Chemical Rescue of Enzymes: Proton Transfer in Mutants of Human Carbonic Anhydrase II

PubMed Central

Maupin, C. Mark; Castillo, Norberto; Taraphder, Srabani; Tu, Chingkuang; McKenna, Robert; Silverman, David N.; Voth, Gregory A.

2011-01-01

In human carbonic anhydrase II (HCA II) the mutation of position 64 from histidine to alanine (H64A) disrupts the rate limiting proton transfer (PT) event, resulting in a reduction of the catalytic activity of the enzyme as compared to the wild-type. Potential of mean force (PMF) calculations utilizing the multistate empirical valence bond (MS-EVB) methodology for H64A HCA II give a PT free energy barrier significantly higher than that found in the wild-type enzyme. This high barrier, determined in the absence of exogenous buffer and assuming no additional ionizable residues in the PT pathway, indicates the likelihood of alternate enzyme pathways that utilize either ionizable enzyme residues (self-rescue) and/or exogenous buffers (chemical rescue). It has been shown experimentally that the catalytic activity of H64A HCA II can be chemically rescued to near wild type levels by the addition of the exogenous buffer 4-methylimidazole (4MI). Crystallographic studies have identified two 4MI binding sites, yet site specific mutations intended to disrupt 4MI binding have demonstrated these sites to be non-productive. In the present work MS-EVB simulations show that binding of 4MI near Thr199 in the H64A HCA II mutant, a binding site determined by NMR spectroscopy, results in a viable chemical rescue pathway. Additional viable rescue pathways are also identified where 4MI acts as a proton transport intermediary from the active site to ionizable residues on the rim of the active site, revealing a probable mode of action for the chemical rescue pathway PMID:21452838

Active-site solvent replenishment observed during human carbonic anhydrase II catalysis.

PubMed

Kim, Jin Kyun; Lomelino, Carrie L; Avvaru, Balendu Sankara; Mahon, Brian P; McKenna, Robert; Park, SangYoun; Kim, Chae Un

2018-01-01

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO 2 /HCO 3 - . Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO 2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (W I ') is observed next to the previously observed intermediate water W I , and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH - on CO 2 . This mechanism explains how the zinc-bound water (W Zn ) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first 'physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.

Superacid synthesized tertiary benzenesulfonamides and benzofuzed sultams act as selective hCA IX inhibitors: toward understanding a new mode of inhibition by tertiary sulfonamides.

PubMed

Métayer, Benoît; Martin-Mingot, Agnès; Vullo, Daniella; Supuran, Claudiu T; Thibaudeau, Sébastien

2013-11-21

A series of tertiary (fluorinated) benzenesulfonamides was synthesized in superacid HF-SbF5. To circumvent the problem of the in situ iminium ion formation, proved by low temperature NMR experiments, a tandem superacid catalysed cross-coupling reaction was employed to synthesize the benzofuzed sultams analogues. These tertiary benzenesulfonamides were tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). These compounds did not inhibit the widespread off target hCA II isoform and showed strong selectivity toward tumor-associated carbonic anhydrase isoform IX. A dramatic effect of the electronic and structural shape of the inhibitors on selectivity was demonstrated, confirming the non-zinc-bonding mode of inhibition of this class of sulfonamides. This work allowed identifying a highly selective hCA IX inhibitor lead in this series.

Dual-tail arylsulfone-based benzenesulfonamides differently match the hydrophobic and hydrophilic halves of human carbonic anhydrases active sites: Selective inhibitors for the tumor-associated hCA IX isoform.

PubMed

Ibrahim, Hany S; Allam, Heba Abdelrasheed; Mahmoud, Walaa R; Bonardi, Alessandro; Nocentini, Alessio; Gratteri, Paola; Ibrahim, Eslam S; Abdel-Aziz, Hatem A; Supuran, Claudiu T

2018-05-25

The synthesis and characterization of two new sets of arylsulfonehydrazone benzenesulfonamides (4a-4i with phenyl tail and 4j-4q with tolyl tail) are reported. The compounds were designed according to a dual-tails approach to modulate the interactions of the ligands portions at the outer rim of both hydrophobic and hydrophilic active site halves of human isoforms of carbonic anhydrase (CA, EC 4.2.1.1). The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) isoforms, hCA I, II, IV and IX. With the latter being a validated anticancer drug target and a marker of tumor hypoxia, attractive results arose from the Compounds' inhibitory screening in terms of potency and selectivity. Indeed, whereas the first subset of compounds 4a-4i exhibited great efficacy in inhibiting both the ubiquitous, off-target hCA II (K I s 9.5-172.0 nM) and hCA IX (K I s 7.5-131.5 nM), the second subset of tolyl-bearing derivatives 4j-4q were shown to possess a selective hCA IX inhibitory action over isoforms I, II and IV. The most selective compounds 4l and 4n were further screened for their in vitro cytotoxic activity against MCF-7 and MDA-MB-231 cancer cell lines under hypoxic conditions. The selective IX/II inhibitory trend of 4j-4q compared to those of compounds 4a-4i was unveiled by docking studies. Further exploration of these molecules could be useful for the development of novel antitumor agents with a selective CA inhibitory mechanism. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Diagnostic Value of Gadoxetic Acid-Enhanced MR Imaging to Distinguish HCA and Its Subtype from FNH: A Systematic Review.

PubMed

Guo, Yongfei; Li, Wenjuan; Cai, Wenli; Zhang, Yi; Fang, Yijie; Hong, Guobin

2017-01-01

Objective: The purpose of this study was to systematically review the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) for differentiation of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), as well as HCA classification by using the low signal intensity (SI) in the hepatobiliary phase (HBP). Methods: A systematic process was used to review all published data in MEDLINE database about Gd-EOB-DTPA-MRI applied to differentiation of HCA and FNH, and classification of HCA by using low SI in the HBP. The pooled sensitivity and specificity were calculated to assess the diagnostic value of low SI in the HBP. Results: A review of 45 articles identified 10 eligible studies with a total of 288 HCA lesions. The pooled proportion of low SI in the HBP of HCA were 91% (95% CI: 0.81-0.97). In specific, the subtypes of HCA were 75% (95% CI: 0.64-0.85) for I-HCA, 100% (95% CI: 0.95-1.00) for H-HCA, 92% (95% CI: 0.70-1.00) for U-HCA, and 59% (95% CI: 0.00-1.00) for b-HCA, respectively. The pooled specificity and sensitivity of low SI in the HBP for distinguishing FNH from HCA were 95% (95% CI: 0.92-0.98) and 92% (95% CI: 0.87-0.96), respectively. Conclusion: Low SI in the HBP of Gd-EOB-DTPA-MRI is associated with higher accuracy for distinguishing HCA from FNH. However, the diagnostic accuracy may be overvalued, especially for the diagnosis of subtypes of b-HCA and I-HCA. Therefore, the risk factors and conventional imaging findings should be take into account simultaneously.

Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with L- and D-phenylalanine and crystallographic analysis of their adducts with isozyme II: stereospecific recognition within the active site of an enzyme and its consequences for the drug design.

PubMed

Temperini, Claudia; Scozzafava, Andrea; Vullo, Daniela; Supuran, Claudiu T

2006-05-18

Activation of six human brain carbonic anhydrases (hCAs, EC 4.2.1.1), hCA I, II, IV, VA, VII, and XIV, with l-/d-phenylalanine was investigated kinetically and by X-ray crystallography. l-Phe was a potent activator of isozymes I, II, and XIV (K(A)s of 13-240 nM), a weaker activator of hCA VA and VII (K(A)s of 9.8-10.9 microM), and a quite inefficient hCA IV activator (K(A) of 52 microM). d-Phe showed good hCA II activatory properties (K(A) of 35 nM), being a moderate hCA VA, VII, and XIV (K(A)s of 4.6-9.7 microM) and a weak hCA I and IV activator (K(A)s of 63-86 microM). X-ray crystallography of the hCA II-l-Phe/d-Phe adducts showed the activators to be anchored at the entrance of the active site, participating in numerous bonds and hydrophobic interactions with amino acid residues His64, Thr200, Trp5, and Pro201. This is the first study showing different binding modes of stereoisomeric activators within the hCA II active site, with consequences for overall proton transfer processes (rate-determining for the catalytic cycle). It also points out differences of activation efficiency between various isozymes with structurally related activators, exploitable for designing alternative proton transfer pathways. CA activators may lead to the design of pharmacologically useful derivatives for the enhancement of synaptic efficacy, which may represent a conceptually new approach for the treatment of Alzheimer's disease, aging, and other conditions in which spatial learning and memory therapy must be enhanced. As the blood and brain concentrations of l-Phe are quite variable (30-73 microM), activity of some brain CAs may strongly be influenced by the level of activator(s) present in such tissues.

Diagnostic Value of Gadoxetic Acid-Enhanced MR Imaging to Distinguish HCA and Its Subtype from FNH: A Systematic Review

PubMed Central

Guo, Yongfei; Li, Wenjuan; Cai, Wenli; Zhang, Yi; Fang, Yijie; Hong, Guobin

2017-01-01

Objective: The purpose of this study was to systematically review the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) for differentiation of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), as well as HCA classification by using the low signal intensity (SI) in the hepatobiliary phase (HBP). Methods: A systematic process was used to review all published data in MEDLINE database about Gd-EOB-DTPA-MRI applied to differentiation of HCA and FNH, and classification of HCA by using low SI in the HBP. The pooled sensitivity and specificity were calculated to assess the diagnostic value of low SI in the HBP. Results: A review of 45 articles identified 10 eligible studies with a total of 288 HCA lesions. The pooled proportion of low SI in the HBP of HCA were 91% (95% CI: 0.81-0.97). In specific, the subtypes of HCA were 75% (95% CI: 0.64-0.85) for I-HCA, 100% (95% CI: 0.95-1.00) for H-HCA, 92% (95% CI: 0.70-1.00) for U-HCA, and 59% (95% CI: 0.00-1.00) for b-HCA, respectively. The pooled specificity and sensitivity of low SI in the HBP for distinguishing FNH from HCA were 95% (95% CI: 0.92-0.98) and 92% (95% CI: 0.87-0.96), respectively. Conclusion: Low SI in the HBP of Gd-EOB-DTPA-MRI is associated with higher accuracy for distinguishing HCA from FNH. However, the diagnostic accuracy may be overvalued, especially for the diagnosis of subtypes of b-HCA and I-HCA. Therefore, the risk factors and conventional imaging findings should be take into account simultaneously. PMID:28824299

Synthesis and Biological Evaluation of 4-Sulfamoylphenyl/Sulfocoumarin Carboxamides as Selective Inhibitors of Carbonic Anhydrase Isoforms hCA II, IX, and XII.

PubMed

Angapelly, Srinivas; Angeli, Andrea; Khan, Arbaj Jabbar; Sri Ramya, P V; Supuran, Claudiu T; Arifuddin, Mohammed

2018-04-19

With the aim to develop potent and selective human carbonic anhydrase inhibitors (hCAIs), we synthesized 4-sulfamoylphenyl/sulfocoumarin benzamides (series 5 a-r and series 7 a-q) and evaluated their inhibition profiles against five isoforms of the zinc-containing human carbonic anhydrase (hCA, EC 4.2.1.1): cytosolic hCA I and II, and the transmembrane isozymes hCA IV, IX, and XII. Compounds 5 a-r were found to selectively inhibit hCA II in the nanomolar range, while being less effective against the other hCA isoforms. As noted from the literature, sulfocoumarin (1,2-benzoxathiine 2,2-dioxide) acts as a "prodrug" inhibitor and is hydrolyzed by the esterase activity of hCA to form 2-hydroxyphenylvinylsulfonic acid, which thereafter binds to the enzyme in a manner similar to that of coumarins and sulfoxocoumarins. All these sulfocoumarins (compounds 7 a-q) were found to be very weak or ineffective as inhibitors of the housekeeping off-target hCA isoforms I and II, and effectively inhibited the transmembrane tumor-associated isoforms IX and XII in the high nanomolar to micromolar ranges. Further structural modifications of these molecules could be useful for the development of effective hCA inhibitors used for the treatment of glaucoma, epilepsy, and cancer. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tracking solvent and protein movement during CO2 release in carbonic anhydrase II crystals

PubMed Central

Kim, Chae Un; Song, HyoJin; Avvaru, Balendu Sankara; Gruner, Sol M.; Park, SangYoun; McKenna, Robert

2016-01-01

Carbonic anhydrases are mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3−. Previously, the X-ray crystal structures of CO2-bound holo (zinc-bound) and apo (zinc-free) human carbonic anhydrase IIs (hCA IIs) were captured at high resolution. Here, we present sequential timeframe structures of holo- [T = 0 s (CO2-bound), 50 s, 3 min, 10 min, 25 min, and 1 h] and apo-hCA IIs [T = 0 s, 50 s, 3 min, and 10 min] during the “slow” release of CO2. Two active site waters, WDW (deep water) and WDW′ (this study), replace the vacated space created on CO2 release, and another water, WI (intermediate water), is seen to translocate to the proton wire position W1. In addition, on the rim of the active site pocket, a water W2′ (this study), in close proximity to residue His64 and W2, gradually exits the active site, whereas His64 concurrently rotates from pointing away (“out”) to pointing toward (“in”) active site rotameric conformation. This study provides for the first time, to our knowledge, structural “snapshots” of hCA II intermediate states during the formation of the His64-mediated proton wire that is induced as CO2 is released. Comparison of the holo- and apo-hCA II structures shows that the solvent network rearrangements require the presence of the zinc ion. PMID:27114542

The inhibitory effects of phenolic Mannich bases on carbonic anhydrase I and II isoenzymes.

PubMed

Yamali, Cem; Tugrak, Mehtap; Gul, Halise Inci; Tanc, Muhammet; Supuran, Claudiu T

2016-12-01

Phenolic mono Mannich bases [2-[4-hydroxy-3-(aminomethyl)benzylidene]-2,3-dihydro-1H-inden-1-one (8-15)] and bis Mannich bases [2-[4-hydroxy-3,5-bis(aminomethyl)benzylidene]-2, 3-dihydro-1H-inden-1-one (2-7)] were synthesized starting from 2-(4-hydroxybenzylidene)-2, 3-dihydro-inden-1-one (1). This study was designed in order to investigate the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties of a library of compounds incorporating the phenol functional group. All prepared compounds showed a low inhibition percentages on both human (h) isoforms hCA I and hCA II compared to the reference sulfonamide acetazolamide. Mannich bases 2-15 had lower inhibition percentages than the compound 1 on hCA I and hCA II, except compound 14, which is a Mannich base derivative of dipropylamine, which had a similar inhibitory power as compound 1 on hCA II. All compounds synthesized 1-15 were 1.3-1.9 times more effective on hCA II comparing with the effectivenes of the compounds on hCA I.

Dominant behaviours in the expression of human carbonic anhydrase hCA I activity.

PubMed

Abdelrahim, M Yahia M; Tanc, Muhammet; Winum, Jean-Yves; Supuran, Claudiu T; Barboiu, Mihail

2014-07-28

Here we describe the screening via Dynamic Deconvolution of DCLs of inhibitors (CAIs) and activators (CAAs) of hCA I. The inhibitory effects dominate over the activating ones, while the CAAs may be identified in the absence of CAIs.

The effect of sodium pertechnetate human carbonic anhydrase I and II

NASA Astrophysics Data System (ADS)

Sahin, Ali; Senturk, Murat

2017-04-01

The inhibitory effects of Na99mTcO4 (Sodium pertechnetate) on human erythrocyte carbonic anhydrase I and II activity were investigated. For this purpose, hCA I was initially purified 114,29-fold at a yield of 69,19 % and hCA II was initially purified 710,82-fold at a yield of 71,72 % using sepharose 4B-tyrosine-sulfanilamide affinity gel chromatography. The in vitro effect of this compound on hCA I and II isoenzyme were studied. It was detected in in vitro studies that the hCA I and II enzymes are inhibited due to Na99mTcO4.

Synthesis and biological evaluation of novel aromatic and heterocyclic bis-sulfonamide Schiff bases as carbonic anhydrase I, II, VII and IX inhibitors.

PubMed

Akocak, Suleyman; Lolak, Nabih; Nocentini, Alessio; Karakoc, Gulcin; Tufan, Anzel; Supuran, Claudiu T

2017-06-15

A series of sixteen novel aromatic and heterocyclic bis-sulfonamide Schiff bases were prepared by conjugation of well known aromatic and heterocyclic aminosulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor pharmacophores with aromatic and heterocyclic bis-aldehydes. The obtained bis-sulfonamide Schiff bases were investigated as inhibitors of four selected human (h) CA isoforms, hCA I, hCA II, hCA VII and hCA IX. Most of the newly synthesized compounds showed a good inhibitory profile against isoforms hCA II and hCA IX, also showing moderate selectivity against hCA I and VII. Several efficient lead compounds were identified among this bis-sulfonamide Schiff bases with low nanomolar to sub-nanomolar activity against hCA II (K i s ranging between 0.4 and 861.1nM) and IX (K i s between 0.5 and 933.6nM). Since hCA II and hCA IX are important drug targets (antiglaucoma and anti-tumor agents), these isoform-selective inhibitors may be considered of interest for various biomedical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spectroscopic characterization of furosemide binding to human carbonic anhydrase II.

PubMed

Ranjbar, Samira; Ghobadi, Sirous; Khodarahmi, Reza; Nemati, Houshang

2012-05-01

This study reports the interaction between furosemide and human carbonic anhydrase II (hCA II) using fluorescence, UV-vis and circular dichroism (CD) spectroscopy. Fluorescence data indicated that furosemide quenches the intrinsic fluorescence of the enzyme via a static mechanism and hydrogen bonding and van der Walls interactions play the major role in the drug binding. The binding average distance between furosemide and hCA II was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity was also documented upon furosemide binding. Chemical modification of hCA II using N-bromosuccinimide indicated decrease of the number of accessible tryptophans in the presence of furosemide. CD results suggested the occurance of some alterations in α-helical content as well as tertiary structure of hCA II upon drug binding. Copyright © 2012 Elsevier B.V. All rights reserved.

The effects of some tumor markers on human erythrocyte (HCA-I and HCA-II), bovine erythrocyte (BCA) and bovine lung (CA-IV) carbonic anhydrase enzyme activities in vitro.

PubMed

Demir, N; Nadaroglu, H; Gungor, A A; Demir, Y

2015-01-01

The influence of prostatic acid phosphatase (PAP) and human chorionic gonadotropin (HCG), tumor markers have been investigated on human erythrocyte carbonic anhydrase (HCA-I and HCA-II) and bovine erythrocyte (BCA) and bovine lung carbonic anhydrase (CA-IV) in vitro. Tumor markers are substances that can often be detected in higher-than-normal amounts in the blood, urine, or body tissues of some patients with certain types of cancer. Tumor markers are produced either by the tumor itself or by the body in response to the presence of cancer or certain benign (noncancerous) conditions. In addition to their role in cancer diagnosis, some tumor marker levels are measured before treatment to help doctors plan appropriate therapy. All of the tumor markers were determined to have inhibition effect, on human CA-I, CA-II, bovine erythrocyte CA (BCA) and bovine lung CA-IV isoenzymes. The effect of each tumor marker on CA was investigated by Wilbur-Andersen method modified by Rickly et al Inhibition effects of two different tumor markers on human CA-I, CA-II, bovine erythrocyte CA (BCA) and bovine lung CA-IV isoenzymes were determined by using the CO2-Hydratase method by plotting activity % vs (tumor markers). I50 values of tumor markers exhibiting inhibition effects were found by means of these graphs (Tab.1, Fig. 2, Ref. 20).

Investigation of the Effect of Some Optically Active Imine Compounds on the Enzyme Activities of hCA-I and hCA-II under In Vitro Conditions: An Experimental and Theoretical Study.

PubMed

Tektas, Osman; Akkemik, Ebru; Baykara, Haci

2016-06-01

Inhibitors of carbonic anhydrase (hCA; EC 4.2.1.1) are used as medicines for many diseases. Therefore, they are very important. In this study, a known series of Schiff bases were synthesized and their effects on the activities of hCA-I and hCA-II, which are cytosolic isoenzymes of carbonic anhydrase, were investigated under in vitro conditions. The synthesized compounds (H1, H2, H3, and H4) were found to cause inhibition on enzyme activities of hCA-1 and hCA-II. IC50 values of H1, H2, H3, and H4 compounds were 140, 88, 201, and 271 μM for hCA-I enzyme activity and 134, 251, 79, and 604 μM for hCA-II enzyme activity, respectively. The synthesized Schiff bases were characterized by several methods, including (1) H NMR, FT-IR, elemental analysis, and polarimetric measurements. Correlation coefficient square values (R(2) ) of comparison of the theoretical and experimental (1) H NMR shifts for H1, H2, H3, and H4 compounds were found as 0.9781, 0.9814, 0.9758, and 0.8635, respectively. © 2016 Wiley Periodicals, Inc.

A Bispidol Chelator with a Phosphonate Pendant Arm: Synthesis, Cu(II) Complexation, and 64Cu Labeling.

PubMed

Gillet, Raphaël; Roux, Amandine; Brandel, Jérémy; Huclier-Markai, Sandrine; Camerel, Franck; Jeannin, Olivier; Nonat, Aline M; Charbonnière, Loïc J

2017-10-02

Here we present the synthesis and characterization of a new bispidine (3,7-diazabicyclo[3.3.1]nonane) ligand with N-methanephosphonate substituents (L 2 ). Its physicochemical properties in water, as well as those of the corresponding Cu(II) and Zn(II) complexes, have been evaluated by using UV-visible absorption spectroscopy, potentiometry, 1 H and 31 P NMR, and cyclic voltammetry. Radiolabeling experiments with 64 Cu II have been carried out, showing excellent radiolabeling properties. Quantitative complexation was achieved within 60 min under stoichiometric conditions, at room temperature and in the nanomolar concentration range. It was also demonstrated that the complexation occurred below pH 2. Properties have been compared to those of the analogue bispidol bearing a N-methanecarboxylate substituent (L 1 ). Although both systems meet the required criteria to be used as new chelator for 64/67 Cu in terms of the kinetics of formation, thermodynamic stability, selectivity for Cu(II), and kinetic inertness regarding redox- or acid-assisted decomplexation processes, substitution of the carboxylic acid function by the phosphonic moiety is responsible for a significant increase in the thermodynamic stability of the Cu(II) complex (+2 log units for pCu) and also leads to an increase in the radiochemical yields with 64 Cu II which is quantitative for L 2 .

31-P NMR studies of intracellular pH (pH/sub i/) of the in vitro resting rat diaphragm (D) exposed to hypercapnia (HC), plus amiloride (HCA)

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

Fitzgerald, R.; Howell, S.; Jacobus, W.

1986-03-05

The authors have previously reported that the pH/sub i/ of the resting rat D in vitro fell when exposed to HC. Since pH/sub i/ influences cellular functions, it is important to understand mechanisms whereby a tissue maintains its pH/sub i/ One mechanism reported to exist in some vertebrate tissues is a sodium-proton pump which is inhibited by amiloride. If the rat D had the Na/sup +/-H/sup +/ pump, the resting rat D pH/sub i/, when exposed to hypercapnia, would decrease more if amiloride was present than if there was no amiloride. The D was placed in a 25 mm NMRmore » sample tube and superfused with buffer gassed with 95%O/sub 2/-5%CO/sub 2/ at 37/sup 0/C. Two 15 minute pulsed Fourier transform spectra were acquired at 72.89 MHz using 2 sec repetition rate during normocapnia. The D was next superfused for 60 minutes with buffer gassed with 80%O/sub 2/-20%CO/sub 2/ and containing 5 x 10/sup -4/M amiloride (n=5; HCA) or not (n=8; HC). Four 15 minute spectra were obtained; pH/sub i/ was determined from the chemical shift of P/sub i/ resonance. The pH/sub i/ (X vector +/- SE) of HC D's fell from 7.14 +/- .04 to 6.85 +/- .05 at 1 hour of exposure. The pH/sub i/ of HCA D's fell from 6.95 +/- .05 to 6.57 +/- .03. The decrease in pH/sub i/ during hypercapnia is significantly greater (P<0.01) for HCA D's. These data suggest that the rat D uses a Na/sup +/-H/sup +/ pump to regulate pH/sub i/ and that this pump operates in the in vitro resting rat D exposed to hypercapnia.« less

Neutron Structure of Human Carbonic Anhydrase II: Implications for Proton Transfer†

PubMed Central

Fisher, S. Zoë; Kovalevsky, Andrey Y.; Domsic, John F.; Mustyakimov, Marat; McKenna, Robert; Silverman, David N.; Langan, Paul A.

2010-01-01

Human carbonic anhydrase II (HCA II) catalyzes the reversible hydration of carbon dioxide to form bicarbonate and a proton. Despite many high-resolution X-ray crystal structures, mutagenesis, and kinetic data, the structural details of the active site, especially the proton transfer pathway, are unclear. A large HCA II crystal was prepared at pH 9.0 and subjected to vapor H–D exchange to replace labile hydrogens with deuteriums. Neutron diffraction studies were conducted at the Protein Crystallography Station at Los Alamos National Laboratory. The structure to 2.0 Å resolution reveals several interesting active site features: (1) the Zn-bound solvent appearing to be predominantly a D2O molecule, (2) the orientation and hydrogen bonding pattern of solvent molecules in the active site cavity, (3) the side chain of His64 being unprotonated (neutral) and predominantly in an inward conformation pointing toward the zinc, and (4) the phenolic side chain of Tyr7 appearing to be unprotonated. The implications of these details are discussed, and a proposed mechanism for proton transfer is presented. PMID:20025241

Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity.

PubMed

Burmaoglu, Serdar; Yilmaz, Ali O; Taslimi, Parham; Algul, Oztekin; Kilic, Deryanur; Gulcin, Ilhami

2018-02-01

A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α-glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K i values of 1.14-3.92 nM against AChE, 0.24-1.64 nM against BChE, 6.73-51.10 nM against α-glycosidase, 1.80-5.10 nM against hCA I, and 1.14-5.45 nM against hCA II. © 2018 Deutsche Pharmazeutische Gesellschaft.

Carbonic anhydrase inhibitors. Inhibition of human cytosolic isoforms I and II with (reduced) Schiff's bases incorporating sulfonamide, carboxylate and carboxymethyl moieties.

PubMed

Nasr, Gihane; Cristian, Alina; Barboiu, Mihail; Vullo, Daniella; Winum, Jean-Yves; Supuran, Claudiu T

2014-05-15

A library of Schiff bases was synthesized by condensation of aromatic amines incorporating sulfonamide, carboxylic acid or carboxymethyl functionalities as Zn(2+)-binding groups, with aromatic aldehydes incorporating tert-butyl, hydroxy and/or methoxy groups. The corresponding amines were thereafter obtained by reduction of the imines. These compounds were assayed for the inhibition of two cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes, hCA I and II. The Ki values of the Schiff bases were in the range of 7.0-21,400nM against hCA II and of 52-8600nM against hCA I, respectively. The corresponding amines showed Ki values in the range of 8.6nM-5.3μM against hCA II, and of 18.7-251nM against hCA I, respectively. Unlike the imines, the reduced Schiff bases are stable to hydrolysis and several low-nanomolar inhibitors were detected, most of them incorporating sulfonamide groups. Some carboxylates also showed interesting CA inhibitory properties. Such hydrosoluble derivatives may show pharmacologic applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators.

PubMed

Akocak, Suleyman; Lolak, Nabih; Vullo, Daniela; Durgun, Mustafa; Supuran, Claudiu T

2017-12-01

A series of 20 histamine Schiff base was synthesised by reaction of histamine, a well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with substituted aldehydes. The obtained histamine Schiff bases were assayed as activators of five selected human (h) CA isozymes, the cytosolic hCA I, hCA II, and hCA VII, the membrane-anchored hCA IV and transmembrane hCA IX. Some of these compounds showed efficient activity (in the nanomolar range) against the cytosolic isoform hCA VII, which is a key CA enzyme involved in brain metabolism. Moderate activity was observed against hCA I and hCA IV (in the nanomolar to low micromolar range). The structure-activity relationship for activation of these isoforms with the new histamine Schiff bases is discussed in detail based on the nature of the aliphatic, aromatic, or heterocyclic moiety present in the aldehyde fragment of the molecule, which may participate in diverse interactions with amino acid residues at the entrance of the active site, where activators bind, and which is the most variable part among the different CA isoforms.

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

HCA regulation.

PubMed

Dory Rogers, Clare

2016-10-26

I'm proud to be a healthcare assistant (HCA) and aim to do my best by patients and provide evidence-based care. I think it's time for regulation of HCAs. We need the protection, as do the nurses who delegate to us.

Neutron structure of human carbonic anhydrase II in complex with methazolamide: Mapping the solvent and hydrogen-bonding patterns of an effective clinical drug

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

Aggarwal, Mayank; Kovalevsky, Andrey Y.; Velazquez, Hector

Carbonic anhydrases (CAs; EC 4.2.1.1) catalyze the interconversion of CO 2 and HCO 3 –, and their inhibitors have long been used as diuretics and as a therapeutic treatment for many disorders such as glaucoma and epilepsy. Acetazolamide (AZM) and methazolamide (MZM, a methyl derivative of AZM) are two of the classical CA inhibitory drugs that have been used clinically for decades. The jointly refined X-ray/neutron structure of MZM in complex with human CA isoform II (hCA II) has been determined to a resolution of 2.2 Å with an R cryst of ~16.0%. Presented in this article, along with onlymore » the second neutron structure of a clinical drug-bound hCA, is an in-depth structural comparison and analyses of differences in hydrogen-bonding network, water-molecule orientation and solvent displacement that take place upon the binding of AZM and MZM in the active site of hCA II. Even though MZM is slightly more hydrophobic and displaces more waters than AZM, the overall binding affinity ( K i) for both of the drugs against hCA II is similar (~10 n M). The plausible reasons behind this finding have also been discussed using molecular dynamics and X-ray crystal structures of hCA II–MZM determined at cryotemperature and room temperature. Furthermore, this study not only allows a direct comparison of the hydrogen bonding, protonation states and solvent orientation/displacement of AZM and MZM, but also shows the significant effect that the methyl derivative has on the solvent organization in the hCA II active site.« less

Neutron structure of human carbonic anhydrase II in complex with methazolamide: Mapping the solvent and hydrogen-bonding patterns of an effective clinical drug

DOE PAGES

Aggarwal, Mayank; Kovalevsky, Andrey Y.; Velazquez, Hector; ...

2016-07-22

Carbonic anhydrases (CAs; EC 4.2.1.1) catalyze the interconversion of CO 2 and HCO 3 –, and their inhibitors have long been used as diuretics and as a therapeutic treatment for many disorders such as glaucoma and epilepsy. Acetazolamide (AZM) and methazolamide (MZM, a methyl derivative of AZM) are two of the classical CA inhibitory drugs that have been used clinically for decades. The jointly refined X-ray/neutron structure of MZM in complex with human CA isoform II (hCA II) has been determined to a resolution of 2.2 Å with an R cryst of ~16.0%. Presented in this article, along with onlymore » the second neutron structure of a clinical drug-bound hCA, is an in-depth structural comparison and analyses of differences in hydrogen-bonding network, water-molecule orientation and solvent displacement that take place upon the binding of AZM and MZM in the active site of hCA II. Even though MZM is slightly more hydrophobic and displaces more waters than AZM, the overall binding affinity ( K i) for both of the drugs against hCA II is similar (~10 n M). The plausible reasons behind this finding have also been discussed using molecular dynamics and X-ray crystal structures of hCA II–MZM determined at cryotemperature and room temperature. Furthermore, this study not only allows a direct comparison of the hydrogen bonding, protonation states and solvent orientation/displacement of AZM and MZM, but also shows the significant effect that the methyl derivative has on the solvent organization in the hCA II active site.« less

A premerger profile of Columbia and HCA hospitals.

PubMed

McCue, M J

1996-01-01

This article profiles the premerger marketing, management, and mission characteristics of the combined Columbia and Hospital Corporation of America (HCA) entity relative to local market hospitals. The findings show that the Columbia/HCA hospitals had fewer Medicaid patients, lower proportion of outpatient revenues, higher operating cash flow per bed, lower occupancy rates, lower salary expense per discharge, higher debt to total assets, fewer beds, and a higher case-mix index relative to local competitors.

77 FR 59985 - Healthcare Corporation of America (HCA), HCA Mountain Division Including Workers Whose Wages Were...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,558] Healthcare Corporation of America (HCA), HCA Mountain Division Including Workers Whose Wages Were Reported Through Mountainstar Health, Inc. Including Workers Whose Wages Were Reported Through Health Trust Utah Management Services, Inc. Cottonwood Heights, UT; Amended...

Acetylcholinesterase and carbonic anhydrase inhibitory properties of novel urea and sulfamide derivatives incorporating dopaminergic 2-aminotetralin scaffolds.

PubMed

Özgeriş, Bünyamin; Göksu, Süleyman; Polat Köse, Leyla; Gülçin, İlhami; Salmas, Ramin Ekhteiari; Durdagi, Serdar; Tümer, Ferhan; Supuran, Claudiu T

2016-05-15

In the present study a series of urea and sulfamide compounds incorporating the tetralin scaffolds were synthesized and evaluated for their acetylcholinesterase (AChE), human carbonic anhydrase (CA, EC 4.2.1.1) isoenzyme I, and II (hCA I and hCA II) inhibitory properties. The urea and their sulfamide analogs were synthesized from the reactions of 2-aminotetralins with N,N-dimethylcarbamoyl chloride and N,N-dimethylsulfamoyl chloride, followed by conversion to the corresponding phenols via O-demethylation with BBr3. The novel urea and sulfamide derivatives were tested for inhibition of hCA I, II and AChE enzymes. These derivatives exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values of 2.61-3.69nM against hCA I, 1.64-2.80nM against hCA II, and in the range of 0.45-1.74nM against AChE. In silico techniques such as, atomistic molecular dynamics (MD) and molecular docking simulations, were used to understand the scenario of the inhibition mechanism upon approaching of the ligands into the active site of the target enzymes. In light of the experimental and computational results, crucial amino acids playing a role in the stabilization of the enzyme-inhibitor adducts were identified. Copyright © 2016 Elsevier Ltd. All rights reserved.

SiRNA-Mediated Down-Regulation of CLIC4 Gene Inhibits Cell Proliferation and Accelerates Cell Apoptosis of Mouse Liver Cancer Hca-F and Hca-P Cells.

PubMed

Yu, Qiu-Yun; Zhou, Xin-Feng; Xia, Qing; Shen, Jia; Yan, Jia; Zhu, Jiu-Ting; Li, Xiang; Shu, Ming

2018-01-01

This study explored the effects involved in silencing CLIC4 on apoptosis and proliferation of mouse liver cancer Hca-F and Hca-P cells. A CLIC4-target small interfering RNA (siRNA) was designed to compound into two individual complementary oligonucleotide chains. A process of annealing and connection to a pSilencer vector was followed by transfection with Hca-F and Hca-P cells. Quantitative real-time polymerase chain reaction and Western blotting techniques were used to determine CLIC4 mRNA and protein expressions. CCK8 assay and flow cytometry were employed for analysis of the survival and apoptosis rate as well as the cell cycle in an octreotide-induced apoptosis model. Expressions of caspase 3, caspase 9, and cleaved PARP were measured using Western blotting. The CLIC4 mRNA and protein expressions in Hca-F and Hca-P cells transfected by pSilencer-CLIC4 siRNA plasmid in the blank group displayed remarkably decreased levels of expression, when compared with both the control and negative control (NC) groups. Decreased survival rates and cleaved PARP expression, increased cell apoptosis rate,expressions of caspase 3 and caspase 9 in Hca-F and Hca-P cells were detected in groups that had been cultured in a medium containing octreotide. The pSilencer-CLIC4 siRNA-2 group when compared with the control and NC groups exhibited decreased survival rates, cleaved PARP expression, increased cell apoptosis rates, and increased expressions of caspase 3 and caspase 9 of Hca-F and Hca-P cells. The results demonstrated that siRNA-induced down-regulation of CLIC4 could proliferation, while in turn promoting apoptosis of mouse liver cancer Hca-F and Hca-P cells. J. Cell. Biochem. 119: 659-668, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

HCA Richmond Hospitals' new marketing strategy a winning plan.

PubMed

Rees, Tom

2003-01-01

HCA Richmond Hospitals, a five-hospital system in Richmond, Va., is positioning itself as a winner in a highly competitive, healthcare-saturated market since overhauling is marketing strategy a little over a year ago. The marketing strategy enables individual hospital to target their own unique constituencies. "Understanding the intricate marketing dynamics of hospital systems is today of critical importance and equal complexity," said Tony Bejamin, principal of Oxygen Advertising Inc., New York, the agency that remodeled HCA Richmond Hospitals' marketing strategy.

Reshaping the folding energy landscape of human carbonic anhydrase II by a single point genetic mutation Pro237His.

PubMed

Jiang, Yan; Su, Jing-Tan; Zhang, Jun; Wei, Xiang; Yan, Yong-Bin; Zhou, Hai-Meng

2008-01-01

Human carbonic anhydrase (HCA) II participates in a variety of important biological processes, and it has long been known that genetic mutations of HCA II are closely correlated to human disease. In this research, we investigated the effects of a genetic single point mutation P237, which is located on the surface of the molecule and does not participate in the HCA II catalysis, on HCA II activity, stability and folding. Spectroscopic studies revealed that the mutation caused more buried Trp residues to become accessible by solvent and caused the NMR signals to become less dispersed, but did not affect the secondary structure or the hydrophobic exposure of the protein. The mutant was less stable than the wild type enzyme against heat- and GdnHCl-induced inactivation, but its pH adaptation was similar to the wild type. The mutation slightly decreased the stability of the molten globular intermediate, but gradually affected the stability of the native state by a 10-fold reduction of the Gibbs free energy for the transition from the native state to the intermediate. This might have led to an accumulation of the aggregation-prone molten globular intermediate, which further trapped the proteins into the off-pathway aggregates during refolding and reduced the levels of active enzyme in vivo. The results herein suggested that the correct positioning of the long loop around P237 might be crucial to the folding of HCA II, particularly the formation of the active site.

How aromatic compounds block DNA binding of HcaR catabolite regulator

DOE PAGES

Kim, Youngchang; Joachimiak, Grazyna; Bigelow, Lance; ...

2016-04-25

Bacterial catabolism of aromatic compounds from various sources including phenylpropanoids and flavonoids that are abundant in soil plays an important role in the recycling of carbon in the ecosystem. We have determined the crystal structures of apo-HcaR from Acinetobacter sp. ADP1, a MarR/SlyA transcription factor, in complexes with hydroxycinnamates and a specific DNA operator. The protein regulates the expression of the hca catabolic operon in Acinetobacter and related bacterial strains, allowing utilization of hydroxycinnamates as sole sources of carbon. HcaR binds multiple ligands, and as a result the transcription of genes encoding several catabolic enzymes is increased. The 1.9-2.4 Åmore » resolution structures presented here explain how HcaR recognizes four ligands (ferulate, 3,4-dihydroxybenzoate, p-coumarate, and vanillin) using the same binding site. The ligand promiscuity appears to be an adaptation to match a broad specificity of hydroxycinnamate catabolic enzymes while responding to toxic thioester intermediates. Structures of apo-HcaR and in complex with a specific DNA hca operator when combined with binding studies of hydroxycinnamates show how aromatic ligands render HcaR unproductive in recognizing a specific DNA target. Furthermore, the current study contributes to a better understanding of the hca catabolic operon regulation mechanism by the transcription factor HcaR.« less

Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors.

PubMed

Vats, Lalit; Sharma, Vikas; Angeli, Andrea; Kumar, Rajiv; Supuran, Claudiu T; Sharma, Pawan K

2018-04-25

The design, synthesis and biological evaluation of a library of 1,2,3-triazole carboxylates incorporating carboxylic acid, hydroxymethyl, carboxylic acid hydrazide, carboxamide and benzenesulfonamide moieties is disclosed. All the novel compounds were investigated for their inhibition potential against carbonic anhydrase (CA, EC 4.2.1.1) human (h) isoforms hCA I, II, IV and IX, well established drug targets. The cytosolic isoform hCA I was inhibited with K i 's ranging between 53.2 nM and 7.616 μM whereas the glaucoma associated cytosolic isoform hCA II was inhibited with K i 's in the range 21.8 nM-0.807 μM. The membrane bound isoform hCA IV, involved in glaucoma and retinitis pigmentosa among others, was effectively inhibited by some of these compounds with K i  < 60 nM, better than the reference drug acetazolamide (AAZ). The tumor associated isoform hCA IX, a recently validated antitumor/antimetastatic drug target, was also effectively inhibited by some of the new sulfonamides, which possess thus the potential to be used as tools for exploring in more details the selective inhibition of hCAs involved in various pathologies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss.

PubMed

Preuss, H G; Bagchi, D; Bagchi, M; Rao, C V S; Dey, D K; Satyanarayana, S

2004-05-01

The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.

European experience of 573 liver resections for hepatocellular adenoma: a cross-sectional study by the AFC-HCA-2013 study group.

PubMed

Laurent, Alexis; Dokmak, Safi; Nault, Jean-Charles; Pruvot, François-René; Fabre, Jean-Michel; Letoublon, Christian; Bachellier, Philippe; Capussotti, Lorenzo; Farges, Olivier; Mabrut, Jean-Yves; Le Treut, Yves-Patrice; Ayav, Ahmet; Suc, Bertrand; Soubrane, Olivier; Mentha, Gilles; Popescu, Irinel; Montorsi, Marco; Demartines, Nicolas; Belghiti, Jacques; Torzilli, Guido; Cherqui, Daniel; Hardwigsen, Jean

2016-09-01

Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation. A retrospective cross-sectional study, from 27 European high-volume HPB units. 573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients. Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation.

PubMed

Offermanns, Stefan; Schwaninger, Markus

2015-04-01

Neuroinflammation is a pathology common to many neurological diseases, including multiple sclerosis (MS) and stroke. However, therapeutic attempts to modulate neuroinflammation have proved difficult. Neuroinflammatory cells express HCA2, a receptor for the endogenous neuroprotective ketone body β-hydroxybutyrate (BHB) as well as for the drugs dimethyl fumarate (DMF) and nicotinic acid, which have established efficacy in the treatment of MS and experimental stroke, respectively. This review summarizes the evidence that HCA2 is involved in the therapeutic effects of DMF, nicotinic acid, and ketone bodies in reducing neuroinflammation. Furthermore, we discuss the mechanisms underlying the beneficial effects of HCA2 activation in neuroinflammatory diseases and the therapeutic potential of recently developed synthetic ligands of HCA2. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis of a new series of dithiocarbamates with effective human carbonic anhydrase inhibitory activity and antiglaucoma action.

PubMed

Bozdag, Murat; Carta, Fabrizio; Vullo, Daniela; Akdemir, Atilla; Isik, Semra; Lanzi, Cecilia; Scozzafava, Andrea; Masini, Emanuela; Supuran, Claudiu T

2015-05-15

A new series of dithiocarbamates (DTCs) was prepared from primary/secondary amines incorporating amino/hydroxyl-alkyl, mono- and bicyclic aliphatic ring systems based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, and carbon disulfide. The compounds were investigated for the inhibition of four mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, that is, the human (h) hCA I, II, IX and XII, drug targets for antiglaucoma (hCA II and XII) or antitumor (hCA IX/XII) agents. The compounds were moderate or inefficient hCA I inhibitors (off-target isoform for both applications), efficiently inhibited hCA II, whereas some of them were low nanomolar/subnanomolar hCA IX/XII inhibitors. One DTC showed excellent intraocular pressure (IOP) lowering properties in an animal model of glaucoma, with a two times better efficiency compared to the clinically used sulfonamide dorzolamide. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects.

PubMed

Gul, Halise Inci; Kucukoglu, Kaan; Yamali, Cem; Bilginer, Sinan; Yuca, Hafize; Ozturk, Iknur; Taslimi, Parham; Gulcin, Ilhami; Supuran, Claudiu T

2016-08-01

In this study, 4-(2-substituted hydrazinyl)benzenesulfonamides were synthesized by microwave irradiation and their chemical structures were confirmed by (1)H NMR, (13)CNMR, and HRMS. Ketones used were: Acetophenone (S1), 4-methylacetophenone (S2), 4-chloroacetophenone (S3), 4-fluoroacetophenone (S4), 4-bromoacetophenone (S5), 4-methoxyacetophenone (S6), 4-nitroacetophenone (S7), 2-acetylthiophene (S8), 2-acetylfuran (S9), 1-indanone (S10), 2-indanone (S11). The compounds S9, S10 and S11 were reported for the first time, while S1-S8 was synthesized by different method than literature reported using microwave irradiation method instead of conventional heating in this study. The inhibitory effects of 4-(2-substituted hydrazinyl)benzenesulfonamide derivatives (S1-S11) against hCA I and II were studied. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized sulphonamide derivatives with Kis in the range of 1.79 ± 0.22-2.73 ± 0.08 nM against hCA I and in the range of 1.72 ± 0.58-11.64 ± 5.21 nM against hCA II, respectively.

