Provisions Applicability to Subpart R Reference Applies to subpart R Comment 63.1(a)(1) Yes 63.1(a)(2) Yes 63.1(a)(3) Yes...

40 CFR Table 1 to Subpart R of... - General Provisions Applicability to Subpart R

Code of Federal Regulations, 2014 CFR

2014-07-01

... Subpart R 1 Table 1 to Subpart R of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Pipeline Breakout Stations) Pt. 63, Subpt. R, Table 1 Table 1 to Subpart R of Part 63—General Provisions Applicability to Subpart R Reference Applies to subpart R Comment 63.1(a)(1) Yes 63.1(a)(2) Yes 63.1(a)(3) Yes...

40 CFR Table 1 to Subpart R of... - General Provisions Applicability to Subpart R

Code of Federal Regulations, 2011 CFR

2011-07-01

... Subpart R 1 Table 1 to Subpart R of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Pipeline Breakout Stations) Pt. 63, Subpt. R, Table 1 Table 1 to Subpart R of Part 63—General Provisions Applicability to Subpart R Reference Applies to subpart R Comment 63.1(a)(1) Yes 63.1(a)(2) Yes 63.1(a)(3) Yes...

40 CFR Table 1 to Subpart R of... - General Provisions Applicability to Subpart R

Code of Federal Regulations, 2010 CFR

2010-07-01

... Subpart R 1 Table 1 to Subpart R of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Pipeline Breakout Stations) Pt. 63, Subpt. R, Table 1 Table 1 to Subpart R of Part 63—General Provisions Applicability to Subpart R Reference Applies to subpart R Comment 63.1(a)(1) Yes 63.1(a)(2) Yes 63.1(a)(3) Yes...

40 CFR Table 1 to Subpart R of... - General Provisions Applicability to Subpart R

Code of Federal Regulations, 2013 CFR

2013-07-01

... Subpart R 1 Table 1 to Subpart R of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Pipeline Breakout Stations) Pt. 63, Subpt. R, Table 1 Table 1 to Subpart R of Part 63—General Provisions Applicability to Subpart R Reference Applies to subpart R Comment 63.1(a)(1) Yes 63.1(a)(2) Yes 63.1(a)(3) Yes...

Evaluation of anti-melanoma activities of (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol from the Red Sea soft coral Sarcophyton glaucum.

PubMed

Szymanski, Pawel T; Ahmed, Safwat A; Radwan, Mohamed M; Khalifa, Sherief I; Fahmy, Hesham

2014-08-01

Three natural cembranoids from the Red Sea soft coral Sarcophyton glaucum namely (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol were evaluated for their inhibitory effects on mouse melanoma B16F10 cell growth. Results show that all the cembranoids strongly inhibit viability of melanoma cells particularly during 48 -72 hrs treatment and also inhibit de novo DNA synthesis and PARP activity and stimulate fragmentation of DNA. (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol was not cytotoxic to monkey kidney CV-1 cells at the concentration that produces the anti-melanoma effects which indicates that this compound may be a good candidate for further development. (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol were found to be cytotoxic to healthy cells.

Simultaneous metal-insulator and antiferromagnetic transitions in orthorhombic perovskite iridate S r0.94I r0.78O2.68 single crystals

NASA Astrophysics Data System (ADS)

Zheng, H.; Terzic, J.; Ye, Feng; Wan, X. G.; Wang, D.; Wang, Jinchen; Wang, Xiaoping; Schlottmann, P.; Yuan, S. J.; Cao, G.

2016-06-01

The orthorhombic perovskite SrIr O3 is a semimetal, an intriguing exception in iridates where the strong spin-orbit interaction coupled with electron correlations tends to impose an insulating state. We report results of our investigation of bulk single-crystal S r0.94I r0.78O2.68 or Ir-deficient, orthorhombic perovskite SrIr O3 . It retains the same crystal structure as stoichiometric SrIr O3 but exhibits a sharp, simultaneous antiferromagnetic (AFM) and metal-insulator (MI) transition occurring in the basal-plane resistivity at 185 K. Above it, the basal-plane resistivity features an extended regime of almost linear temperature dependence up to 800 K but the strong electronic anisotropy renders an insulating behavior in the out-of-plane resistivity. The Hall resistivity undergoes an abrupt sign change and grows below 40 K, which along with the Sommerfeld constant of 20 mJ /mol K2 suggests a multiband effect. All results including our first-principles calculations underscore a delicacy of the paramagnetic, metallic state in SrIr O3 that is in close proximity to an AFM insulating state. The contrasting ground states in isostructural S r0.94I r0.78O2.68 and SrIr O3 illustrate a critical role of lattice distortions and Ir deficiency in rebalancing the ground state in the iridates. Finally, the concurrent AFM and MI transitions reveal a direct correlation between the magnetic transition and formation of an activation gap in the iridate, which is conspicuously absent in S r2Ir O4 .

Using R in Taverna: RShell v1.2

PubMed Central

Wassink, Ingo; Rauwerda, Han; Neerincx, Pieter BT; Vet, Paul E van der; Breit, Timo M; Leunissen, Jack AM; Nijholt, Anton

2009-01-01

Background R is the statistical language commonly used by many life scientists in (omics) data analysis. At the same time, these complex analyses benefit from a workflow approach, such as used by the open source workflow management system Taverna. However, Taverna had limited support for R, because it supported just a few data types and only a single output. Also, there was no support for graphical output and persistent sessions. Altogether this made using R in Taverna impractical. Findings We have developed an R plugin for Taverna: RShell, which provides R functionality within workflows designed in Taverna. In order to fully support the R language, our RShell plugin directly uses the R interpreter. The RShell plugin consists of a Taverna processor for R scripts and an RShell Session Manager that communicates with the R server. We made the RShell processor highly configurable allowing the user to define multiple inputs and outputs. Also, various data types are supported, such as strings, numeric data and images. To limit data transport between multiple RShell processors, the RShell plugin also supports persistent sessions. Here, we will describe the architecture of RShell and the new features that are introduced in version 1.2, i.e.: i) Support for R up to and including R version 2.9; ii) Support for persistent sessions to limit data transfer; iii) Support for vector graphics output through PDF; iv)Syntax highlighting of the R code; v) Improved usability through fewer port types. Our new RShell processor is backwards compatible with workflows that use older versions of the RShell processor. We demonstrate the value of the RShell processor by a use-case workflow that maps oligonucleotide probes designed with DNA sequence information from Vega onto the Ensembl genome assembly. Conclusion Our RShell plugin enables Taverna users to employ R scripts within their workflows in a highly configurable way. PMID:19607662

Nanostructured crystals of fluorite phases Sr{sub 1−x}R{sub x}F{sub 2+x} (R Are Rare Earth Elements) and their ordering: 10. Ordering under spontaneous crystallization and annealing of Sr{sub 1−x}R{sub x}F{sub 2+x} Alloys (R = Tb-Lu, Y) with 23.8–36.1 mol % RF{sub 3}

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

Sulyanova, E. A., E-mail: sulyanova@gmail.com; Karimov, D. N.; Sulyanov, S. N.

The products of spontaneous crystallization (at a cooling rate of ∼200 K/min) of Sr{sub 1−x}R{sub x}F{sub 2+x} melts in the homogeneity range of the fluorite phase have been investigated. Thirty-two irrational compositions with 23.8–36.1 mol % RF{sub 3} and eight rational Sr{sub 2}RF{sub 7} compositions are obtained. With respect to the RF{sub 3} content, these compositions form five groups: (1) Sr{sub 0.762}R{sub 0.238}F{sub 2.238} (23.8% RF{sub 3}), (2) Sr{sub 0.744}R{sub 0.256}F{sub 2.256} (25.6%), (3) Sr{sub 0.718}R{sub 0.282}F{sub 2.282} (28.2%), (4) Sr{sub 2}RF{sub 7} (33.3%), and (5) Sr{sub 0.639}R{sub 0.361}F{sub 2.361} (36.1%). R = Tb-Lu, Y for all groups. Quenching meltsmore » of group 5 with R = Tb, Dy, and Ho leads to the formation of ordered phases with the trigonal distortion of the rhβ-Na{sub 7}Zr{sub 6}F{sub 31} type, while for melts of group 5 with R = Lu, quenching yields a phase of the trigonal rhα′-Sr{sub 4}Lu{sub 3}F{sub 17} type. In group 5 with R = Y, Er, Tm, or Yb and in groups 1–4 with all REEs, fluorite phases are formed. Annealing at 900 ± 20°C for 96 h with subsequent cooling at a rate of ∼200 K/min expands the variety of ordered phases: a phase with a new r type of orthorhombic distortion is formed in group 1 with R = Lu, in group 2 with R = Tm or Lu, and in group 3 with R = Ho-Lu, Y; a t-Sr{sub 2}RF{sub 7} phase with tetragonal distortion is formed in group 4 with R = Tb-Er, Y; and a phase of trigonal rhα′ type is formed in group 5 with R = Y, Yb, or Lu. A fluorite phase arises in group 1 with R = Tb-Lu, Y as a result of quenching and annealing. The tendency to ordering becomes more pronounced with an increase in the RF{sub 3} content and REE atomic number. The annealing conditions do not provide equilibrium or the completely ordered state of all alloys.« less

Nanostructured Crystals of Fluorite Phases Sr1 - x R x F2 + x and Their Ordering: 12. Influence of Structural Ordering on the Fluorine-Ion Conductivity of Sr0.667 R 0.333F2.333 Alloys ( R = Tb or Tm) at Their Annealing

NASA Astrophysics Data System (ADS)

Sorokin, N. I.; Karimov, D. N.; Sul'yanova, E. A.; Sobolev, B. P.

2018-01-01

The ionic conductivity of Sr0.667 R 0.333F2.333 alloys (rational Sr2 RF7 compositions) in SrF2- RF3 systems ( R = Tb or Tm), prepared by spontaneous crystallization, has been investigated for the "as-grown" state and after annealing in CF4 at 900 ± 20°C for 96 h. As-grown samples of both compositions, prepared by fast (200°C/min) melt crystallization, exhibit partial (nonequilibrium) ordering, which increases from Tb to Tm. Annealing of Sr0.667 R 0.333F2.333 alloys yields strong ordering (equilibrium for the annealing temperatures) of the fluorite structure (CaF2 type, sp. gr. Fm3̅ m, Z = 4) at the formation of t-Sr2 RF7 tetragonal compound (sp. gr. I4/ m, Z = 30). It is established that ordering of the alloy fluorite structure reduces the fluorine-ion conductivity. After the annealing, the conductivity of Sr0.667R0.333F2.333 alloys with the initial (nonequilibrium) ordering stage of t-Sr2 RF7 phases with almost complete (equilibrium) ordering decreases by a factor of 3-4.5.

Insilico study of the A(2A)R-D (2)R kinetics and interfacial contact surface for heteromerization.

PubMed

Prakash, Amresh; Luthra, Pratibha Mehta

2012-10-01

G-protein-coupled receptors (GPCRs) are cell surface receptors. The dynamic property of receptor-receptor interactions in GPCRs modulates the kinetics of G-protein signaling and stability. In the present work, the structural and dynamic study of A(2A)R-D(2)R interactions was carried to acquire the understanding of the A(2A)R-D(2)R receptor activation and deactivation process, facilitating the design of novel drugs and therapeutic target for Parkinson's disease. The structure-based features (Alpha, Beta, SurfAlpha, and SurfBeta; GapIndex, Leakiness and Gap Volume) and slow mode model (ENM) facilitated the prediction of kinetics (K (off), K (on), and K (d)) of A(2A)R-D(2)R interactions. The results demonstrated the correlation coefficient 0.294 for K (d) and K (on) and the correlation coefficient 0.635 for K (d) and K (off), and indicated stable interfacial contacts in the formation of heterodimer. The coulombic interaction involving the C-terminal tails of the A(2A)R and intracellular loops (ICLs) of D(2)R led to the formation of interfacial contacts between A(2A)R-D(2)R. The properties of structural dynamics, ENM and KFC server-based hot-spot analysis illustrated the stoichiometry of A(2A)R-D(2)R contact interfaces as dimer. The propensity of amino acid residues involved in A(2A)R-D(2)R interaction revealed the presence of positively (R, H and K) and negatively (E and D) charged structural motif of TMs and ICL3 of A(2A)R and D(2)R at interface of dimer contact. Essentially, in silico structural and dynamic study of A(2A)R-D(2)R interactions will provide the basic understanding of the A(2A)R-D(2)R interfacial contact surface for activation and deactivation processes, and could be used as constructive model to recognize the protein-protein interactions in receptor assimilations.

Building a SuAVE browse interface to R2R's Linked Data

NASA Astrophysics Data System (ADS)

Clark, D.; Stocks, K. I.; Arko, R. A.; Zaslavsky, I.; Whitenack, T.

2017-12-01

The Rolling Deck to Repository program (R2R) is creating and evaluating a new browse portal based on the SuAVE platform and the R2R linked data graph. R2R manages the underway sensor data collected by the fleet of US academic research vessels, and provides a discovery and access point to those data at its website, www.rvdata.us. R2R has a database-driven search interface, but seeks a more capable and extensible browse interface that could be built off of the substantial R2R linked data resources. R2R's Linked Data graph organizes its data holdings around key concepts (e.g. cruise, vessel, device type, operator, award, organization, publication), anchored by persistent identifiers where feasible. The "Survey Analysis via Visual Exploration" or SuAVE platform (suave.sdsc.edu) is a system for online publication, sharing, and analysis of images and metadata. It has been implemented as an interface to diverse data collections, but has not been driven off of linked data in the past. SuAVE supports several features of interest to R2R, including faceted searching, collaborative annotations, efficient subsetting, Google maps-like navigation over an image gallery, and several types of data analysis. Our initial SuAVE-based implementation was through a CSV export from the R2R PostGIS-enabled PostgreSQL database. This served to demonstrate the utility of SuAVE but was static and required reloading as R2R data holdings grew. We are now working to implement a SPARQL-based ("RDF Query Language") service that directly leverages the R2R Linked Data graph and offers the ability to subset and/or customize output.We will show examples of SuAVE faceted searches on R2R linked data concepts, and discuss our experience to date with this work in progress.

Purification, crystallization and preliminary X-ray diffraction analysis of the IL-20-IL-20R1-IL-20R2 complex

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

Logsdon, Naomi J.; Allen, Christopher E.; Rajashankar, Kanagalaghatta R.

2012-02-08

Interleukin-20 (IL-20) is an IL-10-family cytokine that regulates innate and adaptive immunity in skin and other tissues. In addition to protecting the host from various external pathogens, dysregulated IL-20 signaling has been shown to contribute to the pathogenesis of human psoriasis. IL-20 signals through two cell-surface receptor heterodimers, IL-20R1-IL-20R2 and IL-22R1-IL-20R2. In this report, crystals of the IL-20-IL-20R1-IL-20R2 ternary complex have been grown from polyethylene glycol solutions. The crystals belonged to space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = 111, c = 135 {angstrom}, and diffracted X-rays to 3 {angstrom} resolution. The crystallographic asymmetricmore » unit contains one IL-20-IL-20R1-IL-20R2 complex, corresponding to a solvent content of approximately 54%.« less

BCRA 2.0 R Package

Cancer.gov

BCRA is an R package that projects absolute risk of invasive breast cancer according to NCI’s Breast Cancer Risk Assessment Tool (BCRAT) algorithm for specified race/ethnic groups and age intervals.

Up-Regulation of miR-21, miR-25, miR-93, and miR-106b in Gastric Cancer

PubMed

LArki, Pegah; Ahadi, Alireza; Zare, Ali; Tarighi, Shahriar; Zaheri, Mahrokh; Souri, Mojgan; Zali, Mohammad Reza; Ghaedi, Hamid; Omrani, Mir Davood

2018-06-03

Differential expression profile of microRNAs (miRNAs) could be a diagnosis signature for the monitoring of gastric cancer (GC) progression. In this study, we focus on the comparison of expression levels of miR-21, miR-25, miR-93, miR-106b, and miR-375 during the sequential pattern of GC development, including normal gastric, gastric dysplasia, and GC sample. We used SYBR Green-based quantitative-PCR to quantify miRNAs expression. Our analysis revealed the increased expression levels of miR-21 (p = 0.034), miR-25 (p = 0.0003) miR-93 (p = 0.0406), and miR-106b (p = 0.023) in GC samples. In addition, GC patients with positive lymph node metastasis showed the up-regulation of miR-25, miR-93, and miR-106b (p < 0.05). Our findings suggested that miR-21, miR-25, miR-93, and miR-106b altered expression in GC, and some of them may be further investigated as biomarkers for GC early detection and prognosis prediction.

Evaluation of role 2 (R2) medical resources in the Afghanistan combat theater: Initial review of the joint trauma system R2 registry.

PubMed

Mann-Salinas, Elizabeth A; Le, Tuan D; Shackelford, Stacy A; Bailey, Jeffrey A; Stockinger, Zsolt T; Spott, Mary Ann; Wirt, Michael D; Rickard, Rory; Lane, Ian B; Hodgetts, Timothy; Cardin, Sylvain; Remick, Kyle N; Gross, Kirby R

2016-11-01

A Role 2 registry (R2R) was developed in 2008 by the US Joint Trauma System (JTS). The purpose of this project was to undertake a preliminary review of the R2R to understand combat trauma epidemiology and related interventions at these facilities to guide training and optimal use of forward surgical capability in the future. A retrospective review of available JTS R2R records; the registry is a convenience sample entered voluntarily by members of the R2 units. Patients were classified according to basic demographics, affiliation, region where treatment was provided, mechanism of injury, type of injury, time and method of transport from point of injury (POI) to R2 facility, interventions at R2, and survival. Analysis included trauma patients aged ≥18 years or older wounded in year 2008 to 2014, and treated in Afghanistan. A total of 15,404 patients wounded and treated in R2 were included in the R2R from February 2008 to September 2014; 12,849 patients met inclusion criteria. The predominant patient affiliations included US Forces, 4,676 (36.4%); Afghan Forces, 4,549 (35.4%); and Afghan civilians, 2,178 (17.0%). Overall, battle injuries predominated (9,792 [76.2%]). Type of injury included penetrating, 7,665 (59.7%); blunt, 4,026 (31.3%); and other, 633 (4.9%). Primary mechanism of injury included explosion, 5,320 (41.4%); gunshot wounds, 3,082 (24.0%); and crash, 1,209 (9.4%). Of 12,849 patients who arrived at R2, 167 (1.3%) were dead; of 12,682 patients who were alive upon arrival, 342 (2.7%) died at R2. This evaluation of the R2R describes the patient profiles of and common injuries treated in a sample of R2 facilities in Afghanistan. Ongoing and detailed analysis of R2R information may provide evidence-based guidance to military planners and medical leaders to best prepare teams and allocate R2 resources in future operations. Given the limitations of the data set, conclusions must be interpreted in context of other available data and analyses, not in isolation

Stability and Unimolecular Reactivity of Palladate(II) Complexes [Ln PdR3 ]- (L=Phosphine, R=Organyl, n=0 and 1).

PubMed

Kolter, Marlene; Koszinowski, Konrad

2016-10-24

The reduction of Pd II precatalysts to catalytically active Pd 0 species is a key step in many palladium-mediated cross-coupling reactions. Besides phosphines, the stoichiometrically used organometallic reagents can afford this reduction, but do so in a poorly understood way. To elucidate the mechanism of this reaction, we have treated solutions of Pd(OAc) 2 and a phosphine ligand L in tetrahydrofuran with RMgCl (R=Ph, Bn, Bu) as well as other organometallic reagents. Analysis of these model systems by electrospray- ionization mass spectrometry found palladate(II) complexes [L n PdR 3 ] - (n=0 and 1), thus pointing to the occurrence of transmetallation reactions. Upon gas-phase fragmentation, the [L n PdR 3 ] - anions preferentially underwent a reductive elimination to yield Pd 0 species. The sequence of the transmetallation and reductive elimination, thus, constitutes a feasible mechanism for the reduction of the Pd(OAc) 2 precatalyst. Other species of interest observed include the Pd IV complex [PdBn 5 ] - , which did not fragment via a reductive elimination but lost BnH instead. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

IL1R2, CCR2, and CXCR4 May Form Heteroreceptor Complexes with NMDAR and D2R: Relevance for Schizophrenia

PubMed Central

Borroto-Escuela, Dasiel O.; Tarakanov, Alexander O.; Bechter, Karl; Fuxe, Kjell

2017-01-01

The mild neuroinflammation hypothesis of schizophrenia was introduced by Bechter in 2001. It has been hypothesized that a hypofunction of glutamatergic signaling via N-methyl-D-aspartate receptors (NMDARs) and hyperactivation of dopamine D2 receptors play a role in schizophrenia. The triplet puzzle theory states that sets of triplet amino acid homologies guide two different receptors toward each other and contributes to the formation of a receptor heteromer. It is, therefore, proposed that putative NMDAR-C-C chemokine receptor type 2 (CCR2), NMDAR-C-X-C chemokine receptor type 4 (CXCR4), and NMDAR- interleukin 1 receptor type II (IL1R2) heteromers can be formed in the neuronal networks in mild neuroinflammation due to demonstration of Gly-Leu-Leu (GLL), Val-Ser-Thr (VST), and/or Ser-Val-Ser (SVS) amino acid homologies between these receptor protomers. This molecular process may underlie the ability to produce symptoms of schizophrenia in mild neuroinflammation. In this state, volume transmission (VT) is increased involving increased extracellular vesicle-mediated VT from microglia and astroglia. These vesicles may contain CCR2, CXCR4, and/or IL1R2 as well as their ligands and upon internalization by endocytic pathways into neurons can form heteroreceptor complexes with NMDAR in the plasma membrane with pathological allosteric receptor–receptor interactions involving increased internalization and reduced NMDAR signaling. The triplet puzzle theory also suggests the formation of putative D2R-CCR2, D2R-CXCR4, and D2R-IL1R2 heteromers in mild neuroinflammation in view of their demonstrated sets of Leu-Tyr-Ser (LYS), Leu-Pro-Phe (LPF), and/or Ser-Leu-Ala (SLA) triplet homologies. These D2R heteroreceptor complexes may also contribute to schizophrenia-like symptoms in mild neuroinflammation by enhancing D2R protomer function. PMID:28261115

Dielectric and impedance properties of NiFe1.95R0.05O4 (R = Y, Yb and Lu)

NASA Astrophysics Data System (ADS)

Ugendar, Kodam; Kumar, Hanuma; Markaneyulu, G.; Rani, G. Neeraja

2018-04-01

The dielectric and impedance spectroscopic properties of NiFe1.95R0.05O4 (R = Y, Yb and Lu) were investigated. The materials were prepared by solid state reaction and crystallized in the cubic inverse spinel phase with a very small amount additional phase of RFeO3 (R = Y, Yb and Lu) as secondary phase. The scanning electron micrograph images clearly show grains (˜2μm) which are separated by thin grain boundaries. The presences of all elements were confirmed by the energy dispersive X-ray elemental mapping. The frequency variation of ɛ' shows the dispersion, following the Koop's phenomenological theory, which considers the dielectric structure as an inhomogeneous medium of two-layers of the Maxwell-Wagner type. Impedance spectroscopic analysis indicates the different relaxation mechanisms, which corresponds to bulk grain and grain-boundaries. Their contributions to the electrical conductivity and capacitance of these materials were discussed in detailed.

Magnetostructural coupling, magnetic ordering, and cobalt spin reorientation in metallic P r0.5S r0.5Co O3 cobaltite

NASA Astrophysics Data System (ADS)

García-Muñoz, José Luis; Padilla-Pantoja, Jessica; Torrelles, Xavier; Blasco, Javier; Herrero-Martín, Javier; Bozzo, Bernat; Rodríguez-Velamazán, José A.

2016-07-01

In half-doped P r0.50A0.50Co O3 metallic perovskites, the spin-lattice coupling brings about distinct magnetostructural transitions for A =Ca and A =Sr at temperatures close to ˜100 K. However, the ground magnetic properties of P r0.50S r0.50Co O3 (PSCO) strongly differ from P r0.50C a0.50Co O3 ones, where a partial P r3 + to P r4 + valence shift and Co spin transition makes the system insulating below the transition. This paper investigates and describes the relationship between the I m m a →I 4 /m c m symmetry change [Padilla-Pantoja, García-Muñoz, Bozzo, Jirák, and Herrero-Martín, Inorg. Chem. 53, 12297 (2014)] and the original magnetic behavior of PSCO versus temperature and external magnetic fields. The FM1 and FM2 ferromagnetic phases, above and below the magnetostructural transition (TS 1˜120 K ) have been investigated. The FM2 phase of PSCO is composed of [100] FM domains, with magnetic symmetry I m'm'a (mx≠0 , mz=0 ). The magnetic space group of the FM1 phase is F m'm'm (with mx=my ). Neutron data analyses in combination with magnetometry and earlier reports results agrees with a reorientation of the magnetization axis by 45∘ within the a b plane across the transition, in which the system retains its metallic character. The presence below TS 1 of conjugated magnetic domains, both of F m'm'm symmetry but having perpendicular spin orientations along the diagonals in the x y plane of the tetragonal unit cell, is at the origin of the anomalies observed in the macroscopic magnetization. A relatively small field μ0H [⊥ z ] ≳30 mT is able to reorient the magnetization within the a b plane, whereas a higher field (μ0H [∥z ] ≳1.2 T at 2 K) is necessary to align the Co moments perpendicular to the a b plane. Such a spin reorientation, in which the orbital and spin components of the Co moment rotate joined by 45∘, was not observed previously in analogous cobaltites without praseodymium.

miR-139 is up-regulated in osteoarthritis and inhibits chondrocyte proliferation and migration possibly via suppressing EIF4G2 and IGF1R

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

Hu, Weihua; Zhang, Weikai; Li, Feng

Osteoarthritis (OA) is one of the most progressive articular cartilage erosions. microRNAs (miRNAs) play pivotal roles in OA modulation, but the role of miR-139 in OA remains elusive. This study aims to reveal the effects and possible mechanism of miR-139 in OA and chondrocytes. The levels of miR-139 and its possible targets eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) and insulin-like growth factor 1 receptor (IGF1R) were detected by qRT-PCR in the articular cartilages of 20 OA patients and 20 non-OA patients. Human chondrocyte CHON-001 cells were transfected with miR-139 mimic or inhibitor, as well as the siRNAs of EIF4G2more » and IGF1R. Cell viability by MTT assay, proliferation by colony formation assay and migration by Transwell assay were performed. Results showed that miR-139 was up-regulated, while EIF4G2 and IGF1R mRNAs down-regulated in OA cartilages (P < 0.001), and negative correlations existed between the level of miR-139 and EIF4G2 or IGF1R. Overexpression of miR-139 in CHON-001 cells suppressed both mRNA and protein levels of EIF4G2 and IGF1R, and inhibited cell viability, colony formation number and cell migration, while miR-139 inhibitor induced the opposite effects. Knockdown of EIF4G2 or IGF1R in CHON-001 cells reversed the effects of miR-139 inhibitor on cell viability, colony formation and cell migration. These results indicate that miR-139 is capable of inhibiting chondrocyte proliferation and migration, thus being a possible therapeutic target for OA. The mechanism of miR-139 in chondrocytes may be related to its regulation on EIF4G2 and IGF1R.« less

15. 'Southern Pacific R.R., One 236'0' Bet. End Pins S. ...

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

15. 'Southern Pacific R.R., One 236'-0' Bet. End Pins S. Tr. Thro'. Draw Bridge over Sacramento River at Tehama, The Phoenix Bridge Co., Phoenixville, Pa., Jan'y 19th 98, Dwg. 585.' - Southern Pacific Railroad Shasta Route, Bridge No. 210.52, Milepost 210.52, Tehama, Tehama County, CA

MinION Analysis and Reference Consortium: Phase 2 data release and analysis of R9.0 chemistry.

