Mono- and di-bromo platinum(IV) prodrugs via oxidative bromination: synthesis, characterization, and cytotoxicity.

PubMed

Xu, Zoufeng; Wang, Zhigang; Yiu, Shek-Man; Zhu, Guangyu

2015-12-14

Platinum(IV)-based anticancer prodrugs have attracted much attention due to their relative inertness under physiological conditions, being activated inside cells, and their capacity for functionalization with a variety of small-molecule or macromolecule moieties. Novel asymmetric platinum(IV) compounds synthesized through expedient and unique methods are desired. Here we utilize N-bromosuccinimide (NBS) and carry out oxidative bromination on platinum(II) drugs, namely cisplatin, carboplatin, and oxaliplatin, to obtain asymmetric and mono-bromo platinum(IV) prodrugs. Different solvents are used to obtain various compounds, and the compounds are further functionalized. Di-bromo compounds are also obtained through NBS-directed oxidative bromination in ethanol. The crystal structures of representative compounds are discussed, and the reduction potentials of some compounds are examined. A cytotoxicity test shows that the mono- and di-bromo platinum(IV) compounds are active against human ovarian cancer cells. Our study enriches the family of asymmetric platinum(IV) prodrugs and provides with a convenient strategy to obtain brominated platinum(IV) complexes.

Evidence for S(IV) compounds other than dissolved SO2 in precipitation

NASA Astrophysics Data System (ADS)

Chapman, E. G.

1986-12-01

Preliminary results from a study characterizing S(IV) compounds in wintertime precipitation samples indicate that bisulfite ion is not the primary form of S(IV), as previously believed. By employing a differencing technique that permits estimation of both SO2 aq and non-SO2 aq compound concentrations, it was found that, on an average, more than 60 percent of the total S(IV) is present in a form other than dissolved SO2. Formaldehyde analyses on selected samples suggest that the most likely form of the S(IV) is hydroxymethanesulfonate, although other aldehyde-S(IV) adducts may also be present. The non-SO2 compounds represented a significant portion of the total sulfur concentrations present in the samples analyzed, with contributions ranging from 1.2 to 27 percent. Because of the stability and oxidation resistance of these S(IV) compounds, sulfur deposition estimates that are based solely on sulfate measurements are undoubtedly low, especially for wintertime events. The study underscores the importance of S(IV) compounds in atmospheric scavenging processes.

Unusual kinetics of poly(ethylene glycol) oxidation with cerium(IV) ions in sulfuric acid medium and implications for copolymer synthesis.

PubMed

Szymański, Jan K; Temprano-Coleto, Fernando; Pérez-Mercader, Juan

2015-03-14

The cerium(IV)-alcohol couple in an acidic medium is an example of a redox system capable of initiating free radical polymerization. When the alcohol has a polymeric nature, the outcome of such a process is a block copolymer, a member of a class of compounds possessing many useful properties. The most common polymer with a terminal -OH group is poly(ethylene glycol) (PEG); however, the detailed mechanism of its reaction with cerium(IV) remains underexplored. In this paper, we report our findings for this reaction based on spectrophotometric measurements and kinetic modeling. We find that both the reaction order and the net rate constant for the oxidation process depend strongly on the nature of the acidic medium used. In order to account for the experimental observations, we postulate that protonation of PEG decreases its affinity for some of the cerium(IV)-sulfate complexes formed in the system.

Treatment burden in patients with at least one class IV or V CFTR mutation.

PubMed

Dewulf, Jonas; Vermeulen, François; Wanyama, Simeon; Thomas, Muriel; Proesmans, Marijke; Dupont, Lieven; De Boeck, Kris

2015-12-01

CFTR mutations are grouped according to disease-causing mechanism. Several studies demonstrated that patients having at least one mutation of class IV/V, present with a milder phenotype, but little is known about their relative treatment burden. We compared treatment burden between patients with two class I, II, or III mutations and patients with at least one mutation of class IV/V in the 2010 database of the Belgian CF Registry. We calculated a "Treatment Burden Index" (TBI) by assigning long term therapies to categories low, medium and high intensity, for differential weighing in the total score. There were 779 patients with two known class I/II/III mutations and 94 patients with at least one class IV/V mutation. Compared to class I/II/III, class IV/V patients had a lower median number of clinic visits (4 vs. 5; P < 0.001), a lower risk of hospitalization (24.7% vs. 50.8%; P < 0.001) and intravenous antibiotic treatment (23.5% vs. 46.0%; P < 0.001) and a lower median TBI (6 vs. 9; P < 0.001). These differences remained significant when only class IV/V patients with pancreatic insufficiency (n = 31) were considered. This study clearly demonstrates the significantly lower treatment burden in patients with CF and at least one class IV/V mutation compared to patients with two class I/II/III mutations and contributes to providing better individual counseling at time of diagnosis. © 2015 Wiley Periodicals, Inc.

Mediated electrochemical oxidation (MEO) process: a study on nonylphenol ethoxylates (NPE) oxidation in batch mode using cerium (IV) oxidant

NASA Astrophysics Data System (ADS)

Setiyanto, H.; Adyatmika, I. M.; Syaifullah, M. M.; Zulfikar, M. A.; Buchari

2018-05-01

Nonylphenol ethoxylate (NPE-10) is one type of non-ionic surfactants from the class of alkylphenol ethoxylate (APE). This compound is already tightened their use in European Union countries. However, these surfactants are still used widely in Indonesia because the price is relatively cheap. Consequently, these compounds can accumulate in aquatic environments. NPE-10 can disrupt aquatic ecosystems. This study aimed to describe the electro-oxidation process of NPE-10 based on the parameters of a potential difference, concentration of NPE-10, concentration of Ce (III), and oxidation time. The result of oxidation NPE-10 was measured by the amount of current generated from voltammetry technique. Studies of cyclic voltammetry using carbon paste electrodes illustrates the potential value of the oxidation of Ce (III) / Ce (IV) of 1.25 V and the reduction potential value of Ce (IV) / Ce (III) of 1.192 V. NPE-10 are electroactive irreversible because it only provides the potential value of oxidation at 1.44 V. Percent of total degradation of 84.96% was obtained at electro-oxidation of 500 ppm NPE-10 by the addition of 0.015 M Ce (III) for 90 minutes at 0.2 M H2SO4and the use of potential of 6 V.

Novel N-substituted aminobenzamide scaffold derivatives targeting the dipeptidyl peptidase-IV enzyme.

PubMed

Al-Balas, Qosay A; Sowaileh, Munia F; Hassan, Mohammad A; Qandil, Amjad M; Alzoubi, Karem H; Mhaidat, Nizar M; Almaaytah, Ammar M; Khabour, Omar F

2014-01-01

The dipeptidyl peptidase-IV (DPP-IV) enzyme is considered a pivotal target for controlling normal blood sugar levels in the body. Incretins secreted in response to ingestion of meals enhance insulin release to the blood, and DPP-IV inactivates these incretins within a short period and stops their action. Inhibition of this enzyme escalates the action of incretins and induces more insulin to achieve better glucose control in diabetic patients. Thus, inhibition of this enzyme will lead to better control of blood sugar levels. In this study, computer-aided drug design was used to help establish a novel N-substituted aminobenzamide scaffold as a potential inhibitor of DPP-IV. CDOCKER software available from Discovery Studio 3.5 was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the DPP-IV enzyme. The designed compounds were synthesized and tested against a DPP-IV enzyme kit provided by Enzo Life Sciences. The synthesized compounds were characterized using proton and carbon nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and determination of melting point. Sixty-nine novel compounds having an N-aminobenzamide scaffold were prepared, with full characterization. Ten of these compounds showed more in vitro activity against DPP-IV than the reference compounds, with the most active compounds scoring 38% activity at 100 μM concentration. The N-aminobenzamide scaffold was shown in this study to be a valid scaffold for inhibiting the DPP-IV enzyme. Continuing work could unravel more active compounds possessing the same scaffold.

In vitro-in vivo correlation strategy applied to an immediate-release solid oral dosage form with a biopharmaceutical classification system IV compound case study.

PubMed

Bredael, Gerard M; Bowers, Niya; Boulineau, Fabien; Hahn, David

2014-07-01

The ability to predict in vivo response of an oral dosage form based on an in vitro technique has been a sought after goal of the pharmaceutical scientist. Dissolution testing that demonstrates discrimination to various critical formulations or process attributes provides a sensitive quality check that may be representative or may be overpredictive of potential in vivo changes. Dissolution methodology with an established in vitro-in vivo relationship or correlation may provide the desired in vivo predictability. To establish this in vitro-in vivo link, a clinical study must be performed. In this article, recommendations are given in the selection of batches for the clinical study followed by potential outcome scenarios. The investigation of a Level C in vitro-in vivo correlation (IVIVC), which is the most common correlation for immediate-release oral dosage forms, is presented. Lastly, an IVIVC case study involving a biopharmaceutical classification system class IV compound is presented encompassing this strategy and techniques. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

In Vitro Test for Potential Inhibitors of Plasmepsin II and IV as Anti-malarial Agents

NASA Astrophysics Data System (ADS)

Kang, Hee-Kyoung; Hwang, Soon-Wook; Kim, Do-Won; Breton, Vincent; Kim, Doman

Plasmepsins (PMs) are involved in the degradation of host cell hemoglobin during malaria infection. PM II and IV initiate the degradative process, and have been suggested as attractive targets for treatment of malaria. Previously, 30 compounds were identified by post-processing the results of a large docking screen of commercially available compounds using an automated procedure based on molecular dynamics refinement and binding free-energy estimation using MM-PBSA and MM-GBSA (Degliesposti et al., 2009). Presently, these were experimentally validated using an inhibition assay based on fluorescence resonance energy transfer (FRET) and hemoglobin substrate degradation. Remarkably, 26 of the 30 tested compounds were active as PM II inhibitors, with FRET IC50 values ranging from 4.3 nM to 1.8 μM. Also, IC50 value for PM IV inhibition ranged from 9.34 nM to 83 μM and the best inhibitor among the 30 compounds was compound 7. Hemoglobin degradation by recombinant PM II and IV was completely inhibited by 100 μM of compound 7. The newly identified compounds, and one in particular (compound 7), can inhibit PM II and IV activity and hemoglobin degradation in vitro. These experiments suggest an overall approach in the design of powerful and selective PM II and IV inhibitors.

Synthesis of novel carbazole derived substances using some organoboron compounds by palladium catalyzed and investigation of its semiconductor device characteristics

NASA Astrophysics Data System (ADS)

Gorgun, Kamuran; Caglar, Yasemin

2018-04-01

Carbazole compounds in particular represent one of the most intensely used and studied class of semiconducting materials. In this study, considering the information given in the literature the Ullman and Suzuki-Miyaura coupling reaction were carried out using carbazole, 1,4-dibromobenzene and pyrene-1-boronic acid. The synthesized carbazole derivatives are characterized by 1H NMR and elemental analysis. The spectroscopic and thermal properties of the synthesized novel carbazole derivative 9-(4-(pyren-4-yl)phenyl)-9H-carbazole (Cz-py) were investigated. And also, the n-Si/p-Cz:py heterojunction diode was fabricated. The electrical properties of this diode were characterized by current-voltage (I-V) and capacitance-voltage (C-V) measurements.

Tricyclic GyrB/ParE (TriBE) Inhibitors: A New Class of Broad-Spectrum Dual-Targeting Antibacterial Agents

PubMed Central

Tari, Leslie W.; Li, Xiaoming; Trzoss, Michael; Bensen, Daniel C.; Chen, Zhiyong; Lam, Thanh; Zhang, Junhu; Lee, Suk Joong; Hough, Grayson; Phillipson, Doug; Akers-Rodriguez, Suzanne; Cunningham, Mark L.; Kwan, Bryan P.; Nelson, Kirk J.; Castellano, Amanda; Locke, Jeff B.; Brown-Driver, Vickie; Murphy, Timothy M.; Ong, Voon S.; Pillar, Chris M.; Shinabarger, Dean L.; Nix, Jay; Lightstone, Felice C.; Wong, Sergio E.; Nguyen, Toan B.; Shaw, Karen J.; Finn, John

2013-01-01

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models. PMID:24386374

40 CFR 147.650 - State-administrative program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CONTROL PROGRAMS Idaho § 147.650 State-administrative program—Class I, II, III, IV, and V wells. The UIC program for Class I, II, III, IV, and V wells in the State of Idaho, other than those on Indian lands, is the program administered by the Idaho Department of Water Resources, approved by EPA pursuant to...

E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, is a novel, selective and competitive dipeptidyl peptidase-IV inhibitor.

PubMed

Yasuda, Nobuyuki; Nagakura, Tadashi; Inoue, Takashi; Yamazaki, Kazuto; Katsutani, Naruo; Takenaka, Osamu; Clark, Richard; Matsuura, Fumiyoshi; Emori, Eita; Yoshikawa, Seiji; Kira, Kazunobu; Ikuta, Hironori; Okada, Toshimi; Saeki, Takao; Asano, Osamu; Tanaka, Isao

2006-10-24

Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a useful new class of anti-diabetic agent. The aim of the present study is to characterize the in vitro and in vivo profile of E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, which is a novel imidazopyridazinone-derived DPP-IV inhibitor. E3024 inhibited recombinant human and mouse DPP-IV with IC50 values of approximately 100 nM. E3024 inhibited DPP-IV in human, mouse, rat and canine plasma with IC50 values of 140 to 400 nM. In contrast, E3024 did not inhibit DPP-8 or DPP-9 activity. Kinetic analysis indicated that E3024 is a competitive DPP-IV inhibitor. In Zucker fa/fa rats, E3024 (1 mg/kg) reduced glucose excursion after glucose load, with increases in plasma insulin and active glucagon-like peptide-1 levels. In fasted rats, this compound did not cause hypoglycemia. In a rat 4-week toxicological study, no notable changes were found at doses up to 750 mg/kg. The present preclinical studies indicate that E3024 is a novel selective DPP-IV inhibitor with anti-diabetic effects and a good safety profile.

Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in Enhancing Solubility and Permeability of BCS Class II and BCS Class IV Drugs.

PubMed

Abdelkader, Hamdy; Fathalla, Zeinab

2018-06-18

The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need. In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed. Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays. Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, P app for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. P app for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at 'the door step' of absorption sites.

40 CFR 147.2200 - State-administered program-Class I, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the in situ combustion of coal are regulated by the Rail Road Commission of Texas under a separate UIC... program for Class I, III, IV, and V wells in the State of Texas, except for those wells on Indian lands... (SDWA). Notice of the original approval for Class I, III, IV, and V wells was published in the Federal...

40 CFR 147.2200 - State-administered program-Class I, III, IV, and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the in situ combustion of coal are regulated by the Rail Road Commission of Texas under a separate UIC... program for Class I, III, IV, and V wells in the State of Texas, except for those wells on Indian lands... (SDWA). Notice of the original approval for Class I, III, IV, and V wells was published in the Federal...

Mutation spectrum of β-globin gene in thalassemia patients at Hasan Sadikin Hospital - West Java Indonesia.

PubMed

Maskoen, Ani Melani; Rahayu, Nurul S; Reniarti, Lelani; Susanah, Susi; Laksono, Bremmy; Fauziah, Prima Nanda; Zada, Almira; Hidayat, Dadang S

2017-12-30

Thalassemia is the most common hereditary haemolytic anemia in Southeast Asia, in which Indonesia is among countries that are at a high risk for thalassemia. It has been reported that mutation in the beta-globin gene is responsible in severe Thalassemia. However, the spectrum of beta-globin gene mutations in Indonesian population varies in different regions . Thus, this study aimed to identify the most prevalent mutation of Thalassemia patients from the Hasan Sadikin Hospital, Bandung, using this as a reference hospital for Thalassemia in West Java. The three most prevalent mutations of beta globin (IVS1nt5, Cd26 (HbE), and IVS1nt1), were conducted in the beginning of this study. Mutations of 291 samples were detected by PCR-RFLP in the Molecular Genetic Laboratory, Faculty of Medicine Universitas Padjadjaran, Bandung. The prevalence of the beta globin gene mutation types were 47.4% IVS1nt5 homozygote, 9.9% compound heterozygote IVS1nt5/HbE, 5.4% compound heterozygote IVS1nt5/IVS1nt1, 1.4% compound heterozygote HbE/IVS1nt1, 1% HbE homozygote, 14.4% Compound heterzygote IVS1nt5/… (no paired mutation), 2.06% compound heterozygote HbE/… (no paired mutation), 1.3% compound heterozygote IVS1nt1/… (no paired mutation), and 7 samples were unidentified. The thalassemia mutation IVS1nt5 homozygote is the most common mutation found in Thalassemia patients at Hasan Sadikin Hospital, Bandung. The samples with unidentified results might carry mutations other than the three that are observed in the present study.

Class IV polyhydroxyalkanoate (PHA) synthases and PHA-producing Bacillus.

PubMed

Tsuge, Takeharu; Hyakutake, Manami; Mizuno, Kouhei

2015-08-01

This review highlights the recent investigations of class IV polyhydroxyalkanoate (PHA) synthases, the newest classification of PHA synthases. Class IV synthases are prevalent in organisms of the Bacillus genus and are composed of a catalytic subunit PhaC (approximately 40 kDa), which has a PhaC box sequence ([GS]-X-C-X-[GA]-G) at the active site, and a second subunit PhaR (approximately 20 kDa). The representative PHA-producing Bacillus strains are Bacillus megaterium and Bacillus cereus; the nucleotide sequence of phaC and the genetic organization of the PHA biosynthesis gene locus are somewhat different between these two strains. It is generally considered that class IV synthases favor short-chain-length monomers such as 3-hydroxybutyrate (C4) and 3-hydroxyvalerate (C5) for polymerization, but can polymerize some unusual monomers as minor components. In Escherichia coli expressing PhaRC from B. cereus YB-4, the biosynthesized PHA undergoes synthase-catalyzed alcoholytic cleavage using endogenous and exogenous alcohols. This alcoholysis is thought to be shared among class IV synthases, and this reaction is useful not only for the regulation of PHA molecular weight but also for the modification of the PHA carboxy terminus. The novel properties of class IV synthases will open up the possibility for the design of new PHA materials.

Nutrient-dependent increased dendritic arborization of somatosensory neurons.

PubMed

Watanabe, Kaori; Furumizo, Yuki; Usui, Tadao; Hattori, Yukako; Uemura, Tadashi

2017-01-01

Suboptimal nutrition imposes developmental constraints on infant animals, which marshal adaptive responses to eventually become mature adults. Such responses are mounted at multiple levels from systemic to cellular. At the cellular level, the underlying mechanisms of cell proliferation control have been intensively studied. However, less is known about how growth of postmitotic and morphologically complex cells, such as neurons, is controlled by nutritional status. We address this question using Class I and Class IV dendritic arborization neurons in Drosophila larvae. Class IV neurons have been shown to sense nociceptive thermal, mechanical and light stimuli, whereas Class I neurons are proprioceptors. We reared larvae on diets with different protein and carbohydrate content throughout larval stages and examined how morphologies of Class I or Class IV neurons were affected. Dendritic arbors of Class IV neurons became more complex when larvae were reared on a low-yeast diet, which contains lower amounts of amino acids and other ingredients, compared to a high-yeast diet. In contrast, such low-yeast-dependent hyperarborization was not seen in Class I neurons. The physiological and metabolic implications of the hyperarborization phenotype are discussed in relation to a recent hypothesis that Class IV neurons sense protein-deficient stress and to our characterization of how the dietary yeast contents impacted larval metabolism. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

βIV Spectrinopathies Cause Profound Intellectual Disability, Congenital Hypotonia, and Motor Axonal Neuropathy.

PubMed

Wang, Chih-Chuan; Ortiz-González, Xilma R; Yum, Sabrina W; Gill, Sara M; White, Amy; Kelter, Erin; Seaver, Laurie H; Lee, Sansan; Wiley, Graham; Gaffney, Patrick M; Wierenga, Klaas J; Rasband, Matthew N

2018-06-07

βIV spectrin links ankyrinG (AnkG) and clustered ion channels at axon initial segments (AISs) and nodes of Ranvier to the axonal cytoskeleton. Here, we report bi-allelic pathogenic SPTBN4 variants (three homozygous and two compound heterozygous) that cause a severe neurological syndrome that includes congenital hypotonia, intellectual disability, and motor axonal and auditory neuropathy. We introduced these variants into βIV spectrin, expressed these in neurons, and found that 5/7 were loss-of-function variants disrupting AIS localization or abolishing phosphoinositide binding. Nerve biopsies from an individual with a loss-of-function variant had reduced nodal Na + channels and no nodal KCNQ2 K + channels. Modeling the disease in mice revealed that although ankyrinR (AnkR) and βI spectrin can cluster Na + channels and partially compensate for the loss of AnkG and βIV spectrin at nodes of Ranvier, AnkR and βI spectrin cannot cluster KCNQ2- and KCNQ3-subunit-containing K + channels. Our findings define a class of spectrinopathies and reveal the molecular pathologies causing nervous-system dysfunction. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Low Temperature Structure and Properties of Graphite Lamellar Compounds.

DTIC Science & Technology

1984-01-01

IV.RESULTS ACCEPTOR COMPOUNDS IV.1. Compound Syntheses All compounds were prepared by directly reacting the halide vapour with pyrographite (HOPG) in the...1983 "Caractdrisation chimique et struc- turale des compos~s graphite-trichlorure de gallium Synth. Met. 7, 125. Onn D.G., Foley G.M.T. & Fischer

Antibacterial and DNA cleavage activity of carbonyl functionalized N-heterocyclic carbene-silver(I) and selenium compounds

NASA Astrophysics Data System (ADS)

Haque, Rosenani A.; Iqbal, Muhammad Adnan; Mohamad, Faisal; Razali, Mohd R.

2018-03-01

The article describes syntheses and characterizations of carbonyl functionalized benzimidazolium salts, I-IV. While salts I-III are unstable at room temperature, salt IV remained stable and was further utilised to form N-heterocyclic carbene (NHC) compounds of silver(I), V and VI, and selenium compound, VII respectively. Compounds IV-VII were tested for their antibacterial potential against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Salt IV shows a very low inhibition potential (minimum inhibitory concentration, MIC 500 μg/mL) compared to the respective silver(I)-NHC, V and VI (MIC 31.25 μg/mL against both, E. coli and S. aureus) and selenium compound, VII (MIC 125 μg/mL against E. coli and 62.50 μg/mL against S. aureus). In DNA cleavage abilities, all the test compounds cleave DNA in which the VII cleaves the DNA at the faster rate. Meanwhile, the silver(I)-NHC complexes V and VI act at the same mode and pattern of DNA cleavage while VII is similar to IV.

Clinical expression of patients with the D1152H CFTR mutation.

PubMed

Terlizzi, Vito; Carnovale, Vincenzo; Castaldo, Giuseppe; Castellani, Carlo; Cirilli, Natalia; Colombo, Carla; Corti, Fabiola; Cresta, Federico; D'Adda, Alice; Lucarelli, Marco; Lucidi, Vincenzina; Macchiaroli, Annamaria; Madarena, Elisa; Padoan, Rita; Quattrucci, Serena; Salvatore, Donatello; Zarrilli, Federica; Raia, Valeria

2015-07-01

Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Diverse anisotropy of phonon transport in two-dimensional group IV-VI compounds: A comparative study

NASA Astrophysics Data System (ADS)

Qin, Guangzhao; Qin, Zhenzhen; Fang, Wu-Zhang; Zhang, Li-Chuan; Yue, Sheng-Ying; Yan, Qing-Bo; Hu, Ming; Su, Gang

2016-05-01

New classes of two-dimensional (2D) materials beyond graphene, including layered and non-layered, and their heterostructures, are currently attracting increasing interest due to their promising applications in nanoelectronics, optoelectronics and clean energy, where thermal transport is a fundamental physical parameter. In this paper, we systematically investigated the phonon transport properties of the 2D orthorhombic group IV-VI compounds of GeS, GeSe, SnS and SnSe by solving the Boltzmann transport equation (BTE) based on first-principles calculations. Despite their similar puckered (hinge-like) structure along the armchair direction as phosphorene, the four monolayer compounds possess diverse anisotropic properties in many aspects, such as phonon group velocity, Young's modulus and lattice thermal conductivity (κ), etc. Especially, the κ along the zigzag and armchair directions of monolayer GeS shows the strongest anisotropy while monolayer SnS and SnSe show almost isotropy in phonon transport. The origin of the diverse anisotropy is fully studied and the underlying mechanism is discussed in details. With limited size, the κ could be effectively lowered, and the anisotropy could be effectively modulated by nanostructuring, which would extend the applications to nanoscale thermoelectrics and thermal management. Our study offers fundamental understanding of the anisotropic phonon transport properties of 2D materials, and would be of significance for further study, modulation and applications in emerging technologies.

Heterometallic [Mn5-Ln4] single-molecule magnets with high anisotropy barriers.

PubMed

Mereacre, Valeriu; Ako, Ayuk M; Clérac, Rodolphe; Wernsdorfer, Wolfgang; Hewitt, Ian J; Anson, Christopher E; Powell, Annie K

2008-01-01

The reaction of [Mn6O2(Piv)(10)(4-Me-py)(2.5)(PivH)(1.5)] (1) (py: pyridine, Piv: pivilate) with N-methyldiethanolamine (mdeaH2) and Ln(NO3)3 x 6 H2O in MeCN leads to a series of nonanuclear compounds [Mn5Ln4(O)6(mdea)2(mdeaH)2(Piv)6(NO3)4(H2O)2]2 MeCN (Ln=Tb(III) (2), Dy(III) (3), Ho(III) (4), Y(III) (5)). Single-crystal X-ray diffraction shows that compounds 2-5 are isostructural, with the central core composed of two distorted {Mn(IV)Mn(III)Ln2O4} cubanes sharing a Mn(IV) vertex, representing a new heterometallic 3d-4f motif for this class of ligand. The four new compounds display single-molecule magnet (SMM) behaviour, which is modulated by the lanthanide ion used. Moreover, the values found for Delta(eff) and tau(o) for 3 of 38.6 K and 3.0 x 10(-9) s respectively reveal that the complex 3 exhibits the highest energy barrier recorded so far for 3d-4f SMMs. The slow relaxation of the magnetisation for 3 was confirmed by mu-SQUID measurements on an oriented single crystal and the observation of M versus H hysteresis loops below 1.9 K.

Infrared and reflectron time-of-flight mass spectroscopic analysis of methane (CH4)-carbon monoxide (CO) ices exposed to ionization radiation--toward the formation of carbonyl-bearing molecules in extraterrestrial ices.