The impact of HCA's 2006 leveraged buyout on hospital performance.

PubMed

McCue, Michael J; Thompson, Jon M

2012-01-01

Leveraged buyout (LBO) arrangements are a reorganization strategy whereby a firm assumes a substantial amount of debt to buy back its publicly held stock to become privately held. LBOs offer a firm several advantages and have the potential to increase efficiency. In the past 20 years, several healthcare firms have engaged in LBOs, but the literature on performance changes in healthcare organizations as a result of an LBO is limited. In this article, we report on a study that examined the performance of Hospital Corporation of America (HCA) hospitals before and after the LBO that was initiated in 2006. We used data from the Medicare Hospital Cost Report Information System and analyzed data from 130 HCA hospitals and 490 comparison hospitals. Findings show that HCA hospitals reduced expenses and their number of full-time equivalents (FTEs) relative to local competitor hospitals. HCA hospitals' cash-flow-margin ratio was substantially higher when adjusted for its local competing hospitals at the beginning of the LBO as well as at end of the LBO. When compared to local hospitals, HCA hospitals had a significant decrease in their capital investment in fixed assets from 2006 to 2009. These findings underscore the effectiveness of HCA's management strategies to repay debt and increase the value of the company, and they are informative for healthcare firms and their managers who are considering LBOs.

Synthesis, characterization, computational studies, antimicrobial activities and carbonic anhydrase inhibitor effects of 2-hydroxy acetophenone-N-methyl p-toluenesulfonylhydrazone and its Co(II), Pd(II), Pt(II) complexes

NASA Astrophysics Data System (ADS)

Özbek, Neslihan; Alyar, Saliha; Memmi, Burcu Koçak; Gündüzalp, Ayla Balaban; Bahçeci, Zafer; Alyar, Hamit

2017-01-01

2-Hydroxyacetophenone-N-methyl p-toluenesulfonylhydrazone (afptsmh) derived from p-toluenesulfonicacid-1-methylhydrazide (ptsmh) and its Co(II), Pd(II), Pt(II) complexes were synthesized for the first time. Synthesized compounds were characterized by spectroscopic methods (FT-IR, 1Hsbnd 13C NMR, LC-MS, UV-vis), magnetic susceptibility and conductivity measurements. 1H and 13C shielding tensors for crystal structure of ligand were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The vibrational band assignments were performed at B3LYP/6-311++G(d,p) theory level combined with scaled quantum mechanics force field (SQMFF) methodology. The antibacterial activities of synthesized compounds were studied against some Gram positive and Gram negative bacteria by using microdilution and disc diffusion methods. In vitro enzyme inhibitory effects of the compounds were measured by UV-vis spectrophotometer. The enzyme activities against human carbonic anhydrase II (hCA II) were evaluated as IC50 (the half maximal inhibitory concentration) values. It was found that afptsmh and its metal complexes have inhibitory effects on hCA II isoenzyme. General esterase activities were determined using alpha and beta naphtyl acetate substrates (α- and β-NAs) of Drosophila melanogaster (D. melanogaster). Activity results show that afptsmh does not strongly affect the bacteria strains and also shows poor inhibitory activity against hCAII isoenzyme whereas all complexes posses higher biological activities.

Characteristics of the divested HCA and AMI hospitals.

PubMed

McCue, M J; Clement, J P

1992-04-01

The primary aim of this study was to compare and contrast the predivestiture managerial and market characteristics of the following: Divested and nondivested hospitals of Hospital Corporation of America (HCA) and American Medical International (AMI). The findings indicated that HCA hospitals with 1) lower occupancy rates, 2) less growth in revenues, 3) higher debt to total asset position, 4) fewer beds, 5) less growth in their elderly populations, and 6) less growth in their markets' per capita incomes had a higher probability of being divested into HealthTrust. The results for the AMI model were similar to those for the HCA model. AMI hospitals with 1) fewer beds, 2) less growth in their markets' per capita incomes, 3) lower salary expenses per discharge, 4) lower occupancy rates, and 5) increased growth in populations had a higher probability of being divested into EPIC.

DEFPOS H α observations of H II regions

NASA Astrophysics Data System (ADS)

Aksaker, N.; Sahan, M.; Yegingil, I.; Emrahoglu, N.

2011-12-01

We present H α emission line measurements of northern bright H II regions selected from the Sharpless (1959) catalog near the Galactic plane ( b ⩽ ± 6°). A total of 10 H II regions were observed with DEFPOS (Dual Etalon Fabry-Perot Optical Spectrometer) system at the f/48 Coude focus of 150 cm RTT150 telescope located at TUBITAK National Observatory (TUG) in Antalya/Turkey. The intensities, the local standard of rest (LSR) velocities ( VLSR), and the linewidths (Full Width Half Maximum: FWHM) of the H α emission line from our observations were in the range of 84 to 745 Rayleigh ( R [one Rayleigh ( R) is 10 6/4 π photons cm -2 sr -1 s -1 = 2.4110 -7 erg cm -2 sr -1 s -1 at H α and corresponds to an emission measure (EM=∫ne2dl) of 2.3 pc cm -6 for a gas temperature of 8000 K, where ne is the averaged electron density within an emitting region in the interstellar medium; dl is distance element to the source region ( Haffner et al., 2003; Reynolds et al., 2005), 3 to -43 km s -1 and 30 to 73 km s -1, respectively. The LSR velocities and the linewidths from the data were obtained and compared with early results. We found that our results are in close agreement with them. Moreover, associated stars of some of the H II regions were updated by analyzing their location, velocities, and brightness.

Constitutive expression of HCA(2) in human retina and primary human retinal pigment epithelial cells.

PubMed

Yu, Alice L; Birke, Kerstin; Lorenz, Reinhard L; Welge-Lussen, Ulrich

2014-05-01

HCA2, a receptor of β-hydroxybutyrate and niacin, has recently been described in mouse retina and immortalized human retinal pigment epithelial (RPE) cell lines. As HCA2 might be a pharmacologic target, e.g. in diabetic retinopathy, we studied its expression in human retina and primary human RPE cells. Paraffin sections of human retina and primary human RPE cells were obtained from human donor eyes. Expression of HCA2 in human retina was investigated by immunohistochemistry of paraffin sections and by RT-PCR. HCA2 expression in primary human RPE cells was examined by immunocytochemistry and by Western-blot analysis. Positive immunohistochemical staining for HCA2 was found in paraffin sections of human retina, and positive immunocytochemical staining for HCA2 in primary human RPE cells. RT-PCR analysis detected mRNA expression of HCA2 in human retina. The expression of HCA2 protein was found in primary human RPE cells. Based on these results, HCA2 appears to be constitutively expressed in human retina and in primary human RPE cells. Although its functional role is still unknown, HCA2 may be potentially involved in the pathogenesis of various retinopathies and may offer a new therapeutic target.

Amine coupling versus biotin capture for the assessment of sulfonamide as ligands of hCA isoforms.

PubMed

Rogez-Florent, Tiphaine; Goossens, Laurence; Drucbert, Anne-Sophie; Duban-Deweer, Sophie; Six, Perrine; Depreux, Patrick; Danzé, Pierre-Marie; Goossens, Jean-François; Foulon, Catherine

2016-10-15

This work was dedicated to the development of a reliable SPR method allowing the simultaneous and quick determination of the affinity and selectivity of designed sulfonamide derivatives for hCAIX and hCAXII versus hCAII, in order to provide an efficient tool to discover drugs for anticancer therapy of solid tumors. We performed for the first time a comparison of two immobilization approaches of hCA isoforms. First one relies on the use of an amine coupling strategy, using a CM7 chip to obtain higher immobilization levels than with a CM5 chip and consequently the affinity with an higher precision (CV% < 10%). The second corresponds to a capture of proteins on a streptavidin chip, named CAP chip, after optimization of biotinylation conditions (amine versus carboxyl coupling, biotin to protein ratio). Thanks to the amine coupling approach, only hCAII and hCAXII isoforms were efficiently biotinylated to reach relevant immobilization (3000 RU and 2700 RU, respectively) to perform affinity studies. For hCAIX, despite a successful biotinylation, capture on the CAP chip was a failure. Finally, concordance between affinities obtained for the three derivatives to CAs isozymes on both chips has allowed to valid the approaches for a further screening of new derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism-related genes on the association of HCA intake with the risk of colorectal adenomas.

PubMed

Barbir, Aline; Linseisen, Jakob; Hermann, Silke; Kaaks, Rudolf; Teucher, Birgit; Eichholzer, Monika; Rohrmann, Sabine

2012-09-01

Heterocyclic aromatic amines (HCA), formed by high-temperature cooking of meat, are well-known risk factors for colorectal cancer (CRC). Enzymes metabolizing HCAs may influence the risk of CRC depending on the enzyme activity level. We aimed to assess effect modification by polymorphisms in the HCA-metabolizing genes on the association of HCA intake with colorectal adenoma (CRA) risk, which are precursors of CRC. A case-control study nested in the EPIC-Heidelberg cohort was conducted. Between 1994 and 2005, 413 adenoma cases were identified and 796 controls were matched to cases. Genotypes were determined and used to predict phenotypes (i.e., enzyme activities). Odds ratios (OR) and corresponding 95 % confidence intervals (CI) were calculated by logistic regression analysis. CRA risk was positively associated with PhIP, MeIQx, and DiMeIQx (p trend = 0.006, 0.022, and 0.045, respectively) intake. SULT1A1 phenotypes modified the effect of MeIQx on CRA risk (p (Interaction) > 0.01) such that the association of MeIQx intake with CRA was stronger for slow than for normal phenotypes. Other modifying effects by phenotypes did not reach statistical significance. HCA intake is positively associated with CRA risk, regardless of phenotypes involved in the metabolizing process. Due to the number of comparisons made in the analysis, the modifying effect of SULT1A1 on the association of HCA intake with CRA risk may be due to chance.

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

Phytochemical compounds in sport nutrition: Synephrine and hydroxycitric acid (HCA) as examples for evaluation of possible health risks.

PubMed

Bakhiya, Nadiya; Ziegenhagen, Rainer; Hirsch-Ernst, Karen I; Dusemund, Birgit; Richter, Klaus; Schultrich, Katharina; Pevny, Sophie; Schäfer, Bernd; Lampen, Alfonso

2017-06-01

Numerous food supplements contain phytochemical compounds as active ingredients. Although such supplements are often perceived by consumers as being risk-free, the safety of many of them is currently uncertain. The present review provides two examples for risk assessment for phytochemical ingredients that are used in certain supplements marketed for sportspeople-synephrine (extracted from fruits of Citrus aurantium) and hydroxycitric acid (HCA, isolated from fruits of Garcinia cambogia). Animal and human studies, as well as case reports, provide evidence for cardiovascular effects due to ingestion of high synephrine doses, especially in combination with caffeine and physical exertion. A dose of up to 6.7 mg synephrine/day, however, which is equivalent to the median dietary intake from conventional foods in Germany, is presumed to represent a safe intake from supplements. In subchronic animal studies, administration of high doses of certain HCA-containing preparations led to testicular toxicity (i.e., testicular atrophy and impaired spermatogenesis), yielding a no observed adverse effect level of 389 mg HCA/kg bw/day. In view of lack of adequate human data on the safety of HCA preparations, particularly with respect to the human male reproductive system, substantial uncertainties exist regarding the safety of supplements containing high amounts of HCA. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High expression of osteoglycin decreases gelatinase activity of murine hepatocarcinoma Hca-F cells

PubMed Central

Cui, Xiao-Nan; Tang, Jian-Wu; Song, Bo; Wang, Bo; Chen, Shan-Yan; Hou, Li

2009-01-01

AIM: To investigate the possible correlation between osteoglycin expression and gelatinase activity of mouse hepatocarcinoma Hca-F cells. METHODS: A eukaryotic expression plasmid pIRESpuro3 osteoglycin(+) was constructed and transfected into Hca-F cells to investigate the possible correlation between osteoglycin expression and gelatinase activity of Hca-F cells cultured with extract of lymph node, liver, spleen or in DMEM medium. The activity of gelatinases was examined through zymographic analysis. RESULTS: High expression of osteoglycin attenuated the gelatinase activity of Hca-F cells cultured with extract of lymph node, and at the same time, decreased the metastatic potential of Hca-F cells to peripheral lymph nodes in vivo. CONCLUSION: High expression of osteoglycin decreases the gelatinase activity of Hca-F cells cultured with extract of lymph node; regulation of gelatinase activity might be one of mechanisms that osteoglycin contributes to lymphatic metastasis suppression. PMID:20027687

Neutron diffraction of acetazolamide-bound human carbonic anhydrase II reveals atomic details of drug binding

PubMed Central

Fisher, S. Zoë; Aggarwal, Mayank; Kovalevsky, Andrey Y.; Silverman, David N.; McKenna, Robert

2012-01-01

Carbonic anhydrases (CAs) catalyze the hydration of CO2 forming HCO3− and a proton, an important reaction for many physiological processes including respiration, fluid secretion, and pH regulation. As such, CA isoforms are prominent clinical targets for treating various diseases. The clinically used acetazolamide (AZM) is a sulfonamide that binds with high affinity to human CA isoform II (HCA II). There are several X-ray structures available of AZM bound to various CA isoforms, but these complexes do not show the charged state of AZM, or hydrogen (H) atom positions of the protein and solvent. Neutron diffraction is a useful technique for directly observing H atoms and the mapping of H-bonding networks that can greatly contribute to rational drug design. To this end the neutron structure of H/D exchanged HCA II crystals in complex with AZM was determined. The structure reveals the molecular details of AZM binding and the charged state of the bound drug. This represents the first determined neutron structure of a clinically used drug bound to its target. PMID:22928733

Simultaneous occurrence of focal nodular hyperplasia and HNF1A-inactivated hepatocellular adenoma: a collision tumor simulating a composite FNH-HCA.

PubMed

Shih, Angela; Lauwers, Gregory Y; Balabaud, Charles; Bioulac-Sage, Paulette; Misdraji, Joseph

2015-09-01

Mixed focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) within a single tumor mass is rarely reported, and most of these cases are examples of tumors with features intermediate between FNH and HCA. Although a few reported cases are probably examples of true mixed tumors, none was evaluated immunohistochemically or confirmed by molecular analysis. We report a mixed FNH and HCA arising in a woman with several HNF1A-inactivated adenomas. Our case is the first case of mixed FNH and HNF1A-inactivated HCA documented by immunohistochemistry.

New Rh 2 (II,II) Architecture for the Catalytic Reduction of H +

DOE PAGES

White, Travis A.; Witt, Suzanne E.; Li, Zhanyong; ...

2015-09-25

Formamidinate-bridged Rh 2 II,II complexes containing diimine ligands of the formula cis-[Rh 2 II,II(μ-DTolF) 2(NN) 2] 2+ (Rh 2-NN 2), where DTolF = p-ditolylformamidinate and NN = dppn (benzo[i]dipyrido[3,2-a:2',3'-h]quinoxaline), dppz (dipyrido[3,2-a:2',3'-c]phenazine), and phen (1,10-phenanthroline), electrocatalytically reduce H + to H 2 in DMF solutions containing CH 3COOH at a glassy carbon electrode. Cathodic scans in the absence of acid display a Rh III,II/II,II reduction at -0.90 V vs Fc +/Fc followed by NN 0/– reduction at -1.13, -1.36, and -1.65 V for Rh 2-dppn 2, Rh 2-dppz 2, and Rh 2-phen 2, respectively. Upon the addition of acid, Rh 2-dppnmore » 2 and Rh 2-dppz 2 undergo reduction–protonation–reduction at each pyrazine-containing NN ligand prior to the Rh 2 II,II/II,I reduction. The Rh 2 II,I species is thus protonated at one of the metal centers, resulting in the formation of the corresponding Rh 2 II,III-hydride. In the case of Rh 2-phen 2, the reduction of the phen ligand is followed by intramolecular electron transfer to the Rh 2 II,II core in the presence of protons to form a Rh 2 II,III-hydride species. Further reduction and protonation at the Rh 2 core for all three complexes rapidly catalyzes H 2 formation with varied calculated turnover frequencies (TOF) and overpotential values (η): 2.6 × 10 4 s –1 and 0.56 V for Rh 2-dppn, 2.8 × 10 4 s –1 and 0.50 V for Rh 2-dppz 2, and 5.9 × 10 4 s –1 and 0.64 V for Rh 2-phen 2. Bulk electrolysis confirmed H 2 formation, and further CH 3COOH addition regenerates H 2 production, attesting to the robust nature of the architecture. The cis-[Rh 2 II,II(μ-DTolF) 2(NN) 2] 2+ architecture benefits by combining electron-rich formamidinate bridges, a redox-active Rh 2 II,II core, and electron-accepting NN diimine ligands to allow for the electrocatalysis of H + substrate to H 2 fuel.« less

Free fatty acid (FFA) and hydroxy carboxylic acid (HCA) receptors.

PubMed

Offermanns, Stefan

2014-01-01

Saturated and unsaturated free fatty acids (FFAs), as well as hydroxy carboxylic acids (HCAs) such as lactate and ketone bodies, are carriers of metabolic energy, precursors of biological mediators, and components of biological structures. However, they are also able to exert cellular effects through G protein-coupled receptors named FFA1-FFA4 and HCA1-HCA3. Work during the past decade has shown that these receptors are widely expressed in the human body and regulate the metabolic, endocrine, immune and other systems to maintain homeostasis under changing dietary conditions. The development of genetic mouse models and the generation of synthetic ligands of individual FFA and HCA receptors have been instrumental in identifying cellular and biological functions of these receptors. These studies have produced strong evidence that several FFA and HCA receptors can be targets for the prevention and treatment of various diseases, including type 2 diabetes mellitus, obesity, and inflammation.

Separation of time scales in the HCA model for sand

NASA Astrophysics Data System (ADS)

Niemunis, Andrzej; Wichtmann, Torsten

2014-10-01

Separation of time scales is used in a high cycle accumulation (HCA) model for sand. An important difficulty of the model is the limited applicability of the Miner's rule to multiaxial cyclic loadings applied simultaneously or in a combination with monotonic loading. Another problem is the lack of simplified objective HCA formulas for geotechnical settlement problems. Possible solutions of these problems are discussed.

Hybrid capture-II and LCR-E7 PCR assays for HPV typing in cervical cytologic samples.

PubMed

Yamazaki, H; Sasagawa, T; Basha, W; Segawa, T; Inoue, M

2001-10-15

As part of an ongoing cohort study in the Hokuriku region of Japan, cervical cell samples from histologically confirmed normal (n = 114) or abnormal (n = 286) women were examined for the presence of HPV DNA using a second-generation hybrid capture assay (HCA-II) and LCR-E7 PCR. HCA-II detected low-risk (HPV-6, -11, -42, 43 and -44) and high-risk (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59 and -68) HPV types, while LCR-E7 PCR detected an additional 7 HPV types and some uncharacterized types. In screening of high-grade squamous intraepithelial lesions (HSILs) and invasive cervical cancer, the sensitivities of HCA-II and LCR-E7 PCR testing the high-risk HPV types were 83% and 81%, respectively, while the specificity of both assays was 93%. The sensitivity of LCR-E7 PCR increased to 87%, which was significantly higher than that in HCA-II, when testing both high-risk and other HPV types. Sixty-eight inconsistent results (17% of total tested) from HCA-II and LCR-E7 PCR were due to (i) low copy number of HPV genome (false-negative for HCA-II, 5.3% and for LCR-E7 PCR, 1.3%), (ii) infection with HPV types undetectable by HCA-II (4.8%), (iii) multiple HPV infections (5%) or (iv) unknown reasons (0.8%). LCR-E7 PCR revealed that infections with HPV-16, -18, -31, -33, -35, -51, -52, -56, -58 or -67 was a high risk for cancer since these types predominated in HSIL and invasive cervical cancer. Samples showing high relative light units (>20) with a high-risk probe in HCA-II also gave positive results in LCR-E7 PCR and were generally associated with abnormal cervical lesions. Thus, we propose that both HCA-II and LCR-E7 PCR are valuable screening tests for premalignant and malignant cervical lesions. Copyright 2001 Wiley-Liss, Inc.

Dithiocarbamates with potent inhibitory activity against the Saccharomyces cerevisiae β-carbonic anhydrase.

PubMed

Bozdag, Murat; Carta, Fabrizio; Vullo, Daniela; Isik, Semra; AlOthman, Zeid; Osman, Sameh M; Scozzafava, Andrea; Supuran, Claudiu T

2016-01-01

Dithiocarbamates (DTCs) prepared from primary or secondary amines, which incorporated amino/hydroxyl-alkyl, mono-/bicyclic aliphatic/heterocyclic rings based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, were investigated for the inhibition of α- and β-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, such as the human (h) isoform hCA I and II, as well as the Saccharomyces cerevisiae β-CA, scCA. The yeast and its β-CA were shown earlier to be useful models of pathogenic fungal infections. The DTCs investigated here were medium potency hCA I inhibitors (K(I)s of 66.5-910 nM), were more effective as hCA II inhibitors (K(I)s of 8.9-107 nM) and some of them showed excellent, low nanomolar activity against the yeast enzyme, with inhibition constants ranging between 6.4 and 259 nM. The detailed structure activity relationship for inhibition of the yeast and human enzymes is discussed. Several of the investigated DTCs showed excellent selectivity ratios for inhibiting the yeast over the human cytosolic CA isoforms.

HCA Voices Make Council Debut.

PubMed

Cardwell, David

2012-11-28

I have been an RCN member since 2002 when healthcare assistants (HCAs) had to have an NVQ level 3 to join - so I got one. Soon after, with encouragement from the general secretary and chair of congress, I was the first HCA to vote and speak at RCN congress - in a speech in favour of nursery nurses joining the RCN with an NVQ level 2 qualification.

Joint neutron crystallographic and NMR solution studies of Tyr residue ionization and hydrogen bonding: Implications for enzyme-mediated proton transfer

PubMed Central

Michalczyk, Ryszard; Unkefer, Clifford J.; Bacik, John-Paul; Schrader, Tobias E.; Ostermann, Andreas; Kovalevsky, Andrey Y.; McKenna, Robert; Fisher, Suzanne Zoë

2015-01-01

Human carbonic anhydrase II (HCA II) uses a Zn-bound OH−/H2O mechanism to catalyze the reversible hydration of CO2. This catalysis also involves a separate proton transfer step, mediated by an ordered solvent network coordinated by hydrophilic residues. One of these residues, Tyr7, was previously shown to be deprotonated in the neutron crystal structure at pH 10. This observation indicated that Tyr7 has a perturbed pKa compared with free tyrosine. To further probe the pKa of this residue, NMR spectroscopic measurements of [13C]Tyr-labeled holo HCA II (with active-site Zn present) were preformed to titrate all Tyr residues between pH 5.4–11.0. In addition, neutron studies of apo HCA II (with Zn removed from the active site) at pH 7.5 and holo HCA II at pH 6 were conducted. This detailed interrogation of tyrosines in HCA II by NMR and neutron crystallography revealed a significantly lowered pKa of Tyr7 and how pH and Tyr proximity to Zn affect hydrogen-bonding interactions. PMID:25902526

HCA leading the way to change.

PubMed

2014-06-03

A hospital ward run by healthcare assistants? Some might be sceptical, but not patients at Headley Court Defence Medical Rehabilitation Centre in Surrey who are about to be discharged from the military into civvy street. For them, the HCA-led ward is a welcome change from the traditional medically intense nurse-led units.

Omnisphero: a high-content image analysis (HCA) approach for phenotypic developmental neurotoxicity (DNT) screenings of organoid neurosphere cultures in vitro.

PubMed

Schmuck, Martin R; Temme, Thomas; Dach, Katharina; de Boer, Denise; Barenys, Marta; Bendt, Farina; Mosig, Axel; Fritsche, Ellen

2017-04-01

Current developmental neurotoxicity (DNT) testing in animals faces major limitations, such as high cost and time demands as well as uncertainties in their methodology, evaluation and regulation. Therefore, the use of human-based 3D in vitro systems in combination with high-content image analysis (HCA) might contribute to DNT testing with lower costs, increased throughput and enhanced predictivity for human hazard identification. Human neural progenitor cells (hNPCs) grown as 3D neurospheres mimic basic processes of brain development including hNPC migration and differentiation and are therefore useful for DNT hazard identification. HCA of migrated neurospheres creates new challenges for automated evaluations because it encompasses variable cell densities, inconsistent z-layers and heterogeneous cell populations. We tackle those challenges with our Omnisphero software, which assesses multiple endpoints of the 'Neurosphere Assay.' For neuronal identification, Omnisphero reaches a true positive rate (TPR) of 83.8 % and a false discovery rate (FDR) of 11.4 %, thus being comparable to the interindividual difference among two researchers (TPR = 94.3, FDR = 11.0 %) and largely improving the results obtained by an existing HCA approach, whose TPR does not exceed 50 % at a FDR above 50 %. The high FDR of existing methods results in incorrect measurements of neuronal morphological features accompanied by an overestimation of compound effects. Omnisphero additionally includes novel algorithms to assess 'neurosphere-specific' endpoints like radial migration and neuronal density distribution within the migration area. Furthermore, a user-assisted parameter optimization procedure makes Omnisphero accessible to non-expert end users.

The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.

PubMed

Mahon, Brian P; Bhatt, Avni; Socorro, Lilien; Driscoll, Jenna M; Okoh, Cynthia; Lomelino, Carrie L; Mboge, Mam Y; Kurian, Justin J; Tu, Chingkuang; Agbandje-McKenna, Mavis; Frost, Susan C; McKenna, Robert

2016-08-23

Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.

KEY COMPARISON: BIPM comparison BIPM.RI(II)-K1.Cu-64 of the activity measurements of the radionuclide 64Cu

NASA Astrophysics Data System (ADS)

Michotte, C.; Courte, S.; Ratel, G.; Kossert, K.; Nähle, O. J.

2009-01-01

In 2009, the Physikalisch-Technische Bundesanstalt (PTB), Germany, submitted a sample of known activity of 64Cu to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM). The value of the activity submitted was about 9.3 MBq. The result of this new comparison has been approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), comparison identifier BIPM.RI(II)-K1.Cu-64. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI Section II, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

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

Boone, Christopher D.; Tu, Chingkuang; McKenna, Robert, E-mail: rmckenna@ufl.edu

The structure of human carbonic anhydrase II in complex with cholate has been determined to 1.54 Å resolution. Elucidation of the novel inhibition mechanism of cholate will aid in the development of a nonsulfur-containing, isoform-specific therapeutic agent. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO{sub 2} into bicarbonate and a proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells of the gastric mucosa, where it serves an important role in cytoprotection through bicarbonate secretion. Physiological inhibition of HCA II via the bile acids contributes tomore » mucosal injury in ulcerogenic conditions. This study details the weak biophysical interactions associated with the binding of a primary bile acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54 Å resolution revealed that cholate does not make any direct hydrogen-bond interactions with HCA II, but instead reconfigures the well ordered water network within the active site to promote indirect binding to the enzyme. Structural knowledge of the binding interactions of this nonsulfur-containing inhibitor with HCA II could provide the template design for high-affinity, isoform-specific therapeutic agents for a variety of diseases/pathological states, including cancer, glaucoma, epilepsy and osteoporosis.« less

Five-coordinate H64Q neuroglobin as a ligand-trap antidote for carbon monoxide poisoning

PubMed Central

Azarov, Ivan; Wang, Ling; Rose, Jason J.; Xu, Qinzi; Huang, Xueyin N.; Belanger, Andrea; Wang, Ying; Guo, Lanping; Liu, Chen; Ucer, Kamil B.; McTiernan, Charles F.; O’Donnell, Christopher P.; Shiva, Sruti; Tejero, Jesús; Kim-Shapiro, Daniel B.; Gladwin, Mark T.

2016-01-01

Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, with no available antidotal therapy. We introduce a potential treatment paradigm for CO poisoning, based on near-irreversible binding of CO by an engineered human neuroglobin (Ngb). Ngb is a six-coordinate hemoprotein, with the heme iron coordinated by two histidine residues. We mutated the distal histidine to glutamine (H64Q) and substituted three surface cysteines with less reactive amino acids to form a five-coordinate heme protein (Ngb-H64Q-CCC). This molecule exhibited an unusually high affinity for gaseous ligands, with a P50 value for oxygen of 0.015 mmHg. Ngb-H64Q-CCC bound CO about 500 times more strongly than did hemoglobin. Incubation of Ngb-H64Q-CCC with 100% CO-saturated hemoglobin, either cell-free or encapsulated in human red blood cells, reduced the half-life of carboxy-hemoglobin to 0.11 and 0.41 minutes, respectively, from a value that is ≥ 200 minutes when the hemoglobin or cells are only exposed to air. Infusions of Ngb-H64Q-CCC to CO-poisoned mice enhanced CO removal from red blood cells, restored heart rate and blood pressure, increased survival, and were followed by rapid renal elimination of CO-bound Ngb-H64Q-CCC. Heme-based scavenger molecules with very high CO binding affinity such as our mutant five-coordinate Ngb are potential antidotes for CO poisoning by virtue of their ability to bind and eliminate CO. PMID:27928027

ANXA11 regulates the tumorigenesis, lymph node metastasis and 5-fluorouracil sensitivity of murine hepatocarcinoma Hca-P cells by targeting c-Jun.

PubMed

Liu, Shuqing; Guo, Chunmei; Wang, Jiasheng; Wang, Bo; Qi, Houbao; Sun, Ming-Zhong

2016-03-29

Annexin A11 (Anxa11) is associated with various cancers. Using a pair of syngeneic murine hepatocarcinoma cells, Hca-P with ~25% and Hca-F with ~75% lymph node metastatic (LNM) potentials, we demonstrated Anxa11 involvement in hepatocarcinoma lymphatic metastasis. Here, ANXA11 acted as a suppressor for the tumorigenicity, LNM and 5-FU resistance of Hca-P via c-Jun. We constructed monoclonal Hca-P cell line with stable ANXA11 knockdown. Although Bax and Bcl-2 levels increased in shRNA-Anxa11-transfected Hca-P, ANXA11 downregulation showed no clear effect on Hca-P apoptosis. ANXA11 downregulation promoted in vitro migration and invasion capacities of Hca-P. In situ adhesion potential of Hca-P cells toward LN was significantly enhanced following ANXA11 downregulation. Consistently, ANXA11 downregulation promoted the in vivo tumor growth and LNM capacities of Hca-P cells. ANXA11 knockdown enhanced the chemoresistance of Hca-P cells specifically toward 5-FU instead of cisplatin. Its downregulation increased c-Jun (pSer73) and decreased c-Jun (pSer243) levels in Hca-P. c-Jun (pSer243) downregulation seemed to be only correlated with ANXA11 knockdown without the connection to 5-FU treatment. Interestingly, compared with scramble-Hca-P cells, the levels of c-Jun and c-Jun (pSer73) in shRNA-Anxa11-Hca-P cells were upregulated in the presences of 0.1 and 1.0 mg/L 5-FU. The levels changes from c-Jun and c-Jun (pSer73) in Hca-P cells showed a more obvious tendency with the combination of ANXA11 knockdown and 5-FU treatment. ANXA11 level regulates LNM and 5-FU resistance of Hca-P via c-Jun pathway. It might play an important role in hepatocarcinoma cell malignancy and be a therapeutic target for hepatocarcinoma.

CRKL overexpression suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cells.

PubMed

Lin, Qiuyue; Sun, Ming-Zhong; Guo, Chunmei; Shi, Ji; Chen, Xin; Liu, Shuqing

2015-02-01

The signal adaptor CRK family protein play important roles in cancer cell progression, proliferation, migration and invasion. Previously, we showed that CRK was involved in lymphatic metastatic potential of murine hepatocarcinoma cells. In current work, as a member of CRK family, chicken tumour virus number 10 regulator of kinase-like protein (CRKL) was revealed to be associated with malignant behaviors of Hca-P, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. CRKL overexpression in Hca-P by a constructed eukaryotic expression vector of pcDNA3.1/V5-HisB-CRKL significantly ameliorated its malignant biological properties. CCK-8 and soft agar colony formation assays indicated CRKL overexpression significantly inhibits the cell proliferation and colony formation abilities of Hca-P. Additionally, transwell assays indicated that the Hca-P cell migration and invasion capacities were apparently reduced following CRKL overexpression. As Hca-P is an ideal hepatocarcinoma cell model with low (initial) LNM potential, CRKL is shown to act as a potential suppressor and to provide new insight for both the malignant behaviors of hepatocarcinoma cells and lymphatic metastasis mechanism of hepatocarcinoma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

ANXA11 regulates the tumorigenesis, lymph node metastasis and 5-fluorouracil sensitivity of murine hepatocarcinoma Hca-P cells by targeting c-Jun

PubMed Central

Wang, Bo; Qi, Houbao; Sun, Ming-Zhong

2016-01-01

Annexin A11 (Anxa11) is associated with various cancers. Using a pair of syngeneic murine hepatocarcinoma cells, Hca-P with ~25% and Hca-F with ~75% lymph node metastatic (LNM) potentials, we demonstrated Anxa11 involvement in hepatocarcinoma lymphatic metastasis. Here, ANXA11 acted as a suppressor for the tumorigenicity, LNM and 5-FU resistance of Hca-P via c-Jun. We constructed monoclonal Hca-P cell line with stable ANXA11 knockdown. Although Bax and Bcl-2 levels increased in shRNA-Anxa11-transfected Hca-P, ANXA11 downregulation showed no clear effect on Hca-P apoptosis. ANXA11 downregulation promoted in vitro migration and invasion capacities of Hca-P. In situ adhesion potential of Hca-P cells toward LN was significantly enhanced following ANXA11 downregulation. Consistently, ANXA11 downregulation promoted the in vivo tumor growth and LNM capacities of Hca-P cells. ANXA11 knockdown enhanced the chemoresistance of Hca-P cells specifically toward 5-FU instead of cisplatin. Its downregulation increased c-Jun (pSer73) and decreased c-Jun (pSer243) levels in Hca-P. c-Jun (pSer243) downregulation seemed to be only correlated with ANXA11 knockdown without the connection to 5-FU treatment. Interestingly, compared with scramble-Hca-P cells, the levels of c-Jun and c-Jun (pSer73) in shRNA-Anxa11-Hca-P cells were upregulated in the presences of 0.1 and 1.0 mg/L 5-FU. The levels changes from c-Jun and c-Jun (pSer73) in Hca-P cells showed a more obvious tendency with the combination of ANXA11 knockdown and 5-FU treatment. ANXA11 level regulates LNM and 5-FU resistance of Hca-P via c-Jun pathway. It might play an important role in hepatocarcinoma cell malignancy and be a therapeutic target for hepatocarcinoma. PMID:26908448

Activity measurements of the radionuclides 18F and 64Cu for the NIST, USA in the ongoing comparisons BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Cu-64

NASA Astrophysics Data System (ADS)

Michotte, C.; Nonis, M.; Bergeron, D.; Cessna, J.; Fitzgerald, R.; Pibida, L.; Zimmerman, B.; Fenwick, A.; Ferreira, K.; Keightley, J.; Da Silva, I.

2017-01-01

In 2016, comparisons of activity measurements of 18F and 64Cu using the Transfer Instrument of the International Reference System (SIRTI) took place at the National Institute of Standards and Technology (NIST, USA). This is the first SIRTI comparison for 64Cu. Ampoules containing about 27 kBq of 18F and 100 kBq of 64Cu solutions were measured in the SIRTI for about 5 and 1.5 half-lives, respectively. The NIST standardized the activity in the ampoules by ionization chamber measurements traceable to 4π(LS)β-γ anticoincidence measurements. The comparisons, identifiers BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Cu-64, are linked to the corresponding BIPM.RI(II)-K1.F-18 and BIPM.RI(II)-K1.Cu-64 comparisons and degrees of equivalence with the respective key comparison reference values have been evaluated. The NIST replaces its earlier degree of equivalence for 18F obtained in the frame of the CCRI(II)-K3.F-18 comparison in 2001. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Bioactive Natural Product and Superacid Chemistry for Lead Compound Identification: A Case Study of Selective hCA III and L-Type Ca2+ Current Inhibitors for Hypotensive Agent Discovery.

PubMed

Carreyre, Hélène; Carré, Grégoire; Ouedraogo, Maurice; Vandebrouck, Clarisse; Bescond, Jocelyn; Supuran, Claudiu T; Thibaudeau, Sébastien

2017-05-31

Dodoneine (Ddn) is one of the active compounds identified from Agelanthus dodoneifolius , which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine's vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III) and L-type Ca 2+ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins.

Photoinduced transport in an H64Q neuroglobin antidote for carbon monoxide poisoning

NASA Astrophysics Data System (ADS)

Rydzewski, J.; Nowak, W.

2018-03-01

Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, without available antidotal therapy. Recently, a potential treatment for CO poisoning was introduced, based on binding of CO by neuroglobin (Ngb) with a mutated distal histidine (H64Q). Here, we present an atomistic mechanism of CO trapping by H64Q Ngb revealed by nonadiabatic molecular dynamics. We focused on CO photodissociation and recombination of CO to wild type (WT) and H64Q Ngb. Our results demonstrate that the distribution of CO within the proteins differs substantially due to rearrangement of amino acids surrounding the distal heme pocket. This leads to the decrease of the distal pocket volume in H64Q Ngb in comparison to WT Ngb, trapping migrating CO molecules in the distal pocket. We show that the mutation implicates the shortening of the time scale of CO geminate recombination, making H64Q Ngb 2.7 times more frequent binder than WT Ngb.

Photoinduced transport in an H64Q neuroglobin antidote for carbon monoxide poisoning.

PubMed

Rydzewski, J; Nowak, W

2018-03-21

Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, without available antidotal therapy. Recently, a potential treatment for CO poisoning was introduced, based on binding of CO by neuroglobin (Ngb) with a mutated distal histidine (H64Q). Here, we present an atomistic mechanism of CO trapping by H64Q Ngb revealed by nonadiabatic molecular dynamics. We focused on CO photodissociation and recombination of CO to wild type (WT) and H64Q Ngb. Our results demonstrate that the distribution of CO within the proteins differs substantially due to rearrangement of amino acids surrounding the distal heme pocket. This leads to the decrease of the distal pocket volume in H64Q Ngb in comparison to WT Ngb, trapping migrating CO molecules in the distal pocket. We show that the mutation implicates the shortening of the time scale of CO geminate recombination, making H64Q Ngb 2.7 times more frequent binder than WT Ngb.

[Effect of Ech1 overexpression on biological behavior of mouse hepatocarcinoma Hca-P cells in vitro].

PubMed

Wang, Mei; Song, Bo; Wang, Bo; Zhang, Jun; Tang, Jian-wu

2013-05-01

To investigate the effect of enoyl coenzyme A hydratase-1 (Ech1) on the proliferation and invasion ability of mouse hepatocarcinoma Hca-P cells in vitro. Recombinant pcDNA3.1(+)-Ech1 gene and pcDNA3.1(+) were transfected into Hca-P cells by cationic liposomes introduction. Clone of PEch1 cells that stably expressing Ech1 and clone of control Pvector cells were screened by G418. The Ech1 expression was identified subsequently by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The malignant behaviors of the cell lines were compared by proliferation, invasion and migration test. The cell line Hca-P cells stably expressing Ech1 gene was constructed. The relative expression of Ech1 mRNA in the PEch1 group was 3.21 ± 0.43 and in the Pvector group was 1.44 ± 0.03, with a significant difference between the two groups (P = 0.029). The results of ELISA revealed that the expression of Ech1 protein was 0.140 ± 0.005 in the PEch1 group, 0.088 ± 0.003 in the Pvector group, and 0.078 ± 0.006 in the Hca-P group, showing a significant difference between the PEch1 group and the Pvector and Hca-P groups (P < 0.05). Transwell migration test showed that the number of penetrated cells in the PEch1 group was 143.00 ± 7.25 cells, significantly higher than that of the Pvector group (95.73 ± 3.88 cells) and un-treated Hca-1 group (106.67 ± 3.54 cells, both P < 0.05). The Transwell invasion assay showed that the number of penetrated cells was 77.20 ± 5.46 cells in the PEch1 group, significantly higher than 46.34 ± 4.35 cells in the Pvector group and 49.80 ± 5.21 cells in the un-treated Hca-1 group (both P < 0.05). The results showed that overexpressed Ech1 in Hca-P cells may significantly increase the cell proliferation in a time-dependent manner. The up-regulation of Ech1 may increase to some extent the migration and invasion capacity of Hca-P cells. The efforts aiming at up-regulation of Ech1 expression may

Investigation of the imaging characteristics of the ALBIRA II small animal PET system for 18F, 68Ga and 64Cu.

PubMed

Attarwala, Ali Asgar; Karanja, Yvonne Wanjiku; Hardiansyah, Deni; Romanó, Chiara; Roscher, Mareike; Wängler, Björn; Glatting, Gerhard

2017-06-01

In this study the performance characteristics of the Albira II PET sub-system and the response of the system for the following radionuclides 18 F, 68 Ga and 64 Cu was analyzed. The Albira II tri-modal system (Bruker BioSpin MRI GmbH, Ettlingen, Germany) is a pre-clinical device for PET, SPECT and CT. The PET sub-system uses single continuous crystal detectors of lutetium yttrium orthosilicate (LYSO). The detector assembly consists of three rings of 8 detector modules. The transaxial field of view (FOV) has a diameter of 80mm and the axial FOV is 148mm. A NEMA NU-4 image quality phantom (Data Spectrum Corporation, Durham, USA) having five rods with diameters of 1, 2, 3, 4 and 5mm and a uniform central region was used. Measurements with 18 F, 68 Ga and 64 Cu were performed in list mode acquisition over 10h. Data were reconstructed using a maximum-likelihood expectation-maximization (MLEM) algorithm with iteration numbers between 5 and 50. System sensitivity, count rate linearity, convergence and recovery coefficients were analyzed. The sensitivities for the entire FOV (non-NEMA method) for 18 F, 68 Ga and 64 Cu were (3.78±0.05)%, (3.97±0.18)% and (3.79±0.37)%, respectively. The sensitivity based on the NEMA protocol using the 22 Na point source yielded (5.53±0.06)%. Dead-time corrected true counts were linear for activities ≤7MBq ( 18 F and 68 Ga) and ≤17MBq ( 64 Cu) in the phantom. The radial, tangential and axial full widths at half maximum (FWHMs) were 1.52, 1.47 and 1.48mm. Recovery coefficients for the uniform region with a total activity of 8MBq in the phantom were (0.97±0.05), (0.98±0.06), (0.98±0.06) for 18 F, 68 Ga and 64 Cu, respectively. The Albira II pre-clinical PET system has an adequate sensitivity range and the system linearity is suitable for the range of activities used for pre-clinical imaging. Overall, the system showed a favorable image quality for pre-clinical applications. Copyright © 2017. Published by Elsevier GmbH.

Antioxidant Activity, Acetylcholinesterase, and Carbonic Anhydrase Inhibitory Properties of Novel Ureas Derived from Phenethylamines.

PubMed

Aksu, Kadir; Özgeriş, Bünyamin; Taslimi, Parham; Naderi, Ali; Gülçin, İlhami; Göksu, Süleyman

2016-12-01

A series of ureas derived from phenethylamines were synthesized and evaluated for human carbonic anhydrase (hCA) I and II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzyme inhibitory activities and antioxidant properties. The ureas were synthesized from the reactions of substituted phenethylamines with N,N-dimethylcarbamoyl chloride; then, the synthesized compounds were converted to their corresponding phenolic derivatives via O-demethylation. hCA I and II were effectively inhibited by the newly synthesized compounds, with K i values in the range of 0.307-0.432 nM for hCA I and 0.149-0.278 nM for hCA II. On the other hand, the K i parameters of these compounds for AChE and BChE were determined in the range of 0.129-0.434 and 0.095-0.207 nM, respectively. Phenolic ureas also showed good antioxidant activities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Increased Calcium Levels and Prolonged Shelf Life in Tomatoes Expressing Arabidopsis H+/Ca2+ Transporters1

PubMed Central

Park, Sunghun; Cheng, Ning Hui; Pittman, Jon K.; Yoo, Kil Sun; Park, Jungeun; Smith, Roberta H.; Hirschi, Kendal D.

2005-01-01

Here we demonstrate that fruit from tomato (Lycopersicon esculentum) plants expressing Arabidopsis (Arabidopsis thaliana) H+/cation exchangers (CAX) have more calcium (Ca2+) and prolonged shelf life when compared to controls. Previously, using the prototypical CAX1, it has been demonstrated that, in yeast (Saccharomyces cerevisiae) cells, CAX transporters are activated when the N-terminal autoinhibitory region is deleted, to give an N-terminally truncated CAX (sCAX), or altered through specific manipulations. To continue to understand the diversity of CAX function, we used yeast assays to characterize the putative transport properties of CAX4 and N-terminal variants of CAX4. CAX4 variants can suppress the Ca2+ hypersensitive yeast phenotypes and also appear to be more specific Ca2+ transporters than sCAX1. We then compared the phenotypes of sCAX1- and CAX4-expressing tomato lines. The sCAX1-expressing tomato lines demonstrate increased vacuolar H+/Ca2+ transport, when measured in root tissue, elevated fruit Ca2+ level, and prolonged shelf life but have severe alterations in plant development and morphology, including increased incidence of blossom-end rot. The CAX4-expressing plants demonstrate more modest increases in Ca2+ levels and shelf life but no deleterious effects on plant growth. These findings suggest that CAX expression may fortify plants with Ca2+ and may serve as an alternative to the application of CaCl2 used to extend the shelf life of numerous agriculturally important commodities. However, judicious regulation of CAX transport is required to assure optimal plant growth. PMID:16244156

Pilot Study of 64Cu(I) for PET Imaging of Melanoma

DOE PAGES

Jiang, Lei; Tu, Yingfeng; Hu, Xiang; ...