PubMed

Jain, Miten; Tyson, John R; Loose, Matthew; Ip, Camilla L C; Eccles, David A; O'Grady, Justin; Malla, Sunir; Leggett, Richard M; Wallerman, Ola; Jansen, Hans J; Zalunin, Vadim; Birney, Ewan; Brown, Bonnie L; Snutch, Terrance P; Olsen, Hugh E

2017-01-01

Long-read sequencing is rapidly evolving and reshaping the suite of opportunities for genomic analysis. For the MinION in particular, as both the platform and chemistry develop, the user community requires reference data to set performance expectations and maximally exploit third-generation sequencing. We performed an analysis of MinION data derived from whole genome sequencing of Escherichia coli K-12 using the R9.0 chemistry, comparing the results with the older R7.3 chemistry. We computed the error-rate estimates for insertions, deletions, and mismatches in MinION reads. Run-time characteristics of the flow cell and run scripts for R9.0 were similar to those observed for R7.3 chemistry, but with an 8-fold increase in bases per second (from 30 bps in R7.3 and SQK-MAP005 library preparation, to 250 bps in R9.0) processed by individual nanopores, and less drop-off in yield over time. The 2-dimensional ("2D") N50 read length was unchanged from the prior chemistry. Using the proportion of alignable reads as a measure of base-call accuracy, 99.9% of "pass" template reads from 1-dimensional ("1D")  experiments were mappable and ~97% from 2D experiments. The median identity of reads was ~89% for 1D and ~94% for 2D experiments. The total error rate (miscall + insertion + deletion ) decreased for 2D "pass" reads from 9.1% in R7.3 to 7.5% in R9.0 and for template "pass" reads from 26.7% in R7.3 to 14.5% in R9.0. These Phase 2 MinION experiments serve as a baseline by providing estimates for read quality, throughput, and mappability. The datasets further enable the development of bioinformatic tools tailored to the new R9.0 chemistry and the design of novel biological applications for this technology. K: thousand, Kb: kilobase (one thousand base pairs), M: million, Mb: megabase (one million base pairs), Gb: gigabase (one billion base pairs).

Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer.

PubMed

Smith, Kimberly R; Spector, Alan C

2017-10-01

Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are 1 ) detectable when both receptor subunits are absent and 2 ) perceptually distinct from that of sucrose irrespective of viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose sensitivity as controls. However, some KO mice were only sensitive to the higher Polycose concentrations, implicating potential allelic variation in the putative polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 + T1R3. Varied Maltrin and sucrose concentrations of approximately matched viscosities were then presented to render the oral somatosensory features, intensity, and hedonic value of the solutions irrelevant. Although both genotypes competently discriminated Maltrin from sucrose, performance was apparently driven by the different orosensory percepts of the two stimuli in control mice and the presence of a Maltrin but not sucrose orosensory cue in KO mice. These data support the proposed presence of an orosensory receptor mechanism that gives rise to a qualitatively distinguishable sensation from that of sucrose. Copyright © 2017 the American Physiological Society.

The R-Process Alliance: 2MASS J09544277+5246414, the Most Actinide-enhanced R-II Star Known

NASA Astrophysics Data System (ADS)

Holmbeck, Erika M.; Beers, Timothy C.; Roederer, Ian U.; Placco, Vinicius M.; Hansen, Terese T.; Sakari, Charli M.; Sneden, Christopher; Liu, Chao; Lee, Young Sun; Cowan, John J.; Frebel, Anna

2018-06-01

We report the discovery of a new actinide-boost star, 2MASS J09544277+5246414, originally identified as a very bright (V = 10.1), extremely metal-poor ([Fe/H] = ‑2.99) K giant in the LAMOST survey, and found to be highly r-process-enhanced (r-II; [Eu/Fe] = +1.28]), during the snapshot phase of the R-Process Alliance (RPA). Based on a high signal-to-noise ratio (S/N), high-resolution spectrum obtained with the Harlan J. Smith 2.7 m telescope, this star is the first confirmed actinide-boost star found by RPA efforts. With an enhancement of [Th/Eu] = +0.37, 2MASS J09544277+5246414 is also the most actinide-enhanced r-II star yet discovered, and only the sixth metal-poor star with a measured uranium abundance ([U/Fe] = +1.40). Using the Th/U chronometer, we estimate an age of 13.0 ± 4.7 Gyr for this star. The unambiguous actinide-boost signature of this extremely metal-poor star, combined with additional r-process-enhanced and actinide-boost stars identified by the RPA, will provide strong constraints on the nature and origin of the r-process at early times.

Explaining the R_K and R_{K^*} anomalies

NASA Astrophysics Data System (ADS)

Ghosh, Diptimoy

2017-10-01

Recent LHCb results on R_{K^*}, the ratio of the branching fractions of B → K^* μ ^+ μ ^- to that of B → K^* e^+ e^-, for the dilepton invariant mass bins q^2 ≡ m_{ℓ ℓ }^2 = [0.045-1.1] GeV^2 and [1.1-6] GeV^2 show approximately 2.5 σ deviations from the corresponding Standard Model prediction in each of the bins. This, when combined with the measurement of R_K (q^2=[1-6] GeV^2), a similar ratio for the decay to a pseudo-scalar meson, highly suggests lepton non-universal new physics in semi-leptonic B meson decays. In this work, we perform a model independent analysis of these potential new physics signals and identify the operators that do the best job in satisfying all these measurements. We show that heavy new physics, giving rise to q^2 independent local 4-Fermi operators of scalar, pseudo-scalar, vector or axial-vector type, is unable to explain all the three measurements simultaneously, in particular R_{K^*} in the bin [0.045-1.1], within their experimental 1σ regions. We point out the possibility to explain R_{K^*} in the low bin by an additional light (≲ 20 {MeV}) vector boson with appropriate coupling strengths to (\\bar{b} s) and (\\bar{e} e).

Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy.

PubMed

Matsuzaka, Yasunari; Kishi, Soichiro; Aoki, Yoshitsugu; Komaki, Hirofumi; Oya, Yasushi; Takeda, Shin-Ichi; Hashido, Kazuo

2014-11-01

Muscular dystrophies are a clinically and genetically heterogeneous group of inherited myogenic disorders. In clinical tests for these diseases, creatine kinase (CK) is generally used as diagnostic blood-based biomarker. However, because CK levels can be altered by various other factors, such as vigorous exercise, etc., false positive is observed. Therefore, three microRNAs (miRNAs), miR-1, miR-133a, and miR-206, were previously reported as alternative biomarkers for duchenne muscular dystrophy (DMD). However, no alternative biomarkers have been established for the other muscular dystrophies. We, therefore, evaluated whether these miR-1, miR-133a, and miR-206 can be used as powerful biomarkers using the serum from muscular dystrophy patients including DMD, myotonic dystrophy 1 (DM1), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), becker muscular dystrophy (BMD), and distal myopathy with rimmed vacuoles (DMRV) by qualitative polymerase chain reaction (PCR) amplification assay. Statistical analysis indicated that all these miRNA levels in serum represented no significant differences between all muscle disorders examined in this study and controls by Bonferroni correction. However, some of these indicated significant differences without correction for testing multiple diseases (P < 0.05). The median values of miR-1 levels in the serum of patients with LGMD, FSHD, and BMD were approximately 5.5, 3.3 and 1.7 compared to that in controls, 0.68, respectively. Similarly, those of miR-133a and miR-206 levels in the serum of BMD patients were about 2.5 and 2.1 compared to those in controls, 1.03 and 1.32, respectively. Taken together, our data demonstrate that levels of miR-1, miR-133a, and miR-206 in serum of BMD and miR-1 in sera of LGMD and FSHD patients showed no significant differences compared with those of controls by Bonferroni correction. However, the results might need increase in sample sizes to evaluate these three miRNAs as

Independent activity of the homologous small regulatory RNAs AbcR1 and AbcR2 in the legume symbiont Sinorhizobium meliloti.

PubMed

Torres-Quesada, Omar; Millán, Vicenta; Nisa-Martínez, Rafael; Bardou, Florian; Crespi, Martín; Toro, Nicolás; Jiménez-Zurdo, José I

2013-01-01

The legume symbiont Sinorhizobium meliloti expresses a plethora of small noncoding RNAs (sRNAs) whose function is mostly unknown. Here, we have functionally characterized two tandemly encoded S. meliloti Rm1021 sRNAs that are similar in sequence and structure. Homologous sRNAs (designated AbcR1 and AbcR2) have been shown to regulate several ABC transporters in the related α-proteobacteria Agrobacterium tumefaciens and Brucella abortus. In Rm1021, AbcR1 and AbcR2 exhibit divergent unlinked regulation and are stabilized by the RNA chaperone Hfq. AbcR1 is transcribed in actively dividing bacteria, either in culture, rhizosphere or within the invasion zone of mature alfalfa nodules. Conversely, AbcR2 expression is induced upon entry into stationary phase and under abiotic stress. Only deletion of AbcR1 resulted into a discrete growth delay in rich medium, but both are dispensable for symbiosis. Periplasmic proteome profiling revealed down-regulation of the branched-chain amino acid binding protein LivK by AbcR1, but not by AbcR2. A double-plasmid reporter assay confirmed the predicted specific targeting of the 5'-untranslated region of the livK mRNA by AbcR1 in vivo. Our findings provide evidences of independent regulatory functions of these sRNAs, probably to fine-tune nutrient uptake in free-living and undifferentiated symbiotic rhizobia.

Independent Activity of the Homologous Small Regulatory RNAs AbcR1 and AbcR2 in the Legume Symbiont Sinorhizobium meliloti

PubMed Central

Torres-Quesada, Omar; Millán, Vicenta; Nisa-Martínez, Rafael; Bardou, Florian; Crespi, Martín; Toro, Nicolás; Jiménez-Zurdo, José I.

2013-01-01

The legume symbiont Sinorhizobium meliloti expresses a plethora of small noncoding RNAs (sRNAs) whose function is mostly unknown. Here, we have functionally characterized two tandemly encoded S. meliloti Rm1021 sRNAs that are similar in sequence and structure. Homologous sRNAs (designated AbcR1 and AbcR2) have been shown to regulate several ABC transporters in the related α-proteobacteria Agrobacterium tumefaciens and Brucella abortus. In Rm1021, AbcR1 and AbcR2 exhibit divergent unlinked regulation and are stabilized by the RNA chaperone Hfq. AbcR1 is transcribed in actively dividing bacteria, either in culture, rhizosphere or within the invasion zone of mature alfalfa nodules. Conversely, AbcR2 expression is induced upon entry into stationary phase and under abiotic stress. Only deletion of AbcR1 resulted into a discrete growth delay in rich medium, but both are dispensable for symbiosis. Periplasmic proteome profiling revealed down-regulation of the branched-chain amino acid binding protein LivK by AbcR1, but not by AbcR2. A double-plasmid reporter assay confirmed the predicted specific targeting of the 5′-untranslated region of the livK mRNA by AbcR1 in vivo. Our findings provide evidences of independent regulatory functions of these sRNAs, probably to fine-tune nutrient uptake in free-living and undifferentiated symbiotic rhizobia. PMID:23869210

The T1R2/T1R3 sweet receptor and TRPM5 ion channel taste targets with therapeutic potential.

PubMed

Sprous, Dennis; Palmer, Kyle R

2010-01-01

Taste signaling is a critical determinant of ingestive behaviors and thereby linked to obesity and related metabolic dysfunctions. Recent evidence of taste signaling pathways in the gut suggests the link to be more direct, raising the possibility that taste receptor systems could be regarded as therapeutic targets. T1R2/T1R3, the G protein coupled receptor that mediates sweet taste, and the TRPM5 ion channel have been the focus of discovery programs seeking novel compounds that could be useful in modifying taste. We review in this chapter the hypothesis of gastrointestinal taste signaling and discuss the potential for T1R2/T1R3 and TRPM5 as targets of therapeutic intervention in obesity and diabetes. Critical to the development of a drug discovery program is the creation of libraries that enhance the likelihood of identifying novel compounds that modulate the target of interest. We advocate a computer-based chemoinformatic approach for assembling natural and synthetic compound libraries as well as for supporting optimization of structure activity relationships. Strategies for discovering modulators of T1R2/T1R3 and TRPM5 using methods of chemoinformatics are presented herein. Copyright 2010 Elsevier Inc. All rights reserved.

77 FR 1656 - Proposed Establishment of Restricted Areas R-5402, R-5403A, R-5403B, R-5403C, R-5403D, R-5403E, R...

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2012-01-11

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The Onion (Allium cepa L.) R2R3-MYB Gene MYB1 Regulates Anthocyanin Biosynthesis

PubMed Central

Schwinn, Kathy E.; Ngo, Hanh; Kenel, Fernand; Brummell, David A.; Albert, Nick W.; McCallum, John A.; Pither-Joyce, Meeghan; Crowhurst, Ross N.; Eady, Colin; Davies, Kevin M.

2016-01-01

Bulb color is an important consumer trait for onion (Allium cepa L., Allioideae, Asparagales). The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red), flavonols (pale yellow), and chalcones (bright yellow). Flavonoid regulation is poorly characterized in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs) that commonly activate anthocyanin (SG6, MYB1) or flavonol (SG7, MYB29) production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5). MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressed and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic (Allium sativum L.) plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum majus of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species. PMID:28018399

The Onion (Allium cepa L.) R2R3-MYB Gene MYB1 Regulates Anthocyanin Biosynthesis.

PubMed

Schwinn, Kathy E; Ngo, Hanh; Kenel, Fernand; Brummell, David A; Albert, Nick W; McCallum, John A; Pither-Joyce, Meeghan; Crowhurst, Ross N; Eady, Colin; Davies, Kevin M

2016-01-01

Bulb color is an important consumer trait for onion ( Allium cepa L., Allioideae, Asparagales). The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red), flavonols (pale yellow), and chalcones (bright yellow). Flavonoid regulation is poorly characterized in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs) that commonly activate anthocyanin (SG6, MYB1) or flavonol (SG7, MYB29) production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5). MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressed and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic ( Allium sativum L.) plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum maju s of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species.

Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine.

PubMed

Shirayama, Yukihiko; Hashimoto, Kenji

2018-01-01

(R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine's antidepressant actions. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine

PubMed Central

Shirayama, Yukihiko

2018-01-01

Abstract Background (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine’s antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. Methods The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. Results A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Conclusions Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine’s antidepressant actions. PMID:29155993

MicroRNAs modulating angiogenesis: miR-129-1 and miR-133 act as angio-miR in HUVECs.

PubMed

Soufi-Zomorrod, Mina; Hajifathali, Abbas; Kouhkan, Fatemeh; Mehdizadeh, Mahshid; Rad, Seyed Mohammad Ali Hosseini; Soleimani, Masoud

2016-07-01

The sprouting of new blood vessels by angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to enormous pathological conditions such as ischemia and cancer. MicroRNAs (also known as miRNAs or miRs) play key roles in regulation of a range of cellular processes by posttranscriptional suppression of their target genes. Recently, new studies have indicated that miRNAs are involved in certain angiogenic settings and signaling pathways use these non-coding RNAs to promote or suppress angiogenic processes. Herein, VEGFR2 and FGFR1 were identified as miR-129-1 and miR-133 targets using bioinformatic algorithms, respectively. Afterwards, using luciferase reporter assay and gene expression analysis at both mRNA and protein levels, VEGFR2 and FGFR1 were validated as miR-129-1 and miR-133 targets. In addition, we showed that miR-129-1 and miR-133 suppress angiogenesis properties such as proliferation rate, cell viability, and migration activity of human umbilical vein endothelial cells (HUVEC) in vitro. We conclude that these miRNAs can suppress key factors of angiogenesis by directly targeting them. These results have important therapeutic implications for a variety of diseases involving deregulation of angiogenesis, including cancer.

Anisotropic cosmological solutions in R + R^2 gravity

NASA Astrophysics Data System (ADS)

Müller, Daniel; Ricciardone, Angelo; Starobinsky, Alexei A.; Toporensky, Aleksey

2018-04-01

In this paper we investigate the past evolution of an anisotropic Bianchi I universe in R+R^2 gravity. Using the dynamical system approach we show that there exists a new two-parameter set of solutions that includes both an isotropic "false radiation" solution and an anisotropic generalized Kasner solution, which is stable. We derive the analytic behavior of the shear from a specific property of f( R) gravity and the analytic asymptotic form of the Ricci scalar when approaching the initial singularity. Finally, we numerically check our results.

Tyms double (2R) and triple repeat (3R) confers risk for human oral squamous cell carcinoma.

PubMed

Bezerra, Alexandre Medeiros; Sant'Ana, Thalita Araújo; Gomes, Adriana Vieira; de Lacerda Vidal, Aurora Karla; Muniz, Maria Tereza Cartaxo

2014-12-01

The oral cancer is responsible for approximately 3 % of cases of cancer in Brazil. Epidemiological studies have associated low folate intake with an increased risk of epithelial cancers, including oral cancer. Folic acid has a key role in DNA synthesis, repair, methylation and this is the basis of explanations for a putative role for folic acid in cancer prevention. The role of folic acid in carcinogenesis may be modulated by polymorphism C677T in MTHFR and tandem repeats 2R/3R in the promoter site of TYMS gene that are related to decreased enzymatic activity and quantity and availability of the enzyme, respectively. These events cause a decrease in the synthesis, repair and DNA methylation, which can lead to a disruption in the expression of tumor suppressor genes as TP53. The objective of this study was investigate the distribution of polymorphisms C677T and tandem repeats 2R/3R associated with the development of oral squamous cell carcinoma (OSCC). 53 paraffin-embedded samples from patients who underwent surgery but are no longer at the institution and 43 samples collected by method of oral exfoliation by cytobrush were selected. 132 healthy subjects were selected by specialists at the dental clinics of the Faculdade de Odontologia de Pernambuco-FOP. The MTHFR genotyping was performed by PCR-RFLP, and the TYMS genotyping was performed by conventional PCR. Fisher's Exact test at significant level of 5 %. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to measure the strength of association between genotype frequency and OSCC development. The results were statistically significant for the tandem repeats of the TYMS gene (p = 0.015). The TYMS 2R3R genotype was significantly associated with the development of OSCC (OR = 3.582; 95 % CI 1.240-10.348; p = 0.0262) and also the genotype 3R3R (OR = 3.553; 95 % CI 1.293-9.760; p = 0.0345). When analyzed together, the TYMS 2R3R + 3R3R genotypes also showed association (OR = 3.518; 95 % CI 11.188-10.348; p

Neuroprotective Activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in Rodent Models of Brain Ischemia

PubMed Central

Xu, Zhenfeng; Mu, Chaofeng; Alvarez, Paloma; Ford, Byron D.; El Sayed, Khalid; Eterovic, Vesna A.; Ferchmin, Pedro A.; Hao, Jiukuan

2015-01-01

(1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volume (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volume (120±65 mm3) than those in the rats of DMSO group (291±95 mm3). The results from in vitro experiments indicate that 4R decreased neuro2a cells (neuroblastoma cells) apoptosis induced by oxygen glucose deprivation (OGD), and improved the population spikes (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to bEND5 cells (murine brain-derived endothelial cells) and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R. PMID:25677097

Dependences of the density of M{sub 1-x}R{sub x}F{sub 2+x} and R{sub 1-y}M{sub y}F{sub 3-y} single crystals (M = Ca, Sr, Ba, Cd, Pb; R means rare earth elements) on composition

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

Sorokin, N. I., E-mail: sorokin@ns.crys.ras.ru; Krivandina, E. A.; Zhmurova, Z. I.

2013-11-15

The density of single crystals of nonstoichiometric phases Ba{sub 1-x}La{sub x}F{sub 2+x} (0 {<=} x {<=} 0.5) and Sr{sub 0.8}La{sub 0.2-x}Lu{sub x}F{sub 2.2} (0 {<=} x {<=} 0.2) with the fluorite (CaF{sub 2}) structure type and R{sub 1-y}Sr{sub y}F{sub 3-y} (R = Pr, Nd; 0 {<=} y {<=} 0.15) with the tysonite (LaF{sub 3}) structure type has been measured. Single crystals were grown from a melt by the Bridgman method. The measured concentration dependences of single crystal density are linear. The interstitial and vacancy models of defect formation in the fluorite and tysonite phases, respectively, are confirmed. To implement themore » composition control of single crystals of superionic conductors M{sub 1-x}R{sub x}F{sub 2+x} and R{sub 1-y}M{sub y}F{sub 3-y} in practice, calibration graphs of X-ray density in the MF{sub 2}-RF{sub 3} systems (M = Ca, Sr, Ba, Cd, Pb; R = La-Lu, Y) are plotted.« less

Condensed tannins: A proposed route to 2R,3R-(2,3-cis)-proanthocyanidins

Treesearch

Richard W. Hemingway; Peter E. Laks

1985-01-01

Roux,1 Haslam,2-4 and Stafford5-8 have proposed differing biogenetic schemes for the formation of proanthocyanidins (condensed tannins) in plants. All three schemes suffer from difficulties in explaining the formation of the 2R,3R-(2,3-cis)-proanthocyanidins that predominate in...

Can the new RCP R0/R1 classification predict the clinical outcome in ductal adenocarcinoma of the pancreatic head?

PubMed

Janot, M S; Kersting, S; Belyaev, O; Matuschek, A; Chromik, A M; Suelberg, D; Uhl, W; Tannapfel, A; Bergmann, U

2012-08-01

According to the International Union Against Cancer (UICC), R1 is defined as the microscopic presence of tumor cells at the surface of the resection margin (RM). In contrast, the Royal College of Pathologists (RCP) suggested to declare R1 already when tumor cells are found within 1 mm of the RM. The aim of this study was to determine the significance of the RM concerning the prognosis of pancreatic ductal adenocarcinoma (PDAC). From 2007 to 2009, 62 patients underwent a curative operation for PDAC of the pancreatic head. The relevance of R status on cumulative overall survival (OS) was assessed on univariate and multivariate analysis for both the classic R classification (UICC) and the suggestion of the RCP. Following the UICC criteria, a positive RM was detected in 8 %. Along with grading and lymph node ratio, R status revealed a significant impact on OS on univariate and multivariate analysis. Applying the suggestion of the RCP, R1 rate rose to 26 % resulting in no significant impact on OS in univariate analysis. Our study has shown that the RCP suggestion for R status has no impact on the prognosis of PDAC. In contrast, our data confirmed the UICC R classification of RM as well as N category, grading, and lymph node ratio as significant prognostic factors.

CYP2R1 mutations causing vitamin D-deficiency rickets.

PubMed

Thacher, Tom D; Levine, Michael A

2017-10-01

CYP2R1 is the principal hepatic 25-hydroxylase responsible for the hydroxylation of parent vitamin D to 25-hydroxyvitamin D [25(OH)D]. Serum concentrations of 25(OH)D reflect vitamin D status, because 25(OH)D is the major circulating metabolite of vitamin D. The 1α-hydroxylation of 25(OH)D in the kidney by CYP27B1 generates the fully active vitamin D metabolite, 1,25-dihydroxyvitamin D (1,25(OH) 2 D). The human CYP2R1 gene, located at 11p15.2, has five exons, coding for an enzyme with 501 amino acids. In Cyp2r1-/- knockout mice, serum 25(OH)D levels were reduced by more than 50% compared wild-type mice. Genetic polymorphisms of CYP2R1 account for some of the individual variability of circulating 25(OH)D values in the population. We review the evidence that inactivating mutations in CYP2R1 can lead to a novel form of vitamin D-deficiency rickets resulting from impaired 25-hydroxylation of vitamin D. We sequenced the promoter, exons and intron-exon flanking regions of the CYP2R1 gene in members of 12 Nigerian families with rickets in more than one family member. We found missense mutations (L99P and K242N) in affected members of 2 of 12 families. The L99P mutation had previously been reported as a homozygous defect in an unrelated child of Nigerian origin with rickets. In silico analyses predicted impaired CYP2R1 folding or reduced interaction with substrate vitamin D by L99P and K242N mutations, respectively. In vitro studies of the mutant CYP2R1 proteins in HEK293 cells confirmed normal expression levels but completely absent or markedly reduced 25-hydroxylase activity by the L99P and K242N mutations, respectively. Heterozygous subjects had more moderate biochemical and clinical features of vitamin D deficiency than homozygous subjects. After an oral bolus dose of 50,000 IU of vitamin D 2 or vitamin D 3 , heterozygous subjects had lower increases in serum 25(OH)D than control subjects, and homozygous subjects had minimal increases, supporting a semidominant

Nanostructured crystals of fluorite phases Sr1 - x R x F2 + x ( R = Y, La-Lu) and their ordering: Part III. A study of the refractive indices

NASA Astrophysics Data System (ADS)

Glushkova, T. M.; Karimov, D. N.; Krivandina, E. A.; Zhmurova, Z. I.; Sobolev, B. P.

2009-07-01

The refractive indices n of Sr1 - x R x F2 + x crystals ( R = Y, La-Lu; 0 ≤ x ≤ 0.5) have been measured at wavelengths of 0.436, 0.546, and 0.589 μm. It is established that n increases when there is an increase in the RF3 content x according to a weakly quadratic law for each R. For the isoconcentration series of Sr0.9 R 0.1F2.1 crystals, the change in n in the series of rare earth elements has a pronounced nonlinear character, which reflects the nonmonotonous change in the properties of compounds in the R series. It is shown that the method of molecular refraction additivity can be used to calculate n for Sr1 - x R x F2 + x crystals. By varying the RF3 content in them, one can obtain optical media with a gradually varied refractive index n in the range 1.44-1.55, thus filling the gap in the n values between high ones for RF3 crystals and low ones for crystals of alkaline earth fluorides MF2.

Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia.

PubMed

Martins, Antonio H; Hu, Jing; Xu, Zhenfeng; Mu, Chaofeng; Alvarez, Paloma; Ford, Byron D; El Sayed, Khalid; Eterovic, Vesna A; Ferchmin, Pedro A; Hao, Jiukuan

2015-04-16

(1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volumes (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volumes (120±65 mm3) than those in the rats of the DMSO group (291±95 mm3). The results from in vitro experiments indicate that 4R decreased neuro2a cell (neuroblastoma cells) apoptosis induced by oxygen-glucose deprivation (OGD), and improved the population spikes' (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to murine brain-derived endothelial (bEND5) cells and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

rVISTA 2.0: Evolutionary Analysis of Transcription Factor Binding Sites

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

Loots, G G; Ovcharenko, I

2004-01-28

Identifying and characterizing the patterns of DNA cis-regulatory modules represents a challenge that has the potential to reveal the regulatory language the genome uses to dictate transcriptional dynamics. Several studies have demonstrated that regulatory modules are under positive selection and therefore are often conserved between related species. Using this evolutionary principle we have created a comparative tool, rVISTA, for analyzing the regulatory potential of noncoding sequences. The rVISTA tool combines transcription factor binding site (TFBS) predictions, sequence comparisons and cluster analysis to identify noncoding DNA regions that are highly conserved and present in a specific configuration within an alignment. Heremore » we present the newly developed version 2.0 of the rVISTA tool that can process alignments generated by both zPicture and PipMaker alignment programs or use pre-computed pairwise alignments of seven vertebrate genomes available from the ECR Browser. The rVISTA web server is closely interconnected with the TRANSFAC database, allowing users to either search for matrices present in the TRANSFAC library collection or search for user-defined consensus sequences. rVISTA tool is publicly available at http://rvista.dcode.org/.« less

Out-of-Plane Disorder Effects on the Energy Gaps and Electronic Charge Order in Bi2Sr1.7R0.3CuO6+δ (R = La and Eu)

NASA Astrophysics Data System (ADS)

Kurosawa, Tohru; Takeyama, Kohsaku; Baar, Stefan; Shibata, Yuto; Kataoka, Moeko; Mizuta, Shusei; Yoshida, Hiroshi; Momono, Naoki; Oda, Migaku; Ido, Masayuki

2016-04-01

We performed STM/STS experiments at 8 K in Bi2Sr1.7R0.3CuO6+δ (R-Bi2201) systems that had optimal (OP) hole-doping levels (˜0.17) but different Tc values, 35 K for R = La and 20 K for R = Eu, and examined out-of-plane disorder effects on the superconducting (SC) gap (SCG) and the pseudogap (PG) which is associated with the so-called "checkerboard charge order" (CCO). As out-of-plane disorders are strengthened by replacing La with Eu in OP R-Bi2201, the antinodal PG size ΔPG increases from ˜30 to ˜60 meV, the nodal SCG size ΔSC seems to decrease from ˜7 to ˜4 meV, and the pairing gap amplitude Δ0 or d-wave gap size at the antinodes is almost unchanged (Δ0 ˜ 15 meV). These gap sizes for OP doping in Eu-Bi2201 are comparable to those for an underdoping level of ˜0.1 in La-Bi2201. Although out-of-plane disorders strongly affect the electronic system of the Cu-O plane, they have no effect on the period of the CCO, which is five times the lattice constant (5a) along the Cu-O bond directions for OP doping and 4a for p ˜ 0.1. We suggest that the concentration of holes doped into the Cu-O plane may be an essential factor for determining the period of the CCO.