PubMed

Kaiser, Ralf I; Maity, Surajit; Jones, Brant M

2014-02-28

Ice mixtures of methane and carbon monoxide were exposed to ionizing radiation in the form of energetic electrons at 5.5 K to investigate the formation of carbonyl bearing molecules in extraterrestrial ices. The radiation induced chemical processing of the mixed ices along with their isotopically labeled counterparts was probed online and in situ via infrared spectroscopy (solid state) aided with reflectron time-of-flight mass spectrometry (ReTOFMS) coupled to single photon photoionization (PI) at 10.49 eV (gas phase). Deconvolution of the carbonyl absorption feature centered at 1727 cm(-1) in the processed ices and subsequent kinetic fitting to the temporal growth of the newly formed species suggests the formation of acetaldehyde (CH3CHO) together with four key classes of carbonyl-bearing molecules: (i) alkyl aldehydes, (ii) alkyl ketones, (iii) α,β-unsaturated ketones/aldehydes and (iv) α,β,γ,δ-unsaturated ketones/α,β-dicarbonyl compounds in keto-enol form. The mechanistical studies indicate that acetaldehyde acts as the key building block of higher aldehydes (i) and ketones (ii) with unsaturated ketones/aldehydes (iii) and/or α,β-dicarbonyl compounds (iv) formed from the latter. Upon sublimation of the newly synthesized molecules, ReTOFMS together with isotopic shifts of the mass-to-charge ratios was exploited to identify eleven product classes containing molecules with up to six carbon atoms, which can be formally derived from C1-C5 hydrocarbons incorporating up to three carbon monoxide building blocks. The classes are (i) saturated aldehydes/ketones, (ii) unsaturated aldehydes/ketones, (iii) doubly unsaturated aldehydes/ketones, (iv) saturated dicarbonyls (aldehydes/ketones), (v) unsaturated dicarbonyls (aldehydes/ketones), (vi) saturated tricarbonyls (aldehydes/ketones), molecules containing (vii) one carbonyl - one alcohol (viii), two carbonyls - one alcohol, (ix) one carbonyl - two alcohol groups along with (x) alcohols and (xi) diols. Reaction pathways to synthesize these classes were derived as well. The present experiments provide clear evidence for the formation of key organic molecules--acetaldehyde, acetone, and potentially vinylalcohol--which are among the 15 carbonyl containing organic molecules detected in the interstellar medium. Despite numerous previous experimental investigations probing the effect of ionizing radiation on simple astrophysical ice representatives, our results suggest that more complex organic molecules can be formed in extraterrestrial ices than previously suggested. An outlook on further identification of individual isomers is also presented.

Arylglycerol-γ-Formyl Ester as an Aromatic Ring Cleavage Product of Nonphenolic β-O-4 Lignin Substructure Model Compounds Degraded by Coriolus versicolor†

PubMed Central

Kawai, Shingo; Umezawa, Toshiaki; Higuchi, Takayoshi

1985-01-01

4-Ethoxy-3-methoxyphenylglycerol-γ-formyl ester (compound IV) was identified as a degradation product of both 4-ethoxy-3-methoxyphenylglycerol-β-syringaldehyde ether (compound I) and 4-ethoxy-3-methoxyphenylglycerol-β-2,6-dimethoxyphenyl ether (compound II) by a ligninolytic culture of Coriolus versicolor. An isotopic experiment with a 13C-labeled compound (compound II′) indicated that the formyl group of compound IV was derived from the β-phenoxyl group of β-O-4 dimer as an aromatic ring cleavage fragment. However, compound IV was not formed from 4-ethoxy-3-methoxyphenylglycerol-β-guaiacyl ether (compound III). γ-Formyl arylglycerol (compound IV) could be a precursor of 4-ethoxy-3-methoxyphenylglycerol (compound VI), because 3-(4-ethoxy-3-methoxyphenyl)-1-formyloxy propane (compound VII) was cleaved to give 3-(4-ethoxy-3-methoxyphenyl)-1-propanol (compound VIII) by C. versicolor. 4-Ethoxy-3-methoxyphenylglycerol-β,γ-cyclic carbonate (compound V), previously found as a degradation product of compound III by Phanerochaete chrysosporium (T. Umezawa, and T. Higuchi, FEBS Lett., 25:123-126, 1985), was also identified from the cultures with compound I, II, and III and degraded to give the arylglycerol (compound VI). An isotopic experiment with 13C-labeled compounds II′ and III′ indicated that the carbonate carbon of compound V was derived from the β-phenoxyl groups of β-O-4 substructure. PMID:16346950

Tricyclic GyrB/ParE (TriBE) Inhibitors. A new class of broad-spectrum dual-targeting antibacterial agents

DOE PAGES

Tari, Leslie W.; Li, Xiaoming; Trzoss, Michael; ...

2013-12-26

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. Growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highlymore » conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Moreover, lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.« less

Tricyclic GyrB/ParE (TriBE) Inhibitors. A new class of broad-spectrum dual-targeting antibacterial agents

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

Tari, Leslie W.; Li, Xiaoming; Trzoss, Michael

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. Growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highlymore » conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Moreover, lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.« less

Novel Bacterial Topoisomerase Inhibitors with Potent Broad-Spectrum Activity against Drug-Resistant Bacteria.

PubMed

Charrier, Cédric; Salisbury, Anne-Marie; Savage, Victoria J; Duffy, Thomas; Moyo, Emmanuel; Chaffer-Malam, Nathan; Ooi, Nicola; Newman, Rebecca; Cheung, Jonathan; Metzger, Richard; McGarry, David; Pichowicz, Mark; Sigerson, Ralph; Cooper, Ian R; Nelson, Gary; Butler, Hayley S; Craighead, Mark; Ratcliffe, Andrew J; Best, Stuart A; Stokes, Neil R

2017-05-01

The novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that does not have cross-resistance with the quinolones. Here, we report the evaluation of the in vitro properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of Escherichia coli DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms and Mycobacterium tuberculosis No cross-resistance with fluoroquinolone-resistant Staphylococcus aureus and E. coli isolates was observed. Measured MIC 90 values were 4 and 8 μg/ml against a panel of contemporary multidrug-resistant isolates of Acinetobacter baumannii and E. coli , respectively. In addition, representative compounds exhibited greater antibacterial potency than the quinolones against obligate anaerobic species. Spontaneous mutation rates were low, with frequencies of resistance typically <10 -8 against E. coli and A. baumannii at concentrations equivalent to 4-fold the MIC. Compound-resistant E. coli mutants that were isolated following serial passage were characterized by whole-genome sequencing and carried a single Arg38Leu amino acid substitution in the GyrA subunit of DNA gyrase. Preliminary in vitro safety data indicate that the series shows a promising therapeutic index and potential for low human ether-a-go-go-related gene (hERG) inhibition (50% inhibitory concentration [IC 50 ], >100 μM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable in vitro safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents. Copyright © 2017 American Society for Microbiology.

Crystal chemistry of M{sup II}M′{sup IV}(PO{sub 4}){sub 2} double monophosphates

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

Bregiroux, Damien, E-mail: damien.bregiroux@upmc.fr; Popa, Karin; Wallez, Gilles

2015-10-15

M{sup II}M′{sup IV}(PO{sub 4}){sub 2} compounds have been extensively studied for several decades for their potential applications in the field of several domains such as matrices for actinides conditioning, phosphors etc. In this paper, the relationships between composition and crystal structure of these compounds are established. A review of the various processes used for the synthesis of these compounds is also proposed, as well as their most reported properties. M{sup II}M′{sup IV}(PO{sub 4}){sub 2} structures stem from two different archetypes: the cheralite and the yavapaiite structures, with some exceptions that are also described in this article. The ratio of themore » cations radii appears to be the most relevant parameter. The high ratio between the ionic radii of the divalent and tetravalent cations in yavapaiite derivates results in the ordering of these cations into well-differentiated polyhedra whereas cheralite is the only non-ordered structure encountered for M{sup II}M′{sup IV}(PO{sub 4}){sub 2} compounds. - Graphical abstract: In this paper, the relationships between composition and crystal structure of M{sup II}M′{sup IV}(PO{sub 4}){sub 2} compounds are established. A review of the various processes used for the synthesis of these compounds is also proposed, as well as their most reported properties. - Highlights: • Crystal structure–composition relationships of MIIM′IV(PO4)2 compounds. • Review of the various processes used for the synthesis of these compounds. • Their most reported properties are described and discussed.« less

[Preoperative risk assessment with the ASA classification. A prospective study of morbidity and mortality in various ASA classes in 2,937 patients in general surgery].

PubMed

Menke, H; John, K D; Klein, A; Lorenz, W; Junginger, T

1992-12-01

The value of ASA classification in assessment of perioperative risk, i.e. especially postoperative morbidity, was analyzed prospectively using the data of 2937 patients. The analysis took into account the criteria validity, reliability, and sensitivity. The incidence of post-operative morbidity after elective surgery rose from 3.9% in ASA class I to 36% in ASA class IV. Mortality was 0.6% in ASA class II, whereas 9.3% died in ASA class IV. Morbidity, mortality respectively, after emergency surgery was 10.2% in ASA class II compared to 69% in class IV, mortality 1.4% compared to 21.5%. Differences between the ASA classes were confirmed (p-value < 0.05) considering separate kinds of complications and different periods. Furthermore, ASA classification was a valuable reference to length of stay and severity of necessary therapy at the ICU.

Substituted 4-carboxymethylpyroglutamic acid diamides as potent and selective inhibitors of fibroblast activation protein.

PubMed

Tsai, Ting-Yueh; Yeh, Teng-Kuang; Chen, Xin; Hsu, Tsu; Jao, Yu-Chen; Huang, Chih-Hsiang; Song, Jen-Shin; Huang, Yu-Chen; Chien, Chia-Hui; Chiu, Jing-Huai; Yen, Shih-Chieh; Tang, Hung-Kuan; Chao, Yu-Sheng; Jiaang, Weir-Torn

2010-09-23

Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAP inhibitor is needed in evaluating that FAP as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation. To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SAR studies resulted in a number of FAP inhibitors having IC(50) of <100 nM with excellent selectivity over DPP-IV, DPP-II, DPP8, and DPP9 (IC(50) > 100 μM). Compounds 18a, 18b, and 19 are the only known potent and selective FAP inhibitors, which prompts us to further study the physiological role of FAP.

40 CFR 147.251 - EPA-administered program-Class I, III, IV and V wells and Indian lands.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., IV and V wells and Indian lands. 147.251 Section 147.251 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS California § 147.251 EPA-administered program—Class I, III, IV and V wells and...

40 CFR 147.301 - EPA-administered program-Class I, III, IV, V wells and Indian lands.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., IV, V wells and Indian lands. 147.301 Section 147.301 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Colorado § 147.301 EPA-administered program—Class I, III, IV, V wells and Indian...

40 CFR 147.251 - EPA-administered program-Class I, III, IV and V wells and Indian lands.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., IV and V wells and Indian lands. 147.251 Section 147.251 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS California § 147.251 EPA-administered program—Class I, III, IV and V wells and...

40 CFR 147.301 - EPA-administered program-Class I, III, IV, V wells and Indian lands.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., IV, V wells and Indian lands. 147.301 Section 147.301 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Colorado § 147.301 EPA-administered program—Class I, III, IV, V wells and Indian...

Design and synthesis of aminocoumarin derivatives as DPP-IV inhibitors and anticancer agents.

PubMed

Soni, Rina; Soman, Shubhangi S

2018-09-01

DPP-IV "a moonlighting protein" has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 µM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay. One of the compounds has shown very good anticancer activity with IC 50 value 24 ± 0.1 nM against A549 cell line. Copyright © 2018 Elsevier Inc. All rights reserved.

Behavioral and neurosensory responses of the boll weevil,Anthonomus grandis Boh. (Coleoptera: Curculionidae), to fluorinated analogs of aldehyde components of its pheromone.

PubMed

Dickens, J C; Prestwich, G D; Sun, W C

1991-06-01

Competitive field tests with α-fluorinated analogs of compounds III and IV (III-α-F and IV-α-F, respectively) of the boll weevil,Anthonomus grandis Boh., aggregation pheromone showed these compounds, when combined with the other pheromone components [(±)-I and II], to be as attractive as grandlure [(+)-I, II, and III+IV]. Dose-response curves constructed from electroantennograms of male boll weevils to serial stimulus loads of III, IV, III-α-F, IV-α-F, and the corresponding acyl fluorinated analogs (III-acyl-F and IV-acyl-F) showed the α-fiuorinated analogs to be as active as the pheromone components (threshold=0.1 μg), while the acyl fluorinated analogs had a 10-100 x higher threshold (=1-10 μg). Single-neuron recordings showed that IV neurons and II neurons (Dickens, 1990) responded to IV-α-F and III-α-F, respectively, while IV-acyl-F and III-acyl-F were inactive. Since a previous study showed compounds I, II, and IV to be essential for behavioral responses in the field, it seems likely that the activity of the α-fluorinated analogs observed here is due to the stimulation of IV neurons by IV-α-F as indicated in single neuron recordings.

40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...

40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...

40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...

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.

Phase Transitions in Tetramethylammonium Hexachlorometalate Compounds (TMA) 2MCl 6 (M = U, Np, Pt, Sn, Hf, Zr)

DOE PAGES

Autillo, Matthieu; Wilson, Richard E.

2017-09-22

A study of the phase transitions occurring in tetramethylammonium hexachlorometalate compounds with M = U IV, Np IV, Zr IV, Sn IV, Hf IV and Pt IV were performed using single-crystal X-ray diffraction across the temperature range 120 - 400K. When the crystals were cooled, movement of the octahedral [MCl 6] 2- anions induces a phase transition from Fm3m to Fd3c with a doubling of the unit cell. For the actinide compounds, no correlation between the f-electron configuration and the transition temperature was observed, instead, a correlation between the transition temperatures and both the [MCl 6] 2- anion and themore » TMA cation size is highlighted. Two phase transitions were observed and characterized. The first phase transition occurs with the ordering of the TMA cation and the second from a rotation of the [MCl 6] 2- octahedra. A third phase transition was observed at lower temperatures and was ascribed to a tetragonal distortion of the [MCl 6] 2- anions. Synthesis and study of their deuterated compounds did not show a significant isotope effect. As a result, Raman spectra performed on the protonated and deuterated compounds indicate only weak hydrogen bonding interactions between the TMA cations and the [MCl 6] 2- octahedra.« less

Studies of obtaining and stability in aqueous medium of new complex compounds of Ti(IV) and Zr(IV) used in ecological leather tanning

NASA Astrophysics Data System (ADS)

Crudu, Marian; Sibiescu, Doina; Rosca, Ioan; Sutiman, Daniel; Vizitiu, Mihaela

2009-01-01

In this paper, the study of obtaining new coordination compounds of Ti(IV) and Zr(IV) using as ligand: D,L-β-iso-butyric acid, is presented. Also, the stability of these compounds in aqueous medium is studied. The studies of obtaining and of stability of the new compounds were accomplished in aqueous solutions using methods characteristic for coordination compounds: conductance and pH measurements. The combination ratios and the stability were determined with methods characteristic for studies in solutions. From experimental data resulted that the combination ratio of central metallic atoms with the ligand derived from D,L-β-iso-butyric acid was 1:2. From experimental data resulted that in strong acid and strong basic mediums, the coordination compounds could not be obtained. The optimal stability of the studied compounds is limited between 3-6, pH - values. This fact is in accordance with the conditions of using these compounds in ecological leather tanning. Of great importance is that these compounds were used with very good results in tanning processes of different types of leather. This fact evidenced that the ecological alternative of tanning is better than non-ecological tanning using chrome compounds. The importance of this paper consists in obtaining new coordination compounds that can be used in ecological leather tanning.

Metal based biologically active compounds: design, synthesis, and antibacterial/antifungal/cytotoxic properties of triazole-derived Schiff bases and their oxovanadium(IV) complexes.

PubMed

Chohan, Zahid H; Sumrra, Sajjad H; Youssoufi, Moulay H; Hadda, Taibi B

2010-07-01

A new series of oxovanadium(IV) complexes have been designed and synthesized with a new class of triazole Schiff bases derived from the reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2-carboxaldehyde, pyridine-2-carboxaldehyde and acetyl pyridine-2-carboxaldehyde, respectively. Physical (magnetic susceptibility, molar conductance), spectral (IR, (1)H NMR, (13)C NMR, mass and electronic) and analytical data have established the structures of these synthesized Schiff bases and their oxovanadium(IV) complexes. The Schiff bases, predominantly act as bidentate and coordinate with the vanadium(IV) metal to give a stoichiometric ratio of 1:2 [M:L], forming a general formulae, [M(L-H)(2)] and [M(L)(2)]SO(4) where L = (L(1))-(L(4)) and M = VO(IV) of these complexes in a square-pyramidal geometry. In order to evaluate the biological activity of Schiff bases and to assess the role of vanadium(IV) metal on biological activity, the triazole Schiff bases and their oxovanadium(IV) complexes have been studied for in vitro antibacterial activity against four Gram-negative (Escherichia coli, Shigella flexenari, Pseudomonas aeruginosa, Salmonella typhi) and two Gram-positive (Staphylococcus aureus, Bacillus subtilis) bacterial strains, in vitro antifungal activity against Trichophyton longifucus, Candida albican, Aspergillus flavus, Microscopum canis, Fusarium solani and Candida glaberata. The simple Schiff bases showed weaker to significant activity against one or more bacterial and fungal strains. In most of the cases higher activity was exhibited upon coordination with vanadium(IV) metal. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...

40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...

40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...

Spectroscopic Investigations of Catalase Compound II: Characterization of an Iron(IV) Hydroxide Intermediate in a Non-thiolate-Ligated Heme Enzyme

PubMed Central

Yosca, Timothy H.; Langston, Matthew C.; Krest, Courtney M.; Onderko, Elizabeth L.; Grove, Tyler L.; Livada, Jovan; Green, Michael T.

2018-01-01

We report on the protonation state of Helicobacter pylori catalase compound II. UV/visible, Mössbauer, and X-ray absorption spectroscopies have been used to examine the intermediate from pH 5 to 14. We have determined that HPC-II exists in an iron(IV) hydroxide state up to pH 11. Above this pH, the iron(IV) hydroxide complex transitions to a new species (pKa = 13.1) with Mössbauer parameters that are indicative of an iron(IV)-oxo intermediate. Recently, we discussed a role for an elevated compound II pKa in diminishing the compound I reduction potential. This has the effect of shifting the thermodynamic landscape toward the two-electron chemistry that is critical for catalase function. In catalase, a diminished potential would increase the selectivity for peroxide disproportionation over off-pathway one-electron chemistry, reducing the buildup of the inactive compound II state and reducing the need for energetically expensive electron donor molecules. PMID:27960340

The first crystal structures of a family 19 class IV chitinase: the enzyme from Norway spruce.

PubMed

Ubhayasekera, Wimal; Rawat, Reetika; Ho, Sharon Wing Tak; Wiweger, Malgorzata; Von Arnold, Sara; Chye, Mee-Len; Mowbray, Sherry L

2009-10-01

Chitinases help plants defend themselves against fungal attack, and play roles in other processes, including development. The catalytic modules of most plant chitinases belong to glycoside hydrolase family 19. We report here x-ray structures of such a module from a Norway spruce enzyme, the first for any family 19 class IV chitinase. The bi-lobed structure has a wide cleft lined by conserved residues; the most interesting for catalysis are Glu113, the proton donor, and Glu122, believed to be a general base that activate a catalytic water molecule. Comparisons to class I and II enzymes show that loop deletions in the class IV proteins make the catalytic cleft shorter and wider; from modeling studies, it is predicted that only three N-acetylglucosamine-binding subsites exist in class IV. Further, the structural comparisons suggest that the family 19 enzymes become more closed on substrate binding. Attempts to solve the structure of the complete protein including the associated chitin-binding module failed, however, modeling studies based on close relatives indicate that the binding module recognizes at most three N-acetylglucosamine units. The combined results suggest that the class IV enzymes are optimized for shorter substrates than the class I and II enzymes, or alternatively, that they are better suited for action on substrates where only small regions of chitin chain are accessible. Intact spruce chitinase is shown to possess antifungal activity, which requires the binding module; removing this module had no effect on measured chitinase activity.

TTI-237: a novel microtubule-active compound with in vivo antitumor activity.

PubMed

Beyer, Carl F; Zhang, Nan; Hernandez, Richard; Vitale, Danielle; Lucas, Judy; Nguyen, Thai; Discafani, Carolyn; Ayral-Kaloustian, Semiramis; Gibbons, James J

2008-04-01

5-Chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine butanedioate (TTI-237) is a microtubule-active compound of novel structure and function. Structurally, it is one of a class of compounds, triazolo[1,5a]pyrimidines, previously not known to bind to tubulin. Functionally, TTI-237 inhibited the binding of [(3)H]vinblastine to tubulin, but it caused a marked increase in turbidity development that more closely resembled the effect observed with docetaxel than that observed with vincristine. The morphologic character of the presumptive polymer is unknown at present. When applied to cultured human tumor cells at concentrations near its IC(50) value for cytotoxicity (34 nmol/L), TTI-237 induced multiple spindle poles and multinuclear cells, as did paclitaxel, but not vincristine or colchicine. Flow cytometry experiments revealed that, at low concentrations (20-40 nmol/L), TTI-237 produced sub-G(1) nuclei and, at concentrations above 50 nmol/L, it caused a strong G(2)-M block. The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC(50) of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively. TTI-237 was not recognized by the MRP or MXR transporters. TTI-237 was active in vivo in several nude mouse xenograft models of human cancer, including LoVo human colon carcinoma and U87-MG human glioblastoma, when dosed i.v. or p.o. Thus, TTI-237 has a set of properties that distinguish it from other classes of microtubule-active compounds.

Binding of Sudan II and IV to lecithin liposomes and E. coli membranes: insights into the toxicity of hydrophobic azo dyes

PubMed Central

Li, Lu; Gao, Hong-Wen; Ren, Jiao-Rong; Chen, Ling; Li, Yu-Cheng; Zhao, Jian-Fu; Zhao, He-Ping; Yuan, Yuan

2007-01-01

Background Sudan red compounds are hydrophobic azo dyes, still used as food additives in some countries. However, they have been shown to be unsafe, causing tumors in the liver and urinary bladder in rats. They have been classified as category 3 human carcinogens by the International Agency for Research on Cancer. A number of hypotheses that could explain the mechanism of carcinogenesis have been proposed for dyes similar to the Sudan red compounds. Traditionally, investigations of the membrane toxicity of organic substances have focused on hydrocarbons, e.g. polycyclic aromatic hydrocarbons (PAHs), and DDT. In contrast to hydrocarbons, Sudan red compounds contain azo and hydroxy groups, which can form hydrogen bonds with the polar head groups of membrane phospholipids. Thus, entry may be impeded. They could have different toxicities from other lipophilic hydrocarbons. The available data show that because these compounds are lipophilic, interactions with hydrophobic parts of the cell are important for their toxicity. Lipophilic compounds accumulate in the membrane, causing expansion of the membrane surface area, inhibition of primary ion pumps and increased proton permeability. Results This work investigated the interactions of the amphiphilic compounds Sudan II and IV with lecithin liposomes and live Escherichia coli (E. coli). Sudan II and IV binding to lecithin liposomes and live E. coli corresponds to the Langmuir adsorption isotherm. In the Sudan red compounds – lecithin liposome solutions, the binding ratio of Sudan II to lecithin is 1/31 and that of Sudan IV to 1/314. The binding constant of the Sudan II-lecithin complex is 1.75 × 104 and that of the Sudan IV-lecithin complex 2.92 × 105. Besides, the influences of pH, electrolyte and temperature were investigated and analyzed quantitatively. In the Sudan red compounds – E.coli mixture, the binding ratios of Sudan II and Sudan IV to E.coli membrane phospholipid are 1/29 and 1/114. The binding constants of the Sudan II – and Sudan IV- E.coli membrane phospholipid complexes are 1.86 × 104 and 6.02 × 104. Over 60% of Sudan II and 75% of Sudan IV penetrated into E.coli, in which 90% of them remained in the E.coli membrane. Conclusion Experiments of Sudan II and IV binding to lecithin liposomes and live E. coli indicates that amphiphilic compounds may besequestered in thelecithin liposomes and membrane phospholipid bilayer according to the Langmuir adsorption law. Penetration into the cytosol was impeded and inhibited for Sudan red compounds. It is possible for such compounds themselves (excluding their metabolites and by-products)not result directly in terminal toxicity. Therefore, membrane toxicity could be manifested as membrane blocking and membrane expansion. The method established here may be useful for evaluating the interaction of toxins with membranes. PMID:17389047

Sterility of pediatric lipid emulsions repackaged by an automated compounding device.

PubMed

Ybarra, Joseph V; Rose, Warren E; Curtis, Caitlin S; Sacks, Gordon S

2011-05-01

The daily requirement of intravenous (IV) lipid in pediatric patients is often less than the volumes and sizes available in prepackaged, commercially available preparations. In clinical practice, IV lipid emulsions (IVLEs) have been repackaged into syringes to prevent infusions from exceeding 12 hours, to reduce waste, and to improve patient safety. Recent data suggest an increasing risk of contamination when these preparations are repackaged manually. This study investigates the sterility of small volumes of IVLE that have been repackaged into empty IV bags by means of an automated compounding device (ACD). A total of 152 IVLE bags were repackaged with an ACD in an International Standards Organization class 5 environment. IVLE repackaging was conducted over a period of 3 weeks (week 1, n = 52; week 2, n = 52; week 3, n = 48). Forty commercially available bags of IVLE served as controls. At 0, 24, 48, and 120 hours after repackaging, IVLEs were filtered and placed onto blood agar medium. Microbial growth occurred in 12 of the 152 repackaged preparations compared with 0 of the 40 controls (7.9% vs 0%, P = .07). Positive cultures consisted of gram-positive cocci (n = 5, 3.3%), gram-positive rods (n = 5, 3.3%), and yeast (n = 2, 1.3%). There was no difference in positive bacterial or yeast growth between weeks 1, 2, and 3, suggesting an absence of outside contamination during preparation. The positive microbial growth suggests a concerning incidence of contamination of IVLEs repackaged with an ACD. Additional research is needed to further identify and validate the clinical impact of these preparations.

[Results of the use of pumpan preparation in the treatment of severe forms of angina pectoris].

PubMed

Parshina, S S; Golovacheva, T V; Afanas'eva, T N; Panchenko, O V; Baldina, A A; Starostina, N V; Lial'chenko, I F; Egorova, L P

2000-01-01

To assess validity of adjuvant use of pumpan, a homeopathic compound, in patients with unstable angina pectoris and angina of effort (functional class III-IV) receiving conventional treatment. A direct open controlled trial for 15 months performed initially in hospital, then outpatiently, covered 49 patients with severe angina. Examination of the patients included evaluation of clinical condition and the disease course, lipid metabolism, hemostasis, blood plasma electrolytes, aminotransferases, echo-CG, bicycle exercise, rheoencephalography, ultrasonic dopplerography of head and neck vessels. Pumpan produced a positive effect total nonspecific systemic resistance improved, number of hospitalizations reduced, intracardiac hemodynamics improved in some cases with severe angina. Homeopathic compound pumpan can be recommended in the treatment of severe angina to reinforce antianginal effect, improve the disease clinical course, to obtain a hypocoagulative and hypocholesterolemic effect, to normalize intracardiac hemodynamics, to raise myocardial performance and intracoronary reserve as well as nonspecific resistance of the body.

Two-electron high potential and high capacity redox active molecules for energy storage applications

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

Huang, Jinhua; Zhang, Lu; Burrell, Anthony K.

A non-aqueous redox flow battery includes a catholyte including a compound of formula (I), a compound of formula (II), or a compound of formula (III): ##STR00001## wherein two R groups have the formula X, wherein X is X, wherein X is a group of formula IV-A or IV-B; ##STR00002##

Behavior of platinum(iv) complexes in models of tumor hypoxia: cytotoxicity, compound distribution and accumulation.