2017-05-31

Currently, 64Cu(II) labeled tracers including 64CuCl 2 have been widely applied in the research of molecular imaging and therapy. Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells, and specially responsible for the transportation of Cu(I) not Cu(II). Thus, we investigated the feasible application of 64Cu(I) for PET imaging. 64Cu(II) was reduced to 64Cu(I) with the existence of sodium L-ascorbate, DL-Dithiothreitol or cysteine. Cell uptake and efflux assay was investigated using B16F10 and A375 cell lines, respectively. Small animal PET and biodistribution studies were performed in both B16F10 and A375 tumor-bearing mice. Comparedmore » with 64Cu(II), 64Cu(I) exhibited higher cellular uptake by melanoma, which testified CTR1 specially influx of Cu(I). But, due to oxidation reaction in vivo, no significant difference between 64Cu(I) and 64Cu(II) was observed through PET images and biodistribution. In addition, radiation absorbed doses for major tissues of human were calculated based on the mouse biodistribution. Radiodosimetry calculations for 64/67Cu(I) and 64/67Cu(II) were similar, which suggested that although melanoma were with high radiation absorbed doses, high radioactivity accumulation by liver and kidney should be noticed for the further application. Thus, 64Cu(I) should be further studied to evaluate it as a PET imaging radiotracer.« less

Pilot Study of 64Cu(I) for PET Imaging of Melanoma

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

Jiang, Lei; Tu, Yingfeng; Hu, Xiang

Currently, 64Cu(II) labeled tracers including 64CuCl 2 have been widely applied in the research of molecular imaging and therapy. Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells, and specially responsible for the transportation of Cu(I) not Cu(II). Thus, we investigated the feasible application of 64Cu(I) for PET imaging. 64Cu(II) was reduced to 64Cu(I) with the existence of sodium L-ascorbate, DL-Dithiothreitol or cysteine. Cell uptake and efflux assay was investigated using B16F10 and A375 cell lines, respectively. Small animal PET and biodistribution studies were performed in both B16F10 and A375 tumor-bearing mice. Comparedmore » with 64Cu(II), 64Cu(I) exhibited higher cellular uptake by melanoma, which testified CTR1 specially influx of Cu(I). But, due to oxidation reaction in vivo, no significant difference between 64Cu(I) and 64Cu(II) was observed through PET images and biodistribution. In addition, radiation absorbed doses for major tissues of human were calculated based on the mouse biodistribution. Radiodosimetry calculations for 64/67Cu(I) and 64/67Cu(II) were similar, which suggested that although melanoma were with high radiation absorbed doses, high radioactivity accumulation by liver and kidney should be noticed for the further application. Thus, 64Cu(I) should be further studied to evaluate it as a PET imaging radiotracer.« less

Heavy metal ion inhibition studies of human, sheep and fish α-carbonic anhydrases.

PubMed

Demirdağ, Ramazan; Yerlikaya, Emrah; Şentürk, Murat; Küfrevioğlu, Ö İrfan; Supuran, Claudiu T

2013-04-01

Carbonic anhydrases (CAs, EC 4.2.1.1) were purified from sheep kidney (sCA IV), from the liver of the teleost fish Dicentrarchus labrax (dCA) and from human erythrocytes (hCA I and hCA II). The purification procedure consisted of a single step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The kinetic parameters of these enzymes were determined for their esterase activity with 4-nitrophenyl acetate as substrate. The following metal ions, Pb(2+), Co(2+), Hg(2+), Cd(2+), Zn(2+), Se(2+), Cu(2+), Al(3+) and Mn(3+) showed inhibitory effects on these enzymes. The tested metal ions inhibited these CAs competitively in the low milimolar/submillimolar range. The susceptibility to various cations inhibitors differs significantly between these vertebrate α-CAs and is probably due to their binding to His64 or the histidine cluster.

NGC 6334 and NGC 6357: Hα kinematics and the nature of the H II regions

NASA Astrophysics Data System (ADS)

Russeil, D.; Tigé, J.; Adami, C.; Anderson, L. D.; Schneider, N.; Zavagno, A.; Samal, M. R.; Amram, P.; Guennou, L.; Le Coarer, E.; Walsh, A.; Longmore, S. N.; Purcell, C.

2016-03-01

Aims: NGC 6334 and NGC 6357 are amongst the most active, optically visible Galactic star-forming complexes. They are composed of several H II regions that have a significant impact on their surrounding. The aim of this paper is to present a kinematic study of the optical H II regions that belong to NGC 6334 and NGC 6357. Methods: We use Fabry-Perot interferometer observations of the Hα line, which cover NGC 6334 and NGC 6357. These observations allow us to analyse the Hα line profiles to probe the kinematics of the ionised gas of both regions. We complement the Hα observations with multi-wavelength data to specify the nature of the H II regions. Results: We determine the dynamical nature of the optical H II regions that belongs to NGC 6334 and NGC 6357. In NGC 6334, GUM 61 is an expanding wind shell-like H II region, GUM 64b exhibits a champagne flow, GM1-24 is the Hα counterpart of two larger regions and H II 351.2+0.5 is, in fact, composed of two H II regions. In NGC 6357, H II 353.08+0.28 and H II 353.09+0.63 are probably stellar wind-shaped bubble H II regions, while H II 353.42+0.45 is a classical photo-ionised H II region. We suggest that, at large scale, star-formation seems to be triggered where large/old H II regions intersect. Inversely, stellar formation seems to have already started in the NGC 6334 north-east filament, irrespective of any evident external H II region impact. While NGC 6357 shows more complicated kinematics, NGC 6334 is characterised by a more active stellar formation. The Hα data (FITS cubes) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A135

Studies of copper trafficking in a mouse model of Alzheimer's disease by positron emission tomography: comparison of 64Cu acetate and 64CuGTSM.

PubMed

Andreozzi, Erica M; Torres, Julia Baguña; Sunassee, Kavitha; Dunn, Joel; Walker-Samuel, Simon; Szanda, Istvan; Blower, Philip J

2017-11-15

Alzheimer's disease can involve brain copper dyshomeostasis. We aimed to determine the effect of AD-like pathology on 64 Cu trafficking in mice, using positron emission tomography (PET imaging), during 24 hours after intravenous administration of ionic 64 Cu (Cu(ii) acetate) and 64 Cu-GTSM (GTSMH 2 = glyoxalbis(thiosemicarbazone)). Copper trafficking was evaluated in 6-8-month-old and 13-15 month-old TASTPM transgenic and wild-type mice, by imaging 0-30 min and 24-25 h after intravenous administration of 64 Cu tracer. Regional 64 Cu distribution in brains was compared by ex vivo autoradiography to that of amyloid-β plaque. 64 Cu-acetate showed uptake in, and excretion through, liver and kidneys. There was minimal uptake in other tissues by 30 minutes, and little further change after 24 h. Radioactivity within brain was focussed in and around the ventricles and was significantly greater in younger mice. 64 CuGTSM was taken up in all tissues by 30 min, remaining high in brain but clearing substantially from other tissues by 24 h. Distribution in brain was not localised to specific regions. TASTPM mice showed no major changes in global or regional 64 Cu brain uptake compared to wildtype after administration of 64 Cu acetate (unlike 64 Cu-GTSM) but efflux of 64 Cu from brain by 24 h was slightly greater in 6-8 month-old TASTPM mice than in wildtype controls. Changes in copper trafficking associated with Alzheimer's-like pathology after administration of ionic 64 Cu are minor compared to those observed after administration of 64 Cu-GTSM. PET imaging with 64 Cu could help understand changes in brain copper dynamics in AD and underpin new clinical diagnostic imaging methods.

Effects of pyrazole partial agonists on HCA(2) -mediated flushing and VLDL-triglyceride levels in mice.

PubMed

Li, Zhaosha; Blad, Clara C; van der Sluis, Ronald J; de Vries, Henk; Van Berkel, Theo J C; Ijzerman, Adriaan P; Hoekstra, Menno

2012-10-01

Niacin can effectively treat dyslipidaemic disorders. However, its clinical use is limited due to the cutaneous flushing mediated by the nicotinic acid receptor HCA(2) . In the current study, we evaluated two partial agonists for HCA(2) , LUF6281 and LUF6283, with respect to their anti-dyslipidaemic potential and cutaneous flushing effect. In vitro potency and efficacy studies with niacin and the two HCA(2) partial agonists were performed using HEK293T cells stably expressing human HCA(2) . Normolipidaemic C57BL/6 mice received either niacin or the HCA(2) partial agonists (400 mg·kg(-1) ·day(-1) ) once a day for 4 weeks for evaluation of their effects in vivo. Radioligand competitive binding assay showed K(i) values for LUF6281 and LUF6283 of 3 and 0.55 µM. [(35) S]-GTPγS binding revealed the rank order of their potency as niacin > LUF6283 > LUF6281. All three compounds reduced plasma VLDL-triglyceride concentrations similarly, while LUF6281 and LUF6283, in contrast to niacin, did not also exhibit the unwanted flushing side effect in C57BL/6 mice. Niacin reduced the expression of lipolytic genes HSL and ATGL in adipose tissue by 50%, whereas LUF6281 and LUF6283 unexpectedly did not. In contrast, the decrease in VLDL-triglyceride concentration induced by LUF6281 and LUF6283 was associated with a parallel >40% reduced expression of APOB within the liver. The current study identifies LUF6281 and LUF6283, two HCA(2) partial agonists of the pyrazole class, as promising drug candidates to achieve the beneficial lipid lowering effect of niacin without producing the unwanted flushing side effect. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Open saccharin-based secondary sulfonamides as potent and selective inhibitors of cancer-related carbonic anhydrase IX and XII isoforms.

PubMed

D'Ascenzio, Melissa; Guglielmi, Paolo; Carradori, Simone; Secci, Daniela; Florio, Rosalba; Mollica, Adriano; Ceruso, Mariangela; Akdemir, Atilla; Sobolev, Anatoly P; Supuran, Claudiu T

2017-12-01

A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by reductive ring opening of the newly synthesized N-alkylated saccharin derivatives and were shown to be inactive against the two cytosolic off-target hCA I and II (K i s > 10 µM). Interestingly, these compounds inhibited hCA IX in the low nanomolar range with K i s ranging between 20 and 298 nM and were extremely potent inhibitors of hCA XII isoenzyme (K i s ranging between 4.3 and 432 nM). Since hCA IX and XII are the cancer-related isoforms recently validated as drug targets, these results represent an important goal in the development of new anticancer candidates. Finally, a computational approach has been performed to better correlate the biological data to the binding mode of these inhibitors.

Design, Synthesis, and X-ray of Selenides as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology.

PubMed

Angeli, Andrea; di Cesare Mannelli, Lorenzo; Trallori, Elena; Peat, Thomas S; Ghelardini, Carla; Carta, Fabrizio; Supuran, Claudiu T

2018-05-10

A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for their inhibition on six human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms such as the physiologically relevant hCA I, II, VA, VB, VII, and IX and the X-ray complex in adduct with hCA II for some of them investigated. These enzymes are involved in a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy, arthritis, metabolic disorders, and cancer. The investigated compounds showed potent inhibitory action against hCA VA, VII, and IX, in the low nanomolar range, thus making them of interest for the development of isoform-selective inhibitors and as candidates for various biomedical applications.

Indomethacin-Kollidon VA64 Extrudates: A Mechanistic Study of pH-Dependent Controlled Release.

PubMed

Tres, Francesco; Treacher, Kevin; Booth, Jonathan; Hughes, Leslie P; Wren, Stephen A C; Aylott, Jonathan W; Burley, Jonathan C

2016-03-07

Because of its weakly acidic nature (pKa of 4.5), indomethacin presents an aqueous solubility that significantly increases when changing from acidic to neutral/alkaline pH (1.5 μg/mL at pH 1.2 and 105.2 μg/mL at pH 7.4). We have therefore investigated the impact of the dissolution medium pH on the dissolution performance of indomethacin:Kollidon VA64 extrudates. The impact of the drug loading on the dissolution properties of these systems was also examined (5%, 15%, 30%, 50%, 70%, and 90% drug loading). Time-resolved Raman spectroscopy along with in-line UV-vis spectrophotometry was employed to directly relate changes in dissolution behavior to physicochemical changes that occur to the extrudate during the test. The dissolution tests were performed in pH 2 HCl (to mimic the stomach conditions), and this was then switched during the experiment to pH 6.8 phosphate buffer (to simulate the poststomach conditions). The rotating disc dissolution rate test was also used to simultaneously measure the dissolution rate of both the drug and the polymer. We found that in pH 2 HCl buffer, for the 15% or higher drug-loaded extrudates, Kollidon VA64 preferentially dissolves from the exterior of the compact leaving an amorphous drug-rich hydrophobic shell, which, similarly to an enteric coating, inhibits the drug release. The in situ formation of an enteric coating has been previously hypothesized, and this has been the first time that is directly observed in a pH-variable dissolution test. The dissolution medium switch to pH 6.8 phosphate buffer, due to the large increase of the aqueous solubility of indomethacin at this pH, leads to rapid dissolution of the material forming the coating and therefore total drug release. In contrast, the 5% extrudate is fully hydrated and quickly dissolves at low pH pointing to a dissolution performance dependent on highly water-soluble Kollidon VA64.

Cinnamic Acid, an Autoinducer of Its Own Biosynthesis, Is Processed via Hca Enzymes in Photorhabdus luminescens▿

PubMed Central

Chalabaev, Sabina; Turlin, Evelyne; Bay, Sylvie; Ganneau, Christelle; Brito-Fravallo, Emma; Charles, Jean-François; Danchin, Antoine; Biville, Francis

2008-01-01

Photorhabdus luminescens, an entomopathogenic bacterium and nematode symbiont, has homologues of the Hca and Mhp enzymes. In Escherichia coli, these enzymes catalyze the degradation of the aromatic compounds 3-phenylpropionate (3PP) and cinnamic acid (CA) and allow the use of 3PP as sole carbon source. P. luminescens is not able to use 3PP and CA as sole carbon sources but can degrade them. Hca dioxygenase is involved in this degradation pathway. P. luminescens synthesizes CA from phenylalanine via a phenylalanine ammonia-lyase (PAL) and degrades it via the not-yet-characterized biosynthetic pathway of 3,5-dihydroxy-4-isopropylstilbene (ST) antibiotic. CA induces its own synthesis by enhancing the expression of the stlA gene that codes for PAL. P. luminescens bacteria release endogenous CA into the medium at the end of exponential growth and then consume it. Hca dioxygenase is involved in the consumption of endogenous CA but is not required for ST production. This suggests that CA is consumed via at least two separate pathways in P. luminescens: the biosynthesis of ST and a pathway involving the Hca and Mhp enzymes. PMID:18245247

Annexin A11 knockdown inhibits in vitro proliferation and enhances survival of Hca-F cell via Akt2/FoxO1 pathway and MMP-9 expression.

PubMed

Liu, Shuqing; Wang, Jiasheng; Guo, Chunmei; Qi, Houbao; Sun, Ming-Zhong

2015-03-01

Annexin A11 (Anxa11), a Ca(2+)-regulated phospholipid-binding protein, is involved in cell apoptosis, differentiation, vesicle trafficking, cancer progression and autoimmune diseases. Previous study from our group indicated that Anxa11 was associated with lymphatic metastatic potential of murine hepatocarcinoma cells. Herein, we investigated the effects and action mechanism of Anxa11 knockdown on in vitro cell proliferation and apoptosis of Hca-F, a murine hepatocarcinoma cell with∼75% lymph node metastatic potential. Real-time PCR and western blotting assays indicated that Anxa11 was significantly downregulated in monoclonal Anxa11-shRNA-transfected Hca-F cells. Anxa11 knockdown in Hca-F suppressed its in vitro proliferation and cell apoptosis capacities. Following Anxa11 knockdown in Hca-F cells, Bax/Bcl-2 expression level ratio, Akt2 and FoxO1 (pSer319) expression levels as well as MMP-9 mRNA and active MMP-9 protein levels were significantly elevated in Hca-F cells. In conclusion, Annexin A11 knockdown inhibits the in vitro proliferation and cell apoptosis of Hca-F cell via Akt2/FoxO1 and/or MMP-9 expression pathway. Anxa11 might play an important role in hepatocarcinoma cell invasion and metastasis and hepatocarcinoma malignancy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Novel eugenol derivatives: Potent acetylcholinesterase and carbonic anhydrase inhibitors.

PubMed

Topal, Fevzi; Gulcin, Ilhami; Dastan, Arif; Guney, Murat

2017-01-01

Eugenol was used as starting material to obtain some phenolic compounds. The synthesis of these phenolic compounds was performed in a two-step procedure. The structures of the formed products (novel eugenol derivatives 1-6) have been determined on the basis of NMR spectroscopy and other spectroscopic methods. The compounds were tested in terms of carbonic anhydrase (CA) inhibition potency. Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes, which catalyse the reaction between carbon dioxide (CO 2 ) and water (H 2 O), to generate bicarbonate (HCO 3 - ) and protons (H + ). CO 2 , HCO 3 - and H + are essential molecules and ions for many important physiologic processes occurring in all living organisms. Acetylcholinesterase (AChE, E.C.3.1.1.7) is found in high concentrations in the red blood cells and brain. Novel eugenol derivatives (1-6) were tested for the inhibition of two cytosolic CA isoforms I, and II (hCA I, and II) and AChE. These compounds demonstrated effective inhibitory profiles with Ki values in ranging of 113.48-738.69nM against hCA I, 92.35-530.81nM against hCA II, and 90.10-379.57nM against AChE, respectively. On the other hand, acetazolamide clinically used as CA inhibitor, shoed Ki value of 594.11nM against hCA I, and 120.68nM against hCA II, respectively. Also, AChE was inhibited by tacrine as an AChE inhibitor at the 71.18nM level. Copyright © 2016 Elsevier B.V. All rights reserved.

Coupled Abiotic-Biotic Degradation of Bisphenol A

NASA Astrophysics Data System (ADS)

Im, J.; Prevatte, C.; Campagna, S. R.; Loeffler, F.

2014-12-01

Bisphenol A (BPA) is a ubiquitous environmental contaminant with weak estrogenic activity. BPA is readily biodegradable with oxygen available, but is recalcitrant to microbial degradation under anoxic conditions. However, BPA is susceptible to abiotic transformation under anoxic conditions. To better understand the fate of BPA in anoxic environments, the kinetics of BPA transformation by manganese oxide (d-MnO2) were investigated. BPA was rapidly transformed by MnO2 with a pseudo-first-order rate constant of 0.413 min-1. NMR and LC-MS analyses identified 4-hydroxycumyl alcohol (HCA) as a major intermediate. Up to 64% of the initial amount of BPA was recovered as HCA within 5 min, but the conversion efficiency decreased with time, suggesting that HCA was further degraded by MnO2. Further experiments confirmed that HCA was also susceptible to transformation by MnO2, albeit at 5-fold lower rates than BPA transformation. Mass balance approaches suggested that HCA was the major BPA transformation intermediate, but other compounds may also be formed. The abiotic transformation of BPA by MnO2 was affected by pH, and 10-fold higher transformation rates were observed at pH 4.5 than at pH 10. Compared to BPA, HCA has a lower octanol-water partitioning coefficient (Log Kow) of 0.76 vs 2.76 for BPA and a higher aqueous solubility of 2.65 g L-1 vs 0.31 g L-1 for BPA, suggesting higher mobility of HCA in the environment. Microcosms established with freshwater sediment materials collected from four geographically distinct locations and amended with HCA demonstrated rapid HCA biodegradation under oxic, but not under anoxic conditions. These findings suggest that BPA is not inert under anoxic conditions and abiotic reactions with MnO2 generate HCA, which has increased mobility and is susceptible to aerobic degradation. Therefore, coupled abiotic-biotic processes can affect the fate and longevity of BPA in terrestrial environments.

Far Outer Galaxy H II Regions

NASA Technical Reports Server (NTRS)

Rudolph, A. L.; deGues, E. J.; Brand, J.; Wouterloot, J. G. A.; Gross, Anthony R. (Technical Monitor)

1994-01-01

We have made a multifrequency (6, 3.6, and 2 cm), high-resolution (3"-6"), radio continuum survey of IRAS selected sources from the catalogue of Wouterloot & Brand (1989) to search for and study H II regions in the far outer Galaxy. We identified 31 sources in this catalog with well determined galactocentric distances, and with R approx.. greater than 15 kpc and L(sub FIR) approx.greater than 10(exp 4) solar luminosity, indicating the presence of high-mass star-formation. We have observed 11 of these sources with the Very Large Array (VLA). We observed the sources at 6 and 2 cm using "scaled arrays", making possible a direct and reliable comparison of the data at these two wavelengths for the determination of spectral indices. We detected a total of 12 radio sources, of which 10 have spectral indices consistent with optically-thin free-free emission from H II regions. Combined with previous VLA observations by other investigators, we have data on a total of 15 H II regions at galactocentric distances of 15 to 18.2kpc, among the most remote H II regions found in our Galaxy. The sizes of the H II regions range from approx. less than 0.10 to 2.3 pc. Using the measured fluxes and sizes, we determine the electron densities, emission measures, and excitation parameters of the H II regions, as well as the fluxes of Lyman continuum photons needed to keep the nebulae ionized. The sizes and electron densities are consistent with most of the sources detected in this survey being compact or ultracompact H II regions. Seven of the fifteen H II regions have sizes approx. less than 0.20 pc. Assuming simple pressure-driven expansion of the H II regions, these sizes indicate ages approx. less than 5 x 10(exp 4) yr, or only 1% of the lifetime of an O star, which implies an unlikely overabundance of O stars in the outer Galaxy. Thus, the large number of compact H II regions suggests that the time these regions spend in a compact phase must be much longer than their dynamical

A single amino acid substitution modulates low-pH-triggered membrane fusion of GP64 protein in Autographa californica and Bombyx mori nucleopolyhedroviruses

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

Katou, Yasuhiro; Yamada, Hayato; Ikeda, Motoko

2010-09-01

We have previously shown that budded viruses of Bombyx mori nucleopolyhedrovirus (BmNPV) enter the cell cytoplasm but do not migrate into the nuclei of non-permissive Sf9 cells that support a high titer of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) multiplication. Here we show, using the syncytium formation assay, that low-pH-triggered membrane fusion of BmNPV GP64 protein (Bm-GP64) is significantly lower than that of AcMNPV GP64 protein (Ac-GP64). Mutational analyses of GP64 proteins revealed that a single amino acid substitution between Ac-GP64 H155 and Bm-GP64 Y153 can have significant positive or negative effects on membrane fusion activity. Studies using bacmid-based GP64 recombinantmore » AcMNPV harboring point-mutated ac-gp64 and bm-gp64 genes showed that Ac-GP64 H155Y and Bm-GP64 Y153H substitutions decreased and increased, respectively, the multiplication and cell-to-cell spread of progeny viruses. These results indicate that Ac-GP64 H155 facilitates the low-pH-triggered membrane fusion reaction between virus envelopes and endosomal membranes.« less

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

Inhibition of carbonic anhydrase isoforms I, II, IX and XII with novel Schiff bases: identification of selective inhibitors for the tumor-associated isoforms over the cytosolic ones.

PubMed

Sarikaya, Busra; Ceruso, Mariangela; Carta, Fabrizio; Supuran, Claudiu T

2014-11-01

A series of new Schiff bases was obtained from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide and aromatic/heterocyclic aldehydes incorporating both hydrophobic and hydrophilic moieties. The obtained sulfonamides were investigated as inhibitors of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, as well as the transmembrane, tumor-associated CA IX and XII. Most derivatives were medium potency or weak hCA I/II inhibitors, but several of them showed nanomolar affinity for CA IX and/or XII, making them an interesting example of isoform-selective compounds. The nature of the aryl/hetaryl moiety present in the initial aldehyde was the main factor influencing potency and isoform selectivity. The best and most CA IX-selective compounds incorporated moieties such as 4-methylthiophenyl, 4-cyanophenyl-, 4-(2-pyridyl)-phenyl and the 4-aminoethylbenzenesulfonamide scaffold. The best hCA XII inhibitors, also showing selectivity for this isoform, incorporated 2-methoxy-4-nitrophenyl-, 2,3,5,6-tetrafluorophenyl and 4-(2-pyridyl)-phenyl functionalities and were also derivatives of 4-aminoethylbenzenesulfonamide. The sulfanilamide and 3-fluorosulfanilamide derived Schiff bases were less active compared to the corresponding 4-aminoethyl-benzenesulfonamide derivatives. As hCA IX/XII selective inhibition is attractive for obtaining antitumor agents/diagnostic tools with a new mechanism of action, compounds of the type described here may be considered interesting preclinical candidates. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Green Bank Telescope Survey of Large Galactic H II Regions

NASA Astrophysics Data System (ADS)

Anderson, L. D.; Armentrout, W. P.; Luisi, Matteo; Bania, T. M.; Balser, Dana S.; Wenger, Trey V.

2018-02-01

As part of our ongoing H II Region Discovery Survey (HRDS), we report the Green Bank Telescope detection of 148 new angularly large Galactic H II regions in radio recombination line (RRL) emission. Our targets are located at a declination of δ > -45^\\circ , which corresponds to 266^\\circ > {\\ell }> -20^\\circ at b=0^\\circ . All sources were selected from the Wide-field Infrared Survey Explorer Catalog of Galactic H II Regions, and have infrared angular diameters ≥slant 260\\prime\\prime . The Galactic distribution of these “large” H II regions is similar to that of the previously known sample of Galactic H II regions. The large H II region RRL line width and peak line intensity distributions are skewed toward lower values, compared with that of previous HRDS surveys. We discover seven sources with extremely narrow RRLs < 10 {km} {{{s}}}-1. If half the line width is due to turbulence, these seven sources have thermal plasma temperatures < 1100 {{K}}. These temperatures are lower than any measured for Galactic H II regions, and the narrow-line components may arise instead from partially ionized zones in the H II region photodissociation regions. We discover G039.515+00.511, one of the most luminous H II regions in the Galaxy. We also detect the RRL emission from three H II regions with diameters > 100 {pc}, making them some of the physically largest known H II regions in the Galaxy. This survey completes the HRDS H II region census in the Northern sky, where we have discovered 887 H II regions and more than doubled the size of the previously known census of Galactic H II regions.

Navy-NGO Coordination for Health-Related HCA Missions: A Suggested Planning Framework

DTIC Science & Technology

2008-11-01

however, on how to work with NCOs in the HCA setting. As a result, there is currendy no systematic frame - work for military-NGO coordination. The...agencies and NGOs, make up a tertiary audience. The issues are framed in a way that reflects the Navy’s current views and thinking, but NGO perspectives...it is written mainly from a Navy-centric perspective. The framing of the issues, in particular, reflects the Navy’s current views and thinking. NGO

Structure, Stability, and Thermochemistry of the Fullerene Derivatives C64X6 (X = H, F, Cl)

NASA Astrophysics Data System (ADS)

Xu, Lei; Shao, Xueguang; Cai, Wensheng

2009-09-01

The geometrical structures, electronic properties, and stabilities of the unconventional fullerene derivatives C64X6 (X = H, F, Cl) have been systematically studied by the first-principle calculations based on the density functional theory. The fullerene derivatives 1911(2)-C64X6 generated from the pineapple-shaped C64X4 are predicted to possess the lowest energies. The other two X atoms are added to the carbon atoms with the highest local strain assessed by the pyramidalization angles. The calculations of the nucleus-independent chemical shifts suggest that the aromaticity of C64X6 affects the stability order of the derivative isomers. To address why C64H6 was not observed in the experimental study of Wang et al. (J. Am. Chem. Soc. 2006, 128, 6605) and if the halogenated derivatives C64X6 (X = F, Cl) can be synthesized, thermochemical analysis of the reaction C64X4 + X2 → C64X6 was also performed. The results indicate that the formation of C64H6 and C64Cl6 is not favored at high temperatures. The former may be a reason why C64H6 was not found in the experiment. In sharp contrast, the Gibbs free energy change to form C64F6 is found to be -23.29 kcal/mol at 2000 K, suggesting that this compound may be formed and detected in experiments. The NMR and IR spectra of 1911(2)-C64F6 are sequentially calculated and presented to facilitate future experimental identification.

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells.

PubMed

Shi, Ji; Meng, Longlong; Sun, Ming-Zhong; Guo, Chunmei; Sun, Xujuan; Lin, Qiuyue; Liu, Shuqing

2015-04-01

Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over-expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like protein, suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cell, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. In current work, we investigated the effects of CRKL knockdown on the in vitro cell proliferation, migration and invasion, and on the in vivo tumor malignancy and LNM rate and level for Hca-P cells. Western blotting assay indicated that CRKL was down-regulated by ∼90% in a monoclonal CrkL-shRNA-transfected Hca-P cells. Compared with Hca-P and unrelated-shRNA-transfected Hca-P cell, the in vitro proliferation, migration and invasion potentials were significantly enhanced following CRKL stable deregulation. CRKL knock-down significantly promoted the tumorigenicity malignancy, LNM rates and level of Hca-P-transplanted mice. Consistent with our previous work, it can be concluded CRKL plays an important role in hepatocarcinoma cell proliferation, invasion and migration as well hepatocarcinoma malignancy and metastasis. It functions as a potential tumor suppressor in hepatocarcinoma. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Sulfatase-1 knockdown promotes in vitro and in vivo aggressive behavior of murine hepatocarcinoma Hca-P cells through up-regulation of mesothelin.

PubMed

Mahmoud, Salma Abdi; Ibrahim, Mohammed Mohammed; Musa, Ahmed Hago; Huang, Yuhong; Zhang, Jun; Wang, Jingwen; Wei, Yuanyi; Wang, Li; Zhou, Shunting; Xin, Boyi; Xuan, Wei; Tang, Jianwu

2017-12-23

Our previous study (Oncotarget 2016; 7:46) demonstrated that the over-expression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line (a murine HCC cell with lymph node metastatic [LNM] rate of >75%) downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo. In current work, we investigated the effects of Sulf-1 knockdown on mesothelin (Msln) and it's effects on the in vitro cell proliferation, migration, invasion, and in vivo tumor growth and LNM rate for Hca-P cells (a murine HCC cell with LNM rate of <25%). Western blotting and qRT-PCR assay indicated that both in vitro and in vivo Sulf-1 was down-regulated by 75% and 68% and led to up regulation of Msln by 55% in shRNA-transfected-Sulf-1-Hca-P cells compared with Hca-P and nonspecific sequence control plasmid transfected Hca-P cell (shRNA-Nc-Hca-P). The in vitro proliferation, migration and invasion potentials were significantly enhanced following Sulf-1 stable down-regulation. In addition, Sulf-1 knock-down significantly promoted tumor growth and increased LNM rates of shRNA-Sulf-1-Hca-P-transplanted mice by 78.6% (11 out of 14 lymph nodes were positive of cancer). Consistent with our previous work, we confirmed that Sulf-1 plays an important role in hepatocarcinoma cell proliferation, migration, invasion and metastasis. The interaction between Sulf-1 and Msln is a potential therapeutic target in the development of liver cancer therapy.

(Fe II) 1.53 and 1.64 micron emission from pre-main-sequence stars

NASA Technical Reports Server (NTRS)

Hamann, Fred; Simon, Michal; Carr, John S.; Prato, Lisa

1994-01-01

We present flux-calibrated profiles of the (Fe II) 1.53 and 1.64 micron lines in five pre-main-sequence stars, PV Cep, V1331 Cyg, R Mon, and DG and HL Tau. The line centroids are blueshifted in all five sources, and four of the five have only blueshifted flux. In agreement with previous studies, we attribute the line asymmetries to local obscuration by dusty circumstellar disks. The absence of redshifted flux implies a minimum column density of obscuring material. The largest limit, N(sub H) greater than 3 x 10(exp 22)/sq cm, derived for V1331 Cyg, suggests disk surface densities greater than 0.05 g/sq cm and disk masses greater than 0.001 solar mass within a radius of approximately 200 AU. The narrow high-velocity lines in PV Cep, V1331 Cyg, and HL Tau require formation in well collimated winds. The maximum full opening angles of their winds range from less than 20 deg in V1331 Cyg to less than 40 deg in HL Tau. The (Fe II) data also yield estimates of the electron densities (n(sub e) approximately 10(exp 4)/cu cm), hydrogen ionization fractions (f(sub H(+)) approximately 1/3), mass-loss rates (approximately 10(exp -7) to 2 x 10(exp -6) solar mass/yr), and characteristic radii of the emitting regions (approximately 32 to approximately 155 AU). The true radial extents will be larger, and the mass-loss rates smaller, by factors of a few for the outflows with limited opening angles. In our small sample the higher mass stars have stronger lines, larger emitting regions, and greater mass-loss rates. These differences are probably limited to the scale and energetics of the envelopes, because the inferred geometries, kinematics and physical conditions are similar. The measured (Fe II) profiles samples both 'high'- and 'low'-velocity environments. Recent studies indicate that these regions have some distinct physical properties and may be spatially separate. The (Fe II) data show that similar sizes and densities can occur in both environments.

2-Hydroxyethyl substituted NHC precursors: Synthesis, characterization, crystal structure and carbonic anhydrase, α-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties

NASA Astrophysics Data System (ADS)

Erdemir, Fatoş; Barut Celepci, Duygu; Aktaş, Aydın; Taslimi, Parham; Gök, Yetkin; Karabıyık, Hasan; Gülçin, İlhami

2018-03-01

This study contains novel a serie synthesis of N-heterocyclic carbene (NHC) precursors that 2-hydroxyethyl substituted. The NHC precursors have been prepared from 1-(2- hydroxyethyl)benzimidazole and alkyl halides. The novel NHC precursors have been characterized by using 1H NMR, 13C NMR, FTIR spectroscopy and elemental analysis techniques. Molecular and crystal structures of 2a, 2d, 2e, 2f and 2g were obtained with single-crystal X-ray diffraction studies. These novel NHC precursor's derivatives effectively inhibited the α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Inhibition constant (Ki) were found in the range of 0.30-9.22 nM for α-glycosidase, 13.90-41.46 nM for hCA I, 12.82-49.95 nM for hCA II, 145.82-882.01 nM for BChE, and 280.92-1370.01 nM for AChE, respectively.

Kinin effects on ion transport in monolayers of HCA-7 cells, a line from a human colonic adenocarcinoma.

PubMed

Cuthbert, A W; Kirkland, S C; MacVinish, L J

1985-09-01

Using epithelial monolayers of HCA-7 cells, derived from a primary human colonic adenocarcinoma and grown on pervious supports, it is shown that responses to lysylbradykinin can be elicited from either side. It is proposed that kinin receptors are inserted into both apical and basolateral membrane domains.

Neutron structure of human carbonic anhydrase II: a hydrogen-bonded water network "switch" is observed between pH 7.8 and 10.0.

PubMed

Fisher, Zoë; Kovalevsky, Andrey Y; Mustyakimov, Marat; Silverman, David N; McKenna, Robert; Langan, Paul

2011-11-08

The neutron structure of wild-type human carbonic anhydrase II at pH 7.8 has been determined to 2.0 Å resolution. Detailed analysis and comparison to the previously determined structure at pH 10.0 show important differences in the protonation of key catalytic residues in the active site as well as a rearrangement of the H-bonded water network. For the first time, a completed H-bonded network stretching from the Zn-bound solvent to the proton shuttling residue, His64, has been directly observed.

Inhibitory effects and structural insights for a novel series of coumarin-based compounds that selectively target human CA IX and CA XII carbonic anhydrases.

PubMed

De Luca, Laura; Mancuso, Francesca; Ferro, Stefania; Buemi, Maria Rosa; Angeli, Andrea; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T; Gitto, Rosaria

2018-01-01

Coumarin derivatives are a peculiar class of inhibitors of the family of metalloenzymes carbonic anhydrases (CA, EC 4.2.1.1). Several coumarins display higher affinity and selectivity toward most relevant and druggable CA isoforms. By decorating the natural compound umbelliferone (1) we have identified a new series of coumarin-based compounds demonstrating high CA inhibitory effects with nanomolar affinity for hCA IX and hCA XII isoforms that were considered a target amenable to develop antitumor agents. The most active tested compounds proved to be potent inhibitors with K i values equal to that of the well-known inhibitor acetazolamide (AAZ), that lacks selectivity over ubiquitous hCA I and hCA II. As suggested by docking studies the coumarins, that are lacking of the canonical metal binding groups, do not interact with Zinc ion within the catalytic site as found for classical sulfonamide type inhibitors of CAs. Thus, the studied inhibitors might possess a non-classical inhibitory mode of action preventing the carbon dioxide to entry into catalytic cavity and its conversion into bicarbonate ion. Specifically, the most active inhibitor of hCA XII compound 18i (K i value of 5.5 nM) and its supposed hydrolytic products could establish a web of H-bond interactions within the enzymatic cavity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A Refined Sample of Lyman Excess H II Regions

NASA Astrophysics Data System (ADS)

Marshall, Brandon; Kerton, C. R.

2018-05-01

A large number (67) of the compact/ultra-compact H II regions identified in the CORNISH catalogue were determined to be powered by a Lyman continuum flux in excess of what was expected given their corresponding luminosity. In this study we attempt to reasonably explain away this Lyman excess phenomenon in as many of the 67 H II regions as possible through a variety of observational and astrophysical means including new luminosity estimates, new Herschel photometry, new distance determinations, the use of different models for dust and ionized gas covering factors, and the use of different stellar calibrations. This phenomenon has been observed before; however, the objects shown to exhibit this behavior in the literature have decidedly different physical properties than the regions in our sample, and thus the origin of the excess is not the same. We find that the excess can be reproduced using OB stellar atmosphere models that have been slightly modified in the extreme ultraviolet. Though the exact mechanism producing the excess is still uncertain, we do find that a scaled up magnetospheric accretion model, often used to explain similar emission from T Tauri stars, is unable to match our observations. Our results suggest that the Lyman excess may be associated with younger H II regions, and that it is more commonly found in early B-type stars. Our refined sample of 24 Lyman excess H II regions provides an ideal sample for comparative studies with regular H II regions, and can act as the basis for the further detailed study of individual regions.

A two-point diagnostic for the H II galaxy Hubble diagram

NASA Astrophysics Data System (ADS)

Leaf, Kyle; Melia, Fulvio

2018-03-01

A previous analysis of starburst-dominated H II galaxies and H II regions has demonstrated a statistically significant preference for the Friedmann-Robertson-Walker cosmology with zero active mass, known as the Rh = ct universe, over Λcold dark matter (ΛCDM) and its related dark-matter parametrizations. In this paper, we employ a two-point diagnostic with these data to present a complementary statistical comparison of Rh = ct with Planck ΛCDM. Our two-point diagnostic compares, in a pairwise fashion, the difference between the distance modulus measured at two redshifts with that predicted by each cosmology. Our results support the conclusion drawn by a previous comparative analysis demonstrating that Rh = ct is statistically preferred over Planck ΛCDM. But we also find that the reported errors in the H II measurements may not be purely Gaussian, perhaps due to a partial contamination by non-Gaussian systematic effects. The use of H II galaxies and H II regions as standard candles may be improved even further with a better handling of the systematics in these sources.

Reddening and extinction towards H II regions

NASA Technical Reports Server (NTRS)

Caplan, James; Deharveng, Lise

1989-01-01

The light emitted by the gas in H II regions is attenuated by dust. This extinction can be measured by comparing H alpha, H beta, and radio continuum fluxes, since the intrinsic ratios of the Balmer line and thermal radio continuum emissivities are nearly constant for reasonable conditions in H II regions. In the case of giant extragalactic H II regions, the extinction was found to be considerably greater than expected. The dust between the Earth and the emitting gas may have an optical thickness which varies. The dust may be close enough to the source that scattered light contributes to the flux, or the dust may be actually mixed with the emitting gas. It is difficult to decide which configuration is correct. A rediscussion of this question in light of recent observations, with the Fabry-Perot spectrophotometers, of the large Galactic H II region is presented. The color excesses are compared for stars embedded in these H II regions with those derived (assuming the standard law) from the nebular extinction and reddening.

Detection of increased 64Cu uptake by human copper transporter 1 gene overexpression using PET with 64CuCl2 in human breast cancer xenograft model.

PubMed

Kim, Kwang Il; Jang, Su Jin; Park, Ju Hui; Lee, Yong Jin; Lee, Tae Sup; Woo, Kwang Sun; Park, Hyun; Choe, Jae Gol; An, Gwang Il; Kang, Joo Hyun

2014-10-01

Copper is an essential cofactor for a variety of biochemical processes including oxidative phosphorylation, cellular antioxidant activity, and elimination of free radicals. The copper transporter 1 is known to be involved in cellular uptake of copper ions. In this study, we evaluated the utility of human copper transporter 1 (hCTR1) gene as a new reporter gene for (64)Cu PET imaging. Human breast cancer cells (MDA-MB-231) were infected with a lentiviral vector constitutively expressing the hCTR1 gene under super cytomegalovirus promoter, and positive clones (MDA-MB-231-hCTR1) were selected. The expression of hCTR1 gene in MDA-MB-231-hCTR1 cells was measured by reverse transcription polymerase chain reaction, Western blot, and (64)Cu uptake assay. To evaluate the cytotoxic effects induced by hCTR1 expression, the dose-dependent cell survival rate after treatment with cisplatin (Cis-diaminedichloroplatinum (II) [CDDP]) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue dye exclusion. Small-animal PET images were acquired in tumor-bearing mice from 2 to 48 h after an intravenous injection of (64)Cu. The hCTR1 gene expression in MDA-MB-231-hCTR1 cells was confirmed at the RNA and protein expression and the cellular (64)Cu uptake level. MTT assay and trypan blue dye exclusion showed that the cell viability of MDA-MB-231-hCTR1 cells decreased more rapidly than that of MDA-MB-231 cells after treatment with CDDP for 96 or 72 h, respectively. Small-animal PET imaging revealed a higher accumulation of (64)Cu in MDA-MB-231-hCTR1 tumors than in MDA-MB-231 tumors. With respect to the biodistribution data, the percentage injected dose per gram of (64)Cu in the MDA-MB-231 tumors and MDA-MB-231-hCTR1 tumors at 48 h after (64)Cu injection was 2.581 ± 0.254 and 5.373 ± 1.098, respectively. An increase in (64)Cu uptake induced by the expression of hCTR1 gene was demonstrated in vivo and in vitro, suggesting the potential use

Intercalation of the layered solid acid HCa/sub 2/Nb/sub 3/O/sub 10/ by organic amines

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

Jacobson, A.J.; Johnson, J.W.; Lewandowski, J.T.

1987-01-01

Layered compounds of formula C/sub n/H/sub 2n+1/NH/sub 3/Ca/sub 2/Nb/sub 3/O/sub 10/ are formed by reaction of n-alkylamines with the solid acid HCa/sub 2/Nb/sub 3/O/sub 10/. Other organic bases such as pyridine can also be intercalated. The lattice constants of the new compounds have been determined by powder X-ray diffraction. The unit cells are tetragonal with a axes that are unchanged with variation of the intercalated amine. The c axes lengths (layer spacings) vary systematically with the hydrocarbon chain length of the alkylamine.

Stream gradient Hotspot and Cluster Analysis (SL-HCA) for improving the longitudinal profiles metrics

NASA Astrophysics Data System (ADS)

Troiani, Francesco; Piacentini, Daniela; Seta Marta, Della

2016-04-01

Many researches successfully focused on stream longitudinal profiles analysis through Stream Length-gradient (SL) index for detecting, at different spatial scales, either tectonic structures or hillslope processes. The analysis and interpretation of spatial variability of SL values, both at a regional and local scale, is often complicated due to the concomitance of different factors generating SL anomalies, including the bedrock composition. The creation of lithologically-filtered SL maps is often problematic in areas where homogeneously surveyed geological maps, with a sufficient resolution are unavailable. Moreover, both the SL map classification and the unbiased anomaly detection are rather difficult. For instance, which is the best threshold to define the anomalous SL values? Further, is there a minimum along-channel extent of anomalous SL values for objectively defining over-steeped segments on long-profiles? This research investigates the relevance and potential of a new approach based on Hotspot and Cluster Analysis of SL values (SL-HCA) for detecting knickzones on long-profiles at a regional scale and for fine-tuning the interpretation of their geological-geomorphological meaning. We developed this procedure within a 2800 km2-wide area located in the mountainous sector of the Northern Apennines of Italy. The Getis-Ord Gi∗ statistic is applied for the SL-HCA approach. The value of SL, calculated starting from a 5x5 m Digital Elevation Model, is used as weighting factor and the Gi∗ index is calculated for each 50 m-long channel segment for the whole fluvial system. The outcomes indicate that high positive Gi∗ values imply the clustering of SL anomalies, thus the occurrence of knickzones on the stream long-profiles. Results show that high and very high Gi* values (i.e. values beyond two standard deviations from the mean) correlate well with the principal knickzones detected with existent lithologically-filtered SL maps. Field checks and remote sensing

A Herschel [C ii] Galactic plane survey. II. CO-dark H2 in clouds

NASA Astrophysics Data System (ADS)

Langer, W. D.; Velusamy, T.; Pineda, J. L.; Willacy, K.; Goldsmith, P. F.