Thermopower of CexR1-xB6 (R=La, Pr and Nd)

NASA Astrophysics Data System (ADS)

Kim, Moo‑Sung; Nakai, Yuki; Tou, Hideki; Sera, Masafumi; Iga, Fumitoshi; Takabatake, Toshiro; Kunii, Satoru

2006-06-01

The thermopower, S, of CexR1-xB6 (R=La, Pr, Nd) was investigated. S with a positive sign shows a typical behavior observed in the Ce Kondo system, an increase with decreasing temperature at high temperatures and a maximum at low temperatures. The S values of all the systems at high temperatures are roughly linearly dependent on the Ce concentration, indicating the conservation of the single-impurity character of the Kondo effect in a wide x range. However, the maximum value of S, Smax, and the temperature, Tmax, at which Smax is observed exhibit different x dependences between CexLa1-xB6 and CexR1-xB6 (R=Pr, Nd). In CexLa1-xB6, Tmax, which is ˜8 K in CeB6, decreases with decreasing x and converges to ˜1 K in a very dilute alloy and Smax shows an increase below x ˜ 0.1 after decreasing with decreasing x. In CexR1-xB6 (R=Pr, Nd), Tmax shows a weak x dependence but Smax shows a roughly linear decrease in x. These results are discussed from the standpoint of the chemical pressure effect and the Ce-Ce interaction. S in the long-range ordered phase shows very different behaviors between CexPr1-xB6 and CexNd1-xB6.

Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.

PubMed

Edén, Arvid; Andersson, Lars-Magnus; Andersson, Orjan; Flamholc, Leo; Josephson, Filip; Nilsson, Staffan; Ormaasen, Vidar; Svedhem, Veronica; Säll, Christer; Sönnerborg, Anders; Tunbäck, Petra; Gisslén, Magnus

2010-05-01

Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.

Expression of miR-155, miR-146a, and miR-326 in T1D patients from Chile: relationship with autoimmunity and inflammatory markers.

PubMed

García-Díaz, Diego F; Pizarro, Carolina; Camacho-Guillén, Patricia; Codner, Ethel; Soto, Néstor; Pérez-Bravo, Francisco

2018-02-01

Objective The aim of this research was to analyze the expression profile of miR-155, miR-146a, and miR-326 in peripheral blood mononuclear cells (PBMC) of 47 patients with type 1 diabetes mellitus (T1D) and 39 control subjects, as well as the possible association with autoimmune or inflammatory markers. Subjects and methods Expression profile of miRs by means of qPCR using TaqMan probes. Autoantibodies and inflammatory markers by ELISA. Statistical analysis using bivariate correlation. Results The analysis of the results shows an increase in the expression of miR-155 in T1D patients in basal conditions compared to the controls (p < 0.001) and a decreased expression level of miR-326 (p < 0.01) and miR-146a (p < 0.05) compared T1D patients to the controls. miR-155 was the only miRs associated with autoinmmunity (ZnT8) and inflammatory status (vCAM). Conclusion Our data show a possible role of miR-155 related to autoimmunity and inflammation in Chilean patients with T1D.

An ODIP Effort to Map R2R Ocean Data Terms to International Vocabularies

NASA Astrophysics Data System (ADS)

Ferreira, R.; Stocks, K. I.; Arko, R. A.

2014-12-01

The diverseness of terminology used in describing ocean data creates a barrier to efficient discovery and re-use of data, particularly across institutional, programmatic, and disciplinary boundaries. Here we explore the outcomes of a student project to crosswalk terms between the Rolling Deck to Repository (R2R) program and other international systems, as part of the Ocean Data Interoperability Platform (ODIP). R2R is a U.S. program developing and implementing an information management system to preserve and provide access to routine underway data collected by U.S. academic research vessels. R2R participates in ODIP, an international forum for improving interoperability and effective sharing of marine data resources through technical workshops and joint prototypes. The vocabulary mapping effort lays a foundation for future ocean data portals through which users search and access ocean data using familiar terms. R2R describes its data with a suite of controlled vocabularies (http://www.rvdata.us/voc) some of which were developed within R2R or are specific to the U.S. The goal of this student project is to crosswalk local/national vocabularies to authoritative international ones, where they exist, or to vocabularies widely used by ODIP partners. Specifically, R2R developed the following crosswalks: UNOLS ports to SeaDataNet Ports Gazetteer, R2R Device Models to NVS SeaVoX Device Catalog, R2R Organizations to the European Directory of Marine Organizations (EDMO), and R2R chief scientist names to well known professional identifiers such as ORCID, Research Gate, Linkedin, etc. Mappings were done in simple spreadsheets using synonymy relationships, and will be published as part of the R2R Linked Data resources. The level of success in crosswalking was variable. All ports are successfully mapped. Both organizations and device models have initial mappings and R2R has added new terms to EDMO and SeaVoX Device Catalog vocabularies allowing for nearly complete coverage of

Characteristics of surface acoustic waves in (11\\bar 2 0)ZnO film/ R-sapphire substrate structures

NASA Astrophysics Data System (ADS)

Wang, Yan; Zhang, ShuYi; Xu, Jing; Xie, YingCai; Lan, XiaoDong

2018-02-01

(11\\bar 2 0)ZnO film/ R-sapphire substrate structure is promising for high frequency acoustic wave devices. The propagation characteristics of SAWs, including the Rayleigh waves along [0001] direction and Love waves along [1ī00] direction, are investigated by using 3 dimensional finite element method (3D-FEM). The phase velocity ( v p), electromechanical coupling coefficient ( k 2), temperature coefficient of frequency ( TCF) and reflection coefficient ( r) of Rayleigh wave and Love wave devices are theoretically analyzed. Furthermore, the influences of ZnO films with different crystal orientation on SAW properties are also investigated. The results show that the 1st Rayleigh wave has an exceedingly large k 2 of 4.95% in (90°, 90°, 0°) (11\\bar 2 0)ZnO film/ R-sapphire substrate associated with a phase velocity of 5300 m/s; and the 0th Love wave in (0°, 90°, 0°) (11\\bar 2 0)ZnO film/ R-sapphire substrate has a maximum k 2 of 3.86% associated with a phase velocity of 3400 m/s. And (11\\bar 2 0)ZnO film/ R-sapphire substrate structures can be used to design temperature-compensated and wide-band SAW devices. All of the results indicate that the performances of SAW devices can be optimized by suitably selecting ZnO films with different thickness and crystal orientations deposited on R-sapphire substrates.

miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R.

PubMed

Liu, Na; Yang, Hua; Wang, Hong

2018-01-01

In recent years, the aberrant expression of miR-598 in tumorigenesis has been demonstrated, as well as the fact that the IGF-1R pathway is also involved in the development of human gastric cancer (GC). The present study aimed to investigate the molecular mechanisms underlying miR-598-regulated IGF-1R expression in human GC. We analyzed the expression of miR-598 and IGF-1R in GC samples and cells, and evaluated the clinical significance of miR-598 and IGF-1R in GC patients. Furthermore, in vitro and in vivo assays were used to investigate the molecular mechanisms of miR-598 and IGF-1R. miR-598 expression was frequently downregulated in GC tissues and cells, and significantly correlated with poor prognosis, vascular invasion, TNM stage, and lymph node metastases as well as IGF-1R expression. The overexpression of miR-598 obviously inhibited cell proliferation, migration, invasion, and induced cell cycle arrest in the G1/S phase, and increased the apoptosis of GC cells. The overexpression of miR-598 also significantly inhibited ERK1/2 and Akt phosphorylation level. In vivo assay validated the inhibitory effect of miR-598 on tumor growth. Further studies showed that miR-598 inhibited IGF-1R protein expression by directly targeting its 3'-UTR. Besides, over-expression of IGF-1R reversed the inhibitory effects of miR-598, while suppression of IGF-1R expression showed inverse effects. miR-598 suppresses GC cell proliferation, migration and invasion by directly targeting IGF-1R expression. Thus, miR-598 may be a useful target for GC patients.

VizieR Online Data Catalog: EoR0 central field source catalog (Offringa+, 2016)

NASA Astrophysics Data System (ADS)

Offringa, A. R.; Trott, C. M.; Hurley-Walker, N.; Johnston-Hollitt, M.; McKinley, B.; Barry, N.; Beardsley, A. P.; Bowman, J. D.; Briggs, F.; Carroll, P.; Dillon, J. S.; Ewall-Wice, A.; Feng, L.; Gaensler, B. M.; Greenhill, L. J.; Hazelton, B. J.; Hewitt, J. N.; Jacobs, D. C.; Kim, H.-S.; Kittiwisit, P.; Lenc, E.; Line, J.; Loeb, A.; Mitchell, D. A.; Morales, M. F.; Neben, A. R.; Paul, S.; Pindor, B.; Pober, J. C.; Procopio, P.; Riding, J.; Sethi, S. K.; Shankar, N. U.; Subrahmanyan, R.; Sullivan, I. S.; Tegmark, M.; Thyagarajan, N.; Tingay, S. J.; Wayth, R. B.; Webster, R. L.; Wyithe, J. S. B.

2017-05-01

The observations used in this work have been made as part of the MWA EoR project. We have used observations that are centred at RA 0°, Dec. -27°, and recorded between 2013 August and October. The field around this target is referred to as the MWA EoR0 field - one of three fields that were selected based on having weak Galactic foregrounds and passing nearly through zenith at the MWA. The selected 15 nights are listed in Table 1. Of these 15 nights, 3 nights were not included in the analyses because they show RFI or unusual calibration solutions. The MWA can observe 30.72MHz simultaneously. To cover a larger redshift range, a total bandwidth of 138.9-197.7MHz is recorded by observing in two different bands. The low band covers 138.9-169.6MHz and the high band covers 167.0-197.7MHz. Together these cover the HI 21cm line at redshifts 6.1-9.2. The observations have a frequency resolution of 40kHz and time resolution of 0.5s. (1 data file).

Thermal expansion of phosphates with the NaZr2(PO4)3 structure containing lanthanides and zirconium: R 0.33Zr2(PO4)3 ( R = Nd, Eu, Er) and Er0.33(1- x) Zr0.25 x Zr2(PO4)3

NASA Astrophysics Data System (ADS)

Volgutov, V. Yu.; Orlova, A. I.

2015-09-01

Phosphates R 0.33Zr2(PO4)3 ( R = Nd, Eu, or Er) and Er0.33(1- х)Zr0.25Zr2(PO4)3 ( х = 0, 0.25, 0.5, 0.75, 1.0) of the NaZr2(PO4)3 family have been synthesized and investigated by high-temperature X-ray diffraction. The crystallochemical approach is used to obtain compounds with expected small and controllable thermal-expansion parameters. Phosphates with close-to-zero thermal-expansion parameters, including those with low thermal-expansion anisotropy, have been obtained: Nd0.33Zr2(PO4)3 with α a =-2.21 × 10-6 °С-1, α c = 0.81 × 10-6 °С-1, and Δα = 3.02 × 10-6 °С-1 and Er0.08Zr0.19Zr2(PO4)3 with α a =-1.86 × 10-6 °С-1, α c = 1.73 × 10-6 °С-1, and Δα = 3.58 × 10-6 °С-1.

Site-preference and valency for rare-earth sites in (R-Ce)2Fe14B [R =La,Nd] magnets

NASA Astrophysics Data System (ADS)

Alam, Aftab; Khan, Mahmud; McCallum, R. W.; Johnson, D. D.

2013-03-01

Rare-earth (R) permanent magnets of R2Fe14B have technological importance due to their high energy products, and they have two symmetry distinct R-sites (Wyckoff 4f and 4g) that affect chemistry and valence. Designing magnetic behavior and stability via alloying is technologically relevant to reduce critical (expensive) R-content while retaining key properties; cerium, an abundant (cheap) R-element, offers this potential. We calculate magnetic properties and Ce site preference in (R1-xCex)Fe14B [R=La,Nd] using density functional theory (DFT) methods. The Fe moments compare well with neutron scattering data - remain weakly affected by Hubbard U, but improved with spin-orbit coupling. In (La,Ce)2Fe14B, Ce alloys for 0 < x < 1 with a preference for smaller R(4f) sites, as observed, a trend we find unaffected by valence. Whereas in (Nd,Ce)2Fe14B, Ce is predicted to have limited alloying (x < 0.3) with a preference for larger R(4g) sites, resulting in weak partial ordering and segregation. Curie temperatures versus x were predicted for a typical sample processing and verified experimentally. We shall also present some initial results on the critical mixed valency of Ce in related compounds. Work at Ames Laboratory was supported by the U.S. Department of Energy, ARPA-E under the REACT program (0472-1526)

Immobilization of R-ω-transaminase on MnO2 nanorods for catalyzing the conversion of (R)-1-phenylethylamine.

PubMed

Sun, Jian; Cui, Wen-Hui; Du, Kun; Gao, Qian; Du, Mengmeng; Ji, Peijun; Feng, Wei

2017-03-10

R-ɷ-transaminases transfer an amino group from an amino donor (e.g. (R)-1-phenylethylamine) onto an amino acceptor (e.g. pyruvate), resulting a co-product (e.g. d-alanine). This work intends to immobilize R-ɷ-Transaminase on MnO 2 nanorods to achieve multienzyme catalysis. R-ɷ-Transaminase (RTA) and d-amino acid oxidase (DAAO) have been fused to an elastin-like polypeptide (ELP) separately through genetic engineering of the enzymes. ELP-RTA and ELP-DAAO have been separately immobilized on polydopamine-coated MnO 2 nanorods. When the two immobilized enzymes were used together in one pot, the transformation of (R)-1-phenylethylamine was catalyzed by the immobilized ELP-RTA, and the co-product d-alanine was converted back to pyruvate under the catalysis of the immobilized ELP-DAAO, achieving the recycling of pyruvate in situ. Thus pyruvate was maintained at a low concentration in order to reduce its negative effect. On the other hand, the generated H 2 O 2 of ELP-DAAO was decomposed by the MnO 2 nanorods, and the evolved oxygen oxidized the reduced cofactors of ELP-DAAO. Forming the circles of hydrogen peroxide→oxygen→hydrogen peroxide accelerated the deamination reaction. The highly efficient conversion of the co-product d-alanine back to pyruvate accelerated the forming of the pyruvate→d-alanine→pyruvate cycle between the two immobilized enzymes. The coordination of the pyruvate→d-alanine→pyruvate and hydrogen peroxide→oxygen→hydrogen peroxide cycles accelerated the transformation of (R)-1-phenylethylamine. As a result, As a result, the immobilized enzymes achieved a conversion of 98±1.8% in comparison to 69.6±1.2% by free enzymes. Copyright © 2017 Elsevier B.V. All rights reserved.

26 CFR 1.414(r)-0 - Table of contents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... its lines of business. (1) In general. (2) Property and services provided to customers. (i) In general... illustrating property and services provided to customers. § 1.414(r)-3Separate line of business. (a) General... required. (i) Applicability. (ii) Requirement. (iii) Defined benefit minimum. (A) In general. (B) Normal...

From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor.

PubMed

Morini, Gabriella; Bassoli, Angela; Temussi, Piero A

2005-08-25

The sweet taste receptor, a heterodimeric G protein coupled receptor (GPCR) protein, formed by the T1R2 and T1R3 subunits, recognizes several sweet compounds including carbohydrates, amino acids, peptides, proteins, and synthetic sweeteners. Its similarity with the metabotropic glutamate mGluR1 receptor allowed us to build homology models. All possible dimers formed by combinations of the human T1R2 and T1R3 subunits, modeled on the A (closed) or B (open) chains of the extracellular ligand binding domain of the mGluR1 template, yield four ligand binding sites for low-molecular-weight sweeteners. These sites were probed by docking a set of molecules representative of all classes of sweet compounds and calculating the free energy of ligand binding. These sites are not easily accessible to sweet proteins, but docking experiments in silico showed that sweet proteins can bind to a secondary site without entering the deep cleft. Our models account for many experimental observations on the tastes of sweeteners, including sweetness synergy, and can help to design new sweeteners.

Biotransformation of (-)-(1R,4S)-Menthone and (+)-(1S,4R)-Menthone by the Common Cutworm Spodoptera litura Larvae.

PubMed

Marumoto, Shinsuke; Okuno, Yoshiharu; Hagiwara, Yuki; Miyazawa, Mitsuo

2017-08-01

Using biotransformation as a biocatalytic process has the advantage of being able to proceed under mild conditions and with high regio- and enantioselectivity. This study investigated the biotransformation of (-)-(1R,4S)-menthone (1) and (+)-(1S,4R)-menthone (2) by Spodoptera litura larvae. Compound 1 was converted to (-)-(1R,4S)-7-hydroxymenthone (1-1), (+)-(1R,3S,4S)-7-hydroxyneomenthol (1-2) and (-)-(1R,4S,8R)-p-menth-3-one-9-oic acid (1-3). The metabolism of substrate 2 generated three enantiomers of the above metabolites, designated as 2-1 to 2-3, respectively. The C-9 position of (-)-menthone and (+)-menthone was oxidized to carboxylic acid by S. litura, which is a metabolic pathway not observed in any other example of biocatalysis.

Screening of allergic components mediated by H(1)R in homoharringtonine injection through H(1)R/CMC-HPLC/MS.

PubMed

Guo, Ying; Han, Shengli; Cao, Jingjing; Liu, Qi; Zhang, Tao

2014-12-01

It has been reported that the histamine H1 receptor (H(1)R) gene is up-regulated in patients with allergic rhinitis and H(1)R expression level strongly correlates with the severity of allergy symptoms. Drugs for therapy should avoid allergy symptoms, especially for patients with over-expressed H(1)R. Therefore, screening of the components which could induce H(1)R activation is urgently needed for drug safety evaluation. Homoharringtonine injection is a preparation for acute nonlymphocytic leukemia, which is approved by China Food and Drug Administration (CFDA) and US Food and Drug Administration. However, severely adverse reactions often occur with intravenous injection of the preparation. In present study, an H(1)R/CMC model was applied for capturing membrane retained components which could induce H(1)R activation. Retention components were enriched and analyzed by H(1)R/CMC-HPLC/MS. Homoharringtonine was recognized, separated and identified in homoharringtonine injection. Ca(2+) flux assay and p-IP3R expression founded that homoharringtonine retained by the H1 R/CMC model increased phosphorylation of IP3R and promoted cytosolic free Ca(2+) elevation in a dose-dependent manner which further verified the activity of homoharringtonine in activating the H1 R. In conclusion, homoharringtonine was screened and identified as a potential allergic factor. This provides an indication that a patient with over-expressed H1 R should be aware of possible allergic reaction when applying homoharringtonine injection. Copyright © 2014 John Wiley & Sons, Ltd.

An ODIP effort to map R2R ocean data terms to international vocabularies

NASA Astrophysics Data System (ADS)

Ferreira, Renata; Stocks, Karen; Arko, Robert

2014-05-01

The heterogeneity of terminology used in describing data creates a barrier to the efficient discovery and re-use of data, particularly across institutional, programmatic, and disciplinary boundaries. Here we explore the outcomes of a student project to crosswalk terms between the Rolling Deck to Repository (R2R) program and other international systems, as part of the Ocean Data Interoperability Platform (ODIP). R2R is a US program developing and implementing an information management system to preserve and provide access to routine underway data collected by U.S academic research vessels. R2R participates in ODIP, an international forum for improving the interoperability and effective sharing of marine data resources through technical workshops and joint prototypes. The vocabulary mapping effort lays a foundation for future ocean data portals through which users search and access international ocean data using familiar terms. R2R describes its data with a suite of controlled vocabularies (http://www.rvdata.us/voc) some of which were developed locally or are specific to the US. The goal of this student project is to crosswalk local/national vocabularies to authoritative international vocabularies, where they exist, or to vocabularies widely used by ODIP partners. Specifically, R2R developed the following crosswalks: R2R science party names to ORCID person identifiers, UNOLS ports to SeaDataNet Ports Gazetteer, R2R Device Models to NVS SeaVoX Device Catalog, and R2R Organizations to the European Directory of Marine Organizations (EDMO). Mappings were done in simple spreadsheets using synonymy relationships only, and will be published as part of the R2R Linked Data resources. The level of success in crosswalking was variable. The majority of ports were successfully mapped. Differences in the character sets (i.e. whether diacritic marks were used) caused automated matching to fail occasionally, but the number of ports was small enough that these could be manually

Th1 stimulatory proteins of Leishmania donovani: comparative cellular and protective responses of rTriose phosphate isomerase, rProtein disulfide isomerase and rElongation factor-2 in combination with rHSP70 against visceral leishmaniasis.

PubMed

Jaiswal, Anil Kumar; Khare, Prashant; Joshi, Sumit; Kushawaha, Pramod Kumar; Sundar, Shyam; Dube, Anuradha

2014-01-01

In visceral leishmaniasis, the recovery from the disease is always associated with the generation of Th1-type of cellular responses. Based on this, we have previously identified several Th1-stimulatory proteins of Leishmania donovani -triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and elongation factor-2 (EL-2) etc. including heat shock protein 70 (HSP70) which induced Th1-type of cellular responses in both cured Leishmania patients/hamsters. Since, HSPs, being the logical targets for vaccines aimed at augmenting cellular immunity and can be early targets in the immune response against intracellular pathogens; they could be exploited as vaccine/adjuvant to induce long-term immunity more effectively. Therefore, in this study, we checked whether HSP70 can further enhance the immunogenicity and protective responses of the above said Th1-stimulatory proteins. Since, in most of the studies, immunogenicity of HSP70 of L. donovani was assessed in native condition, herein we generated recombinant HSP70 and tested its potential to stimulate immune responses in lymphocytes of cured Leishmania infected hamsters as well as in the peripheral blood mononuclear cells (PBMCs) of cured patients of VL either individually or in combination with above mentioned recombinant proteins. rLdHSP70 alone elicited strong cellular responses along with remarkable up-regulation of IFN-γ and IL-12 cytokines and extremely lower level of IL-4 and IL-10. Among the various combinations, rLdHSP70 + rLdPDI emerged as superior one augmenting improved cellular responses followed by rLdHSP70 + rLdEL-2. These combinations were further evaluated for its protective potential wherein rLdHSP70 + rLdPDI again conferred utmost protection (∼80%) followed by rLdHSP70 + rLdEL-2 (∼75%) and generated a strong cellular immune response with significant increase in the levels of iNOS transcript as well as IFN-γ and IL-12 cytokines which was further supported by the high level of IgG2 antibody

Th1 Stimulatory Proteins of Leishmania donovani: Comparative Cellular and Protective Responses of rTriose Phosphate Isomerase, rProtein Disulfide Isomerase and rElongation Factor-2 in Combination with rHSP70 against Visceral Leishmaniasis

PubMed Central

Jaiswal, Anil Kumar; Khare, Prashant; Joshi, Sumit; Kushawaha, Pramod Kumar; Sundar, Shyam; Dube, Anuradha

2014-01-01

In visceral leishmaniasis, the recovery from the disease is always associated with the generation of Th1-type of cellular responses. Based on this, we have previously identified several Th1-stimulatory proteins of Leishmania donovani -triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and elongation factor-2 (EL-2) etc. including heat shock protein 70 (HSP70) which induced Th1-type of cellular responses in both cured Leishmania patients/hamsters. Since, HSPs, being the logical targets for vaccines aimed at augmenting cellular immunity and can be early targets in the immune response against intracellular pathogens; they could be exploited as vaccine/adjuvant to induce long-term immunity more effectively. Therefore, in this study, we checked whether HSP70 can further enhance the immunogenicity and protective responses of the above said Th1-stimulatory proteins. Since, in most of the studies, immunogenicity of HSP70 of L. donovani was assessed in native condition, herein we generated recombinant HSP70 and tested its potential to stimulate immune responses in lymphocytes of cured Leishmania infected hamsters as well as in the peripheral blood mononuclear cells (PBMCs) of cured patients of VL either individually or in combination with above mentioned recombinant proteins. rLdHSP70 alone elicited strong cellular responses along with remarkable up-regulation of IFN-γ and IL-12 cytokines and extremely lower level of IL-4 and IL-10. Among the various combinations, rLdHSP70 + rLdPDI emerged as superior one augmenting improved cellular responses followed by rLdHSP70 + rLdEL-2. These combinations were further evaluated for its protective potential wherein rLdHSP70 + rLdPDI again conferred utmost protection (∼80%) followed by rLdHSP70 + rLdEL-2 (∼75%) and generated a strong cellular immune response with significant increase in the levels of iNOS transcript as well as IFN-γ and IL-12 cytokines which was further supported by the high level of IgG2 antibody

5. SWITCH TOWER AND JUNCTION OF S.A.R. #1 & S.A.R. ...

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

5. SWITCH TOWER AND JUNCTION OF S.A.R. #1 & S.A.R. #2 TRANSMISSION LINES, MARCH 7, 1916. SCE drawing no. 4932. - Santa Ana River Hydroelectric System, Transmission Lines, Redlands, San Bernardino County, CA

Structures of exocyclic R,R- and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine adducts induced by 1,2,3,4-diepoxybutane.

PubMed

Kowal, Ewa A; Seneviratne, Uthpala; Wickramaratne, Susith; Doherty, Kathleen E; Cao, Xiangkun; Tretyakova, Natalia; Stone, Michael P

2014-05-19

1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N(6) position of adenine in DNA. Two enantiomers of bis-N(6)-dA adducts of DEB have been identified: R,R-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (R,R-DHB-dA), and S,S-N(6),N(6)-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (S,S-DHB-dA) [ Seneviratne , U. , Antsypovich , S. , Dorr , D. Q. , Dissanayake , T. , Kotapati , S. , and Tretyakova , N. ( 2010 ) Chem. Res. Toxicol. 23 , 1556 -1567 ]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have been incorporated into the 5'-d(C(1)G(2)G(3)A(4)C(5)X(6)A(7)G(8)A(9)A(10)G(11))-3':5'-d(C(12)T(13)T(14)C(15)T(16)T(17)G(18)T(19)C(20)C(21)G(22))-3' duplex [X(6) = R,R-DHB-dA (R(6)) or S,S-DHB-dA (S(6))]. The structures of the duplexes were determined by molecular dynamics calculations, which were restrained by experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA adducts are positioned in the major groove of DNA. In both instances, the bulky 3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about the C6-N(6) bond of the bis-alkylated adenine. In both instances, the directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both instances, the anti conformation of the glycosyl bond is maintained, which combined with the out-of-plane rotation about the C6-N(6) bond, allows the complementary thymine, T(17), to remain stacked within the duplex, and form one hydrogen bond with the modified base, between the imine nitrogen of the modified base and the T(17) N3H imino proton. The loss of the second Watson-Crick hydrogen bonding interaction at the lesion sites correlates with the lower thermal stabilities of the R,R- and S,S-DHB-dA duplexes, as

Gastric cancer: the role of insulin-like growth factor 2 (IGF 2) and its receptors (IGF 1R and M6-P/IGF 2R).

PubMed

Pavelić, Kresimir; Kolak, Toni; Kapitanović, Sanja; Radosević, Senka; Spaventi, Sime; Kruslin, Bozo; Pavelić, Jasminka

2003-11-01

Insulin-like growth factor 2 (IGF 2) appears to be involved in the progression of many tumours. It binds to at least two different types of receptor: IGF type 1 (IGF 1R) and mannose 6-phosphate/IGF type 2 (M6-P/IGF 2R). Ligand binding to IGF 1R provokes mitogenic and anti-apoptotic effects. M6-P/IGF 2R has a tumour suppressor function--it mediates IGF 2 degradation. Mutation of M6-P/IGF 2R causes both diminished growth suppression and augmented growth stimulation. The aim of this study was to investigate the role of IGF 2 and its receptors (IGF 1R and IGF 2R) in human gastric cancer. The expression of IGF 2 and its receptors was measured in order to analyse the possible correlation between the activity of these genes and cell proliferation in two different gastric tumour types: diffuse and intestinal. The effect of IGF 1 receptor blockage on cell proliferation and anchorage-independent cell growth was also examined. Increased expression of IGF 2 and IGF 1R genes (at the mRNA and protein level) was found in gastric cancer when compared with non-tumour tissue. Furthermore, there was a significant difference between IGF 2 expression in the more aggressive diffuse type and that in the intestinal type of gastric cancer. Moreover, the IGF 2 peptide level in the culture media obtained from the diffuse type of cancer cells was significantly higher when compared with the intestinal type. The level of IGF 2 peptide in the conditioned media strongly correlated with [3H]thymidine incorporation and cell proliferation. On the contrary, IGF 2R mRNA expression was much higher in the intestinal type of cancer than in the diffuse type. In addition, IGF 2R protein expression was substantially lower with progression of the diffuse cancer type to a higher stage. The alphaIR3 monoclonal antibody strongly inhibited [3H]thymidine incorporation and decreased the number of colonies in soft agar of cells overexpressing IGF 2. These findings suggest that members of the IGF family are involved

Nonstoichiometry in inorganic fluorides: 2. Ionic conductivity of nonstoichiometric M 1 - x R xF2 + x and R 1 - y M yF3 - y crystals ( M = Ca, Sr, Ba; R are rare earth elements)

NASA Astrophysics Data System (ADS)

Sobolev, B. P.; Sorokin, N. I.