PubMed

Schreiber-Brynzak, Ekaterina; Pichler, Verena; Heffeter, Petra; Hanson, Buck; Theiner, Sarah; Lichtscheidl-Schultz, Irene; Kornauth, Christoph; Bamonti, Luca; Dhery, Vineet; Groza, Diana; Berry, David; Berger, Walter; Galanski, Markus; Jakupec, Michael A; Keppler, Bernhard K

2016-04-01

Hypoxia in solid tumors remains a challenge for conventional cancer therapeutics. As a source for resistance, metastasis development and drug bioprocessing, it influences treatment results and disease outcome. Bioreductive platinum(iv) prodrugs might be advantageous over conventional metal-based therapeutics, as biotransformation in a reductive milieu, such as under hypoxia, is required for drug activation. This study deals with a two-step screening of experimental platinum(iv) prodrugs with different rates of reduction and lipophilicity with the aim of identifying the most appropriate compounds for further investigations. In the first step, the cytotoxicity of all compounds was compared in hypoxic multicellular spheroids and monolayer culture using a set of cancer cell lines with different sensitivities to platinum(ii) compounds. Secondly, two selected compounds were tested in hypoxic xenografts in SCID mouse models in comparison to satraplatin, and, additionally, (LA)-ICP-MS-based accumulation and distribution studies were performed for these compounds in hypoxic spheroids and xenografts. Our findings suggest that, while cellular uptake and cytotoxicity strongly correlate with lipophilicity, cytotoxicity under hypoxia compared to non-hypoxic conditions and antitumor activity of platinum(iv) prodrugs are dependent on their rate of reduction.

Lattice thermal expansion for normal tetrahedral compound semiconductors

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

Omar, M.S.

2007-02-15

The cubic root of the deviation of the lattice thermal expansion from that of the expected value of diamond for group IV semiconductors, binary compounds of III-V and II-VI, as well as several ternary compounds from groups I-III-VI{sub 2}, II-IV-V{sub 2} and I-IV{sub 2}V{sub 3} semiconductors versus their bonding length are given straight lines. Their slopes were found to be 0.0256, 0.0210, 0.0170, 0.0259, 0.0196, and 0.02840 for the groups above, respectively. Depending on the valence electrons of the elements forming these groups, a formula was found to correlate all the values of the slopes mentioned above to that ofmore » group IV. This new formula which depends on the melting point and the bonding length as well as the number of valence electrons for the elements forming the compounds, will gives best calculated values for lattice thermal expansion for all compounds forming the groups mentioned above. An empirical relation is also found between the mean ionicity of the compounds forming the groups and their slopes mentioned above and that gave the mean ionicity for the compound CuGe{sub 2}P{sub 3} in the range of 0.442.« less

The Effect of Excipients on the Permeability of BCS Class III Compounds and Implications for Biowaivers.

PubMed

Parr, Alan; Hidalgo, Ismael J; Bode, Chris; Brown, William; Yazdanian, Mehran; Gonzalez, Mario A; Sagawa, Kazuko; Miller, Kevin; Jiang, Wenlei; Stippler, Erika S

2016-01-01

Currently, the FDA allows biowaivers for Class I (high solubility and high permeability) and Class III (high solubility and low permeability) compounds of the Biopharmaceutics Classification System (BCS). Scientific evidence should be provided to support biowaivers for BCS Class I and Class III (high solubility and low permeability) compounds. Data on the effects of excipients on drug permeability are needed to demonstrate that commonly used excipients do not affect the permeability of BCS Class III compounds, which would support the application of biowaivers to Class III compounds. This study was designed to generate such data by assessing the permeability of four BCS Class III compounds and one Class I compound in the presence and absence of five commonly used excipients. The permeability of each of the compounds was assessed, at three to five concentrations, with each excipient in two different models: Caco-2 cell monolayers, and in situ rat intestinal perfusion. No substantial increases in the permeability of any of the compounds were observed in the presence of any of the tested excipients in either of the models, with the exception of disruption of Caco-2 cell monolayer integrity by sodium lauryl sulfate at 0.1 mg/ml and higher. The results suggest that the absorption of these four BCS Class III compounds would not be greatly affected by the tested excipients. This may have implications in supporting biowaivers for BCS Class III compounds in general.

Finite element analysis of maxillary bone stress caused by Aramany Class IV obturator prostheses.

PubMed

Miyashita, Elcio Ricardo; Mattos, Beatriz Silva Câmara; Noritomi, Pedro Yoshito; Navarro, Hamilton

2012-05-01

The retention of an Aramany Class IV removable partial dental prosthesis can be compromised by a lack of support. The biomechanics of this obturator prosthesis result in an unusual stress distribution on the residual maxillary bone. This study evaluated the biomechanics of an Aramany Class IV obturator prosthesis with finite element analysis and a digital 3-dimensional (3-D) model developed from a computed tomography scan; bone stress was evaluated according to the load placed on the prosthesis. A 3-D model of an Aramany Class IV maxillary resection and prosthesis was constructed. This model was used to develop a finite element mesh. A 120 N load was applied to the occlusal and incisal platforms corresponding to the prosthetic teeth. Qualitative analysis was based on the scale of maximum principal stress; values obtained through quantitative analysis were expressed in MPa. Under posterior load, tensile and compressive stresses were observed; the tensile stress was greater than the compressive stress, regardless of the bone region, and the greatest compressive stress was observed on the anterior palate near the midline. Under an anterior load, tensile stress was observed in all of the evaluated bone regions; the tensile stress was greater than the compressive stress, regardless of the bone region. The Aramany Class IV obturator prosthesis tended to rotate toward the surgical resection when subjected to posterior or anterior loads. The amount of tensile and compressive stress caused by the Aramany Class IV obturator prosthesis did not exceed the physiological limits of the maxillary bone tissue. (J Prosthet Dent 2012;107:336-342). Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

Discovery of new erbB4 inhibitors: Repositioning an orphan chemical library by inverse virtual screening.

PubMed

Giordano, Assunta; Forte, Giovanni; Massimo, Luigia; Riccio, Raffaele; Bifulco, Giuseppe; Di Micco, Simone

2018-04-12

Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range. Among these, compound 20 exhibited an interesting value of IC 50 on MCF7 cell lines, thus validating IVS in lead repurposing. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Synthesis, antimalarial properties, and SAR studies of alkoxyurea-based HDAC inhibitors.

PubMed

Hansen, Finn K; Skinner-Adams, Tina S; Duffy, Sandra; Marek, Linda; Sumanadasa, Subathdrage D M; Kuna, Krystina; Held, Jana; Avery, Vicky M; Andrews, Katherine T; Kurz, Thomas

2014-03-01

Histone deacetylase (HDAC) inhibitors are an emerging class of potential antimalarial drugs. We investigated the antiplasmodial properties of 16 alkoxyurea-based HDAC inhibitors containing various cap and zinc binding groups (ZBGs). Ten compounds displayed sub-micromolar activity against the 3D7 line of Plasmodium falciparum. Structure-activity relationship studies revealed that a hydroxamic acid ZBG is crucial for antiplasmodial activity, and that the introduction of bulky alkyl substituents to cap groups increases potency against asexual blood-stage parasites. We also demonstrate that selected compounds cause hyperacetylation of P. falciparum histone H4, indicating inhibition of one or more PfHDACs. To assess the selectivity of alkoxyurea-based HDAC inhibitors for parasite over normal mammalian cells, the cytotoxicity of representative compounds was evaluated against neonatal foreskin fibroblast (NFF) cells. The most active compound, 6-((3-(4-(tert-butyl)phenyl)ureido)oxy)-N-hydroxyhexanamide (1 e, Pf3D7 IC50 : 0.16 μM) was 31-fold more toxic against the asexual blood stages than towards normal mammalian cells. Moreover, a subset of four structurally diverse HDAC inhibitors revealed moderate activity against late-stage (IV-V) gametocytes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

A general analytical strategy for the characterization of phenolic compounds in fruit juices by high-performance liquid chromatography with diode array detection coupled to electrospray ionization and triple quadrupole mass spectrometry.

PubMed

Abad-García, Beatriz; Berrueta, Luis A; Garmón-Lobato, Sergio; Gallo, Blanca; Vicente, Francisca

2009-07-10

In the present study, a methodology based on liquid chromatography with diode array detection (HPLC/DAD) coupled to an electrospray ionization (ESI) interface and a triple quadrupole mass spectrometer for the simultaneous identification of phenolic compounds in fruit juices has been developed. 72 available phenolic compound standards from diverse families present in fruits have been studied in order to analyze their fragmentation pattern. As a result, a general strategy for the characterization of unknown phenolic compounds in fruit juices was designed: (i) taking into account its UV-visible spectrum and elution order, assign the unknown polyphenol to a polyphenol class, (ii) identify the quasi-molecular ion using positive and negative MS spectra, being supported by adducts generated with solvent or sodium and molecular complexes, (iii) determinate the pattern of glycosylation in positive mode using ESI(+)-CID MS/MS product ion scan experiments, selecting the quasi-molecular ion as precursor ion, and finally, (iv) study the identity of the aglycone through ESI(+)-CID MS/MS product ion spectra from the protonated aglycone, [Y(0)](+). This strategy was successfully employed for the characterization of known and unknown phenolic compounds in juices from 17 different fruits.

Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management

PubMed Central

Fan, Junfeng; Lila, Mary Ann; Yousef, Gad

2013-01-01

Beneficial health effects of fruits and vegetables in the diet have been attributed to their high flavonoid content. Dipeptidyl peptidase IV (DPP-IV) is a serine aminopeptidase that is a novel target for type 2 diabetes therapy due to its incretin hormone regulatory effects. In this study, well-characterized anthocyanins (ANC) isolated from berry wine blends and twenty-seven other phenolic compounds commonly present in citrus, berry, grape, and soybean, were individually investigated for their inhibitory effects on DPP-IV by using a luminescence assay and computational modeling. ANC from blueberry-blackberry wine blends strongly inhibited DPP-IV activity (IC50, 0.07 ± 0.02 to >300 μM). Of the twenty-seven phenolics tested, the most potent DPP-IV inhibitors were resveratrol (IC50, 0.6 ± 0.4 nM), luteolin (0.12 ± 0.01 μM), apigenin (0.14 ± 0.02 μM), and flavone (0.17 ± 0.01 μM), with IC50 values lower than diprotin A (4.21 ± 2.01 μM), a reference standard inhibitory compound. Analyses of computational modeling showed that resveratrol and flavone were competitive inhibitors which could dock directly into all three active sites of DPP-IV, while luteolin and apigenin docked in a noncompetitive manner. Hydrogen bonding was the main binding mode of all tested phenolic compounds with DPP-IV. These results indicate that flavonoids, particularly luteolin, apigenin, and flavone, and the stilbenoid resveratrol can act as naturally occurring DPP-IV inhibitors. PMID:24069048

Deviation between the chemistry of Ce(IV) and Pu(IV) and routes to ordered and disordered heterobimetallic 4f/5f and 5f/5f phosphonates

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

Diwu, Juan; Wang, Shuao; Good, Justin J.

2011-06-06

The heterobimetallic actinide compound UO₂Ce(H₂O)[C₆H₄(PO₃H)₂]₂·H₂O was prepared via the hydrothermal reaction of U(VI) and Ce(IV) in the presence of 1,2-phenylenediphosphonic acid. We demonstrate that this is a kinetic product that is not stable with respect to decomposition to the monometallic compounds. Similar reactions have been explored with U(VI) and Ce(III), resulting in the oxidation of Ce(III) to Ce(IV) and the formation of the Ce(IV) phosphonate, Ce[C₆H₄(PO₃H)(PO₃H₂)][C₆H₄(PO₃H)(PO₃)]·2H₂O, UO₂Ce(H₂O)[C₆H₄(PO₃H)₂]₂·H₂O, and UO₂[C₆H₄(PO₃H)₂](H₂O)·H₂O. In comparison, the reaction of U(VI) with Np(VI) only yields Np[C₆H₄(PO₃H)₂]₂·2H₂O and aqueous U(VI), whereas the reaction of U(VI) with Pu(VI) yields the disordered U(VI)/Pu(VI) compound, (U 0.9Pu 0.1)O₂[C₆H₄(PO₃H)₂](H₂O)·H₂O, and themore » Pu(IV) phosphonate, Pu[C₆H₄(PO₃H)(PO₃H₂)][C₆H₄(PO₃H)(PO₃)]·2H₂O. The reactions of Ce(IV) with Np(VI) yield disordered heterobimetallic phosphonates with both M[C₆H₄(PO₃H)(PO₃H₂)][C₆H₄(PO₃H)(PO₃)]·2H₂O (M = Ce, Np) and M[C₆H₄(PO₃H)₂]₂·2H₂O (M = Ce, Np) structures, as well as the Ce(IV) phosphonate Ce[C₆H₄(PO₃H)(PO₃H₂)][C₆H₄(PO₃H)(PO₃)]·2H₂O. Ce(IV) reacts with Pu(IV) to yield the Pu(VI) compound, PuO₂[C₆H₄(PO₃H)₂](H₂O)·3H₂O, and a disordered heterobimetallic Pu(IV)/Ce(IV) compound with the M[C₆H₄(PO₃H)(PO₃H₂)][C₆H₄(PO₃H)(PO₃)]·2H₂O (M = Ce, Pu) structure. Mixtures of Np(VI) and Pu(VI) yield disordered heterobimetallic Np(IV)/Pu(IV) phosphonates with both the An[C₆H₄(PO₃H)(PO₃H₂)][C₆H₄(PO₃H)(PO₃)]·2H₂O (M = Np, Pu) and An[C₆H₄(PO₃H)₂]₂·2H₂O (M = Np, Pu) formulas.« less

Lupus nephritis in Lebanon.

PubMed

Uthman, I W; Muffarij, A A; Mudawar, W A; Nasr, F W; Masri, A F

2001-01-01

This is a retrospective study of the clinicopathological characteristics of 50 systemic lupus erythematosus patients with nephritis who underwent a kidney biopsy and were admitted to the American University of Beirut Medical Center, in Lebanon, between 1979 and 1999. There were 43 females and seven males, with a median age of 24 y. Renal histology slides from these patients were assessed according to the World Health Organization classification, and were distributed as follows: class I (n = 3, 6%); class II (n = 14, 28%); class III (n = 11, 22%); class IV (n = 19, 38%); class V (n = 1, 2%); class VI (n = 2, 4%). All the patients received oral prednisone, in addition the following treatments were used: pulse intravenous (i.v.) cyclophosphamide (n = 23, 46%); azathioprine (n = 22, 44%); pulse i.v. steroids (n = 19, 38%); chloroquine sulfate (n = 17, 34%); methotrexate (n = 5, 10%); and plasmapheresis (n = 2, 4%). The median duration of follow-up was 5 y (range 1-33 y). On their last evaluation, out of 37 patients who were followed, 20 patients (54%) had controlled disease, eight patients (22%) were still on active medical treatment, four patients (11%) were on chronic hemodialysis, and five patients (13%) had died. Unlike three other Arab populations studies from Kuwait, United Arab Emirates and Saudi Arabia, where the most frequent histopathologic abnormality was class III, diffuse proliferative LN (class IV) was the most common type of lupus nephritis in Lebanon, similarly to reports from USA, France, Netherlands, South Africa, Thailand and Taiwan.

Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

PubMed

Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

2017-04-01

The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator ( CFTR ) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans , or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (p<0.001) higher CFTR activity compared with compound heterozygous for class I-II mutations. Furthermore, five of six compounds heterozygous with the p.[Arg117Leu;Leu997Phe] had mild CF, whereas the p.Leu997Phe, in trans with a class I-II CFTR mutation, caused CFTR-RD or a healthy status (CFTR activity: 21.3-36.9%). Finally, compounds heterozygous for the c.[1210-34TG[12];1210-12T[5];2930C>T] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the mutation in trans . Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Automated compound classification using a chemical ontology.

PubMed

Bobach, Claudia; Böhme, Timo; Laube, Ulf; Püschel, Anett; Weber, Lutz

2012-12-29

Classification of chemical compounds into compound classes by using structure derived descriptors is a well-established method to aid the evaluation and abstraction of compound properties in chemical compound databases. MeSH and recently ChEBI are examples of chemical ontologies that provide a hierarchical classification of compounds into general compound classes of biological interest based on their structural as well as property or use features. In these ontologies, compounds have been assigned manually to their respective classes. However, with the ever increasing possibilities to extract new compounds from text documents using name-to-structure tools and considering the large number of compounds deposited in databases, automated and comprehensive chemical classification methods are needed to avoid the error prone and time consuming manual classification of compounds. In the present work we implement principles and methods to construct a chemical ontology of classes that shall support the automated, high-quality compound classification in chemical databases or text documents. While SMARTS expressions have already been used to define chemical structure class concepts, in the present work we have extended the expressive power of such class definitions by expanding their structure-based reasoning logic. Thus, to achieve the required precision and granularity of chemical class definitions, sets of SMARTS class definitions are connected by OR and NOT logical operators. In addition, AND logic has been implemented to allow the concomitant use of flexible atom lists and stereochemistry definitions. The resulting chemical ontology is a multi-hierarchical taxonomy of concept nodes connected by directed, transitive relationships. A proposal for a rule based definition of chemical classes has been made that allows to define chemical compound classes more precisely than before. The proposed structure-based reasoning logic allows to translate chemistry expert knowledge into a computer interpretable form, preventing erroneous compound assignments and allowing automatic compound classification. The automated assignment of compounds in databases, compound structure files or text documents to their related ontology classes is possible through the integration with a chemical structure search engine. As an application example, the annotation of chemical structure files with a prototypic ontology is demonstrated.

Automated compound classification using a chemical ontology

PubMed Central

2012-01-01

Background Classification of chemical compounds into compound classes by using structure derived descriptors is a well-established method to aid the evaluation and abstraction of compound properties in chemical compound databases. MeSH and recently ChEBI are examples of chemical ontologies that provide a hierarchical classification of compounds into general compound classes of biological interest based on their structural as well as property or use features. In these ontologies, compounds have been assigned manually to their respective classes. However, with the ever increasing possibilities to extract new compounds from text documents using name-to-structure tools and considering the large number of compounds deposited in databases, automated and comprehensive chemical classification methods are needed to avoid the error prone and time consuming manual classification of compounds. Results In the present work we implement principles and methods to construct a chemical ontology of classes that shall support the automated, high-quality compound classification in chemical databases or text documents. While SMARTS expressions have already been used to define chemical structure class concepts, in the present work we have extended the expressive power of such class definitions by expanding their structure-based reasoning logic. Thus, to achieve the required precision and granularity of chemical class definitions, sets of SMARTS class definitions are connected by OR and NOT logical operators. In addition, AND logic has been implemented to allow the concomitant use of flexible atom lists and stereochemistry definitions. The resulting chemical ontology is a multi-hierarchical taxonomy of concept nodes connected by directed, transitive relationships. Conclusions A proposal for a rule based definition of chemical classes has been made that allows to define chemical compound classes more precisely than before. The proposed structure-based reasoning logic allows to translate chemistry expert knowledge into a computer interpretable form, preventing erroneous compound assignments and allowing automatic compound classification. The automated assignment of compounds in databases, compound structure files or text documents to their related ontology classes is possible through the integration with a chemical structure search engine. As an application example, the annotation of chemical structure files with a prototypic ontology is demonstrated. PMID:23273256

Evaluation of the intestinal permeability of rosemary (Rosmarinus officinalis L.) extract polyphenols and terpenoids in Caco-2 cell monolayers.

PubMed

Pérez-Sánchez, Almudena; Borrás-Linares, Isabel; Barrajón-Catalán, Enrique; Arráez-Román, David; González-Álvarez, Isabel; Ibáñez, Elena; Segura-Carretero, Antonio; Bermejo, Marival; Micol, Vicente

2017-01-01

Rosemary (Rosmarinus officinalis) is grown throughout the world and is widely used as a medicinal herb and to season and preserve food. Rosemary polyphenols and terpenoids have attracted great interest due to their potential health benefits. However, complete information regarding their absorption and bioavailability in Caco-2 cell model is scarce. The permeation properties of the bioactive compounds (flavonoids, diterpenes, triterpenes and phenylpropanoids) of a rosemary extract (RE), obtained by supercritical fluid extraction, was studied in Caco-2 cell monolayer model, both in a free form or liposomed. Compounds were identified and quantitated by liquid chromatography coupled to quadrupole time-of-flight with electrospray ionization mass spectrometry analysis (HPLC-ESI-QTOF-MS), and the apparent permeability values (Papp) were determined, for the first time in the extract, for 24 compounds in both directions across cell monolayer. For some compounds, such as triterpenoids and some flavonoids, Papp values found were reported for the first time in Caco-2 cells.Our results indicate that most compounds are scarcely absorbed, and passive diffusion is suggested to be the primary mechanism of absorption. The use of liposomes to vehiculize the extract resulted in reduced permeability for most compounds. Finally, the biopharmaceutical classification (BCS) of all the compounds was achieved according to their permeability and solubility data for bioequivalence purposes. BCS study reveal that most of the RE compounds could be classified as classes III and IV (low permeability); therefore, RE itself should also be classified into this category.

A modified model for calculating lattice thermal expansion of I{sub 2}-IV-VI{sub 3} and I{sub 3}-V-VI{sub 4} tetrahedral compounds

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

Omar, M.S.

2007-05-03

A general empirical formula was found for calculating lattice thermal expansion for compounds having their properties extended for compound groups having different mean ionicity as well as more than one type of cation atoms with that of different numbers of them such as I{sub 2}-IV-VI{sub 3} and I{sub 3}-V-VI{sub 4}. The difference in the valence electrons for cations and anions in the compound was used to correlate the deviations caused by the compound ionicity. The ionicity effects, which are due to their different numbers for their types, were also added to the correlation equation. In general, the lattice thermal expansionmore » for a compound semiconductor can be calculated from a relation containing melting point, mean atomic distance and number of valence electrons for the atoms forming the compound. The mean ionicity for the group compounds forming I{sub 2}-IV-VI{sub 3} was found to be 0.323 and 0.785 for the ternary group compounds of I{sub 3}-V-VI{sub 4}.« less

49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...

49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...

49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...

49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...

49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...

Photophysical properties of a novel axially substituted tetra-α-(pentyloxy) Titanium(IV) Phthalocyanine - Hematoxylin

NASA Astrophysics Data System (ADS)

Jiang, Yufeng; Lv, Huafei; Yu, Xinxin; Pan, Sujuan; Zhang, Tiantian; Huang, Yide; Wang, Yuhua; Xie, Shusen; Yang, Hongqin; Peng, Yiru

2017-06-01

Metal phthalocyanines (MPcs) are a very important class of widespread application compounds. They are not only used as dyes but also used as catalysts, data storage, electron charge carriers in photocopiers, photoconductors in chemical sensors, and photo-antenna devices in photosysthesis, photovoltaic cells. A particular application of Pcs is that it was used as a photosensitizers (PS) for treatment of certain cancer by photodynamic therapy of cancer and non-cancer diseases. However, the molecular aggregation of phthalocyanines, which is an intrinsic property of these large π-π conjugated systems, provides an efficient non-radioactive energy relaxation pathway, thereby shortening the excited state lifetimes, and reducing the photosensitizing and target efficiency. To overcome these problems, the introduction of axial ligands to phthalocyanine can prevent the formation of aggregation to some extend. In this paper, hematoxylin axially substituted tetra-α-(pentoxy) titanium (IV) phthalocyanine (TiPc(OC5H11)4-Hematoxylin) were characterized by elemental analysis, IR, 1H NMR, UV-Vis, fluorescence spectra. No obviously Q band change was observed after the hematoxylin was substituted at the peripheral position of substituted phthalocyanine ring. Because of the rigidity structure of the hematoxylin, the fluorescence intensity of hematoxylin peripheral substituted phthalocyanine decreased compared with free substituted phthalocyanines. The fluorescence lifetimes of axially substituted phthalocyanine was fitted to be 3.613 ns. This compound may be considered as a promising photosensitizer for PDT.

Biochemistry of plant class IV chitinases and fungal chitinase-modifying proteins

USDA-ARS?s Scientific Manuscript database

Plant class IV chitinases have 2 domains, a small (3 kDa) amino-terminal domain with homology to carbohydrate binding peptides, and a larger (25 kDa) catalytic domain. The biological function of these chitinases is not known. But it is known that some pathogenic fungi secrete chitinase modifying pro...

Polyglycine hydrolases secreted by Pleosporineae fungi that target the linker region of plant class IV chitinases*

USDA-ARS?s Scientific Manuscript database

Chitinase modifying proteins (cmps) are fungal proteases that truncate plant class IV chitinases by cleaving near their amino termini. We previously described Fv-cmp, a fungalysin protease that cleaves a conserved glycine-cysteine bond within the hevein domain. Here we describe a new type of cmp—pol...

Alcoholytic Cleavage of Polyhydroxyalkanoate Chains by Class IV Synthases Induced by Endogenous and Exogenous Ethanol

PubMed Central

Hyakutake, Manami; Tomizawa, Satoshi; Mizuno, Kouhei; Abe, Hideki

2014-01-01

Polyhydroxyalkanoate (PHA)-producing Bacillus strains express class IV PHA synthase, which is composed of the subunits PhaR and PhaC. Recombinant Escherichia coli expressing PHA synthase from Bacillus cereus strain YB-4 (PhaRCYB-4) showed an unusual reduction of the molecular weight of PHA produced during the stationary phase of growth. Nuclear magnetic resonance analysis of the low-molecular-weight PHA revealed that its carboxy end structure was capped by ethanol, suggesting that the molecular weight reduction was the result of alcoholytic cleavage of PHA chains by PhaRCYB-4 induced by endogenous ethanol. This scission reaction was also induced by exogenous ethanol in both in vivo and in vitro assays. In addition, PhaRCYB-4 was observed to have alcoholysis activity for PHA chains synthesized by other synthases. The PHA synthase from Bacillus megaterium (PhaRCBm) from another subgroup of class IV synthases was also assayed and was shown to have weak alcoholysis activity for PHA chains. These results suggest that class IV synthases may commonly share alcoholysis activity as an inherent feature. PMID:24334666

Home inotropic therapy in advanced heart failure: cost analysis and clinical outcomes.

PubMed

Harjai, K J; Mehra, M R; Ventura, H O; Lapeyre, Y M; Murgo, J P; Stapleton, D D; Smart, F W

1997-11-05

This study was conducted to assess cost savings and clinical outcomes associated with the use of home i.v. inotropic therapy in patients with advanced (New York Heart Association [NYHA] class IV) heart failure. Retrospective analysis. Tertiary care referral center. Twenty-four patients (13 men, 11 women; age, 61+/-12 years) with left ventricular ejection fraction <30% and heart failure refractory to oral agents required home i.v. inotropic therapy for at least 4 consecutive weeks between May 1994 and April 1996. Inotropic agents used included dobutamine (n=20; dose, 5.0+/-2.2 microg/kg/min) or milrinone (n=7; dose, 0.53+/-0.05 microg/kg/min). Cost of care and clinical outcomes (hospital admissions, length of hospital stay, NYHA functional class) were compared during the period of inotropic therapy (study period) and the immediate preceding period of equal duration (control period). In comparison to the control period, the study period (3.9+/-2.7 months) was associated with a 16% reduction in cost, amounting to a calculated savings of $5,700 per patient or $1,465 per patient per month. Concomitantly, a decrease in the number of hospital admissions from 2.7+/-2.6 to 1.3+/-1.3 (p=0.056) and length of hospital stay from 20.9+/-12.7 to 5.5+/-5.4 days (p=0.0004) was observed with improvement in NYHA functional class from 4.0+/-0.0 to 2.7+/-0.9 (p<0.0001). Eight patients (38%) died after 2.8+/-1.7 months of home i.v. inotropic therapy. Home i.v. inotropic therapy reduces hospital admissions, length of stay, and cost of care and improves functional class in patients with advanced (NYHA class IV) heart failure.

Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes.

PubMed

Sagar, Sneha R; Agarwal, Jessica K; Pandya, Dhaivat H; Dash, Ranjeet Prasad; Nivsarkar, Manish; Vasu, Kamala K

2015-10-15

We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amongst all the synthesized compounds, 6-methyl-5-(4-methylpyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (5k) was found to be the most active based on in vitro DPP-IV studies and also exhibited promising in vivo blood glucose lowering activity in male Wistar rats. Copyright © 2015. Published by Elsevier Ltd.

The impact of whole human blood on the kinetic inertness of platinum(iv) prodrugs - an HPLC-ICP-MS study.

PubMed

Theiner, Sarah; Grabarics, Márkó; Galvez, Luis; Varbanov, Hristo P; Sommerfeld, Nadine S; Galanski, Markus; Keppler, Bernhard K; Koellensperger, Gunda

2018-04-17

The potential advantage of platinum(iv) complexes as alternatives to classical platinum(ii)-based drugs relies on their kinetic stability in the body before reaching the tumor site and on their activation by reduction inside cancer cells. In this study, an analytical workflow has been developed to investigate the reductive biotransformation and kinetic inertness of platinum(iv) prodrugs comprising different ligand coordination spheres (respectively, lipophilicity and redox behavior) in whole human blood. The distribution of platinum(iv) complexes in blood pellets and plasma was determined by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave digestion. An analytical approach based on reversed-phase (RP)-ICP-MS was used to monitor the parent compound and the formation of metabolites using two different extraction procedures. The ligand coordination sphere of the platinum(iv) complexes had a significant impact on their accumulation in red blood cells and on their degree of kinetic inertness in whole human blood. The most lipophilic platinum(iv) compound featuring equatorial chlorido ligands showed a pronounced penetration into blood cells and a rapid reductive biotransformation. In contrast, the more hydrophilic platinum(iv) complexes with a carboplatin- and oxaliplatin-core exerted kinetic inertness on a pharmacologically relevant time scale with notable amounts of the compound accumulated in the plasma fraction.

[Fat soluble constituents of the leaves of Vaccinium bracteatum Thunb].

PubMed

Tu, P; Liu, J; Li, J

1997-07-01

Four compounds were isolated from the fat soluble fraction of the leaves of Vaccinium bracteatum and identified as friedelin (I), epifriedelinol (II), beta-sitosterol(III) and ursolic acid(IV) by IR, NMR and MS. Compound III and IV are isolated from the leaves of this plant for the first time.

Growth, structural, thermal, dielectric and nonlinear optical properties of potassium hexachloro cadmate (IV) a novel single crystal

NASA Astrophysics Data System (ADS)

Umarani, P.; Jagannathan, K.

2018-02-01

The Potassium hexachloro cadmate (IV) (PHC) single crystal was grown from the aqueous of the solution by a controlled evaporation method. Single crystal XRD solved the structure. FTIR is used to identify the functional groups of grown crystal. The UV-Vis-NIR spectrometer was used to find out the UV cut off region and to calculate the optical band gap of the Potassium hexachloro cadmate (IV) single crystal. The EDAX spectrum has been used to identify the compounds present in title compound. The TG-DTA profile shows the thermal stability of the grown crystal of Potassium hexachloro cadmate (IV). The Vicker's hardness measurement was used to calculate the material hardness of the title compound. The dielectric loss and constant varied with frequencies and activation energy is also calculated. The solid state parameters like plasma energy, Penn gap, Fermi energy, electronic polarizability using Penn analysis and Clausius-Mossotti equation were also calculated for the title compound. The Z-scan technique is used to calculate the third order nonlinear susceptibility of a real and imaginary part.

49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...

49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...

49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...

49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...

49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...

Synthesis, Biological Evaluation, and Molecular Docking of (R)-2-((8-(3-aminopiperidin-1-yl)-3-methyl-7-(3-methylbut-2-en-1-yl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)methyl)benzonitrile as Dipeptidyl Peptidase IV Inhibitors.

PubMed

Ran, Yan; Pei, Heying; Shao, Mingfeng; Chen, Lijuan

2016-02-01

Type 2 diabetes (T2D) is classified as a major metabolic disorder, which has affected approximately 194 million people worldwide. DPP-IV inhibitors as a new therapy have shown several advantages over traditional antidiabetic drugs. Based on the similar binding modes of Alogliptin and Linagliptin, molecular operation was conducted via combining pharmacophore hybridization with structural optimization between the two market drugs and racemic compounds 40 and 43 were reported as DPP-IV inhibitors in our previous studies. But the majority of DPP-IV inhibitors have developed into a small molecule with certain conformation; in this study, we described the synthesis, biological evaluation, and molecular docking of corresponding enantiomers of compounds 40 and 43. The most potent inhibitor is (R)-40 (IC50  = 23.5 nm, F = 74.67%, T1/2  = 4 h), which exhibited moderate antihyperglycemic activity as compared to the standard antidiabetic drug Linagliptin in OGTT. In addition, compound (R)-40 effectively improved the pathological state of DIO mice. Molecular docking studies clarified the favorable binding affinity between compound (R)-40 and DPP-IV active site. Thus, compound (R)-40 would be entitled to further development as a drug candidate on the basis of the suitable pharmacokinetic (PK) and desirable pharmacodynamic (PD) profiles. © 2015 John Wiley & Sons A/S.

Classification and Short-Term Course of DSM-IV Cannabis, Hallucinogen, Cocaine, and Opioid Disorders in Treated Adolescents

ERIC Educational Resources Information Center

Chung, Tammy; Martin, Christoper S.

2005-01-01

This study examined the latent class structure of Diagnostic and Statistical Manual of Mental Disorders (text rev.; DSM-IV; American Psychiatric Association, 2000) symptoms used to diagnose cannabis, hallucinogen, cocaine, and opiate disorders among 501 adolescents recruited from addictions treatment. Latent class results were compared with the…

40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...

40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...

40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...

40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...

40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 24 2013-07-01 2013-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...

Abundance of truncated and full-length ChitA and ChitB chitinases in healthy and diseased maize tissues

USDA-ARS?s Scientific Manuscript database

Chitinase modifying proteins, cmps, are secreted fungal proteases that combat plant defenses by truncating plant class IV chitinases. We initially discovered that ChitA and ChitB, two plant class IV chitinases that are abundant in developing and mature kernels of corn, are truncated by cmps during e...

Cloning and identification of Fv-cmp, a protease from Fusarium verticillioides that truncates Zea mays and Arabidopsis thaliana class IV chitinases

USDA-ARS?s Scientific Manuscript database

Chitinase modifying proteins (cmps) are proteases, secreted by fungal pathogens, that were originally identified as proteins that truncate class IV chitinases of maize during ear rot. Cmps from Bipolaris zeicola and Stenocarpella maydis have been characterized, but the identities of the proteases h...

40 CFR 147.2550 - State-administered program-Class I, III, IV and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Rules and Regulations, Wyoming Department of Environmental Quality, Chapter XXI: In Situ Mining... program for Class I, III, IV and V wells in the State of Wyoming, except those on Indian lands is the... section 1422 of the SDWA. Notice of this approval was published in the Federal Register on July 15, 1983...

40 CFR 147.2550 - State-administered program-Class I, III, IV and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Rules and Regulations, Wyoming Department of Environmental Quality, Chapter XXI: In Situ Mining... program for Class I, III, IV and V wells in the State of Wyoming, except those on Indian lands is the... section 1422 of the SDWA. Notice of this approval was published in the Federal Register on July 15, 1983...

Targeting histone deacetylases: perspectives for epigenetic-based therapy in cardio-cerebrovascular disease

PubMed Central

Wang, Zi-Ying; Qin, Wen; Yi, Fan

2015-01-01

Although the pathogenesis of cardio-cerebrovascular disease (CCVD) is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase (HDAC)-mediated epigenetic processes in the development of cardio-cerebrovascular injury. HDACs are a family of enzymes to balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. To date, 18 mammalian HDACs are identified and grouped into four classes based on similarity to yeast orthologs. The zinc-dependent HDAC family currently consists of 11 members divided into three classes (class I, II, and IV) on the basis of structure, sequence homology, and domain organization. In comparison, class III HDACs (also known as the sirtuins) are composed of a family of NAD+-dependent protein-modifying enzymes related to the Sir2 gene. HDAC inhibitors are a group of compounds that block HDAC activities typically by binding to the zinc-containing catalytic domain of HDACs and have displayed anti-inflammatory and antifibrotic effects in the cardio-cerebrovascular system. In this review, we summarize the current knowledge about classifications, functions of HDACs and their roles and regulatory mechanisms in the cardio-cerebrovascular system. Pharmacological targeting of HDAC-mediated epigenetic processes may open new therapeutic avenues for the treatment of CCVD. PMID:25870619

[Microinvasive dental treatment in pre-school children].

PubMed

Korolenkova, M V

The aim of the study was to assess the efficiency of atraumatic restorative treatment (ART) with cavity preparation by means of dental endo motor. ART method was applied in 94 children (50 females and 44 males, 301 teeth treated) aged 21-96 months. Wireless dental endo motor (Endo Mate TC2, NSK, Japan) was used for cavity preparation. The cavities (102 (33.9%) class I, 156 (51.8%) class V, 20 (6.6%) class II, 18 (6%) class III and 5 (1.7%) class IV) were then filled with glass-ionomer cement (Fuji IX, GC, Japan). Success rate was assessed 3, 6, 12 and 18 months after treatment. Overall ART procedure success rate (good marginal fit, no occlusal wearing or restoration fractures) at 18-month follow up was 88.7% (267 fillings out of 301) with the highest survival in class I (96.1%) and class V (96.2%) restoration and poorest in class II (50%), class III (44.4%) and class IV (20%) restorations. Cavity preparation with wireless dental endo motor was well tolerated even by infants (12 children were younger than 24 months), as it is noiseless and significantly faster than conventional manual preparation. ART method with the use of dental endo motor showed good success rate and proved to be highly efficient in small and apprehensive children. The method, however, should be avoided in class III and IV cavities as the success rate is poor mostly because of restoration fractures.

Derivation of a human equivalent concentration for n-butanol using a physiologically based pharmacokinetic model for n-butyl acetate and metabolites n-butanol and n-butyric acid

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

Teeguarden, Justin G.; Deisinger, P. J.; Poet, Torka S.

2005-05-01

The metabolic series (family) approach for risk assessment uses a dosimetry-based analysis to develop toxicity information for a group of metabolically linked compounds using pharmacokinetic (PK) data for each compound and toxicity data for the parent compound. An initial physiologically-based pharmacokinetic (PBPK) model was developed to support the implementation of the metabolic series approach for n-butyl acetate and its subsequent metabolites, n-butanol, and n-butyric acid (the butyl series) (Barton et al. 2000). In conjunction with pilot pharmacokinetic studies, the model was used to design the definitive intravenous (i.v.) PK studies. Rats were implanted with dual indwelling cannulae and administered testmore » compounds by i.v. bolus dose, i.v. infusion, or by inhalation in a recirculating closed chamber. Hepatic, vascular and extravascular metabolic constants for metabolism were estimated by fitting the model to the blood time course data from these experiments. The respiratory bioavailability of n-butyl acetate and n-butanol was estimated from closed chamber inhalation studies and measured ventilation rates. The resulting butyl series PBPK model successfully reproduces the blood time course of these compounds following i.v. administration, and inhalation exposure to n-butyl acetate and n-butanol. A fully scaled human version of the model successfully reproduces arterial blood n-butanol kinetics following inhalation exposure to n-butanol. These validated i.v (rat) and inhalation route models (rat, butyl acetate, n-butanol; human, butanol only) can be used to support species and dose-route extrapolations required for risk assessment of butyl series family of compounds. Further, this work demonstrates the usefulness of i.v. kinetic data for parameterization of systemic metabolism and the value of collaboration between experimentalists and kineticists in the development of PBPK models. The product of this effort, validated rat and human PBPK models for the butyl series compounds, illustrates the effectiveness of broad multi-institutional public/private collaborations in the pursuit of developing state of the art tools for risk assessment.« less

[A new secoiridoid from the flowers of Jasminum officinale L. var. grandiflorum].

PubMed

Zhao, Gui-Qin; Yin, Zhi-Feng; Dong, Jun-Xing

2008-05-01

To study the chemical constituents of the flowers of Jasminum officinale L. var. grandiflorum, the compounds were isolated and purified by HPLC, recrystallization and chromatography on silica gel and Sephadex LH-20 column. Their structures were elucidated on the basis of physicochemical properties and spectral analysis. Six secoiridoids were identified as jasgranoside (I), jaspolyoside (II), 8-epi-kingiside (III), 10-hydroxy-oleuropein (IV), 10-hydroxy-ligstroside (V), oleoside-7, 11-dimethyl ester (VI). Compound I is a new compound. Compounds II, III, IV, V and VI were isolated from Jasminum officinale L. var. grandiflorum for the first time.

Evaluation of the intestinal permeability of rosemary (Rosmarinus officinalis L.) extract polyphenols and terpenoids in Caco-2 cell monolayers

PubMed Central

Arráez-Román, David; González-Álvarez, Isabel; Ibáñez, Elena; Segura-Carretero, Antonio; Bermejo, Marival; Micol, Vicente

2017-01-01

Rosemary (Rosmarinus officinalis) is grown throughout the world and is widely used as a medicinal herb and to season and preserve food. Rosemary polyphenols and terpenoids have attracted great interest due to their potential health benefits. However, complete information regarding their absorption and bioavailability in Caco-2 cell model is scarce. The permeation properties of the bioactive compounds (flavonoids, diterpenes, triterpenes and phenylpropanoids) of a rosemary extract (RE), obtained by supercritical fluid extraction, was studied in Caco-2 cell monolayer model, both in a free form or liposomed. Compounds were identified and quantitated by liquid chromatography coupled to quadrupole time-of-flight with electrospray ionization mass spectrometry analysis (HPLC-ESI-QTOF-MS), and the apparent permeability values (Papp) were determined, for the first time in the extract, for 24 compounds in both directions across cell monolayer. For some compounds, such as triterpenoids and some flavonoids, Papp values found were reported for the first time in Caco-2 cells.Our results indicate that most compounds are scarcely absorbed, and passive diffusion is suggested to be the primary mechanism of absorption. The use of liposomes to vehiculize the extract resulted in reduced permeability for most compounds. Finally, the biopharmaceutical classification (BCS) of all the compounds was achieved according to their permeability and solubility data for bioequivalence purposes. BCS study reveal that most of the RE compounds could be classified as classes III and IV (low permeability); therefore, RE itself should also be classified into this category. PMID:28234919

Radio- and photosensitization of DNA with compounds containing platinum and bromine atoms

NASA Astrophysics Data System (ADS)

Śmiałek, Małgorzata A.; Ptasińska, Sylwia; Gow, Jason; Vrønning Hoffmann, Søren; Mason, Nigel J.

2015-05-01

Irradiations of plasmid DNA by both X-rays and UV light in the presence and absence of compounds containing platinum and bromine atoms were performed in order to asses the sensitization potential of these compounds. Plasmid DNA pBR322 was incubated with platinum (II) bromide, hydrogen hexabromoplatinate (IV), hydrogen hexahydroxyplatinate (IV) and sodium hexahydroxyplatinate (IV). Incubation was followed by X-ray or UV irradiations. It was found that amongst the sensitizers tested, during irradiations carried out in the presence of platinum (II) bromide, the highest levels of double strand breaks formation upon X-ray treatment were recorded. In contrast much less damage was induced by UV light. Data presented here suggests that this compound may be a promising radiosensitizer for cancer treatment. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey Solov'yov, Nigel Mason, Gustavo García, Eugene Surdutovich.

Anaerobic biodegradation of BTEX using Mn(IV) and Fe(III) as alternative electron acceptors.

PubMed

Villatoro-Monzón, W R; Mesta-Howard, A M; Razo-Flores, E

2003-01-01

Anaerobic BTEX biodegradation was tested in batch experiments using an anaerobic sediment as inoculum under Fe(III) and Mn(IV) reducing conditions. All BTEX were degraded under the conditions tested, specially under Mn(IV) reducing conditions, where benzene was degraded at a rate of 0.8 micromol l(-1) d(-1), significantly much faster than Fe(III) reducing conditions. Under Fe(III) reducing conditions, ethylbenzene was the compound that degraded at the faster rate of 0.19 micromol l(-1) d(-1). Mn(IV) reducing conditions are energetically more favourable than Fe(III), therefore, BTEX were more rapidly degraded under Mn(IV) reducing conditions. These results represent the first report of the degradation of benzene with Mn(IV) as the final electron acceptor. Amorphous manganese oxide is a natural widely distributed metal in groundwater, where it can be microbiologically reduced, leading to the degradation of monoaromatic compounds.

How Y-Family DNA polymerase IV is more accurate than Dpo4 at dCTP insertion opposite an N2-dG adduct of benzo[a]pyrene.

PubMed

Sholder, Gabriel; Creech, Amanda; Loechler, Edward L

2015-11-01

To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N(2)-dG. To investigate structural differences between Y-Family-classes, regions are swapped between DNAP IV (a κ/IV-class-member) and Dpo4 (a η/V-class-member); the kinetic consequences are evaluated via primer-extension studies with a BP-N(2)-dG-containing template. Four key structural elements are revealed. (1) Y-Family DNAPs have discreet non-covalent contacts between their little finger-domain (LF-Domain) and their catalytic core-domain (CC-Domain), which we call "non-covalent bridges" (NCBs). Arg37 and Arg38 in DNAP IV's CC-Domain near the active site form a non-covalent bridge (AS-NCB) by interacting with Glu251 and Asp252, respectively, in DNAP IV's LF-Domain. Without these interactions dATP/dGTP/dTTP misinsertions increase. DNAP IV's AS-NCB suppresses misinsertions better than Dpo4's equivalent AS-NCB. (2) DNAP IV also suppresses dATP/dGTP/dTTP misinsertions via a second non-covalent bridge, which is ∼8Å from the active site (Distal-NCB). Dpo4 has no Distal-NCB, rendering it inferior at dATP/dGTP/dTTP suppression. (3) dCTP insertion is facilitated by the larger minor groove opening near the active site in DNAP IV versus Dpo4, which is sensible given that Watson/Crick-like [dCTP:BP-N(2)-dG] pairing requires the BP-moiety to be in the minor groove. (4) Compared to Dpo4, DNAP IV has a smaller major groove opening, which suppresses dGTP misinsertion, implying BP-N(2)-dG bulk in the major groove during Hoogsteen syn-adduct-dG:dGTP pairing. In summary, DNAP IV has a large minor groove opening to enhance dCTP insertion, a plugged major groove opening to suppress dGTP misinsertion, and two non-covalent bridges (near and distal to the active site) to suppress dATP/dGTP/dTTP misinsertions; collectively these four structural features enhance DNAP IV's dNTP insertion fidelity opposite a BP-N(2)-dG adduct compared to Dpo4. Copyright © 2015 Elsevier B.V. All rights reserved.

[Isolation and characterization of polyphenols in seed of Litchi chinensis].

PubMed

Yan, Ren-Liang; Liu, Zhi-Gang

2009-04-01

To study the chemical constituents of polyphenols in seed of Litchi chinensis. The seeds of Litchi chinensis were extracted by 65% ethanol, then the compounds were separated by repeated silica gel, polyamide and preparative TLC. The structures of polyphones isolated were identified by analysis of their spectral datas and chemical properties. Four polyphones compounds were isolated as protocatechuic aldehyde (I), protocatechuic acid (II), daucosterol (III) and (-) -epicatichin (IV). Compounds I , III and IV are isolated from this plant for the first time.

The utility of rat jejunal permeability for biopharmaceutics classification system.

PubMed

Zakeri-Milani, Parvin; Valizadeh, Hadi; Tajerzadeh, Hosnieh; Islambulchilar, Ziba

2009-12-01

The biopharmaceutical classification system has been developed to provide a scientific approach for classifying drug compounds based on their dose/solubility ratio and human intestinal permeability. Therefore in this study a new classification is presented, which is based on a correlation between rat and human intestinal permeability values. In situ technique in rat jejunum was used to determine the effective intestinal permeability of tested drugs. Then three dimensionless parameters--dose number, absorption number, and dissolution number (D(o), A(n), and D(n))--were calculated for each drug. Four classes of drugs were defined, that is, class I, D(0) < 0.5, P(eff(rat)) > 5.09 x 10(-5) cm/s; class II, D(o) > 1, P(eff(rat)) > 5.09 x 10( -5) cm/s; class III, D(0) < 0.5, P(eff(rat)) < 4.2 x 10(-5) cm/s; and class IV, D(o) > 1, P(eff(rat)) < 4.2 x 10(-5) cm/s. A region of borderline drugs (0.5 < D(o) < 1, 4.2 x 10(-5) < P(eff(rat)) < 5.09 x 10(-5) cm/s) was also defined. According to obtained results and proposed classification for drugs, it is concluded that drugs could be categorized correctly based on dose number and their intestinal permeability values in rat model using single-pass intestinal perfusion technique. This classification enables us to remark defined characteristics for intestinal absorption of all four classes using suitable cutoff points for both dose number and rat effective intestinal permeability values.

Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices.

PubMed

Bajema, Ingeborg M; Wilhelmus, Suzanne; Alpers, Charles E; Bruijn, Jan A; Colvin, Robert B; Cook, H Terence; D'Agati, Vivette D; Ferrario, Franco; Haas, Mark; Jennette, J Charles; Joh, Kensuke; Nast, Cynthia C; Noël, Laure-Hélène; Rijnink, Emilie C; Roberts, Ian S D; Seshan, Surya V; Sethi, Sanjeev; Fogo, Agnes B

2018-04-01

We present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting of 18 members of an international nephropathology working group in Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues for which we can propose adjustments based on existing evidence and current consensus opinion (phase 1). New definitions are provided for mesangial hypercellularity and for cellular, fibrocellular, and fibrous crescents. The term "endocapillary proliferation" is eliminated and the definition of endocapillary hypercellularity considered in some detail. We also eliminate the class IV-S and IV-G subdivisions of class IV lupus nephritis. The active and chronic designations for class III/IV lesions are replaced by a proposal for activity and chronicity indices that should be applied to all classes. In the activity index, we include fibrinoid necrosis as a specific descriptor. We also make recommendations on issues for which there are limited data at present and that can best be addressed in future studies (phase 2). We propose to proceed to these investigations, with clinicopathologic studies and tests of interobserver reproducibility to evaluate the applications of the proposed definitions and to classify lupus nephritis lesions. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Examining the Stability of "DSM-IV" and Empirically Derived Eating Disorder Classification: Implications for "DSM-5"

ERIC Educational Resources Information Center

Peterson, Carol B.; Crow, Scott J.; Swanson, Sonja A.; Crosby, Ross D.; Wonderlich, Stephen A.; Mitchell, James E.; Agras, W. Stewart; Halmi, Katherine A.

2011-01-01

Objective: The purpose of this investigation was to derive an empirical classification of eating disorder symptoms in a heterogeneous eating disorder sample using latent class analysis (LCA) and to examine the longitudinal stability of these latent classes (LCs) and the stability of DSM-IV eating disorder (ED) diagnoses. Method: A total of 429…

Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

NASA Astrophysics Data System (ADS)

Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

The role of single immediate loading implant in long Class IV Kennedy mandibular partial denture.

PubMed

Mohamed, Gehan F; El Sawy, Amal A

2012-10-01

The treatment of long-span Kennedy class IV considers a prosthodontic challenge. This study evaluated the integrity of principle abutments in long Kennedy class IV clinically and radiographically, when rehabilitated with conventional metallic partial denture as a control group and mandibular partial overdentures supported with single immediately loaded implant in symphyseal as a study group. Twelve male patients were divided randomly allotted into two equal groups. First group patients received removable metallic partial denture, whereas in the second group, patients received partial overdentures supported with single immediately loaded implant in symphyseal region. The partial dentures design in both groups was the same. Long-cone paralleling technique and transmission densitometer were used at the time of denture insertion, 3, 6, and 12 months. Gingival index, bone loss, and optical density were measured for principle abutments during the follow-up. A significant reduction in bone loss and density were detected in group II comparing with group I. Gingival index had no significant change (p-value < 0.05). A single symphyseal implant in long span class IV Kennedy can play a pivotal role to improve the integrity of the principle abutments and alveolar bone support. © 2010 Wiley Periodicals, Inc.

A validated UPLC-MS/MS method for the analysis of linezolid and a novel oxazolidinone derivative (PH027) in plasma and its application to tissue distribution study in rabbits.

PubMed

Hedaya, Mohsen A; Thomas, Vidhya; Abdel-Hamid, Mohamed E; Kehinde, Elijah O; Phillips, Oludotun A

2017-01-01

Linezolid is the first approved oxazolidinone antibacterial agent, whereas PH027 is a novel compound of the same class that exhibits good in vitro antibacterial activity. The objective of this study was to develop an UPLC-MS/MS assay for the analysis of linezolid and PH027 in plasma and to apply the method for comparative pharmacokinetic and tissue distribution studies of both compounds. Plasma samples and calibrators were extracted with diethyl ether after addition of the internal standard solution. After evaporation of the ether layer, the residue was reconstituted in mobile phase and injected into UPLC-MS/MS. The mobile phase consisted of 2mM ammonium acetate buffer solution and acetonitrile (70:30) at a flow rate of 0.2ml/min. Separation was achieved using UPLC BEH C 18 column, and quantitative determination of the analytes was performed using multiple-reaction monitoring (MRM) scanning mode. The method was validated by analyzing quality control tissue homogenate samples, and was applied to analyze tissue homogenate samples obtained following IV injections of linezolid and PH027 in rabbits. The developed UPLC-MS/MS method was linear in the concentration range of 50-5000ng/ml. Validation of the method proved that the method's precision, selectivity and stability were all within the acceptable limits. Linezolid and PH027 concentrations were accurately determined in the quality control tissue homogenate samples, and analysis of samples obtained following IV administration of the two compounds showed that the tissue to plasma concentration ratio of PH027 was higher than that of linezolid probably due to its higher lipophilicity. The developed UPLC-MS/MS method for the analysis of linezolid and PH027 in rabbit's plasma can accurately determine the concentrations of these compounds in different tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

Dissimilatory Fe(III) and Mn(IV) reduction.