2014-01-01

Context. H i and CO large scale surveys of the Milky Way trace the diffuse atomic clouds and the dense shielded regions of molecular hydrogen clouds, respectively. However, until recently, we have not had spectrally resolved C+ surveys in sufficient lines of sight to characterize the ionized and photon dominated components of the interstellar medium, in particular, the H2 gas without CO, referred to as CO-dark H2, in a large sample of interstellar clouds. Aims: We use a sparse Galactic plane survey of the 1.9 THz (158 μm) [C ii] spectral line from the Herschel open time key programme, Galactic Observations of Terahertz C+ (GOT C+), to characterize the H2 gas without CO in a statistically significant sample of interstellar clouds. Methods: We identify individual clouds in the inner Galaxy by fitting the [C ii] and CO isotopologue spectra along each line of sight. We then combine these spectra with those of H i and use them along with excitation models and cloud models of C+ to determine the column densities and fractional mass of CO-dark H2 clouds. Results: We identify1804 narrow velocity [C ii] components corresponding to interstellar clouds in different categories and evolutionary states. About 840 are diffuse molecular clouds with no CO, ~510 are transition clouds containing [C ii] and 12CO, but no 13CO, and the remainder are dense molecular clouds containing 13CO emission. The CO-dark H2 clouds are concentrated between Galactic radii of ~3.5 to 7.5 kpc and the column density of the CO-dark H2 layer varies significantly from cloud to cloud with a global average of 9 × 1020 cm-2. These clouds contain a significant fraction by mass of CO-dark H2, that varies from ~75% for diffuse molecular clouds to ~20% for dense molecular clouds. Conclusions: We find a significant fraction of the warm molecular ISM gas is invisible in H i and CO, but is detected in [C ii]. The fraction of CO-dark H2 is greatest in the diffuse clouds and decreases with increasing total column

Cu(II) binding by a pH-fractionated fulvic acid

USGS Publications Warehouse

Brown, G.K.; Cabaniss, S.E.; MacCarthy, P.; Leenheer, J.A.

1999-01-01

The relationship between acidity, Cu(II) binding and sorption to XAD resin was examined using Suwannee River fulvic acid (SRFA). The work was based on the hypothesis that fractions of SRFA eluted from an XAD column at various pH's from 1.0 to 12.0 would show systematic variations in acidity and possibly aromaticity which in turn would lead to different Cu(II) binding properties. We measured equilibrium Cu(II) binding to these fractions using Cu2+ ion-selective electrode (ISE) potentiometry at pH 6.0. Several model ligands were also examined, including cyclopentane-1,2,3,4-tetracarboxylic acid (CP-TCA) and tetrahydrofuran-2,3,4,5-tetracarboxylic acid (THF-TCA), the latter binding Cu(II) much more strongly as a consequence of the ether linkage. The SRFA Cu(II) binding properties agreed with previous work at high ionic strength, and binding was enhanced substantially at lower ionic strength, in agreement with Poisson-Boltzmann predictions for small spheres. Determining Cu binding constants (K(i)) by non-linear regression with total ligand concentrations (L(Ti)) taken from previous work, the fractions eluted at varying pH had K(i) similar to the unfractionated SRFA, with a maximum enhancement of 0.50 log units. We conclude that variable-pH elution from XAD does not isolate significantly strong (or weak) Cu(II)-binding components from the SRFA mixture. Copyright (C) 1999 Elsevier Science B.V.

End of an era. Justice Department ends nine-year criminal probe of Columbia/HCA executives, but company recovery began earlier.

PubMed

Galloro, Vince

2002-07-29

The longest, costlest criminal healthcare fraud probe in U.S. history is finally over, but its ripple effects are likely to continue. The Columbia/HCA Healthcare Corp. case raised questions about healthcare accounting practices long before the current wave of corporate scandals. But the consensus is that the most crucial step in retooling HCA's image was restoring Thomas First Jr. (left) as chairman and CEO.

The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity.

PubMed

Zhao, Jian; Barkla, Bronwyn J; Marshall, Joy; Pittman, Jon K; Hirschi, Kendal D

2008-02-01

Perturbing CAX1, an Arabidopsis vacuolar H+/Ca2+ antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among cax1 and cax3 including an increased sensitivity to both abscisic acid (ABA) and sugar during germination, and an increased tolerance to ethylene during early seedling development. We have also identified phenotypes unique to cax3, namely salt, lithium and low pH sensitivity. We used biochemical measurements to ascribe these cax3 sensitivities to a reduction in vacuolar H+/Ca2+ transport during salt stress and decreased plasma membrane H+-ATPase activity. These findings catalog an array of CAX phenotypes and assign a specific role for CAX3 in response to salt tolerance.

Hydrodynamical models of cometary H II regions

NASA Astrophysics Data System (ADS)

Steggles, H. G.; Hoare, M. G.; Pittard, J. M.

2017-04-01

We have modelled the evolution of cometary H II regions produced by zero-age main-sequence stars of O and B spectral types, which are driving strong winds and are born off-centre from spherically symmetric cores with power-law (α = 2) density slopes. A model parameter grid was produced that spans stellar mass, age and core density. Exploring this parameter space, we investigated limb-brightening, a feature commonly seen in cometary H II regions. We found that stars with mass M⋆ ≥ 12 M⊙ produce this feature. Our models have a cavity bounded by a contact discontinuity separating hot shocked wind and ionized ambient gas that is similar in size to the surrounding H II region. Because of early pressure confinement, we did not see shocks outside of the contact discontinuity for stars with M⋆ ≤ 40 M⊙, but the cavities were found to continue to grow. The cavity size in each model plateaus as the H II region stagnates. The spectral energy distributions of our models are similar to those from identical stars evolving in uniform density fields. The turn-over frequency is slightly lower in our power-law models as a result of a higher proportion of low-density gas covered by the H II regions.

LM1-64: a Newly Reported Lmc-Pn with WR Nucleus

NASA Astrophysics Data System (ADS)

Pena, M.; Olguin, L.; Ruiz, M. T.; Torres-Peimbert, S.

1993-05-01

The object LM1-64 was reported by Lindsay & Mullan (1963, Irish Astron. J., 5, 51) as a probable PN in the LMC. Optical and UV spectra taken by us confirm that suggestion. LM1-64 is a high excitation planetary nebulae which shows evidence of having a WC central star. Broad stellar emission at lambda 4650 is detected in the optical spectrum obtained with the CTIO 4m telescope, in 1989. A UV spectrum in the range from 1200 Angstroms to 2000 Angstroms was obtained with IUE in 1990. We have measured all the emission line fluxes available and determined values for the physical conditions and chemical abundances of the nebular ionized gas. The derived values are T(OIII) = 14000K, log He/H = 11.05, log C/H = 9.48, log O/H = 8.55 and log Ne/H = 7.94. LM1-64 shows a large C enhancement in the envelope as result of the central star activity, while He, O and Ne are comparable to the average values reported for the LMC-PNe (Monk, Barlow & Clegg, 1988, MNRAS, 234, 583). We have estimated the He II Zanstra temperature of the central star to be ~ 80,000 K. This temperature is much higher than the values reported for the known LMC-PNe with WR nucleus that Monk et al. have classified as W4 to W8. The only other high temperature WR nucleus in a LMC-PN is N66 which recently showed evidence of undergoing a WR episode (Torres-Peimbert, Ruiz, Peimbert & Pe\\ na, 1993, IAU Symp. 155, eds. A. Acker & R. Weinberger, in press).

3-Helium in Obscure H II Regions

NASA Astrophysics Data System (ADS)

Bania, T. M.; Rood, R. T.; Balser, D. S.

1999-05-01

The light isotope of helium, (3) He, can serve as a probe of cosmology, the evolution of low mass stars, and the chemical evolution of the Galaxy. Its abundance can be determined via measurements of the 3.46 cm hyperfine transition of (3) He(+) . Potentially observable sources of ionized gas include H ii regions and planetary nebulae. The selection of (3) He targets is counter-intuitive because the (3) He(+) hyperfine line strength is proportional to the source density, while one usually thinks of H ii regions in terms of radio continuum or recombination line strength both of which depend on the square of the density. The (3) He(+) line strength depends on the (3) He(+) abundance ratio and a number of other factors: $ TL(A}({) (3) He(+)) ~ frac {N((3) He(+)}{N() H(+)}) frac {({TC(A}}D)({1/2)) Te(1/4) (theta_obs (2) - theta_beam (2})({3/4}}{Delta {v}({)) (3) He(+)) [ln(5.717 x 10(-3}Te({3/2})]^{1/2)) theta_obs } where T_L^A and Delta v are the antenna temperature and FWHM of the ^3He^+ line, D is the nebular distance, T_C^A and theta_obs are the antenna temperature and observed FWHM angular size of the continuum emission, theta_beam is the telescope's FWHM beam, and Te is the nebular electron temperature. For H {sc ii} regions much larger than the telescope beam we can select targets using the criterion: TLA(^3He^+)\\sim\\sqrt{TCA D\\theta_obs}. This is the case since we can neglect the weak dependence on T_e and because we do not know either ^3He^{+}/H^+ or Delta v. Thus big, distant H ii regions could be potential ^3He^+ targets even if their continuum emission is weak. Armed with this knowledge we included H ii regions like S209 in our early observing list along with more famous sources like W43. Still we did not have the temerity to push this reasoning to the limit. We have now found, however, that this selection criterion is valid for even the wimpiest known H ii regions. Here we report on the detection of ^3He^+$ emission in 8 distant, low density H ii regions.

The impact of the Tulane-HCA joint venture on academic and clinical missions.

PubMed

Whitecloud, T S; Smathers, J E; Barrack, R L

2001-10-01

As with any joint venture in any given industry, positive and negative impacts are felt. Tulane University School of Medicine experienced impacts on its academic and clinical missions as a result of the joint venture between Tulane University and HCA, a for-profit public company. The laws of business had entered the halls of medicine. Although patients, personnel, and physicians experienced culture shock and inconveniences, Tulane University School of Medicine has been able to maintain viable training programs, and its faculty physicians have a hospital and corporately run clinics across the street. In addition, multidisciplinary centers of excellence, long spoken of in the academic realm, came to fruition through the corporate world. This may not have been the case, had Tulane University not entered into ajoint venture with HCA. Is it worth the effort? For Tulane University, whether one likes the entire package or not, the answer must be yes. The greatest impact is that the orthopaedic surgeons still are in a position to fulfill their academic and clinical missions.

(Fe II) 1.53 and 1.64 micron emission from pre-main-sequence stars

NASA Astrophysics Data System (ADS)

Hamann, Fred; Simon, Michal; Carr, John S.; Prato, Lisa

1994-11-01

We present flux-calibrated profiles of the (Fe II) 1.53 and 1.64 micron lines in five pre-main-sequence stars, PV Cep, V1331 Cyg, R Mon, and DG and HL Tau. The line centroids are blueshifted in all five sources, and four of the five have only blueshifted flux. In agreement with previous studies, we attribute the line asymmetries to local obscuration by dusty circumstellar disks. The absence of redshifted flux implies a minimum column density of obscuring material. The largest limit, NH greater than 3 x 1022/sq cm, derived for V1331 Cyg, suggests disk surface densities greater than 0.05 g/sq cm and disk masses greater than 0.001 solar mass within a radius of approximately 200 AU. The narrow high-velocity lines in PV Cep, V1331 Cyg, and HL Tau require formation in well collimated winds. The maximum full opening angles of their winds range from less than 20 deg in V1331 Cyg to less than 40 deg in HL Tau. The (Fe II) data also yield estimates of the electron densities (ne approximately 104/cu cm), hydrogen ionization fractions (fH(+) approximately 1/3), mass-loss rates (approximately 10-7 to 2 x 10-6 solar mass/yr), and characteristic radii of the emitting regions (approximately 32 to approximately 155 AU). The true radial extents will be larger, and the mass-loss rates smaller, by factors of a few for the outflows with limited opening angles. In our small sample the higher mass stars have stronger lines, larger emitting regions, and greater mass-loss rates. These differences are probably limited to the scale and energetics of the envelopes, because the inferred geometries, kinematics and physical conditions are similar. The measured (Fe II) profiles samples both 'high'- and 'low'-velocity environments. Recent studies indicate that these regions have some distinct physical properties and may be spatially separate. The (Fe II) data show that similar sizes and densities can occur in both environments.

40 CFR 142.64 - Variances and exemptions from the requirements of part 141, subpart H-Filtration and Disinfection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... requirements of part 141, subpart H-Filtration and Disinfection. 142.64 Section 142.64 Protection of...—Filtration and Disinfection. (a) No variances from the requirements in part 141, subpart H are permitted. (b) No exemptions from the requirements in § 141.72 (a)(3) and (b)(2) to provide disinfection are...

40 CFR 142.64 - Variances and exemptions from the requirements of part 141, subpart H-Filtration and Disinfection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... requirements of part 141, subpart H-Filtration and Disinfection. 142.64 Section 142.64 Protection of...—Filtration and Disinfection. (a) No variances from the requirements in part 141, subpart H are permitted. (b) No exemptions from the requirements in § 141.72 (a)(3) and (b)(2) to provide disinfection are...

40 CFR 142.64 - Variances and exemptions from the requirements of part 141, subpart H-Filtration and Disinfection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... requirements of part 141, subpart H-Filtration and Disinfection. 142.64 Section 142.64 Protection of...—Filtration and Disinfection. (a) No variances from the requirements in part 141, subpart H are permitted. (b) No exemptions from the requirements in § 141.72 (a)(3) and (b)(2) to provide disinfection are...

40 CFR 142.64 - Variances and exemptions from the requirements of part 141, subpart H-Filtration and Disinfection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirements of part 141, subpart H-Filtration and Disinfection. 142.64 Section 142.64 Protection of...—Filtration and Disinfection. (a) No variances from the requirements in part 141, subpart H are permitted. (b) No exemptions from the requirements in § 141.72 (a)(3) and (b)(2) to provide disinfection are...

A shortcut to high-affinity Ga-68 and Cu-64 radiopharmaceuticals: one-pot click chemistry trimerisation on the TRAP platform.

PubMed

Baranyai, Zsolt; Reich, Dominik; Vágner, Adrienn; Weineisen, Martina; Tóth, Imre; Wester, Hans-Jürgen; Notni, Johannes

2015-06-28

Due to its 3 carbonic acid groups being available for bioconjugation, the TRAP chelator (1,4,7-triazacyclononane-1,4,7-tris(methylene(2-carboxyethylphosphinic acid))) is chosen for the synthesis of trimeric bioconjugates for radiolabelling. We optimized a protocol for bio-orthogonal TRAP conjugation via Cu(I)-catalyzed Huisgen-cycloaddition of terminal azides and alkynes (CuAAC), including a detailed investigation of kinetic properties of Cu(II)-TRAP complexes. TRAP building blocks for CuAAC, TRAP(alkyne)3 and TRAP(azide)3 were obtained by amide coupling of propargylamine/3-azidopropyl-1-amine, respectively. For Cu(II) complexes of neat and triply amide-functionalized TRAP, the equilibrium properties as well as pseudo-first-order Cu(II)-transchelation, using 10 to 30 eq. of NOTA and EDTA, were studied by UV-spectrophotometry. Dissociation of any Cu(II)-TRAP species was found to be independent on the nature or excess of a competing chelator, confirming a proton-driven two-step mechanism. The respective thermodynamic stability constants (log K(ML): 19.1 and 17.6) and dissociation rates (k: 38 × 10(-6) and 7 × 10(-6) s(-1), 298 K, pH 4) show that the Cu(II) complex of the TRAP-conjugate possesses lower thermodynamic stability but higher kinetic inertness. At pH 2-3, its demetallation with NOTA was complete within several hours/days at room temperature, respectively, enabling facile Cu(II) removal after click coupling by direct addition of NOTA trihydrochloride to the CuAAC reaction mixture. Notwithstanding this, an extrapolated dissociation half life of >100 h at 37 °C and pH 7 confirms the suitability of TRAP-bioconjugates for application in Cu-64 PET (cf. t(1/2)(Cu-64) = 12.7 h). To showcase advantages of the method, TRAP(DUPA-Pep)3, a trimer of the PSMA inhibitor DUPA-Pep, was synthesized using 1 eq. TRAP(alkyne)3, 3.3 eq. DUPA-Pep-azide, 10 eq. Na ascorbate, and 1.2 eq. Cu(II)-acetate. Its PSMA affinity (IC50), determined by the competition assay on LNCa

Inhibitory Effects of Culinary Herbs and Spices on the Growth of HCA-7 Colorectal Cancer Cells and Their COX-2 Expression.

PubMed

Jaksevicius, Andrius; Carew, Mark; Mistry, Calli; Modjtahedi, Helmout; Opara, Elizabeth I

2017-09-21

It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells' cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7's cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential.

Inhibitory Effects of Culinary Herbs and Spices on the Growth of HCA-7 Colorectal Cancer Cells and Their COX-2 Expression

PubMed Central

Jaksevicius, Andrius; Carew, Mark; Mistry, Calli

2017-01-01

It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells’ cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7’s cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential. PMID:28934138

New bioactive silver(I) complexes: Synthesis, characterization, anticancer, antibacterial and anticarbonic anhydrase II activities

NASA Astrophysics Data System (ADS)

Ozdemir, Ummuhan O.; Ozbek, Neslihan; Genc, Zuhal Karagoz; İlbiz, Firdevs; Gündüzalp, Ayla Balaban

2017-06-01

Silver(I) complexes of alkyl sulfonic acide hydrazides were newly synthesized as homologous series. Methanesulfonic acide hydrazide (L1), ethanesulfonic acide hydrazide (L2), propanesulfonic acide hydrazide (L3) and butanesulfonic acide hydrazide (L4) were used for complexation with Ag(I) ions. The silver complexes obtained in the mol ratio of 1:2 have the structural formula as Ag(L1)2NO3 (I), Ag(L2)2NO3 (II), Ag(L3)2NO3(III), (Ag(L4)2NO3 (IV). The Ag(I) complexes exhibit distorted linear two-fold coordination in [AgL2]+ cations with uncoordinated nitrates. Ligands are chelated with silver(I) ions through unsubstituted primary nitrogen in hydrazide group. Ag(I) complexes were characterized by using elemental analysis, spectroscopic methods (FT-IR, LC-MS), magnetic susceptibility and conductivity measurements. Silver(I) complexes were optimized using PBEPBE/LanL2DZ/DEF2SV basic set performed by DFT method with the Gaussian 09 program package. The geometrical parameters, frontier molecular orbitals (HOMOs and LUMOs) and molecular electrostatic potential (MEP) mapped surfaces of the optimized geometries were also determined by this quantum set. The anticancer activities of silver(I) complexes on MCF-7 human breast cancer cell line were investigated by comparing IC50 values. The antibacterial activities of complexes were studied against Gram positive bacteria; S. aureus ATCC 6538, B. subtilis ATCC 6633, B. cereus NRRL-B-3711, E. faecalis ATCC 29212 and Gram negative bacteria; E. coli ATCC 11230, P. aeruginosa ATCC 15442, K. pneumonia ATCC 70063 by using disc diffusion method. The inhibition activities of Ag(I) complexes on carbonic anhydrase II enzyme (hCA II) were also investigated by comparing IC50 and Ki values. The biological activity screening shows that Ag(I) complex of butanesulfonicacidehydrazide (IV) has the highest activity against tested breast cancer cell lines MCF-7, Gram positive/Gram negative bacteria and carbonic anhydrase II (hCA II) isoenzyme.

Anti-metastasis effect of fucoidan from Undaria pinnatifida sporophylls in mouse hepatocarcinoma Hca-F cells.

PubMed

Wang, Peisheng; Liu, Zhichao; Liu, Xianli; Teng, Hongming; Zhang, Cuili; Hou, Lin; Zou, Xiangyang

2014-01-01

Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways.

Anti-Metastasis Effect of Fucoidan from Undaria pinnatifida Sporophylls in Mouse Hepatocarcinoma Hca-F Cells

PubMed Central

Wang, Peisheng; Liu, Zhichao; Liu, Xianli; Teng, Hongming; Zhang, Cuili; Hou, Lin; Zou, Xiangyang

2014-01-01

Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways. PMID:25162296

Integral field spectroscopy of a sample of nearby galaxies. II. Properties of the H ii regions

NASA Astrophysics Data System (ADS)

Sánchez, S. F.; Rosales-Ortega, F. F.; Marino, R. A.; Iglesias-Páramo, J.; Vílchez, J. M.; Kennicutt, R. C.; Díaz, A. I.; Mast, D.; Monreal-Ibero, A.; García-Benito, R.; Bland-Hawthorn, J.; Pérez, E.; González Delgado, R.; Husemann, B.; López-Sánchez, Á. R.; Cid Fernandes, R.; Kehrig, C.; Walcher, C. J.; Gil de Paz, A.; Ellis, S.

2012-10-01

We analyse the spectroscopic properties of thousands of H ii regions identified in 38 face-on spiral galaxies. All galaxies were observed out to 2.4 effective radii using integral field spectroscopy (IFS) over the wavelength range ~3700 to ~6900 Å. The near uniform sample has been assembled from the PPAK IFS Nearby Galaxy (PINGS) survey and a sample described in Paper I. We develop a new automatic procedure to detect H ii regions, based on the contrast of the Hα intensity maps extracted from the datacubes. Once detected, the algorithm provides us with the integrated spectra of each individual segmented region. In total, we derive good quality spectroscopic information for ~2600 independent H ii regions/complexes. This is by far the largest H ii region survey of its kind. Our selection criteria and the use of 3D spectroscopy guarantee that we cover the regions in an unbiased way. A well-tested automatic decoupling procedure has been applied to remove the underlying stellar population, deriving the main properties (intensity, dispersion and velocity) of the strongest emission lines in the considered wavelength range (covering from [O ii] λ3727 to [S ii] λ6731). A final catalogue of the spectroscopic properties of H ii regions has been created for each galaxy, which includes information on morphology, spiral structure, gaskinematics, and surface brightness of the underlying stellar population. In the current study, we focus on the understanding of the average properties of the H ii regions and their radial distributions. We find a significant change in the ionisation characteristics of H ii regions within r < 0.25 re due to contamination from sources with different ionising characteristics, as we discuss. We find that the gas-phase oxygen abundance and the Hα equivalent width present a negative and positive gradient, respectively. The distribution of slopes is statistically compatible with a random Gaussian distribution around the mean value, if the radial

47 CFR 64.1190 - Preferred carrier freezes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... or social security number) and the information required in §§ 64.1190(d)(3)(ii)(A) through (D... subscriber's date of birth or social security number) and the information required in § 64.1190(d)(3)(ii)(A... or the carrier's marketing agent; must not have any financial incentive to confirm preferred carrier...

Improved selection criteria for H II regions, based on IRAS sources

NASA Astrophysics Data System (ADS)

Yan, Qing-Zeng; Xu, Ye; Walsh, A. J.; Macquart, J. P.; MacLeod, G. C.; Zhang, Bo; Hancock, P. J.; Chen, Xi; Tang, Zheng-Hong

2018-05-01

We present new criteria for selecting H II regions from the Infrared Astronomical Satellite (IRAS) Point Source Catalogue (PSC), based on an H II region catalogue derived manually from the all-sky Wide-field Infrared Survey Explorer (WISE). The criteria are used to augment the number of H II region candidates in the Milky Way. The criteria are defined by the linear decision boundary of two samples: IRAS point sources associated with known H II regions, which serve as the H II region sample, and IRAS point sources at high Galactic latitudes, which serve as the non-H II region sample. A machine learning classifier, specifically a support vector machine, is used to determine the decision boundary. We investigate all combinations of four IRAS bands and suggest that the optimal criterion is log(F_{60}/F_{12})≥ ( -0.19 × log(F_{100}/F_{25})+ 1.52), with detections at 60 and 100 {μ}m. This selects 3041 H II region candidates from the IRAS PSC. We find that IRAS H II region candidates show evidence of evolution on the two-colour diagram. Merging the WISE H II catalogue with IRAS H II region candidates, we estimate a lower limit of approximately 10 200 for the number of H II regions in the Milky Way.

On the status report of the H-II launch vehicle

NASA Astrophysics Data System (ADS)

Eto, Takao; Shibato, Yoji; Takatsuka, H.; Fukushima, Y.

1988-10-01

This paper describes the present status of the design and the development of the H-II launch vehicle which is being presently developed by NASDA to meet the demand for larger satellite launches at a lower cost. The H-II systems, including its solid rocket boosters and the guidance and control system, are discussed together with the launch facilities and launch operation. The paper includes diagrams of the H-II systems and a table listing H-II characteristics.

Structure and evolution of fossil H II regions

NASA Technical Reports Server (NTRS)

Mccray, R.; Schwarz, J.

1971-01-01

The structure and evolution of a fossil H II region created by a burst of ionizing radiation from a supernova is considered. The cooling time scale for the shell is about 10 to the 6th power years. Superposition of million-year-old fossil H II regions may account for the temperature and ionization of the interstellar medium. Fossil H II regions are unstable to growth of thermal condensations. Highly ionized filamentary structures form and dissipate in about 10,000 years. Partially ionized clouds form and dissipate in about 10 to the 6th power years.

Morphological Properties of Slender Ca II H Fibrils Observed by Sunrise II

NASA Astrophysics Data System (ADS)

Gafeira, R.; Lagg, A.; Solanki, S. K.; Jafarzadeh, S.; van Noort, M.; Barthol, P.; Blanco Rodríguez, J.; del Toro Iniesta, J. C.; Gandorfer, A.; Gizon, L.; Hirzberger, J.; Knölker, M.; Orozco Suárez, D.; Riethmüller, T. L.; Schmidt, W.

2017-03-01

We use seeing-free high spatial resolution Ca II H data obtained by the Sunrise observatory to determine properties of slender fibrils in the lower solar chromosphere. In this work we use intensity images taken with the SuFI instrument in the Ca II H line during the second scientific flight of the Sunrise observatory to identify and track elongated bright structures. After identification, we analyze theses structures to extract their morphological properties. We identify 598 slender Ca II H fibrils (SCFs) with an average width of around 180 km, length between 500 and 4000 km, average lifetime of ≈400 s, and average curvature of 0.002 arcsec-1. The maximum lifetime of the SCFs within our time series of 57 minutes is ≈2000 s. We discuss similarities and differences of the SCFs with other small-scale, chromospheric structures such as spicules of type I and II, or Ca II K fibrils.

The Southern H ii Region Discovery Survey (SHRDS): Pilot Survey

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

Brown, C.; Dickey, John M.; Jordan, C.

The Southern H ii Region Discovery Survey is a survey of the third and fourth quadrants of the Galactic plane that will detect radio recombination line (RRL) and continuum emission at cm-wavelengths from several hundred H ii region candidates using the Australia Telescope Compact Array. The targets for this survey come from the WISE Catalog of Galactic H ii Regions and were identified based on mid-infrared and radio continuum emission. In this pilot project, two different configurations of the Compact Array Broad Band receiver and spectrometer system were used for short test observations. The pilot surveys detected RRL emission frommore » 36 of 53 H ii region candidates, as well as seven known H ii regions that were included for calibration. These 36 recombination line detections confirm that the candidates are true H ii regions and allow us to estimate their distances.« less

A New Catalog of H II Regions in M31

NASA Astrophysics Data System (ADS)

Azimlu, M.; Marciniak, R.; Barmby, P.

2011-10-01

We present a new catalog of H II regions in M31. The full disk of the galaxy (~24 kpc from the galaxy center) is covered in a 2.2 deg2 mosaic of 10 fields observed with the Mosaic Camera on the Mayall 4 m telescope as part of the Local Group Galaxies survey. We used HIIphot, a code for automated photometry of H II regions, to identify the regions and measure their fluxes and sizes. A 10σ detection level was used to exclude diffuse gas fluctuations and star residuals after continuum subtraction. That selection limit may result in missing some faint H II regions, but our catalog of 3691 H II regions is still complete to a luminosity of L Hα = 1034 erg s-1. This is five times fainter than the only previous CCD-based study which contained 967 objects in the NE half of M31. We determined the Hα luminosity function (LF) by fitting a power law to luminosities larger than L Hα = 1036.7 and determined a slope of 2.52 ± 0.07. The in-arm and inter-arm LFs peak at different luminosities but they have similar bright-end slopes. The inter-arm regions are less populated (40% of total detected regions) and constitute only 14% of the total luminosity of L Hα = 5.6 × 1040 erg s-1 (after extinction correction and considering 65% contribution from diffused ionized gas). A star formation rate of 0.44 M sun yr-1 was estimated from the Hα total luminosity; this value is consistent with the determination from the Spitzer 8 μm image. We removed all known and potential planetary nebulae, yet we found a double-peaked LF. The inter-arm older population suggests a starburst between 15 and 20 million years ago. This result is in agreement with UV studies of the star formation history in M31 which found a star formation rate decrease in the recent past. We found a fair spatial correlation between the H II regions and stellar clusters in selected star-forming regions. Most of the matched regions lie within the arm regions.

Multiwavelength studies of H II region NGC 2467

NASA Astrophysics Data System (ADS)

Yadav, Ram Kesh; Pandey, A. K.; Sharma, Saurabh; Eswaraiah, C.

2013-06-01

We present the multiwavelength studies of the H II region Sh2-311 to explore the effects of massive stars on low-mass star formation. In this study we have used optical (UBVI) data from ESO 2.2m Wide Field Imager (WFI), Near-Infrared (NIR) (JHKs) data from CTIO 4m Blanco Telescope and archival Spitzer 8μm data. Based on stellar density contours and dust distribution we have divided the complex into three regions i.e., Haffner 19 (H19), Haffner 18 (H18) and NGC 2467. Using the UBVI data we have estimated the basic parameters of these regions. We have constructed the (J - H)/(H - Ks) color-color diagram and a J/(J - H) color-magnitude diagram to identify young stellar objects (YSOs) and to estimate their masses. Spatial distribution of the YSOs indicates that most of them are distributed at the periphery of the H II region and ionizing star may be responsible for the triggering of star formation at the periphery of the H II region.

Synthesis, Characterization and Antibacterial Activity of 1,4-di[ aminomethylene carboxyl] phenylene (H2L) and its Complexes Co(II), Cu (II), Zn(II) and Cd (II)

NASA Astrophysics Data System (ADS)

Sultan, J. S.; Fezea, S. M.; Mousa, F. H.

2018-05-01

A binucleating tetradentate Schiff base ligand, 1,4- di[amino methylene carboxylic] phenylene (H2L) and its forth new binuclear complexes [Co(II), Cu(II), Zn(II) and Cd(II)] were prepared via reaction metal (II) chloride with ligand (H2L) using 2:1 (M:L) in ethanol solvent. The new ligand (H2L) and its complexes were characterized by elemental microanalysis (C.H.N), atomic absorption, chloride content, molar conductance’s magnetic susceptibility, FTIR UV- Vis spectral and, 1H, 13 C- NMR (for H2L). The antibacterial activity with bacteria activity with bacteria, Staphylococcus aureus, Bacillus and Esccherichia Coli were studied.

L alpha, L beta /of H I/, K and H /of MG II/, K and H /of CA II/ observations in a quiescent prominence with the OSO-8 LPSP instrument

NASA Astrophysics Data System (ADS)

Vial, J. C.; Martres, M. J.; Salm-Platzer, J.

1981-04-01

A sequence of images taken at different positions in the resonance lines of Ca II, Mg II, and H I was obtained over a quiescent prominence with the LPSP instrument on OSO-8. Ca II K (and H) profiles are reconstructed at different locations in the prominence with a (10 × 5) arc sec2 resolution. Significant variations of FWHM and line shifts are found: FWHM range from 0.14 Å to 0.5 Å; blue shifts reach about 14 km s-1. The ratio of K to H absolute intensities shows a large spread around the average value of 1.2. The same ratio for the Mg II lines in the whole prominence is higher (1.7), a fact already noticed at the edge of an active prominence (Vial et al., 1979). The ionization degree, as measured by the Lα/Ca K ratio, shows noticeable variations within the prominence. The La intensity is about 0.3 times the intensity measured in the quiet Sun, and the Lα/Lβ ratio is less than one half the disk value. These results indicate important variations of the thermal conditions inside the prominence.

On the association between core-collapse supernovae and H ii regions

NASA Astrophysics Data System (ADS)

Crowther, Paul A.

2013-01-01

Previous studies of the location of core-collapse supernovae (ccSNe) in their host galaxies have variously claimed an association with H ii regions; no association or an association only with hydrogen-deficient ccSNe. Here, we examine the immediate environments of 39 ccSNe whose positions are well known in nearby (≤15 Mpc), low-inclination (≤65°) hosts using mostly archival, continuum-subtracted Hα ground-based imaging. We find that 11 out of 29 hydrogen-rich ccSNe are spatially associated with H ii regions (38 ± 11 per cent), versus 7 out of 10 hydrogen-poor ccSNe (70 ± 26 per cent). Similar results from Anderson et al. led to an interpretation that the progenitors of Type Ib/c ccSNe are more massive than those of Type II ccSNe. Here, we quantify the luminosities of H ii region either coincident with or nearby to the ccSNe. Characteristic nebulae are long-lived (˜20 Myr) giant H ii regions rather than short-lived (˜4 Myr) isolated, compact H ii regions. Therefore, the absence of an H ii region from most Type II ccSNe merely reflects the longer lifetime of stars with ⪉12 M⊙ than giant H ii regions. Conversely, the association of an H ii region with most Type Ib/c ccSNe is due to the shorter lifetime of stars with >12 M⊙ stars than the duty cycle of giant H ii regions. Therefore, we conclude that the observed association between certain ccSNe and H ii provides only weak constraints upon their progenitor masses. Nevertheless, we do favour lower mass progenitors for two Type Ib/c ccSNe that lack associated nebular emission, a host cluster or a nearby giant H ii region. Finally, we also reconsider the association between long gamma-ray bursts and the peak continuum light from their (mostly) dwarf hosts, and conclude that this is suggestive of very high mass progenitors, in common with previous studies.

Copper(II) complexes of alloferon 1 with point mutations (H1A) and (H9A) stability structure and biological activity.

PubMed

Matusiak, Agnieszka; Kuczer, Mariola; Czarniewska, Elżbieta; Rosiński, Grzegorz; Kowalik-Jankowska, Teresa

2014-09-01

Mono- and polynuclear copper(II) complexes of the alloferon 1 with point mutations (H1A) A(1)GVSGH(6)GQH(9)GVH(12)G (Allo1A) and (H9A) H(1)GVSGH(6)GQA(9)GVH(12)G (Allo9A) have been studied by potentiometric, UV-visible, CD, EPR spectroscopic and mass spectrometry (MS) methods. To obtain a complete complex speciation different metal-to-ligand molar ratios ranging from 1:1 to 4:1 for Allo1A and to 3:1 for Allo9A were studied. The presence of the His residue in first position of the peptide chain changes the coordination abilities of the Allo9A peptide in comparison to that of the Allo1A. Imidazole-N3 atom of N-terminal His residue of the Allo9A peptide forms stable 6-membered chelate with the terminal amino group. Furthermore, the presence of two additional histidine residues in the Allo9A peptide (H(6),H(12)) leads to the formation of the CuL complex with 4N {NH2,NIm-H(1),NIm-H(6),NIm-H(12)} binding site in wide pH range (5-8). For the Cu(II)-Allo1A system, the results demonstrated that at physiological pH7.4 the predominant complex the CuH-1L consists of the 3N {NH2,N(-),CO,NIm} coordination mode. The inductions of phenoloxidase activity and apoptosis in vivo in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 were studied. The Allo1A, Allo1K peptides and their copper(II) complexes displayed the lowest hemocytotoxic activity while the most active was the Cu(II)-Allo9A complex formed at pH7.4. The results may suggest that the N-terminal-His(1) and His(6) residues may be more important for their proapoptotic properties in insects than those at positions 9 and 12 in the peptide chain. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynamics of H II regions around exiled O stars

NASA Astrophysics Data System (ADS)

Mackey, Jonathan; Langer, Norbert; Gvaramadze, Vasilii V.

2013-11-01

At least 25 per cent of massive stars are ejected from their parent cluster, becoming runaways or exiles, travelling with often-supersonic space velocities through the interstellar medium (ISM). Their overpressurized H II regions impart kinetic energy and momentum to the ISM, compress and/or evaporate dense clouds, and can constrain properties of both the star and the ISM. Here, we present one-, two- and (the first) three-dimensional simulations of the H II region around a massive star moving supersonically through a uniform, magnetized ISM, with properties appropriate for the nearby O star ζ Oph. The H II region leaves an expanding overdense shell behind the star and, inside this, an underdense wake that should be filled with hot gas from the shocked stellar wind. The gas column density in the shell is strongly influenced by the ISM magnetic field strength and orientation. Hα emission maps show that H II region remains roughly circular, although the star is displaced somewhat from the centre of emission. For our model parameters, the kinetic energy feedback from the H II region is comparable to the mechanical luminosity of the stellar wind, and the momentum feedback rate is >100 times larger than that from the wind and ≈10 times larger than the total momentum input rate available from radiation pressure. Compared to the star's eventual supernova explosion, the kinetic energy feedback from the H II region over the star's main-sequence lifetime is >100 times less, but the momentum feedback is up to 4 times larger. H II region dynamics are found to have only a small effect on the ISM conditions that a bow shock close to the star would encounter.

Ionised gas kinematics in bipolar H II regions

NASA Astrophysics Data System (ADS)

Dalgleish, Hannah S.; Longmore, Steven N.; Peters, Thomas; Henshaw, Jonathan D.; Veitch-Michaelis, Joshua L.; Urquhart, James S.

2018-05-01

Stellar feedback plays a fundamental role in shaping the evolution of galaxies. Here we explore the use of ionised gas kinematics in young, bipolar H II regions as a probe of early feedback in these star-forming environments. We have undertaken a multi-wavelength study of a young, bipolar H II region in the Galactic disc, G316.81-0.06, which lies at the centre of a massive (˜103 M⊙) infrared-dark cloud filament. It is still accreting molecular gas as well as driving a ˜0.2 pc ionised gas outflow perpendicular to the filament. Intriguingly, we observe a large velocity gradient (47.81 ± 3.21 km s-1 pc-1) across the ionised gas in a direction perpendicular to the outflow. This kinematic signature of the ionised gas shows a reasonable correspondence with the simulations of young H II regions. Based on a qualitative comparison between our observations and these simulations, we put forward a possible explanation for the velocity gradients observed in G316.81-0.06. If the velocity gradient perpendicular to the outflow is caused by rotation of the ionised gas, then we infer that this rotation is a direct result of the initial net angular momentum in the natal molecular cloud. If this explanation is correct, this kinematic signature should be common in other young (bipolar) H II regions. We suggest that further quantitative analysis of the ionised gas kinematics of young H II regions, combined with additional simulations, should improve our understanding of feedback at these early stages.

A SUBSTELLAR COMMON PROPER-MOTION COMPANION TO THE PLEIAD H II 1348

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

Geissler, Kerstin; Metchev, Stanimir A.; Pham, Alfonse

2012-02-10

We announce the identification of a proper-motion companion to the star H II 1348, a K5 V member of the Pleiades open cluster. The existence of a faint point source 1.''1 away from H II 1348 was previously known from adaptive optics imaging by Bouvier et al. However, because of a high likelihood of background star contamination and in the absence of follow-up astrometry, Bouvier et al. tentatively concluded that the candidate companion was not physically associated with H II 1348. We establish the proper-motion association of the pair from adaptive optics imaging with the Palomar 5 m telescope. Adaptivemore » optics spectroscopy with the integral field spectrograph OSIRIS on the Keck 10 m telescope reveals that the companion has a spectral type of M8 {+-} 1. According to substellar evolution models, the M8 spectral type resides within the substellar mass regime at the age of the Pleiades. The primary itself is a known double-lined spectroscopic binary, which makes the resolved companion, H II 1348B, the least massive and widest component of this hierarchical triple system and the first substellar companion to a stellar primary in the Pleiades.« less

THE ORION H ii REGION AND THE ORION BAR IN THE MID-INFRARED

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

Salgado, F.; Tielens, A. G. G. M.; Berné, O.

2016-10-20

We present mid-infrared photometry of the Orion bar obtained with the Faint Object infraRed Camera for the SOFIA Telescope (FORCAST) on board SOFIA at 6.4, 6.6, 7.7, 19.7, 31.5, and 37.1 μ m. By complementing this observation with archival FORCAST and Herschel /PACS images, we are able to construct a complete infrared spectral energy distribution of the Huygens region in the Orion nebula. Comparing the infrared images with gas tracers, we find that PACS maps trace the molecular cloud, while the FORCAST data trace the photodissociation region (PDR) and the H ii region. Analysis of the energetics of the regionmore » reveal that the PDR extends for 0.28 pc along the line of sight and that the bar is inclined at an angle of 4°. The infrared and submillimeter images reveal that the Orion bar represents a swept-up shell with a thickness of 0.1 pc. The mass of the shell implies a shock velocity of ≃3 km s{sup −1} and an age of ≃10{sup 5} years for the H ii region. Our analysis shows that the UV and infrared dust opacities in the H ii region and the PDR are a factor 5 to 10 lower than in the diffuse interstellar medium. In the ionized gas, Ly α photons are a major source of dust heating at distances larger than ≃0.06 pc from θ {sup 1} Ori C. Dust temperatures can be explained if the size of the grains is between 0.1 and 1 μ m. We derive the photoelectric heating efficiency of the atomic gas in the Orion bar. The results are in good qualitative agreement with models and the quantitative differences indicate a decreased polycyclic aromatic hydrocarbon abundance in this region.« less

Seizures induced in immature rats by homocysteic acid and the associated brain damage are prevented by group II metabotropic glutamate receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate.

PubMed

Folbergrová, Jaroslava; Druga, Rastislav; Otáhal, Jakub; Haugvicová, Renata; Mares, Pavel; Kubová, Hana

2005-04-01

The present study has examined the anticonvulsant and neuroprotective effect of group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the model of seizures induced in immature 12-day-old rats by bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-tonic seizures, approximately 45-50 min after infusion. Comparable time intervals were used for sacrificing the pups which had received 2R,4R-APDC. Low doses of 2R,4R-APDC (0.05 nmol/side) provided a pronounced anticonvulsant effect which was abolished by pretreatment with a selective group II mGluR antagonist LY341495. Generalized clonic-tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these seizures were either normalized (decrease of glucose and glycogen) or markedly reduced (an accumulation of lactate). EEG recordings support the marked anticonvulsant effect of 2R,4R-APDC, nevertheless, this was only partial. In spite of the absence of obvious motor phenomena, isolated spikes or even short periods of partial ictal activity could be observed. Isolated spikes could also be seen in some animals after application of 2R,4R-APDC alone, reflecting most likely subclinical proconvulsant activity of this agonist. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration, as revealed by Fluoro-Jade B staining, was observed in a number of brain regions following infusion of DL-HCA alone (seizure group), whereas 2R,4R-APDC pretreatment provided substantial neuroprotection. The present findings support the possibility that group II mGluRs are a promising target for a novel approach to treating epilepsy.

A Fe(II)/citrate/UV/PMS process for carbamazepine degradation at a very low Fe(II)/PMS ratio and neutral pH: The mechanisms.