2014-11-01

The peak manifestation of nonstoichiometry in fluoride systems in the number of phases with valuable properties and wide homogeneity ranges is 45 MF2- RF3 systems, where M = Ca, Sr, Ba and R are 15 rare earth elements from La to Lu and Y (with Pm and Sc excluded). A deviation from stoichiometry in crystals of the M 1 - x R xF2 + x (CaF2 fluorite type) and R 1 - y M yF3 - y (LaF3 tysonite type) phases is responsible for the fluorine superionic conductivity σ. The range of variation in σ with changes in the qualitative ( M, R) and quantitative ( x, y) compositions in both structure types is very wide. The σ value changes by a factor of 108 in the M 1 - x R xF2 + x phases (at 500 K) and by a factor of 106 in the R 1 - y M yF3 - y phases (at 293 K). Changing compositions, one can also obtain crystals with σ values large enough for their use as fluorine-conducting solid electrolytes. Phases promising for solid electrolytes were revealed in the MFm- RFn systems ( m < n ≤ 4), which were studied within the program of searching for new multicomponent fluoride materials at the Institute of Crystallography, Russian Academy of Sciences (IC RAS). Superionic conductivity is one of the peak manifestations of the influence of defect structure of nonstoichiometric crystals on their properties. The subject of this review is the results of the studies performed at the IC RAS on the ionic conductivity of single crystals of the M 1 - x R xF2 + x and R 1 - y M yF3 - y nonstoichiometric phases.

Nanostructured crystals of fluorite phases Sr1 - x R x F2 + x ( R are rare-earth elements) and their ordering: IV. Study of the optical transmission spectra in the 2-17-μm wavelength range

NASA Astrophysics Data System (ADS)

Fedorov, V. A.; Karimov, D. N.; Komar'kova, O. N.; Krivandina, E. A.; Zhmurova, Z. I.; Sobolev, B. P.

2010-01-01

Transmission spectra of two-component crystals of Sr1- x R x F2+ x ( R = Y, La-Lu; 0 ≤ x ≤ 0.5) in the 1-17-μm wavelength range were studied. The spectral characteristics of these crystals and of single-component crystals of MF2 ( M = Ca, Sr, or Ba) and RF3 ( R = La-Nd) were compared. The transmission cutoff of Sr1- x R x F2+ x crystals is shifted to shorter wavelengths with increasing x. The same tendency is observed with the increasing atomic number R of rare-earth elements for two isoconcentration series of Sr1- x R x F2+ x ( x ˜ 0.10 and 0.28). This tendency is pronounced at large x. The transmission cutoff of Sr1- x R x F2+ x crystals can be varied in the range of from 10.7 to 12.2 μm by changing their qualitative ( R) and quantitative ( x) composition. Hence, these crystals can be assigned to multicomponent fluoride optical materials with controlled optical characteristics. The Sr1- x R x F2+ x crystals, where R = Ce-Sm, were shown to be promising materials for the design of selective optical filters in the 2-10-μm spectral range.

The elusive role of the SPRY2 domain in RyR1

PubMed Central

Willemse, Hermia; Mirza, Shamaruh; Gallant, Esther M; Board, Philip G

2011-01-01

The second of three SPRY domains (SPRY2, S1085-V1208) located in the skeletal muscle ryanodine receptor (RyR1) is contained within regions of RyR1 that influence EC coupling and bind to imperatoxin A, a toxin probe of RyR1 channel gating. We examined the binding of the F loop (P1107-A1121) in SPRY2 to the ASI/basic region in RyR1 (T3471-G3500, containing both alternatively spliced (ASI) residues and neighboring basic amino acids). We then investigated the possible influence of this interaction on excitation contraction (EC) coupling. A peptide with the F loop sequence and an antibody to the SPRY2 domain each enhanced RyR1 activity at low concentrations and inhibited at higher concentrations. A peptide containing the ASI/basic sequence bound to SPRY2 and binding decreased ∼10-fold following mutation or structural disruption of the basic residues. Binding was abolished by mutation of three critical acidic F loop residues. Together these results suggest that the ASI/basic and SPRY2 domains interact in an F loop regulatory module. Although a region that includes the SPRY2 domain influences EC coupling, as does the ASI/basic region, Ca2+ release during ligand- and depolarization-induced RyR1 activation were not altered by mutation of the three critical F loop residues following expression of mutant RyR1 in RyR1-null myotubes. Therefore the electrostatic regulatory interaction between the SPRY2 F loop residues (that bind to imperatoxin A) and the ASI/basic residues of RyR1 does not influence bi-directional DHPR-RyR1 signaling during skeletal EC coupling, possibly because the interaction is interrupted by the influence of factors present in intact muscle cells. PMID:21239886

InsR/IGF1R pathway mediates resistance to EGFR inhibitors in glioblastoma

PubMed Central

Ma, Yufang; Tang, Nan; Thompson, Reid; Mobley, Bret C.; Clark, Steven W.; Sarkaria, Jann N.; Wang, Jialiang

2015-01-01

Purpose Aberrant activation of epidermal growth factor receptor (EGFR) is a hallmark of glioblastoma. However, EGFR inhibitors exhibit at best modest efficacy in glioblastoma. This is in sharp contrast to the observations in EGFR-mutant lung cancer. We examined whether activation of functionally redundant receptor tyrosine kinases (RTKs) conferred resistance to EGFR inhibitors in glioblastoma. Experimental Design We collected a panel of patient-derived glioblastoma xenograft (PDX) lines that maintained expression of wild type or mutant EGFR in serial xenotransplantation and tissue cultures. Using this physiologically relevant platform, we tested the abilities of several RTK ligands to protect glioblastoma cells against an EGFR inhibitor, gefitinib. Based on the screening results, we further developed a combination therapy co-targeting EGFR and insulin receptor (InsR)/insulin-like growth factor 1 receptor (IGF1R). Results Insulin and IGF1 induced significant protection against gefitinib in the majority of EGFR-dependent PDX lines with one exception that did not expression InsR or IGF1R. Blockade of the InsR/IGF1R pathway synergistically improved sensitivity to gefitinib or dacomitinib. Gefitinib alone effectively attenuated EGFR activities and the downstream MEK/ERK pathway. However, repression of AKT and induction of apoptosis required concurrent inhibition of both EGFR and InsR/IGF1R. A combination of gefitinib and OSI-906, a dual InsR/IGF1R inhibitor, was more effective than either agent alone to treat subcutaneous glioblastoma xenograft tumors. Conclusions Our results suggest that activation of the InsR/IGF1R pathway confers resistance to EGFR inhibitors in EGFR-dependent glioblastoma through AKT regulation. Concurrent blockade of these two pathways holds promise to treat EGFR-dependent glioblastoma. PMID:26561558

Genome-wide identification, functional prediction, and evolutionary analysis of the R2R3-MYB superfamily in Brassica napus.

PubMed

Hajiebrahimi, Ali; Owji, Hajar; Hemmati, Shiva

2017-10-01

R2R3-MYB transcription factors (TFs) have been shown to play important roles in plants, including in development and in various stress conditions. Phylogenetic analysis showed the presence of 249 R2R3-MYB TFs in Brassica napus, called BnaR2R3-MYB TFs, clustered into 38 clades. BnaR2R3-MYB TFs were distributed on 19 chromosomes of B. napus. Sixteen gene clusters were identified. BnaR2R3-MYB TFs were characterized by motif prediction, gene structure analysis, and gene ontology. Evolutionary analysis revealed that BnaR2R3-MYB TFs are mainly formed as a result of whole-genome duplication. Orthologs and paralogs of BnaR2R3-MYB TFs were identified in B. napus, B. rapa, B. oleracea, and Arabidopsis thaliana using synteny-based methods. Purifying selection was pervasive within R2R3-MYB TFs. K n /K s values lower than 0.3 indicated that BnaR2R3-MYB TFs are being functionally converged. The role of gene conversion in the formation of BnaR2R3-MYB TFs was significant. Cis-regulatory elements in the upstream regions of BnaR2R3-MYB genes, miRNA targeting BnaR2R3MYB TFs, and post translational modifications were identified. Digital expression data revealed that BnaR2R3-MYB genes were highly expressed in the roots and under high salinity treatment after 24 h. BnaMYB21, BnaMYB141, and BnaMYB148 have been suggested for improving salt-tolerant B. napus. BnaR2R3-MYB genes were mostly up regulated on the 14th day post inoculation with Leptosphaeria biglobosa and L. maculan. BnaMYB150 is a candidate for increased tolerance to Leptospheria in B. napus.

A new human IgG avidity test, using mixtures of recombinant antigens (rROP1, rSAG2, rGRA6), for the diagnosis of difficult-to-identify phases of toxoplasmosis.

PubMed

Drapała, Dorota; Holec-Gąsior, Lucyna; Kur, Józef; Ferra, Bartłomiej; Hiszczyńska-Sawicka, Elżbieta; Lautenbach, Dariusz

2014-07-01

The preliminary diagnostic utility of two mixtures of Toxoplasma gondii recombinant antigens (rROP1+rSAG2 and rROP1+rGRA6) in IgG ELISA and IgG avidity test has been evaluated. A total of 173 serum samples from patients with toxoplasmosis and seronegative people were examined. The sensitivity of IgG ELISA for rROP1+rSAG2 and rROP1+rGRA6 was 91.1% and 76.7%, respectively, while the reactivity for sera from patients where acute toxoplasmosis was suspected was higher, at 100% and 95.4%, respectively, than for people with chronic infection, at 88.2% and 70.6%. In this study a different trend in avidity maturation of IgG antibodies for two mixtures of proteins in comparison with native antigen was observed. The results suggest that a new IgG avidity test using the mixtures of recombinant antigens may be useful for the diagnosis of difficult-to-identify phases of toxoplasmosis. For this reason, selected mixtures after the additional tests on groups of sera with well-defined dates of infection could be used as a better alternative to the native antigens of the parasite in the serodiagnosis of human T. gondii infection. Copyright © 2014 Elsevier Inc. All rights reserved.

Distinct Contributions of T1R2 and T1R3 Taste Receptor Subunits to the Detection of Sweet Stimuli

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

Nie,Y.; Vigues, S.; Hobbs, J.

2005-01-01

The molecular mechanisms by which G protein-coupled receptor (GPCR)-type chemosensory receptors of animals selectively interact with their cognate ligands remain poorly understood. There is growing evidence that many chemosensory receptors exist in multimeric complexes, though little is known about the relative contributions of individual subunits to receptor functions. This study showed that each of the two subunits in the mammalian heteromeric T1R2:T1R3 sweet taste receptor binds sweet stimuli, though with distinct affinities and conformational changes. Furthermore, ligand affinities for T1R3 are drastically reduced by the introduction of a single amino acid change associated with decreased sweet taste sensitivity in mice.more » Thus, individual T1R subunits increase the receptive range of the sweet taste receptor, offering a functional mechanism for phenotypic variations in sweet taste.« less

Ionic conductivity of cold-pressed ceramics from grinding of R0.95M0.05F2.95 solid electrolytes ( R = La, Nd; M = Ca, Sr, Ba) synthesized by reaction in melt

NASA Astrophysics Data System (ADS)

Sorokin, N. I.; Ivanovskaya, N. A.; Sobolev, B. P.

2014-03-01

Cold-pressed ceramics of fluorine-conducting solid electrolytes La1 - y M y F3 - y ( M = Ca, Sr, Ba) and Nd1 - y Ca y F3 - y with y = 0.95 have been synthesized in a melt of RF3 ( R = La, Nd) and MF2 components in a fluorinating atmosphere and ground in a ball mill. The as-prepared ceramics require annealing, during which their porosity decreases and the conductivity is stably increased (by a factor of 250 for the R 1 - y M y F3 - y composition at 293 K). The Nd0.95Ca0.05F2.95 and Nd0.95Ca0.05F2.95 compositions have a maximum ionic conductivity σ(293 K) ˜ 5 × 10-6 Sm/cm. This value is larger (by a factor of about 10) than σ (293 K) for the R 1 - y M y F3 - y ceramics of tysonite phases prepared by mechanochemical synthesis with the cold pressing of reaction products.

Wormholes in R^2-gravity within the f( R, T) formalism

NASA Astrophysics Data System (ADS)

Sahoo, P. K.; Moraes, P. H. R. S.; Sahoo, Parbati

2018-01-01

We propose, as a novelty in the literature, the modeling of wormholes within a particular case of f( R, T) gravity, namely f(R,T)=R+α R2+λ T, with R and T being the Ricci scalar and trace of the energy-momentum tensor, respectively, while α and λ are constants. Although such a functional form application can be found in the literature, those concern compact astrophysical objects, such that no wormhole analysis has been done so far. The quadratic geometric and linear material corrections of this theory render the matter content of the wormhole remarkably able to obey the energy conditions.

R2R - software to speed the depiction of aesthetic consensus RNA secondary structures

PubMed Central

2011-01-01

Background With continuing identification of novel structured noncoding RNAs, there is an increasing need to create schematic diagrams showing the consensus features of these molecules. RNA structural diagrams are typically made either with general-purpose drawing programs like Adobe Illustrator, or with automated or interactive programs specific to RNA. Unfortunately, the use of applications like Illustrator is extremely time consuming, while existing RNA-specific programs produce figures that are useful, but usually not of the same aesthetic quality as those produced at great cost in Illustrator. Additionally, most existing RNA-specific applications are designed for drawing single RNA molecules, not consensus diagrams. Results We created R2R, a computer program that facilitates the generation of aesthetic and readable drawings of RNA consensus diagrams in a fraction of the time required with general-purpose drawing programs. Since the inference of a consensus RNA structure typically requires a multiple-sequence alignment, the R2R user annotates the alignment with commands directing the layout and annotation of the RNA. R2R creates SVG or PDF output that can be imported into Adobe Illustrator, Inkscape or CorelDRAW. R2R can be used to create consensus sequence and secondary structure models for novel RNA structures or to revise models when new representatives for known RNA classes become available. Although R2R does not currently have a graphical user interface, it has proven useful in our efforts to create 100 schematic models of distinct noncoding RNA classes. Conclusions R2R makes it possible to obtain high-quality drawings of the consensus sequence and structural models of many diverse RNA structures with a more practical amount of effort. R2R software is available at http://breaker.research.yale.edu/R2R and as an Additional file. PMID:21205310

R2R--software to speed the depiction of aesthetic consensus RNA secondary structures.

PubMed

Weinberg, Zasha; Breaker, Ronald R

2011-01-04

With continuing identification of novel structured noncoding RNAs, there is an increasing need to create schematic diagrams showing the consensus features of these molecules. RNA structural diagrams are typically made either with general-purpose drawing programs like Adobe Illustrator, or with automated or interactive programs specific to RNA. Unfortunately, the use of applications like Illustrator is extremely time consuming, while existing RNA-specific programs produce figures that are useful, but usually not of the same aesthetic quality as those produced at great cost in Illustrator. Additionally, most existing RNA-specific applications are designed for drawing single RNA molecules, not consensus diagrams. We created R2R, a computer program that facilitates the generation of aesthetic and readable drawings of RNA consensus diagrams in a fraction of the time required with general-purpose drawing programs. Since the inference of a consensus RNA structure typically requires a multiple-sequence alignment, the R2R user annotates the alignment with commands directing the layout and annotation of the RNA. R2R creates SVG or PDF output that can be imported into Adobe Illustrator, Inkscape or CorelDRAW. R2R can be used to create consensus sequence and secondary structure models for novel RNA structures or to revise models when new representatives for known RNA classes become available. Although R2R does not currently have a graphical user interface, it has proven useful in our efforts to create 100 schematic models of distinct noncoding RNA classes. R2R makes it possible to obtain high-quality drawings of the consensus sequence and structural models of many diverse RNA structures with a more practical amount of effort. R2R software is available at http://breaker.research.yale.edu/R2R and as an Additional file.

R2R Eventlogger: Community-wide Recording of Oceanographic Cruise Science Events

NASA Astrophysics Data System (ADS)

Maffei, A. R.; Chandler, C. L.; Stolp, L.; Lerner, S.; Avery, J.; Thiel, T.

2012-12-01

Methods used by researchers to track science events during a science research cruise - and to note when and where these occur - varies widely. Handwritten notebooks, printed forms, watch-keeper logbooks, data-logging software, and customized software have all been employed. The quality of scientific results is affected by the consistency and care with which such events are recorded and integration of multi-cruise results is hampered because recording methods vary widely from cruise to cruise. The Rolling Deck to Repository (R2R) program has developed an Eventlogger system that will eventually be deployed on most vessels in the academic research fleet. It is based on the open software package called ELOG (http://midas.psi.ch/elog/) originally authored by Stefan Ritt and enhanced by our team. Lessons have been learned in its development and use on several research cruises. We have worked hard to find approaches that encourage cruise participants to use tools like the eventlogger. We examine these lessons and several eventlogger datasets from past cruises. We further describe how the R2R Science Eventlogger works in concert with the other R2R program elements to help coordinate research vessels into a coordinated mobile observing fleet. Making use of data collected on different research cruises is enabled by adopting common ways of describing science events, the science instruments employed, the data collected, etc. The use of controlled vocabularies and the practice of mapping these local vocabularies to accepted oceanographic community vocabularies helps to bind shipboard research events from different cruises into a more cohesive set of fleet-wide events that can be queried and examined in a cross-cruise manner. Examples of the use of the eventlogger during multi-cruise oceanographic research programs along with examples of resultant eventlogger data will be presented. Additionally we will highlight the importance of vocabulary use strategies to the success of the

The transcriptional terminator sequences downstream of the covR gene terminate covR/S operon transcription to generate covR monocistronic transcripts in Streptococcus pyogenes.

PubMed

Chiang-Ni, Chuan; Tsou, Chih-Cheng; Lin, Yee-Shin; Chuang, Woei-Jer; Lin, Ming-T; Liu, Ching-Chuan; Wu, Jiunn-Jong

2008-12-31

CovR/S is an important two component regulatory system, which regulates about 15% of the gene expression in Streptococcus pyogenes. The covR/S locus was identified as an operon generating an RNA transcript around 2.5-kb in size. In this study, we found the covR/S operon produced three RNA transcripts (around 2.5-, 1.0-, and 0.8-kb in size). Using RNA transcriptional terminator sequence prediction and transcriptional terminator analysis, we identified two atypical rho-independent terminator sequences downstream of the covR gene and showed these terminator sequences terminate RNA transcription efficiently. These results indicate that covR/S operon generates covR/S transcript and monocistronic covR transcripts.

Clinical impact of circulating miR-133, miR-1291 and miR-663b in plasma of patients with acute myocardial infarction.

PubMed

Peng, Liu; Chun-guang, Qiu; Bei-fang, Li; Xue-zhi, Ding; Zi-hao, Wang; Yun-fu, Li; Yan-ping, Dang; Yang-gui, Liu; Wei-guo, Li; Tian-yong, Hu; Zhen-wen, Huang

2014-05-01

Acute myocardial infarction (AMI) is one of the leading causes for death in both developed and developing countries and it is the single largest cause of death in the United States, responsible for 1 out of every 6 deaths. The objective of this study was to determine microRNA (miRNA) expression in AMI and determine whether miR-133, miR-1291 and miR-663b could be measured in plasma as a biomarker for recurrence. Patients with AMI and those without AMI were retrospectively recruited for a comparison of their plasma miR-133, miR-1291 and miR-663b expression. miR-133, miR-1291 and miR-663b levels were significantly overexpressed in AMI compared with Non-AMI. MiR-133 showed an AUC of 0.912, with a sensitivity of 81.1% and a specificity of 91.2%. The AUC for miR-1291 was 0.695, with a sensitivity of 78.4% and a specificity of 89.5%. The AUC for miR-663b was 0.611, with a sensitivity of 72.4% and a specificity of 76.5%. This study demonstrated that the levels of miR-133, miR-1291 and miR-663b are associated with AMI. The potential of these miRNAs as biomarkers to improve patient stratification according to the risk of AMI and as circulating biomarkers for the AMI progonos warrants further study. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8183629061241474.

Microbial Routes to (2R,3R)-2,3-Butanediol: Recent Advances and Future Prospects.

PubMed

Xie, Neng-Zhong; Chen, Xian-Rui; Wang, Qing-Yan; Chen, Dong; Du, Qi-Shi; Zhou, Guo-Ping; Huang, Ri-Bo

2017-01-01

(2R,3R)-2,3-Butanediol has many industrial applications, such as it is used as an antifreeze agent and low freezing point fuel. In addition, it is particularly important to provide chiral groups in drugs. In recent years, this valuable bio-based chemical has attracted increasing attention, and significant progress has been made in the development of microbial cell factories for (2R,3R)-2,3-butanediol production. This article reviews recent advances and challenges in microbial routes to (2R,3R)-2,3- butanediol production, and highlights the metabolic engineering and synthetic biological approaches used to improve titers, yields, productivities, and optical purities. Finally, a systematic and integrative strategy for developing high-performance microbial cell factories is proposed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval.

PubMed

Ansermot, Nicolas; Albayrak, Ozgür; Schläpfer, Jürg; Crettol, Séverine; Croquette-Krokar, Marina; Bourquin, Michel; Déglon, Jean-Jacques; Faouzi, Mohamed; Scherbaum, Norbert; Eap, Chin B

2010-03-22

Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R)-methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death.

Final Closure Letter for Administrative Complaint Numbers 03R-07-R9, 10R-07-R9 and 01R-11R9

EPA Pesticide Factsheets

On 6-7-2017, ECRCO issued a closure letter for Admin Complaint Numbers 03r-07-r9, 10r-07-r9 and 01r-11-r9 involving the Maricopa County Air Quality Department regarding alleged complaints that MCAQD violated Title 6 of the Civil Rights Act of 1964.

Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice

PubMed Central

Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F.; Vasselli, Joseph R.; Sclafani, Anthony

2015-01-01

Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. PMID:26157055

Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

PubMed

Glendinning, John I; Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F; Vasselli, Joseph R; Sclafani, Anthony

2015-09-01

Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. Copyright © 2015 the American Physiological Society.

Magnetic field structure in Monoceros R2

NASA Technical Reports Server (NTRS)

Jarrett, T. H.; Novak, G.; Xie, T.; Goldsmith, P. F.

1994-01-01

We have carried out polarimetric observations to investigate the geometry of the magnetic field in the giant molecular cloud Monoceros R2. This study is based upon deep R-band charge coupled device (CCD) polarimetry, covering a total area of 0.5 deg(exp 2) of the giant molecular cloud. The data were calibrated using a new technique that relies on obtaining broad-band photometry of stars simultaneously with polarimetric photometry of the Mon R2 fields, thus providing an accurate means of measuring the electric vectors of starlight which is polarized by the fore-ground dust grains aligned by the magnetic field in the Mon R2 GMC. In this work, (1) we were able to continuously trace magnetic field lines from the largest scales in Mon R2 to the detailed structure of the field in the dense core, as determined from infrared polarimetry; and (2) we have found that the ambient field is apparently modified by a large-scale structure in the Mon R2 cloud. The mean angle of polarization for the complete sample we measured is 158 deg, which is roughly coincident with the local Galactic magnetic field (155 deg). The dispersion in the angle of polarization is 33 deg, similar to that found in the Orion GMC. The dispersion in angle of polarization for stars located along the western side of the three CCD fields is 22 deg. The CCD fields are bisected by a dense ridge of gas defining the boundary of an expanding gas shell that recent observational results at millimeter wavelengths now reveal dominates the Mon R2 GMC. Our results suggest th at the expanding shell has distorted the magnetic field lines extending from the core to the northern gas structure comprising Mon R2.

Structures of Exocyclic R,R- and S,S-N6,N6-(2,3-Dihydroxybutan-1,4-diyl)-2′-Deoxyadenosine Adducts Induced by 1,2,3,4-Diepoxybutane

PubMed Central

2015-01-01

1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N6 position of adenine in DNA. Two enantiomers of bis-N6-dA adducts of DEB have been identified: R,R-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (R,R-DHB-dA), and S,S-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (S,S-DHB-dA) [SeneviratneU., AntsypovichS., DorrD. Q., DissanayakeT., KotapatiS., and TretyakovaN. (2010) Chem. Res. Toxicol.23, 1556−156720873715]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have been incorporated into the 5′-d(C1G2G3A4C5X6A7G8A9A10G11)-3′:5′-d(C12T13T14C15T16T17G18T19C20C21G22)-3′ duplex [X6 = R,R-DHB-dA (R6) or S,S-DHB-dA (S6)]. The structures of the duplexes were determined by molecular dynamics calculations, which were restrained by experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA adducts are positioned in the major groove of DNA. In both instances, the bulky 3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about the C6-N6 bond of the bis-alkylated adenine. In both instances, the directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both instances, the anti conformation of the glycosyl bond is maintained, which combined with the out-of-plane rotation about the C6-N6 bond, allows the complementary thymine, T17, to remain stacked within the duplex, and form one hydrogen bond with the modified base, between the imine nitrogen of the modified base and the T17 N3H imino proton. The loss of the second Watson–Crick hydrogen bonding interaction at the lesion sites correlates with the lower thermal stabilities of the R,R- and S,S-DHB-dA duplexes, as compared to the corresponding unmodified duplex. The reduced base stacking at the

The giant molecular cloud Monoceros R2. 1: Shell structure

NASA Technical Reports Server (NTRS)

Xie, Taoling; Goldsmith, Paul F.

1994-01-01

We have obtained a 45 sec resolution, Nyquist-sampled map in CO J = 1-0 covering approximately a 3 deg x 3 deg region of the giant molecular cloud Monoceros R2. The map consists of 167,000 spectra observed with the 15 element focal-plane array system on the FCRAO 14 m telescope. The data reveal that the large-scale structure of Mon R2 is dominated by a is approximately 30 pc diameter largely hemispherical shell containing approximately 4 x 10(exp 4) solar mass of molecular material and expanding at approximately 3-4 km s(exp -1) with symmetric axis roughly along the line of sight. The dynamical timescale of the shell is estimated to be approximately 4 x 10(exp 6) yr, which is consistent with the age of main-sequence stars powering the clusters of reflection nebulea in this region. There is no evidence for a redshifted shell on the far side of the interior 'bubble,' which is largely devoid of molecular material. Distortions of the shell are obvious, suggesting inhomogeneity of the cloud and possible presence of a magnetic field prior to its formation. Dense clumps in Mon R2, including the main core and the GGD 12-15 core, appear to be condensations located on the large shell. The reflection nebulea with their illuminating stars as well as embedded IRAS sources suggest that triggered star formation has taken place over a large part of the Mon R2 shell.

miR15a and miR16 in Chilean type 1 diabetes patients: possible association with apoptosis, inflammatory, or autoimmunity markers.

PubMed

Garcia-Diaz, D F; Camacho-Guillén, P; Codner, E; Pérez-Bravo, F

2018-01-31

Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the progressive destruction of β cells, mediated by the interaction between T cells and several cytokines. The pathogenesis of T1D has established its possible relationship with miRNAs. In this study, we analyze the expression profile of miR-15a and miR-16 in peripheral blood mononuclear cells (PBMCs) and their possible association with apoptosis, inflammation, or autoimmunity markers. 38 T1D patients and 41 control subjects were recruited. mRNAs were analyzed by means of qPCR and TaqMan probes. PBMCs were treated with different concentrations of glucose (baseline, 11 and 25 mM) with or without an inflammatory stimulus as TNF-α (10 ng/ml). A decrease in the levels of the miR-15a expression in basal conditions is observed in T1D patients compared to healthy control subjects (relative units 0.5 vs. 1.8, p < 0.05). This change in miR-15a and miR-16 is not affected by the addition of TNF-α. No association is observed with inflammatory markers (IL-6, TNF-α, vCAM) or apoptosis (bcl2 expression). The relationship with immunological markers shows an interaction effect between miR16 and IA-2 (p < 0.03). TNF-α does not affect the expression profile of miR-15a and miR16 in PBMCs. A weak correlation is observed between miR-16 and with the autoimmunity profile (IA-2 autoantibody).

miR15a and miR16 in Chilean type 1 diabetes patients: possible association with apoptosis, inflammatory, or autoimmunity markers.