PubMed Central

Lovley, D R

1991-01-01

The oxidation of organic matter coupled to the reduction of Fe(III) or Mn(IV) is one of the most important biogeochemical reactions in aquatic sediments, soils, and groundwater. This process, which may have been the first globally significant mechanism for the oxidation of organic matter to carbon dioxide, plays an important role in the oxidation of natural and contaminant organic compounds in a variety of environments and contributes to other phenomena of widespread significance such as the release of metals and nutrients into water supplies, the magnetization of sediments, and the corrosion of metal. Until recently, much of the Fe(III) and Mn(IV) reduction in sedimentary environments was considered to be the result of nonenzymatic processes. However, microorganisms which can effectively couple the oxidation of organic compounds to the reduction of Fe(III) or Mn(IV) have recently been discovered. With Fe(III) or Mn(IV) as the sole electron acceptor, these organisms can completely oxidize fatty acids, hydrogen, or a variety of monoaromatic compounds. This metabolism provides energy to support growth. Sugars and amino acids can be completely oxidized by the cooperative activity of fermentative microorganisms and hydrogen- and fatty-acid-oxidizing Fe(III) and Mn(IV) reducers. This provides a microbial mechanism for the oxidation of the complex assemblage of sedimentary organic matter in Fe(III)- or Mn(IV)-reducing environments. The available evidence indicates that this enzymatic reduction of Fe(III) or Mn(IV) accounts for most of the oxidation of organic matter coupled to reduction of Fe(III) and Mn(IV) in sedimentary environments. Little is known about the diversity and ecology of the microorganisms responsible for Fe(III) and Mn(IV) reduction, and only preliminary studies have been conducted on the physiology and biochemistry of this process. PMID:1886521

Latent class instrumental variables: A clinical and biostatistical perspective

PubMed Central

Baker, Stuart G.; Kramer, Barnett S.; Lindeman, Karen S.

2015-01-01

In some two-arm randomized trials, some participants receive the treatment assigned to the other arm as a result of technical problems, refusal of a treatment invitation, or a choice of treatment in an encouragement design. In some before-and-after studies, the availability of a new treatment changes from one time period to this next. Under assumptions that are often reasonable, the latent class instrumental variable (IV) method estimates the effect of treatment received in the aforementioned scenarios involving all-or-none compliance and all-or-none availability. Key aspects are four initial latent classes (sometimes called principal strata) based on treatment received if in each randomization group or time period, the exclusion restriction assumption (in which randomization group or time period is an instrumental variable), the monotonicity assumption (which drops an implausible latent class from the analysis), and the estimated effect of receiving treatment in one latent class (sometimes called efficacy, the local average treatment effect, or the complier average causal effect). Since its independent formulations in the biostatistics and econometrics literatures, the latent class IV method (which has no well-established name) has gained increasing popularity. We review the latent class IV method from a clinical and biostatistical perspective, focusing on underlying assumptions, methodological extensions, and applications in our fields of obstetrics and cancer research. PMID:26239275

In vitro biphasic dissolution tests and their suitability for establishing in vitro-in vivo correlations: A historical review.

PubMed

Pestieau, Aude; Evrard, Brigitte

2017-05-01

For many decades, one of the most critical issues in the pharmaceutical industry has been the poor solubility of some drugs. Indeed, a prerequisite for drug absorption is the presence of dissolved drug at the absorption site and this can be challenging for compounds with low aqueous solubility such as BCS class II (low solubility, high permeability) and IV (low solubility, low permeability) compounds. If the development of oral delivery formulations of these compounds is frequently challenging to formulation scientists in the pharmaceutical industry, the in vitro evaluation of these new formulations is also a great challenge. One alternative approach to overcome the problems encountered with conventional dissolution methods is the use of biphasic dissolution systems. This review provides an overview of the origin and the evolution over time of the biphasic systems and the growing interest among scientists regarding their suitability for establishing in vitro-in vivo correlations. The evolution of these systems and their applications from the 1960s to the present day, such as in system variants and improvements, analysis of complex formulations, discriminatory power, bio-relevance, precipitation and supersaturation visualization, etc. will be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

INORGANIC COORDINATION POLYMERS. IV. THE ATTEMPTED REPLACEMENT OF ACETYLACETONATE LIGANDS WITH PICOLINATE LIGANDS,

DTIC Science & Technology

HETEROCYCLIC COMPOUNDS, PHOSPHENE OXIDES, BENZENE, CHROMIUM COMPOUNDS, CHEMICAL REAC, SYNTHESIS (CHEMISTRY), CHEMICAL ANALY, SPECTRA (INFRARED), ABSORPTION, DISPLACE, POLYMERIZATION, ORGANIC NITROGEN, AROMATIC COMPOUNDS.

Luminescent and thermochromic properties of tellurium(IV) halide complexes with cesium

NASA Astrophysics Data System (ADS)

Sedakova, T. V.; Mirochnik, A. G.

2016-02-01

The spectral-luminescent and thermochromic properties of complex compounds of the composition Cs2TeHal6 (Hal = Cl, Br, I) are studied. The interrelation between the geometric structure and spectral-luminescent properties is studied using the example on complex compounds of tellurium(IV) halides with cesium. The Stokes shift and the luminescence intensity of Te(IV) ions with island octahedral coordination are found to depend on the position of the A band in the luminescence excitation spectra, the diffuse reflection, and the energy of the luminescent 3 P 1 → 1 S 0 transition of the tellurium(IV) ion. The maximum luminescence intensity and the minimum Stokes shift at 77 and 300 K are observed for Cs2TeCl6. The geometrical and electronic factors responsible for luminescence intensification in Te(IV) complexes under study are analyzed.

[Studies on chemical constituents of cultivated Cistanche salsa].

PubMed

Yang, Jian-Hu; Hu, Jun-Ping; Rena, Kasimu; Du, Nian-Sheng

2008-11-01

To study the chemical constituents of cultivated Cistanche salsa. Compounds were isolated and purified on several chromatography, and then were identified by physico-chemical properties and structurally elucidated by spectral analysis. Seven compounds were isolated and identified as beta-sitosterol (I), daucosterol (II), beta-sitosteryl glucoside 3'-O-heptadecoicate (III), 8-hydroxygeraniol 1-beta-D-glucopyranoside (IV), 2-methanol-5-hydroxy-pyridine (V), betaine (VI), galactitol (VII). The chemical constituents of artificial cultivated Cistanche salsa are studied for the first time. Among them, compound III and IV are isolated from the plant for the first time, compound V is isolated from this genus for the first time.

Evaluation of spiropiperidine hydantoins as a novel class of antimalarial agents.

PubMed

Meyers, Marvin J; Anderson, Elizabeth J; McNitt, Sarah A; Krenning, Thomas M; Singh, Megh; Xu, Jing; Zeng, Wentian; Qin, Limei; Xu, Wanwan; Zhao, Siting; Qin, Li; Eickhoff, Christopher S; Oliva, Jonathan; Campbell, Mary A; Arnett, Stacy D; Prinsen, Michael J; Griggs, David W; Ruminski, Peter G; Goldberg, Daniel E; Ding, Ke; Liu, Xiaorong; Tu, Zhengchao; Tortorella, Micky D; Sverdrup, Francis M; Chen, Xiaoping

2015-08-15

Given the rise of parasite resistance to all currently used antimalarial drugs, the identification of novel chemotypes with unique mechanisms of action is of paramount importance. Since Plasmodium expresses a number of aspartic proteases necessary for its survival, we have mined antimalarial datasets for drug-like aspartic protease inhibitors. This effort led to the identification of spiropiperidine hydantoins, bearing similarity to known inhibitors of the human aspartic protease β-secretase (BACE), as new leads for antimalarial drug discovery. Spiropiperidine hydantoins have a dynamic structure-activity relationship profile with positions identified as being tolerant of a variety of substitution patterns as well as a key piperidine N-benzyl phenol pharmacophore. Lead compounds 4e (CWHM-123) and 12k (CWHM-505) are potent antimalarials with IC50 values against Plasmodium falciparum 3D7 of 0.310 μM and 0.099 μM, respectively, and the former features equivalent potency on the chloroquine-resistant Dd2 strain. Remarkably, these compounds do not inhibit human aspartic proteases BACE, cathepsins D and E, or Plasmodium plasmepsins II and IV despite their similarity to known BACE inhibitors. Although the current leads suffer from poor metabolic stability, they do fit into a drug-like chemical property space and provide a new class of potent antimalarial agents for further study. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

PubMed

Choi, Yookyung Christy; Saw, Stephen; Soliman, Daniel; Bingham, Angela L; Pontiggia, Laura; Hunter, Krystal; Chuang, Linda; Siemianowski, Laura A; Ereshefsky, Benjamin; Hollands, James M

2017-11-01

A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m 2 ), obesity class I and II (BMI 30-39.9kg/m 2 ), and obesity class III (BMI≥40 kg/m 2 ) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

Digitized Speech Characteristics in Patients with Maxillectomy Defects.

PubMed

Elbashti, Mahmoud E; Sumita, Yuka I; Hattori, Mariko; Aswehlee, Amel M; Taniguchi, Hisashi

2017-12-06

Accurate evaluation of speech characteristics through formant frequency measurement is important for proper speech rehabilitation in patients after maxillectomy. This study aimed to evaluate the utility of digital acoustic analysis and vowel pentagon space for the prediction of speech ability after maxillectomy, by comparing the acoustic characteristics of vowel articulation in three classes of maxillectomy defects. Aramany's classifications I, II, and IV were used to group 27 male patients after maxillectomy. Digital acoustic analysis of five Japanese vowels-/a/, /e/, /i/, /o/, and /u/-was performed using a speech analysis system. First formant (F1) and second formant (F2) frequencies were calculated using an autocorrelation method. Data were plotted on an F1-F2 plane for each patient, and the F1 and F2 ranges were calculated. The vowel pentagon spaces were also determined. One-way ANOVA was applied to compare all results between the three groups. Class II maxillectomy patients had a significantly higher F2 range than did Class I and Class IV patients (p = 0.002). In contrast, there was no significant difference in the F1 range between the three classes. The vowel pentagon spaces were significantly larger in class II maxillectomy patients than in Class I and Class IV patients (p = 0.014). The results of this study indicate that the acoustic characteristics of maxillectomy patients are affected by the defect area. This finding may provide information for obturator design based on vowel articulation and defect class. © 2017 by the American College of Prosthodontists.

Studies on the chemical constituents from the stem and leaves of Tagetes erecta.

PubMed

Zhang, Yu; Zhang, Ting-Ting

2010-09-01

To investigate the chemical constituents of the stem and leaves of Tagetes erecta. The materials extracted with ethanol were first purified with D101 resin and then separated by repeated silica gel column chromatography as well as recrystallization to get single compounds. The chemical structures of the compounds were elucidated on the basis of physicochemical properties, spectroscopic analysis and comparing with standard sample and literatures. Six compounds were identified as 4'-methoxy-eupatolitin-3-O-glucoside (I), kaempferitrin (II), rutin (III), beta-sitosterol (IV), daucosterol (V) and gallic acid (VI). Compounds I, II, III are isolated from the plant for the first time; the compounds IV, V, VI are isolated from the stem and leaves of the plant for the first time.

Drug formulations intended for the global market should be tested for stability under tropical climatic conditions.

PubMed

Risha, P G; Vervaet, C; Vergote, G; Bortel, L Van; Remon, J P

2003-06-01

The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.

[Studies on the chemical constituents of the ethyl acetate portion of Nervilia fordii].

PubMed

Zhen, Han-shen; Zhou, Yan-yuan; Yuan, Ye-fei; Mo, Huan-heng; Zhong, Zhen-guo; Liang, Chen-yan

2007-08-01

To study the chemical constituents of the ethyl acetate portion in the herb of Nervilia fordii from guangxi. The constituents were separated and purified by using column chromatography with silica gel. These compounds were identified by their physical and spectral data. Five compounds were isolated and identified as norleucine (crystal I), 24 (S/beta)-dihydrocycloeucalenol-(E)-p-hydroxy cinnamate (crystal II) , rhamnocitrin (crystal III), rhamnazin (crystal IV), daucosterol (crystal V). Compounds I , II, III, IV, V were isolated from this plant for the first time.

[Studies on the flavonoids from Dendranthema lavandulifolium].

PubMed

Shen, Y X; Quan, L H; Guan, L; Chen, J M

1997-06-01

From the whole plant of Dendranthema lavandulifolium, two flavonoides (I, II) and two flavone glycosides (III, IV) were isolated. They were identified as luteolin (I), apigenin (II), 5-hydroxy-4'-methoxy-flavone-7-O-alpha-L-rhamnopyranosyl(1-->6)-beta- D-glucopyranosyl (acaciin III) and 5-hydroxy-4'-methoxy-flavone-7-O-alpha-L-rhamnopyranosyl (1-->6) [2-O-acetyl-beta-D-glucopyranosyl(1-->2)]-beta-D-glucopyranoside (IV) by means of IR, UV, 1H-NMR, 13C-NMR, EI-MS, HRFAB, etc. Among these four compounds, I, II were isolated for the first time from this plant, IV is a new compound.

A novel arctigenin-containing latex glove prevents latex allergy by inhibiting type I/IV allergic reactions.

PubMed

Wang, Yong-Xin; Xue, Dan-Ting; Liu, Meng; Zhou, Zheng-Min; Shang, Jing

2016-03-01

The present study aimed at developing a natural compound with anti-allergic effect and stability under latex glove manufacturing conditions and investigating whether its anti-allergic effect is maintained after its addition into the latex. The effects of nine natural compounds on growth of the RBL-2H3 cells and mouse primary spleen lymphocytes were determined using MTT assay. The compounds included glycyrrhizin, osthole, tetrandrine, tea polyphenol, catechin, arctigenin, oleanolic acid, baicalin and oxymatrine. An ELISA assay was used for the in vitro anti-type I/IV allergy screening; in this process β-hexosaminidase, histamine, and IL-4 released from RBL-2H3 cell lines and IFN-γ and IL-2 released from mouse primary spleen lymphocytes were taken as screening indices. The physical stability of eight natural compounds and the dissolubility of arctigenin, selected based on the in vitro pharnacodynamaic screening and the stability evaluation, were detected by HPLC. The in vivo pharmacodynamic confirmation of arctigenin and final latex product was evaluated with a passive cutaneous anaphylaxis (PCA) model and an allergen-specific skin response model. Nine natural compounds showed minor growth inhibition on RBL-2H3 cells and mouse primary spleen lymphocytes. Baicalin and arctigenin had the best anti-type I and IV allergic effects among the natural compounds based on the in vitro pharmacodynamic screening. Arctigenin and catechin had the best physical stability under different manufacturing conditions. Arctigenin was the selected for further evaluation and proven to have anti-type I and IV allergic effects in vivo in a dose-dependent manner. The final product of the arctigenin-containing latex glove had anti-type I and IV allergic effects in vivo which were mainly attributed to arctigenin as proved from the dissolubility results. Arctigenin showed anti-type I and IV allergic effects in vitro and in vivo, with a good stability under latex glove manufacturing conditions, and a persistent anti-allergic effect after being added into the latex to prevent latex allergy. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Interobserver agreement on histopathological lesions in class III or IV lupus nephritis.

PubMed

Wilhelmus, Suzanne; Cook, H Terence; Noël, Laure-Hélène; Ferrario, Franco; Wolterbeek, Ron; Bruijn, Jan A; Bajema, Ingeborg M

2015-01-07

To treat lupus nephritis effectively, proper identification of the histologic class is essential. Although the classification system for lupus nephritis is nearly 40 years old, remarkably few studies have investigated interobserver agreement. Interobserver agreement among nephropathologists was studied, particularly with respect to the recognition of class III/IV lupus nephritis lesions, and possible causes of disagreement were determined. A link to a survey containing pictures of 30 glomeruli was provided to all 360 members of the Renal Pathology Society; 34 responses were received from 12 countries (a response rate of 9.4%). The nephropathologist was asked whether glomerular lesions were present that would categorize the biopsy as class III/IV. If so, additional parameters were scored. To determine the interobserver agreement among the participants, κ or intraclass correlation values were calculated. The intraclass correlation or κ-value was also calculated for two separate levels of experience (specifically, nephropathologists who were new to the field or moderately experienced [less experienced] and nephropathologists who were highly experienced). Intraclass correlation for the presence of a class III/IV lesion was 0.39 (poor). The κ/intraclass correlation values for the additional parameters were as follows: active, chronic, or both: 0.36; segmental versus global: 0.39; endocapillary proliferation: 0.46; influx of inflammatory cells: 0.32; swelling of endothelial cells: 0.46; extracapillary proliferation: 0.57; type of crescent: 0.46; and wire loops: 0.35. The highly experienced nephropathologists had significantly less interobserver variability compared with the less experienced nephropathologists (P=0.004). There is generally poor agreement in terms of recognizing class III/IV lesions. Because experience clearly increases interobserver agreement, this agreement may be improved by training nephropathologists. These results also underscore the importance of a central review by experienced nephropathologists in clinical trials. Copyright © 2015 by the American Society of Nephrology.

A 3-tier classification of cerebral arteriovenous malformations. Clinical article.

PubMed

Spetzler, Robert F; Ponce, Francisco A

2011-03-01

The authors propose a 3-tier classification for cerebral arteriovenous malformations (AVMs). The classification is based on the original 5-tier Spetzler-Martin grading system, and reflects the treatment paradigm for these lesions. The implications of this modification in the literature are explored. Class A combines Grades I and II AVMs, Class B are Grade III AVMs, and Class C combines Grades IV and V AVMs. Recommended management is surgery for Class A AVMs, multimodality treatment for Class B, and observation for Class C, with exceptions to the latter including recurrent hemorrhages and progressive neurological deficits. To evaluate whether combining grades is warranted from the perspective of surgical outcomes, the 3-tier system was applied to 1476 patients from 7 surgical series in which results were stratified according to Spetzler-Martin grades. Pairwise comparisons of individual Spetzler-Martin grades in the series analyzed showed the fewest significant differences (p < 0.05) in outcomes between Grades I and II AVMs and between Grades IV and V AVMs. In the pooled data analysis, significant differences in outcomes were found between all grades except IV and V (p = 0.38), and the lowest relative risks were found between Grades I and II (1.066) and between Grades IV and V (1.095). Using the pooled data, the predictive accuracies for surgical outcomes of the 5-tier and 3-tier systems were equivalent (receiver operating characteristic curve area 0.711 and 0.713, respectively). Combining Grades I and II AVMs and combining Grades IV and V AVMs is justified in part because the differences in surgical results between these respective pairs are small. The proposed 3-tier classification of AVMs offers simplification of the Spetzler-Martin system, provides a guide to treatment, and is predictive of outcome. The revised classification not only simplifies treatment recommendations; by placing patients into 3 as opposed to 5 groups, statistical power is markedly increased for series comparisons.

Action mechanism of 6, 6'-dihydroxythiobinupharidine from Nuphar japonicum, which showed anti-MRSA and anti-VRE activities.

PubMed

Okamura, Shinya; Nishiyama, Eri; Yamazaki, Tomohiro; Otsuka, Nao; Taniguchi, Shoko; Ogawa, Wakano; Hatano, Tsutomu; Tsuchiya, Tomofusa; Kuroda, Teruo

2015-06-01

Multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE), cause serious infections at clinical sites, for which the development of new drugs is necessary. We screened candidates for new antibiotics and investigated its action mechanism. An antimicrobial compound was isolated from an extract of Nuphar japonicum. Its chemical structure was determined by NMR, MS, and optical rotation. We measured its minimum inhibitory concentration (MIC) using the microdilution method. The effects of the compound on DNA gyrase and DNA topoisomerase IV were investigated with DNA supercoiling, decatenation, and cleavage assay. We isolated and identified 6,6'-dihydroxythiobinupharidine as the antimicrobial compound. The MIC of this compound was 1-4 μg/mL against various MRSA and VRE strains. We also demonstrated that this compound inhibited DNA topoisomerase IV (IC50 was 10-15 μM), but not DNA gyrase in S. aureus, both of which are known to be the targets of quinolone antibiotics and necessary for DNA replication. However, this compound only exhibited slight cross-resistance to norfloxacin-resistant S. aureus, which indicated that DTBN might inhibit other targets besides topoisomerase IV. These results suggest that 6,6'-dihydroxythiobinupharidine may be a potent candidate or seed for novel antibacterial agents. DTBN from N. japonicum showed anti-MRSA and anti-VRE activities. DTBN might be involved in the inhibition of DNA topoisomerase IV. DTBN might be useful as a seed compound. The information on the inhibition mechanism of DTBN will be useful for the modification of DTBN towards developing novel anti-MRSA and anti-VRE drug. Copyright © 2015 Elsevier B.V. All rights reserved.

37 CFR 2.6 - Trademark fees.

Code of Federal Regulations, 2010 CFR

2010-07-01

... filing an application on paper, per class $375.00 (ii) For filing an application through TEAS, per class $325.00 (iii) For filing a TEAS Plus application under § 2.22, per class $275.00 (iv) Additional...

X-ray Emission Spectroscopy of Biomimetic Mn Coordination Complexes.

PubMed

Jensen, Scott C; Davis, Katherine M; Sullivan, Brendan; Hartzler, Daniel A; Seidler, Gerald T; Casa, Diego M; Kasman, Elina; Colmer, Hannah E; Massie, Allyssa A; Jackson, Timothy A; Pushkar, Yulia

2017-06-15

Understanding the function of Mn ions in biological and chemical redox catalysis requires precise knowledge of their electronic structure. X-ray emission spectroscopy (XES) is an emerging technique with a growing application to biological and biomimetic systems. Here, we report an improved, cost-effective spectrometer used to analyze two biomimetic coordination compounds, [Mn IV (OH) 2 (Me 2 EBC)] 2+ and [Mn IV (O)(OH)(Me 2 EBC)] + , the second of which contains a key Mn IV ═O structural fragment. Despite having the same formal oxidation state (Mn IV ) and tetradentate ligands, XES spectra from these two compounds demonstrate different electronic structures. Experimental measurements and DFT calculations yield different localized spin densities for the two complexes resulting from Mn IV -OH conversion to Mn IV ═O. The relevance of the observed spectroscopic changes is discussed for applications in analyzing complex biological systems such as photosystem II. A model of the S 3 intermediate state of photosystem II containing a Mn IV ═O fragment is compared to recent time-resolved X-ray diffraction data of the same state.

Cloning and heterologous expression of a novel subgroup of class IV polyhydroxyalkanoate synthase genes from the genus Bacillus.

PubMed

Mizuno, Kouhei; Kihara, Takahiro; Tsuge, Takeharu; Lundgren, Benjamin R; Sarwar, Zaara; Pinto, Atahualpa; Nomura, Christopher T

2017-01-01

Many microorganisms harbor genes necessary to synthesize biodegradable plastics known as polyhydroxyalkanoates (PHAs). We surveyed a genomic database and discovered a new cluster of class IV PHA synthase genes (phaRC). These genes are different in sequence and operon structure from any previously reported PHA synthase. The newly discovered PhaRC synthase was demonstrated to produce PHAs in recombinant Escherichia coli.

Optical radiation hazards of laser welding processes. Part II: CO2 laser.

PubMed

Rockwell, R J; Moss, C E

1989-08-01

There has been an extensive growth within the last five years in the use of high-powered lasers in various metalworking processes. The two types of lasers used most frequently for laser welding/cutting processes are the Neodymium-yttrium-aluminum-garnet (Nd:YAG) and the carbon dioxide (CO2) systems. When such lasers are operated in an open beam configuration, they are designated as a Class IV laser system. Class IV lasers are high-powered lasers that may present an eye and skin hazard under most common exposure conditions, either directly or when the beam has been diffusely scattered. Significant control measures are required for unenclosed (open beam), Class IV laser systems since workers may be exposed to scattered or reflected beams during the operation, maintenance, and service of these lasers. In addition to ocular and/or skin exposure hazards, such lasers also may present a multitude of nonlaser beam occupational concerns. Radiant energy measurements are reported for both the scattered laser radiation and the plasma-related plume radiations released during typical high-powered CO2 laser-target interactions. In addition, the application of the nominal hazard zone (NHZ) and other control measures also are discussed with special emphasis on Class IV industrial CO2 laser systems.

Deviation between the chemistry of Ce(IV) and Pu(IV) and routes to ordered and disordered heterobimetallic 4f/5f and 5f/5f phosphonates.

PubMed

Diwu, Juan; Wang, Shuao; Good, Justin J; DiStefano, Victoria H; Albrecht-Schmitt, Thomas E

2011-06-06

The heterobimetallic actinide compound UO(2)Ce(H(2)O)[C(6)H(4)(PO(3)H)(2)](2)·H(2)O was prepared via the hydrothermal reaction of U(VI) and Ce(IV) in the presence of 1,2-phenylenediphosphonic acid. We demonstrate that this is a kinetic product that is not stable with respect to decomposition to the monometallic compounds. Similar reactions have been explored with U(VI) and Ce(III), resulting in the oxidation of Ce(III) to Ce(IV) and the formation of the Ce(IV) phosphonate, Ce[C(6)H(4)(PO(3)H)(PO(3)H(2))][C(6)H(4)(PO(3)H)(PO(3))]·2H(2)O, UO(2)Ce(H(2)O)[C(6)H(4)(PO(3)H)(2)](2)·H(2)O, and UO(2)[C(6)H(4)(PO(3)H)(2)](H(2)O)·H(2)O. In comparison, the reaction of U(VI) with Np(VI) only yields Np[C(6)H(4)(PO(3)H)(2)](2)·2H(2)O and aqueous U(VI), whereas the reaction of U(VI) with Pu(VI) yields the disordered U(VI)/Pu(VI) compound, (U(0.9)Pu(0.1))O(2)[C(6)H(4)(PO(3)H)(2)](H(2)O)·H(2)O, and the Pu(IV) phosphonate, Pu[C(6)H(4)(PO(3)H)(PO(3)H(2))][C(6)H(4)(PO(3)H)(PO(3))]·2H(2)O. The reactions of Ce(IV) with Np(VI) yield disordered heterobimetallic phosphonates with both M[C(6)H(4)(PO(3)H)(PO(3)H(2))][C(6)H(4)(PO(3)H)(PO(3))]·2H(2)O (M = Ce, Np) and M[C(6)H(4)(PO(3)H)(2)](2)·2H(2)O (M = Ce, Np) structures, as well as the Ce(IV) phosphonate Ce[C(6)H(4)(PO(3)H)(PO(3)H(2))][C(6)H(4)(PO(3)H)(PO(3))]·2H(2)O. Ce(IV) reacts with Pu(IV) to yield the Pu(VI) compound, PuO(2)[C(6)H(4)(PO(3)H)(2)](H(2)O)·3H(2)O, and a disordered heterobimetallic Pu(IV)/Ce(IV) compound with the M[C(6)H(4)(PO(3)H)(PO(3)H(2))][C(6)H(4)(PO(3)H)(PO(3))]·2H(2)O (M = Ce, Pu) structure. Mixtures of Np(VI) and Pu(VI) yield disordered heterobimetallic Np(IV)/Pu(IV) phosphonates with both the An[C(6)H(4)(PO(3)H)(PO(3)H(2))][C(6)H(4)(PO(3)H)(PO(3))]·2H(2)O (M = Np, Pu) and An[C(6)H(4)(PO(3)H)(2)](2)·2H(2)O (M = Np, Pu) formulas. © 2011 American Chemical Society

Synthesis and in vitro activity of dicationic bis-benzimidazoles as a new class of anti-MRSA and anti-VRE agents.

PubMed

Hu, Laixing; Kully, Maureen L; Boykin, David W; Abood, Norman

2009-03-01

A new class of novel bis-benzimidazole diamidine compounds have been synthesized and evaluated for in vitro antibacterial activities, including drug-resistant bacterial strains. Anti-MRSA and anti-VRE activities of the most potent compound 1 were more active than Vancomycin. The mechanism of action for this class of compounds appears to be different from existing antibiotics. Bis-benzimidazole diamidine compounds have potential for further investigation as a new class of potent anti-MRSA and anti-VRE agents.