PubMed

Ling, Li; Zhang, Dapeng; Fan, Chihhao; Shang, Chii

2017-11-01

A novel Fe(II)/citrate/UV/PMS process for degrading a model micropollutant, carbamazepine (CBZ), at a low Fe(II)/PMS ratio and neutral pH has been proposed in this study, and the mechanisms of radical generation in the system was explored. With a UV dose of 302.4 mJ/cm 2 , an initial pH of 7, and CBZ, PMS, Fe(II) and citrate at initial concentrations of 10, 100, 12 and 26 μM, respectively, the CBZ degradation efficiency reached 71% in 20 min in the Fe(II)/citrate/UV/PMS process, which was 4.7 times higher than that in either the citrate/UV/PMS or Fe(II)/citrate/PMS process. The enhanced CBZ degradation in the Fe(II)/citrate/UV/PMS process was mainly attributed to the continuous activation of PMS by the UV-catalyzed regenerated Fe(II) from a Fe(III)-citrate complex, [Fe 3 O(cit) 3 H 3 ] 2- , which not only maintained Fe(III) soluble at neutral pH, but also increased 6.6 and 2.6 times of its molar absorbance and quantum yield as compared to those of ionic Fe(III), respectively. In the Fe(II)/citrate/UV/PMS process, the SO 4 •- produced from the fast reaction between PMS and the initially-added Fe(II) contributed 11% of CBZ degradation. The PMS activation by the UV radiation and regenerated Fe(II) contributed additional 14% and 46% of CBZ removal, respectively. The low iron and citrate doses and the fast radical generation at neutral pH make the Fe(II)/citrate/UV/PMS process suitable for degrading recalcitrant organic compounds in potable water. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bipolar H II regions produced by cloud-cloud collisions

NASA Astrophysics Data System (ADS)

Whitworth, Anthony; Lomax, Oliver; Balfour, Scott; Mège, Pierre; Zavagno, Annie; Deharveng, Lise

2018-05-01

We suggest that bipolar H II regions may be the aftermath of collisions between clouds. Such a collision will produce a shock-compressed layer, and a star cluster can then condense out of the dense gas near the center of the layer. If the clouds are sufficiently massive, the star cluster is likely to contain at least one massive star, which emits ionizing radiation, and excites an H II region, which then expands, sweeping up the surrounding neutral gas. Once most of the matter in the clouds has accreted onto the layer, expansion of the H II region meets little resistance in directions perpendicular to the midplane of the layer, and so it expands rapidly to produce two lobes of ionized gas, one on each side of the layer. Conversely, in directions parallel to the midplane of the layer, expansion of the H II region stalls due to the ram pressure of the gas that continues to fall towards the star cluster from the outer parts of the layer; a ring of dense neutral gas builds up around the waist of the bipolar H II region, and may spawn a second generation of star formation. We present a dimensionless model for the flow of ionized gas in a bipolar H II region created according to the above scenario, and predict the characteristics of the resulting free-free continuum and recombination-line emission. This dimensionless model can be scaled to the physical parameters of any particular system. Our intention is that these predictions will be useful in testing the scenario outlined above, and thereby providing indirect support for the role of cloud-cloud collisions in triggering star formation.

40 CFR 142.64 - Variances and exemptions from the requirements of part 141, subpart H-Filtration and Disinfection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... requirements of part 141, subpart H-Filtration and Disinfection. 142.64 Section 142.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Identification of Best Technology, Treatment Techniques or Other Means...

Nitrosoamphetamine binding to myoglobin and hemoglobin: Crystal structure of the H64A myoglobin-nitrosoamphetamine adduct

PubMed Central

Wang, Bing; Powell, Samantha M.; Guan, Ye; Xu, Nan; Thomas, Leonard M.; Richter-Addo, George B.

2017-01-01

N-hydroxyamphetamine (AmphNHOH) is an oxidative metabolite of amphetamine and methamphetamine. It is known to form inhibitory complexes upon binding to heme proteins. However, its interactions with myoglobin (Mb) and hemoglobin (Hb) have not been reported. We demonstrate that the reactions of AmphNHOH with ferric Mb and Hb generate the respective heme-nitrosoamphetamine derivatives characterized by UV-vis spectroscopy. We have determined the X-ray crystal structure of the H64A Mb-nitrosoamphetamine complex to 1.73 Å resolution. The structure reveals the N-binding of the nitroso-d-amphetamine isomer, with no significant H-bonding interactions between the ligand and the distal pocket amino acid residues. PMID:28450187

Removal of Pb(II), Cd(II), Cu(II), and Zn(II) by hematite nanoparticles: effect of sorbent concentration, pH, temperature, and exhaustion.

PubMed

Shipley, Heather J; Engates, Karen E; Grover, Valerie A

2013-03-01

Nanoparticles offer the potential to improve environmental treatment technologies due to their unique properties. Adsorption of metal ions (Pb(II), Cd(II), Cu(II), Zn(II)) to nanohematite was examined as a function of sorbent concentration, pH, temperature, and exhaustion. Adsorption experiments were conducted with 0.05, 0.1, and 0.5 g/L nanoparticles in a pH 8 solution and in spiked San Antonio tap water. The adsorption data showed the ability of nanohematite to remove Pb, Cd, Cu, and Zn species from solution with adsorption increasing as the nanoparticle concentration increased. At 0.5 g/L nanohematite, 100 % Pb species adsorbed, 94 % Cd species adsorbed, 89 % Cu species adsorbed and 100 % Zn species adsorbed. Adsorption kinetics for all metals tested was described by a pseudo second-order rate equation with lead having the fastest rate of adsorption. The effect of temperature on adsorption showed that Pb(II), Cu(II), and Cd(II) underwent an endothermic reaction, while Zn(II) underwent an exothermic reaction. The nanoparticles were able to simultaneously remove multiple metals species (Zn, Cd, Pb, and Cu) from both a pH 8 solution and spiked San Antonio tap water. Exhaustion experiments showed that at pH 8, exhaustion did not occur for the nanoparticles but adsorption does decrease for Cd, Cu, and Zn species but not Pb species. The strong adsorption coupled with the ability to simultaneously remove multiple metal ions offers a potential remediation method for the removal of metals from water.

SYNTHESIS AND EVALUATION OF NEW PHTHALAZINE SUBSTITUTED β-LACTAM DERIVATIVES AS CARBONIC ANHYDRASE INHIBITORS.

PubMed

Berber, Nurcan; Arslan, Mustafa; Bilen, Çiğdem; Sackes, Zübeyde; Gençer, Nahit; Arslan, Oktay

2015-01-01

A new series of phthalazine substituted β-lactam derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA I and II) were evaluated. 2H-Indazolo[2,1-b]phthala- zine-trione derivative was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and the nitro group was reduced to 13-(4-aminophenyl)-3,3-dimethyl-3,4-dihydro- 2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione with SnCl2 · 2H2O. The reduced compound was re- acted with different aromatic aldehydes, and phthalazine substituted imines were synthesized. The imine compounds undergo (2+2) cycloaddition reactions with ketenes to produce 2H-indazolo[2,1-b]phthala-zine-trione substituted β-lactam derivatives. The β-lactam compounds were tested as inhibitors of the CA isoenzyme activity. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. 1-(4-(3,3-dimethyl- 1,6,1 1-trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2-b]phthalazin-13- yl)phenyl)-2-oxo-4-p-tolylazetidin-3-yl acetate (IC50 = 6.97 µM for hCA I and 8.48 µM for hCA II) had the most inhibitory effect.

Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) and E-cadherin.

PubMed

Sun, Xujuan; Wei, Bin; Liu, Shuqing; Guo, Chunmei; Wu, Na; Liu, Qinlong; Sun, Ming-Zhong

2016-12-01

Annexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism. RNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5- Hca-F cells were obtained via G418 screening by limited dilution method. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting (WB) were applied to measure Anxa5 expression levels. CCK-8, Boyden transwell-chamber and in situ LN adhesion assays were performed to explore the effects of Anxa5 on the proliferation, migration, invasion and adhesion capacities of Hca-F. WB and qRT-PCR were used to detect the level changes of key molecules in corresponding signal pathways. We obtained two monoclonal shRNA-Anxa5-transfected Hca-F cell lines with stable knockdowns of Anxa5. Anxa5 knockdown resulted in significantly reduced proliferation, migration, invasion and in situ LN adhesion potentials of Hca-F in proportion to its knockdown extent. Anxa5 downregulation enhanced E-cadherin levels in Hca-F. Moreover, Anxa5 affected Hca-F behaviours specifically via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) instead of p38MAPK/c-Jun, Jnk/c-Jun and AKT/c-Jun pathways. Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells via ERK2/c-Jun/p-c-Jun(Ser73) and ERK2/E-cadherin pathways. It is an important molecule in metastasis (especially LNM) and a potential therapeutic target for hepatocarcinoma. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Detection of l-Cysteine in wheat flour by Raman microspectroscopy combined chemometrics of HCA and PCA.

PubMed

Cebi, Nur; Dogan, Canan Ekinci; Develioglu, Ayşen; Yayla, Mediha Esra Altuntop; Sagdic, Osman

2017-08-01

l-Cysteine is deliberately added to various flour types since l-Cysteine has enabled favorable baking conditions such as low viscosity, increased elasticity and rise during baking. In Turkey, usage of l-Cysteine as a food additive isn't allowed in wheat flour according to the Turkish Food Codex Regulation on food additives. There is an urgent need for effective methods to detect l-Cysteine in wheat flour. In this study, for the first time, a new, rapid, effective, non-destructive and cost-effective method was developed for detection of l-Cysteine in wheat flour using Raman microscopy. Detection of l-Cysteine in wheat flour was accomplished successfully using Raman microscopy combined chemometrics of PCA (Principal Component Analysis) and HCA (Hierarchical Cluster Analysis). In this work, 500-2000cm -1 spectral range (fingerprint region) was determined to perform PCA and HCA analysis. l-Cysteine and l-Cystine were determined with detection limit of 0.125% (w/w) in different wheat flour samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prostaglandin E₂ regulates cellular migration via induction of vascular endothelial growth factor receptor-1 in HCA-7 human colon cancer cells.

PubMed

Fujino, Hiromichi; Toyomura, Kaori; Chen, Xiao-bo; Regan, John W; Murayama, Toshihiko

2011-02-01

An important event in the development of tumors is angiogenesis, or the formation of new blood vessels. Angiogenesis is also known to be involved in tumor cell metastasis and is dependent upon the activity of the vascular endothelial growth factor (VEGF) signaling pathway. Studies of mice in which the EP3 prostanoid receptors have been genetically deleted have shown a role for these receptors in cancer growth and angiogenesis. In the present study, human colon cancer HCA-7 cells were used as a model system to understand the potential role of EP3 receptors in tumor cell migration. We now show that stimulation of HCA-7 cells with PGE₂ enhanced the up-regulation of VEGF receptor-1 (VEGFR-1) expression by a mechanism involving EP3 receptor-mediated activation of phosphatidylinositol 3-kinase and the extracellular signal-regulated kinases. Moreover, the PGE₂ stimulated increase in VEGFR-1 expression was accompanied by an increase in the cellular migration of HCA-7 cells. Given the known involvement of VEGFR-1 in cellular migration, our results suggest that EP3 receptors may contribute to tumor cell metastasis by increasing cellular migration through the up-regulation of VEGFR-1 signaling. Copyright © 2010 Elsevier Inc. All rights reserved.

Expression, purification, and characterization of protective MPT64 antigen protein and identification of its multimers isolated from nontoxic Mycobacterium tuberculosis H37Ra.

PubMed

Chu, Teng-Ping J; Yuann, Jeu-Ming P

2011-05-01

MPT64, a secreted protein of Mycobacterium tuberculosis (MTB), stimulates the immune reactions within cells and is a protective antigen that is lost by the bacilli Calmette-Guérin (BCG) vaccine during propagation. To minimize the toxicity caused by MTB, we used the MPT64 gene encoded by nontoxic H37Ra MTB to carry out genetic expansion via polymerase chain reaction and gene clone MPT64. The plasmid DNA encoded MPT64 was expressed at 20°C for 22 H, and a large quantity of MPT64 was obtained. In the absence of urea, MPT64 multimers with subunits being covalently connected via disulfide bonds were detected by Western blot showing strong protein-protein interactions, as evidenced by the formation of MPT64 tetramers. Finally, with urea of decreasing concentrations, we refolded MPT64 purified in the presence of urea and determined its secondary structures using circular dichroism. MPT64 was found to contain 2.2% α-helix, 50.9% β-sheet, 19.5% turn, and 27.4% random coil. The molecular weight of MPT64 was determined by a matrix-assisted laser desorption ionization-time of flight mass spectrometer and found to be 23,497 Da, very close to the theoretical molecular weight of MPT64. The results presented here provide a sound basis for future biochemical and biophysical studies of MPT64 or any other proteins encoded by nontoxic H37Ra MTB. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Wind bubbles within H ii regions around slowly moving stars

NASA Astrophysics Data System (ADS)

Mackey, Jonathan; Gvaramadze, Vasilii V.; Mohamed, Shazrene; Langer, Norbert

2015-01-01

Interstellar bubbles around O stars are driven by a combination of the star's wind and ionizing radiation output. The wind contribution is uncertain because the boundary between the wind and interstellar medium is difficult to observe. Mid-infrared observations (e.g., of the H ii region RCW 120) show arcs of dust emission around O stars, contained well within the H ii region bubble. These arcs could indicate the edge of an asymmetric stellar wind bubble, distorted by density gradients and/or stellar motion. We present two-dimensional, radiation-hydrodynamics simulations investigating the evolution of wind bubbles and H ii regions around massive stars moving through a dense (nH = 3000 cm-3), uniform medium with velocities ranging from 4 to 16 km s-1. The H ii region morphology is strongly affected by stellar motion, as expected, but the wind bubble is also very aspherical from birth, even for the lowest space velocity considered. Wind bubbles do not fill their H ii regions (we find filling factors of 10-20 per cent), at least for a main sequence star with mass M⋆ ~ 30 M⊙. Furthermore, even for supersonic velocities the wind bow shock does not significantly trap the ionization front. X-ray emission from the wind bubble is soft, faint, and comes mainly from the turbulent mixing layer between the wind bubble and the H ii region. The wind bubble radiates <1 per cent of its energy in X-rays; it loses most of its energy by turbulent mixing with cooler photoionized gas. Comparison of the simulations with the H ii region RCW 120 shows that its dynamical age is ≲0.4 Myr and that stellar motion ≲4 km s-1 is allowed, implying that the ionizing source is unlikely to be a runaway star but more likely formed in situ. The region's youth, and apparent isolation from other O or B stars, makes it very interesting for studies of massive star formation and of initial mass functions. Movies are available in electronic form at http://www.aanda.org

Formation of Hg(II) tetrathiolate complexes with cysteine at neutral pH

DOE PAGES

Warner, Thomas; Jalilehvand, Farideh

2016-01-04

Mercury(II) ions precipitate from aqueous cysteine (H 2Cys) solutions containing H 2Cys/Hg(II) mole ratio ≥ 2.0 as Hg( S-HCys) 2. In absence of additional cysteine, the precipitate dissolves at pH ~12 with the [Hg( S, N-Cys) 2] 2- complex dominating. With excess cysteine (H 2Cys/Hg(II) mole ratio ≥ 4.0), higher complexes form and the precipitate dissolves at lower pH values. Previously, we found that tetrathiolate [Hg( S-Cys) 4] 6- complexes form at pH = 11.0; in this work we extend the investigation to pH values of physiological interest. We examined two series of Hg(II)-cysteine solutions in which C Hg(II) variedmore » between 8 – 9 mM and 80 – 100 mM, respectively, with H 2Cys/Hg(II) mole ratios from 4 to ~20. The solutions were prepared in the pH range 7.1 – 8.8, at the pH at which the initial Hg( S-HCys) 2 precipitate dissolved. The variations in the Hg(II) speciation were followed by 199Hg NMR, X-ray absorption and Raman spectroscopic techniques. Our results show that in the dilute solutions (C Hg(II) = 8 – 9 mM), mixtures of di-, tri- (major) and tetrathiolate complexes exist at moderate cysteine excess (C H2Cys ~ 0.16 M) at pH 7.1. In the more concentrated solutions (C Hg(II) = 80 – 100 mM) with high cysteine excess (C H2Cys > 0.9 M), tetrathiolate [Hg( S-cysteinate) 4] m-6 ( m = 0 – 4) complexes dominate in the pH range 7.3 – 7.8, with lower charge than for the [Hg( S-Cys) 4] 6- complex due to protonation of some ( m) of the amino groups of the coordinated cysteine ligands. In conclusion, the results of this investigation could provide a key to the mechanism of biosorption and accumulation of Hg(II) ions in biological / environmental systems.« less

Assessment of 16 chemicals on proliferation and apoptosis in human neuroprogenitor cells using high-content image analysis (HCA).

EPA Science Inventory

The need for efficient methods of screening chemicals for the potential to cause developmental neurotoxicity is paramount. We previously described optimization of an HCA assay for proliferation and apoptosis in ReNcell CX cells (ReN), identifying appropriate controls. Utility of ...

Investigation of the Iron(II) Release Mechanism of Human H-Ferritin as a Function of pH.

PubMed

Sala, Davide; Ciambellotti, Silvia; Giachetti, Andrea; Turano, Paola; Rosato, Antonio

2017-09-25

We investigated the kinetics of the release of iron(II) ions from the internal cavity of human H-ferritin as a function of pH. Extensive molecular dynamics simulations of the entire 24-mer ferritin provided atomic-level information on the release mechanism. Double protonation of His residues at pH 4 facilitates the removal of the iron ligands within the C3 channel through the formation of salt bridges, resulting in a significantly lower release energy barrier than pH 9.

Blue-wing enhancement of the chromospheric Mg II h and k lines in a solar flare

NASA Astrophysics Data System (ADS)

Tei, Akiko; Sakaue, Takahito; Okamoto, Takenori J.; Kawate, Tomoko; Heinzel, Petr; UeNo, Satoru; Asai, Ayumi; Ichimoto, Kiyoshi; Shibata, Kazunari

2018-05-01

We performed coordinated observations of AR 12205, which showed a C-class flare on 2014 November 11, with the Interface Region Imaging Spectrograph (IRIS) and the Domeless Solar Telescope (DST) at Hida Observatory. Using spectral data in the Si IV 1403 Å, C II 1335 Å, and Mg II h and k lines from IRIS and the Ca II K, Ca II 8542 Å, and Hα lines from DST, we investigated a moving flare kernel during the flare. In the Mg II h line, the leading edge of the flare kernel showed an intensity enhancement in the blue wing and a smaller intensity of the blue-side peak (h2v) than that of the red-side one (h2r). The blueshift lasted for 9-48 s with a typical speed of 10.1 ± 2.6 km s-1, which was followed by a high intensity and a large redshift with a speed of up to 51 km s-1 detected in the Mg II h line. The large redshift was a common property for all six lines, but the blueshift prior to it was found only in the Mg II lines. Cloud modeling of the Mg II h line suggests that the blue-wing enhancement with such a peak difference could have been caused by a chromospheric-temperature (cool) upflow. We discuss a scenario in which an upflow of cool plasma is lifted up by expanding hot plasma owing to the deep penetration of non-thermal electrons into the chromosphere. Furthermore, we found that the blueshift persisted without any subsequent redshift in the leading edge of the flare kernel during its decaying phase. The cause of such a long-lasting blueshift is also discussed.

Biological Low-pH Mn(II) Oxidation in a Manganese Deposit Influenced by Metal-Rich Groundwater

PubMed Central

Bohu, Tsing; Akob, Denise M.; Abratis, Michael; Lazar, Cassandre S.

2016-01-01

ABSTRACT The mechanisms, key organisms, and geochemical significance of biological low-pH Mn(II) oxidation are largely unexplored. Here, we investigated the structure of indigenous Mn(II)-oxidizing microbial communities in a secondary subsurface Mn oxide deposit influenced by acidic (pH 4.8) metal-rich groundwater in a former uranium mining area. Microbial diversity was highest in the Mn deposit compared to the adjacent soil layers and included the majority of known Mn(II)-oxidizing bacteria (MOB) and two genera of known Mn(II)-oxidizing fungi (MOF). Electron X-ray microanalysis showed that romanechite [(Ba,H2O)2(Mn4+,Mn3+)5O10] was conspicuously enriched in the deposit. Canonical correspondence analysis revealed that certain fungal, bacterial, and archaeal groups were firmly associated with the autochthonous Mn oxides. Eight MOB within the Proteobacteria, Actinobacteria, and Bacteroidetes and one MOF strain belonging to Ascomycota were isolated at pH 5.5 or 7.2 from the acidic Mn deposit. Soil-groundwater microcosms demonstrated 2.5-fold-faster Mn(II) depletion in the Mn deposit than adjacent soil layers. No depletion was observed in the abiotic controls, suggesting that biological contribution is the main driver for Mn(II) oxidation at low pH. The composition and species specificity of the native low-pH Mn(II) oxidizers were highly adapted to in situ conditions, and these organisms may play a central role in the fundamental biogeochemical processes (e.g., metal natural attenuation) occurring in the acidic, oligotrophic, and metalliferous subsoil ecosystems. IMPORTANCE This study provides multiple lines of evidence to show that microbes are the main drivers of Mn(II) oxidation even at acidic pH, offering new insights into Mn biogeochemical cycling. A distinct, highly adapted microbial community inhabits acidic, oligotrophic Mn deposits and mediates biological Mn oxidation. These data highlight the importance of biological processes for Mn biogeochemical cycling

Thermal Pressure in Diffuse H2 Gas Measured by Herschel [C II] Emission and FUSE UV H2 Absorption

NASA Astrophysics Data System (ADS)

Velusamy, T.; Langer, W. D.; Goldsmith, P. F.; Pineda, J. L.

2017-04-01

UV absorption studies with the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite have made important observations of H2 molecular gas in Galactic interstellar translucent and diffuse clouds. Observations of the 158 μm [C II] fine-structure line with Herschel trace the same H2 molecular gas in emission. We present [C II] observations along 27 lines of sight (LOSs) toward target stars of which 25 have FUSE H2 UV absorption. Two stars have only HST STIS C II λ2325 absorption data. We detect [C II] 158 μm emission features in all but one target LOS. For three target LOSs that are close to the Galactic plane, | {\\text{}}b| < 1°, we also present position-velocity maps of [C II] emission observed by Herschel Heterodyne Instrument in the Far Infrared (HIFI) in on-the-fly spectral-line mapping. We use the velocity-resolved [C II] spectra observed by the HIFI instrument toward the target LOSs observed by FUSE to identify [C II] velocity components associated with the H2 clouds. We analyze the observed velocity integrated [C II] spectral-line intensities in terms of the densities and thermal pressures in the H2 gas using the H2 column densities and temperatures measured by the UV absorption data. We present the H2 gas densities and thermal pressures for 26 target LOSs and from the [C II] intensities derive a mean thermal pressure in the range of ˜6100-7700 K cm-3 in diffuse H2 clouds. We discuss the thermal pressures and densities toward 14 targets, comparing them to results obtained using the UV absorption data for two other tracers C I and CO. Our results demonstrate the richness of the far-IR [C II] spectral data which is a valuable complement to the UV H2 absorption data for studying diffuse H2 molecular clouds. While the UV absorption is restricted to the directions of the target star, far-IR [C II] line emission offers an opportunity to employ velocity-resolved spectral-line mapping capability to study in detail the clouds’ spatial and velocity structures.

Chapter A6. Section 6.4. pH

USGS Publications Warehouse

Wilde, Franceska D.; Busenberg, Eurybiades; Radtke, Dean B.

2006-01-01

Measurement of pH is critical to the understanding of the viability and vulnerability of environmental waters and is considered a master variable in determining the aqueous geochemistry of an aqueous system. pH is a measure that represents the hydrogen-ion concentration (activity) of a solution. This section of the National Field Manual (NFM) describes U.S. Geological Survey (USGS) guidance and protocols for measurement of pH in ground and surface waters.

Biological low pH Mn(II) oxidation in a manganese deposit influenced by metal-rich groundwater

USGS Publications Warehouse

Bohu, Tsing; Akob, Denise M.; Abratis, Michael; Lazar, Cassandre S.; Küsel, Kirsten

2016-01-01

The mechanisms, key organisms, and geochemical significance of biological low-pH Mn(II) oxidation are largely unexplored. Here, we investigated the structure of indigenous Mn(II)-oxidizing microbial communities in a secondary subsurface Mn oxide deposit influenced by acidic (pH 4.8) metal-rich groundwater in a former uranium mining area. Microbial diversity was highest in the Mn deposit compared to the adjacent soil layers and included the majority of known Mn(II)-oxidizing bacteria (MOB) and two genera of known Mn(II)-oxidizing fungi (MOF). Electron X-ray microanalysis showed that romanechite [(Ba,H2O)2(Mn4+,Mn3+)5O10] was conspicuously enriched in the deposit. Canonical correspondence analysis revealed that certain fungal, bacterial, and archaeal groups were firmly associated with the autochthonous Mn oxides. Eight MOB within the Proteobacteria, Actinobacteria, and Bacteroidetes and one MOF strain belonging to Ascomycota were isolated at pH 5.5 or 7.2 from the acidic Mn deposit. Soil-groundwater microcosms demonstrated 2.5-fold-faster Mn(II) depletion in the Mn deposit than adjacent soil layers. No depletion was observed in the abiotic controls, suggesting that biological contribution is the main driver for Mn(II) oxidation at low pH. The composition and species specificity of the native low-pH Mn(II) oxidizers were highly adapted to in situ conditions, and these organisms may play a central role in the fundamental biogeochemical processes (e.g., metal natural attenuation) occurring in the acidic, oligotrophic, and metalliferous subsoil ecosystems.

The early evolution of giant H II regions formed by supernova explosions

NASA Technical Reports Server (NTRS)

Kafatos, M. C.

1971-01-01

The evolution of a giant H II region, which cools after an initial ionization, is discussed. The discussion is applied to the Vela X and Tycho supernovae. Other giant H II regions might not be as easily detectable as the Vela X region. The Tycho region may be just detectable in the O(II) or O(III) optical lines or as a hole in the 21-cm emission line profiles, as is suggested in the data. These giant H II regions last appreciably longer than the continuum radio sources within them.

2-Benzylpiperazine: A new scaffold for potent human carbonic anhydrase inhibitors. Synthesis, enzyme inhibition, enantioselectivity, computational and crystallographic studies and in vivo activity for a new class of intraocular pressure lowering agents.

PubMed

Chiaramonte, Niccolò; Bua, Silvia; Ferraroni, Marta; Nocentini, Alessio; Bonardi, Alessandro; Bartolucci, Gianluca; Durante, Mariaconcetta; Lucarini, Laura; Chiapponi, Donata; Dei, Silvia; Manetti, Dina; Teodori, Elisabetta; Gratteri, Paola; Masini, Emanuela; Supuran, Claudiu T; Romanelli, Maria Novella

2018-05-10

Two series of 2-benzylpiperazines have been prepared and tested for the inhibition of physiologically relevant isoforms of human carbonic anhydrases (hCA, EC 4.2.1.1). The new compounds carry on one nitrogen atom of the piperazine ring a sulfamoylbenzamide group as zinc-binding moiety, and different alkyl/acyl/sulfonyl groups on the other nitrogen. Regio- and stero-isomers are described. The majority of these compounds showed Ki values in the low-medium nanomolar range against hCA I, II and IV, but not IX. In many instances interaction with the enzyme was enantioselective. The binding mode has been studied by means of X-ray crystallography and molecular modelling. Two compounds, evaluated in rabbit models of glaucoma, were able to significantly reduce intraocular pressure, making them interesting candidates for further studies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Thermodynamic controls on the kinetics of microbial low-pH Fe(II) oxidation.

PubMed

Larson, Lance N; Sánchez-España, Javier; Kaley, Bradley; Sheng, Yizhi; Bibby, Kyle; Burgos, William D

2014-08-19

Acid mine drainage (AMD) is a major worldwide environmental threat to surface and groundwater quality. Microbial low-pH Fe(II) oxidation could be exploited for cost-effective AMD treatment; however, its use is limited because of uncertainties associated with its rate and ability to remove Fe from solution. We developed a thermodynamic-based framework to evaluate the kinetics of low-pH Fe(II) oxidation. We measured the kinetics of low-pH Fe(II) oxidation at five sites in the Appalachian Coal Basin in the US and three sites in the Iberian Pyrite Belt in Spain and found that the fastest rates of Fe(II) oxidation occurred at the sites with the lowest pH values. Thermodynamic calculations showed that the Gibbs free energy of Fe(II) oxidation (ΔG(oxidation)) was also most negative at the sites with the lowest pH values. We then conducted two series of microbial Fe(II) oxidation experiments in laboratory-scale chemostatic bioreactors operated through a series of pH values (2.1-4.2) and found the same relationships between Fe(II) oxidation kinetics, ΔG(oxidation), and pH. Conditions that favored the fastest rates of Fe(II) oxidation coincided with higher Fe(III) solubility. The solubility of Fe(III) minerals, thus plays an important role on Fe(II) oxidation kinetics. Methods to incorporate microbial low-pH Fe(II) oxidation into active and passive AMD treatment systems are discussed in the context of these findings. This study presents a simplified model that describes the relationship between free energy and microbial kinetics and should be broadly applicable to many biogeochemical systems.

GUM 48d: AN EVOLVED H II REGION WITH ONGOING STAR FORMATION

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

Karr, J. L.; Ohashi, N.; Manoj, P.

2009-05-20

High-mass star formation and the evolution of H II regions have a substantial impact on the morphology and star formation history of molecular clouds. The H II region Gum 48d, located in the Centaurus Arm at a distance of 3.5 kpc, is an old, well evolved H II region whose ionizing stars have moved off the main sequence. As such, it represents a phase in the evolution of H II regions that is less well studied than the earlier, more energetic, main-sequence phase. In this paper, we use multiwavelength archive data from a variety of sources to perform a detailedmore » study of this interesting region. Morphologically, Gum 48d displays a ring-like faint H II region associated with diffuse emission from the associated photodissociation region, and is formed from part of a large, massive molecular cloud complex. There is extensive ongoing star formation in the region, at scales ranging from low to high mass, which is consistent with triggered star formation scenarios. We investigate the dynamical history and evolution of this region, and conclude that the original H II region was once larger and more energetic than the faint region currently seen. The proposed history of this molecular cloud complex is one of multiple, linked generations of star formation, over a period of 10 Myr. Gum 48d differs significantly in morphology and star formation from the other H II regions in the molecular cloud; these differences are likely the result of the advanced age of the region, and its different evolutionary status.« less

Integral field spectroscopy of H II regions in M33

NASA Astrophysics Data System (ADS)

López-Hernández, Jesús; Terlevich, Elena; Terlevich, Roberto; Rosa-González, Daniel; Díaz, Ángeles; García-Benito, Rubén; Vílchez, José; Hägele, Guillermo

2013-03-01

Integral field spectroscopy is presented for star-forming regions in M33. A central area of 300 × 500 pc2 and the external H II region IC 132, at a galactocentric distance ˜19 arcmin (4.69 kpc), were observed with the Potsdam Multi-Aperture Spectrophotometer instrument at the 3.5-m telescope of the Centro Astronómico Hispano-Alemán (CAHA, aka Calar Alto Observatory). The spectral coverage goes from 3600 Å to 1 μm to include from [O II] λ3727 Å to the near-infrared lines required for deriving sulphur electron temperature and abundance diagnostics. Local conditions within individual H II regions are presented in the form of emission-line fluxes and physical conditions for each spatial resolution element (spaxel) and for segments with similar Hα surface brightness. A clear dichotomy is observed when comparing the central to outer disc H II regions. While the external H II region has higher electron temperature plus larger Hβ equivalent width, size and excitation, the central region has higher extinction and metal content. The dichotomy extends to the Baldwin-Phillips-Terlevich (BPT) diagnostic diagrams that show two orthogonal broad distributions of points. By comparing with pseudo-3D photoionization models, we conclude that the bulk of observed differences are probably related to a different ionization parameter and metallicity. Wolf-Rayet (WR) features are detected in IC 132, and resolved into two concentrations whose integrated spectra were used to estimate the characteristic number of WR stars. No WR features were detected in the central H II regions despite their higher metallicity.

Near-Infrared [Fe II] and H2 Study of the Galactic Supernova Remnants

NASA Astrophysics Data System (ADS)

Lee, Yong-Hyun; Koo, Bon-Chul; Lee, Jae-Joon; Jaffe, Daniel T.; Burton, Michael G.; Ryder, Stuart D.

2018-01-01

We have searched for near-infrared (NIR) [Fe II] (1.644 μm) and H2 1-0 S(1) (2.122 μm) emission features associated with Galactic supernova remnants (SNRs) using the narrow-band imaging surveys UWIFE / UWISH2 (UKIRT Widefield Infrared Survey for [Fe II] / H2). Both surveys cover about 180 square degrees of the first Galactic quadrant (7° < l < 65° -1.3° < b < +1.3°), and a total of 79 SNRs are falling in the survey area. We have found 19 [Fe II]- and 19 H2-emitting SNRs, giving a detection rate of 24%. Eleven SNRs show both emission features. Some of the SNRs show bright, complex, and interesting structures that have never been reported in previous studies. The brightest SNR in the both emission is W49B, contributing ~70% of the total [Fe II] luminosity of the detected SNRs. The total [Fe II] luminosity, however, is considerably less than what we would expect from the SN rate of our Galaxy.Among the SNRs showing both [Fe II] and H2 emission lines, some SNRs show the “[Fe II]-H2 reversal” phenomenon, i.e., the H2 emission features are detected outside the [Fe II] emission boundary. We carried out high resolution (R~40,000) NIR H- and K-band spectroscopy of the five SNRs showing the [Fe II]-H2 reversal (G11.2-0.3, KES 73, W44, 3C 396, W49B) using IGRINS (Immersion GRating INfrared Spectrograph). Various ro-vibrational H2 lines have been detected, which are used to derive the kinematic distances to the SNRs and to investigate the origin of the H2 emission. The detected H2 lines show broad line width (> 10 km s-1) and line flux ratios of thermal excitation. We discuss the origin of the extended H2 emission features beyond the the [Fe II] emission boundary.

Design of crashworthy structures with controlled behavior in HCA framework

NASA Astrophysics Data System (ADS)

Bandi, Punit

The field of crashworthiness design is gaining more interest and attention from automakers around the world due to increasing competition and tighter safety norms. In the last two decades, topology and topometry optimization methods from structural optimization have been widely explored to improve existing designs or conceive new designs with better crashworthiness. Although many gradient-based and heuristic methods for topology- and topometry-based crashworthiness design are available these days, most of them result in stiff structures that are suitable only for a set of vehicle components in which maximizing the energy absorption or minimizing the intrusion is the main concern. However, there are some other components in a vehicle structure that should have characteristics of both stiffness and flexibility. Moreover, the load paths within the structure and potential buckle modes also play an important role in efficient functioning of such components. For example, the front bumper, side frame rails, steering column, and occupant protection devices like the knee bolster should all exhibit controlled deformation and collapse behavior. The primary objective of this research is to develop new methodologies to design crashworthy structures with controlled behavior. The well established Hybrid Cellular Automaton (HCA) method is used as the basic framework for the new methodologies, and compliant mechanism-type (sub)structures are the highlight of this research. The ability of compliant mechanisms to efficiently transfer force and/or motion from points of application of input loads to desired points within the structure is used to design solid and tubular components that exhibit controlled deformation and collapse behavior under crash loads. In addition, a new methodology for controlling the behavior of a structure under multiple crash load scenarios by adaptively changing the contributions from individual load cases is developed. Applied to practical design problems

The classical D-type expansion of spherical H II regions

NASA Astrophysics Data System (ADS)

Williams, Robin J. R.; Bibas, Thomas G.; Haworth, Thomas J.; Mackey, Jonathan

2018-06-01

Recent numerical and analytic work has highlighted some shortcomings in our understanding of the dynamics of H II region expansion, especially at late times, when the H II region approaches pressure equilibrium with the ambient medium. Here we reconsider the idealized case of a constant radiation source in a uniform and spherically symmetric ambient medium, with an isothermal equation of state. A thick-shell solution is developed which captures the stalling of the ionization front and the decay of the leading shock to a weak compression wave as it escapes to large radii. An acoustic approximation is introduced to capture the late-time damped oscillations of the H II region about the stagnation radius. Putting these together, a matched asymptotic equation is derived for the radius of the ionization front which accounts for both the inertia of the expanding shell and the finite temperature of the ambient medium. The solution to this equation is shown to agree very well with the numerical solution at all times, and is superior to all previously published solutions. The matched asymptotic solution can also accurately model the variation of H II region radius for a time-varying radiation source.

The "Arabidopsis cax3" mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H(+)-ATPase activity

USDA-ARS?s Scientific Manuscript database

Perturbing CAX1, an "Arabidopsis" vacuolar H(+)/Ca(2+) antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among "cax1" and "ca...

40 CFR 53.64 - Test procedure: Static fractionator test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Test procedure: Static fractionator test. 53.64 Section 53.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Performance Characteristics of Class II Equivalent Methods for PM2.5 § 53.64 Test procedure: Static...

40 CFR 53.64 - Test procedure: Static fractionator test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Test procedure: Static fractionator test. 53.64 Section 53.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Performance Characteristics of Class II Equivalent Methods for PM2.5 § 53.64 Test procedure: Static...

Emission-line diagnostics of nearby H II regions including interacting binary populations

NASA Astrophysics Data System (ADS)

Xiao, Lin; Stanway, Elizabeth R.; Eldridge, J. J.

2018-06-01

We present numerical models of the nebular emission from H II regions around young stellar populations over a range of compositions and ages. The synthetic stellar populations include both single stars and interacting binary stars. We compare these models to the observed emission lines of 254 H II regions of 13 nearby spiral galaxies and 21 dwarf galaxies drawn from archival data. The models are created using the combination of the BPASS (Binary Population and Spectral Synthesis) code with the photoionization code CLOUDY to study the differences caused by the inclusion of interacting binary stars in the stellar population. We obtain agreement with the observed emission line ratios from the nearby star-forming regions and discuss the effect of binary-star evolution pathways on the nebular ionization of H II regions. We find that at population ages above 10 Myr, single-star models rapidly decrease in flux and ionization strength, while binary-star models still produce strong flux and high [O III]/H β ratios. Our models can reproduce the metallicity of H II regions from spiral galaxies, but we find higher metallicities than previously estimated for the H II regions from dwarf galaxies. Comparing the equivalent width of H β emission between models and observations, we find that accounting for ionizing photon leakage can affect age estimates for H II regions. When it is included, the typical age derived for H II regions is 5 Myr from single-star models, and up to 10 Myr with binary-star models. This is due to the existence of binary-star evolution pathways, which produce more hot Wolf-Rayet and helium stars at older ages. For future reference, we calculate new BPASS binary maximal starburst lines as a function of metallicity, and for the total model population, and present these in Appendix A.

The binding of manganese(II) and zinc(II) to the synthetic oligonucleotide d(C-G-C-G-A-A-T-T-C-G-C-G)2. A 1H NMR study.

PubMed

Frøystein, N A; Sletten, E

1991-03-01

The interaction of the synthetic oligonucleotide d(C-G-C-G-A-A-T-T-C-G-C-G)2 with two different transition-metal ions has been investigated in aqueous solution by means of 1H NMR spectroscopy. The effects on the DNA due to the presence of manganese(II) or zinc(II) have been monitored by observing the paramagnetic broadening and diamagnetic shifts of the non-exchangeable proton resonance lines, respectively. The 1H NMR spectra acquired during the course of the manganese(II) titration show very distinct broadening effects on certain DNA resonance lines. Primarily, the H8 resonance of G4 is affected, but also the H5 and H6 resonances of C3 are clearly affected by the metal. The results imply that the binding of manganese(II) to DNA is sequence specific. The 1H spectra obtained during the zinc(II) titration reveal diamagnetic shift effects which largely conform with the paramagnetic broadening effects due to the presence of manganese(II), although this picture is somewhat more complex. The H8 resonance of G4 displays a clearly visible high-field shift, while for the other guanosine H8 protons this effect is absent. The H1' and H2' protons of C3 show an effect of similar strength, although in the opposite direction, while H5 and H6 of C3 are only slightly affected. Local differences in the structure of the DNA and the basicities of potential binding sites on different base steps in the sequence might account for the observed sequence selectivity.

Far-infrared observations of the evolved H II region M16

NASA Technical Reports Server (NTRS)

Mcbreen, B.; Fazio, G. G.; Jaffe, D. T.

1982-01-01

The results of far infrared (FIR) observations of the larger H II region M16, associated with the young open star cluster NGC 6611, are discussed. Three FIR sources detected on an extended ridge of FIR emission within the scanned region are described. The observations confirm that M16 is an H II region in a late stage of evolution. The H II region has expanded and is now extremely density bounded, consisting of an extended region of ionized gas and a series of ionization fronts located at the surrounding molecular cloud boundaries nearest to the exciting OB star cluster. The FIR radiation arises from heated dust at these boundaries.

Temperature relations and abundance determinations in H II regions

NASA Astrophysics Data System (ADS)

Arellano-Córdova, K. Z.; Rodríguez, M.; Delgado-Inglada, G.

2017-11-01

Most abundance determinations in H II regions, especially for extragalactic regions, are based on the use of temperature relations, usually between Te[N II] and Te[O III]. The calibration of strong-line methods also generally rely on the use of these relations. We explore here the reliability of old and new Te[N II]-Te[O III] relations, their dispersions, and their effects on the calculation of chemical abundances. In order to do so, we have compiled and analyzed in a homogeneous way a sample of 155 H II regions that have measurements of both temperatures. We find that some of the largest departures from the temperature relation are probably due to shocks affecting Te[N II]. We consider the effects of recombination in Te[N II] and of line blending in Te[O III], and find a residual dependence of the temperature relation on the degree of ionization. We provide new robust fits of the relation and show that our fits lead to better abundance determinations. Our fits are very similar to the most used temperature relation, based on a grid of photoionization models by Stasińska (1982), and variously cited as Campbell et al. (1986) or Garnett (1992).

The Mg II h and k lines. II - Comparison with synthesized profiles and Ca II K. [solar spectra

NASA Technical Reports Server (NTRS)

Ayres, T. R.; Linsky, J. L.

1976-01-01

Measured high-dispersion center and limb profiles of the solar Mg II h and k resonance lines are compared with synthetic spectra computed with a partial-redistribution formalism and based on several upper-photosphere and lower-chromosphere temperature distributions. Profiles of the analogously formed Ca II K resonance line are also synthesized for the same atmospheric models. The spectrum-synthesis approach is outlined, and the collisional and fixed radiative rates appropriate to the adopted model atoms and solar atmosphere are discussed. It is found that the HSRA and VAL models predict systematically lower intensities in the h, k, and K inner wings than observed and that models with a somewhat higher minimum temperature (about 4450 K) can reproduce the measured inner wings and limb darkening. A 'Ca II' solar model with a minimum temperature of 4450 K is proposed as an alternative to the class of models based on continuum observations.

On the formation and expansion of H II regions

NASA Technical Reports Server (NTRS)

Franco, Jose; Tenorio-Tagle, Guillermo; Bodenheimer, Peter

1990-01-01

The evolution of H II regions in spherical clouds with small, constant-density cores and power-law density distributions r exp -w outside the core is described analytically. It is found that there is a critical exponent above which the cloud becomes completely ionized. Its value in the formation phase depends on the initial conditions, but it has a well-defined value w(crit) = 3/2 during the expansion phase. For w less than w(crit), the radius of the H II region grows at a given rate, while neutral mass accumulates in the interphase between the ionization and shock fronts. For w = w(crit), the fronts move together without mass accumulation. Cases with w greater than w(crit) lead to the champagne phase: once the cloud is fully ionized, the expansion becomes supersonic. For self-gravitating disks without magnetic fields, the main features include a new 'variable-size' stage. The initial shape of the H II region has a critical point beyond which the disk becomes completely ionized.

Change of motion and localization of cholesterol molecule during L(alpha)-H(II) transition.

PubMed Central

Hayakawa, E; Naganuma, M; Mukasa, K; Shimozawa, T; Araiso, T

1998-01-01

Formation of the inverted hexagonal (H(II)) phase from the lamellar (L(alpha)) phase of bovine brain-extracted phosphatidylcholine (BBPC) and phosphatidylethanolamine (BBPE) was investigated using 31P-NMR with or without cholesterol. When the ratio of BBPC to BBPE was 1:1, the H(II) formation was observed in the presence of 33 mol% cholesterol (i.e., BBPC:BBPE:cholesterol = 1:1:1) at 47 degrees C. The fraction of the H(II) phase in the BBPC/BBPE/cholesterol system could be controlled by the addition of dioleoylglycerol. The change of molecular motion of cholesterol affected by the H(II) formation was measured at various ratios of the L(alpha) to H(II) phase with the time-resolved fluorescence depolarization method, using dehydroergosterol as a fluorescent probe. It is observed that the motion of cholesterol became vigorous in the mixture state of the L(alpha) and the H(II) phases compared to that in the L(alpha) or the H(II) phase only. These facts show that cholesterol has the strong ability to induce the H(II) phase, probably by special molecular motion, which includes change of its location from the headgroup area to the acyl-chain area. PMID:9533700

Synthesis and evaluation of new thiadiazole derivatives as potential inhibitors of human carbonic anhydrase isozymes (hCA-I and hCA-II).

PubMed

Altintop, Mehlika Dilek; Ozdemir, Ahmet; Kucukoglu, Kaan; Turan-Zitouni, Gulhan; Nadaroglu, Hayrunnisa; Kaplancikli, Zafer Asim

2015-02-01

2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio] acetophenone derivatives (3a--s) were designed as human carbonic anhydrase isozymes (hCA-I and hCA-II) inhibitors and synthesized. hCA-I and hCA-II were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of 18 newly synthesized acetophenones on hydratase activity of these isoenzymes were studied in vitro. The average IC50 values of the new compounds for hydratase activity ranged from 0.033 to 0.14 μM for hCA-I and from 0.030 to 0.11 μM for hCA-II. Among the newly synthesized compounds, 2-[[5-(2,4-dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]-4'-bromoacetophenone (3n) can be considered as a promising hCA-II inhibitor owing to its selective and potent inhibitory effect on hCA-II.