PubMed

Garcia-Diaz, D F; Camacho-Guillén, P; Codner, E; Pérez-Bravo, F

2018-01-30

Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the progressive destruction of β cells, mediated by the interaction between T cells and several cytokines. The pathogenesis of T1D has established its possible relationship with miRNAs. In this study, we analyze the expression profile of miR-15a and miR-16 in peripheral blood mononuclear cells (PBMCs) and their possible association with apoptosis, inflammation, or autoimmunity markers. 38 T1D patients and 41 control subjects were recruited. mRNAs were analyzed by means of qPCR and TaqMan probes. PBMCs were treated with different concentrations of glucose (baseline, 11 and 25 mM) with or without an inflammatory stimulus as TNF-α (10 ng/ml). A decrease in the levels of the miR-15a expression in basal conditions is observed in T1D patients compared to healthy control subjects (relative units 0.5 vs. 1.8, p < 0.05). This change in miR-15a and miR-16 is not affected by the addition of TNF-α. No association is observed with inflammatory markers (IL-6, TNF-α, vCAM) or apoptosis (bcl2 expression). The relationship with immunological markers shows an interaction effect between miR16 and IA-2 (p < 0.03). TNF-α does not affect the expression profile of miR-15a and miR16 in PBMCs. A weak correlation is observed between miR-16 and with the autoimmunity profile (IA-2 autoantibody).

76 FR 72869 - Proposed Establishment of Restricted Areas R-5402, R-5403A, R-5403B, R-5403C, R-5403D, R-5403E...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

...-0117; Airspace Docket No. 09-AGL-31] Proposed Establishment of Restricted Areas R-5402, R-5403A, R- 5403B, R-5403C, R-5403D, R-5403E, and R-5403F; Devils Lake, ND AGENCY: Federal Aviation Administration... Camp Grafton Range, the existing R-5401 restricted area surrounding the range is inadequate to satisfy...

Rolling Deck to Repository (R2R): Technical Design - Experiences and Lessons (Invited)

NASA Astrophysics Data System (ADS)

Arko, R. A.; Carbotte, S. M.; Miller, S. P.; Chandler, C. L.; Ferrini, V.; Stocks, K.; Maffei, A. R.; Smith, S. R.; Bourassa, M. A.; McLean, S. J.; Alberts, J. C.

2009-12-01

The NSF-funded Rolling Deck to Repository (R2R) project envisions the academic research fleet as an integrated global observing system, with routine “underway” sensor data flowing directly from research vessels to a central shore-side repository. It is a complex endeavor involving many stakeholders - technicians at sea, data managers on shore, ship schedulers, clearance officers, funding agencies, National Data Centers, data synthesis projects, the science community, and the public - working toward a common goal of acquiring, documenting, archiving, evaluating, and disseminating high-quality scientific data. The technical design for R2R is guided by several key principles: 1) The data pipeline is modular, so that initial stages (e.g. inventory and review of data shipments, posting of catalog records and track maps) may proceed routinely for every cruise, while later stages (e.g. quality assessment and production of file-level metadata) may proceed at different rates for different data types; 2) Cruise documentation (e.g. sailing orders, review/release of data inventories, vessel profiles) is gathered primarily via an authenticated Web portal, linked with the UNOLS scheduling database to synchronize vocabularies and eliminate redundancies; and 3) Every data set will be documented and delivered to the appropriate National Data Center for long-term archiving and dissemination after proprietary holds are cleared, while R2R maintains a master cruise catalog that links all the data sets together. This design accommodates the diversity of instrument types, data volumes, and shipment schedules among fleet operators. During its pilot development period, R2R has solicited feedback at community workshops, UNOLS meetings, and conference presentations, including fleet-wide surveys of current practices and instrument inventories. Several vessel operators began submitting cruise data and documentation during the pilot, providing a test bed for database development and Web

A R2R3-MYB Transcription Factor from Epimedium sagittatum Regulates the Flavonoid Biosynthetic Pathway

PubMed Central

Lv, Haiyan; Luo, Ming; Zeng, Shaohua; Pattanaik, Sitakanta; Yuan, Ling; Wang, Ying

2013-01-01

Herba epimedii (Epimedium), a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Many R2R3-MYB transcription factors (TFs) have been identified to regulate the flavonoid and anthocyanin biosynthetic pathways. However, little is known about the R2R3-MYB TFs involved in regulation of the flavonoid pathway in Epimedium. Here, we reported the isolation and functional characterization of the first R2R3-MYB TF (EsMYBA1) from Epimedium sagittatum (Sieb. Et Zucc.) Maxim. Conserved domains and phylogenetic analysis showed that EsMYBA1 belonged to the subgroup 6 clade (anthocyanin-related MYB clade) of R2R3-MYB family, which includes Arabidopsis AtPAP1, apple MdMYB10 and legume MtLAP1. EsMYBA1 was preferentially expressed in leaves, especially in red leaves that contain higher content of anthocyanin. Alternative splicing of EsMYBA1 resulted in three transcripts and two of them encoded a MYB-related protein. Yeast two-hybrid and transient luciferase expression assay showed that EsMYBA1 can interact with several bHLH regulators of the flavonoid pathway and activate the promoters of dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS). In both transgenic tobacco and Arabidopsis, overexpression of EsMYBA1 induced strong anthocyanin accumulation in reproductive and/or vegetative tissues via up-regulation of the main flavonoid-related genes. Furthermore, transient expression of EsMYBA1 in E. sagittatum leaves by Agrobacterium infiltration also induced anthocyanin accumulation in the wounded area. This first functional characterization of R2R3-MYB TFs in Epimedium species will promote further studies of the flavonoid biosynthesis and regulation in medicinal plants. PMID:23936468

IDH1 R132H mutation regulates glioma chemosensitivity through Nrf2 pathway.

PubMed

Li, Kaishu; Ouyang, Leping; He, Mingliang; Luo, Ming; Cai, Wangqing; Tu, Yalin; Pi, Rongbiao; Liu, Anmin

2017-04-25

Numerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance. Wild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated. Phenotypic differences between IDH1-WT and IDH1 R132H overexpressing cells were evaluated using MTT, cell colony formation assay, scratch test assay and flow cytometry. Expression of IDH1 and its associated targets, nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1), multidrug resistant protein 1 (MRP1) and p53 were analyzed. The IDH1 R132H overexpressing cells were more sensitive to temozolomide than WT and the control, and Nrf2 was significantly decreased in IDH1 R132H overexpressing cells. We found that knocking down Nrf2 could decrease resistance to temozolomide. The nuclear translocation of Nrf2 in IDH1 R132H overexpressing cells was lower than the WT and the control groups after temozolomide treatment. When compared with WT cells, NQO1 expression was reduced in IDH1 R132H cells, especially after temozolomide treatment. P53 was involved in the resistance mechanism of temozolomide mediated by Nrf2 and NQO1. Nrf2 played an important role in IDH1 R132H-mediated drug resistance. The present study provides new insight for glioma chemotherapy with temozolomide.

IDH1 R132H mutation regulates glioma chemosensitivity through Nrf2 pathway

PubMed Central

Luo, Ming; Cai, Wangqing; Tu, Yalin; Pi, Rongbiao; Liu, Anmin

2017-01-01

Purpose Numerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance. Methods Wild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated. Phenotypic differences between IDH1-WT and IDH1 R132H overexpressing cells were evaluated using MTT, cell colony formation assay, scratch test assay and flow cytometry. Expression of IDH1 and its associated targets, nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1), multidrug resistant protein 1 (MRP1) and p53 were analyzed. Results The IDH1 R132H overexpressing cells were more sensitive to temozolomide than WT and the control, and Nrf2 was significantly decreased in IDH1 R132H overexpressing cells. We found that knocking down Nrf2 could decrease resistance to temozolomide. The nuclear translocation of Nrf2 in IDH1 R132H overexpressing cells was lower than the WT and the control groups after temozolomide treatment. When compared with WT cells, NQO1 expression was reduced in IDH1 R132H cells, especially after temozolomide treatment. P53 was involved in the resistance mechanism of temozolomide mediated by Nrf2 and NQO1. Conclusions Nrf2 played an important role in IDH1 R132H-mediated drug resistance. The present study provides new insight for glioma chemotherapy with temozolomide. PMID:28427200

The realistic models of relativistic stars in f (R) = R + αR 2 gravity

NASA Astrophysics Data System (ADS)

Astashenok, Artyom V.; Odintsov, Sergei D.; de la Cruz-Dombriz, Álvaro

2017-10-01

In the context of f(R)=R+α R2 gravity, we study the existence of neutron and quark stars for various α with no intermediate approximation in the system of equations. Analysis shows that for positive α the scalar curvature does not drop to zero at the star surface (as in general relativity) but exponentially decreases with distance. Also the stellar mass bounded by star surface decreases when the value α increases. Nonetheless distant observers would observe a gravitational mass due to appearance of a so-called gravitational sphere around the star. The non-zero curvature contribution to the gravitational mass eventually is shown to compensate the stellar mass decrease for growing α’s. We perform our analysis for several equations of state including purely hadronic configurations as well as hyperons and quark stars. In all cases, we assess that the relation between the parameter α and the gravitational mass weakly depends upon the chosen equation of state. Another interesting feature is the increase of the star radius in comparison with general relativity for stars with masses close to maximal, whereas for intermediate masses 1.4 -1.6 M_⊙ the radius of star depends upon α very weakly. Also the decrease in the mass bounded by star surface may cause the surface redshift to decrease in R 2-gravity when compared to Einsteinian predictions. This effect is shown to hardly depend upon the observed gravitational mass. Finally, for negative values of α our analysis shows that outside the star the scalar curvature has damped oscillations but the contribution of the gravitational sphere into the gravitational mass increases indefinitely with radial distance putting into question the very existence of such relativistic stars.

Insight into a conformation of the PNA-PNA duplex with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones

NASA Astrophysics Data System (ADS)

Maitarad, Amphawan; Poomsuk, Nattawee; Vilaivan, Chotima; Vilaivan, Tirayut; Siriwong, Khatcharin

2018-04-01

Suitable conformations for peptide nucleic acid (PNA) self-hybrids with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones (namely, acpcPNA and epi-acpcPNA, respectively) were investigated based on molecular dynamics simulations. The results revealed that hybridization of the acpcPNA was observed only in the parallel direction, with a conformation close to the P-type structure. In contrast, self-hybrids of the epi-acpcPNA were formed in the antiparallel and parallel directions; the antiparallel duplex adopted the B-form conformation, and the parallel duplex was between B- and P-forms. The calculated binding energies and the experimental data indicate that the antiparallel epi-acpcPNA self-hybrid was more stable than the parallel duplex.

The association of circulating miR-30a, miR-29 and miR-133 with white-coat hypertension.

PubMed

Huang, Yu-Qing; Huang, Cheng; Chen, Ji-Yan; Li, Jie; Feng, Ying-Qing

2016-12-01

The aim of the present study was to investigate the association of circulating miRNAs with white-coat hypertension (WCH) and further analyze whether miRNAs could be as potential biomarkers for WCH. Quantitative reverse transcriptase PCR (qRT-PCR) was used to evaluate the expression of selected miRNAs. The area under the receiver-operating characteristic curve was used to evaluate diagnostic accuracy. MiR-30a yielded an AUC of 0.984 (95% CI: 0.001-1.00; p < 0.001) and 0.816 (95% CI: 0.718-0.915; p < 0.001); miR-29 yielded an AUC of 0.955 (95% CI: 0.913-0.998; p < 0.001) and 0.799 (95% CI: 0.697-0.902; p < 0.001); miR-133 yielded an AUC of 0.949 (95% CI: 0.900-0.999; p < 0.001) and 0.713 (95% CI: 0.593-0.834; p < 0.001), respectively. The study suggested that miR-30a, miR-29 and miR-133 have great potential to be noninvasive screening tools for WCH detection.

Synthesis of novel (2R,4R)- and (2S,4S)-iso dideoxynucleosides with exocyclic methylene as potential antiviral agents.

PubMed

Yoo, Su Jeong; Kim, Hea Ok; Lim, Yoongho; Kim, Jeongmin; Jeong, Lak Shin

2002-01-01

Novel (2R,4R)- and (2S,4S)-iso dideoxynucleosides with exocyclic methylene have been designed and synthesized, based on the lead BMS-200475 (3) which exhibited potent anti-HBV activity. For the synthesis of D types of (2R,4R)-nucleosides, L-xylose was converted to the key intermediate 14. The intermediate 14 was converted to the uracil derivative 4a and the cytosine derivative 4b. Compound 14 was also converted to the purine derivatives such as adenine derivative 4c, hypoxanthine derivative 4d, and guanine derivative 4e. The corresponding L types of (2S,4S)-enantiomers were more efficiently synthesized from the commercially available 1,2-isopropylidene-D-xylose (20) than the synthetic method used in the synthesis of (2R,4R)-nucleosides. The key intermediate 25 was converted to the pyrimidine analogues 5a and 5b and the purine derivatives 5c, 5d, and 5e using the similar method used in the preparation of 4c, 4d, and 4e. The synthesized final (2R,4R)- and (2S,4S)-nucleosides were tested against several viruses such as HIV-1, HSV-1, HSV-2, HCMV and HBV. (2R,4R)-Adenine analogue 4c exhibited potent anti-HBV activity (EC(50)=1.5 microM in 2.2.15 cells) among compounds tested, while (2R,4R)-uracil derivative 4a was the most active against HCMV among compounds tested and (2R,4R)-adenine derivative 4c was found to be moderately active against the same virus. However, the corresponding (2S,4S)-isomers were found to be totally inactive against all tested viruses. Both (2R,4R)-adenine derivative 4c and (2S,4S)-adenine analogue 5c were totally resistant to the adenosine deaminase like iso-ddA (1). From the molecular modeling study the hydroxymethyl side chains of BMS-200475 (3) and 4c were almost overlapped, indicating that 4c may be suitable for phosphorylation by cellular kinases like the lead 3, but some discrepancy between two bases was observed, indicating why 4c is less potent against HBV than 3. It is concluded that discovery of (2R,4R)-adenine analogue 4c as potent

Salivary leptin and TAS1R2/TAS1R3 polymorphisms are related to sweet taste sensitivity and carbohydrate intake from a buffet meal in healthy young adults.

PubMed

Han, Pengfei; Keast, Russell S J; Roura, Eugeni

2017-11-01

The influence of sweet taste sensitivity on food intake is not well understood. We investigated the involvement of salivary leptin and SNP of the sweet taste receptor genes (TAS1R2/TAS1R3) on sweet taste sensitivity, sensory-specific satiety (SSS) and macronutrient intake in healthy human adults. In all, nineteen high sweet sensitivity (HS) and eleven low sweet sensitivity (LS) subjects were classified based on the sweetness perception of one solution (9 mm sucrose) forced-choice triangle test. All participants completed a randomised crossover design experiment where they consumed one of three iso-energetic soup preloads differing in primary taste quality (sweet, non-sweet taste-control or no-taste energy-control). A period of 1 h after the preload, participants were offered a buffet meal consisting of foods varying in taste (sweet or non-sweet) and fat content. Subjective measures included hunger/fullness and SSS for sweetness. Saliva and buccal cells were collected to measure leptin level and to study the TAS1R2/TAS1R3 specific SNP, respectively. Salivary leptin concentrations were significantly higher in LS than HS participants (P<0·05). In addition, HS showed stronger sweet SSS compared with LH participants (P<0·05), and consumed less carbohydrate (% energy) and more non-sweet foods than LS (P<0·01 and P<0·05, respectively). Alleles from each TAS1R2 locus (GG compared with AA alleles of rs12033832, and CT/CC compared with TT alleles of rs35874116) were related to higher consumption of carbohydrates (% energy) and higher amount of sweet foods, respectively (P<0·05). In contrast, no associations were found for the TAS1R3 alleles. These results contribute to understand the links between taste sensitivity, macronutrient appetite and food consumption.

Derivation of the MMPI-2-RF Henry-Heilbronner Index-r (HHI-r) scale.

PubMed

Henry, George K; Heilbronner, Robert L; Algina, James; Kaya, Yasemin

2013-01-01

The 15-item Henry-Heilbronner Index (HHI) was published in 2006 as an MMPI-2 embedded measure of psychological response validity. When the MMPI-2 was revised in 2008 only 11 of the 15 original HHI items were retained on the MMPI-2-RF, prohibiting use of the HHI as an embedded validity indicator on the MMPI-2-RF. Using the original HHI sample an 11-item version of the HHI, the HHI-r, was evaluated for use as an embedded measure of psychological response validity for the MMPI-2-RF. The 11-item HHI-r was very similar to the HHI in classification accuracy. An HHI-r cutoff score of ≥7 was associated with a classification accuracy rate of 84.0%, good sensitivity (68.9%), and high specificity (93.2%) in identifying symptom exaggeration in personal injury and disability litigants versus non-litigating head-injured patients. These preliminary results suggest the HHI-r functions in a manner similar to the original HHI as a measure of psychological response validity, and may be used by psychologists and neuropsychologists as an MMPI-2-RF embedded validity indicator.

HPLC–electrospray mass spectrometric assay for the determination of (R,R)-fenoterol in rat plasma

PubMed Central

Siluk, Danuta; Kim, Hee Seung; Cole, Tyler; Wainer, Irving W.

2008-01-01

A fast and specific liquid chromatography–mass spectrometry method for the determination of (R,R)-fenoterol ((R,R)-Fen) in rat plasma has been developed and validated. (R,R)-Fen was extracted from 125 µl of plasma using solid phase extraction and analyzed on Atlantis HILIC Silica 3 µm column. The mobile phase was composed of acetonitrile:ammonium acetate (pH 4.1; 20 mM) (85:15, v/v), at a flow rate of 0.2 ml/min. The lower limit of detection (LLOD) was 2 ng/ml . The procedure was validated and applied to the analysis of plasma samples from rats previously administered (R,R)-Fen in an intravenous bolus. PMID:18617349

HPLC-electrospray mass spectrometric assay for the determination of (R,R)-fenoterol in rat plasma.

PubMed

Siluk, Danuta; Kim, Hee Seung; Cole, Tyler; Wainer, Irving W

2008-11-04

A fast and specific liquid chromatography-mass spectrometry method for the determination of (R,R)-fenoterol ((R,R)-Fen) in rat plasma has been developed and validated. (R,R)-Fen was extracted from 125 microl of plasma using solid phase extraction and analyzed on Atlantis HILIC Silica 3 microm column. The mobile phase was composed of acetonitrile:ammonium acetate (pH 4.1; 20mM) (85:15, v/v), at a flow rate of 0.2 ml/min. The lower limit of detection (LLOD) was 2 ng/ml . The procedure was validated and applied to the analysis of plasma samples from rats previously administered (R,R)-Fen in an intravenous bolus.

Relationship between the melanocortin-1 receptor (MC1R) variant R306ter and physiological responses to mechanical or thermal stimuli in Labrador Retriever dogs.

PubMed

Perez, Tania E; Mealey, Katrina L; Burke, Neal S; Grubb, Tamara L; Court, Michael H; Greene, Stephen A

2017-03-01

Variants in the MC1R gene have been associated with red hair color and sensitivity to pain in humans. The study objective was to determine if a relationship exists between MC1R genotype and physiological thermal or mechanical nociceptive thresholds in Labrador Retriever dogs. Prospective experimental study. Thirty-four Labrador Retriever dogs were included in the study following public requests for volunteers. Owner consent was obtained and owners verified that their dog was apparently not experiencing pain and had not been treated for pain during the previous 14 days. The study was approved by the Institutional Animal Care and Use Committee. Nociceptive thresholds were determined from a mean of three thermal and five mechanical replications using commercially available algometers. Each dog was genotyped for the previously described MC1R variant (R306ter). Data were analyzed using one-way anova with post hoc comparisons using Tukey's test (p < 0.05). Thirteen dogs were homozygous wild-type (WT/WT), nine were heterozygous (WT/R306ter), and eight were homozygous variant (R306ter/R306ter) genotype. Four dogs could not be genotyped. A significant difference (p = 0.04) in mechanical nociceptive thresholds was identified between dogs with the WT/WT genotype (12.1±2.1 N) and those with the WT/R306ter genotype (9.2±2.4 N). A difference in mechanical, but not thermal, nociceptive threshold was observed between wild-type and heterozygous MC1R variants. Differences in nociceptive thresholds between homozygous R306ter variants and other genotypes for MC1R were not observed. Compared with the wild-type MC1R genotype, nociceptive sensitivity to mechanical force in dogs with a single variant R306ter allele may be greater. However, in contrast to the reported association between homozygous MC1R variants (associated with red hair color) and nociception in humans, we found no evidence of a similar relationship in dogs with the homozygous variant genotype. Copyright © 2017

Search for Compounds with Hypoglycemic Activity in the Series of 1-[2-(1H-Tetrazol-5-yl)-R1-phenyl]-3-R2-phenyl(ethyl)ureas and R1-Tetrazolo[1,5-c]quinazolin-5(6H)-ones

PubMed Central

Antypenko, Oleksii M.; Kovalenko, Sergiy I.; Zhernova, Galina O.

2016-01-01

Methods of 1-[2-(1H-tetrazol-5-yl)-R1-phenyl]-3-R2-phenyl(ethyl)ureas and R1-tetrazolo[1,5-c]quinazolin-5(6H)-ones synthesis were designed. IR, LC-MS, 1H NMR, and elemental analysis data evaluated the structure and purity of the obtained compounds. Different products, depending on the reaction conditions, were distinguished and discussed. The preliminary hypoglycemic activity of 36 synthesized compounds was revealed. Docking studies to 11β-hydroxysteroid dehydrogenase 1, γ-peroxisome proliferator-activated receptor, and dipeptidyl peptidase-4 were conducted. Eight of these substances were further tested on glucocorticoid-induced insulin resistance models, namely glucose tolerance, oral rapid insulin, and adrenalin tests. One of the most active compounds turned out to be tetrazolo[1,5-c]quinazolin-5(6H)-one 3.1, exceeding the reference drugs Metformin (50 and 200 mg/kg) and Gliclazide (50 mg/kg). PMID:27222601

Rolling Deck to Repository (R2R): Standards and Semantics for Open Access to Research Data

NASA Astrophysics Data System (ADS)

Arko, Robert; Carbotte, Suzanne; Chandler, Cynthia; Smith, Shawn; Stocks, Karen

2015-04-01

In recent years, a growing number of funding agencies and professional societies have issued policies calling for open access to research data. The Rolling Deck to Repository (R2R) program is working to ensure open access to the environmental sensor data routinely acquired by the U.S. academic research fleet. Currently 25 vessels deliver 7 terabytes of data to R2R each year, acquired from a suite of geophysical, oceanographic, meteorological, and navigational sensors on over 400 cruises worldwide. R2R is working to ensure these data are preserved in trusted repositories, discoverable via standard protocols, and adequately documented for reuse. R2R maintains a master catalog of cruises for the U.S. academic research fleet, currently holding essential documentation for over 3,800 expeditions including vessel and cruise identifiers, start/end dates and ports, project titles and funding awards, science parties, dataset inventories with instrument types and file formats, data quality assessments, and links to related content at other repositories. A Digital Object Identifier (DOI) is published for 1) each cruise, 2) each original field sensor dataset, 3) each post-field data product such as quality-controlled shiptrack navigation produced by the R2R program, and 4) each document such as a cruise report submitted by the science party. Scientists are linked to personal identifiers, such as the Open Researcher and Contributor ID (ORCID), where known. Using standard global identifiers such as DOIs and ORCIDs facilitates linking with journal publications and generation of citation metrics. Since its inception, the R2R program has worked in close collaboration with other data repositories in the development of shared semantics for oceanographic research. The R2R cruise catalog uses community-standard terms and definitions hosted by the NERC Vocabulary Server, and publishes ISO metadata records for each cruise that use community-standard profiles developed with the NOAA Data

Enantioselective separation and online affinity chromatographic characterization of R,R- and S,S-fenoterol.

PubMed

Beigi, Farideh; Bertucci, Carlo; Zhu, Weizhong; Chakir, Khalid; Wainer, Irving W; Xiao, Rui-Ping; Abernethy, Darrell R

2006-11-01

rac-Fenoterol is a beta2-adrenoceptor agonist (beta2-AR) used in the treatment of asthma. It has two chiral centers and is marketed as a racemic mixture of R,R'- and S,S'-fenoterol (R-F and S-F). Here we report the separation of the R-F and S-F enantiomers and the evaluation of their binding to and activation of the beta2-AR. R-F and S-F were separated from the enantiomeric mixture by chiral chromatography and absolute configuration determined by circular dichroism. Beta2-AR binding was evaluated using frontal affinity chromatography with a stationary phase containing immobilized membranes from HEK-293 cells that express human beta2-AR and standard membrane binding studies using the same membranes. The effect of R-F and S-F on cardiomyocyte contractility was also investigated using freshly isolated adult rat cardiomyocytes. Chiral chromatography of rac-fenoterol yielded separated peaks with an enantioselectivity factor of 1.21. The less retained peak was assigned the absolute configuration of S-F and the more retained peak R-F. Frontal chromatography using membrane-bound beta2-AR as the stationary phase and rac-3H-fenoterol as a marker ligand showed that addition of increasing concentrations of R-F to the mobile phase produced concentration-dependent decreases in rac-3H-fenoterol retention, while similar addition of S-F produced no change in rac-3H-fenoterol retention. The calculated dissociation constant of R-F was 472 nM and the number of available binding sites 176 pmol/column, which was consistent with the results from the membrane binding study 460 +/- 55 nM (R-F) and 109,000 +/- 10,400 nM (S-F). In the cardiomyocytes, R-F increased maximum contractile response from (265 +/- 11.6)% to (306 +/- 11.8)% of resting cell length (P < 0.05) and reduced EC50 from -7.0 +/- 0.270 to -7.1 +/- 0.2 log[M] (P < 0.05), while S-F had no significant effect. Previous studies have shown that rac-fenoterol acts as an apparent beta2-AR/G(s) selective agonist and fully restores

LRRK2 G2385R and R1628P Mutations Are Associated with an Increased Risk of Parkinson's Disease in the Malaysian Population

PubMed Central

Chua, Jing Yi; Lim, Thien Thien; Mohamed Ibrahim, Norlinah; Tan, Ai Huey; Eow, Gaik Bee; Abdul Aziz, Zariah; Puvanarajah, Santhi Datuk; Viswanathan, Shanthi; Lim, Soo Kun; Tan, Li Ping; Chong, Yip Boon; Tan, Chong Tin; Zhao, Yi; Tan, E. K.

2014-01-01

The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson's disease (PD). The G2019S variant is commonly found in North African Arab and Caucasian PD patients, but this locus is monomorphic in Asians. The G2385R and R1628P variants are associated with a higher risk of developing PD in certain Asian populations but have not been studied in the Malaysian population. Therefore, we screened the G2385R and R1628P variants in 1,202 Malaysian subjects consisting of 695 cases and 507 controls. The G2385R and R1628P variants were associated with a 2.2-fold (P = 0.019) and 1.2-fold (P = 0.054) increased risk of PD, respectively. Our data concur with other reported findings in Chinese, Taiwanese, Singaporean, and Korean studies. PMID:25243190

Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans

NASA Technical Reports Server (NTRS)

Zhang, Rong; Iwasaki, Kenichi; Zuckerman, Julie H.; Behbehani, Khosrow; Crandall, Craig G.; Levine, Benjamin D.; Blomqvist, C. G. (Principal Investigator)

2002-01-01

Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (< 0.15 Hz) is probably mediated by both sympathetic nerve activity and intrinsic vasomotor rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other

Tellurium(0) as a ligand: synthesis and characterization of 2-pyridyltellurolates of platinum(II) and structures of [Pt{2-Te-3-(R)C5H3N}2Te(PR'3)] (R = H or Me).

PubMed

Chauhan, Rohit Singh; Kedarnath, G; Wadawale, Amey; Muñoz-Castro, Alvaro; Arratia-Perez, Ramiro; Jain, Vimal K; Kaim, Wolfgang

2010-05-03

Treatment of toluene solutions of the ditellurides [Te(2){C(5)H(3)N(R)-3}(2)] (R = H or Me) with [Pt(PPh(3))(4)] yielded two types of complexes, [Pt{2-Te-3-(R)C(5)H(3)N}(2)(PPh(3))(2)] (1a-d) as the major products and [Pt{2-Te-3-(R)C(5)H(3)N}(2)Te(PPh(3))] (2a-d) as minor products. The above complexes can also be obtained by the reaction of [PtCl(2)(PR'(3))(2)] (PR'(3) = PPh(3) or PPh(2)(2-C(5)H(4)N)) with 2 equiv of Na(2-Te-C(5)H(3)R). The complexes were characterized by elemental analyses and UV-vis, NMR ((1)H and (31)P), and (in part) XPS spectroscopy. The molecular structures of [Pt(2-Te-C(5)H(4)N)(2)Te(PPh(3))] (2a) and [Pt{2-Te-C(5)H(3)(Me)N}(2)Te(PPh(3))] (2b) were established by single crystal X-ray diffraction. Both complexes exhibit a distorted square-planar configuration at the platinum(II) centers. The two mutually trans positioned 2-pyridinetellurolate ligands [2-Te-C(5)H(3)(R)N] coordinate to the central platinum atom in a monodentate fashion through the tellurium atoms. The tellurium(0) atom adopts a "bent T" configuration as it is bridging the 2-Te- C(5)H(3)(R)N molecules via N-Te-N bonds (166 degrees angle) and coordinates to Pt(II) in the trans position to PPh(3). The novel bis(pyridine)tellurium(0) arrangement resembles the bis(pyridine)iodonium structure. The calculated NICS indices and ELF functions clearly show that the compounds 2a and 2b are aromatic in the region defined by the Te-C-N-Te-Pt five-membered rings.