Organization and variation analysis of 5S rDNA in different ploidy-level hybrids of red crucian carp × topmouth culter.

PubMed

He, Weiguo; Qin, Qinbo; Liu, Shaojun; Li, Tangluo; Wang, Jing; Xiao, Jun; Xie, Lihua; Zhang, Chun; Liu, Yun

2012-01-01

Through distant crossing, diploid, triploid and tetraploid hybrids of red crucian carp (Carassius auratus red var., RCC♀, Cyprininae, 2n = 100) × topmouth culter (Erythroculter ilishaeformis Bleeker, TC♂, Cultrinae, 2n = 48) were successfully produced. Diploid hybrids possessed 74 chromosomes with one set from RCC and one set from TC; triploid hybrids harbored 124 chromosomes with two sets from RCC and one set from TC; tetraploid hybrids had 148 chromosomes with two sets from RCC and two sets from TC. The 5S rDNA of the three different ploidy-level hybrids and their parents were sequenced and analyzed. There were three monomeric 5S rDNA classes (designated class I: 203 bp; class II: 340 bp; and class III: 477 bp) in RCC and two monomeric 5S rDNA classes (designated class IV: 188 bp, and class V: 286 bp) in TC. In the hybrid offspring, diploid hybrids inherited three 5S rDNA classes from their female parent (RCC) and only class IV from their male parent (TC). Triploid hybrids inherited class II and class III from their female parent (RCC) and class IV from their male parent (TC). Tetraploid hybrids gained class II and class III from their female parent (RCC), and generated a new 5S rDNA sequence (designated class I-N). The specific paternal 5S rDNA sequence of class V was not found in the hybrid offspring. Sequence analysis of 5S rDNA revealed the influence of hybridization and polyploidization on the organization and variation of 5S rDNA in fish. This is the first report on the coexistence in vertebrates of viable diploid, triploid and tetraploid hybrids produced by crossing parents with different chromosome numbers, and these new hybrids are novel specimens for studying the genomic variation in the first generation of interspecific hybrids, which has significance for evolution and fish genetics.

Latent class instrumental variables: a clinical and biostatistical perspective.

PubMed

Baker, Stuart G; Kramer, Barnett S; Lindeman, Karen S

2016-01-15

In some two-arm randomized trials, some participants receive the treatment assigned to the other arm as a result of technical problems, refusal of a treatment invitation, or a choice of treatment in an encouragement design. In some before-and-after studies, the availability of a new treatment changes from one time period to this next. Under assumptions that are often reasonable, the latent class instrumental variable (IV) method estimates the effect of treatment received in the aforementioned scenarios involving all-or-none compliance and all-or-none availability. Key aspects are four initial latent classes (sometimes called principal strata) based on treatment received if in each randomization group or time period, the exclusion restriction assumption (in which randomization group or time period is an instrumental variable), the monotonicity assumption (which drops an implausible latent class from the analysis), and the estimated effect of receiving treatment in one latent class (sometimes called efficacy, the local average treatment effect, or the complier average causal effect). Since its independent formulations in the biostatistics and econometrics literatures, the latent class IV method (which has no well-established name) has gained increasing popularity. We review the latent class IV method from a clinical and biostatistical perspective, focusing on underlying assumptions, methodological extensions, and applications in our fields of obstetrics and cancer research. Copyright © 2015 John Wiley & Sons, Ltd.

Histone deacetylase inhibitors: Potential in cancer therapy.

PubMed

Marks, P A; Xu, W-S

2009-07-01

The role of histone deacetylases (HDAC) and the potential of these enzymes as therapeutic targets for cancer, neurodegenerative diseases and a number of other disorders is an area of rapidly expanding investigation. There are 18 HDACs in humans. These enzymes are not redundant in function. Eleven of the HDACs are zinc dependent, classified on the basis of homology to yeast HDACs: Class I includes HDACs 1, 2, 3, and 8; Class IIA includes HDACs 4, 5, 7, and 9; Class IIB, HDACs 6 and 10; and Class IV, HDAC 11. Class III HDACs, sirtuins 1-7, have an absolute requirement for NAD(+), are not zinc dependent and generally not inhibited by compounds that inhibit zinc dependent deacetylases. In addition to histones, HDACs have many nonhistone protein substrates which have a role in regulation of gene expression, cell proliferation, cell migration, cell death, and angiogenesis. HDAC inhibitors (HDACi) have been discovered of different chemical structure. HDACi cause accumulation of acetylated forms of proteins which can alter their structure and function. HDACi can induce different phenotypes in various transformed cells, including growth arrest, apoptosis, reactive oxygen species facilitated cell death and mitotic cell death. Normal cells are relatively resistant to HDACi induced cell death. Several HDACi are in various stages of development, including clinical trials as monotherapy and in combination with other anti-cancer drugs and radiation. The first HDACi approved by the FDA for cancer therapy is suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza), approved for treatment of cutaneous T-cell lymphoma. 2009 Wiley-Liss, Inc.

Groundwater-quality characteristics for the Wyoming Groundwater-Quality Monitoring Network, November 2009 through September 2012

USGS Publications Warehouse

Boughton, Gregory K.

2014-01-01

Groundwater samples were collected from 146 shallow (less than or equal to 500 feet deep) wells for the Wyoming Groundwater-Quality Monitoring Network, from November 2009 through September 2012. Groundwater samples were analyzed for physical characteristics, major ions and dissolved solids, trace elements, nutrients and dissolved organic carbon, uranium, stable isotopes of hydrogen and oxygen, volatile organic compounds, and coliform bacteria. Selected samples also were analyzed for gross alpha radioactivity, gross beta radioactivity, radon, tritium, gasoline range organics, diesel range organics, dissolved hydrocarbon gases (methane, ethene, and ethane), and wastewater compounds. Water-quality measurements and concentrations in some samples exceeded numerous U.S. Environmental Protection Agency (EPA) drinking water standards. Physical characteristics and constituents that exceeded EPA Maximum Contaminant Levels (MCLs) in some samples were arsenic, selenium, nitrite, nitrate, gross alpha activity, and uranium. Total coliforms and Escherichia coli in some samples exceeded EPA Maximum Contaminant Level Goals. Measurements of pH and turbidity and concentrations of chloride, sulfate, fluoride, dissolved solids, aluminum, iron, and manganese exceeded EPA Secondary Maximum Contaminant Levels in some samples. Radon concentrations in some samples exceeded the alternative MCL proposed by the EPA. Molybdenum and boron concentrations in some samples exceeded EPA Health Advisory Levels. Water-quality measurements and concentrations also exceeded numerous Wyoming Department of Environmental Quality (WDEQ) groundwater standards. Physical characteristics and constituents that exceeded WDEQ Class I domestic groundwater standards in some samples were measurements of pH and concentrations of chloride, sulfate, dissolved solids, iron, manganese, boron, selenium, nitrite, and nitrate. Measurements of pH and concentrations of chloride, sulfate, dissolved solids, aluminum, iron, manganese, boron, and selenium exceeded WDEQ Class II agriculture groundwater standards in some samples. Measurements of pH and concentrations of sulfate, dissolved solids, aluminum, boron, and selenium exceeded WDEQ Class III livestock groundwater standards in some samples. The concentrations of dissolved solids in two samples exceeded the WDEQ Class IV industry groundwater standard. Measurements of pH and concentrations of dissolved solids, aluminum, iron, manganese, and selenium exceeded WDEQ Class special (A) fish and aquatic life groundwater standards in some samples. Stable isotopes of hydrogen and oxygen measured in water samples were compared to the Global Meteoric Water Line and Local Meteoric Water Lines. Results indicated that recharge to all of the wells was derived from precipitation and that the water has undergone some fractionation, possibly because of evaporation. Concentrations of organic compounds did not exceed any State or Federal water-quality standards. Few volatile organic compounds were detected in samples, whereas gasoline range organics, diesel range organics, and methane were detected most frequently. Concentrations of wastewater compounds did not exceed any State or Federal water-quality standards. The compounds N,N-diethyl-meta-toluamide (DEET), benzophenone, and phenanthrene were detected most frequently. Bacteria samples were collected, processed, incubated, and enumerated in the field or at the U.S. Geological Survey Wyoming-Montana Water Science Center. Total coliforms and Escherichia coli were detected in some samples.

Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase IV inhibitors obtained by combinatorial biosynthesis.

PubMed

Flatman, Ruth H; Eustaquio, Alessandra; Li, Shu-Ming; Heide, Lutz; Maxwell, Anthony

2006-04-01

Novobiocin and clorobiocin are gyrase inhibitors produced by Streptomyces strains. Structurally, the two compounds differ only by substitution at two positions: CH3 versus Cl at position 8' of the aminocoumarin ring and carbamoyl versus 5-methyl-pyrrol-2-carbonyl (MePC) at the 3"-OH of noviose. Using genetic engineering, we generated a series of analogs carrying H, CH3, or Cl at 8' and H, carbamoyl, or MePC at 3"-OH. Comparison of the gyrase inhibitory activities of all nine structural permutations confirmed that acylation of 3"-OH is essential for activity, with MePC being more effective than carbamoyl. Substitution at 8' further enhanced activity, but the effect of CH3 or Cl depended on the nature of the acyl group at 3": in the presence of carbamoyl at 3", CH3 resulted in higher activity; in the presence of MePC at 3", Cl resulted in higher activity. This suggests that the structures of both natural compounds are highly evolved for optimal interaction with gyrase. In a second series of experiments, clorobiocin derivatives with and without the methyl group at 4"-OH of noviose, and with different positions of the MePC group of noviose, were tested. Again clorobiocin was superior to all of its analogs. The activities of all compounds were also tested against topoisomerase IV (topo IV). Clorobiocin stood out as a remarkably effective topo IV inhibitor. The relative activities of the different compounds toward topo IV showed a pattern similar to that of the relative gyrase-inhibitory activities. This is the first report of a systematic evaluation of a series of aminocoumarins against both gyrase and topo IV. The results give further insight into the structure-activity relationships of aminocoumarin antibiotics.

Structure-Activity Relationships of Aminocoumarin-Type Gyrase and Topoisomerase IV Inhibitors Obtained by Combinatorial Biosynthesis

PubMed Central

Flatman, Ruth H.; Eustaquio, Alessandra; Li, Shu-Ming; Heide, Lutz; Maxwell, Anthony

2006-01-01

Novobiocin and clorobiocin are gyrase inhibitors produced by Streptomyces strains. Structurally, the two compounds differ only by substitution at two positions: CH3 versus Cl at position 8′ of the aminocoumarin ring and carbamoyl versus 5-methyl-pyrrol-2-carbonyl (MePC) at the 3"-OH of noviose. Using genetic engineering, we generated a series of analogs carrying H, CH3, or Cl at 8′ and H, carbamoyl, or MePC at 3"-OH. Comparison of the gyrase inhibitory activities of all nine structural permutations confirmed that acylation of 3"-OH is essential for activity, with MePC being more effective than carbamoyl. Substitution at 8′ further enhanced activity, but the effect of CH3 or Cl depended on the nature of the acyl group at 3": in the presence of carbamoyl at 3", CH3 resulted in higher activity; in the presence of MePC at 3", Cl resulted in higher activity. This suggests that the structures of both natural compounds are highly evolved for optimal interaction with gyrase. In a second series of experiments, clorobiocin derivatives with and without the methyl group at 4"-OH of noviose, and with different positions of the MePC group of noviose, were tested. Again clorobiocin was superior to all of its analogs. The activities of all compounds were also tested against topoisomerase IV (topo IV). Clorobiocin stood out as a remarkably effective topo IV inhibitor. The relative activities of the different compounds toward topo IV showed a pattern similar to that of the relative gyrase-inhibitory activities. This is the first report of a systematic evaluation of a series of aminocoumarins against both gyrase and topo IV. The results give further insight into the structure-activity relationships of aminocoumarin antibiotics. PMID:16569821

Feasibility of Active Machine Learning for Multiclass Compound Classification.

PubMed

Lang, Tobias; Flachsenberg, Florian; von Luxburg, Ulrike; Rarey, Matthias

2016-01-25

A common task in the hit-to-lead process is classifying sets of compounds into multiple, usually structural classes, which build the groundwork for subsequent SAR studies. Machine learning techniques can be used to automate this process by learning classification models from training compounds of each class. Gathering class information for compounds can be cost-intensive as the required data needs to be provided by human experts or experiments. This paper studies whether active machine learning can be used to reduce the required number of training compounds. Active learning is a machine learning method which processes class label data in an iterative fashion. It has gained much attention in a broad range of application areas. In this paper, an active learning method for multiclass compound classification is proposed. This method selects informative training compounds so as to optimally support the learning progress. The combination with human feedback leads to a semiautomated interactive multiclass classification procedure. This method was investigated empirically on 15 compound classification tasks containing 86-2870 compounds in 3-38 classes. The empirical results show that active learning can solve these classification tasks using 10-80% of the data which would be necessary for standard learning techniques.

[Glycosides from flowers of Jasminum officinale L. var. grandiflorum].

PubMed

Zhao, Gui-qin; Xia, Jing-jing; Dong, Jun-xing

2007-10-01

To study the chemical constituents of the flower of Jasminum officinale L. var. grandiflorum. The compounds were isolated and purified by re-crystallization and chromatography on silica gel and Sephadex LH-20 column. Their structures were elucidated on the physicochemical properties and spectral analysis. Seven glycosides were identified as kaempferol-3-O-alpha-L-rhamnopyranosyl (1-->3)-[alpha-L-rhamnopyranosyl (1-->6)]-beta-D-galactopyranoside (I), kaempferol-3-O-rutinoside (II), 7-ketologanin (III), oleoside-11-methyl ester (IV), 7-glucosyl-l1-methyl oleoside (V), ligstroside (VI), oleuropein (VII). Compound I is a new compound. Compounds III and V were isolated from the family of Jasminum for the first time and compounds II, IV and VI were isolated from Jasminum officinale L. var. grandiflorum for the first time.

Large scale simulations of the mechanical properties of layered transition metal ternary compounds for fossil energy power system applications

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

Ching, Wai-Yim

2014-12-31

Advanced materials with applications in extreme conditions such as high temperature, high pressure, and corrosive environments play a critical role in the development of new technologies to significantly improve the performance of different types of power plants. Materials that are currently employed in fossil energy conversion systems are typically the Ni-based alloys and stainless steels that have already reached their ultimate performance limits. Incremental improvements are unlikely to meet the more stringent requirements aimed at increased efficiency and reduce risks while addressing environmental concerns and keeping costs low. Computational studies can lead the way in the search for novel materialsmore » or for significant improvements in existing materials that can meet such requirements. Detailed computational studies with sufficient predictive power can provide an atomistic level understanding of the key characteristics that lead to desirable properties. This project focuses on the comprehensive study of a new class of materials called MAX phases, or Mn+1AXn (M = a transition metal, A = Al or other group III, IV, and V elements, X = C or N). The MAX phases are layered transition metal carbides or nitrides with a rare combination of metallic and ceramic properties. Due to their unique structural arrangements and special types of bonding, these thermodynamically stable alloys possess some of the most outstanding properties. We used a genomic approach in screening a large number of potential MAX phases and established a database for 665 viable MAX compounds on the structure, mechanical and electronic properties and investigated the correlations between them. This database if then used as a tool for materials informatics for further exploration of this class of intermetallic compounds.« less

Characterization of some amino acid derivatives of benzoyl isothiocyanate: Crystal structures and theoretical prediction of their reactivity

NASA Astrophysics Data System (ADS)

Odame, Felix; Hosten, Eric C.; Betz, Richard; Lobb, Kevin; Tshentu, Zenixole R.

2015-11-01

The reaction of benzoyl isothiocyanate with L-serine, L-proline, D-methionine and L-alanine gave 2-[(benzoylcarbamothioyl)amino]-3-hydroxypropanoic acid (I), 1-(benzoylcarbamothioyl)pyrrolidine-2-carboxylic acid (II), 2-[(benzoylcarbamothioyl)amino]-4-(methylsulfanyl)butanoic acid (III) and 2-[(benzoylcarbamothioyl)amino]propanoic acid (IV), respectively. The compounds have been characterized by IR, NMR, microanalyses and mass spectrometry. The crystal structures of all the compounds have also been discussed. Compound II showed rotamers in solution. DFT calculations of the frontier orbitals of the compounds have been carried out to ascertain the groups that contribute to the HOMO and LUMO, and to study their contribution to the reactivity of these compounds. The calculations indicated that the carboxylic acid group in these compounds is unreactive hence making the conversion to benzimidazoles via cyclization on the carboxylic acids impractical. This has been further confirmed by the reaction of compounds I-IV, respectively, with o-phenylene diamine which was unsuccessful but gave compound V.

Immunoaffinity Knockout of Saponin Glycosides from Asparagus racemosus to Assess Anti-lipid Peroxidation.

PubMed

Onlom, Churanya; Phrompittayarat, Watoo; Putalun, Waraporn; Waranuch, Neti; Ingkaninan, Kornkanok

2017-07-01

Asparagus racemosus Willd (Asparagaceae family), known as Shatavari, is important in Ayurveda and traditional Thai medicines. The saponin glycosides, shatavarin I and IV are major constituents in its roots and may be responsible for their actions including protection against lipid peroxidation and carcinogenesis. To develop an immunoaffinity column for isolating compounds with structures related to shatavarin IV from crude extracts of A. racemosus root. The monoclonal antibody recognising shatavarin IV (mAbShavIV) was coupled to an Affi-Gel Hz gel to isolate compounds with structures related to shatavarin IV from the other components of crude extracts of A. racemosus root. The saponin glycosides in each fraction were analysed by mAbShavIV ELISA and LC-MS/MS. The pooled wash-through fractions contained 3% of loaded mAbShavIV reactive saponin glycosides, while eluted fractions released ~ 90% of shatavarin saponin glycosides in a single step. Using thiobarbiturate (TBARs) to measure lipid-peroxidation, the extract, and the pooled wash-through fractions showed moderate protection against Cu + -induced oxidation of human low density lipoprotein (LDL) (IC 50 11.3 ± 1.4 and 12.6 ± 0.9 μg/mL, respectively). In contrast, the saponin glycosides eluted from the mAbShavIV-column had weaker protectant (IC 50 29.7 ± 1.8 μg/mL) suggesting that A. racemosus shatavarins do not inhibit carcinogenesis through preventing lipid peroxidation. The strategy described here demonstrates its utility for isolating a group of related compounds from the rest of the extract with selectivity and recovery rate. Pharmacological efficacy and synergistic effects of the components obtained can be further investigated. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2014 CFR

2014-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...

40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2012 CFR

2012-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...

40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2013 CFR

2013-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...

40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2010 CFR

2010-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...

40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2011 CFR

2011-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2012 CFR

2012-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

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

Knight, Steven D.; Adams, Nicholas D.; Burgess, Joelle L.

Phosphoinositide 3-kinase {alpha} (PI3K{alpha}) is a critical regulator of cell growth and transformation, and its signaling pathway is the most commonly mutated pathway in human cancers. The mammalian target of rapamycin (mTOR), a class IV PI3K protein kinase, is also a central regulator of cell growth, and mTOR inhibitors are believed to augment the antiproliferative efficacy of PI3K/AKT pathway inhibition. 2,4-Difluoro-N-{l_brace}2-(methyloxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl{r_brace}benzenesulfonamide (GSK2126458, 1) has been identified as a highly potent, orally bioavailable inhibitor of PI3K{alpha} and mTOR with in vivo activity in both pharmacodynamic and tumor growth efficacy models. Compound 1 is currently being evaluated in human clinical trials formore » the treatment of cancer.« less

[Study on the chemical constituents of the leaves of Ipomoea batatas].

PubMed

Lv, Ling-Yuz; Shi, Gao-Feng; Li, Chun-Lei; Han, Xue-Zhe; Lv, Qiu-Nan

2009-06-01

To study the chemical constituents of the leaves of Ipomoea batatas. The constituents were isolated and purified by silica gel and TLC, and their structures were elucidated by spectroscopy. Six compounds were isolated from 90% ethanol extract and identified as tetracosane (I ), myristic acid (II), beta-sitosterol (II), beta-carotene (IV), daucosterol (V) and quercetin (VI). Compounds I, II, IV, V are isolated from this plant for the first time.

Method of synthesis of anhydrous thorium(IV) complexes

DOEpatents

Kiplinger, Jaqueline L; Cantat, Thibault

2013-04-30

Method of producing anhydrous thorium(IV) tetrahalide complexes, utilizing Th(NO.sub.3).sub.4(H.sub.2O).sub.x, where x is at least 4, as a reagent; method of producing thorium-containing complexes utilizing ThCl.sub.4(DME).sub.2 as a precursor; method of producing purified ThCl.sub.4(ligand).sub.x compounds, where x is from 2 to 9; and novel compounds having the structures: ##STR00001##

Discovery of biochemical biomarkers for aggression: A role for metabolomics in psychiatry.

PubMed

Hagenbeek, Fiona A; Kluft, Cornelis; Hankemeier, Thomas; Bartels, Meike; Draisma, Harmen H M; Middeldorp, Christel M; Berger, Ruud; Noto, Antonio; Lussu, Milena; Pool, René; Fanos, Vassilios; Boomsma, Dorret I

2016-07-01

Human aggression encompasses a wide range of behaviors and is related to many psychiatric disorders. We introduce the different classification systems of aggression and related disorders as a basis for discussing biochemical biomarkers and then present an overview of studies in humans (published between 1990 and 2015) that reported statistically significant associations of biochemical biomarkers with aggression, DSM-IV disorders involving aggression, and their subtypes. The markers are of different types, including inflammation markers, neurotransmitters, lipoproteins, and hormones from various classes. Most studies focused on only a limited portfolio of biomarkers, frequently a specific class only. When integrating the data, it is clear that compounds from several biological pathways have been found to be associated with aggressive behavior, indicating complexity and the need for a broad approach. In the second part of the paper, using examples from the aggression literature and psychiatric metabolomics studies, we argue that a better understanding of aggression would benefit from a more holistic approach such as provided by metabolomics. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hemodynamic-GUIDEd Management of Heart Failure

ClinicalTrials.gov

2018-03-29

Heart Failure; Heart Failure, Systolic; Heart Failure, Diastolic; Heart Failure NYHA Class II; Heart Failure NYHA Class III; Heart Failure NYHA Class IV; Heart Failure，Congestive; Heart Failure With Reduced Ejection Fraction; Heart Failure With Normal Ejection Fraction; Heart Failure; With Decompensation

Synthesis, characterization and antioxidant/cytotoxic activity of oxovanadium(IV) complexes of methyliminodiacetic acid and ethylenediaminetetracetic acid

NASA Astrophysics Data System (ADS)

Ibrahim, Mohamed M.; Mersal, Gaber A. M.; Ramadan, Abdel-Motaleb M.; Shaban, Shaban Y.; Mohamed, Mahmoud A.; Al-Juaid, Salih

2017-06-01

Two oxovanadium(IV) complexes, viz., [VO(Me-IDA)(H2O)2] (1) and NaH[VO(EDTA)]·4H2O (2) (Me-IDA = methyliminodiacetic acid and EDTA = ethylenediaminetetraacetic acid) have been synthesized and characterized by FT-IR, UV-Vis, mass spectrometry, elemental analysis, magnetic moment and thermal analysis, as well as electrochemical measurements including cyclic voltammetry. Both compounds are monomeric with distorted octahedral geometries. Compound 2 has been structurally characterized by using X-ray crystallography. It shows an octahedral V(O)N2O3 coordination geometry, which exhibits chemically significant hydrogen bonding interactions besides showing coordination polymer formation. Compounds 1 and 2 show an irreversible redox peak around +0.80 V versus Ag/AgCl corresponding to one-electron oxidation of V(IV) to V(V). The free radical scavenging activity of compounds 1 and 2 were done using 2,2-diphenyl- 1-picrylhydrazyl (DPPH). Both compounds have shown encouraging ROS scavenging activities. The cytotoxicity effects of both compounds toward two different tumor cells (HePG2 and MCF-7) have been also studied by MTT assay. The IC50 values obtained, after 48 h incubation at 37 °C for HepG2 and MCF-7 cell lines were 74.23 and 42.04 μg/mL for compound 1 and 65.56 and 48.34 μg/mL for compound 2, respectively. Conclusively, the present investigation provides preliminary results which suggest that such compounds can be promising alternative antitumor agents.

Acylated Gly-(2-cyano)pyrrolidines as inhibitors of fibroblast activation protein (FAP) and the issue of FAP/prolyl oligopeptidase (PREP)-selectivity.

PubMed

Ryabtsova, Oxana; Jansen, Koen; Van Goethem, Sebastiaan; Joossens, Jurgen; Cheng, Jonathan D; Lambeir, Anne-Marie; De Meester, Ingrid; Augustyns, Koen; Van der Veken, Pieter

2012-05-15

A series of N-acylated glycyl-(2-cyano)pyrrolidines were synthesized with the aim of generating structure-activity relationship (SAR) data for this class of compounds as inhibitors of fibroblast activation protein (FAP). Specifically, the influence of (1) the choice of the N-acyl group and (2) structural modification of the 2-cyanopyrrolidine residue were investigated. The inhibitors displayed inhibitory potency in the micromolar to nanomolar range and showed good to excellent selectivity with respect to the proline selective dipeptidyl peptidases (DPPs) DPP IV, DPP9 and DPP II. Additionally, selectivity for FAP with respect to prolyl oligopeptidase (PREP) is reported. Not unexpectedly, the latter data suggest significant overlap in the pharmacophoric features that define FAP or PREP-inhibitory activity and underscore the importance of systematically evaluating the FAP/PREP-selectivity index for inhibitors of either of these two enzymes. Finally, this study forwards several compounds that can serve as leads or prototypic structures for future FAP-selective-inhibitor discovery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthesis and Characterization of Cerium(IV) Metallocenes

DOE PAGES

Sutton, Andrew; Clark, David Lewis; Scott, Brian Lindley; ...

2015-12-11

In this study, by applying a salt metathesis approach between Ce(OtBu 3) 2(NO 3) 2(THF) 2 and the potassium salts of mono- and ditrimethylsilyl substituted cyclopentadienes, we were able to isolate two new Ce(IV) metallocenes, including to the best of our knowledge, the first structurally characterized bis-cyclopentadiene Ce(IV) compound.

X-ray emission spectroscopy of biomimetic Mn coordination complexes

DOE PAGES

Jensen, Scott C.; Davis, Katherine M.; Sullivan,

2017-05-19

Understanding the function of Mn ions in biological and chemical redox catalysis requires precise knowledge of their electronic structure. X-ray emission spectroscopy (XES) is an emerging technique with a growing application to biological and biomimetic systems. Here, we report an improved, cost-effective spectrometer used to analyze two biomimetic coordination compounds, [Mn IV(OH) 2(Me 2EBC)] 2+ and [Mn IV(O)(OH)(Me 2EBC)] +, the second of which contains a key Mn IV=O structural fragment. Despite having the same formal oxidation state (Mn IV) and tetradentate ligands, XES spectra from these two compounds demonstrate different electronic structures. Experimental measurements and DFT calculations yield differentmore » localized spin densities for the two complexes resulting from Mn IV–OH conversion to Mn IV=O. The relevance of the observed spectroscopic changes is discussed for applications in analyzing complex biological systems such as photosystem II. In conclusion, a model of the S 3 intermediate state of photosystem II containing a Mn IV=O fragment is compared to recent time-resolved X-ray diffraction data of the same state.« less

The Activity of Class I-IV Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in Bladder Cancer Cells.