Influenza A (H1N1) 2009 monovalent and seasonal influenza vaccination among adults 25 to 64 years of age with high-risk conditions—United States, 2010

PubMed Central

Lu, Peng-jun; Gonzalez-Feliciano, Amparo; Ding, Helen; Bryan, Leah N.; Yankey, David; Monsell, Elizabeth A.; Greby, Stacie M.; Euler, Gary L.

2018-01-01

Background Seasonal influenza vaccination has been routinely recommended for adults with high-risk conditions. The Advisory Committee on Immunization Practices recommended that persons 25 to 64 years of age with high-risk conditions be one of the initial target groups to receive H1N1 vaccination during the 2009-2010 season. Methods We used data from the 2009-2010 Behavioral Risk Factor Surveillance System survey. Vaccination levels of H1N1 and seasonal influenza vaccination among respondents 25 to 64 years with high-risk conditions were assessed. Multivariable logistic regression models were performed to identify factors independently associated with vaccination. Results Overall, 24.8% of adults 25 to 64 years of age were identified to have high-risk conditions. Among adults 25 to 64 years of age with high-risk conditions, H1N1 and seasonal vaccination coverage were 26.3% and 47.6%, respectively. Characteristics independently associated with an increased likelihood of H1N1 vaccination were as follows: higher age; Hispanic race/ethnicity; medical insurance; ability to see a doctor if needed; having a primary doctor; a routine checkup in the previous year; not being a current smoker; and having high-risk conditions other than asthma, diabetes, and heart disease. Characteristics independently associated with seasonal influenza vaccination were similar compared with factors associated with H1N1 vaccination. Conclusion Immunization programs should work with provider organizations to review efforts made to reach adults with high-risk conditions during the recent pandemic and assess how and where they can increase vaccination coverage during future pandemics. PMID:23419613

A one-dimensional zinc(II) coordination polymer with a three-dimensional supramolecular architecture incorporating 1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole and adipate.

PubMed

Liu, Chun Li; Huang, Qiu Ying; Meng, Xiang Ru

2016-12-01

The synthesis of coordination polymers or metal-organic frameworks (MOFs) has attracted considerable interest owing to the interesting structures and potential applications of these compounds. It is still a challenge to predict the exact structures and compositions of the final products. A new one-dimensional coordination polymer, catena-poly[[[bis{1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole-κN 3 }zinc(II)]-μ-hexane-1,6-dicarboxylato-κ 4 O 1 ,O 1' :O 6 ,O 6' ] monohydrate], {[Zn(C 6 H 8 O 4 )(C 9 H 8 N 6 ) 2 ]·H 2 O} n , has been synthesized by the reaction of Zn(Ac) 2 (Ac is acetate) with 1-[(1H-benzimidazol-2-yl)methyl]-1H-tetrazole (bimt) and adipic acid (H 2 adi) at room temperature. In the polymer, each Zn II ion exhibits an irregular octahedral ZnN 2 O 4 coordination geometry and is coordinated by two N atoms from two symmetry-related bimt ligands and four O atoms from two symmetry-related dianionic adipate ligands. Zn II ions are connected by adipate ligands into a one-dimensional chain which runs parallel to the c axis. The bimt ligands coordinate to the Zn II ions in a monodentate mode on both sides of the main chain. In the crystal, the one-dimensional chains are further connected through N-H...O hydrogen bonds, leading to a three-dimensional supramolecular architecture. In addition, the title polymer exhibits fluorescence, with emissions at 334 and 350 nm in the solid state at room temperature.

Detecting stellar-wind bubbles through infrared arcs in H II regions

NASA Astrophysics Data System (ADS)

Mackey, Jonathan; Haworth, Thomas J.; Gvaramadze, Vasilii V.; Mohamed, Shazrene; Langer, Norbert; Harries, Tim J.

2016-02-01

Mid-infrared arcs of dust emission are often seen near ionizing stars within H II regions. A possible explanations for these arcs is that they could show the outer edges of asymmetric stellar wind bubbles. We use two-dimensional, radiation-hydrodynamics simulations of wind bubbles within H II regions around individual stars to predict the infrared emission properties of the dust within the H II region. We assume that dust and gas are dynamically well-coupled and that dust properties (composition, size distribution) are the same in the H II region as outside it, and that the wind bubble contains no dust. We post-process the simulations to make synthetic intensity maps at infrared wavebands using the torus code. We find that the outer edge of a wind bubble emits brightly at 24 μm through starlight absorbed by dust grains and re-radiated thermally in the infrared. This produces a bright arc of emission for slowly moving stars that have asymmetric wind bubbles, even for cases where there is no bow shock or any corresponding feature in tracers of gas emission. The 24 μm intensity decreases exponentially from the arc with increasing distance from the star because the dust temperature decreases with distance. The size distribution and composition of the dust grains has quantitative but not qualitative effects on our results. Despite the simplifications of our model, we find good qualitative agreement with observations of the H II region RCW 120, and can provide physical explanations for any quantitative differences. Our model produces an infrared arc with the same shape and size as the arc around CD -38°11636 in RCW 120, and with comparable brightness. This suggests that infrared arcs around O stars in H II regions may be revealing the extent of stellar wind bubbles, although we have not excluded other explanations.

Coupling Protein Dynamics with Proton Transport in Human Carbonic Anhydrase II

PubMed Central

2016-01-01

The role of protein dynamics in enzyme catalysis is one of the most highly debated topics in enzymology. The main controversy centers around what may be defined as functionally significant conformational fluctuations and how, if at all, these fluctuations couple to enzyme catalyzed events. To shed light on this debate, the conformational dynamics along the transition path surmounting the highest free energy barrier have been herein investigated for the rate limiting proton transport event in human carbonic anhydrase (HCA) II. Special attention has been placed on whether the motion of an excess proton is correlated with fluctuations in the surrounding protein and solvent matrix, which may be rare on the picosecond and subpicosecond time scales of molecular motions. It is found that several active site residues, which do not directly participate in the proton transport event, have a significant impact on the dynamics of the excess proton. These secondary participants are shown to strongly influence the active site environment, resulting in the creation of water clusters that are conducive to fast, moderately slow, or slow proton transport events. The identification and characterization of these secondary participants illuminates the role of protein dynamics in the catalytic efficiency of HCA II. PMID:27063577

Sorption and desorption of Pb(II) to biochar as affected by oxidation and pH.

PubMed

Wang, Qian; Wang, Bing; Lee, Xinqing; Lehmann, Johannes; Gao, Bin

2018-09-01

The use of biochar for the removal of heavy metals from water has environmental benefits. In order to elucidate the potential application of highly functionalized biochar for the removal of Pb(II) in aqueous solution, maple wood biochar was oxidized using hydrogen peroxide. The pH values of oxidized biochar ranged from 8.1 to 3.7, with one set being adjusted to a pH of 7 as a comparison. It was found that oxidizing the biochars increased their Pb(II) adsorption capacity if the pH remained below 6 (strong oxidation), but decreased their Pb(II) adsorption ability above pH6 (weak oxidation). After adjusting the pH of oxidized biochar to pH7, the Pb(II) adsorption capacity further increased two to sixfold for oxidized biochars originally at pH3.7-6. The adsorption characteristics of Pb(II) were well described by the Langmuir equation. Adsorption of Pb(II) was not fully reversible in water. Less than 6% of Pb(II) desorbed in water in two consecutive steps than was previously adsorbed, for biochars with a pH below 7, irrespective of oxidation. Recovery using an extraction with 0.1M NaNO 3 increased from 0.7% to 32.7% of Pb(II) undesorbed by both preceding water extractions with increasing oxidation, for biochars with a pH below 7. Unextractable Pb(II) was lower at low oxidation but increased to 99.0% of initially adsorbed amounts at low pH, which indicated that the adsorption of Pb(II) on oxidized biochar is pH independent. Copyright © 2018 Elsevier B.V. All rights reserved.

A spectroscopic and voltammetric study of the pH-dependent Cu(II) coordination to the peptide GGGTH: relevance to the fifth Cu(II) site in the prion protein.

PubMed

Hureau, Christelle; Charlet, Laurent; Dorlet, Pierre; Gonnet, Florence; Spadini, Lorenzo; Anxolabéhère-Mallart, Elodie; Girerd, Jean-Jacques

2006-09-01

The GGGTH sequence has been proposed to be the minimal sequence involved in the binding of a fifth Cu(II) ion in addition to the octarepeat region of the prion protein (PrP) which binds four Cu(II) ions. Coordination of Cu(II) by the N- and C-protected Ac-GGGTH-NH(2) pentapeptide (P(5)) was investigated by using potentiometric titration, electrospray ionization mass spectrometry, UV-vis spectroscopy, electron paramagnetic resonance (EPR) spectroscopy and cyclic voltammetry experiments. Four different Cu(II) complexes were identified and characterized as a function of pH. The Cu(II) binding mode switches from NO(3) to N(4) for pH values ranging from 6.0 to 10.0. Quasi-reversible reduction of the [Cu(II)(P(5))H(-2)] complex formed at pH 6.7 occurs at E (1/2)=0.04 V versus Ag/AgCl, whereas reversible oxidation of the [Cu(II)(P(5))H(-3)](-) complex formed at pH 10.0 occurs at E (1/2)=0.66 V versus Ag/AgCl. Comparison of our EPR data with those of the rSHaPrP(90-231) (Burns et al. in Biochemistry 42:6794-6803, 2003) strongly suggests an N(3)O binding mode at physiological pH for the fifth Cu(II) site in the protein.

Ionization correction factors for H II regions in blue compact dwarf galaxies

NASA Astrophysics Data System (ADS)

Holovatyi, V. V.; Melekh, B. Ya.

2002-08-01

Energy distributions in the spectra of the ionizing nuclei of H II regions beyond λ <= 91.2 nm were calculated. A grid of photoionization models of 270 H II regions was constructed. The free parameters of the model grid are the hydrogen density nH in the nebular gas, filling factor, energy Lc-spectrum of ionizing nuclei, and metallicity. The chemical composition from the studies of Izotov et al. were used for model grid initialization. The integral linear spectra calculated for the photoionization models were used to determine the concentration ne, temperatures Te of electrons, and ionic concentrations n(A+i)/n(H+) by the nebular gas diagnostic method. The averaged relative ionic abundances n(A+i)/n(H+) thus calculated were used to determine new expressions for ionization correction factors which we recommend for the determination of abundances in the H II regions of blue compact dwarf galaxies.

Water-Soluble Fe(II)−H2O Complex with a Weak O−H Bond Transfers a Hydrogen Atom via an Observable Monomeric Fe(III)−OH

PubMed Central

Brines, Lisa M.; Coggins, Michael K.; Poon, Penny Chaau Yan; Toledo, Santiago; Kaminsky, Werner; Kirk, Martin L.

2015-01-01

Understanding the metal ion properties that favor O−H bond formation versus cleavage should facilitate the development of catalysts tailored to promote a specific reaction, e.g., C−H activation or H2O oxidation. The first step in H2O oxidation involves the endothermic cleavage of a strong O−H bond (BDFE = 122.7 kcal/mol), promoted by binding the H2O to a metal ion, and by coupling electron transfer to proton transfer (PCET). This study focuses on details regarding how a metal ion’s electronic structure and ligand environment can tune the energetics of M(HO−H) bond cleavage. The synthesis and characterization of an Fe(II)−H2O complex, 1, that undergoes PCET in H2O to afford a rare example of a monomeric Fe(III)−OH, 7, is described. High-spin 7 is also reproducibly generated via the addition of H2O to {[FeIII(OMe2N4(tren))]2-(µ-O)}2+ (8). The O−H bond BDFE of Fe(II)−H2O (1) (68.6 kcal/mol) is calculated using linear fits to its Pourbaix diagram and shown to be 54.1 kcal/mol less than that of H2O and 10.9 kcal/mol less than that of [Fe(II)(H2O)6]2+. The O−H bond of 1 is noticeably weaker than the majority of reported Mn+(HxO−H) (M = Mn, Fe; n+ = 2+, 3+; x = 0, 1) complexes. Consistent with their relative BDFEs, Fe(II)−H2O (1) is found to donate a H atom to TEMPO•, whereas the majority of previously reported Mn+−O(H) complexes, including [MnIII(SMe2N4(tren))(OH)]+ (2), have been shown to abstract H atoms from TEMPOH. Factors responsible for the weaker O−H bond of 1, such as differences in the electron-donating properties of the ligand, metal ion Lewis acidity, and electronic structure, are discussed. PMID:25611075

Massive Star Formation of the SGR a East H (sub II) Regions Near the Galactic Center

NASA Technical Reports Server (NTRS)

Yusef-Zadeh, F.; Lacy, J. H.; Wardle, M.; Whitney, B.; Bushouse, H.; Roberts, D. A.; Arendt, R. G.

2010-01-01

A group of four compact H II regions associated with the well-known 50 km/s molecular cloud is the closest site of on-going star formation to the dynamical center of the Galaxy, at a projected distance of approximately 6 pc. We present a study of ionized gas based on the [Ne II] (12.8 micron) line, as well as multi-frequency radio continuum, Hubble Space Telescope Pa alpha, and Spitzer Infrared Array Camera observations of the most compact member of the H II group, Sgr A East H II D. The radio continuum image at 6 cm shows that this source breaks up into two equally bright ionized features, D1 and D2. The spectral energy distribution of the D source is consistent with it being due to a 25 =/- 3 solar mass star with a luminosity of 8 +/- 3 x 10(exp 4) Solar luminosity . The inferred mass, effective temperature of the UV source, and the ionization rate are compatible with a young O9-B0 star. The ionized features D1 and D2 are considered to be ionized by UV radiation collimated by an accretion disk. We consider that the central massive star photoevaporates its circumstellar disk on a timescale of 3x (exp 4) years giving a mass flux approximately 3 x 10(exp -5) Solar Mass / year and producing the ionized material in D1 and D2 expanding in an inhomogeneous medium. The ionized gas kinematics, as traced by the [Ne II] emission, is difficult to interpret, but it could be explained by the interaction of a bipolar jet with surrounding gas along with what appears to be a conical wall of lower velocity gas. The other H II regions, Sgr A East A-C, have morphologies and kinematics that more closely resemble cometary flows seen in other compact H II regions, where gas moves along a paraboloidal surface formed by the interaction of a stellar wind with a molecular cloud.

Carbon dioxide "trapped" in a β-carbonic anhydrase

DOE PAGES

Aggarwal, Mayank; Chua, Teck Khiang; Pinard, Melissa A.; ...

2015-10-12

Carbonic anhydrases (CAs) are enzymes that catalyze the hydration/ dehydration of CO 2/HCO 3 - with rates approaching diffusion-controlled limits (k cat/K M ~ 10 8 M –1s –1). Here, this family of enzymes has evolved disparate protein folds that all perform the same reaction at near catalytic perfection. Presented here is a structural study of a beta-CA (psCA3) expressed in Pseudomonas aeruginosa, in complex with CO 2, using pressurized cryocooled crystallography. The structure has been refined to 1.6 angstrom resolution with R cryst and R free values of 17.3 and 19.9%, respectively, and is compared with the α-CA, humanmore » CA isoform II (hCA II), the only other CA to have CO 2, captured in its active site. Despite the lack of structural similarity between psCA3 and hCA II, the CO 2, binding orientation relative to the zinc-bound solvent is identical. In addition, a second CO 2, binding site was located at the dimer interface of psCA3. Interestingly, all β-CAs function as dirners or higher-order oligomeric states, and the CO 2, bound at the interface may contribute to the allosteric nature of this family of enzymes or may be a convenient alternative binding site as this pocket has been previously shown to be a promiscuous site for a variety of ligands, including bicarbonate, sulfate, and phosphate ions.« less

A β-cyclodextrin, polyethyleneimine and silk fibroin hydrogel containing Centella asiatica extract and hydrocortisone acetate: releasing properties and in vivo efficacy for healing of pressure sores.

PubMed

Lee, M S; Seo, S R; Kim, J-C

2012-10-01

  Pressure sores are lesions caused by impaired blood flow. Conventional dressings can absorb exudates, but do not promote wound healing. A hydrogel composed of β-cyclodextrin (β-CD), polyethyleneimine (PEI) and silk fibroin (SF) was assessed for use in healing of pressure sores. The hydrogel was prepared by crosslinking β-CD-grafted PEI and SF using epichlorohydrin. The gel was then immersed in an aqueous solution of Centella asiatica extract (CAE) 0.7 mg/mL and/or hydrocortisone acetate (HCA) 0.5 mg/mL. The in vivo pressure sore-healing efficacy of the dry gel (with or without the drugs) was investigated in terms of the hyperplasia of epidermis and the number of neutrophils in the skin tissue. The specific loading of CAE was 0.0091 g/g of dry gel. The percentage of CAE released at 24 h at pH 3.0, 5.0 and 7.4 was approximately 63.9%, 55.0% and 44.4%, respectively. This pH-dependent release is possibly due to the degree of gel swelling, which decreased with increasing pH. The specific loading of HCA was 0.0050 g/g dry gel, and the percentage release of HCA at 24 h was around 20% at all three pH points. It is likely that HCA release is independent of pH. HCA is a hydrophobic compound, and therefore the release of HCA is affected by the partitioning of HCA between the β-CD cavity and the bulk water phase, but not by the degree of swelling of the hydrogel. The pressure sores treated with the hydrogel healed in 6 days, compared with 10 days for controls. In this study, a β-CD/PEI/SF hydrogel containing CAE and HCA reduced the healing time for pressure sores. © The Author(s). CED © 2012 British Association of Dermatologists.

Pycup – A bifunctional, cage-like ligand for 64Cu radiolabeling

PubMed Central

Boros, Eszter; Rybak-Akimova, Elena; Holland, Jason P.; Rietz, Tyson; Rotile, Nicholas; Blasi, Francesco; Day, Helen; Latifi, Reza; Caravan, Peter

2014-01-01

In developing targeted probes for positron emission tomography (PET) based on 64Cu, stable complexation of the radiometal is key, and a flexible handle for bioconjugation is highly advantageous. Here, we present the synthesis and characterization of the chelator pycup and 4 derivatives. Pycup is a cross-bridged cyclam derivative with a pyridyl donor atom integrated into the cross-bridge resulting in a pentadentate ligand. The pycup platform provides kinetic inertness toward 64Cu de-chelation and offers versatile bioconjugation chemistry. We varied the number and type of additional donor atoms by alkylation of the remaining two secondary amines, providing three model ligands, pycup2A, pycup1A1Bn and pycup2Bn in 3–4 synthetic steps from cyclam. All model copper complexes displayed very slow decomplexation in 5 M HCl and 90 °C (t1/2: 1.5 h for pycup1A1Bn, 2.7 h for pycup2A, 20.3 h for pycup2Bn). The single crystal crystal X-ray structure of the [Cu(pycup2Bn)]2+ complex showed that the copper was coordinated in a trigonal, bi-pyramidal manner. The corresponding radiochemical complexes were at least 94% stable in rat plasma after 24 h. Biodistribution studies conducted in Balb/c mice at 2 h post-injection of 64Cu labeled pycup2A revealed low residual activity in kidney, liver and blood pool with predominantly renal clearance observed. Pycup2A was readily conjugated to a fibrin-targeted peptide and labeled with 64Cu for successful PET imaging of arterial thrombosis in a rat model, demonstrating the utility of our new chelator in vivo. PMID:24294970

Syntheses, structures and characterization of isomorphous CoII and NiII coordination polymers based on 2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole and benzene-1,4-dicarboxylate.

PubMed

Huang, Qiu Ying; Zhao, Yang; Meng, Xiang Ru

2017-08-01

Careful choice of the organic ligands is one of the most important parameters in the rational design and synthesis of coordination polymers. Aromatic polycarboxylates have been widely used in the preparation of metal-organic polymers since they can utilize various coordination modes to form diverse structures and can act as hydrogen-bond acceptors and donors in the assembly of supramolecular structures. Nitrogen-heterocyclic organic compounds have also been used extensively as ligands for the construction of polymers with interesting structures. In the polymers catena-poly[[[diaquabis{2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole-κN 3 }cobalt(II)]-μ 2 -benzene-1,4-dicarboxylato-κ 2 O 1 :O 4 ] dihydrate], {[Co(C 8 H 4 O 4 )(C 12 H 11 N 4 ) 2 (H 2 O) 2 ]·2H 2 O} n , (I), and catena-poly[[[diaquabis{2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole-κN 3 }nickel(II)]-μ 2 -benzene-1,4-dicarboxylato-κ 2 O 1 :O 4 ] dihydrate], {[Ni(C 8 H 4 O 4 )(C 12 H 11 N 4 ) 2 (H 2 O) 2 ]·2H 2 O} n , (II), the Co II or Ni II ion lies on an inversion centre and exhibits a slightly distorted octahedral coordination geometry, coordinated by two N atoms from two imidazole rings and four O atoms from two monodentate carboxylate groups and two water molecules. The dicarboxylate ligands bridge metal ions forming a polymeric chain. The 2-[(1H-imidazol-1-yl)methyl]-6-methyl-1H-benzimidazole ligands coordinate to the Co II or Ni II centres in monodentate modes through an imidazole N atom and are pendant on opposite sides of the main chain. The two structures are isomorphous. In the crystal, the one-dimensional chains are further connected through O-H...O, O-H...N and N-H...O hydrogen bonds, leading to a three-dimensional supramolecular architecture. In addition, the IR spectroscopic properties, PXRD patterns, thermogravimetric behaviours and fluorescence properties of both polymers have been investigated.

Kinematic and chemical study of planetary nebulae and H II regions in NGC 3109

NASA Astrophysics Data System (ADS)

Flores-Durán, S. N.; Peña, M.; Ruiz, M. T.

2017-05-01

Aims: We present high-resolution spectroscopy of a number of planetary nebulae (PNe) and H II regions distributed along the dwarf irregular galaxy NGC 3109 and compare their kinematical behavior with that of H I data. We aim to determine if there is a kinematical connection among these objects. We also aim to determine the chemical composition of some PNe and H II regions in this galaxy and discuss it in comparison with stellar evolution models. Methods: Data for eight PNe and one H II region were obtained with the high-resolution spectrograph Magellan Inamori Kyocera Echelle (MIKE) at Las Campanas Observatory, Chile. Data for three PNe, six compact H II regions, and nine knots or clumps in extended H II regions were obtained with the high-resolution spectrograph Manchester Echelle Spectrometer (MES) attached to the 2.1m telescope at the Observatorio Astronómico Nacional, SPM, B.C., Mexico. An additional object was obtained from The SPM Catalogue of Extragalactic Planetary Nebulae. Thus, in total we have high-quality data for nine of the 20 PNe detected in this galaxy, and many H II regions. In the wavelength calibrated spectra, the heliocentric radial velocities were measured with a precision better than 7.8 km s-1. Data for blue supergiant stars were collected from the literature to be included in the analysis. The heliocentric radial velocities of the different objects were compared to the velocities of the H I disk at the same position. Physical conditions and ionic abundances of PNe and H II regions were obtained from the emission lines, and we used recent ionization correction factors to derive the total chemical abundances. Results: From the analysis of radial velocities we found that H II regions in NGC 3109 share the kinematics of the H I disk at the same projected position with very low dispersion in velocities. Blue supergiant stars and PNe rotate in the same direction as the H I disk but these objects have much larger dispersion; this larger dispersion

Lactobacillus casei 64H Contains a Phosphoenolpyruvate-Dependent Phosphotransferase System for Uptake of Galactose, as Confirmed by Analysis of ptsH and Different gal Mutants

PubMed Central

Bettenbrock, Katja; Siebers, Ulrike; Ehrenreich, Petra; Alpert, Carl-Alfred

1999-01-01

Galactose metabolism in Lactobacillus casei 64H was analyzed by genetic and biochemical methods. Mutants with defects in ptsH, galK, or the tagatose 6-phosphate pathway were isolated either by positive selection using 2-deoxyglucose or 2-deoxygalactose or by an enrichment procedure with streptozotocin. ptsH mutations abolish growth on lactose, cellobiose, N-acetylglucosamine, mannose, fructose, mannitol, glucitol, and ribitol, while growth on galactose continues at a reduced rate. Growth on galactose is also reduced, but not abolished, in galK mutants. A mutation in galK in combination with a mutation in the tagatose 6-phosphate pathway results in sensitivity to galactose and lactose, while a galK mutation in combination with a mutation in ptsH completely abolishes galactose metabolism. Transport assays, in vitro phosphorylation assays, and thin-layer chromatography of intermediates of galactose metabolism also indicate the functioning of a permease/Leloir pathway and a phosphoenolpyruvate-dependent phosphotransferase system (PTS)/tagatose 6-phosphate pathway. The galactose-PTS is induced by growth on either galactose or lactose, but the induction kinetics for the two substrates are different. PMID:9864334

A Parameter Study for Modeling Mg ii h and k Emission during Solar Flares

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

Rubio da Costa, Fatima; Kleint, Lucia, E-mail: frubio@stanford.edu

2017-06-20

Solar flares show highly unusual spectra in which the thermodynamic conditions of the solar atmosphere are encoded. Current models are unable to fully reproduce the spectroscopic flare observations, especially the single-peaked spectral profiles of the Mg ii h and k lines. We aim to understand the formation of the chromospheric and optically thick Mg ii h and k lines in flares through radiative transfer calculations. We take a flare atmosphere obtained from a simulation with the radiative hydrodynamic code RADYN as input for a radiative transfer modeling with the RH code. By iteratively changing this model atmosphere and varying thermodynamicmore » parameters such as temperature, electron density, and velocity, we study their effects on the emergent intensity spectra. We reproduce the typical single-peaked Mg ii h and k flare spectral shape and approximate the intensity ratios to the subordinate Mg ii lines by increasing either densities, temperatures, or velocities at the line core formation height range. Additionally, by combining unresolved upflows and downflows up to ∼250 km s{sup −1} within one resolution element, we reproduce the widely broadened line wings. While we cannot unambiguously determine which mechanism dominates in flares, future modeling efforts should investigate unresolved components, additional heat dissipation, larger velocities, and higher densities and combine the analysis of multiple spectral lines.« less

Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation in vaginal atrophy?

PubMed

Tuntiviriyapun, P; Panyakhamlerd, K; Triratanachat, S; Chatsuwan, T; Chaikittisilpa, S; Jaisamrarn, U; Taechakraichana, N

2015-04-01

The primary objective of this study was to evaluate the correlation among symptoms, signs, and the number of lactobacilli in postmenopausal vaginal atrophy. The secondary objective was to develop a new parameter to improve the correlation. A cross-sectional descriptive study. Naturally postmenopausal women aged 45-70 years with at least one clinical symptom of vaginal atrophy of moderate to severe intensity were included in this study. All of the objective parameters (vaginal atrophy score, vaginal pH, the number of lactobacilli, vaginal maturation index, and vaginal maturation value) were evaluated and correlated with vaginal atrophy symptoms. A new parameter of vaginal atrophy, vaginal atrophy symptoms II, was developed and consists of the two most bothersome symptoms (vaginal dryness and dyspareunia). Vaginal atrophy symptoms II was analyzed for correlation with the objective parameters. A total of 132 naturally postmenopausal women were recruited for analysis. Vaginal pH was the only objective parameter found to have a weak correlation with vaginal atrophy symptoms (r = 0.273, p = 0.002). The newly developed vaginal atrophy symptoms II parameter showed moderate correlation with vaginal pH (r = 0.356, p < 0.001) and a weak correlation with the vaginal atrophy score (r = 0.230, p < 0.001). History of sexual intercourse within 3 months was associated with a better correlation between vaginal atrophy symptoms and the objective parameters. Vaginal pH was significantly correlated with vaginal atrophy symptoms. The newly developed vaginal atrophy symptoms II was associated with a better correlation. The vaginal atrophy symptoms II and vaginal pH may be better tools for clinical evaluation and future study of the vaginal ecosystem.

Structural properties of the intrinsically disordered, multiple calcium ion-binding otolith matrix macromolecule-64 (OMM-64).

PubMed

Poznar, Monika; Hołubowicz, Rafał; Wojtas, Magdalena; Gapiński, Jacek; Banachowicz, Ewa; Patkowski, Adam; Ożyhar, Andrzej; Dobryszycki, Piotr

2017-11-01

Fish otoliths are calcium carbonate biominerals that are involved in hearing and balance sensing. An organic matrix plays a crucial role in their formation. Otolith matrix macromolecule-64 (OMM-64) is a highly acidic, calcium-binding protein (CBP) found in rainbow trout otoliths. It is a component of high-molecular-weight aggregates, which influence the size, shape and polymorph of calcium carbonate in vitro. In this study, a protocol for the efficient expression and purification of OMM-64 was developed. For the first time, the complete structural characteristics of OMM-64 were described. Various biophysical methods were combined to show that OMM-64 occurs as an intrinsically disordered monomer. Under denaturing conditions (pH, temperature) OMM-64 exhibits folding propensity. It was determined that OMM-64 binds approximately 61 calcium ions with millimolar affinity. The folding-unfolding experiments showed that calcium ions induced the collapse of OMM-64. The effect of other counter ions present in trout endolymph on OMM-64 conformational changes was studied. The significance of disordered properties of OMM-64 and the possible function of this protein is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel method to label preformed liposomes with 64Cu for positron emission tomography (PET) imaging.

PubMed

Seo, Jai Woong; Zhang, Hua; Kukis, David L; Meares, Claude F; Ferrara, Katherine W

2008-12-01

Radiolabeling of liposomes with 64Cu (t(1/2)=12.7 h) is attractive for molecular imaging and monitoring drug delivery. A simple chelation procedure, performed at a low temperature and under mild conditions, is required to radiolabel preloaded liposomes without lipid hydrolysis or the release of the encapsulated contents. Here, we report a 64Cu postlabeling method for liposomes. A 64Cu-specific chelator, 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (BAT), was conjugated with an artificial lipid to form a BAT-PEG-lipid. After incorporation of 0.5% (mol/mol) BAT-PEG-lipid during liposome formulation, liposomes were successfully labeled with 64Cu in 0.1 M NH4OAc pH 5 buffer at 35 degrees C for 30-40 min with an incorporation yield as high as 95%. After 48 h of incubation of 64Cu-liposomes in 50/50 serum/PBS solution, more than 88% of the 64Cu label was still associated with liposomes. After injection of liposomal 64Cu in a mouse model, 44+/-6.9, 21+/-2.7, 15+/-2.5, and 7.4+/-1.1 (n=4) % of the injected dose per cubic centimeter remained within the blood pool at 30 min, 18, 28, and 48 h, respectively. The biodistribution at 48 h after injection verified that 7.0+/-0.47 (n=4) and 1.4+/-0.58 (n=3) % of the injected dose per gram of liposomal 64Cu and free 64Cu remained in the blood pool, respectively. Our results suggest that this fast and easy 64Cu labeling of liposomes could be exploited in tracking liposomes in vivo for medical imaging and targeted delivery.

50 CFR Figure 17 to Part 679 - Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA)

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA) 17 Figure 17 to part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE...

50 CFR Figure 17 to Part 679 - Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA)

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA) 17 Figure 17 to part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE...

50 CFR Figure 17 to Part 679 - Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA)

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA) 17 Figure 17 to part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE...

50 CFR Figure 17 to Part 679 - Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA)

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA) 17 Figure 17 to part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE...

A pH-sensitive heparin-binding sequence from Baculovirus gp64 protein is important for binding to mammalian cells but not to Sf9 insect cells.

PubMed

Wu, Chunxiao; Wang, Shu

2012-01-01

Binding to heparan sulfate is essential for baculovirus transduction of mammalian cells. Our previous study shows that gp64, the major glycoprotein on the virus surface, binds to heparin in a pH-dependent way, with a stronger binding at pH 6.2 than at 7.4. Using fluorescently labeled peptides, we mapped the pH-dependent heparin-binding sequence of gp64 to a 22-amino-acid region between residues 271 and 292. Binding of this region to the cell surface was also pH dependent, and peptides containing this sequence could efficiently inhibit baculovirus transduction of mammalian cells at pH 6.2. When the heparin-binding peptide was immobilized onto the bead surface to mimic the high local concentration of gp64 on the virus surface, the peptide-coated magnetic beads could efficiently pull down cells expressing heparan sulfate but not cells pretreated with heparinase or cells not expressing heparan sulfate. Interestingly, although this heparin-binding function is essential for baculovirus transduction of mammalian cells, it is dispensable for infection of Sf9 insect cells. Virus infectivity on Sf9 cells was not reduced by the presence of heparin or the identified heparin-binding peptide, even though the peptide could bind to Sf9 cell surface and be efficiently internalized. Thus, our data suggest that, depending on the availability of the target molecules on the cell surface, baculoviruses can use two different methods, electrostatic interaction with heparan sulfate and more specific receptor binding, for cell attachment.

Human transcription factor hTAF(II)150 (CIF150) is involved in transcriptional regulation of cell cycle progression.

PubMed

Martin, J; Halenbeck, R; Kaufmann, J

1999-08-01

Here we present evidence that CIF150 (hTAF(II)150), the human homolog of Drosophila TAF(II)150, plays an important and selective role in establishing gene expression patterns necessary for progression through the cell cycle. Gel filtration experiments demonstrate that CIF150 (hTAF(II)150) seems to be less tightly associated with human transcription factor IID than hTAF(II)130 is associated with hTAF(II)250. The transient functional knockout of CIF150 (hTAF(II)150) protein led to cell cycle arrest at the G(2)/M transition in mammalian cell lines. PCR display analysis with the RNA derived from CIF150-depleted cells indicated that CIF150 (hTAF(II)150) is required for the transcription of only a subset of RNA polymerase II genes. CIF150 (hTAF(II)150) directly stimulated cyclin B1 and cyclin A transcription in cotransfection assays and in vitro assays, suggesting that the expression of these genes is dependent on CIF150 (hTAF(II)150) function. We defined a CIF150 (hTAF(II)150) consensus binding site and demonstrated that a CIF150-responsive cis element is present in the cyclin B1 core promoter. These results suggest that one function of CIF150 (hTAF(II)150) is to select specific RNA polymerase II core promoter elements involved in cell cycle progression.

Star Formation and Young Population of the H II Complex Sh2-294

NASA Astrophysics Data System (ADS)

Samal, M. R.; Pandey, A. K.; Ojha, D. K.; Chauhan, N.; Jose, J.; Pandey, B.

2012-08-01

The Sh2-294 H II region ionized by a single B0V star features several infrared excess sources, a photodissociation region, and also a group of reddened stars at its border. The star formation scenario in this region seems to be quite complex. In this paper, we present follow-up results of Sh2-294 H II region at 3.6, 4.5, 5.8, and 8.0 μm observed with the Spitzer Space Telescope Infrared Array Camera (IRAC), coupled with H2 (2.12 μm) observation, to characterize the young population of the region and to understand its star formation history. We identified 36 young stellar object (YSO, Class I, Class II, and Class I/II) candidates using IRAC color-color diagrams. It is found that Class I sources are preferentially located at the outskirts of the H II region and associated with enhanced H2 emission; none of them are located near the central cluster. Combining the optical to mid-infrared (MIR) photometry of the YSO candidates and using the spectral energy distribution fitting models, we constrained stellar parameters and the evolutionary status of 33 YSO candidates. Most of them are interpreted by the model as low-mass (<4 M ⊙) YSOs; however, we also detected a massive YSO (~9 M ⊙) of Class I nature, embedded in a cloud of visual extinction of ~24 mag. Present analysis suggests that the Class I sources are indeed a younger population of the region relative to Class II sources (age ~ 4.5 × 106 yr). We suggest that the majority of the Class I sources, including the massive YSOs, are second-generation stars of the region whose formation is possibly induced by the expansion of the H II region powered by a ~4 × 106 yr B0 main-sequence star.

A Comparative Observational Study of YSO Classification in Four Small Star-forming H ii Regions

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

Kang, Sung-Ju; Choi, Minho; Kang, Miju

We have developed a new young stellar object (YSO) identification and classification technique using mid-infrared Wide-field Infrared Survey Explorer (WISE) data. We compare this new technique with previous WISE YSO detection and classification methods that used either infrared colors or spectral energy distribution slopes. In this study, we also use the new technique to detect and examine the YSO population associated with four small H ii regions: KR 7, KR 81, KR 120, and KR 140. The relatively simple structure of these regions allows us to effectively use both spatial and temporal constraints to identify YSOs that are potential productsmore » of triggered star formation. We are also able to identify regions of active star formation around these H ii regions that are clearly not influenced by the H ii region expansion, and thus demonstrate that star formation is on-going on megayear timescales in some of these molecular clouds.« less

(Cryptand-222)potassium(+) (hydrogensulfido)[5,10,15,20-tetra-kis(2-pival-amido-phen-yl)porphyrinato]ferrate(II).

PubMed

Dhifet, Mondher; Belkhiria, Mohamed Salah; Daran, Jean-Claude; Nasri, Habib

2009-07-22

As part of a systematic investigation for a number of Fe(II) porphyrin complexes used as biomimetic models for cytochrome P450, crystals of the title compound, [K(C(18)H(36)N(2)O(6))][Fe(II)(C(64)H(64)N(8)O(4))(HS)], were prepared. The compound exhibits a non-planar conformation with major ruffling and saddling distortions. The average equatorial iron-pyrrole N atom [Fe-N(p) = 2.102 (2) Å] bond length and the distance between the Fe(II) atom and the 24-atom core of the porphyrin ring (Fe-P(C)= 0.558 Å) are typical for high-spin iron(II) penta-coordinate porphyrinates. One of the tert-butyl groups in the structure is disordered over two sets with occupancies of 0.84 and 0.16.

NGC628 with SITELLE: I. Imaging spectroscopy of 4285 H II region candidates

NASA Astrophysics Data System (ADS)

Rousseau-Nepton, L.; Robert, C.; Martin, R. P.; Drissen, L.; Martin, T.

2018-07-01

This is the first paper of a series dedicated to nebular physics and the chemical evolution of nearby galaxies by investigating large samples of H II regions with the Canada-France-Hawaii Telescope imaging spectrograph SITELLE (Spectro-Imageur à Transformée de Fourier pour l'Étude en Long et en Large des raies d'Émission). We present a technique adapted to imaging spectroscopy to identify and extract parameters from 4285 H II region candidates found in the disc of NGC 628. Using both the spatial and spectral capabilities of SITELLE, our technique enables the extraction of the position, dust extinction, velocity, H α profile, diffuse ionized gas (DIG) background, luminosity, size, morphological type, and the emission-line fluxes for individual spaxels and the integrated spectrum for each region. We have produced a well-sampled H II region luminosity function and studied its variation with galactocentric radius and level of the DIG background. We found a slope α of -1.12 ± 0.03 with no evidence of a break at high luminosity. Based on the width of the region profile, bright regions are rather compact, while faint regions are seen over a wide range of sizes. The radius function reveals a slope of -1.81 ± 0.02. BPT diagrams of the individual spaxels and integrated line ratios confirm that most detections are H II regions. Also, maps of the line ratios show complex variations of the ionization conditions within H II regions. All this information is compiled in a new catalogue for H II regions. The objective of this data base is to provide a complete sample which will be used to study the whole parameter space covered by the physical conditions in active star-forming regions.

46 CFR 64.81 - 30-month inspection of an MPT.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false 30-month inspection of an MPT. 64.81 Section 64.81 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS... external examination for— (i) Corrosion; (ii) Cracking of base material; and (iii) Weld defects; and (2) A...

A bimodal dust grain distribution in the IC 434 H ii region

NASA Astrophysics Data System (ADS)

Ochsendorf, B. B.; Tielens, A. G. G. M.

2015-04-01

Context. Studies of dust evolution and processing in different phases of the interstellar medium (ISM) is essential to understanding the lifecycle of dust in space. Recent results have challenged the capabilities and validity of current dust models, indicating that the properties of interstellar dust evolve as it transits between different phases of the ISM. Aims: We characterize the dust content from the IC 434 H ii region, and present a scenario that results in the large-scale structure of the region seen to date. Methods: We conduct a multi-wavelength study of the dust emission from the ionized gas, and combine this with modeling, from large scales that provide insight into the history of the IC 434/L1630 region, to small scales that allow us to infer quantitative properties of the dust content inside the H ii region. Results: The dust enters the H ii region through momentum transfer with a champagne flow of ionized gas, set up by a chance encounter between the L1630 molecular cloud and the star cluster of σ Ori. We observe two clearly separated dust populations inside the ionized gas, that show different observational properties, as well as contrasting optical properties. Population A is colder (~25 K) than predicted by widely-used dust models, its temperature is insensitive to an increase of the impinging radiation field, it is momentum-coupled to the gas, and efficiently absorbs radiation pressure to form a dust wave at 1.0 pc ahead of σ Ori AB. Population B is characterized by a constant [20/30] flux ratio throughout the H ii region, heats up to ~75 K close to the star, and is less efficient in absorbing radiation pressure, forming a dust wave at 0.1 pc from the star. Conclusions: The dust inside IC 434 is bimodal. The characteristics of population A are remarkable and cannot be explained by current dust models. We argue that large porous grains or fluffy aggregates are potential candidates to explain much of the observational characteristics. Population B

Reactivity of Hydride Bridges in High-Spin [3M-3(μ-H)] Clusters (M = FeII, CoII).

PubMed

Lee, Yousoon; Anderton, Kevin J; Sloane, Forrest T; Ermert, David M; Abboud, Khalil A; García-Serres, Ricardo; Murray, Leslie J

2015-08-26

The designed [3M-3(μ-H)] clusters (M = Fe(II), Co(II)) Fe3H3L (1-H) and Co3H3L (2-H) [where L(3-) is a tris(β-diketiminate) cyclophane] were synthesized by treating the corresponding M3Br3L complexes with KBEt3H. From single-crystal X-ray analysis, the hydride ligands are sterically protected by the cyclophane ligand, and these complexes selectively react with CO2 over other unsaturated substrates (e.g., CS2, Me3SiCCH, C2H2, and CH3CN). The reaction of 1-H or 2-H with CO2 at room temperature yielded Fe3(OCHO)(H)2L (1-CO2) or Co3(OCHO)(H)2L (2-CO2), respectively, which evidence the differential reactivity of the hydride ligands within these complexes. The analogous reactions at elevated temperatures revealed a distinct difference in the reactivity pattern for 2-H as compared to 1-H; Fe3(OCHO)3L (1-3CO2) was generated from 1-H, while 2-H afforded only 2-CO2.

On the Measurement of Elemental Abundance Ratios in Inner Galaxy H II Regions

NASA Technical Reports Server (NTRS)

Simpson, Janet P.; Rubin, Robert H.; Colgan, Sean W. J.; Erickson, Edwin F.; Haas, Michael R.

2004-01-01

Although abundance gradients in the Milky Way Galaxy certainly exist, details remain uncertain, particularly in the inner Galaxy, where stars and H II regions in the Galactic plane are obscured optically. In this paper we revisit two previously studied, inner Galaxy H II regions: G333.6-0.2 and W43. We observed three new positions in G333.6-0.2 with the Kuiper Airborne Observatory and reobserved the central position with the Infrared Space Observatory's Long Wavelength Spectrometer in far-infrared lines of S++, N++, N+, and O++. We also added the N+ lines at 122 and 205 microns to the suite of lines measured in W43 by Simpson et al.. The measured electron densities range from approx. 40 to over 4000 per cu cm in a single HII region, indicating that abundance analyses must consider density variations, since the critical densities of the observed lines range from 40 to 9000 per cu cm. We propose a method to handle density variations and make new estimates of the S/H and N/H abundance ratios. We find that our sulfur abundance estimates for G333.6-0.2 and W43 agree with the S/H abundance ratios expected for the gradient previously reported by Simpson et al., with the S/H values revised to be smaller owing to changes in collisional excitation cross sections. The estimated N/H, S/H, and N/S ratios are the most reliable because of their small corrections for unseen ionization states (< or approx. 10%). The estimated N/S ratios for the two sources are smaller than what would be calculated from the N/H and S/H ratios in our previous paper. If all low excitation H II regions had similar changes to their N/S ratios as a result of adding measurements of N+ to previous measurements of N++, there would be no or only a very small gradient in N/S. This is interesting because nitrogen is considered to be a secondary element and sulfur is a primary element in galactic chemical evolution calculations. We compute models of the two H II regions to estimate corrections for the other

Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases.