The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules.

PubMed

Goralski, Kerry B; Lou, Ganlu; Prowse, Matthew T; Gorboulev, Valentin; Volk, Christopher; Koepsell, Hermann; Sitar, Daniel S

2002-12-01

In renal proximal tubules, the organic cation transporters rOCT1 and rOCT2 are supposed to mediate the first step in organic cation secretion. We investigated whether previously described differences in amantadine and tetraethylammonium (TEA) uptake into isolated renal proximal tubules could be explained by differences in their transport by rOCT1 and rOCT2. By expressing rOCT1 and rOCT2 in Xenopus oocytes and HEK 293 cells, we demonstrated that both transporters translocated amantadine. In Xenopus oocytes, the inhibitory potency of several rOCT1/2 inhibitors was similar for amantadine compared to TEA uptake and supports amantadine transport by rOCT1 and rOCT2. In proximal tubules, procainamide, quinine, cyanine(863), choline, and guanidine in concentrations that inhibit rOCT1/2-mediated TEA or amantadine uptake in Xenopus oocytes exhibited no effect on amantadine uptake. At variance, these inhibitors blocked TEA uptake into proximal tubules. Amantadine and TEA transport were sensitive to modulation by 25 mM bicarbonate. The effect of bicarbonate on organic cation transport was dependent on substrate (amantadine or TEA), cell system (oocytes, HEK 293 cells, or proximal tubules), and transporter (rOCT1 or rOCT2). In proximal tubules, only amantadine uptake was stimulated by bicarbonate. The data suggested that rat renal proximal tubules contain an organic cation transporter in addition to rOCT1 and rOCT2 that mediates amantadine uptake and requires bicarbonate for optimal function. TEA uptake by the basolateral membrane may be mediated mainly by rOCT1 and rOCT2, but these transporters may be in a different functional or regulatory state when expressed in cells or oocytes compared with expression in vivo.

Association of Corynebacterium pseudotuberculosis recombinant proteins rCP09720 or rCP01850 with rPLD as immunogens in caseous lymphadenitis immunoprophylaxis.

PubMed

Silva, Mara Thais de Oliveira; Bezerra, Francisco Silvestre Brilhante; de Pinho, Rodrigo Barros; Begnini, Karine Rech; Seixas, Fabiana Kommling; Collares, Tiago; Portela, Ricardo Dias; Azevedo, Vasco; Dellagostin, Odir; Borsuk, Sibele

2018-01-02

Caseous lymphadenitis (CLA) is a chronic disease responsible for significant economic losses in sheep and goat breeding worldwide. The treatment for this disease is not effective, and an intense vaccination schedule would be the best control strategy. In this study, we evaluated the associations of rCP09720 or rCP01850 proteins from Corynebacterium pseudotuberculosis with recombinant exotoxin phospholipase D (rPLD) as subunit vaccines in mice. Four experimental groups (10 animals each) were immunized with a sterile 0.9% saline solution (G1), rPLD (G2), rPLD + rCP09720 (G3), and rPLD + rCP01850 (G4). The mice received two doses of each vaccine at a 21-day interval and were challenged 21 days after the last immunization. The animals were evaluated daily for 40 days after the challenge, and mortality rate was recorded. The total IgG production level increased significantly in the experimental groups on day 42 after the first vaccination. Similarly, higher levels of specific IgG2a were observed in experimental groups G2, G3, and G4 compared to the IgG1 levels on day 42. G4 showed a significant (p < .05) humoral response against both antigens of the antigenic formulations. The cellular immune response induced by immunization was characterized by a significant (p < .05) production of interferon-γ compared to that in the control, while the concentrations of interleukin (IL)-4 and IL-12 were not significant in any group. A significant increase of tumor necrosis factor was observed only in G4. The survival rates after the challenge were 30% (rPLD), 40% (rPLD + rCP09720), and 50% (rPLD + rCP01850). Thus, the association of rCP01850 with rPLD resulted in the best protection against the challenge with C. pseudotuberculosis and induced a more intense type 1 T-helper cell immune response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and structure of R{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (R = Rb or Cs)

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

Serezhkin, V. N., E-mail: lserezh@samsu.ru; Peresypkina, E. V.; Grigor’eva, V. A.

2015-01-15

Crystals Rb{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (I) and Cs{sub 2}[UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}] (II) have been synthesized and studied by IR spectroscopy and X-ray diffraction. Crystals I are monoclinic, with the following parameters: a = 12.2118(5) Å, b = 10.2545(3) Å, c = 11.8754(4) Å, β = 110.287(1)°, sp. gr. C2/c, Z = 4, and R = 0.0523. Crystals II are orthorhombic, with a = 13.7309(3) Å, b = 10.5749(2) Å, c = 10.1891(2) Å, sp. gr. Pnma, Z = 4, and R = 0.0411. The basic structural units of crystals I and II are one-core complexes [UO{submore » 2}(NO{sub 3}){sub 2}(NCS){sub 2}]{sup 2−}, which belong to the crystallochemical group cis-AB{sub 2}{sup 01}M{sub 2}{sup 1} (A = UO{sub 2}{sup 2+}, B{sup 01} = NO{sub 3}{sup −}, M{sup 1} = NCS{sup −}), which are combined into a framework via electrostatic interactions with ions of alkaline metals R (R = Rb or Cs). The structural features of crystals I and II, which condition the formation of [UO{sub 2}(NO{sub 3}){sub 2}(NCS){sub 2}]{sup 2−} complexes with a cis rather than a trans position of isothiocyanate ions in the coordination sphere of uranyl ions, are discussed.« less

(2R,3S,2”R,3”R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract

PubMed Central

Balemba, Onesmo B.; Stark, Timo D.; Lösch, Sofie; Patterson, Savannah; McMillan, John S.; Mawe, Gary M.; Hofmann, Thomas

2014-01-01

Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca2+) imaging was used to analyze the effect of GBB on Ca2+ flashes and Ca2+ waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1–5 and M7, and (2R,3S,2”R,3”R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2”R,3”R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2”R,3”R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca2+ flashes and Ca2+ waves. GBB, M3 and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials. L-type Ca2+ channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2”R,3”R)-manniflavanone. GBB and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3S,2”R,3”R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2”R,3”R)-manniflavanone relax smooth muscle by inhibiting L-type Ca2+ channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. PMID:26081368

Assessing the accuracy of predictive models for numerical data: Not r nor r2, why not? Then what?

PubMed Central

2017-01-01

Assessing the accuracy of predictive models is critical because predictive models have been increasingly used across various disciplines and predictive accuracy determines the quality of resultant predictions. Pearson product-moment correlation coefficient (r) and the coefficient of determination (r2) are among the most widely used measures for assessing predictive models for numerical data, although they are argued to be biased, insufficient and misleading. In this study, geometrical graphs were used to illustrate what were used in the calculation of r and r2 and simulations were used to demonstrate the behaviour of r and r2 and to compare three accuracy measures under various scenarios. Relevant confusions about r and r2, has been clarified. The calculation of r and r2 is not based on the differences between the predicted and observed values. The existing error measures suffer various limitations and are unable to tell the accuracy. Variance explained by predictive models based on cross-validation (VEcv) is free of these limitations and is a reliable accuracy measure. Legates and McCabe’s efficiency (E1) is also an alternative accuracy measure. The r and r2 do not measure the accuracy and are incorrect accuracy measures. The existing error measures suffer limitations. VEcv and E1 are recommended for assessing the accuracy. The applications of these accuracy measures would encourage accuracy-improved predictive models to be developed to generate predictions for evidence-informed decision-making. PMID:28837692

Rolling Deck to Repository (R2R): Building the Data Pipeline - Initial Results

NASA Astrophysics Data System (ADS)

Arko, R. A.; Clark, P. D.; Rioux, M. A.; McGovern, T. M.; Deering, T. W.; Hagg, R. K.; Payne, A. A.; Fischman, D. E.; Ferrini, V.

2009-12-01

The NSF-funded Rolling Deck to Repository (R2R) project is working with U.S. academic research vessel operators to ensure the documentation and preservation of data from routine “underway” (meteorological, geophysical, and oceanographic) sensor systems. A standard pipeline is being developed in which data are submitted by vessel operators directly to a central repository; inventoried in an integrated fleet-wide catalog; organized into discrete data sets with persistent unique identifiers; associated with essential cruise-level metadata; and delivered to the National Data Centers for archiving and dissemination. Several vessels including Atlantis, Healy, Hugh R. Sharp, Ka'imikai-O-Kanaloa, Kilo Moana, Knorr, Marcus G. Langseth, Melville, Oceanus, Roger Revelle, and Thomas G. Thompson began submitting data and documentation to R2R during the project’s pilot phase, and a repository infrastructure has been established. Cruise metadata, track maps, and data inventories are published at the R2R Web portal, with controlled vocabularies drawn from community standards (e.g. International Council for the Exploration of the Sea (ICES) ship codes). A direct connection has been established to the University-National Oceanographic Laboratory System (UNOLS) Ship Time Request and Scheduling System (STRS) via Web services to synchronize port codes and cruise schedules. A secure portal is being developed where operators may login to upload sailing orders, review data inventories, and create vessel profiles. R2R has established a standard procedure for submission of data to the National Geophysical Data Center (NGDC) that incorporates persistent unique identifiers for cruises, data sets, and individual files, using multibeam data as a test bed. Once proprietary holds are cleared and a data set is delivered to NGDC, the R2R catalog record is updated with the URL for direct download and it becomes immediately available to integration and synthesis projects such as the NSF

MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals.

PubMed

Ying, Hou-Qun; Peng, Hong-Xin; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Sun, Hui-Ling; Liu, Xian; Chen, Jie; Lin, Kang; Wang, Shu-Kui

2016-11-15

Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.

Thermal and fluid flow analyses of sounding rocket experiment 74-21/2R and 74-21/3R. [low gravity crystallization of a 27.8 percent ammonium chloride

NASA Technical Reports Server (NTRS)

Robertson, S. J.

1979-01-01

The thermal convective velocities during the 4-21/2R and 74-21/3R flight tests were calculated. The 74-21/2R and 74-21/3R ground tests were analyzed using a convection formula. Thermal convection velocities of 0.1 to 0.5 cm/sec were calculated for the 74-21/2R and 74-21/3R ground tests which were two to four orders of magnitude greater than for the flight tests. For the 74-21/2R flight test, solutal effects do not produce any convective motion. For the 74-21/3R flight test closed form convection equations estimated the solutal convective velocities on the order of 1/0.003 cm/sec.

Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors.

PubMed

Hata, Shuko; Ise, Kazue; Azmahani, Abdullah; Konosu-Fukaya, Sachiko; McNamara, Keely May; Fujishima, Fumiyoshi; Shimada, Keiji; Mitsuzuka, Koji; Arai, Yoichi; Sasano, Hironobu; Nakamura, Yasuhiro

2017-12-01

Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored. The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT). DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity. Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

DLEU2, frequently deleted in malignancy, functions as a critical host gene of the cell cycle inhibitory microRNAs miR-15a and miR-16-1

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

Lerner, Mikael; Harada, Masako; Loven, Jakob

The microRNAs miR-15a and miR-16-1 are downregulated in multiple tumor types and are frequently deleted in chronic lymphocytic leukemia (CLL), myeloma and mantle cell lymphoma. Despite their abundance in most cells the transcriptional regulation of miR-15a/16-1 remains unclear. Here we demonstrate that the putative tumor suppressor DLEU2 acts as a host gene of these microRNAs. Mature miR-15a/miR-16-1 are produced in a Drosha-dependent process from DLEU2 and binding of the Myc oncoprotein to two alterative DLEU2 promoters represses both the host gene transcript and levels of mature miR-15a/miR-16-1. In line with a functional role for DLEU2 in the expression of themore » microRNAs, the miR-15a/miR-16-1 locus is retained in four CLL cases that delete both promoters of this gene and expression analysis indicates that this leads to functional loss of mature miR-15a/16-1. We additionally show that DLEU2 negatively regulates the G1 Cyclins E1 and D1 through miR-15a/miR-16-1 and provide evidence that these oncoproteins are subject to miR-15a/miR-16-1-mediated repression under normal conditions. We also demonstrate that DLEU2 overexpression blocks cellular proliferation and inhibits the colony-forming ability of tumor cell lines in a miR-15a/miR-16-1-dependent way. Together the data illuminate how inactivation of DLEU2 promotes cell proliferation and tumor progression through functional loss of miR-15a/miR-16-1.« less

Magnetic behavior of R 2Co 14B hydrides (R = La, Pr, Sm, Gd, Tb and Y)

NASA Astrophysics Data System (ADS)

Zhang, L. Y.; Pourarian, F.; Wallace, W. E.

1988-08-01

The structure and magnetic properties of R 2Co 14B sysstems(R = La, Pr, Nd, Sm, Gd, Tb and Y) and their hydrides were studied by means of bulk magnetometry. All R 2Co 14B hydrides presently studied occur in the tetragonal Nd 2Fe 14B-type crystal structure. The composition-temperature isotherms measured fro selected Gd- and Nd- containing systems exhibit some indication of a platuau pressure at higher hydrogen concentrations. Hydrogenation expands the unit volume, Vc, by 1.5 to 3.0%, depending on the nature of R and the content of hydrogen. It was found that introduction of hydrogen into the lattice decreases Ms of the Co sublittice. This is attributed to the effect of electron charge transfer from Hto Co-3d sublittice. Hydrogennation significantly decreases the anistropy fields, HA, and the spin-reorientation transition temperatur, TSR, for Prand Tb-based intermetallics. The results indicates that the hydrogen makes the compounds magnetically softer, which is attributed to the influence of hydrogen on both the 3d and R sublittices. Two types of spin-reorientation transition for the Nd 2Co 14B system were observed. Hydrogenaration reduces both the low transition temperature, TSR 1, and the high transition temperature, TSR 2, which is explained using the Boltich-Wallace mechanism.

Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations

NASA Technical Reports Server (NTRS)

Koh, J.; Brown, T. E.; Beightol, L. A.; Eckberg, D. L.

1998-01-01

We studied the effects of mechanical lung inflation on respiratory frequency R-R interval and arterial pressure fluctuations in nine healthy young adults undergoing elective orthopedic surgery. We conducted this research to define the contribution of pulmonary and thoracic stretch receptor input to respiratory sinus arrhythmia. We compared fast Fourier transform spectral power during three modes of ventilation: (1) spontaneous, frequency-controlled (0.25 Hz) breathing, (2) intermittent positive pressure ventilation (0.25 Hz, with a tidal volume of 8 ml/kg) and (3) high frequency jet ventilation (5.0 Hz, 2.5 kg/cm2), after sedation and vecuronium paralysis. Mean R-R intervals, arterial pressures and arterial blood gas levels were comparable during all three breathing conditions. Respiratory frequency systolic pressure spectral power was comparable during spontaneous breathing and conventional mechanical ventilation, but was significantly reduced during high frequency jet ventilation (P < 0.05). Respiratory frequency R-R interval spectral power (used as an index of respiratory sinus arrhythmia) declined dramatically with sedation and muscle paralysis (P < 0.05), but was greater during conventional mechanical, than high frequency jet ventilation (P < 0.05). These results suggest that although phasic inputs from pulmonary and thoracic stretch receptors make a statistically significant contribution to respiratory sinus arrhythmia, that contribution is small.

[Study on the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse].

PubMed

Wang, Hui; Zhang, Jiaxiang; Li, Shulong; Zha, Wansheng; Wang, Feng; Zhu, Qixing

2015-07-01

To study the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (ODMLT). On the first days, intradermal injection by 50% TCE and the amount of FCA mixture 100 µl for initial sensitization; on 4, 7, 10 days, painted abdominal skin by 100 µl 50% TCE for three sensitization, on 17, 19 days, painted on the back skin by 100 µl 30% TCE for initial excitation and the last challenge; 24 h before each challenge, PKSI-527+TCE group received intraperitoneal injection by inhibitor PKSI-527 (50 mg/kg); solvent control group treat without TCE and sensitization and excitation reagent the same proportion of olive oil and acetone mixture, blank control group without any treatment. Before killing the mouse, renal weight and body weight were recorded. The renals and plasma were separated at 24 h, 48 h, 72 h and 7 d after the last challenge and observed pathological of the renals. Expression of B1R and B2R in renal were examined by immunofluorescence technique. Plasma were examined by ELISA for BK. The renal pathological examination revealed the apparent damage of TCE sensitized mice which compared to solvent control group showed obvious cellular infiltration, vacuolar degeneration of renal tubular epithelial cells. The renal damage of PKSI-527+TCE-sensitized groups which compared to the corresponding point of TCE-sensitized groups showed significantly reduced. The expression of BK in 24 h, 48 h and 72 h TCE-sensitized groups were significant higher than solvent control group and related TCE non-sensitized groups (P < 0.05) and 72 h point compared to the corresponding point of PKSI-527+TCE group was also increased, the difference was statistically significant (P < 0.05). The expression levels of B1R and B2R in the kidney in 24 h, 48 h, 72 h and 7 d TCE-sensitized groups were obviously higher than solvent control group and related TCE non

1/ r potential in higher dimensions

NASA Astrophysics Data System (ADS)

Chakraborty, Sumanta; Dadhich, Naresh

2018-01-01

In Einstein gravity, gravitational potential goes as 1/r^{d-3} in d non-compactified spacetime dimensions, which assumes the familiar 1 / r form in four dimensions. On the other hand, it goes as 1/r^{α }, with α =(d-2m-1)/m, in pure Lovelock gravity involving only one mth order term of the Lovelock polynomial in the gravitational action. The latter offers a novel possibility of having 1 / r potential for the non-compactified dimension spectrum given by d=3m+1. Thus it turns out that in the two prototype gravitational settings of isolated objects, like black holes and the universe as a whole - cosmological models, the Einstein gravity in four and mth order pure Lovelock gravity in 3m+1 dimensions behave in a similar fashion as far as gravitational interactions are considered. However propagation of gravitational waves (or the number of degrees of freedom) does indeed serve as a discriminator because it has two polarizations only in four dimensions.

Electronic and optical properties of La-doped S r3I r2O7 epitaxial thin films

NASA Astrophysics Data System (ADS)

Souri, M.; Terzic, J.; Johnson, J. M.; Connell, J. G.; Gruenewald, J. H.; Thompson, J.; Brill, J. W.; Hwang, J.; Cao, G.; Seo, A.

2018-02-01

We have investigated structural, transport, and optical properties of tensile strained (Sr1-xL ax ) 3I r2O7 (x =0 , 0.025, 0.05) epitaxial thin films. While high-Tc superconductivity is predicted theoretically in the system, we have observed that all of the samples remain insulating with finite optical gap energies and Mott variable-range hopping characteristics in transport. Cross-sectional scanning transmission electron microscopy indicates that structural defects such as stacking faults appear in this system. The insulating behavior of the La-doped S r3I r2O7 thin films is presumably due to disorder-induced localization and ineffective electron doping of La, which brings to light the intriguing difference between epitaxial thin films and bulk single crystals of the iridates.

Important influence of respiration on human R-R interval power spectra is largely ignored

NASA Technical Reports Server (NTRS)

Brown, T. E.; Beightol, L. A.; Koh, J.; Eckberg, D. L.

1993-01-01

Frequency-domain analyses of R-R intervals are used widely to estimate levels of autonomic neural traffic to the human heart. Because respiration modulates autonomic activity, we determined for nine healthy subjects the influence of breathing frequency and tidal volume on R-R interval power spectra (fast-Fourier transform method). We also surveyed published literature to determine current practices in this burgeoning field of scientific inquiry. Supine subjects breathed at rates of 6, 7.5, 10, 15, 17.1, 20, and 24 breaths/min and with nominal tidal volumes of 1,000 and 1,500 ml. R-R interval power at respiratory and low (0.06-0.14 Hz) frequencies declined significantly as breathing frequency increased. R-R interval power at respiratory frequencies was significantly greater at a tidal volume of 1,500 than 1,000 ml. Neither breathing frequency nor tidal volume influenced average R-R intervals significantly. Our review of studies reporting human R-R interval power spectra showed that 51% of the studies controlled respiratory rate, 11% controlled tidal volume, and 11% controlled both respiratory rate and tidal volume. The major implications of our analyses are that breathing parameters strongly influence low-frequency as well as respiratory frequency R-R interval power spectra and that this influence is largely ignored in published research.

Haudenosaunee Territory for Consultation Purposes (EPA.TRIBCONSULTBND_R2)

EPA Pesticide Factsheets

Layer for displaying areas in New York State that are of interest to Region 2 Haudenosaunee tribes for consultation on environmental issues. The boundaries are based on a hard copy map provided by Janice Whitney of R2/DEPP. See the following URLs for scans of source maps: http://r2quickplace1.r02.epa.gov/QuickPlace/r2gis/Main.nsf/$defaultview/50AA19DAB434F06685257154004F8180/$File/morgan-map.gif?OpenElementhttp://r2quickplace1.r02.epa.gov/QuickPlace/r2gis/Main.nsf/$defaultview/50AA19DAB434F06685257154004F8180/$File/indiannation_land_claim_areas_time_life.jpg?OpenElement

Mutations Inactivating Herpes Simplex Virus 1 MicroRNA miR-H2 Do Not Detectably Increase ICP0 Gene Expression in Infected Cultured Cells or Mouse Trigeminal Ganglia.

PubMed

Pan, Dongli; Pesola, Jean M; Li, Gang; McCarron, Seamus; Coen, Donald M

2017-01-15

Herpes simplex virus 1 (HSV-1) latency entails the repression of productive ("lytic") gene expression. An attractive hypothesis to explain some of this repression involves inhibition of the expression of ICP0, a lytic gene activator, by a viral microRNA, miR-H2, which is completely complementary to ICP0 mRNA. To test this hypothesis, we engineered mutations that disrupt miR-H2 without affecting ICP0 in HSV-1. The mutant virus exhibited drastically reduced expression of miR-H2 but showed wild-type levels of infectious virus production and no increase in ICP0 expression in lytically infected cells, which is consistent with the weak expression of miR-H2 relative to the level of ICP0 mRNA in that setting. Following corneal inoculation of mice, the mutant was not significantly different from wild-type virus in terms of infectious virus production in the trigeminal ganglia during acute infection, mouse mortality, or the rate of reactivation from explanted latently infected ganglia. Critically, the mutant was indistinguishable from wild-type virus for the expression of ICP0 and other lytic genes in acutely and latently infected mouse trigeminal ganglia. The latter result may be related to miR-H2 being less effective in inhibiting ICP0 expression in transfection assays than a host microRNA, miR-138, which has previously been shown to inhibit lytic gene expression in infected ganglia by targeting ICP0 mRNA. Additionally, transfected miR-138 reduced lytic gene expression in infected cells more effectively than miR-H2. While this study provides little support for the hypothesis that miR-H2 promotes latency by inhibiting ICP0 expression, the possibility remains that miR-H2 might target other genes during latency. Herpes simplex virus 1 (HSV-1), which causes a variety of diseases, can establish lifelong latent infections from which virus can reactivate to cause recurrent disease. Latency is the most biologically interesting and clinically vexing feature of the virus. Ever since

R{sub 4}Ir{sub 13}Ge{sub 9} (R=La, Ce, Pr, Nd, Sm) and RIr{sub 3}Ge{sub 2} (R=La, Ce, Pr, Nd): Crystal structures with nets of Ir atoms

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

Yarema, Maksym; Swiss Federal Laboratories for Materials Science and Technology; Zaremba, Oksana

The crystal structures of the new ternary compounds Sm{sub 4}Ir{sub 13}Ge{sub 9} and LaIr{sub 3}Ge{sub 2} were determined and refined on the basis of single-crystal X-ray diffraction data. They belong to the Ho{sub 4}Ir{sub 13}Ge{sub 9} (oP52, Pmmn) and CeCo{sub 3}B{sub 2} (hP5, P6/mmm) structure types, respectively. The formation of isotypic compounds R{sub 4}Ir{sub 13}Ge{sub 9} with R=La, Ce, Pr, Nd, and RIr{sub 3}Ge{sub 2} with R=Ce, Pr, Nd, was established by powder X-ray diffraction. The RIr{sub 3}Ge{sub 2} (R=La, Ce, Pr, Nd) compounds exist only in as-cast samples and decompose during annealing at 800 Degree-Sign C with the formationmore » of R{sub 4}Ir{sub 13}Ge{sub 9}. The structure of Sm{sub 4}Ir{sub 13}Ge{sub 9} contains intersecting, slightly puckered nets of Ir atoms (4{sup 4})(4{sup 3}.6){sub 2}(4.6{sup 2}){sub 2} and (4{sup 4}){sub 2}(4{sup 3}.6){sub 4}(4.6{sup 2}){sub 2} that are perpendicular to [0 1 1] as well as to [0 -1 1] and [0 0 1]. The Ir atoms are surrounded by Ge atoms that form tetrahedra or square pyramids (where the layers intersect). The Sm and additional Ir atoms (in trigonal-planar coordination) are situated in channels along [1 0 0] (short translation vector). In the structure of LaIr{sub 3}Ge{sub 2} the Ir atoms form planar Kagome nets (3.6.3.6) perpendicular to [0 0 1]. These nets alternate along the short translation vector with layers of La and Ge atoms. - Graphical abstract: The crystal structures contain the nets of Ir atoms as main structural motif: R{sub 4}Ir{sub 13}Ge{sub 9} contains intersecting slightly puckered nets of Ir atoms, whereas in the structure of RIr{sub 3}Ge{sub 2} the Ir atoms form planar Kagome nets. Highlights: Black-Right-Pointing-Pointer The Ir-rich ternary germanides R{sub 4}Ir{sub 13}Ge{sub 9} (R=La, Ce, Pr, Nd, Sm) and RIr{sub 3}Ge{sub 2} (R=La, Ce, Pr, Nd) have been synthesized. Black-Right-Pointing-Pointer The RIr{sub 3}Ge{sub 2} compounds exist only in as-cast samples and decompose during annealing

Significant reduction of acute cardiac allograft rejection by selective janus kinase-1/3 inhibition using R507 and R545.

PubMed

Deuse, Tobias; Hua, Xiaoqin; Taylor, Vanessa; Stubbendorff, Mandy; Baluom, Muhammad; Chen, Yan; Park, Gary; Velden, Joachim; Streichert, Thomas; Reichenspurner, Hermann; Robbins, Robert C; Schrepfer, Sonja

2012-10-15

Selective inhibition of lymphocyte activation through abrogation of signal 3-cytokine transduction emerges as a new strategy for immunosuppression. This is the first report on the novel Janus kinase (JAK)1/3 inhibitors R507 and R545 for prevention of acute allograft rejection. Pharmacokinetic and in vitro enzyme inhibition assays were performed to characterize the drugs. Heterotopic Brown Norway-Lewis heart transplantations were performed to study acute cardiac allograft rejection, graft survival, suppression of cellular host responsiveness, and antibody production. Therapeutic and subtherapeutic doses of R507 (60 and 15 mg/kg 2 times per day) and R545 (20 and 5 mg/kg 2 times per day) were compared with those of tacrolimus (Tac; 4 and 1 mg/kg once per day). Plasma levels of R507 and R545 were sustained high for several hours. Cell-based enzyme assays showed selective inhibition of JAK1/3-dependent pathways with 20-fold or greater selectivity over JAK2 and Tyrosine kinase 2 kinases. After heart transplantation, both JAK1/3 inhibitors reduced early mononuclear graft infiltration, even significantly more potent than Tac. Intragraft interferon-γ release was significantly reduced by R507 and R545, and for interleukin-10 suppression, they were even significantly more potent than Tac. Both JAK1/3 inhibitors and Tac were similarly effective in reducing the host Th1 and Th2, but not Th17, responsiveness and similarly prevented donor-specific immunoglobulin M antibody production. Subtherapeutic and therapeutic R507 and R545 doses prolonged the mean graft survival and were similarly effective as 1 and 4 mg/kg Tac, respectively. In combination regimens, however, only R507 showed highly beneficial synergistic drug interactions with Tac. Both R507 and R545 are potent novel immunosuppressants with favorable pharmacokinetics and high JAK1/3 selectivity, but only R507 synergistically interacts with Tac.

r.randomwalk v1.0, a multi-functional conceptual tool for mass movement routing

NASA Astrophysics Data System (ADS)

Mergili, M.; Krenn, J.; Chu, H.-J.