PubMed

Orywal, Karolina; Jelski, Wojciech; Werel, Tadeusz; Szmitkowski, Maciej

2018-01-02

The aim of this study was to determine the differences in the activity of Alcohol Dehydrogenase (ADH) isoenzymes and Aldehyde Dehydrogenase (ALDH) in normal and cancerous bladder cells. Class III, IV of ADH and total ADH activity were measured by the photometric method and class I, II ADH and ALDH activity by the fluorometric method. Significantly higher total activity of ADH was found in both, low-grade and high-grade bladder cancer, in comparison to healthy tissues. The increased activity of total ADH in bladder cancer cells may be the cause of metabolic disorders in cancer cells, which may intensify carcinogenesis.

New laser protective eyewear

NASA Astrophysics Data System (ADS)

McLear, Mark

1996-04-01

Laser technology has significantly impacted our everyday life. Lasers are now used to correct your vision, clear your arteries, and are used in the manufacturing of such diverse products as automobiles, cigarettes, and computers. Lasers are no longer a research tool looking for an application. They are now an integral part of manufacturing. In the case of Class IV lasers, this explosion in laser applications has exposed thousands of individuals to potential safety hazards including eye damage. Specific protective eyewear designed to attenuate the energy of the laser beam below the maximum permissible exposure is required for Class 3B and Class IV lasers according to laser safety standards.

Enhanced chemiluminescence of cerium(IV)-Tween 85 system and the analytical application.

PubMed

Li, Shifeng; Qian, Li; Zhu, Yan; Liu, Manman; Gao, Yinping; Ni, Yonghong

2013-01-01

The oxidation reaction between cerium(IV) and Tween 85 in sulfuric acid medium produced weak chemiluminescence (CL). In this paper, it was found that citrate could strongly enhance the CL of cerium(IV)-Tween 85-polyphenol system. Based on studies of ultraviolet-visible spectra and CL spectra, the CL enhancement mechanism had been proposed. It was surmised that the light emission was from an excited oxygen molecular pair O2((1)Δg)O2((1)∑g(-)). The maximum emission wavelength was about 478 nm. The effects of 17 amino acids and 29 organic compounds on cerium(IV)-Tween 85-citrate CL were investigated by a flow injection procedure. This study showed the present system had a wide application for the determination of these compounds. Copyright © 2012 John Wiley & Sons, Ltd.

Dancing with chemical formulae of antivirals: A panoramic view (Part 2).

PubMed

De Clercq, Erik

2013-11-15

In this second part of "Dancing with antivirals as chemical formulae" I will focus on a number of chemical compounds that in the last few years have elicited more than common attraction from a commercial viewpoint: (i) favipiravir (T-705), as it is active against influenza, but also several other RNA viruses; (ii) neuraminidase inhibitors such as zanamivir and oseltamivir; (iii) peramivir and laninamivir octanoate, which might be effective against influenza virus following a single (intravenous or inhalation) administration; (iv) sofosbuvir, the (anticipated) cornerstone for the interferon-free therapy of HCV infections; (v) combinations of DAAs (direct antiviral agents) to achieve, in no time, a sustained virus response (SVR) against HCV infection; (vi) HIV protease inhibitors, the latest and most promising being darunavir; (vii) the integrase inhibitors (INIs) (raltegravir, elvitegravir, dolutegravir), representing a new dimension in the anti-HIV armamentarium; (viii), a new class of helicase primase inhibitors (HPIs) that may exceed acyclovir and the other anti-herpes compounds in both potency and safety; (ix) CMX-001, as the latest of Dr. Antonín Holý's legacy for its activity against poxviruses and CMV infections, and (x) noroviruses for which the ideal antiviral compounds are still awaited for. Copyright © 2013 Elsevier Inc. All rights reserved.

Reactivity of the Donor-Stabilized Silylenes [iPrNC(Ph)NiPr]2 Si and [iPrNC(NiPr2 )NiPr]2 Si: Activation of CO2 and CS2.

PubMed

Mück, Felix M; Baus, Johannes A; Nutz, Marco; Burschka, Christian; Poater, Jordi; Bickelhaupt, F Matthias; Tacke, Reinhold

2015-11-09

Activation of CO2 by the bis(amidinato)silylene 1 and the analogous bis(guanidinato)silylene 2 leads to the structurally analogous six-coordinate silicon(IV) complexes 4 (previous work) and 8, respectively, the first silicon compounds with a chelating carbonato ligand. Likewise, CS2 activation by silylene 1 affords the analogous six-coordinate silicon(IV) complex 10, the first silicon compound with a chelating trithiocarbonato ligand. CS2 activation by silylene 2, however, yields the five-coordinate silicon(IV) complex 13 with a carbon-bound CS2 (2-) ligand, which also represents an unprecedented coordination mode in silicon coordination chemistry. Treatment of the dinuclear silicon(IV) complexes 5 and 6 with CO2 also affords the six-coordinate carbonatosilicon(IV) complexes 4 and 8, respectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Independent Review of the Defense Logistics Agencys Roles and Missions

DTIC Science & Technology

2014-12-01

remaining wholesale consumables missions of tires, packaged petroleum, oils , and lubricants, and gases and cylinders were transferred from the...housekeeping supplies and equipment. Class III: Petroleum, oils , and lubricants. Class IV: Construction materials. Class V: Ammunition. Class VI...own appropriated funds that are deposited 9 The Construction and Equipment program within DLA Troop Support provides some Class VII non- weapons

Investigating the effect of emetic compounds on chemotaxis in Dictyostelium identifies a non-sentient model for bitter and hot tastant research.

PubMed

Robery, Steven; Mukanowa, Janina; Percie du Sert, Nathalie; Andrews, Paul L R; Williams, Robin S B

2011-01-01

Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence reduce adverse animal experimentation in this area. Twenty eight emetic or taste aversive compounds were employed to investigate the acute (10 min) effect of compounds on Dictyostelium cell behaviour (shape, speed and direction of movement) in a shallow chemotaxic gradient (Dunn chamber). Compound concentrations were chosen based on those previously reported to be emetic or aversive in in vivo studies and results were recorded and quantified by automated image analysis. Dictyostelium cell motility was rapidly and strongly inhibited by four structurally distinct tastants (three bitter tasting compounds--denatonium benzoate, quinine hydrochloride, phenylthiourea, and the pungent constituent of chilli peppers--capsaicin). In addition, stomach irritants (copper chloride and copper sulphate), and a phosphodiesterase IV inhibitor also rapidly blocked movement. A concentration-dependant relationship was established for five of these compounds, showing potency of inhibition as capsaicin (IC(50) = 11.9 ± 4.0 µM) > quinine hydrochloride (IC(50) = 44.3 ± 6.8 µM) > denatonium benzoate (IC(50) = 129 ± 4 µM) > phenylthiourea (IC(50) = 366 ± 5 µM) > copper sulphate (IC(50) = 1433 ± 3 µM). In contrast, 21 compounds within the cytotoxic and receptor agonist/antagonist classes did not affect cell behaviour. Further analysis of bitter and pungent compounds showed that the effect on cell behaviour was reversible and not cytotoxic, suggesting an uncharacterised molecular mechanism of action for these compounds. These results therefore demonstrate that Dictyostelium has potential as a non-sentient model in the analysis of the molecular effects of tastants, although it has limited utility in identification of emetic agents in general.

Multiple resistance to acaricides in field populations of Rhipicephalus microplus from Rio Grande do Sul state, Southern Brazil.

PubMed

Klafke, Guilherme; Webster, Anelise; Dall Agnol, Bruno; Pradel, Endrigo; Silva, Jeniffer; de La Canal, Luiz Henrique; Becker, Marcelo; Osório, Mateus Felipe; Mansson, Melanie; Barreto, Rafael; Scheffer, Ramon; Souza, Ugo Araújo; Corassini, Vivian Bamberg; Dos Santos, Julsan; Reck, José; Martins, João Ricardo

2017-01-01

Acaricide resistance is a major obstacle to the control of Rhipicephalus microplus. Historically, the indiscriminate use of chemical compounds has contributed to the selection of populations resistant to different classes of acaricides. Therefore, multiple acaricide resistance is an important threat to the chemical control of the cattle tick. To investigate the occurrence and extent of multiple resistance to acaricides in Southern Brazil we performed larval tests with cypermethrin, chlorpyriphos, amitraz, fipronil and ivermectin on 104 cattle tick field samples from different ranches in Rio Grande do Sul, between the years 2013 and 2015. Adult immersion tests with a commercial formulation mixture of chlorpyriphos and cypermethrin were performed on 75 samples. Four levels of resistance were established according to the mortality of larvae: Level I: mortality between 82% and 95%; Level II: mortality between 57% and 82%; Level III: mortality between 25% and 57%; and Level IV: mortality lower than 25%. Resistance to cypermethrin was detected in 98.08% of the samples evaluated, mostly at resistance level IV. The frequency of samples resistant to amitraz, chlorpyriphos, ivermectin and fipronil was 76.92%, 60.58%, 60.58% and 53.85% respectively. Multiple resistance to three or more compounds was found in 78.85% of the samples. The results obtained in this study are alarming and reveal a new scenario for the challenge of tick control using chemicals. This is an issue of high importance to cattle production systems where this tick is responsible for a high economic impact. Copyright © 2016 Elsevier GmbH. All rights reserved.

Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation.

PubMed

Shimamoto, Ken; Kusumoto, Miyako; Sakai, Rieko; Watanabe, Hirota; Ihara, Syunichi; Koike, Natsuka; Kawana, Masatoshi

2007-03-15

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were characterized in subjects with mitral regurgitation (MR). Sixty-two cases of moderate or severe chronic MR were studied. The blood levels of neurohormonal factors were stratified by the known MR prognostic factors of New York Heart Association (NYHA) functional class, left ventricular end-diastolic diameters, left ventricular end-systolic diameter (LVDs), ejection fraction (EF), left atrial diameter and presence of atrial fibrillation (AF). ANP levels were higher in NYHA class II and lower in classes I and III/IV (P=0.0206). BNP levels were higher in NYHA class II than class I (P=0.0355). The BNP/ANP ratio was significantly higher in NYHA classes II and III/IV than in class I (P=0.0007). To differentiate between NYHA classes I/II and III/IV, a cut-off BNP/ANP ratio of 2.97 produced a sensitivity of 78% and specificity of 87%. Compared with subjects in sinus rhythm, patients with AF had an enlarged left atrium and lower ANP levels. The BNP/ANP ratio correlated significantly with left atrial diameter, LVDs and EF (r=0.429, P=0.0017; r=0.351, P=0.0117; and r=-0.349, P=0.0122; respectively), and was significantly higher among all the known operative indications for MR tested (LVDs 45 mm or more, EF 60% or less, NYHA class II or greater and AF; P=0.0073, P=0.003, P=0.0102 and P=0.0149, respectively). In chronic MR, levels of ANP and BNP, and the BNP/ANP ratio are potential indicators of disease severity.

Redo surgery risk in patients with cardiac prosthetic valve dysfunction

PubMed Central

Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Bielecka-Dąbrowa, Agata; Piechowiak, Monika; Jaszewski, Ryszard

2011-01-01

Introduction The aim of the study was to analyse the risk factors of early and late mortality in patients undergoing the first reoperation for prosthetic valve dysfunction. Material and methods A retrospective observational study was performed in 194 consecutive patients (M = 75, F = 119; mean age 53.2 ±11 years) with a mechanical prosthetic valve (n = 103 cases; 53%) or bioprosthesis (91; 47%). Univariate and multivariate Cox statistical analysis was performed to determine risk factors of early and late mortality. Results The overall early mortality was 18.6%: 31.4% in patients with symptoms of NYHA functional class III-IV and 3.4% in pts in NYHA class I-II. Multivariate analysis identified symptoms of NYHA class III-IV and endocarditis as independent predictors of early mortality. The overall late mortality (> 30 days) was 8.2% (0.62% year/patient). Multivariate analysis identified age at the time of reoperation as a strong independent predictor of late mortality. Conclusions Reoperation in patients with prosthetic valves, performed urgently, especially in patients with symptoms of NYHA class III-IV or in the case of endocarditis, bears a high mortality rate. Risk of planned reoperation, mostly in patients with symptoms of NYHA class I-II, does not differ from the risk of the first operation. PMID:22291767

An Ultrastable Heterobimetallic Uranium(IV)/Vanadium(III) Solid Compound Protected by a Redox-Active Phosphite Ligand: Crystal Structure, Oxidative Dissolution, and First-Principles Simulation.

PubMed

Gui, Daxiang; Dai, Xing; Zheng, Tao; Wang, Xiangxiang; Silver, Mark A; Chen, Lanhua; Zhang, Chao; Diwu, Juan; Zhou, Ruhong; Chai, Zhifang; Wang, Shuao

2018-02-05

The first heterobimetallic uranium(IV)/vanadium(III) phosphite compound, Na 2 UV 2 (HPO 3 ) 6 (denoted as UVP), was synthesized via an in situ redox-active hydrothermal reaction. It exhibits superior hydrolytic and antioxidant stability compared to the majority of structures containing low-valent uranium or vanadium, further elucidated by first-principles simulations, and therefore shows potential applications in nuclear waste management.

The Capsicum annuum class IV chitinase ChitIV interacts with receptor-like cytoplasmic protein kinase PIK1 to accelerate PIK1-triggered cell death and defence responses

PubMed Central

Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

2015-01-01

The pepper receptor-like cytoplasmic protein kinase, CaPIK1, which mediates signalling of plant cell death and defence responses was previously identified. Here, the identification of a class IV chitinase, CaChitIV, from pepper plants (Capsicum annuum), which interacts with CaPIK1 and promotes CaPIK1-triggered cell death and defence responses, is reported. CaChitIV contains a signal peptide, chitin-binding domain, and glycol hydrolase domain. CaChitIV expression was up-regulated by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Notably, avirulent Xcv infection rapidly induced CaChitIV expression in pepper leaves. Bimolecular fluorescence complementation and co-immunoprecipitation revealed that CaPIK1 interacts with CaChitIV in planta, and that the CaPIK1–CaChitIV complex is localized mainly in the cytoplasm and plasma membrane. CaChitIV is also localized in the endoplasmic reticulum. Transient co-expression of CaChitIV with CaPIK1 enhanced CaPIK1-triggered cell death response and reactive oxygen species (ROS) and nitric oxide (NO) bursts. Co-silencing of both CaChitIV and CaPIK1 in pepper plants conferred enhanced susceptibility to Xcv infection, which was accompanied by a reduced induction of cell death response, ROS and NO bursts, and defence response genes. Ectopic expression of CaPIK1 in Arabidopsis enhanced basal resistance to Hyaloperonospora arabidopsidis infection. Together, the results suggest that CaChitIV positively regulates CaPIK1-triggered cell death and defence responses through its interaction with CaPIK1. PMID:25694549

The Capsicum annuum class IV chitinase ChitIV interacts with receptor-like cytoplasmic protein kinase PIK1 to accelerate PIK1-triggered cell death and defence responses.

PubMed

Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

2015-04-01

The pepper receptor-like cytoplasmic protein kinase, CaPIK1, which mediates signalling of plant cell death and defence responses was previously identified. Here, the identification of a class IV chitinase, CaChitIV, from pepper plants (Capsicum annuum), which interacts with CaPIK1 and promotes CaPIK1-triggered cell death and defence responses, is reported. CaChitIV contains a signal peptide, chitin-binding domain, and glycol hydrolase domain. CaChitIV expression was up-regulated by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Notably, avirulent Xcv infection rapidly induced CaChitIV expression in pepper leaves. Bimolecular fluorescence complementation and co-immunoprecipitation revealed that CaPIK1 interacts with CaChitIV in planta, and that the CaPIK1-CaChitIV complex is localized mainly in the cytoplasm and plasma membrane. CaChitIV is also localized in the endoplasmic reticulum. Transient co-expression of CaChitIV with CaPIK1 enhanced CaPIK1-triggered cell death response and reactive oxygen species (ROS) and nitric oxide (NO) bursts. Co-silencing of both CaChitIV and CaPIK1 in pepper plants conferred enhanced susceptibility to Xcv infection, which was accompanied by a reduced induction of cell death response, ROS and NO bursts, and defence response genes. Ectopic expression of CaPIK1 in Arabidopsis enhanced basal resistance to Hyaloperonospora arabidopsidis infection. Together, the results suggest that CaChitIV positively regulates CaPIK1-triggered cell death and defence responses through its interaction with CaPIK1. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Evidence That the [beta] Subunit of Chlamydia trachomatis Ribonucleotide Reductase Is Active with the Manganese Ion of Its Manganese(IV)/Iron(III) Cofactor in Site 1

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

Dassama, Laura M.K.; Boal, Amie K.; Krebs, Carsten

2014-10-02

The reaction of a class I ribonucleotide reductase (RNR) begins when a cofactor in the {beta} subunit oxidizes a cysteine residue {approx}35 {angstrom} away in the {alpha} subunit, generating a thiyl radical. In the class Ic enzyme from Chlamydia trachomatis (Ct), the cysteine oxidant is the Mn{sup IV} ion of a Mn{sup IV}/Fe{sup III} cluster, which assembles in a reaction between O{sub 2} and the Mn{sup II}/Fe{sup II} complex of {beta}. The heterodinuclear nature of the cofactor raises the question of which site, 1 or 2, contains the Mn{sup IV} ion. Because site 1 is closer to the conserved locationmore » of the cysteine-oxidizing tyrosyl radical of class Ia and Ib RNRs, we suggested that the Mn{sup IV} ion most likely resides in this site (i.e., {sup 1}Mn{sup IV}/{sup 2}Fe{sup III}), but a subsequent computational study favored its occupation of site 2 ({sup 1}Fe{sup III}/{sup 2}Mn{sup IV}). In this work, we have sought to resolve the location of the Mn{sup IV} ion in Ct RNR-{beta} by correlating X-ray crystallographic anomalous scattering intensities with catalytic activity for samples of the protein reconstituted in vitro by two different procedures. In samples containing primarily Mn{sup IV}/Fe{sup III} clusters, Mn preferentially occupies site 1, but some anomalous scattering from site 2 is observed, implying that both {sup 1}Mn{sup II}/{sup 2}Fe{sup II} and {sup 1}Fe{sup II}/{sup 2}Mn{sup II} complexes are competent to react with O{sub 2} to produce the corresponding oxidized states. However, with diminished Mn{sup II} loading in the reconstitution, there is no evidence for Mn occupancy of site 2, and the greater activity of these 'low-Mn' samples on a per-Mn basis implies that the {sup 1}Mn{sup IV}/{sup 2}Fe{sup III}-{beta} is at least the more active of the two oxidized forms and may be the only active form.« less

Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development

PubMed Central

Moon, Robert W.; Whalley, David; Bowyer, Paul W.; Wallace, Claire; Rochani, Ankit; Nageshan, Rishi K.; Howell, Steven A.; Grainger, Munira; Jones, Hayley M.; Ansell, Keith H.; Chapman, Timothy M.; Taylor, Debra L.; Osborne, Simon A.; Baker, David A.; Tatu, Utpal

2015-01-01

Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme's gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90. PMID:26711771

Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development.

PubMed

Green, Judith L; Moon, Robert W; Whalley, David; Bowyer, Paul W; Wallace, Claire; Rochani, Ankit; Nageshan, Rishi K; Howell, Steven A; Grainger, Munira; Jones, Hayley M; Ansell, Keith H; Chapman, Timothy M; Taylor, Debra L; Osborne, Simon A; Baker, David A; Tatu, Utpal; Holder, Anthony A

2015-12-28

Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme's gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90. Copyright © 2016 Green et al.

Magneto-structural correlations in a family of Fe(II)Re(IV)(CN)2 single-chain magnets: density functional theory and ab initio calculations.

PubMed

Zhang, Yi-Quan; Luo, Cheng-Lin; Wu, Xin-Bao; Wang, Bing-Wu; Gao, Song

2014-04-07

Until now, the expressions of the anisotropic energy barriers Δξ and ΔA, using the uniaxial magnetic anisotropy D, the intrachain coupling strength J, and the high-spin ground state S for single-chain magnets (SCMs) in the intermediate region between the Ising and the Heisenberg limits, were unknown. To explore this relationship, we used density functional theory and ab initio methods to obtain expressions of Δξ and ΔA in terms of D, J, and S of six R4Fe(II)-Re(IV)Cl4(CN)2 (R = diethylformamide (1), dibutylformamide (2), dimethylformamide (3), dimethylbutyramide (4), dimethylpropionamide (5), and diethylacetamide (6)) SCMs in the intermediate region. The ΔA value for compounds 1-3 was very similar to the magnetic anisotropic energy of a single Fe(II), while the value of Δξ was predicted using the exchange interaction of Fe(II) with the neighboring Re(IV), which could be expressed as 2JSReSFe. Similar to compounds 1-3, the anisotropy energy barrier ΔA of compounds 4 and 5 was also equal to (Di - Ei)SFe(2), but the correlation energy Δξ was closely equal to 2JSReSFe(cos 98.4 - cos 180) due to the reversal of the spins on the opposite Fe(II). For compound 6, one unit cell of Re(IV)Fe(II) was regarded as a domain wall since it had two different Re(IV)-Fe(II) couplings. Thus, the Δξ of compound 6 was expressed as 4J″SRe1Fe1SRe2Fe2, where J″ was the coupling constant of the neighboring unit cells of Re1Fe1 and Re2Fe2, and ΔA was equal to the anisotropic energy barrier of one domain wall given by DRe1Fe1(S(2)Re1Fe1 - 1/4).

Overlapping and Divergent Actions of Structurally Distinct Histone Deacetylase Inhibitors in Cardiac Fibroblasts

PubMed Central

Schuetze, Katherine B.; Stratton, Matthew S.; Blakeslee, Weston W.; Wempe, Michael F.; Wagner, Florence F.; Holson, Edward B.; Kuo, Yin-Ming; Andrews, Andrew J.; Gilbert, Tonya M.; Hooker, Jacob M.

2017-01-01

Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly affect cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II, and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiologic and pathophysiological processes. For example, the benzamide class I HDAC-selective inhibitor, MGCD0103 [N-(2-aminophenyl)-4-[[(4-pyridin-3-ylpyrimidin-2-yl)amino]methyl] benzamide], was shown to block cardiac fibrosis, a process involving excess extracellular matrix deposition, which often results in heart dysfunction. Here, we compare the mechanisms of action of structurally distinct HDAC inhibitors in isolated primary cardiac fibroblasts, which are the major extracellular matrix–producing cells of the heart. TSA, MGCD0103, and the cyclic peptide class I HDAC inhibitor, apicidin, exhibited a common ability to enhance histone acetylation, and all potently blocked cardiac fibroblast cell cycle progression. In contrast, MGCD0103, but not TSA or apicidin, paradoxically increased expression of a subset of fibrosis-associated genes. Using the cellular thermal shift assay, we provide evidence that the divergent effects of HDAC inhibitors on cardiac fibroblast gene expression relate to differential engagement of HDAC1- and HDAC2-containing complexes. These findings illustrate the importance of employing multiple compounds when pharmacologically assessing HDAC function in a cellular context and during HDAC inhibitor drug development. PMID:28174211

Clinical profile of patients with biopsy proven lupus nephritis at a tertiary care hospital from Northern Pakistan, 1995 to 2012.

PubMed

Ali, Akhtar; Mehmood, Anjum; Ali, Muhammad Usman

2017-01-01

TTo highlight the clinical spectrum of biopsy-proven lupus nephritis by analysing any variations in its histological subtypes across gender, varying age groups, serum creatinine levels and anti-double stranded deoxyribonucleic acid levels. This retrospective, observational study was conducted at the Lady Reading Hospital in collaboration with the Fauji Foundation Hospital, Peshawar, Pakistan, and comprised patient records of biopsy-proven lupus nephritis from 1995 to 2012. The cases were analysed according to clinical presentations and histological pattern of systemic lupus erythematosus nephritis. EpiData 3.1 and SPSS 17 were used for data analyses. Of the 2,000 renal biopsies performed, lupus nephritis was found in 74(3.7%) cases. Of them, 63(85.1%) were females and 11(14.9%) males. The mean age of the cases was 23.88±9.73 years (range: 10-55 years). Class IV lupus nephritis was seen in 38(51.4%) patients, followed by Class II in 15(20.3%), Class III in 10(13.5%), Class V and VI in 4(5.4%) each and Class I in 3(4.1%). Out of the combined Class III and IV cases, 25(52.08%) had serum creatinine levels of >1.2 mg/dL, whereas positive anti-double stranded deoxyribonucleic acid titers up to 50 IU/L were seen in all of the 48(100%) such patients. Overall, microscopic haematuria was found in 52(70.3%) cases, followed by arthralgia in 40(54.1%). Moreover, 32(50.8%) females and 6(54.5%) males had Type IV nephritis. Class VI lupus nephritis, in particular, were significantly more prominent in 31-40 years of age group when compared to other histological subtypes and age groups (p=0.0096, odds ratio: 23.25, 95% confidence interval: 2.15-251.21). Female predominance was observed in all histological sub-types of lupus nephritis. Class IV lupus was the most common histological pattern. Microscopic haematuria was the most common clinical presentation.

Simulation of dendritic growth reveals necessary and sufficient parameters to describe the shapes of dendritic trees

NASA Astrophysics Data System (ADS)

Trottier, Olivier; Ganguly, Sujoy; Bowne-Anderson, Hugo; Liang, Xin; Howard, Jonathon

For the last 120 years, the development of neuronal shapes has been of great interest to the scientific community. Over the last 30 years, significant work has been done on the molecular processes responsible for dendritic development. In our ongoing research, we use the class IV sensory neurons of the Drosophila melanogaster larva as a model system to understand the growth of dendritic arbors. Our main goal is to elucidate the mechanisms that the neuron uses to determine the shape of its dendritic tree. We have observed the development of the class IV neuron's dendritic tree in the larval stage and have concluded that morphogenesis is defined by 3 distinct processes: 1) branch growth, 2) branching and 3) branch retraction. As the first step towards understanding dendritic growth, we have implemented these three processes in a computational model. Our simulations are able to reproduce the branch length distribution, number of branches and fractal dimension of the class IV neurons for a small range of parameters.

A new class of relativistic stellar models

NASA Astrophysics Data System (ADS)

Haggag, Salah

1995-03-01

Einstein field equations for a static and spherically symmetric perfect fluid are considered. A formulation given by Patino and Rago is used to obtain a class of nine solutions, two of them are Tolman solutions I, IV and the remaining seven are new. The solutions are the correct ones corresponding to expressions derived by Patino and Rago which have been shown by Knutsen to be incorrect. Similar to Tolan solution IV each of the new solutions satisfies energy conditions inside a sphere in some range of two independent parameters. Besides, each solution could be matched to the exterior Schwarzschild solution at a boundary where the pressure vanishes and thus the solutions constitute a class of new physically reasonable stellar models.

[Studies on chemical constituents of Heterosmilax yunnanensis].