PubMed

Yamali, Cem; Gul, Halise Inci; Sakagami, Hiroshi; Supuran, Claudiu T

2016-01-01

Phenolic bis Mannich bases having the chemical structure of 1-[3,5-bis-aminomethyl-4-hydroxyphenyl]-3-(4-halogenophenyl)-2-propen-1-ones (1a-c, 2a-c, 3a-c) were synthesized (Numbers 1, 2, and 3 represent fluorine, chlorine, and bromine bearing compounds, respectively, while a, b, and c letters represent the compounds having piperidine, morpholine, and N-methyl piperazine) and their cytotoxic and carbonic anhydrase (CA, EC 4.2.1.1) enzyme inhibitory effects were evaluated. Lead compounds should possess both marked cytotoxic potencies and selective toxicity for tumors. To reflect this potency, PSE values of the compounds were calculated. According to PSE values, the compounds 2b and 3b may serve as lead molecules for further anticancer drug candidate developments. Although the compounds showed a low inhibition potency toward hCA I (25-43%) and hCA II (6-25%) isoforms at 10 μM concentration of inhibitor, the compounds were more selective (1.5-5.2 times) toward hCA I isoenzyme. It seems that the compounds need molecular modifications for the development of better CA inhibitors.

pH-Dependent Assembly and Conversions of Six Cadmium(II)-Based Coordination Complexes

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

Fang, Hua-Cai; Zhu, Ji-Qin; Zhou, Li-Jiang

2010-07-07

Six cadmium(II) complexes containing N2O2 donor tetradentate asymmetrical Schiff base ligand 2-{[2-(dimethylamino)ethylimino]methyl}-6-methoxyphenol (HL5), namely, [(Cd3L52Cl4)2]•CH3OH•H2O (1), [Cd(L5)Cl]2•CH3OH (2), [Cd2(HL5)Cl4]n (3), {[Cd3(H2L5)2Cl8]•2H2O}n (4), [(H2L5)2]2+•[CdCl4]2-•H2O (5), and [(H2L5)2]2+•[CdCl4]2- (6), have been synthesized using cadmium(II) chloride and asymmetrical Schiff base ligand HL5 under different pH conditions at room temperature. The diverse structures show the marked sensitivity of the structural chemistry of the tetradentate asymmetrical Schiff base ligand HL5. Complex 1 formed at pH = 10 exhibits a rare zero- dimensional structure of trinuclear cadmium (II). At pH = 8-9, a dinuclear cadmium (II) complex 2 is formed. The reaction at pH = 5-7more » leads to two one-dimensional structures of 3 and 4. A further decrease of the pH to 3-5 results in a zero-dimensional structure 5. Owing to the departure of lattice water molecules in the crystal, complex 5 at room temperature can gradually undergo single-crystal-to-single-crystal transformation to result complex 6. The results further show that conversions of complex 1 to 5 can also be achieved by adjusting the pH value of the reaction solution, 1→2pH=8→5pH=3 and 3→4pH=5. Comparing these experimental results, it is clear that the pH plays a crucial role in the formation of the resulting structures, which simultaneously provide very effective strategies for constructing the CdII compounds with N2O2 donor tetradentate asymmetrical Schiff base ligand. The strong fluorescent emissions of the six compounds (1-6) make them potentially useful photoactive materials. Furthermore, six Schiff base cadmium complexes (1–6), with DPPH (2,2-dipheny1-1-picrylhydrazy1) as a co-oxidant exhibited the stronger scavenging activity.« less

Ratiometric pH Imaging with a CoII2 MRI Probe via CEST Effects of Opposing pH Dependences (Postprint)

DTIC Science & Technology

2017-10-13

7b08574 14. ABSTRACT (Maximum 200 words) We report a Co2-based magnetic resonance (MR) probe that enables the ratiometric quantitation and imaging of...ratios of CEST peak intensities at 104 and 64 ppm are correlated with solution pH in the physiological range 6.5−7.6 to construct a linear calibration...magnetic resonance (MR); ratiometric quantitation ; chemical exchange saturation transfer (CEST); carboxamide; hydroxyl-substituted bisphosphonate

[Reduction of nitrobenzene by iron oxides bound Fe(II) system at different pH values].

PubMed

Luan, Fu-Bo; Xie, Li; Li, Jun; Zhou, Qi

2009-07-15

Batch tests were conducted to investigate the reductive transformation of nitrobenzene by goethite, hematite, magnetite and steel converter slag bound Fe(II) system. And the reduction mechanism was explored at different pH values. Experimental results showed that hematite, magnetite and steel converter slag could adsorb Fe(II) on surfaces and form iron oxides bound Fe(II) system at pH from 6.5 to 7.0. The systems had strong reductive capacity and could reduce nitrobenzene to aniline. The reduction efficiency of nitrobenzene in surface bound Fe(II) system followed the sequence of magnetite, hematite and steel converter slag from high to low. The reduction efficiency of hematite and magnetite system increased with pH increasing. While it was almost pH independent in steel converter slag system. Although goethite adsorbed most of Fe(II) in solution, the adsorbed Fe(II) had no reductive activity for nitrobenzene. At pH 6.0, small amount of Fe(II) was adsorbed on magnetite and hematite and the systems did not show reductive activity for nitrobenzene. However, steel converter slag could adsorb Fe(II) at pH 6.0 and reduction efficiency almost equaled to the value at pH 7.0. When pH was above 7.5, dissolved Fe(II) could be converted to Fe(OH)2 and the newly formed Fe(OH)2 became the main redactor in the system. Under alkali condition, the presence of iron oxides inhibited the reduction capacity of system.

A MULTIWAVELENGTH STUDY OF STAR FORMATION IN THE VICINITY OF GALACTIC H II REGION Sh 2-100

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

Samal, M. R.; Pandey, A. K.; Sagar, R.

We present multiwavelength investigation of morphology, physical-environment, stellar contents, and star formation activity in the vicinity of star-forming region Sh 2-100. It is found that the Sh 2-100 region contains seven H II regions of ultracompact and compact nature. The present estimation of distance for three H II regions, along with the kinematic distance for others, suggests that all of them belong to the same molecular cloud complex. Using near-infrared photometry, we identified the most probable ionizing sources of six H II regions. Their approximate photometric spectral type estimates suggest that they are massive early-B to mid-O zero-age-main-sequence stars andmore » agree well with radio continuum observations at 1280 MHz, for sources whose emissions are optically thin at this frequency. The morphology of the complex shows a non-uniform distribution of warm and hot dust, well mixed with the ionized gas, which correlates well with the variation of average visual extinction ({approx}4.2-97 mag) across the region. We estimated the physical parameters of ionized gas with the help of radio continuum observations. We detected an optically visible compact nebula located to the south of the 850 {mu}m emission associated with one of the H II regions and the diagnostic of the optical emission line ratios gives electron density and electron temperature of {approx}0.67 x 10{sup 3} cm{sup -3} and {approx}10{sup 4} K, respectively. The physical parameters suggest that all the H II regions are in different stages of evolution, which correlate well with the probable ages in the range {approx}0.01-2 Myr of the ionizing sources. The spatial distribution of infrared excess stars, selected from near-infrared and Infrared Array Camera color-color diagrams, correlates well with the association of gas and dust. The positions of infrared excess stars, ultracompact and compact H II regions at the periphery of an H I shell, possibly created by a WR star, indicate that star

Synthesis of layered perovskite oxides, ACa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (A = K, Rb, Cs), and characterization of new solid acids, HCa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (O < x [le] 2), exhibiting variable Bronsted acidity

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

Gopalakrishnan, J.; Uma, S.; Bhat, V.

1993-01-01

Layered perovskite oxides of the formula ACa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (A = K, Rb, Cs and 0 , x [le] 2) have been prepared. The members adopt the structures of the parent ACa[sub 2]Nb[sub 3]O[sub 10]. Interlayer alkali cations in the niobium-titanium oxide series can be ion-exchanged with Li[sup +], Na[sup +], NG[sub 4][sup +], of H[sup +] to give new derivatives. Intercalation of the protonated derivatives with organic bases reveals that the Bronsted acidity of the solid solution series, HCa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10], depends on the titanium content. While the x = 1 member (HCaLaNb[submore » 2]TiO[sub 10]) is nearly as acidic as the parent HCa[sub 2]Nb[sub 3]O[sub 10], the x = 2 member (HLA[sub 2]NbTi[sub 2]O[sub 10]) is a weak acid hardly intercalating organic bases with pK[sub a] [approximately] 11.3. The variation of acidity is probably due to an ordering of Nb/Ti atoms in the triple octahedral perovskite slabs, [Ca[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10

Fluorescent probe based subcellular distribution of Cu(II) ions in living electrotrophs isolated from Cu(II)-reduced biocathodes of microbial fuel cells.

PubMed

Tao, Ye; Xue, Hua; Huang, Liping; Zhou, Peng; Yang, Wei; Quan, Xie; Yuan, Jinxiu

2017-02-01

Based on the four indigenous electrotrophs (Stenotrophomonas maltophilia JY1, Citrobacter sp. JY3, Pseudomonas aeruginosa JY5 and Stenotrophomonas sp. JY6) isolated from well adapted Cu(II)-reduced biocathodes of microbial fuel cells (MFCs), a rhodamine based Cu(II) fluorescent probe was used to imaginably and quantitatively track subcellular Cu(II) ions in these electrotrophs. Cathodic electrons led to more Cu(II) ions (14.3-30.1%) in the intracellular sites at operation time of 2-3h with Cu(II) removal rates of 2.90-3.64mg/Lh whereas the absence of cathodic electrons prolonged the appearance of more Cu(II) ions (16.6-22.5%) to 5h with Cu(II) removal rates of 1.96-2.28mg/Lh. This study illustrates that cathodic electrons directed more Cu(II) ions for quicker entrance into the electrotrophic cytoplasm, and gives an alternative approach for developing imaging and functionally tracking Cu(II) ions in the electrotrophs of MFCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reshaping the folding energy landscape by chloride salt: impact on molten-globule formation and aggregation behavior of carbonic anhydrase.

PubMed

Borén, Kristina; Grankvist, Hannah; Hammarström, Per; Carlsson, Uno

2004-05-21

During chemical denaturation different intermediate states are populated or suppressed due to the nature of the denaturant used. Chemical denaturation by guanidine-HCl (GuHCl) of human carbonic anhydrase II (HCA II) leads to a three-state unfolding process (Cm,NI=1.0 and Cm,IU=1.9 M GuHCl) with formation of an equilibrium molten-globule intermediate that is stable at moderate concentrations of the denaturant (1-2 M) with a maximum at 1.5 M GuHCl. On the contrary, urea denaturation gives rise to an apparent two-state unfolding transition (Cm=4.4 M urea). However, 8-anilino-1-naphthalene sulfonate (ANS) binding and decreased refolding capacity revealed the presence of the molten globule in the middle of the unfolding transition zone, although to a lesser extent than in GuHCl. Cross-linking studies showed the formation of moderate oligomer sized (300 kDa) and large soluble aggregates (>1000 kDa). Inclusion of 1.5 M NaCl to the urea denaturant to mimic the ionic character of GuHCl leads to a three-state unfolding behavior (Cm,NI=3.0 and Cm,IU=6.4 M urea) with a significantly stabilized molten-globule intermediate by the chloride salt. Comparisons between NaCl and LiCl of the impact on the stability of the various states of HCA II in urea showed that the effects followed what could be expected from the Hofmeister series, where Li+ is a chaotropic ion leading to decreased stability of the native state. Salt addition to the completely urea unfolded HCA II also led to an aggregation prone unfolded state, that has not been observed before for carbonic anhydrase. Refolding from this state only provided low recoveries of native enzyme.

STAR FORMATION AND YOUNG POPULATION OF THE H II COMPLEX Sh2-294

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

Samal, M. R.; Pandey, A. K.; Chauhan, N.

The Sh2-294 H II region ionized by a single B0V star features several infrared excess sources, a photodissociation region, and also a group of reddened stars at its border. The star formation scenario in this region seems to be quite complex. In this paper, we present follow-up results of Sh2-294 H II region at 3.6, 4.5, 5.8, and 8.0 {mu}m observed with the Spitzer Space Telescope Infrared Array Camera (IRAC), coupled with H{sub 2} (2.12 {mu}m) observation, to characterize the young population of the region and to understand its star formation history. We identified 36 young stellar object (YSO, Classmore » I, Class II, and Class I/II) candidates using IRAC color-color diagrams. It is found that Class I sources are preferentially located at the outskirts of the H II region and associated with enhanced H{sub 2} emission; none of them are located near the central cluster. Combining the optical to mid-infrared (MIR) photometry of the YSO candidates and using the spectral energy distribution fitting models, we constrained stellar parameters and the evolutionary status of 33 YSO candidates. Most of them are interpreted by the model as low-mass (<4 M{sub Sun }) YSOs; however, we also detected a massive YSO ({approx}9 M{sub Sun }) of Class I nature, embedded in a cloud of visual extinction of {approx}24 mag. Present analysis suggests that the Class I sources are indeed a younger population of the region relative to Class II sources (age {approx} 4.5 Multiplication-Sign 10{sup 6} yr). We suggest that the majority of the Class I sources, including the massive YSOs, are second-generation stars of the region whose formation is possibly induced by the expansion of the H II region powered by a {approx}4 Multiplication-Sign 10{sup 6} yr B0 main-sequence star.« less

Activation cross sections of the 64Ni(d,2n) reaction for the production of the medical radionuclide 64Cu

NASA Astrophysics Data System (ADS)

Hermanne, A.; Tárkányi, F.; Takács, S.; Kovalev, S. F.; Ignatyuk, A.

2007-05-01

Deuteron particle induced reactions for generation of 64Cu used in diagnostic and therapeutic nuclear medicine and its possible short lived contaminant 61Cu were investigated with the stacked foil activation technique on natural nickel targets up to Ed = 20.5 MeV. Excitation functions for the reactions 64Ni(d,2n) 64Cu and natNi(d, x) 61Cu are obtained by gamma spectroscopy and are compared with earlier literature values. Thick target yields have been deduced from the experimental cross sections and the predictive capability of the ALICE-IPPE, EMPIRE II and GNASH model codes is tested.

Ultraviolet imaging telescope and optical emission-line observations of H II regions in M81

NASA Technical Reports Server (NTRS)

Hill, Jesse K.; Cheng, K.-P.; Bohlin, Ralph C.; Cornett, Robert H.; Hintzen, P. M. N.; O'Connell, Robert W.; Roberts, Morton S.; Smith, Andrew M.; Smith, Eric P.; Stecher, Theodore P.

1995-01-01

Images of the type Sab spiral galaxy M81 were obtained in far-UV and near-UV bands by the Ultraviolet Imaging Telescope (UIT) during the Astro-1 Spacelab mission of 1990 December. Magnitudes in the two UV bands are determined for 52 H II regions from the catalog of Petit, Sivan, & Karachentsev (1988). Fluxes of the H-alpha and H-beta emission lines are determined from CCD images. Extinctions for the brightest H II regions are determined from observed Balmer decrements. Fainter H II regions are assigned the average of published radio-H-alpha extinctions for several bright H II regions. The radiative transfer models of Witt, Thronson, & Capuano (1992) are shown to predict a relationship between Balmer Decrement and H-alpha extinction consistent with observed line and radio fluxes for the brightest 7 H II regions and are used to estimate the UV extinction. Ratios of Lyman continuum with ratios predicted by model spectra computed for initial mass function (IMF) slope equal to -1.0 and stellar masses ranging from 5 to 120 solar mass. Ages and masses are estimated by comparing the H-alpha and far-UV fluxes and their ratio with the models. The total of the estimated stellar masses for the 52 H II regions is 1.4 x 10(exp 5) solar mass. The star-formation rate inferred for M81 from the observed UV and H-alpha fluxes is low for a spiral galaxy at approximately 0.13 solar mass/yr, but consistent with the low star-formation rates obtained by Kennicutt (1983) and Caldwell et al. (1991) for early-type spirals.

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission.

PubMed

McMillan, Dayton D; Maeda, Junko; Bell, Justin J; Genet, Matthew D; Phoonswadi, Garrett; Mann, Kelly A; Kraft, Susan L; Kitamura, Hisashi; Fujimori, Akira; Yoshii, Yukie; Furukawa, Takako; Fujibayashi, Yasuhisa; Kato, Takamitsu A

2015-09-01

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a (64)Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of (64)Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from (64)Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair-deficient xrs5 cells were exposed to (64)Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D(10) values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that (64)Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from (64)Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after (64)Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that (64)Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of (64)Cu-ATSM as a cancer treatment modality for hypoxic tumors. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission

PubMed Central

McMillan, Dayton D.; Maeda, Junko; Bell, Justin J.; Genet, Matthew D.; Phoonswadi, Garrett; Mann, Kelly A.; Kraft, Susan L.; Kitamura, Hisashi; Fujimori, Akira; Yoshii, Yukie; Furukawa, Takako; Fujibayashi, Yasuhisa; Kato, Takamitsu A.

2015-01-01

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a 64Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of 64Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from 64Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to 64Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D10 values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that 64Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from 64Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after 64Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that 64Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of 64Cu-ATSM as a cancer treatment modality for hypoxic tumors. PMID:26251463

Inhibitory effects of isatin Mannich bases on carbonic anhydrases, acetylcholinesterase, and butyrylcholinesterase.

PubMed

Ozgun, Dilan Ozmen; Yamali, Cem; Gul, Halise Inci; Taslimi, Parham; Gulcin, Ilhami; Yanik, Telat; Supuran, Claudiu T

2016-12-01

The effects of isatin Mannich bases incorporating (1-[piperidin-1-yl (P1)/morpholin-4-yl (P2)/N-methylpiperazin-1-yl (P3)]methyl)-1H-indole-2,3-dione) moieties against human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoenzymes hCA I and hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes were evaluated. P1-P3 demonstrated impressive inhibition profiles against AChE and BChE and also inhibited both CAs at nanomolar level. These inhibitory effects were more powerful in all cases than the reference compounds used for all these enzymes. This study suggests that isatin Mannich bases P1-P3 are good candidate compounds especially for the development of new cholinesterase inhibitors since they were 2.2-5.9 times better inhibitors than clinically used drug Tacrine.

Cyclam Derivatives with a Bis(phosphinate) or a Phosphinato-Phosphonate Pendant Arm: Ligands for Fast and Efficient Copper(II) Complexation for Nuclear Medical Applications.

PubMed

David, Tomáš; Kubíček, Vojtěch; Gutten, Ondrej; Lubal, Přemysl; Kotek, Jan; Pietzsch, Hans-Jürgen; Rulíšek, Lubomír; Hermann, Petr

2015-12-21

Cyclam derivatives bearing one geminal bis(phosphinic acid), -CH2PO2HCH2PO2H2 (H2L(1)), or phosphinic-phosphonic acid, -CH2PO2HCH2PO3H2 (H3L(2)), pendant arm were synthesized and studied as potential copper(II) chelators for nuclear medical applications. The ligands showed good selectivity for copper(II) over zinc(II) and nickel(II) ions (log KCuL = 25.8 and 27.7 for H2L(1) and H3L(2), respectively). Kinetic study revealed an unusual three-step complex formation mechanism. The initial equilibrium step leads to out-of-cage complexes with Cu(2+) bound by the phosphorus-containing pendant arm. These species quickly rearrange to an in-cage complex with cyclam conformation II, which isomerizes to another in-cage complex with cyclam conformation I. The first in-cage complex is quantitatively formed in seconds (pH ≈5, 25 °C, Cu:L = 1:1, cM ≈ 1 mM). At pH >12, I isomers undergo nitrogen atom inversion, leading to III isomers; the structure of the III-[Cu(HL(2))] complex in the solid state was confirmed by X-ray diffraction analysis. In an alkaline solution, interconversion of the I and III isomers is mutual, leading to the same equilibrium isomeric mixture; such behavior has been observed here for the first time for copper(II) complexes of cyclam derivatives. Quantum-chemical calculations showed small energetic differences between the isomeric complexes of H3L(2) compared with analogous data for isomeric complexes of cyclam derivatives with one or two methylphosphonic acid pendant arm(s). Acid-assisted dissociation proved the kinetic inertness of the complexes. Preliminary radiolabeling of H2L(1) and H3L(2) with (64)Cu was fast and efficient, even at room temperature, giving specific activities of around 70 GBq of (64)Cu per 1 μmol of the ligand (pH 6.2, 10 min, ca. 90 equiv of the ligand). These specific activities were much higher than those of H3nota and H4dota complexes prepared under identical conditions. The rare combination of simple ligand synthesis, very

Extraplanar H II Regions in Spiral Galaxies. II. In Situ Star Formation in the Interstellar Thick Disk of NGC 4013

NASA Astrophysics Data System (ADS)

Howk, J. Christopher; Rueff, Katherine M.; Lehner, Nicolas; Wotta, Christopher B.; Croxall, Kevin; Savage, Blair D.

2018-04-01

We present observations of an Hα-emitting knot in the thick disk of NGC 4013, demonstrating it is an H II region surrounding a cluster of young hot stars z = 860 pc above the plane of this edge-on spiral galaxy. With LBT/MODS spectroscopy we show that this H II region has an Hα luminosity ∼4–7 times that of the Orion nebula, with an implied ionizing photon production rate log Q 0 ≈ 49.4 (photons s‑1). HST/WFPC2 imaging reveals an associated blue continuum source with M V = ‑8.21 ± 0.24. Together, these properties demonstrate that the H II region is powered by a young cluster of stars formed in situ in the thick disk, with an ionizing photon flux equivalent to ∼6 O7 V stars. If we assume ≈6 other extraplanar Hα-emitting knots are H II regions, the total thick disk star formation rate of NGC 4013 is ∼5 × 10‑4 M ⊙ yr‑1. The star formation likely occurs in the dense clouds of the interstellar thick disk seen in optical images of dust extinction and CO emission.

Desorption of Hg(II) and Sb(V) on extracellular polymeric substances: effects of pH, EDTA, Ca(II) and temperature shocks.

PubMed

Zhang, Daoyong; Lee, Duu-Jong; Pan, Xiangliang

2013-01-01

Extracellular polymeric substances (EPS) existed ubiquitously in biological systems affect the mobility and availability of heavy metals in the environments. The adsorption-desorption behaviors of Hg(II) and Sb(V) on EPS were investigated. The sorption rates follow Sb(V) > Hg(II), and the desorption rates follow reverse order. Applications of ethylene diamine tetraacetic acid (EDTA), Ca(II) and pH shocks affect desorption rates and desorbed quantities of Hg(II) from EPS-Hg complex. Temperature shock minimally affects the desorption rate of Hg(II). Conversely, the EPS-Sb complex is stable subjected to EDTA, Ca(II), temperature or pH shocks. The excitation-emission matrix (EEM) fluorescence spectroscopy and fast-Fourier (FT-IR) analysis showed that Hg(II) and Sb(V) principally interacted with polysaccharides and protein-like compounds in the EPS, respectively. The EPS-Hg complex presents a time bomb that may release high levels of Hg(II) in short time period under environmental shocks. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sulforaphane protects H9c2 cardiomyocytes from angiotensin II-induced hypertrophy.

PubMed

Wu, Q-Q; Zong, J; Gao, L; Dai, J; Yang, Z; Xu, M; Fang, Y; Ma, Z-G; Tang, Q-Z

2014-05-01

Cardiac hypertrophy is an adaptive process of the heart in response to various stimuli, but sustained cardiac hypertrophy will finally lead to heart failure. Sulforaphane-extracted from cruciferous vegetables of the genus Brassica such as broccoli, brussels sprouts, and cabbage-has been evaluated for its anticarcinogenic and antioxidant effects. To investigate the effect of sulforaphane on angiotensin II (Ang II)-induced cardiac hypertrophy in vitro. Embryonic rat heart-derived H9c2 cells were co-incubated with sulforaphane and Ang II. The cell surface area and mRNA levels of hypertrophic markers were measured to clarify the effect of sulforaphane on cardiac hypertrophy. The underlying mechanism was further investigated by detecting the activation of Akt and NF-κB signaling pathways. We found that H9c2 cells pretreated with sulforaphane were protected from Ang II-induced hypertrophy. The increasing mRNA levels of ANP, BNP, and β-MHC in Ang II-stimulated cells were also down-regulated after sulforaphane treatment. Moreover, sulforaphane repressed the Ang II-induced phosphorylation of Akt, GSK3β, mTOR, eIF4e, as well as of IκBα and NF-κB. Based on our results, sulforaphane attenuates Ang II-induced hypertrophy of H9c2 cardiomyocytes mediated by the inhibition of intracellular signaling pathways including Akt and NF-κB.

EGF receptor-targeting peptide conjugate incorporating a near-IR fluorescent dye and a novel 1,4,7-triazacyclononane-based (64)Cu(II) chelator assembled via click chemistry.

PubMed

Viehweger, Katrin; Barbaro, Lisa; García, Karina Pombo; Joshi, Tanmaya; Geipel, Gerhard; Steinbach, Jörg; Stephan, Holger; Spiccia, Leone; Graham, Bim

2014-05-21

A new Boc-protected 1,4,7-triazacyclononane (TACN)-based pro-chelator compound featuring a "clickable" azidomethylpyridine pendant has been developed as a building block for the construction of multimodal imaging agents. Conjugation to a model alkyne (propargyl alcohol), followed by deprotection, generates a pentadentate ligand, as confirmed by X-ray crystallographic analysis of the corresponding distorted square-pyramidal Cu(II) complex. The ligand exhibits rapid (64)Cu(II)-binding kinetics (>95% radiochemical yield in <5 min) and a high resistance to demetalation. It may thus prove suitable for use in (64)Cu(II)-based in vivo positron emission tomography (PET). The new chelating building block has been applied to the construction of a bimodal (PET/fluorescence) peptide-based imaging probe targeting the epidermal growth factor (EGF) receptor, which is highly overexpressed on the surface of several types of cancer cells. The probe consists of a hexapeptide sequence, Leu-Ala-Arg-Leu-Leu-Thr (designated "D4"), followed by a Cys-β-Ala-β-Ala spacer, then a β-homopropargylglycine residue with the TACN-based chelator "clicked" to its side chain. A sulfonated near-infrared (NIR) fluorescent cyanine dye (sulfo-Cy5) was introduced at the N-terminus to study the EGF receptor-binding ability of the probe by laser-fluorescence spectroscopy. Binding was also confirmed by coimmunoprecipitation methods, and an apparent dissociation constant (Kd) of ca. 10 nM was determined from radioactivity-based measurements of probe binding to two EGF receptor-expressing cell lines (FaDu and A431). The probe is shown to be a biased or partial allosteric agonist of the EGF receptor, inducing phosphorylation of Thr669 and Tyr992, but not the Tyr845, Tyr998, Tyr1045, Tyr1068, or Tyr1148 residues of the receptor, in the absence of the orthosteric EGF ligand. Additionally, the probe was found to suppress the EGF-stimulated autophosphorylation of these latter residues, indicating that it is also

(Cryptand-222)potassium(+) (hydrogensulfido)[5,10,15,20-tetra­kis(2-pival­amido­phen­yl)porphyrinato]ferrate(II)

PubMed Central

Dhifet, Mondher; Belkhiria, Mohamed Salah; Daran, Jean-Claude; Nasri, Habib

2009-01-01

As part of a systematic investigation for a number of FeII porphyrin complexes used as biomimetic models for cytochrome P450, crystals of the title compound, [K(C18H36N2O6)][FeII(C64H64N8O4)(HS)], were prepared. The compound exhibits a non-planar conformation with major ruffling and saddling distortions. The average equatorial iron–pyrrole N atom [Fe—Np = 2.102 (2) Å] bond length and the distance between the FeII atom and the 24-atom core of the porphyrin ring (Fe—PC= 0.558 Å) are typical for high-spin iron(II) penta­coordinate porphyrinates. One of the tert-butyl groups in the structure is disordered over two sets with occupancies of 0.84 and 0.16. PMID:21583412

Shape analysis of H II regions - I. Statistical clustering

NASA Astrophysics Data System (ADS)

Campbell-White, Justyn; Froebrich, Dirk; Kume, Alfred

2018-07-01

We present here our shape analysis method for a sample of 76 Galactic H II regions from MAGPIS 1.4 GHz data. The main goal is to determine whether physical properties and initial conditions of massive star cluster formation are linked to the shape of the regions. We outline a systematic procedure for extracting region shapes and perform hierarchical clustering on the shape data. We identified six groups that categorize H II regions by common morphologies. We confirmed the validity of these groupings by bootstrap re-sampling and the ordinance technique multidimensional scaling. We then investigated associations between physical parameters and the assigned groups. Location is mostly independent of group, with a small preference for regions of similar longitudes to share common morphologies. The shapes are homogeneously distributed across Galactocentric distance and latitude. One group contains regions that are all younger than 0.5 Myr and ionized by low- to intermediate-mass sources. Those in another group are all driven by intermediate- to high-mass sources. One group was distinctly separated from the other five and contained regions at the surface brightness detection limit for the survey. We find that our hierarchical procedure is most sensitive to the spatial sampling resolution used, which is determined for each region from its distance. We discuss how these errors can be further quantified and reduced in future work by utilizing synthetic observations from numerical simulations of H II regions. We also outline how this shape analysis has further applications to other diffuse astronomical objects.

Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

PubMed Central

Bohu, Tsing; Santelli, Cara M.; Akob, Denise M.; Neu, Thomas R.; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

2015-01-01

Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling. PMID:26236307

Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

USGS Publications Warehouse

Bohu, Tsing; Santelli, Cara M; Akob, Denise M.; Neu, Thomas R; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

2015-01-01

Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1.

PubMed

Bohu, Tsing; Santelli, Cara M; Akob, Denise M; Neu, Thomas R; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

2015-01-01

Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling.

THE HYDRODYNAMICAL MODELS OF THE COMETARY COMPACT H ii REGION

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

Zhu, Feng-Yao; Zhu, Qing-Feng; Li, Juan

2015-10-10

We have developed a full numerical method to study the gas dynamics of cometary ultracompact H ii regions, and associated photodissociation regions (PDRs). The bow-shock and champagne-flow models with a 40.9/21.9 M{sub ⊙} star are simulated. In the bow-shock models, the massive star is assumed to move through dense (n = 8000 cm{sup −3}) molecular material with a stellar velocity of 15 km s{sup −1}. In the champagne-flow models, an exponential distribution of density with a scale height of 0.2 pc is assumed. The profiles of the [Ne ii] 12.81 μm and H{sub 2} S(2) lines from the ionized regionsmore » and PDRs are compared for two sets of models. In champagne-flow models, emission lines from the ionized gas clearly show the effect of acceleration along the direction toward the tail due to the density gradient. The kinematics of the molecular gas inside the dense shell are mainly due to the expansion of the H ii region. However, in bow-shock models the ionized gas mainly moves in the same direction as the stellar motion. The kinematics of the molecular gas inside the dense shell simply reflects the motion of the dense shell with respect to the star. These differences can be used to distinguish two sets of models.« less

Nardosinone protects H9c2 cardiac cells from angiotensin II-induced hypertrophy.

PubMed

Du, Meng; Huang, Kun; Gao, Lu; Yang, Liu; Wang, Wen-Shuo; Wang, Bo; Huang, Kai; Huang, Dan

2013-12-01

Pathological cardiac hypertrophy induced by angiotensin II (AngII) can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots of Nardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on AngII-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosinone (25, 50, 100, and 200 μmol/L) or AngII (1 μmol/L). Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by AngII. The mRNA expression of ANP, BNP and β-MHC was obviously elevated in AngII-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100 μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang II-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.

An EPR study of the pH dependence of formate effects on Photosystem II.

PubMed

Jajoo, Anjana; Katsuta, Nobuhiro; Kawamori, Asako

2006-04-01

Effects of formate on rates of O(2) evolution and electron paramagnetic resonance (EPR) signals were observed in the oxygen evolving PS II membranes as a function of pH. In formate treated PS II membranes, decrease in pH value resulted in the inhibition of the O(2) evolving activity, a decrease in the intensity of S(2) state multiline signal but an increase in the intensity of the Q(A)(-)Fe(2+) EPR signal. Time-resolved EPR study of the Y(Z)(*) decay kinetics showed that the light-induced intensity of Y(Z)(*) EPR signal was proportional to the formate concentration. The change in the pH affected both the light-induced intensities and the decay rates of Y(Z)(*), which was found to be faster at lower pH. At 253 K, t(1/e) value of Y(Z)(*) decay kinetics was found to be 8-10 s at pH 6.0 and 18-21 s at pH 5.0. The results presented here indicate that the extent of inhibition at the donor and the acceptor side of PS II due to formate is pH dependent, being more effective at lower pH.

Bioremediation of agricultural solid waste leachates with diverse species of Cu (II) and Cd (II) by periphyton.

PubMed

Yang, Jiali; Liu, Junzhuo; Wu, Chenxi; Kerr, Philip G; Wong, Po-Keung; Wu, Yonghong

2016-12-01

The aim of this work was to study the bioremediation of agricultural solid waste leachates with high-concentrations of Cu (II) and Cd (II) after washing the wastes with water and Na 2 EDTA solution (0.2M). Results indicate that Cu (II) and Cd (II) are mainly comprised of Cu 2 (OH) 2 2+ , Cu 3 (OH) 4 2+ , CuOH + , Cu(H 2 O) 4 (OH) 2 , Cd 2+ and CdOH + in the water-washed leachates and Cu(EDTA) 2- , Cu(HEDTA) - , Cd(EDTA) 2- and Cd(HEDTA) - in the Na 2 EDTA-washed leachates. Cu (II) removal efficiency by selected native periphyton from the water- and Na 2 EDTA-washed leachates were 80.5% and 68.4% respectively, and for Cd (II) it was 57.1% and 64.6%, because the periphyton was able to maintain a stable pH of the leachates and regulate its microbial composition and carbon metabolic capability to acclimate the chemical conditions of the leachates. This study provides a new biomeasure to treat leachates with high-concentration Cu 2+ and Cd 2+ , and contribute valuable insights into the relationships between periphyton characteristics and heavy metals. Copyright © 2016 Elsevier Ltd. All rights reserved.

64Cu-ATSM and 18FDG PET uptake and 64Cu-ATSM autoradiography in spontaneous canine tumors: comparison with pimonidazole hypoxia immunohistochemistry

PubMed Central

2012-01-01

Background The aim of this study was to compare 64Cu-diacetyl-bis(N4-methylsemicarbazone) (64Cu-ATSM) and 18FDG PET uptake characteristics and 64Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas. Methods Biopsies were collected from individual tumors between approximately 3 and 25 hours after the intravenous injection of 64Cu-ATSM and pimonidazole. 64Cu-ATSM autoradiography and pimonidazole immunostaining was performed on sectioned biopsies. Acquired 64Cu-ATSM autoradiography and pimonidazole images were rescaled, aligned and their distribution patterns compared. 64Cu-ATSM and 18FDG PET/CT scans were performed in a concurrent study and uptake characteristics were obtained for tumors where available. Results Maximum pimonidazole pixel value and mean pimonidazole labeled fraction was found to be strongly correlated to 18FDG PET uptake levels, whereas more varying results were obtained for the comparison to 64Cu-ATSM. In the case of the latter, uptake at scans performed 3 h post injection (pi) generally showed strong positive correlated to pimonidazole uptake. Comparison of distribution patterns of pimonidazole immunohistochemistry and 64Cu-ATSM autoradiography yielded varying results. Significant positive correlations were mainly found in sections displaying a heterogeneous distribution of tracers. Conclusions Tumors with high levels of pimonidazole staining generally displayed high uptake of 18FDG and 64Cu-ATSM (3 h pi.). Similar regional distribution of 64Cu-ATSM and pimonidazole was observed in most heterogeneous tumor regions. However, tumor and hypoxia level dependent differences may exist with regard to the hypoxia specificity of 64Cu-ATSM in canine tumors. PMID:22704363

1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads.

PubMed

Ferraroni, Marta; Lucarini, Laura; Masini, Emanuela; Korsakov, Mikhail; Scozzafava, Andrea; Supuran, Claudiu T; Krasavin, Mikhail

2017-09-01

Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development. These compounds were found to be comparable in efficacy to dorzolamide eye drops when applied in the eye drop form as well. Finally, the reasons for unusually high potency of these compounds became understood from their high-resolution X-ray crystallography structures. These data significantly expand our understanding of heterocycle-based primary sulfonamides, many of which have recently emerged from our labs - particularly, from the corneal permeability standpoint. Copyright © 2017 Elsevier Ltd. All rights reserved.

A survey of Mg II h and k emission in near-solar type stars

NASA Technical Reports Server (NTRS)

Doherty, L. R.

1984-01-01

International Ultraviolet Explorer measurements of Mg II h and k emission fluxes are presented for 30 F and G stars that are on or near the main sequence and compared with Wilson's measurements of the Ca II H and K fluxes in these stars. The survey includes a large proportion of stars with very low chromospheric activity as well as 111 Tau, X(1) Ori and other examples of strong chromospheric emission. Emission cores are presented in all of the stars observed. A sharp lower limit to the flux in the cores of the k lines implies the existence of a minimum level of chromospheric activity in which the k line flux is a constant fraction of stellar luminosity. Reduction of Wilson's values to absolute fluxes produces a close correlation between Mg and Ca strength with possibly some dependence on color. For the most active stars, the Mg k and Ca fluxes are consistent with the presence of solar plage covering up to one half of the stellar surface. However, the ratio of k to h in these stars is much less than this simple interpretation predicts.

Generating a Metal-responsive Transcriptional Regulator to Test What Confers Metal Sensing in Cells*

PubMed Central

Osman, Deenah; Piergentili, Cecilia; Chen, Junjun; Chakrabarti, Buddhapriya; Foster, Andrew W.; Lurie-Luke, Elena; Huggins, Thomas G.; Robinson, Nigel J.

2015-01-01

FrmR from Salmonella enterica serovar typhimurium (a CsoR/RcnR-like transcriptional de-repressor) is shown to repress the frmRA operator-promoter, and repression is alleviated by formaldehyde but not manganese, iron, cobalt, nickel, copper, or Zn(II) within cells. In contrast, repression by a mutant FrmRE64H (which gains an RcnR metal ligand) is alleviated by cobalt and Zn(II). Unexpectedly, FrmR was found to already bind Co(II), Zn(II), and Cu(I), and moreover metals, as well as formaldehyde, trigger an allosteric response that weakens DNA affinity. However, the sensory metal sites of the cells' endogenous metal sensors (RcnR, ZntR, Zur, and CueR) are all tighter than FrmR for their cognate metals. Furthermore, the endogenous metal sensors are shown to out-compete FrmR. The metal-sensing FrmRE64H mutant has tighter metal affinities than FrmR by approximately 1 order of magnitude. Gain of cobalt sensing by FrmRE64H remains enigmatic because the cobalt affinity of FrmRE64H is substantially weaker than that of the endogenous cobalt sensor. Cobalt sensing requires glutathione, which may assist cobalt access, conferring a kinetic advantage. For Zn(II), the metal affinity of FrmRE64H approaches the metal affinities of cognate Zn(II) sensors. Counter-intuitively, the allosteric coupling free energy for Zn(II) is smaller in metal-sensing FrmRE64H compared with nonsensing FrmR. By determining the copies of FrmR and FrmRE64H tetramers per cell, then estimating promoter occupancy as a function of intracellular Zn(II) concentration, we show how a modest tightening of Zn(II) affinity, plus weakened DNA affinity of the apoprotein, conspires to make the relative properties of FrmRE64H (compared with ZntR and Zur) sufficient to sense Zn(II) inside cells. PMID:26109070

Evaluation of (64)Cu-labeled DOTA-D-Phe(1)-Tyr (3)-octreotide ((64)Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors.

PubMed

Hanaoka, Hirofumi; Tominaga, Hideyuki; Yamada, Keiich; Paudyal, Pramila; Iida, Yasuhiko; Watanabe, Shigeki; Paudyal, Bishnuhari; Higuchi, Tetsuya; Oriuchi, Noboru; Endo, Keigo

2009-08-01

In-111 ((111)In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 ((64)Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a (64)Cu-labeled octreotide analog, (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D: -Phe(1)-Tyr(3)-octreotide ((64)Cu-DOTA-TOC). (64)Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45 degrees C. The stability of (64)Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by HPLC analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of (64)Cu-DOTA-TOC and (111)In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of (64)Cu-DOTA-TOC or (64)Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide ((64)Cu-TETA-OC). The tumor was imaged using (64)Cu-DOTA-TOC, (64)Cu-TETA-OC, and FDG with an animal PET scanner. (64)Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. (64)Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of (64)Cu was higher than that of (111)In in all organs except kidney. In tumor-bearing mice, (64)Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81 +/- 1.17 at 6 h after administration. (64)Cu-DOTA-TOC showed significantly higher accumulation in the tumor than (64)Cu-TETA-OC. (64)Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of (18)F-FDG PET and very similar to that of (64)Cu

Down-regulation of ether-a-go-go-related gene potassium channel protein through sustained stimulation of AT1 receptor by angiotensin II.

PubMed

Cai, Yue; Wang, Yuhong; Xu, Jia; Zuo, Xu; Xu, Yanfang

2014-09-26

We investigated the effects of AT1 receptor stimulation by angiotensin II (Ang II) on human ether-a-go-go-related gene (hERG) potassium channel protein in a heterogeneous expression system with the human embryonic kidney (HEK) 293 cells which stably expressed hERG channel protein and were transiently transfected with the human AT1 receptors (HEK293/hERG). Western-blot analysis showed that Ang II significantly decreased the expression of mature hERG channel protein (155-kDa band) in a time- and dose-dependent manner without affecting the level of immature hERG channel protein (135-kDa band). The relative intensity of 155-kDa band was 64.7±6.8% of control (P<0.01) after treatment of Ang II at 100nM for 24h. To investigate the effect of Ang II on the degradation of mature hERG channel protein, we blocked forward trafficking from ER to Golgi with a Golgi transit inhibitor brefeldin A (10μM). Ang II significantly enhanced the time-dependent reduction of mature hERG channel protein. In addition, the proteasomal inhibitor lactacystin (5μM) inhibited Ang II-mediated the reduction of mature hERG channel protein, but the lysosomal inhibitor bafilomycin A1 (1μM) had no effect on the protein. The protein kinase C (PKC) inhibitor bisindolylmaleimide 1 (1μM) antagonized the reduction of mature hERG channel protein induced by Ang II. The results indicate that sustained stimulation of AT1 receptors by Ang II reduces the mature hERG channel protein via accelerating channel proteasomal degradation involving the PKC pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

Primordial 4He abundance: a determination based on the largest sample of H II regions with a methodology tested on model H II regions

NASA Astrophysics Data System (ADS)

Izotov, Y. I.; Stasińska, G.; Guseva, N. G.

2013-10-01

We verified the validity of the empirical method to derive the 4He abundance used in our previous papers by applying it to CLOUDY (v13.01) models. Using newly published He i emissivities for which we present convenient fits as well as the output CLOUDY case B hydrogen and He i line intensities, we found that the empirical method is able to reproduce the input CLOUDY 4He abundance with an accuracy of better than 1%. The CLOUDY output data also allowed us to derive the non-recombination contribution to the intensities of the strongest Balmer hydrogen Hα, Hβ, Hγ, and Hδ emission lines and the ionisation correction factors for He. With these improvements we used our updated empirical method to derive the 4He abundances and to test corrections for several systematic effects in a sample of 1610 spectra of low-metallicity extragalactic H ii regions, the largest sample used so far. From this sample we extracted a subsample of 111 H ii regions with Hβ equivalent width EW(Hβ) ≥ 150 Å, with excitation parameter x = O2+/O ≥ 0.8, and with helium mass fraction Y derived with an accuracy better than 3%. With this subsample we derived the primordial 4He mass fraction Yp = 0.254 ± 0.003 from linear regression Y - O/H. The derived value of Yp is higher at the 68% confidence level (CL) than that predicted by the standard big bang nucleosynthesis (SBBN) model, possibly implying the existence of different types of neutrino species in addition to the three known types of active neutrinos. Using the most recently derived primordial abundances D/H = (2.60 ± 0.12) × 10-5 and Yp = 0.254 ± 0.003 and the χ2 technique, we found that the best agreement between abundances of these light elements is achieved in a cosmological model with baryon mass density Ωbh2 = 0.0234 ± 0.0019 (68% CL) and an effective number of the neutrino species Neff = 3.51 ± 0.35 (68% CL). Based on observations collected at the European Southern Observatory, Chile, programs 073.B-0283(A), 081.C-0113(A

The cometary H II regions of DR 21: Bow shocks or champagne flows or both?

NASA Astrophysics Data System (ADS)

Immer, K.; Cyganowski, C.; Reid, M. J.; Menten, K. M.

2014-03-01

We present deep Very Large Array H66α radio recombination line (RRL) observations of the two cometary H II regions in DR 21. With these sensitive data, we test the "hybrid" bow shock/champagne flow model previously proposed for the DR 21 H II regions. The ionized gas down the tail of the southern H II region is redshifted by up to ~30 km s-1 with respect to the ambient molecular gas, as expected in the hybrid scenario. The RRL velocity structure, however, reveals the presence of two velocity components in both the northern and southern H II regions. This suggests that the ionized gas is flowing along cone-like shells, swept-up by stellar winds. The observed velocity structure of the well-resolved southern H II region is most consistent with a picture that combines a stellar wind with stellar motion (as in bow shock models) along a density gradient (as in champagne flow models). The direction of the implied density gradient is consistent with that suggested by maps of dust continuum and molecular line emission in the DR 21 region. The image cubes are only available as a FITS file at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/563/A39Table 2, Fig. 4, and Appendices A and B are available in electronic form at http://www.aanda.org

NON-LTE INVERSIONS OF THE Mg ii h and k AND UV TRIPLET LINES

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

De la Cruz Rodríguez, Jaime; Leenaarts, Jorrit; Ramos, Andrés Asensio

The Mg ii h and k lines are powerful diagnostics for studying the solar chromosphere. They have become particularly popular with the launch of the Interface Region Imaging Spectrograph ( IRIS ) satellite, and a number of studies that include these lines have lead to great progress in understanding chromospheric heating, in many cases thanks to the support from 3D MHD simulations. In this study, we utilize another approach to analyze observations: non-LTE inversions of the Mg ii h and k and UV triplet lines including the effects of partial redistribution. Our inversion code attempts to construct a model atmospheremore » that is compatible with the observed spectra. We have assessed the capabilities and limitations of the inversions using the FALC atmosphere and a snapshot from a 3D radiation-MHD simulation. We find that Mg ii h and k allow reconstructing a model atmosphere from the middle photosphere to the transition region. We have also explored the capabilities of a multi-line/multi-atom setup, including the Mg ii h and k, the Ca ii 854.2 nm, and the Fe i 630.25 lines to recover the full stratification of physical parameters, including the magnetic field vector, from the photosphere to the chromosphere. Finally, we present the first inversions of observed IRIS spectra from quiet-Sun, plage, and sunspot, with very promising results.« less

Density Bounded H II Regions: Ionization of the Diffuse Interstellar and Intergalactic Media

NASA Astrophysics Data System (ADS)

Zurita, A.; Rozas, M.; Beckman, J. E.