2015-09-01

We introduce r.randomwalk, a flexible and multi-functional open source tool for backward- and forward-analyses of mass movement propagation. r.randomwalk builds on GRASS GIS, the R software for statistical computing and the programming languages Python and C. Using constrained random walks, mass points are routed from defined release pixels of one to many mass movements through a digital elevation model until a defined break criterion is reached. Compared to existing tools, the major innovative features of r.randomwalk are: (i) multiple break criteria can be combined to compute an impact indicator score, (ii) the uncertainties of break criteria can be included by performing multiple parallel computations with randomized parameter settings, resulting in an impact indicator index in the range 0-1, (iii) built-in functions for validation and visualization of the results are provided, (iv) observed landslides can be back-analyzed to derive the density distribution of the observed angles of reach. This distribution can be employed to compute impact probabilities for each pixel. Further, impact indicator scores and probabilities can be combined with release indicator scores or probabilities, and with exposure indicator scores. We demonstrate the key functionalities of r.randomwalk (i) for a single event, the Acheron Rock Avalanche in New Zealand, (ii) for landslides in a 61.5 km2 study area in the Kao Ping Watershed, Taiwan; and (iii) for lake outburst floods in a 2106 km2 area in the Gunt Valley, Tajikistan.

Optically active antifungal azoles. XII. Synthesis and antifungal activity of the water-soluble prodrugs of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone.

PubMed

Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K

2001-09-01

1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.

An open and extensible framework for spatially explicit land use change modelling in R: the lulccR package (0.1.0)

NASA Astrophysics Data System (ADS)

Moulds, S.; Buytaert, W.; Mijic, A.

2015-04-01

Land use change has important consequences for biodiversity and the sustainability of ecosystem services, as well as for global environmental change. Spatially explicit land use change models improve our understanding of the processes driving change and make predictions about the quantity and location of future and past change. Here we present the lulccR package, an object-oriented framework for land use change modelling written in the R programming language. The contribution of the work is to resolve the following limitations associated with the current land use change modelling paradigm: (1) the source code for model implementations is frequently unavailable, severely compromising the reproducibility of scientific results and making it impossible for members of the community to improve or adapt models for their own purposes; (2) ensemble experiments to capture model structural uncertainty are difficult because of fundamental differences between implementations of different models; (3) different aspects of the modelling procedure must be performed in different environments because existing applications usually only perform the spatial allocation of change. The package includes a stochastic ordered allocation procedure as well as an implementation of the widely used CLUE-S algorithm. We demonstrate its functionality by simulating land use change at the Plum Island Ecosystems site, using a dataset included with the package. It is envisaged that lulccR will enable future model development and comparison within an open environment.

circ-SHKBP1 Regulates the Angiogenesis of U87 Glioma-Exposed Endothelial Cells through miR-544a/FOXP1 and miR-379/FOXP2 Pathways.

PubMed

He, Qianru; Zhao, Lini; Liu, Yunhui; Liu, Xiaobai; Zheng, Jian; Yu, Hai; Cai, Heng; Ma, Jun; Liu, Libo; Wang, Ping; Li, Zhen; Xue, Yixue

2018-03-02

Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which have been considered to mediate diverse tumorigenesis including angiogenesis. The present study aims to elucidate the potential role and molecular mechanism of circ-SHKBP1 in regulating the angiogenesis of U87 glioma-exposed endothelial cells (GECs). The expression of circ-SHKBP1, but not linear SHKBP1, was significantly upregulated in GECs compared with astrocyte-exposed endothelial cells (AECs). circ-SHKBP1 knockdown inhibited the viability, migration, and tube formation of GECs dramatically. The expressions of miR-379/miR-544a were downregulated in GECs, and circ-SHKBP1 functionally targeted miR-544a/miR-379 in an RNA-induced silencing complex (RISC) manner. Dual-luciferase reporter assay demonstrated that forkhead box P1/P2 (FOXP1/FOXP2) were targets of miR-544a/miR-379. The expressions of FOXP1/FOXP2 were upregulated in GECs, and silencing of FOXP1/FOXP2 inhibited the viability, migration, and tube formation of GECs. Meanwhile, FOXP1/FOXP2 promoted angiogenic factor with G patch and FHA domains 1 (AGGF1) expression at the transcriptional level. Furthermore, knockdown of AGGF1 suppressed the viability, migration, and tube formation of GECs via phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK)1/2 pathways. Taken together, the present study demonstrated that circ-SHKBP1 regulated the angiogenesis of GECs through miR-544a/FOXP1 and miR-379/FOXP2 pathways, and these findings might provide a potential target and effective strategy for combined therapy of gliomas. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Differentiation of Forebrain and Hippocampal Dopamine 1-Class Receptors, D1R and D5R, in Spatial Learning and Memory

PubMed Central

Sariñana, Joshua; Tonegawa, Susumu

2017-01-01

Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R- specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory. PMID:26174222

The effect of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel and normal cell lines.

PubMed

Alileche, Abdelkrim; Hampikian, Greg

2017-08-09

Nullomer peptides are the smallest sequences absent from databases of natural proteins. We first began compiling a list of absent 5-amino acid strings in 2006 (1). We report here the effects of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel, derived from human cancers of 9 organs (kidney, ovary, skin melanoma, lung, brain, lung, colon, prostate and the hematopoietic system), and four normal cell lines (endothelial HUVEC, skin fibroblasts BJ, colon epithelial FHC and normal prostate RWPE-1). NCI-60 cancer cell panel and four normal cell lines were cultured in vitro in RPMI1640 supplemented with 10% Hyclone fetal bovine serum and exposed for 48 h to 5 μM, 25 μM and 50 μM of peptides 9R, 9S1R and 124R. Viability was assessed by CCK-8 assay. For peptide ATP depletion effects, one cell line representing each organ in the NCI-60 panel, and four normal cell lines were exposed to 50 μM of peptides 9R, 9S1R and 124R for 3 h. The ATP content was assessed in whole cells, and their supernatants. Peptides 9S1R and 9R are respectively lethal to 95 and 81.6% of the 60 cancer cell lines tested. Control peptide 124R has no effect on the growth of these cells. Especially interesting the fact that peptides 9R and 9S1R are capable of killing drug-resistant and hormone-resistant cell lines, and even cancer stem cells. Peptides 9R and 9S1R have a broader activity spectrum than many cancer drugs in current use, can completely deplete cellular ATP within 3 h, and are less toxic to 3 of the 4 normal cell lines tested than they are to several cancers. Nullomer peptides 9R and 9S1R have a large broad lethal effect on cancer cell lines derived from nine organs represented in the NCI-60 panel. This broad activity crosses many of the categorical divisions used in the general classification of cancers: solid vs liquid cancers, drug sensitive vs drug resistant, hormone sensitive vs hormone resistant, cytokine sensitive vs cytokine non sensitive, slow growing vs rapid

Absolute structure and structure-function relationships of 4R,2‧R and 4S,2‧S Pidotimod®

NASA Astrophysics Data System (ADS)

Sarno, Simone; Manzo, Angelo M.; Ferraris, Davide M.; Miggiano, Riccardo; Rizzi, Menico; Palin, Luca; Boccaleri, Enrico; Milanesio, Marco

2017-11-01

Pidotimod® is a dipeptide with widely recognized immunomodulatory properties and with particularly beneficial effects for the treatment of acute respiratory and urinary tract infections. Pidotimod® presents two chiral centres which originate four stereoisomers. (4R,2‧S, 4S,2‧R, 4R,2‧R and 4S,2‧S). To date, only the 4R,2‧S and 4S,2‧R stereoisomers are reported in the literature. We report here the absolute crystal structure of the 4R,2‧R and 4S,2‧S diastereoisomers of Pidotimod®, obtained by crystals grown by slow evaporation of a mixture of water and ethanol. The analysis of the crystal structures revealed the key role of a solvent water molecule in the crystal packing engaged in an extended hydrogen bonds network. This water-assisted H-bond network explained the recalcitrance of 4R,2‧R and 4S,2‧S Pidotimod® to crystallize in pure ethanol, despite their high solubility, and the growth of well-diffracting crystals only in presence of water. Hence, Pidotimod®4R,2‧R and 4S,2‧S stereoisomers markedly differ from the 4R,2‧S and 4S,2‧R ones, which crystallize in absence of water. The molecular and crystal structures of the 4R,2‧R and 4S,2‧S Pidotimod® stereoisomers here presented gave some hints on the differences in bioactivity with respect to the 4R,2‧S stereoisomer. In fact, beyond an expected different dispositions of hydrophilic ligands, 4R,2‧R and 4S,2‧S showed an incremented tendency to intermolecular H-bonds with water.

Identification and Characterization of Small-Molecule Inhibitors of the R132H/R132H Mutant Isocitrate Dehydrogenase 1 Homodimer and R132H/Wild-Type Heterodimer.

PubMed

Brooks, Eric; Wu, Xiang; Hanel, Art; Nguyen, Shaun; Wang, Jing; Zhang, Jeffrey H; Harrison, Amanda; Zhang, Wentao

2014-09-01

Recurrent genetic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been identified in multiple tumor types. The most frequent mutation, IDH1 R132H, is a gain-of-function mutation resulting in an enzyme-catalyzing conversion of α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG). A high-throughput assay quantifying consumption of NADPH by IDH1 R132H has been optimized and implemented to screen 3 million compounds in 1536-well formats. The primary high-throughput screening hits were further characterized by RapidFire-mass spectrometry measuring 2-HG directly. Multiple distinct chemotypes were identified with nanomolar potencies (6-300 nM). All inhibitors were found to be inactive against the wild-type IDH1 homodimers. An IDH1 heterodimer between wild-type and R132H mutant is capable of catalyzing conversion of α-KG to 2-HG and isocitrate to α-KG. Interestingly, one of the inhibitors, EXEL-9324, was found to inhibit both conversions by the IDH1 heterodimer. This indicates the R132H/WT heterodimer may adopt conformations distinct from that of the R132H/R132H homodimer. Further enzymatic studies support this conclusion as the heterodimer exhibited a significantly lower apparent Michaelis-Menten constant for α-KG (K(m)=110 µM) compared with the R132H homodimer (K(m)= 1200 µM). The enhanced apparent affinity for α-KG suggests R132H/WT heterodimeric IDH1 can produce 2-HG more efficiently at normal intracellular levels of α-KG (approximately 100 µM). © 2014 Society for Laboratory Automation and Screening.

Phase relations in the pseudobinary systems RAO3-R2Ti2O7 (R: rare earth element and Y, A: Fe, Ga, Al, Cr and Mn) and syntheses of new compounds R(A1-xTix)O3+x/2 (2/3≤x≤3/4) at elevated temperatures in air

NASA Astrophysics Data System (ADS)

Brown, Francisco; Jacobo-Herrera, Ivan; Alvarez-Montaño, Victor; Kimizuka, Noboru; Kurashina, Keiji; Michiue, Yuichi; Matsuo, Yoji; Mori, Shigeo; Ikeda, Naoshi; Medrano, Felipe

2017-07-01

Phase relations in the pseudo-binary systems RFeO3-R2Ti2O7 (R: Lu, Ho and Dy), RGaO3-R2Ti2O7 (R: Lu and Er), LuAlO3-Lu2Ti2O7 and RAO3-R2Ti2O7 (R: Lu and Yb. A: Cr and Mn) at elevated temperatures in air were determined by means of a classic quenching method. There exist Lu(Fe1-xTix)O3+x/2, R(Ga1-xTix)O3+x/2 (R: Lu and Er) and Lu(Al1-xTix)O3+x/2 (2/3≤ x≤3/4) having the Yb(Fe1-xTix)O3+x/2-type of crystal structure (x=0.72, space group: R3m, a(Å)=17.9773 and c(Å)=16.978 as a hexagonal setting) in these pseudo binary systems. Eighteen compounds R(A1-xTix)O3+x/2 (R: Lu-Sm and Y, A: Fe, Ga and Al) were newly synthesized and their lattice constants as a hexagonal setting were measured by means of the X-ray powder diffraction method. The R occupies the octahedral site and both A and Ti does the trigonalbipyramidal one in these compounds. Relation between lattice constants for the rhombic R(A1-xTix)O3+x/2 and the monoclinic In(A1-xTix)O3+x/2 are as follows, ah≈5 x bm, ch≈3 x cm x sin β and am=31/2 x bm, where ah and ch are the lattice constants as a hexagonal setting for R(A1-xTix)O3+x/2 and am, bm, cm and β are those of the monoclinic In(A1-xTix)O3+x/2. Crystal structural relationships among α-InGaO3 (hexagonal, high pressure form, space group: P63/mmc), InGaO3 (rhombic, hypothetical), (RAO3)n(BO)m and RAO3(ZnO)m (R: Lu-Ho, Y and In, A: Fe, Ga, and Al, B: divalent cation element, m, n: natural number), the orthorhombic-and monoclinic In(A1-xTix)O3+x/2 (A: Fe, Ga, Al, Cr and Mn) and the hexagonal-and rhombic R(A1-xTix)O3+x/2 (R: Lu-Sm and Y, A: Fe, Ga and Al) are schematically presented. We concluded that the crystal structures of both the α-InGaO3 (high pressure form, hexagonal, space group: P63/mmc) and the hypothetical InGaO3 (rhombic) are the key structures for constructing the crystal structures of these compounds having the cations with CN=5.

Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance

PubMed Central

Danza, Katia; Silvestris, Nicola; Simone, Giovanni; Signorile, Michele; Saragoni, Luca; Brunetti, Oronzo; Monti, Manlio; Mazzotta, Annalisa; De Summa, Simona; Mangia, Anita; Tommasi, Stefania

2016-01-01

ABSTRACT Despite the search for new therapeutic strategies for gastric cancer (GC), there is much evidence of progression due to resistance to chemotherapy. Multidrug resistance (MDR) is the ability of cancer cells to survive after exposure to chemotherapeutic agents. The involvement of miRNAs in the development of MDR has been well described but miRNAs able to modulate the sensitivity to chemotherapy by regulating hypoxia signaling pathways have not yet been fully addressed in GC. Our aim was to analyze miR-20b, miR-27a and miR-181a expression with respect to (epirubicin/oxaliplatin/capecitabine (EOX)) chemotherapy regimen in a set of GC patients, in order to investigate whether miRNAs deregulation may influence GC MDR also via hypoxia signaling modulation. Cancer biopsy were obtained from 21 untreated HER2 negative advanced GC patients, retrospectively analyzed. All patients received a first-line chemotherapy (EOX) regimen. MirWalk database was used to identify miR-27a, miR-181a and miR-20b target genes. The expression of miRNAs and of HIPK2, HIF1A and MDR1 genes were detected by real-time PCR. HIPK2 localization was assessed by immunohistochemistry. Our data showed the down-regulation of miR-20b, miR-27a, miR-181a concomitantly to higher levels of MDR1, HIF1A and HIPK2 genes in GC patients with a progressive disease respect to those with a disease control rate. Moreover, immunohistochemistry assay highlighted a higher cytoplasmic HIPK2 staining, suggesting a different role for it. We showed that aberrant expression of miR-20b, miR27a and miR-181a was associated with chemotherapeutic response in GC through HIF1A, MDR1 and HIPK2 genes modulation, suggesting a possible novel therapeutic strategy. PMID:26793992

Divergent assembly mechanisms of the manganese/iron cofactors in R2lox and R2c proteins.

PubMed

Kutin, Yuri; Srinivas, Vivek; Fritz, Matthieu; Kositzki, Ramona; Shafaat, Hannah S; Birrell, James; Bill, Eckhard; Haumann, Michael; Lubitz, Wolfgang; Högbom, Martin; Griese, Julia J; Cox, Nicholas

2016-09-01

A manganese/iron cofactor which performs multi-electron oxidative chemistry is found in two classes of ferritin-like proteins, the small subunit (R2) of class Ic ribonucleotide reductase (R2c) and the R2-like ligand-binding oxidase (R2lox). It is unclear how a heterodimeric Mn/Fe metallocofactor is assembled in these two related proteins as opposed to a homodimeric Fe/Fe cofactor, especially considering the structural similarity and proximity of the two metal-binding sites in both protein scaffolds and the similar first coordination sphere ligand preferences of Mn II and Fe II . Using EPR and Mössbauer spectroscopies as well as X-ray anomalous dispersion, we examined metal loading and cofactor activation of both proteins in vitro (in solution). We find divergent cofactor assembly mechanisms for the two systems. In both cases, excess Mn II promotes heterobimetallic cofactor assembly. In the absence of Fe II , R2c cooperatively binds Mn II at both metal sites, whereas R2lox does not readily bind Mn II at either site. Heterometallic cofactor assembly is favored at substoichiometric Fe II concentrations in R2lox. Fe II and Mn II likely bind to the protein in a stepwise fashion, with Fe II binding to site 2 initiating cofactor assembly. In R2c, however, heterometallic assembly is presumably achieved by the displacement of Mn II by Fe II at site 2. The divergent metal loading mechanisms are correlated with the putative in vivo functions of R2c and R2lox, and most likely with the intracellular Mn II /Fe II concentrations in the host organisms from which they were isolated. Copyright © 2016 Elsevier Inc. All rights reserved.

Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers.

PubMed

Mlynarsky, Liat; Bejarano-Achache, Idit; Muszkat, Mordechai; Caraco, Yoseph

2012-05-01

Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore

Rolling Deck to Repository (R2R): Collaborative Development of Linked Data for Oceanographic Research

NASA Astrophysics Data System (ADS)

Arko, Robert; Chandler, Cynthia; Stocks, Karen; Smith, Shawn; Clark, Paul; Shepherd, Adam; Moore, Carla; Beaulieu, Stace

2013-04-01

The Rolling Deck to Repository (R2R) program is developing infrastructure to ensure the underway sensor data from U.S. academic oceanographic research vessels are routinely and consistently documented, preserved in long-term archives, and disseminated to the science community. The entire R2R Catalog is published online as a Linked Data collection, making it easily accessible to encourage discovery and integration with data at other repositories. We are developing the R2R Linked Data collection with specific goals in mind: 1.) We facilitate data access and reuse by publishing the richest possible collection of resources to describe vessels, cruises, instruments, and datasets from the U.S. academic fleet, including data quality assessment results and clean trackline navigation; 2.) We facilitate data citation through the entire lifecycle from field acquisition to shoreside archiving to journal articles and global syntheses, by publishing Digital Object Identifiers (DOIs) for datasets and encoding them directly into our Linked Data resources; and 3.) We facilitate federation with other repositories such as the Biological and Chemical Oceanography Data Management Office (BCO-DMO), InterRidge Vents Database, and Index to Marine and Lacustrine Geological Samples (IMLGS), by reciprocal linking between RDF resources and supporting the RDF Query Language. R2R participates in the Ocean Data Interoperability Platform (ODIP), a joint European-U.S.-Australian partnership to facilitate the sharing of data and documentation across international borders. We publish our controlled vocabularies as a Simple Knowledge Organization System (SKOS) concept collection, and are working toward alignment with SeaDataNet and other community-standard terms using the NERC Vocabulary Server (NVS). http://rvdata.us/

Bound on largest r ∼< 0.1 from sub-Planckian excursions of inflaton

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

Chatterjee, Arindam; Mazumdar, Anupam, E-mail: arindam@hri.res.in, E-mail: a.mazumdar@lancaster.ac.uk

2015-01-01

In this paper we will discuss the range of large tensor to scalar ratio, r, obtainable from a sub-Planckian excursion of a single, slow roll driven inflaton field. In order to obtain a large r for such a scenario one has to depart from a monotonic evolution of the slow roll parameters in such a way that one still satisfies all the current constraints of \\texttt(Planck), such as the scalar amplitude, the tilt in the scalar power spectrum, running and running of the tilt close to the pivot scale. Since the slow roll parameters evolve non-monotonically, we will also considermore » the evolution of the power spectrum on the smallest scales, i.e. at P{sub s}(k ∼ 10{sup 16} Mpc{sup −1})∼< 10{sup −2}, to make sure that the amplitude does not become too large. All these constraints tend to keep the tensor to scalar ratio, r ∼< 0.1. We scan three different kinds of potential for supersymmetric flat directions and obtain the benchmark points which satisfy all the constraints. We also show that it is possible to go beyond r ∼> 0.1 provided we relax the upper bound on the power spectrum on the smallest scales.« less

Novel fermentation: the production of R(-)-1,2-propanediol and acetol by Clostridium thermosaccharolyticum

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

Cameron, D.C.; Cooney, C.L.

1986-07-01

Three strains of Clostridium thermosaccharolyticum were found that produce R(-)-1,2-propanediol from a variety of sugars, including D-glucose and D-xylose. The fermentation of glucose by strain HG-8 (ATCC 31960) gave 7.9 g/l of R(-)-1,2-propanediol with a best yield of 0.27 g/g glucose and an enantiomeric excess of greater than 99%. Acetol accumulated to 1.47 g/l. Product formation was not affected by phosphate concentrations up to 113 mM. A possible pathway to these products involves a variation of the methylglyoxal bypass. Methylglyoxal is reduced to acetol, which is further reduced to %(-)-1,2-propanediol. This fermentation provides a unique route to R(-)-1,2-propanediol and acetolmore » from inexpensive, readily available substrates.« less

The 3R polymorph of CaSi{sub 2}

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

Nedumkandathil, Reji; Benson, Daryn E.; Grins, Jekabs

The Zintl phase CaSi{sub 2} commonly occurs in the 6R structure where puckered hexagon layers of Si atoms are stacked in an AA′BB′CC′ fashion. In this study we show that sintering of CaSi{sub 2} in a hydrogen atmosphere (30 bar) at temperatures between 200 and 700 °C transforms 6R-CaSi{sub 2} quantitatively into 3R-CaSi{sub 2}. In the 3R polymorph (space group R-3m (no. 166), a=3.8284(1), c=15.8966(4), Z=3) puckered hexagon layers are stacked in an ABC fashion. The volume per formula unit is about 3% larger compared to 6R-CaSi{sub 2}. First principles density functional calculations reveal that 6R and 3R-CaSi{sub 2} aremore » energetically degenerate at zero Kelvin. With increasing temperature 6R-CaSi{sub 2} stabilizes over 3R because of its higher entropy. This suggests that 3R-CaSi{sub 2} should revert to 6R at elevated temperatures, which however is not observed up to 800 °C. 3R-CaSi{sub 2} may be stabilized by small amounts of incorporated hydrogen and/or defects. - Graphical abstract: The common 6R form of CaSi{sub 2} can be transformed quantitatively into 3R-CaSi{sub 2} upon sintering in a hydrogen atmosphere. - Highlights: • Quantitative and reproducible bulk synthesis of the rare 3R polymorph of CaSi{sub 2}. • Clarification of the energetic relation between 3R and conventional 6R form. • 3R-CaSi{sub 2} is presumably stabilized by small amounts of incorporated hydrogen and/or defects.« less

The basic reproduction number (R0) of measles: a systematic review.

PubMed

Guerra, Fiona M; Bolotin, Shelly; Lim, Gillian; Heffernan, Jane; Deeks, Shelley L; Li, Ye; Crowcroft, Natasha S

2017-12-01

The basic reproduction number, R nought (R 0 ), is defined as the average number of secondary cases of an infectious disease arising from a typical case in a totally susceptible population, and can be estimated in populations if pre-existing immunity can be accounted for in the calculation. R 0 determines the herd immunity threshold and therefore the immunisation coverage required to achieve elimination of an infectious disease. As R 0 increases, higher immunisation coverage is required to achieve herd immunity. In July, 2010, a panel of experts convened by WHO concluded that measles can and should be eradicated. Despite the existence of an effective vaccine, regions have had varying success in measles control, in part because measles is one of the most contagious infections. For measles, R 0 is often cited to be 12-18, which means that each person with measles would, on average, infect 12-18 other people in a totally susceptible population. We did a systematic review to find studies reporting rigorous estimates and determinants of measles R 0 . Studies were included if they were a primary source of R 0 , addressed pre-existing immunity, and accounted for pre-existing immunity in their calculation of R 0 . A search of key databases was done in January, 2015, and repeated in November, 2016, and yielded 10 883 unique citations. After screening for relevancy and quality, 18 studies met inclusion criteria, providing 58 R 0 estimates. We calculated median measles R 0 values stratified by key covariates. We found that R 0 estimates vary more than the often cited range of 12-18. Our results highlight the importance of countries calculating R 0 using locally derived data or, if this is not possible, using parameter estimates from similar settings. Additional data and agreed review methods are needed to strengthen the evidence base for measles elimination modelling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence of the CHEK2 R95* germline mutation.

PubMed

Knappskog, Stian; Leirvaag, Beryl; Gansmo, Liv B; Romundstad, Pål; Hveem, Kristian; Vatten, Lars; Lønning, Per E

2016-01-01

While germline CHEK2 mutations have been linked to a moderately elevated cancer risk, to date, a limited number of such mutations have been identified. Recently, we reported a germline nonsense mutation (C283T; R95*), introducing an early stop-codon, in two Norwegian patients diagnosed with locally advanced breast cancer. Both patients were resistant to anthracycline therapy, resembling what has been observed for TP53 mutations. In the present study, we screened a large population based sample, including 3748 non-cancer individuals and 7081 incident cancer cases (breast cancer, n  = 1717; prostate cancer n  = 2501, lung cancer n  = 1331 and colorectal cancer n  = 1532), for the distribution of CHEK2 R95*. We found that 12 individuals (0.11 %) carried the R95* variant: 4 non-cancer individuals (0.11 %), 4 breast cancer cases (0.23 %), and 4 prostate cancer cases (0.16 %). Although the low number of observations precluded formal statistical assessment, our data may indicate an elevated risk for breast (OR: 2.19, 95 % CI: 0.55-8.75) and prostate cancer (OR: 1.5, 95 % CI: 0.36-6.00) associated with CHEK2 R95*. By mining international databanks, we found no individuals carrying the R95* mutation, indicating it to be restricted to the Norwegian population. We provide proof-of-concept that previously unknown CHEK2 germline mutations may be present in certain populations. Notably, germline mutations in tumours are in general missed by contemporary massive parallel sequencing strategies, since tumour mutations are usually filtered against the germline. The fact that the CHEK2 R95* mutation may be associated with resistance to anthracyclines in cancer patients emphasizes its possible clinical importance.

Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells.

PubMed

Sarría, R; Díez, J; Losada, J; Doñate-Oliver, F; Kuhn, R; Grandes, P

2006-02-01

The localization of metabotropic glutamate receptors of groups II (mGluR2/3) and III (mGluR4a) and the subunits 2 and 3 of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (GluR2/3) was investigated with immunocytochemical methods in the rat adrenal gland. MGluR2/3, mGluR4a and GluR2/3 immunoreactivities were observed in large-sized, centrally located type I adrenal medullary ganglion neurons. Furthermore, the small-sized type II adrenal ganglion neurons identified by their immunoreactivity to brain nitric oxide synthase (bNOS), also expressed mGluR2/3, mGluR4a and GluR2/3. These cells were disposed in the peripheral portion of the adrenal medulla. None of the type I neurons were positively labeled for bNOS. These morphological observations suggest that activation of glutamate receptors in ganglion neurons may be instrumental in the control of adrenal endocrine systems as well as blood regulation.

rTANDEM, an R/Bioconductor package for MS/MS protein identification.

PubMed

Fournier, Frédéric; Joly Beauparlant, Charles; Paradis, René; Droit, Arnaud

2014-08-01

rTANDEM is an R/Bioconductor package that interfaces the X!Tandem protein identification algorithm. The package can run the multi-threaded algorithm on proteomic data files directly from R. It also provides functions to convert search parameters and results to/from R as well as functions to manipulate parameters and automate searches. An associated R package, shinyTANDEM, provides a web-based graphical interface to visualize and interpret the results. Together, those two packages form an entry point for a general MS/MS-based proteomic pipeline in R/Bioconductor. rTANDEM and shinyTANDEM are distributed in R/Bioconductor, http://bioconductor.org/packages/release/bioc/. The packages are under open licenses (GPL-3 and Artistice-1.0). frederic.fournier@crchuq.ulaval.ca or arnaud.droit@crchuq.ulaval.ca Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

UV Imaging of R136 with the GHRS and the WFPC-2

NASA Astrophysics Data System (ADS)

Malumuth, E. M.; Ebbets, D.; Heap, S. R.; Maran, S. P.; Hutchings, J. B.; Lindler, D. J.

1994-05-01

Now that the COSTAR corrective optics have been installed and aligned in the Hubble Space Telescope (HST), the Goddard High Resolution Spectrograph (GHRS) can obtain clean spectra and images of stars in very crowded fields. To demonstrate this restored capability, an Early Release Observation program to observe hot, luminous stars in the center of R136a (the central cluster of the 30 Doradus complex in the Large Magellanic Cloud) has been scheduled in early April. Through this program we will obtain a series of UV images through the Small Science Aperture (SSA) and Large Science Aperture (LSA) of the GHRS. The images will be taken with the N2 mirror and D2 detector (CsTe cathode on a MgF_2 window) and thus will have a bandpass that extends from 1150 to 3200 Angstroms. The SSA images will consist of 13 x 13 pixels with a pixel spacing of 0\\farcs027 pixel(-1) . Each pixel covers a 0\\farcs11 x 0\\farcs11 area on the sky. Thus each image will cover the entire SSA (0\\farcs22 x 0\\farcs22). The SSA images will include one centered on the initial pointing (located between R136a1 and R136a2; separation = 0\\farcs12), an image of R136a2, and an image of R136a5 (0\\farcs18 from R136a2). Two LSA images of the central region of R136 will be taken. The first, a 3 x 3 mosaic centered on R136a5, will consist of 22 x 22 pixels each, with a pixel spacing of 0\\farcs11 pixel(-1) . Together these images cover a 5\\farcs22 x 5\\farcs22 area. The second, will cover the central 1\\farcs2 x 1\\farcs2 with a pixel spacing of 0\\farcs055 pixel(-1) . These images will be examined to determine the true pointing for the spectra of R136a2 and R136a5, the imaging characteristics of the GHRS, and the UV brightnesses of all of the stars within the field. In addition to these images, 3 WFPC-2 PC exposures will be obtained with the F336W filter. These images are 5, 10 and 20 seconds in duration. Photometry of the stars in these images will be compared with the GHRS UV photometry, as well as

[Phenotype and mechanism of inducible ppp2r1a knockout mouse model].

PubMed

Fan, J L; Wang, F P; Wang, S; Liu, X L; Wu, X N; Chen, W; Chen, L P; Li, W X

2018-05-06

Objective: Investigate the effects of inducible ppp2r1a knockout on main physiological function in adult mice and study the mechanism. Methods: Ppp2r1a(flox/flox) mice and CAGG-CreER mice were hybridized to obtain 20 CAGG-CreER ppp2r1a(flox/flox) and 20 mice in homozygous group. Two groups of mice were divided into 4 groups respectively, finally we got 8 groups with 5 mice in each group. Tamoxifen was injected intraperitoneally to acquire inducible ppp2r1a knockout mice. The knockout efficiency of PP2A Aα in vital organs was measured by Western blot. At 0, 2, 4 and 6 days after injection, we measured body weight, histopathological change, peripheral blood cell counts and blood biochemical. Real-time PCR was performed to measure expression of liver glucolipid metabolism genes. Results: After tamoxifen injection for 6 days, the knockout efficiency of PP2A Aα in vital organs was 35%, 12%, 15%, 60%, 69% and 72%, respectively in heart, liver, spleen, lung, kidney and brain. After tamoxifen injection for 6 days, the weight of homozygous mice was lower than that of wild type mice, with values of (17.42±1.76) g and (21.69±1.82) g, respectively ( P< 0.05). Moreover, the activity level, abdominal and renal fat were significantly decreased in homozygous mice. Homozygous mice survived no more than 7 days. Compared with wild type mice, the organ coefficient of spleen of homozygous mice was decreased at the 6th day, with values of (0.59±0.10)% and (0.36±0.05)% respectively ( P< 0.05). Obvious spleen atrophy and marked decrease of nucleated cells were showed by performing HE staining. Tunel staining revealed increased apoptosis ratio of splenic lymphocytes in homozygous mice. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) of homozygous mice were higher than wild type mice ( P< 0.05). The values of ALT and AST in homozygous mice were (153.68±62.80) U/L and (193.2±44.28) U/L. The corresponding values in wild type mice were (41.02±12.91) U

VS{sub 2}/rGO hybrid nanosheets prepared by annealing of VS{sub 4}/rGO

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

Mohan, Pandurangan; Yang, Jieun; Jena, Anirudha

Layered transition metal dichalcogenides and their hybrids with reduced grpahene oxide (rGO) have attracted much interest due to many potential applications for electrode materials in Li ion batteries and supercapacitors and electro-catalysts for hydrogen evolution reaction. Among them, synthesis of VS{sub 2} sheets and VS{sub 4}/rGO hybrid via a hydrothermal reaction was recently reported, whereas VS{sub 2}/rGO hybrid sheets have not been reported. In this study, we report VS{sub 2}/rGO hybrid sheets after annealing VS{sub 4}/rGO hybrid materials at 350 °C. The conversion of VS{sub 4} to VS{sub 2} on rGO sheets after annealing is attributed to a thermal cleavagemore » of VS{sub 4}. - Highlights: • VS2/rGO hybrid sheets were obtained by annealing of VS4/rGO at 350 °C. • The phase transition from monoclinic to hexagonal is occurred. • The HER performance of VS2/rGO is investigated.« less

Expanding the Chemistry of Actinide Metallocene Bromides. Synthesis, Properties and Molecular Structures of the Tetravalent and Trivalent Uranium Bromide Complexes: (C 5Me 4R) 2UBr 2, (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(Br), and [K(THF)][(C 5Me 4R) 2UBr 2] (R = Me, Et)

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

Lichtscheidl, Alejandro Gaston; Pagano, Justin K.; Scott, Brian Lindley

The organometallic uranium species (C 5Me 4R) 2UBr 2 (R = Me, Et) were obtained by treating their chloride analogues (C 5Me 4R) 2UCl 2 (R = Me, Et) with Me 3SiBr. Treatment of (C 5Me 4R) 2UCl 2 and (C 5Me 4R) 2UBr 2 (R = Me, Et) with K(O-2,6- iPr 2C 6H 3) afforded the halide aryloxide mixed-ligand complexes (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(X) (R = Me, Et; X = Cl, Br). Complexes (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(Br) (R = Me, Et) can also be synthesized by treating (C 5Me 4R) 2U(O-2,6-more » iPr 2C 6H 3)(Cl) (R = Me, Et) with Me 3SiBr, respectively. Reduction of (C 5Me 4R) 2UCl 2 and (C 5Me 4R) 2UBr 2 (R = Me, Et) with KC 8 led to isolation of uranium(III) “ate” species [K(THF)][(C 5Me 5) 2UX 2] (X = Cl, Br) and [K(THF) 0.5][(C 5Me 4Et) 2UX 2] (X = Cl, Br), which can be converted to the neutral complexes (C 5Me 4R) 2U[N(SiMe 3) 2] (R = Me, Et). Analyses by nuclear magnetic resonance spectroscopy, X-ray crystallography, and elemental analysis are also presented.« less

Expanding the Chemistry of Actinide Metallocene Bromides. Synthesis, Properties and Molecular Structures of the Tetravalent and Trivalent Uranium Bromide Complexes: (C 5Me 4R) 2UBr 2, (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(Br), and [K(THF)][(C 5Me 4R) 2UBr 2] (R = Me, Et)

DOE PAGES

Lichtscheidl, Alejandro Gaston; Pagano, Justin K.; Scott, Brian Lindley; ...

2016-01-06

The organometallic uranium species (C 5Me 4R) 2UBr 2 (R = Me, Et) were obtained by treating their chloride analogues (C 5Me 4R) 2UCl 2 (R = Me, Et) with Me 3SiBr. Treatment of (C 5Me 4R) 2UCl 2 and (C 5Me 4R) 2UBr 2 (R = Me, Et) with K(O-2,6- iPr 2C 6H 3) afforded the halide aryloxide mixed-ligand complexes (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(X) (R = Me, Et; X = Cl, Br). Complexes (C 5Me 4R) 2U(O-2,6- iPr 2C 6H 3)(Br) (R = Me, Et) can also be synthesized by treating (C 5Me 4R) 2U(O-2,6-more » iPr 2C 6H 3)(Cl) (R = Me, Et) with Me 3SiBr, respectively. Reduction of (C 5Me 4R) 2UCl 2 and (C 5Me 4R) 2UBr 2 (R = Me, Et) with KC 8 led to isolation of uranium(III) “ate” species [K(THF)][(C 5Me 5) 2UX 2] (X = Cl, Br) and [K(THF) 0.5][(C 5Me 4Et) 2UX 2] (X = Cl, Br), which can be converted to the neutral complexes (C 5Me 4R) 2U[N(SiMe 3) 2] (R = Me, Et). Analyses by nuclear magnetic resonance spectroscopy, X-ray crystallography, and elemental analysis are also presented.« less

Tomato R2R3-MYB Proteins SlANT1 and SlAN2: Same Protein Activity, Different Roles

PubMed Central

Bassolino, Laura; Povero, Giovanni; Spelt, Cornelis; Buti, Sara; Giuliano, Giovanni; Quattrocchio, Francesca; Koes, Ronald; Perata, Pierdomenico; Gonzali, Silvia

2015-01-01

Anthocyanins are water-soluble polyphenolic compounds with a high nutraceutical value. Despite the fact that cultivated tomato varieties do not accumulate anthocyanins in the fruit, the biosynthetic pathway can be activated in the vegetative organs by several environmental stimuli. Little is known about the molecular mechanisms regulating anthocyanin synthesis in tomato. Here, we carried out a molecular and functional characterization of two genes, SlAN2 and SlANT1, encoding two R2R3-MYB transcription factors. We show that both can induce ectopic anthocyanin synthesis in transgenic tomato lines, including the fruit. However, only SlAN2 acts as a positive regulator of anthocyanin synthesis in vegetative tissues under high light or low temperature conditions. PMID:26308527

MPTinR: analysis of multinomial processing tree models in R.

PubMed

Singmann, Henrik; Kellen, David

2013-06-01

We introduce MPTinR, a software package developed for the analysis of multinomial processing tree (MPT) models. MPT models represent a prominent class of cognitive measurement models for categorical data with applications in a wide variety of fields. MPTinR is the first software for the analysis of MPT models in the statistical programming language R, providing a modeling framework that is more flexible than standalone software packages. MPTinR also introduces important features such as (1) the ability to calculate the Fisher information approximation measure of model complexity for MPT models, (2) the ability to fit models for categorical data outside the MPT model class, such as signal detection models, (3) a function for model selection across a set of nested and nonnested candidate models (using several model selection indices), and (4) multicore fitting. MPTinR is available from the Comprehensive R Archive Network at http://cran.r-project.org/web/packages/MPTinR/ .

Cannabinoid receptor activation correlates with the proapoptotic action of the β2-adrenergic agonist (R,R')-4-methoxy-1-naphthylfenoterol in HepG2 hepatocarcinoma cells.

PubMed

Paul, Rajib K; Ramamoorthy, Anuradha; Scheers, Jade; Wersto, Robert P; Toll, Lawrence; Jimenez, Lucita; Bernier, Michel; Wainer, Irving W

2012-10-01

Inhibition of cell proliferation by fenoterol and fenoterol derivatives in 1321N1 astrocytoma cells is consistent with β(2)-adrenergic receptor (β(2)-AR) stimulation. However, the events that result in fenoterol-mediated control of cell proliferation in other cell types are not clear. Here, we compare the effect of the β(2)-AR agonists (R,R')-fenoterol (Fen) and (R,R')-4-methoxy-1-naphthylfenoterol (MNF) on signaling and cell proliferation in HepG2 hepatocarcinoma cells by using Western blotting and [(3)H]thymidine incorporation assays. Despite the expression of β(2)-AR, no cAMP accumulation was observed when cells were stimulated with isoproterenol or Fen, although the treatment elicited both mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt activation. Unexpectedly, isoproterenol and Fen promoted HepG2 cell growth, but MNF reduced proliferation together with increased apoptosis. The mitogenic responses of Fen were attenuated by 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118,551), a β(2)-AR antagonist, whereas those of MNF were unaffected. Because of the coexpression of β(2)-AR and cannabinoid receptors (CBRs) and their impact on HepG2 cell proliferation, these Gα(i)/Gα(o)-linked receptors may be implicated in MNF signaling. Cell treatment with (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone (WIN 55,212-2), a synthetic agonist of CB(1)R and CB(2)R, led to growth inhibition, whereas inverse agonists of these receptors blocked MNF mitogenic responses without affecting Fen signaling. MNF responses were sensitive to pertussis toxin. The β(2)-AR-deficient U87MG cells were refractory to Fen, but responsive to the antiproliferative actions of MNF and WIN 55,212-2. The data indicate that the presence of the naphthyl moiety in MNF results in functional coupling to the CBR pathway, providing one of the first examples of a dually acting β(2)-AR-CBR ligand.

BCoR-L1 variation and breast cancer.

PubMed

Lose, Felicity; Arnold, Jeremy; Young, David B; Brown, Carolyn J; Mann, Graham J; Pupo, Gulietta M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Spurdle, Amanda B

2007-01-01

BRCA1 is involved in numerous essential processes in the cell, and the effects of BRCA1 dysfunction in breast cancer carcinogenesis are well described. Many of the breast cancer susceptibility genes such as BRCA2, p53, ATM, CHEK2, and BRIP1 encode proteins that interact with BRCA1. BCL6 corepressor-like 1 (BCoR-L1) is a newly described BRCA1-interacting protein that displays high homology to several proteins known to be involved in the fundamental processes of DNA damage repair and transcription regulation. BCoR-L1 has been shown to play a role in transcription corepression, and expression of the X-linked BCoR-L1 gene has been reported to be dysregulated in breast cancer subjects. BCoR-L1 is located on the X chromosome and is subject to X inactivation. We performed mutation analysis of 38 BRCA1/2 mutation-negative breast cancer families with male breast cancer, prostate cancer, and/or haplotype sharing around BCoR-L1 to determine whether there is a role for BCoR-L1 as a high-risk breast cancer predisposition gene. In addition, we conducted quantitative real-time PCR (qRT-PCR) on lymphoblastoid cell lines (LCLs) from the index cases from these families and a number of cancer cell lines to assess the role of BCoR-L1 dysregulation in cancer and cancer families. Very little variation was detected in the coding region, and qRT-PCR analysis revealed that BCoR-L1 expression is highly variable in cancer-free subjects, high-risk breast cancer patients, and cancer cell lines. We also report the investigation of a new expression control, DIDO1 (death inducer-obliterator 1), that is superior to GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and UBC (ubiquitin C) for analysis of expression in LCLs. Our results suggest that BCoR-L1 expression does not play a large role in predisposition to familial breast cancer.

Novel chiral core-shell silica microspheres with trans-(1R,2R)-diaminocyclohexane bridged in the mesoporous shell: synthesis, characterization and application in high performance liquid chromatography.

PubMed

Wu, Xiabing; You, Linjun; Di, Bin; Hao, Weiqiang; Su, Mengxiang; Gu, Yu; Shen, Lingling

2013-07-19

Novel chiral core-shell silica microspheres with trans-(1R,2R)-diaminocyclohexane (DACH) moiety bridged in the mesoporous shell were synthesized using layer-by-layer method. The chiral mesoporous shell around the nonporous silica core was formed by the co-condensation of N,N'-bis-[(triethoxysilyl)propyl]-trans-(1R,2R)-bis-(ureido)-cyclohexane (DACH-BS) and tetraethoxysilane (TEOS) using octadecyltrimethylammonium chloride (C18TMACl) and triblock poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) copolymer (P123) as the templates. The functionalized core-shell silica microspheres were characterized and tested as chiral stationary phases for high performance liquid chromatography (HPLC). R/S-1,1'-bi-2,2'-naphthol, R/S-6,6'-dibromo-1,1'-bi-2-naphthol and R/S-1,1'-bi-2,2'-phenanthrol were enantioseparated rapidly on the column packed with the DACH core-shell silica particles. Moreover, the column packed with core-shell particles exhibited better performance than the column packed with the DACH functionalized periodic mesoporous organosilicas. Copyright © 2013 Elsevier B.V. All rights reserved.

1. Historic American Buildings Survey, Photocopy from P.R.R. General Library, ...

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

1. Historic American Buildings Survey, Photocopy from P.R.R. General Library, TRAIN SIDE FRONT (NORTH) c.1870 TRANSPORTATION BUILDING, 17TH STREET AND PENNSYLVANIA AVENUE, PHILADELPHIA, PENNSYLVANIA. - Pennsylvania Railroad Bryn Mawr Station, Bryn Mawr & Morris Avenues, Bryn Mawr, Montgomery County, PA

Rolling Deck to Repository (R2R): Linking and Integrating Data for Oceanographic Research

NASA Astrophysics Data System (ADS)

Arko, R. A.; Chandler, C. L.; Clark, P. D.; Shepherd, A.; Moore, C.

2012-12-01

The Rolling Deck to Repository (R2R) program is developing infrastructure to ensure the underway sensor data from NSF-supported oceanographic research vessels are routinely and consistently documented, preserved in long-term archives, and disseminated to the science community. We have published the entire R2R Catalog as a Linked Data collection, making it easily accessible to encourage linking and integration with data at other repositories. We are developing the R2R Linked Data collection with specific goals in mind: 1.) We facilitate data access and reuse by providing the richest possible collection of resources to describe vessels, cruises, instruments, and datasets from the U.S. academic fleet, including data quality assessment results and clean trackline navigation. We are leveraging or adopting existing community-standard concepts and vocabularies, particularly concepts from the Biological and Chemical Oceanography Data Management Office (BCO-DMO) ontology and terms from the pan-European SeaDataNet vocabularies, and continually re-publish resources as new concepts and terms are mapped. 2.) We facilitate data citation through the entire data lifecycle from field acquisition to shoreside archiving to (ultimately) global syntheses and journal articles. We are implementing globally unique and persistent identifiers at the collection, dataset, and granule levels, and encoding these citable identifiers directly into the Linked Data resources. 3.) We facilitate linking and integration with other repositories that publish Linked Data collections for the U.S. academic fleet, such as BCO-DMO and the Index to Marine and Lacustrine Geological Samples (IMLGS). We are initially mapping datasets at the resource level, and plan to eventually implement rule-based mapping at the concept level. We work collaboratively with partner repositories to develop best practices for URI patterns and consensus on shared vocabularies. The R2R Linked Data collection is implemented as a

lumpR 2.0.0: an R package facilitating landscape discretisation for hillslope-based hydrological models

NASA Astrophysics Data System (ADS)

Pilz, Tobias; Francke, Till; Bronstert, Axel

2017-08-01

The characteristics of a landscape pose essential factors for hydrological processes. Therefore, an adequate representation of the landscape of a catchment in hydrological models is vital. However, many of such models exist differing, amongst others, in spatial concept and discretisation. The latter constitutes an essential pre-processing step, for which many different algorithms along with numerous software implementations exist. In that context, existing solutions are often model specific, commercial, or depend on commercial back-end software, and allow only a limited or no workflow automation at all. Consequently, a new package for the scientific software and scripting environment R, called lumpR, was developed. lumpR employs an algorithm for hillslope-based landscape discretisation directed to large-scale application via a hierarchical multi-scale approach. The package addresses existing limitations as it is free and open source, easily extendible to other hydrological models, and the workflow can be fully automated. Moreover, it is user-friendly as the direct coupling to a GIS allows for immediate visual inspection and manual adjustment. Sufficient control is furthermore retained via parameter specification and the option to include expert knowledge. Conversely, completely automatic operation also allows for extensive analysis of aspects related to landscape discretisation. In a case study, the application of the package is presented. A sensitivity analysis of the most important discretisation parameters demonstrates its efficient workflow automation. Considering multiple streamflow metrics, the employed model proved reasonably robust to the discretisation parameters. However, parameters determining the sizes of subbasins and hillslopes proved to be more important than the others, including the number of representative hillslopes, the number of attributes employed for the lumping algorithm, and the number of sub-discretisations of the representative hillslopes.

78 FR 63867 - Change of Using Agency for Restricted Areas R-5115, NM, and R-6316, R-6317, and R-6318, TX

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... realignment of organizational responsibilities between federal agencies, U.S. Customs and Border Protection..., R-6317, and R-6318 in Texas. The transfer of using agency operational control occurs October 1, 2013...-6316, R- 6317, and R-6318 to reflect current organizational responsibilities. Environmental Review The...

Simple synthesis of graphene nanocomposites MgO-rGO and Fe2O3-rGO for multifunctional applications

NASA Astrophysics Data System (ADS)

Abdel-Aal, Seham K.; Ionov, Andrey; Mozhchil, R. N.; Naqvi, Alim H.

2018-05-01

Hummer's method was used to prepare graphene oxide (GO) by chemical exfoliation of graphite. Simple precipitation method was used for the preparation of hybrid nanocomposites MgO-rGO and Fe2O3-rGO. A 0.3 Molar of corresponding metal nitrate solution and GO solution are used for the preparation process. XRD, FT-IR, and XPS were used to characterize the prepared nanocomposites. The reduction of GO into reduced rGO in the formed nanocomposites was confirmed. Morphological characterization showed the formation of needle-shaped nanocrystals of MgO successfully grown on graphene nanosheet with average crystallite size 8.4 nm. Hematite nanocomposite Fe2O3-rGO forms rod-shaped crystals with average crystallite size 27.5 nm. The saturation magnetization observed for Fe2O3-rGO is less than reported value for the pure Fe2O3 nanoparticles. Thermal properties of as-prepared hybrid nanocomposites MgO-rGO and Fe2O3-rGO showed thermal stability of the prepared nanocomposite over long range of temperature.

Analysis of various types of single-polypeptide-chain (sc) heterodimeric A{sub 2A}R/D{sub 2}R complexes and their allosteric receptor–receptor interactions

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

Kamiya, Toshio, E-mail: kamiya@z2.keio.jp; Department of Neurology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526; Cell Biology Laboratory, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502

Highlights: • Various scA{sub 2A}R/D{sub 2}R constructs, with spacers between the two receptors, were created. • Using whole cell binding assay, constructs were examined for their binding activity. • Although the apparent ratio of A{sub 2A}R to D{sub 2}R binding sites should be 1, neither was 1. • Counter agonist-independent binding cooperativity occurred in context of scA{sub 2A}R/D{sub 2}R. - Abstract: Adenosine A{sub 2A} receptor (A{sub 2A}R) heteromerizes with dopamine D{sub 2} receptor (D{sub 2}R). However, these class A G protein-coupled receptor (GPCR) dimers are not fully formed, but depend on the equilibrium between monomer and dimer. In order tomore » stimulate the heteromerization, we have previously shown a successful design for a fusion receptor, single-polypeptide-chain (sc) heterodimeric A{sub 2A}R/D{sub 2}R complex. Here, using whole cell binding assay, six more different scA{sub 2A}R/D{sub 2}R constructs were examined. Not only in scA{sub 2A}R/D{sub 2}R ‘liberated’ with longer spacers between the two receptors, which confer the same configuration as the prototype, the A{sub 2A}R-odr4TM-D{sub 2L}R, but differ in size (Forms 1–3), but also in scA{sub 2A}R/D{sub 2L}R (Form 6) fused with a transmembrane (TM) of another type II TM protein, instead of odr4TM, neither of their fixed stoichiometry (the apparent ratios of A{sub 2A}R to D{sub 2}R binding sites) was 1, suggesting their compact folding. This suggests that type II TM, either odr4 or another, facilitates the equilibrial process of the dimer formation between A{sub 2A}R and D{sub 2L}R, resulting in the higher-order oligomer formation from monomer of scA{sub 2A}R/D{sub 2L}R itself. Also, in the reverse type scA{sub 2A}R/D{sub 2L}R, i.e., the D{sub 2L}R-odr4TM-A{sub 2A}R, counter agonist-independent binding cooperativity (cooperative folding) was found to occur (Forms 4 and 5). In this way, the scA{sub 2A}R/D{sub 2L}R system has unveiled the cellular phenomenon as a snapshot of the

Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats.

PubMed

Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas

2018-01-01

Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

Pretreatment predictive value of blood neutrophil/lymphocyte ratio in R0 gastric cancer resectability.

PubMed

Borda, Ana; Vila, Juan; Fernández-Urién, Ignacio; Zozaya, José Manuel; Guerra, Ana; Borda, Fernando

2017-01-01

New parameters complementary to clinical TNM classification are needed, to orient preoperative on the possibility of a R0 gastric cancer resection. We analysed the possible predictive value of blood neutrophil/lymphocytic ratio (N/L) in relation to resectability. Two hundred and fifty-seven gastric cancers consecutively diagnosed and without neoadjuvant treatment were retrospectively studied. Univariate and multivariate analysis of the frequency of R0 cases was performed between groups with a normal N/L ratio (<5) and pathological N/L ratio (≥5). Furthermore, we studied the subgroup of operated patients (n=156) analysing the frequency of R0 resection according to N/L ratio<5 or≥5. One hundred and fifty-six patients underwent surgical intervention, of which 139 had R0 resections. A high N/L ratio was registered in 46 cases (17.9%). Globally, resectability was higher in patients with a N/L ratio<5: 59.7% vs. N/L ratio≥5: 28.6% (P<.001; OR=3.76; 95% CI=1.78-8.04). The relation between N/L ratio<5 and R0 resection was confirmed in the multivariate (P=.006; OR=3.86; 95% CI=1.46-10.22). In the operated subgroup, the higher frequency of R0 resection achievement is maintained in cases with N/L ratio<5: 91.3% vs. 72.2% (P=.015; OR=4.04; 95% CI=1.23-13.26). The presence of a N/L ratio<5 at the diagnosis of a gastric carcinoma is related in a significant and independent way with a higher frequency of R0 tumoral resection, globally. This higher proportion of R0 resection cases in patients with a N/L<5 ratio is confirmed in the subgroup of operated patients. Copyright © 2016 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

Rare Examples of Fe(IV) Alkyl-Imide Migratory Insertions: Impact of Fe-C Covalency in (Me2IPr)Fe(═NAd)R2 (R = neoPe, 1-nor).

PubMed

Jacobs, Brian P; Wolczanski, Peter T; Jiang, Quan; Cundari, Thomas R; MacMillan, Samantha N

2017-09-06

The iron(IV) imide complexes, (Me 2 IPr)-R 2 Fe=NAd (R = neo Pe (3a), 1-nor (3b)) undergo migratory insertion to iron(II) amides (Me 2 IPr)RFe{NR(Ad)} (R = neo Pe (4a), 1-nor (4b)) without evidence of imidyl or free nitrene character. By increasing the field strength about iron, odd-electron reactivity was circumvented via increased covalency.

Rolling Deck to Repository (R2R): Products and Services for the U.S. Research Fleet Community

NASA Astrophysics Data System (ADS)

Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Smith, S. R.; Stocks, K. I.

2016-02-01

The Rolling Deck to Repository (R2R) program is working to ensure open access to environmental sensor data routinely acquired by the U.S. academic research fleet. Currently 25 vessels deliver 7 TB/year of data to R2R from a suite of geophysical, oceanographic, meteorological, and navigational sensors on over 400 cruises worldwide. R2R ensures these data are preserved in trusted repositories, discoverable via standard protocols, and adequately documented for reuse. R2R has recently expanded to include the vessels Sikuliaq, operated by the University of Alaska; Falkor, operated by the Schmidt Ocean Institute; and Ronald H. Brown and Okeanos Explorer, operated by NOAA. R2R maintains a master catalog of U.S. research cruises, currently holding over 4,670 expeditions including vessel and cruise identifiers, start/end dates and ports, project titles and funding awards, science parties, dataset inventories with instrument types and file formats, data quality assessments, and links to related content at other repositories. Standard post-field cruise products are published including shiptrack navigation, near-real-time MET/TSG data, underway geophysical profiles, and CTD profiles. Software tools available to users include the R2R Event Logger and the R2R Nav Manager. A Digital Object Identifier (DOI) is published for each cruise, original field sensor dataset, standard post-field product, and document (e.g. cruise report) submitted by the science party. Scientists are linked to personal identifiers such as ORCIDs where available. Using standard identifiers such as DOIs and ORCIDs facilitates linking with journal publications and generation of citation metrics. R2R collaborates in the Ocean Data Interoperability Platform (ODIP) to strengthen links among regional and national data systems, populates U.S. cruises in the POGO global catalog, and is working toward membership in the DataONE alliance. It is a lead partner in the EarthCube GeoLink project, developing Semantic Web