2000-05-01

We present a study of the diffuse ionized gas (DIG) for a sample of nearby spiral galaxies using Hα images, after constructing their H II region catalogues. The integrated Hα emission of the DIG accounts for between 25% to 60% of the total Hα of the galaxy and a high ionizing photon flux is necessary to keep this gas ionized. We suggest that Lyman photons leaking from the most luminous H II regions are the prime source of the ionization of the DIG; they are more than enough to ionize the measured DIG in the model in which H II regions with luminosity in Hα greater than LStr=1038.6 erg sme are density bounded. We go on to show that this model can quantify the ionization observed in the skins of the high velocity clouds well above the plane of our Galaxy and predicts the ionization of the intergalactic medium.

O2 Activation and Double C-H Oxidation by a Mononuclear Manganese(II) Complex.

PubMed

Deville, Claire; Padamati, Sandeep K; Sundberg, Jonas; McKee, Vickie; Browne, Wesley R; McKenzie, Christine J

2016-01-11

A Mn(II) complex, [Mn(dpeo)2](2+) (dpeo=1,2-di(pyridin-2-yl)ethanone oxime), activates O2, with ensuing stepwise oxidation of the methylene group in the ligands providing an alkoxide and ultimately a ketone group. X-ray crystal-structure analysis of an intermediate homoleptic alkoxide Mn(III) complex shows tridentate binding of the ligand via the two pyridyl groups and the newly installed alkoxide moiety, with the oxime group no longer coordinated. The structure of a Mn(II) complex of the final ketone ligand, cis-[MnBr2(hidpe)2] (hidpe=2-(hydroxyimino)-1,2-di(pyridine-2-yl)ethanone) shows that bidentate oxime/pyridine coordination has been resumed. H2(18)O and (18)O2 labeling experiments suggest that the inserted O atoms originate from two different O2 molecules. The progress of the oxygenation was monitored through changes in the resonance-enhanced Raman bands of the oxime unit. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fotometria Hβ en el O.A.N. Aplicación a estrellas en regiones H II.

NASA Astrophysics Data System (ADS)

Lahulla, J. F.

Photoelectric Hβ photometry is reported for some UBVRI standard stars from the list of Neckel and Chini (1980). Complementary UBVRI and Hβ photometry was carried out for stars located in several H II regions.

A novel ruthenium(II)-cobaloxime supramolecular complex for photocatalytic H2 evolution: Synthesis, characterisation, and mechanistic studies

PubMed Central

Cropek, Donald M.; Metz, Anja; Müller, Astrid M.; Gray, Harry B.; Horne, Toyketa; Horton, Dorothy C.; Poluektov, Oleg; Tiede, David M.; Weber, Ralph T.; Jarrett, William L.; Phillips, Joshua D.

2012-01-01

We report the synthesis and characterization of novel mixed-metal binuclear ruthenium(II)-cobalt(II) photocatalysts for hydrogen evolution in acidic acetonitrile. First, 2-(2′-pyridyl)benzothiazole (pbt), 1, was reacted with RuCl3·xH2O to produce [Ru(pbt)2Cl2] ·0.25CH3COCH3, 2, which was then reacted with 1,10-phenanthroline-5,6-dione (phendione), 3 in order to produce [Ru(pbt)2(phendione)](PF6)2·4H2O, 4. Compound 4 was then reacted with 4-pyridinecarboxaldehyde in order to produce [Ru(pbt)2(L-pyr)](PF6)2·9.5H2O, 5 (where L-pyr = (4-pyridine)oxazolo[4,5-f]phenanthroline). Compound 5 was then reacted with [Co(dmgBF2)2(H2O)2] (where dmgBF2 = difluorboryldimethylglyoximate) in order to produce the mixed-metal binuclear complex, [Ru(pbt)2(L-pyr)Co(dmgBF2)2(H2O)](PF6)2·11H2O·1.5CH3COCH3, 6. [Ru(Me2bpy)2(L-pyr)Co(dmgBF2)2(OH2)](PF6)2, 7 (where Me2bpy = 1,10-phenanthroline, 4,4′-dimethyl-2,2′-bipyridine) and [Ru(phen)2(L-pyr)Co(dmgBF2)2(OH2)](PF6)2, 8 were also synthesised. All complexes were characterized by elemental analysis, UV-visible absorption, 11B, 19F, and 59Co NMR, ESR spectroscopy, and cyclic voltammetry, where appropriate. Photocatalytic studies carried out in acidified acetonitrile demonstrated constant hydrogen generation longer than a 42 hour period as detected by gas chromatography. Time resolved spectroscopic measurements were performed on compound 6, which proved an intramolecular electron transfer from an excited Ru(II) metal centre to the Co(II) metal centre via the bridging L-pyr ligand. This resulted in the formation of a cobalt(I)-containing species that is essential for the production of H2 gas in the presence of H+ ions. A proposed mechanism for the generation of hydrogen is presented. PMID:23001132

Spectroscopic (FT-IR, FT-Raman, 1H, 13C NMR, UV/VIS), thermogravimetric and antimicrobial studies of Ca(II), Mn(II), Cu(II), Zn(II) and Cd(II) complexes of ferulic acid

NASA Astrophysics Data System (ADS)

Kalinowska, M.; Piekut, J.; Bruss, A.; Follet, C.; Sienkiewicz-Gromiuk, J.; Świsłocka, R.; Rzączyńska, Z.; Lewandowski, W.

2014-03-01

The molecular structure of Mn(II), Cu(II), Zn(II), Cd(II) and Ca(II) ferulates (4-hydroxy-3-methoxycinnamates) was studied. The selected metal ferulates were synthesized. Their composition was established by means of elementary and thermogravimetric analysis. The following spectroscopic methods were used: infrared (FT-IR), Raman (FT-Raman), nuclear magnetic resonance (13C, 1H NMR) and ultraviolet-visible (UV/VIS). On the basis of obtained results the electronic charge distribution in studied metal complexes in comparison with ferulic acid molecule was discussed. The microbiological study of ferulic acid and ferulates toward Escherichia coli, Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus and Proteus vulgaris was done.

The Role of Coordination Environment and pH in Tuning the Oxidation Rate of Europium(II).

PubMed

Ekanger, Levi A; Basal, Lina A; Allen, Matthew J

2017-01-23

The Eu II/III redox couple offers metal-based oxidation-sensing with magnetic resonance imaging making the study of Eu II oxidation chemistry important in the design of new probes. Accordingly, we explored oxidation reactions with a set of Eu II -containing complexes. Superoxide formation from the reaction between Eu II and dioxygen was observed using electron paramagnetic resonance spectroscopy. Additionally, oxidation kinetics of three Eu II -containing complexes with bromate and glutathione disulfide at pH values, including 5 and 7, is reported. In the reaction with bromate, the oxidation rate of two of the complexes increased by 7.3 and 6.7 times upon decreasing pH from 7 to 5, but the rate increased by 17 times for a complex containing amide functional groups over the same pH range. The oxidation rate of a fluorobenzo-functionalized cryptate was relatively slow, indicating that the ligand used to impart thermodynamic oxidative stability might also be useful for controlling oxidation kinetics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relative abundance of chemical forms of Cu(II) and Cd(II) on soybean roots as influenced by pH, cations and organic acids

PubMed Central

Zhou, Qin; Liu, Zhao-dong; Liu, Yuan; Jiang, Jun; Xu, Ren-kou

2016-01-01

Little information is available on chemical forms of heavy metals on integrate plant roots. KNO3 (1 M), 0.05M EDTA at pH6 and 0.01 M HCl were used sequentially to extract the exchangeable, complexed and precipitated forms of Cu(II) and Cd(II) from soybean roots and then to investigate chemical form distribution of Cu(II) and Cd(II) on soybean roots. Cu(II) and Cd(II) adsorbed on soybean roots were mainly exchangeable form, followed by complexed form, while their precipitated forms were very low under acidic conditions. Soybean roots had a higher adsorption affinity to Cu(II) than Cd(II), leading to higher toxic of Cu(II) than Cd(II). An increase in solution pH increased negative charge on soybean and thus increased exchangeable Cu(II) and Cd(II) on the roots. Ca2+, Mg2+ and NH4+ reduced exchangeable Cu(II) and Cd(II) levels on soybean roots and these cations showed greater effects on Cd(II) than Cu(II) due to greater adsorption affinity of the roots to Cu(II) than Cd(II). L-malic and citric acids decreased exchangeable and complexed Cu(II) on soybean roots. In conclusion, Cu(II) and Cd(II) mainly existed as exchangeable and complexed forms on soybean roots. Ca2+ and Mg2+ cations and citric and L-malic acids can potentially alleviate Cu(II) and Cd(II) toxicity to plants. PMID:27805020

Product-Improvement Test (Phase II), Jetcal Tester, Model H119A.

DTIC Science & Technology

1969-03-05

Ao—A0 51 113 ARMY AVIATION ‘Cs’ BOARD FORT tUCKER ALA — P*OOUCTeII ROVEMCNT TEST ( FHAS ~ I I ) . JETCAL TESTER, MODEL M119A~~’ETC(U) MAR S9...Phase i i ) , Jetcal Tester , Model H 119A , USATECOM Project No. 4-6-5011-03 b . No fur ther consideration be given to the TEMPCAL heater probe as a...essen t i a l component of the Jetcal Tester. e. The service manual instruct ions for con t inu i ty te s t ing of EG1 thermocouples be revised to

RGS2 is regulated by angiotensin II and functions as a negative feedback of aldosterone production in H295R human adrenocortical cells.

PubMed

Romero, Damian G; Plonczynski, Maria W; Gomez-Sanchez, Elise P; Yanes, Licy L; Gomez-Sanchez, Celso E

2006-08-01

Regulator of G protein signaling (RGS) proteins interact with Galpha-subunits of heterotrimeric G proteins, accelerating the rate of GTP hydrolysis and finalizing the intracellular signaling triggered by the G protein-coupled receptor-ligand interaction. Angiotensin (Ang) II interacts with its G protein-coupled receptor in zona glomerulosa adrenal cells and triggers a cascade of intracellular signals that regulates steroidogenesis and proliferation. We studied Ang II-mediated regulation of RGS2, the role of RGS2 in steroidogenesis, and the intracellular signal events involved in H295R human adrenal cells. We report that both H295R cells and human adrenal gland express RGS2 mRNA. In H295R cells, Ang II caused a rapid and transient increase in RGS2 mRNA levels quantified by real-time RT-PCR. Ang II effects were mimicked by calcium ionophore A23187 and blocked by calcium channel blocker nifedipine. Ang II effects also were blocked by calmodulin antagonists (W-7 and calmidazolium) and calcium/calmodulin-dependent kinase antagonist KN-93. RGS2 overexpression by retroviral infection in H295R cells caused a decrease in Ang II-stimulated aldosterone secretion but did not modify cortisol secretion. In reporter assays, RGS2 decreased Ang II-mediated aldosterone synthase up-regulation. These results suggest that Ang II up-regulates RGS2 mRNA by the calcium/calmodulin-dependent kinase pathway in H295R cells. RGS2 overexpression specifically decreases aldosterone secretion through a decrease in Ang II-mediated aldosterone synthase-induced expression. In conclusion, RGS2 expression is induced by Ang II to terminate the intracellular signaling cascade generated by Ang II. RGS2 alterations in expression levels or functionality could be implicated in deregulations of Ang II signaling and abnormal aldosterone secretion by the adrenal gland.

STAR FORMATION ACTIVITY IN THE GALACTIC H II REGION Sh2-297

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

Mallick, K. K.; Ojha, D. K.; Dewangan, L. K.

We present a multiwavelength study of the Galactic H II region Sh2-297, located in the Canis Major OB1 complex. Optical spectroscopic observations are used to constrain the spectral type of ionizing star HD 53623 as B0V. The classical nature of this H II region is affirmed by the low values of electron density and emission measure, which are calculated to be 756 cm{sup -3} and 9.15 Multiplication-Sign 10{sup 5} cm{sup -6} pc using the radio continuum observations at 610 and 1280 MHz, and Very Large Array archival data at 1420 MHz. To understand local star formation, we identified the youngmore » stellar object (YSO) candidates in a region of area {approx}7.'5 Multiplication-Sign 7.'5 centered on Sh2-297 using grism slitless spectroscopy (to identify the H{alpha} emission line stars), and near infrared (NIR) observations. NIR YSO candidates are further classified into various evolutionary stages using color-color and color-magnitude (CM) diagrams, giving 50 red sources (H - K > 0.6) and 26 Class II-like sources. The mass and age range of the YSOs are estimated to be {approx}0.1-2 M {sub Sun} and 0.5-2 Myr using optical (V/V-I) and NIR (J/J-H) CM diagrams. The mean age of the YSOs is found to be {approx}1 Myr, which is of the order of dynamical age of 1.07 Myr of the H II region. Using the estimated range of visual extinction (1.1-25 mag) from literature and NIR data for the region, spectral energy distribution models have been implemented for selected YSOs which show masses and ages to be consistent with estimated values. The spatial distribution of YSOs shows an evolutionary sequence, suggesting triggered star formation in the region. The star formation seems to have propagated from the ionizing star toward the cold dark cloud LDN1657A located west of Sh2-297.« less

Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature.

PubMed

Ogielska, Maja; Lanotte, Philippe; Le Brun, Cécile; Valentin, Anne Sophie; Garot, Denis; Tellier, Anne-Charlotte; Halimi, Jean Michel; Colombat, Philippe; Guilleminault, Laurent; Lioger, Bertrand; Vegas, Hélène; De Toffol, Bertrand; Constans, Thierry; Bernard, Louis

2015-08-01

Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhoea. People in the general community are not usually considered to be at risk of CDI. CDI is associated with a high risk of morbidity and mortality. The risk of severity is defined by the Clostridium Severity Index (CSI). The cases of 136 adult patients with CDI treated at the University Hospital of Tours, France between 2008 and 2012 are described. This was a retrospective study. Among the 136 patients included, 62 were men and 74 were women. Their median age was 64.4 years (range 18-97 years). Twenty-six of the 136 (19%) cases were community-acquired (CA) and 110 (81%) were healthcare-acquired (HCA). The major risk factors for both groups were long-term treatment with proton pump inhibitors (54% of CA, 53% of HCA patients) and antibiotic treatment within the 2.5 months preceding the CDI (50% of CA, 91% of HCA). The CSI was higher in the CA-CDI group (1.56) than in the HCA-CDI group (1.39). Intensive care was required for 8% of CA-CDI and 16.5% of HCA-CDI patients. CDI can cause community-acquired diarrhoea, and CA-CDI may be more severe than HCA-CDI. Prospective studies of CDI involving people from the general community without risk factors are required to confirm this observation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

On the determination of Te by radio erecombination lines in H II regions

NASA Astrophysics Data System (ADS)

Guzmán, F.

2017-11-01

Radio recombination alpha and beta lines originate in high-n Rydberg levels of H I and He I are used to determine temperatures and densities of H II regions and galactic abundance gradients. Calculations of the departures from local thermodynamical equilibrium are very important for the determination of intensities, opacities, and abundances. I will show how uncertainties in atomic collisions are translated to large changes in emissivities and absorption coefficients in H II regions. I will show how these predictions can be tackled using the new GTM/LMT facility.

A New Test of Copper and Zinc Abundances in Late-type Stars Using Ultraviolet Cu II and Zn II Lines

NASA Astrophysics Data System (ADS)

Roederer, Ian U.; Barklem, Paul S.

2018-04-01

We present new abundances derived from Cu I, Cu II, Zn I, and Zn II lines in six warm (5766 ≤ {T}eff} ≤ 6427 K), metal-poor (‑2.50 ≤ [Fe/H] ≤ ‑0.95) dwarf and subgiant (3.64 ≤ log g ≤ 4.44) stars. These abundances are derived from archival high-resolution ultraviolet spectra from the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope and ground-based optical spectra from several observatories. Ionized Cu and Zn are the majority species, and abundances derived from Cu II and Zn II lines should be largely insensitive to departures from local thermodynamic equilibrium (LTE). We find good agreement between the [Zn/H] ratios derived separately from Zn I and Zn II lines, suggesting that departures from LTE are, at most, minimal (≲0.1 dex). We find that the [Cu/H] ratios derived from Cu II lines are 0.36 ± 0.06 dex larger than those derived from Cu I lines in the most metal-poor stars ([Fe/H] < ‑1.8), suggesting that LTE underestimates the Cu abundance derived from Cu I lines. The deviations decrease in more metal-rich stars. Our results validate previous theoretical non-LTE calculations for both Cu and Zn, supporting earlier conclusions that the enhancement of [Zn/Fe] in metal-poor stars is legitimate, and the deficiency of [Cu/Fe] in metal-poor stars may not be as large as previously thought. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute (STScI), which is operated by the Association of Universities for Research in Astronomy, Inc. (AURA) under NASA contract NAS 5-26555. This work is supported by NASA through grant number AR-15051 and makes use of data from programs GO-7348, GO-8197, GO-9804, GO-14161, and GO-14672. This research has also made use of the Keck Observatory Archive (KOA), which is operated by the W.M. Keck Observatory and the NASA Exoplanet Science Institute (NExScI), under contract with NASA. These data are associated

Adsorption of aliphatic polyhydroxy carboxylic acids on gibbsite: pH dependency and importance of adsorbate structure.

PubMed

Schneckenburger, Tatjana; Riefstahl, Jens; Fischer, Klaus

2018-01-01

Aliphatic (poly)hydroxy carboxylic acids [(P)HCA] occur in natural, e.g. soils, and in technical (waste disposal sites, nuclear waste repositories) compartments . Their distribution, mobility and chemical reactivity, e.g. complex formation with metal ions and radionuclides, depend, among others, on their adsorption onto mineral surfaces. Aluminium hydroxides, e.g. gibbsite [α-Al(OH) 3 ], are common constituents of related solid materials and mimic the molecular surface properties of clay minerals. Thus, the study was pursued to characterize the adsorption of glycolic, threonic, tartaric, gluconic, and glucaric acids onto gibbsite over a wide pH and (P)HCA concentration range. To consider specific conditions occurring in radioactive wastes, adsorption applying an artificial cement pore water (pH 13.3) as solution phase was investigated additionally. The sorption of gluconic acid at pH 4, 7, 9, and 12 was best described by the "two-site" Langmuir isotherm, combining "high affinity" sorption sites (adsorption affinity constants [Formula: see text] > 1 L mmol -1 , adsorption capacities < 6.5 mmol kg -1 ) with "low affinity" sites ([Formula: see text] < 0.1 L mmol -1 , adsorption capacities ≥ 19 mmol kg -1 ). The total adsorption capacities at pH 9 and 12 were roughly tenfold of that at pH 4 and 7. The S-shaped pH sorption edge of gluconic acid was modelled applying a constant capacitance model, considering electrostatic interactions, hydrogen bonding, surface complex formation, and formation of solved polynuclear complexes between Al 3+ ions and gluconic acid. A Pearson and Spearman rank correlation between (P)HCA molecular properties and adsorption parameters revealed the high importance of the size and the charge of the adsorbates. The adsorption behaviour of (P)HCAs is best described by a combination of adsorption properties of carboxylic acids at acidic pH and of polyols at alkaline pH. Depending on the molecular properties of the adsorbates and

Vibrational investigation on the copper(II) binding mode of carcinine and its pH dependence

NASA Astrophysics Data System (ADS)

Torreggiani, Armida; Reggiani, Matteo; Manco, Immacolata; Tinti, Anna

2007-05-01

A comparative FT-Raman and FT-IR study of Carcinine (Carc), a natural imidazole dipeptide, and its complexes with Cu(II) ions was performed at different pH's. Both Raman and IR spectra present marker bands useful for the identification of the predominant complexes; in particular, Raman spectroscopy appears useful for identifying the metal-coordination site of the imidazole ring (N π or N τ atoms) of Carc. Free Carc shows a strong network of H-bonds and tautomer I (N τ-H) is the preferred form of the imidazolic ring (bands at 1578, 1292 and 988 cm -1). The presence of Cu(II) does not affect the tautomeric equilibrium at pH 7, whereas the deprotonation of both N-imidazolic nitrogens is strongly induced at higher pH. Under neutral and alkaline conditions the primary amino group takes part to the Cu(II) chelation, whereas all the peptidic moieties are involved in coordination only at pH 7. Thus, Carc acts as a tri-dentate ligand at neutral pH, mainly giving a monomeric complex, [CuLH -1], containing tautomer I, whereas an oligonuclear complex, probably [Cu 4L 4H -8], where metal-imidazolate ions connect different ligand molecules, predominates at alkaline pH.

Terminal NiII-OH/-OH2 complexes in trigonal bipyramidal geometries derived from H2O.

PubMed

Lau, Nathanael; Sano, Yohei; Ziller, Joseph W; Borovik, A S

2017-03-29

The preparation and characterization of two Ni II complexes are described, a terminal Ni II -OH complex with the tripodal ligand tris[(N)-tertbutylureaylato)-N-ethyl)]aminato ([H 3 buea] 3- ) and a terminal Ni II -OH 2 complex with the tripodal ligand N , N ', N ″-[2,2',2″-nitrilotris(ethane-2,1-diyl)]tris(2,4,6-trimethylbenzenesulfonamido) ([MST] 3- ). For both complexes, the source of the -OH and -OH 2 ligand is water. The salts K 2 [Ni II H 3 buea(OH)] and NMe 4 [Ni II MST(OH 2 )] were characterized using perpendicular-mode X-band electronic paramagnetic resonance, Fourier transform infrared, UV-visible spectroscopies, and its electrochemical properties were evaluated using cyclic voltammetry. The solid state structures of these complexes determined by X-ray diffraction methods reveal that they adopt a distorted trigonal bipyramidal geometry, an unusual structure for 5-coordinate Ni II complexes. Moreover, the Ni II -OH and Ni II -OH 2 units form intramolecular hydrogen bonding networks with the [H 3 buea] 3- and [MST] 3- ligands. The oxidation chemistry of these complexes was explored by treating the high-spin Ni II compounds with one-electron oxidants. Species were formed with S = 1/2 spin ground states that are consistent with formation of monomeric Ni III species. While the formation of Ni III -OH complexes cannot be ruled out, the lack of observable O-H vibrations from the putative Ni-OH units suggest the possibility that other high valent Ni species are formed.

The somatostatin receptor 2 antagonist 64Cu-NODAGA-JR11 outperforms 64Cu-DOTA-TATE in a mouse xenograft model

PubMed Central

Rylova, Svetlana N.; Stoykow, Christian; Del Pozzo, Luigi; Abiraj, Keelara; Tamma, Maria Luisa; Kiefer, Yvonne; Fani, Melpomeni; Maecke, Helmut R.

2018-01-01

Copper-64 is an attractive radionuclide for PET imaging and is frequently used in clinical applications. The aim of this study was to perform a side-by-side comparison of the in vitro and in vivo performance of 64Cu-NODAGA-JR11 (NODAGA = 1,4,7-triazacyclononane,1-glutaric acid,4,7-acetic acid, JR11 = p-Cl-Phe-cyclo(D-Cys-Aph(Hor)-D-Aph(cbm)-Lys-Thr-Cys)D-Tyr-NH2), a somatostatin receptor 2 antagonist, with the clinically used sst2 agonist 64Cu-DOTA-TATE ((TATE = D-Phe-cyclo(Cys-Tyr-D-Trp-Lys-Thr-Cys)Thr). In vitro studies demonstrated Kd values of 5.7±0.95 nM (Bmax = 4.1±0.18 nM) for the antagonist 64/natCu-NODAGA-JR11 and 20.1±4.4. nM (Bmax = 0.48±0.18 nM) for the agonist 64/natCu-DOTA-TATE. Cell uptake studies showed the expected differences between agonists and antagonists. Whereas 64Cu-DOTA-TATE (the agonist) showed very effective internalization in the cell culture assay (with 50% internalized at 4 hours post-peptide addition under the given experimental conditions), 64Cu-NODAGA-JR11 (the antagonist) showed little internalization but strong receptor-mediated uptake at the cell membrane. Biodistribution studies of 64Cu-NODAGA-JR11 showed rapid blood clearance and tumor uptake with increasing tumor-to-relevant organ ratios within the first 4 hours and in some cases, 24 hours, respectively. The tumor washout was slow or non-existent in the first 4 hours, whereas the kidney washout was very efficient, leading to high and increasing tumor-to-kidney ratios over time. Specificity of tumor uptake was proven by co-injection of high excess of non-radiolabeled peptide, which led to >80% tumor blocking. 64Cu-DOTA-TATE showed less favorable pharmacokinetics, with the exception of lower kidney uptake. Blood clearance was distinctly slower and persistent higher blood values were found at 24 hours. Uptake in the liver and lung was relatively high and also persistent. The tumor uptake was specific and similar to that of 64Cu-NODAGA-JR11 at 1 h, but release from the tumor

The somatostatin receptor 2 antagonist 64Cu-NODAGA-JR11 outperforms 64Cu-DOTA-TATE in a mouse xenograft model.

PubMed

Rylova, Svetlana N; Stoykow, Christian; Del Pozzo, Luigi; Abiraj, Keelara; Tamma, Maria Luisa; Kiefer, Yvonne; Fani, Melpomeni; Maecke, Helmut R

2018-01-01

Copper-64 is an attractive radionuclide for PET imaging and is frequently used in clinical applications. The aim of this study was to perform a side-by-side comparison of the in vitro and in vivo performance of 64Cu-NODAGA-JR11 (NODAGA = 1,4,7-triazacyclononane,1-glutaric acid,4,7-acetic acid, JR11 = p-Cl-Phe-cyclo(D-Cys-Aph(Hor)-D-Aph(cbm)-Lys-Thr-Cys)D-Tyr-NH2), a somatostatin receptor 2 antagonist, with the clinically used sst2 agonist 64Cu-DOTA-TATE ((TATE = D-Phe-cyclo(Cys-Tyr-D-Trp-Lys-Thr-Cys)Thr). In vitro studies demonstrated Kd values of 5.7±0.95 nM (Bmax = 4.1±0.18 nM) for the antagonist 64/natCu-NODAGA-JR11 and 20.1±4.4. nM (Bmax = 0.48±0.18 nM) for the agonist 64/natCu-DOTA-TATE. Cell uptake studies showed the expected differences between agonists and antagonists. Whereas 64Cu-DOTA-TATE (the agonist) showed very effective internalization in the cell culture assay (with 50% internalized at 4 hours post-peptide addition under the given experimental conditions), 64Cu-NODAGA-JR11 (the antagonist) showed little internalization but strong receptor-mediated uptake at the cell membrane. Biodistribution studies of 64Cu-NODAGA-JR11 showed rapid blood clearance and tumor uptake with increasing tumor-to-relevant organ ratios within the first 4 hours and in some cases, 24 hours, respectively. The tumor washout was slow or non-existent in the first 4 hours, whereas the kidney washout was very efficient, leading to high and increasing tumor-to-kidney ratios over time. Specificity of tumor uptake was proven by co-injection of high excess of non-radiolabeled peptide, which led to >80% tumor blocking. 64Cu-DOTA-TATE showed less favorable pharmacokinetics, with the exception of lower kidney uptake. Blood clearance was distinctly slower and persistent higher blood values were found at 24 hours. Uptake in the liver and lung was relatively high and also persistent. The tumor uptake was specific and similar to that of 64Cu-NODAGA-JR11 at 1 h, but release from the tumor

Synthesis, spectroscopic characterization, DNA interaction and biological activities of Mn(II), Co(II), Ni(II) and Cu(II) complexes with [(1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol

NASA Astrophysics Data System (ADS)

Gaber, Mohamed; El-Wakiel, Nadia A.; El-Ghamry, Hoda; Fathalla, Shaimaa K.

2014-11-01

Manganese(II), cobalt(II), nickel(II) and copper(II) complexes of [(1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol have been synthesized. The structure of complexes have been characterized by elemental analysis, molar conductance, magnetic moment measurements and spectral (IR, 1H NMR, EI-mass, UV-Vis and ESR), and thermal studies. The results showed that the chloro and nitrato Cu(II) complexes have octahedral geometry while Ni(II), Co(II) and Mn(II) complexes in addition to acetato Cu(II) complex have tetrahedral geometry. The possible structures of the metal complexes have been computed using the molecular mechanic calculations using the hyper chem. 8.03 molecular modeling program to confirm the proposed structures. The kinetic and thermodynamic parameters of the thermal decomposition steps were calculated from the TG curves. The binding modes of the complexes with DNA have been investigated by UV-Vis absorption titration. The results showed that the mode of binding of the complexes to DNA is intercalative or non-intercalative binding modes. Schiff base and its metal complexes have been screened for their in vitro antimicrobial activities against Gram positive bacteria (Staphylococcus aureus), Gram negative bacteria (Escherichia coli and Pesudomonas aeruginosa), fungi (Asperigllus flavus and Mucer) and yeast (Candida albicans and Malassezia furfur).

A multi-wavelength analysis of the diffuse H II region G25.8700+0.1350

NASA Astrophysics Data System (ADS)

Cichowolski, S.; Duronea, N. U.; Suad, L. A.; Reynoso, E. M.; Dorda, R.

2018-02-01

We present a multi-wavelength investigation of the H II region G25.8700+0.1350, located in the inner part of the Galaxy. In radio continuum emission, the region is seen as a bright arc-shaped structure. An analysis of the H I line suggests that G25.8700+0.1350 lies at a distance of 6.5 kpc. The ionized gas is bordered by a photodissociation region, which is encircled by a molecular structure where four molecular clumps are detected. At infrared wavelengths, the region is also very conspicuous. Given the high level of visual absorption in the region, the exciting stars should be searched for in the infrared band. In this context, we found in the literature one Wolf-Rayet and one red supergiant, which, together with 37 2MASS sources that are candidate O-type stars, could be related to the origin of G25.8700+0.1350. Finally, as expanding H II regions are hypothesized to trigger star formation, we used different infrared point source catalogues to search for young stellar object candidates (cYSOs). A total of 45 cYSOs were identified projected on to the molecular clouds.

A Multi-ionic Kinematic Investigation of NGC 595, a Giant Extragalactic H II Region in M33

NASA Astrophysics Data System (ADS)

Lagrois, Dominic; Joncas, Gilles

2009-08-01

Spectro-interferometric observations of the Hα, [O III], and [S II] optical emission lines are combined with radio observations of the 21 cm line in order to obtain a reliable kinematic image of NGC 595, the second largest giant extragalactic H II region in M33. The Hα and [O III] observations reveal that the nebula is exposed to two distinct kinematical regimes. While symmetric, broad velocity profiles dominate a sizeable fraction of the ionized extent, evidence for line splitting is detected in a small region near the most massive stars of the star cluster. A quantitative investigation proposes that two expanding wind-blown bubbles could be held responsible for the observed line splitting. The kinematics of the ionized material presenting one-component velocity profiles likely indicates that Champagne flows are present at the periphery of the molecular component leading to accelerated ionized material in the ambient interstellar medium. In areas not dominated by the photoionization of the molecular clouds, the H+ and S+ material shows a kinematical behavior roughly in agreement with the atomic gas. Mean nonthermal line widths show relatively large, supersonic values especially in [O III]. Models of structure functions indicate that the Hα and [O III] components could be exposed to different turbulent motions which could explain the broadening excess observed for the latter ion. On the full ionized extent of the nebula, the S+ material shows narrower line widths than the two other ions. Combined with the absence of line splitting, these peculiar characteristics indicate that the [S II] component is likely located at the periphery of the nebula and probably does not coexist with Hα and [O III]. The shape of the [S II] structure function is in agreement with a relatively low number of large-scale velocity gradients which partially explains the narrower profiles observed. The mean electron density in the nebula is estimated at 162 ± 106(1σ) cm-3, in agreement

An enzyme kinetics study of the pH dependence of chloride activation of oxygen evolution in photosystem II.

PubMed

Baranov, Sergei; Haddy, Alice

2017-03-01

Oxygen evolution by photosystem II (PSII) involves activation by Cl - ion, which is regulated by extrinsic subunits PsbQ and PsbP. In this study, the kinetics of chloride activation of oxygen evolution was studied in preparations of PSII depleted of the PsbQ and PsbP subunits (NaCl-washed and Na 2 SO 4 /pH 7.5-treated) over a pH range from 5.3 to 8.0. At low pH, activation by chloride was followed by inhibition at chloride concentrations >100 mM, whereas at high pH activation continued as the chloride concentration increased above 100 mM. Both activation and inhibition were more pronounced at lower pH, indicating that Cl - binding depended on protonation events in each case. The simplest kinetic model that could account for the complete data set included binding of Cl - at two sites, one for activation and one for inhibition, and four protonation steps. The intrinsic (pH-independent) dissociation constant for Cl - activation, K S , was found to be 0.9 ± 0.2 mM for both preparations, and three of the four pK a s were determined, with the fourth falling below the pH range studied. The intrinsic inhibition constant, K I , was found to be 64 ± 2 and 103 ± 7 mM for the NaCl-washed and Na 2 SO 4 /pH7.5-treated preparations, respectively, and is considered in terms of the conditions likely to be present in the thylakoid lumen. This enzyme kinetics analysis provides a more complete characterization of chloride and pH dependence of O 2 evolution activity than has been previously presented.

Fe(II) oxidation during acid mine drainage neutralization in a pilot-scale Sequencing Batch Reactor.

PubMed

Zvimba, J N; Mathye, M; Vadapalli, V R K; Swanepoel, H; Bologo, L

2013-01-01

This study investigated Fe(II) oxidation during acid mine drainage (AMD) neutralization using CaCO3 in a pilot-scale Sequencing Batch Reactor (SBR) of hydraulic retention time (HRT) of 90 min and sludge retention time (SRT) of 360 min in the presence of air. The removal kinetics of Fe(II), of initial concentration 1,033 ± 0 mg/L, from AMD through oxidation to Fe(III) was observed to depend on both pH and suspended solids, resulting in Fe(II) levels of 679 ± 32, 242 ± 64, 46 ± 16 and 28 ± 0 mg/L recorded after cycles 1, 2, 3 and 4 respectively, with complete Fe(II) oxidation only achieved after complete neutralization of AMD. Generally, it takes 30 min to completely oxidize Fe(II) during cycle 4, suggesting that further optimization of SBR operation based on both pH and suspended solids manipulation can result in significant reduction of the number of cycles required to achieve acceptable Fe(II) oxidation for removal as ferric hydroxide. Overall, complete removal of Fe(II) during AMD neutralization is attractive as it promotes recovery of better quality waste gypsum, key to downstream gypsum beneficiation for recovery of valuables, thereby enabling some treatment-cost recovery and prevention of environmental pollution from dumping of sludge into landfills.

Logistics support of the Japanese Experiment Module by the H-II rocket

NASA Astrophysics Data System (ADS)

Shibato, Yoji; Eto, Takao; Fukushima, Yukio; Takatsuka, Hitoshi

1988-10-01

This paper describes salient design features of the Japanese Experiment Module (JEM), which will be attached to the Space Station. Special attention is given to the logistic support of the JEM (which is planned to become operational in 1990s) by the HOPE orbiter, which will be used for the resupply and the retrieval of the JEM, and the H-II rocket, which will be used to launch the HOPE. The concepts of HOPE and the H-II rocket are discussed together with the estimated logistics requirements of this system. Configuration diagrams are included.

Host regulation of lysogenic decision in bacteriophage lambda: transmembrane modulation of FtsH (HflB), the cII degrading protease, by HflKC (HflA).

PubMed

Kihara, A; Akiyama, Y; Ito, K

1997-05-27

The cII gene product of bacteriophage lambda is unstable and required for the establishment of lysogenization. Its intracellular amount is important for the decision between lytic growth and lysogenization. Two genetic loci of Escherichia coli are crucial for these commitments of infecting lambda genome. One of them, hflA encodes the HflKC membrane protein complex, which has been believed to be a protease degrading the cII protein. However, both its absence and overproduction stabilized cII in vivo and the proposed serine protease-like sequence motif in HflC was dispensable for the lysogenization control. Moreover, the HflKC protein was found to reside on the periplasmic side of the plasma membrane. In contrast, the other host gene, ftsH (hflB) encoding an integral membrane ATPase/protease, is positively required for degradation of cII, since loss of its function stabilized cII and its overexpression accelerated the cII degradation. In vitro, purified FtsH catalyzed ATP-dependent proteolysis of cII and HflKC antagonized the FtsH action. These results, together with our previous finding that FtsH and HflKC form a complex, suggest that FtsH is the cII degrading protease and HflKC is a modulator of the FtsH function. We propose that this transmembrane modulation differentiates the FtsH actions to different substrate proteins such as the membrane-bound SecY protein and the cytosolic cII protein. This study necessitates a revision of the prevailing view about the host control over lambda lysogenic decision.

Novel hexadentate and pentadentate chelators for 64Cu-based targeted PET imaging

PubMed Central

Sin, Inseok; Kang, Chisoo; Bandara, Nilantha; Sun, Xiang; Zhong, Yongliang; Rogers, Buck E.; Chong, Hyun-Soon

2014-01-01

A series of new hexadentate and pentadentate chelators were designed and synthesized as chelators of 64Cu. The new pentadentate and hexadentate chelators contain different types of donor groups and are expected to form neutral complexes with Cu(II). The new chelators were evaluated for complex kinetics and stability with 64Cu. The new chelators instantly bound to 64Cu with high labeling efficiency and maximum specific activity. All 64Cu-radiolabeled complexes in human serum remained intact for 2 days. The 64Cu-radiolabeled complexes were further challenged by EDTA in a 100-fold molar excess. Among the 64Cu-radiolabeled complexes evaluated, 64Cu-complex of the new chelator E was well tolerated with a minimal transfer of 64Cu to EDTA. 64Cu-radiolabeled complex of the new chelator E was further evaluated for biodistribution studies using mice and displayed rapid blood clearance and low organ uptake. 64Cu-chelator E produced a favorable in vitro and in vivo complex stability profiles comparable to 64Cu complex of the known hexadentate NOTA chelator. The in vitro and in vivo data highlight strong potential of the new chelator E for targeted PET imaging application. PMID:24657050

Star Formation Activity in the Galactic H II Region Sh2-297

NASA Astrophysics Data System (ADS)

Mallick, K. K.; Ojha, D. K.; Samal, M. R.; Pandey, A. K.; Bhatt, B. C.; Ghosh, S. K.; Dewangan, L. K.; Tamura, M.

2012-11-01

We present a multiwavelength study of the Galactic H II region Sh2-297, located in the Canis Major OB1 complex. Optical spectroscopic observations are used to constrain the spectral type of ionizing star HD 53623 as B0V. The classical nature of this H II region is affirmed by the low values of electron density and emission measure, which are calculated to be 756 cm-3 and 9.15 × 105 cm-6 pc using the radio continuum observations at 610 and 1280 MHz, and Very Large Array archival data at 1420 MHz. To understand local star formation, we identified the young stellar object (YSO) candidates in a region of area ~7farcm5 × 7farcm5 centered on Sh2-297 using grism slitless spectroscopy (to identify the Hα emission line stars), and near infrared (NIR) observations. NIR YSO candidates are further classified into various evolutionary stages using color-color and color-magnitude (CM) diagrams, giving 50 red sources (H - K > 0.6) and 26 Class II-like sources. The mass and age range of the YSOs are estimated to be ~0.1-2 M ⊙ and 0.5-2 Myr using optical (V/V-I) and NIR (J/J-H) CM diagrams. The mean age of the YSOs is found to be ~1 Myr, which is of the order of dynamical age of 1.07 Myr of the H II region. Using the estimated range of visual extinction (1.1-25 mag) from literature and NIR data for the region, spectral energy distribution models have been implemented for selected YSOs which show masses and ages to be consistent with estimated values. The spatial distribution of YSOs shows an evolutionary sequence, suggesting triggered star formation in the region. The star formation seems to have propagated from the ionizing star toward the cold dark cloud LDN1657A located west of Sh2-297.

Overexpression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo.

PubMed

Mahmoud, Salma; Ibrahim, Mohammed; Hago, Ahmed; Huang, Yuhong; Wei, Yuanyi; Zhang, Jun; Zhang, Qingqing; Xiao, Yu; Wang, Jingwen; Adam, Munkaila; Guo, Yu; Wang, Li; Zhou, Shuting; Xin, Boyi; Xuan, Wei; Tang, Jianwu

2016-11-15

Lymphatic vessels function as transport channels for tumor cells to metastasize from the primary site into the lymph nodes. In this experiment we evaluated the effect of Sulfatase-1 (Sulf-1) on metastasis by upregulating it in murine hepatocarcinoma cell line Hca-F with high lymph node metastatic rate of >75%. The study in vitro showed that up regulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 down regulated Mesothelin (Msln) at both the protein and mRNA levels. The experiment in vivo further showed that up-regulation of Sulf-1 with the attendant downregulation of mesothelin delayed tumor growth and decreased lymph node metastasis. In conclusion, our findings show that Sulf-1 is an important tumor suppressor gene in hepatocellular carcinoma (HCC), and its over expression downregulates Msln and results in a decrease in HCC cell proliferation, migration, invasion, and lymphatic metastasis. This functional relationship between Sulf-1 and Msln could be exploited for the development of a novel liver cancer therapy.

Overexpression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo

PubMed Central

Mahmoud, Salma; Ibrahim, Mohammed; Hago, Ahmed; Huang, Yuhong; Wei, Yuanyi; Zhang, Jun; Zhang, Qingqing; Xiao, Yu; Wang, Jingwen; Adam, Munkaila; Guo, Yu; Wang, Li; Zhou, Shuting; Xin, Boyi; Xuan, Wei; Tang, Jianwu

2016-01-01

Lymphatic vessels function as transport channels for tumor cells to metastasize from the primary site into the lymph nodes. In this experiment we evaluated the effect of Sulfatase-1 (Sulf-1) on metastasis by upregulating it in murine hepatocarcinoma cell line Hca-F with high lymph node metastatic rate of >75%. The study in vitro showed that upregulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 downregulated Mesothelin (Msln) at both the protein and mRNA levels. The experiment in vivo further showed that up-regulation of Sulf-1 with the attendant downregulation of mesothelin delayed tumor growth and decreased lymph node metastasis. In conclusion, our findings show that Sulf-1 is an important tumor suppressor gene in hepatocellular carcinoma (HCC), and its overexpression downregulates Msln and results in a decrease in HCC cell proliferation, migration, invasion, and lymphatic metastasis. This functional relationship between Sulf-1 and Msln could be exploited for the development of a novel liver cancer therapy. PMID:27626699

Cometary compact H II regions are stellar-wind bow shocks

NASA Technical Reports Server (NTRS)

Van Buren, Dave; Mac Low, Mordecai-Mark; Wood, Douglas O. S.; Churchwell, ED

1990-01-01

Comet-shaped H II regions, like G34.3 + 0.2, are easily explained as bow shocks created by wind-blowing massive stars moving supersonically through molecular clouds. The required velocities of the stars through dense clumps are less than about 10 km/s, comparable to the velocity dispersion of stars in OB associations. An analytic model of bow shocks matches the gross characteristics seen in the radio continuum and the velocity structure inferred from hydrogen recombination and molecular line observations. The champagne flow model cannot account for these structures. VLBI observations of masers associated with the shells of cometary compact H II regions should reveal tailward proper motions predominantly parallel to the shell, rather than perpendicular. It is predicted that over a decade baseline, high signal-to-noise VLA observations of this class of objects will show headward pattern motion in the direction of the symmetry axis, but not expansion. Finally, shock-generated and coronal infrared lines are also predicted.

42 CFR 64a.101 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Purpose. 64a.101 Section 64a.101 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING OBLIGATED SERVICE FOR MENTAL HEALTH TRAINEESHIPS § 64a.101 Purpose. This part establishes requirements to...

42 CFR 64a.101 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Purpose. 64a.101 Section 64a.101 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING OBLIGATED SERVICE FOR MENTAL HEALTH TRAINEESHIPS § 64a.101 Purpose. This part establishes requirements to...

42 CFR 64a.101 - Purpose.