PubMed

Qin, Wen-jie; Wang, Gang-li; Lin, Rui-chao

2007-08-01

To study the chemical constituents of Heterosmilax yunianensis. The compounds were isolated and repeatedly purified with chromatograph and the structures were elucidated by physico-chemical properties and spectral analysis. Eight compounds were obtained and elucidated as beta-sitosterol (I), glycerol monopalmitate (II), daucosterol (IIl), hexacosanoic acid (IV), 5-hydroxymethyl furaldehyde (V), hergapen (VI), ursolic acid (VII), liquiritigenin (VIII). They have been isolated from this plant for the first time, and IV - VIII are obtained from the plants of Heterosmilax for the first time.

Insights into the Mechanism of Action of Bactericidal Lipophosphonoxins.

PubMed

Panova, Natalya; Zborníková, Eva; Šimák, Ondřej; Pohl, Radek; Kolář, Milan; Bogdanová, Kateřina; Večeřová, Renata; Seydlová, Gabriela; Fišer, Radovan; Hadravová, Romana; Šanderová, Hana; Vítovská, Dragana; Šiková, Michaela; Látal, Tomáš; Lovecká, Petra; Barvík, Ivan; Krásný, Libor; Rejman, Dominik

2015-01-01

The advantages offered by established antibiotics in the treatment of infectious diseases are endangered due to the increase in the number of antibiotic-resistant bacterial strains. This leads to a need for new antibacterial compounds. Recently, we discovered a series of compounds termed lipophosphonoxins (LPPOs) that exhibit selective cytotoxicity towards Gram-positive bacteria that include pathogens and resistant strains. For further development of these compounds, it was necessary to identify the mechanism of their action and characterize their interaction with eukaryotic cells/organisms in more detail. Here, we show that at their bactericidal concentrations LPPOs localize to the plasmatic membrane in bacteria but not in eukaryotes. In an in vitro system we demonstrate that LPPOs create pores in the membrane. This provides an explanation of their action in vivo where they cause serious damage of the cellular membrane, efflux of the cytosol, and cell disintegration. Further, we show that (i) LPPOs are not genotoxic as determined by the Ames test, (ii) do not cross a monolayer of Caco-2 cells, suggesting they are unable of transepithelial transport, (iii) are well tolerated by living mice when administered orally but not peritoneally, and (iv) are stable at low pH, indicating they could survive the acidic environment in the stomach. Finally, using one of the most potent LPPOs, we attempted and failed to select resistant strains against this compound while we were able to readily select resistant strains against a known antibiotic, rifampicin. In summary, LPPOs represent a new class of compounds with a potential for development as antibacterial agents for topical applications and perhaps also for treatment of gastrointestinal infections.

X-ray absorption spectroscopy systematics at the tungsten L-edge.

PubMed

Jayarathne, Upul; Chandrasekaran, Perumalreddy; Greene, Angelique F; Mague, Joel T; DeBeer, Serena; Lancaster, Kyle M; Sproules, Stephen; Donahue, James P

2014-08-18

A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, was interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W(0)(PMe3)6], [W(II)Cl2(PMePh2)4], [W(III)Cl2(dppe)2][PF6] (dppe = 1,2-bis(diphenylphosphino)ethane), [W(IV)Cl4(PMePh2)2], [W(V)(NPh)Cl3(PMe3)2], and [W(VI)Cl6], correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio of the L3,2-edges and the L1 rising-edge energy with metal Zeff, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [W(IV)(mdt)2(CO)2] and [W(IV)(mdt)2(CN)2](2-) (mdt(2-) = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively W(IV) species even though the mdt ligands exist at different redox levels in the two compounds. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: (1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Zeff in the species of interest. (2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS. (3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal-ligand distances, exaggerate the difference between formal oxidation state and metal Zeff or, as in the case of [W(IV)(mdt)2(CO)2], exert the subtle effect of modulating the redox level of other ligands in the coordination sphere.

The effect of a class IV hurricane on emergency department operations.

PubMed

Sheppa, C M; Stevens, J; Philbrick, J T; Canada, M

1993-09-01

The objective of this study was to determine the impact on emergency department (ED) operations of Hurricane Hugo, a class IV hurricane that struck Charleston, South Carolina, on September 21, 1989. The study design was a retrospective record-based descriptive study and mail survey of the ED of a 300-bed regional medical center directly in the path of the storm. During the 3 weeks after the storm, ED patient volume increased 19% over that of the 3 weeks before the storm. Increased visit volumes were evident for at least 3 months. Compared with a similar period of the previous year, there was an increase in the proportion of patients seen for lacerations of all types, puncture wounds, stings, and falls. Sixty-two percent of physician offices were still closed 7 days after the storm. The direct effects of a class IV hurricane on ED operations included major alterations in the volume and types of patient visits. Because of the evacuation of approximately 40% of the coastal population and storm damage hindering travel, the increase in visit volume was less in magnitude but of longer duration has been reported in class III hurricanes.

New oxyfluorotellurates(IV): MTeO3F (M = FeIII, GaIII and CrIII).

PubMed

Laval, Jean Paul; Jennene Boukharrata, Nefla; Thomas, Philippe

2008-02-01

The crystal structures of the new isomorphous compounds iron(III) oxyfluorotellurate(IV), FeTeO(3)F, gallium(III) oxyfluorotellurate(IV), GaTeO(3)F, and chromium(III) oxyfluorotellurate(IV), CrTeO(3)F, consist of zigzag chains of MO(4)F(2) distorted octahedra alternately sharing O-O and F-F edges and connected via TeO(3) trigonal pyramids. A full O/F anionic ordering is observed and the electronic lone pair of the Te(IV) cation is stereochemically active.

Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension.

PubMed

Mansoor, J K; Schelegle, Edward S; Davis, Cristina E; Walby, William F; Zhao, Weixiang; Aksenov, Alexander A; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.

Analysis of Volatile Compounds in Exhaled Breath Condensate in Patients with Severe Pulmonary Arterial Hypertension

PubMed Central

Mansoor, J. K.; Schelegle, Edward S.; Davis, Cristina E.; Walby, William F.; Zhao, Weixiang; Aksenov, Alexander A.; Pasamontes, Alberto; Figueroa, Jennifer; Allen, Roblee

2014-01-01

Background An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH. Methodolgy and Findings Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients. Conclusions These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH. PMID:24748102

Predictors of Operative Mortality for Coronary Bypass Grafting in Patients with Ischemic Heart Disease

PubMed Central

Langou, Rene A.; Wiles, John C.; Peduzzi, Peter N.; Hammond, Graeme; Cohen, Lawrence S.

1978-01-01

Predictors for operative mortality (OM) were studied in 172 consecutive patients (pts) undergoing coronary artery grafts (CAG) for angina pectoris. Seventy eight pts had Class IV angina; of the 147 patients given propranolol, 41 were gradually withdrawn from propranolol and finally discontinued 24 hours before surgery, and 106 were abruptly withdrawn from propranolol 24 hours before CAG; 20 pts had left main coronary disease; 156 pts had cardiopulmonary bypass (CPB) time shorter than 20 minutes, and 16 pts had a CPB longer than 120 minutes. The operative mortality was 5.2% (9/172) for the entire group. Class IV angina (OM 7%), abrupt propranolol withdrawal (OM 6.6%), left main coronary artery disease (OM 25%), and CPB longer than 120 minutes (OM 50%), all significantly increased OM. These variables were interdependent, however, as many pts belonged to several predictor categories, combinations of predictors were examined, in order to more accurately predict the risk of individual pts. The combination of left main coronary artery disease and CPB longer than 120 minutes; and Class IV angina and CPB longer than 120 minutes were significantly associated with higher operative mortality. We conclude that Class IV angina, abrupt propranolol withdrawal, left main coronary artery disease and prolonged CPB are potent, interdependent predictors of OM in pts undergoing CAG. Consideration of these predictors, alone and in combination, allows effective prediction of OM for CAG in patients with stable angina pectoris. PMID:307873

Biomechanical 3-Dimensional Finite Element Analysis of Obturator Protheses Retained with Zygomatic and Dental Implants in Maxillary Defects

PubMed Central

Akay, Canan; Yaluğ, Suat

2015-01-01

Background The objective of this study was to investigate the stress distribution in the bone around zygomatic and dental implants for 3 different implant-retained obturator prostheses designs in a Aramany class IV maxillary defect using 3-dimensional finite element analysis (FEA). Material\\Methods A 3-dimensional finite element model of an Aramany class IV defect was created. Three different implant-retained obturator prostheses were modeled: model 1 with 1 zygomatic implant and 1 dental implant, model 2 with 1 zygomatic implant and 2 dental implants, and model 3 with 2 zygomatic implants. Locator attachments were used as a superstructure. A 150-N load was applied 3 different ways. Qualitative analysis was based on the scale of maximum principal stress; values obtained through quantitative analysis are expressed in MPa. Results In all loading conditions, model 3 (when compared models 1 and 2) showed the lowest maximum principal stress value. Model 3 is the most appropirate reconstruction in Aramany class IV maxillary defects. Two zygomatic implants can reduce the stresses in model 3. The distribution of stresses on prostheses were more rational with the help of zygoma implants, which can distribute the stresses on each part of the maxilla. Conclusions Aramany class IV obturator prosthesis placement of 2 zygomatic implants in each side of the maxilla is more advantageous than placement of dental implants. In the non-defective side, increasing the number of dental implants is not as suitable as zygomatic implants. PMID:25714086

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

21 CFR 880.5440 - Intravascular administration set.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Classification. Class II (special controls). The special control for pharmacy compounding systems within this classification is the FDA guidance document entitled “Class II Special Controls Guidance Document: Pharmacy Compounding Systems; Final Guidance for Industry and FDA Reviewers.” Pharmacy compounding systems classified...

Intravenous Alcohol Self-Administration in the P Rat

PubMed Central

Windisch, Kyle A.; Kosobud, Ann E. K.; Czachowski, Cristine L.

2014-01-01

Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally “relevant” effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding “non-pharmacological” effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol’s effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol self-administration methodology cannot overcome the aversive properties of ethanol via this route in the rat. PMID:24835637

Framing of Transitional Pedagogic Practices in the Sciences: Enabling Access

ERIC Educational Resources Information Center

Ellery, Karen

2017-01-01

Educational literature shows that students from working-class backgrounds are significantly less likely to persist to completion in higher education than middle-class students. This paper draws theoretically and analytically on Bernstein's ([1990. "Class, Codes and Control, Volume IV: The Structuring of Pedagogic Discourse." London:…

Antibiotic activity of Emerimicin IV isolated from Emericellopsis minima from Talcahuano Bay, Chile.

PubMed

Inostroza, Alejandro; Lara, Liliana; Paz, Cristian; Perez, Andrés; Galleguillos, Felipe; Hernandez, Victor; Becerra, José; González-Rocha, Gerardo; Silva, Mario

2018-06-01

Due to the increasing emergence of resistance of bacterial pathogens to current antibiotics, we have examined the marine fungi present in sea sediments obtained 200 m offshore to discover new antibacterial compounds active against multidrug-resistant bacteria. One strain, identified as Emericellopsis minima, was isolated from sediments of Talcahuano Bay (Chile). From the liquid culture of E. minima, we isolated Emerimicin IV, a unique fungal peptaibol that exhibited antibacterial activity. The structure of this compound was assigned by interpretation of 1 H NMR and HR-LCMS data. Emerimicin IV showed bacteriostatic activity against clinical isolates of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis with MIC values ranging between 100 and 12.5 μg/mL.

Studies on the mechanism of salicylate-induced increase of insulin secretion in man.

PubMed

Giugliano, D; Cozzolino, D; Ceriello, A; Cerciello, T; Varano, R; Saccomanno, F; Torella, R

1988-01-01

Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.

[Studies on chemical constituents of the seeds of Allium cepa].

PubMed

Yuan, Ling; Ji, Teng-Fei; Wang, Ai-Guo; Yang, Jian-Bo; Su, Ya-Lun

2008-02-01

To study the chemical constituents from the seeds of Allium cepa L., the constituents of the seeds of Allium cepa L. To isolate and purify by silica gel, macroporous resin HP-20, Sephadex LH-20, RP-18 column. Seven compounds were isolated from the EtOH extract of the seeds of Allium cepa., their structures were elucidated by physico-chemical properties and spectroscopic analysis as tianshic acid (I), N-trans-feruloyl tyramine (II), beta-sitosterol-3 beta-glucopyranoside-6'-palmitate (III), sitosterol (IV), daucosterol (V), tryptophane (VI), adenine riboside (VI). Compounds V-VIII are obtained from this plant for the first time, compounds I-IV are isolated from the genus Allium for the first time.

Notes from the Field: Fungal Bloodstream Infections Associated with a Compounded Intravenous Medication at an Outpatient Oncology Clinic - New York City, 2016.

PubMed

Vasquez, Amber M; Lake, Jason; Ngai, Stephanie; Halbrook, Megan; Vallabhaneni, Snigdha; Keckler, M Shannon; Moulton-Meissner, Heather; Lockhart, Shawn R; Lee, Christopher T; Perkins, Kiran; Perz, Joseph F; Antwi, Mike; Moore, Miranda S; Greenko, Jane; Adams, Eleanor; Haas, Janet; Elkind, Sandra; Berman, Marjorie; Zavasky, Dani; Chiller, Tom; Ackelsberg, Joel

2016-11-18

On May 24, 2016, the New York City Department of Health and Mental Hygiene notified CDC of two cases of Exophiala dermatitidis bloodstream infections among patients with malignancies who had received care from a single physician at an outpatient oncology facility (clinic A). Review of January 1-May 31, 2016 microbiology records identified E. dermatitidis bloodstream infections in two additional patients who also had received care at clinic A. All four patients had implanted vascular access ports and had received intravenous (IV) medications, including a compounded IV flush solution containing saline, heparin, vancomycin, and ceftazidime, compounded and administered at clinic A.

Analysis of class II (hydrolytic) and class I (beta-lyase) apurinic/apyrimidinic endonucleases with a synthetic DNA substrate.

PubMed Central

Levin, J D; Demple, B

1990-01-01

We have developed simple and sensitive assays that distinguish the main classes of apurinic/apyrimidinic (AP) endonucleases: Class I enzymes that cleave on the 3' side of AP sites by beta-elimination, and Class II enzymes that cleave by hydrolysis on the 5' side. The distinction of the two types depends on the use of a synthetic DNA polymer that contains AP sites with 5'-[32P]phosphate residues. Using this approach, we now show directly that Escherichia coli endonuclease IV and human AP endonuclease are Class II enzymes, as inferred previously on the basis of indirect assays. The assay method does not exhibit significant interference by nonspecific nucleases or primary amines, which allows the ready determination of different AP endonuclease activities in crude cell extracts. In this way, we show that virtually all of the Class II AP endonuclease activity in E. coli can be accounted for by two enzymes: exonuclease III and endonuclease IV. In the yeast Saccharomyces cerevisiae, the Class II AP endonuclease activity is totally dependent on a single enzyme, the Apn1 protein, but there are probably multiple Class I enzymes. The versatility and ease of our approach should be useful for characterizing this important class of DNA repair enzymes in diverse systems. PMID:1698278

Anaerobic biodegradability of alkylphenols and fuel oxygenates in the presence of alternative electron acceptors.

PubMed

Puig-Grajales, L; Tan, N G; van der Zee, F; Razo-Flores, E; Field, J A

2000-11-01

Alkylphenols and fuel oxygenates are important environmental pollutants produced by the petrochemical industry. A batch biodegradability test was conducted with selected ortho-substituted alkylphenols (2-cresol, 2,6-dimethylphenol and 2-ethylphenol), fuel oxygenates (methyl tert-butyl ether, ethyl tert-butyl ether and tert-amylmethyl ether) and tert-butyl alcohol (TBA) as model compounds. The ortho-substituted alkylphenols were not biodegraded after 100 days of incubation under methanogenic, sulfate-, or nitrate-reducing conditions. However, biodegradation of 2-cresol and 2-ethylphenol (150 mg l(-1)) was observed in the presence of Mn (IV) as electron acceptor. The biodegradation of these two compounds took place in less than 15 days and more than 90% removal was observed for both compounds. Mineralization was indicated since no UV-absorbing metabolites accumulated after 23 days of incubation. These alkylphenols were also slowly chemically oxidized by Mn (IV). No biodegradation of fuel oxygenates or TBA (1 g l(-1)) was observed after 80 or more days of incubation under methanogenic, Fe (III)-, or Mn (IV)-reducing conditions, suggesting that these compounds are recalcitrant under anaerobic conditions. The fuel oxygenates caused no toxicity towards acetoclastic methanogens activity in anaerobic granular sludge.

How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors.

PubMed

Aziz, Imran; Törnblom, Hans; Palsson, Olafur S; Whitehead, William E; Simrén, Magnus

2018-06-08

The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with ≥2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis.

Previously unknown class of metalorganic compounds revealed in meteorites

PubMed Central

Ruf, Alexander; Kanawati, Basem; Hertkorn, Norbert; Yin, Qing-Zhu; Moritz, Franco; Harir, Mourad; Lucio, Marianna; Michalke, Bernhard; Wimpenny, Joshua; Shilobreeva, Svetlana; Bronsky, Basil; Saraykin, Vladimir; Gabelica, Zelimir; Gougeon, Régis D.; Quirico, Eric; Ralew, Stefan; Jakubowski, Tomasz; Haack, Henning; Gonsior, Michael; Jenniskens, Peter; Hinman, Nancy W.; Schmitt-Kopplin, Philippe

2017-01-01

The rich diversity and complexity of organic matter found in meteorites is rapidly expanding our knowledge and understanding of extreme environments from which the early solar system emerged and evolved. Here, we report the discovery of a hitherto unknown chemical class, dihydroxymagnesium carboxylates [(OH)2MgO2CR]−, in meteoritic soluble organic matter. High collision energies, which are required for fragmentation, suggest substantial thermal stability of these Mg-metalorganics (CHOMg compounds). This was corroborated by their higher abundance in thermally processed meteorites. CHOMg compounds were found to be present in a set of 61 meteorites of diverse petrological classes. The appearance of this CHOMg chemical class extends the previously investigated, diverse set of CHNOS molecules. A connection between the evolution of organic compounds and minerals is made, as Mg released from minerals gets trapped into organic compounds. These CHOMg metalorganic compounds and their relation to thermal processing in meteorites might shed new light on our understanding of carbon speciation at a molecular level in meteorite parent bodies. PMID:28242686

Psychosocial stressors and the prognosis of major depression: a test of Axis IV

PubMed Central

Gilman, Stephen E.; Trinh, Nhi-Ha; Smoller, Jordan W.; Fava, Maurizio; Murphy, Jane M.; Breslau, Joshua

2013-01-01

Background Axis IV is for reporting “psychosocial and environmental problems that may affect the diagnosis, treatment, and prognosis of mental disorders.” No studies have examined the prognostic value of Axis IV in DSM-IV. Method We analyzed data from 2,497 participants in the National Epidemiologic Survey on Alcohol and Related Conditions with major depressive episode (MDE). We hypothesized that psychosocial stressors predict a poor prognosis of MDE. Secondarily, we hypothesized that psychosocial stressors predict a poor prognosis of anxiety and substance use disorders. Stressors were defined according to DSM-IV’s taxonomy, and empirically using latent class analysis. Results Primary support group problems, occupational problems, and childhood adversity increased the risks of depressive episodes and suicidal ideation by 20–30%. Associations of the empirically derived classes of stressors with depression were larger in magnitude. Economic stressors conferred a 1.5-fold increase in risk for a depressive episode (CI=1.2–1.9); financial and interpersonal instability conferred a 1.3-fold increased risk of recurrent depression (CI=1.1–1.6). These two classes of stressors also predicted the recurrence of anxiety and substance use disorders. Stressors were not related to suicidal ideation independent from depression severity. Conclusions Psychosocial and environmental problems are associated with the prognosis of MDE and other Axis I disorders. Though DSM-IV’s taxonomy of stressors stands to be improved, these results provide empirical support for the prognostic value of Axis IV. Future work is needed to determine the reliability of Axis IV assessments in clinical practice, and the usefulness of this information to improving the clinical course of mental disorders. PMID:22640506

Changes in the social class gradient of cirrhosis mortality in England and Wales across the 20th century.

PubMed

Crombie, Iain K; Precious, Elaine

2011-01-01

To explore the nature of the social class gradient of cirrhosis mortality in England and Wales across the 20th century. Data on male cirrhosis mortality by social class were obtained from the Registrar General's Decennial Supplements for the years 1921-1991. Data for 1941 were not collected because of the second World War. In 1921, cirrhosis mortality was substantially higher among the professional and managerial classes (I and II) than among the other social classes (III-V). This marked social class difference persisted until 1961 when the differences between the social classes were inconsistent. By 1991, the gradient had reversed and the lower social classes (IV and V) had the higher mortality. The excess mortality was greatest for social class V. The change in the mortality gradient is stark: in 1921social classes I and II had a cirrhosis mortality at least twice that of social classes IV and V, but by 1991 this ratio had reversed. The reversal in the social class gradient of cirrhosis mortality indicates a major change in risk factor distribution across social classes. Differential changes in alcohol consumption are a possible explanation for this change, although the 1991 social class gradient in cirrhosis is inconsistent with alcohol consumption data from national surveys. Further research is required to clarify the explanation for the observed gradient, so that appropriate preventive measures can be put into place.

40 CFR 144.26 - Inventory requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... “Inventory of Injection Wells,” OMB No. 158-R0170. (b) Additional contents. For EPA administered programs...) Class II enhanced recovery wells; (ii) Class IV wells; (iii) The following Class V wells: (A) Sand or... (40 CFR 146.5 (e)(11)) (C) Geothermal energy recovery wells [§ 146.5(e)(12)]; (D) Brine return flow...

Programmatic Summary: Self-Regulating, Self-Pressurizing Tubules for Integrated Circulatory Systems

DTIC Science & Technology

2009-02-01

Conditions: (i) 3- aminopropyl silane; (ii) 2-furoyl chloride, Et3N, CH2Cl2, 0 C to RT, 24 h; (iii) Compound 2, THF, RT, 24 h.; and (iv) Toluene, reflux... aminopropyl )trimethoxy silane. Next, we treated the amino-terminated slides with a solution of 2-furoyl chloride to yield furan functionalized slides...Conditions: (i) 3- aminopropyl silane; (ii) 2-furoyl chloride, Et3N, CH2Cl2, 0 C to RT, 24 h; (iii) Compound 2, THF, RT, 24 h.; and (iv) Toluene, reflux

International Conference on Phonon Physics, 31 August-3 September 1981. Bloomington, Indiana,

DTIC Science & Technology

1981-12-01

sics.Dept., Bloomington, IN 565, Japan. 47405, U.S.A. IWASA, I.- Dept. of Physics, Univ. of Tokyo, 7-3-1 Bongo , Bunkyo- ku, 113 Tokyo, Japan...electron phonon interaction in IV compounds (4). In IV compounds with NaCl structure the phonons mostly affected by the coupling to the RE ion are those...photo-Induced bend edge shift which io on the order of 0.1 *Y towardI the red.* None of the phoson parameters discussed In this paper were affected by

Intravenous Solutions for Exploration Missions

NASA Technical Reports Server (NTRS)

Miller, Fletcher J.; Niederhaus, Charles; Barlow, Karen; Griffin, DeVon

2007-01-01

This paper describes the intravenous (IV) fluids requirements being developed for medical care during NASA s future exploration class missions. Previous research on IV solution generation and mixing in space is summarized. The current exploration baseline mission profiles are introduced, potential medical conditions described and evaluated for fluidic needs, and operational issues assessed. We briefly introduce potential methods for generating IV fluids in microgravity. Conclusions on the recommended fluid volume requirements are presented.

ADHD latent class clusters: DSM-IV subtypes and comorbidity

PubMed Central

Elia, Josephine; Arcos-Burgos, Mauricio; Bolton, Kelly L.; Ambrosini, Paul J.; Berrettini, Wade; Muenke, Maximilian

2014-01-01

ADHD (Attention Deficit Hyperactivity Disorder) has a complex, heterogeneous phenotype only partially captured by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. In this report, latent class analyses (LCA) are used to identify ADHD phenotypes using K-SADS-IVR (Schedule for Affective Disorders & Schizophrenia for School Age Children-IV-Revised) symptoms and symptom severity data from a clinical sample of 500 ADHD subjects, ages 6–18, participating in an ADHD genetic study. Results show that LCA identified six separate ADHD clusters, some corresponding to specific DSM-IV subtypes while others included several subtypes. DSM-IV comorbid anxiety and mood disorders were generally similar across all clusters, and subjects without comorbidity did not aggregate within any one cluster. Age and gender composition also varied. These results support findings from population-based LCA studies. The six clusters provide additional homogenous groups that can be used to define ADHD phenotypes in genetic association studies. The limited age ranges aggregating in the different clusters may prove to be a particular advantage in genetic studies where candidate gene expression may vary during developmental phases. DSM-IV comorbid mood and anxiety disorders also do not appear to increase cluster heterogeneity; however, longitudinal studies that cover period of risk are needed to support this finding. PMID:19900717

Crystallization tendency of active pharmaceutical ingredients following rapid solvent evaporation--classification and comparison with crystallization tendency from undercooled melts.

PubMed

Van Eerdenbrugh, Bernard; Baird, Jared A; Taylor, Lynne S

2010-09-01

In this study, the crystallization behavior of a variety of compounds was studied following rapid solvent evaporation using spin coating. Initial screening to determine model compound suitability was performed using a structurally diverse set of 51 compounds in three different solvent systems [dichloromethane (DCM), a 1:1 (w/w) dichloromethane/ethanol mixture (MIX), and ethanol (EtOH)]. Of this starting set of 153 drug-solvent combinations, 93 (40 compounds) were selected for further evaluation based on solubility, chemical solution stability, and processability criteria. These systems were spin coated and their crystallization was monitored using polarized light microscopy (7 days, dry conditions). The crystallization behavior of the samples could be classified as rapid (Class I: 39 cases), intermediate (Class II: 23 cases), or slow (Class III: 31 cases). The solvent system employed influenced the classification outcome for only four of the compounds. The various compounds showed very diverse crystallization behavior. Upon comparison of classification results with those of a previous study, where cooling from the melt was used as a preparation technique, a good similarity was found whereby 68% of the cases were identically classified. Multivariate analysis was performed using a set of relevant physicochemical compound characteristics. It was found that a number of these parameters tended to differ between the different classes. These could be further interpreted in terms of the nature of the crystallization process. Additional multivariate analysis on the separate classes of compounds indicated some potential in predicting the crystallization tendency of a given compound.

Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model.

PubMed

León, I E; Cadavid-Vargas, J F; Tiscornia, I; Porro, V; Castelli, S; Katkar, P; Desideri, A; Bollati-Fogolin, M; Etcheverry, S B

2015-10-01

Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na₂[VO(silibinin)₂2]·6H₂O (VOsil) and chrysin [VO(chrysin)₂EtOH]₂(VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments.

The "index cutback technique": a three-dimensional guided layering approach in direct class IV composite restorations.

PubMed

Ammannato, Riccardo; Ferraris, Federico; Allegri, Mario

One of the main difficulties encountered with conventional class IV direct composite restorations is the layering management in terms of three-dimensionality and shape control. The major concern is the predictability of the esthetic outcome, which is closely linked to the clinician's skills. This article presents a predictable approach to treat class IV direct composite restorations. The technique allows for the shape and thickness of different composite layers to be guided through transparent indexes that have been carried out previously on a planned wax-up. The final goal is to achieve a good esthetic outcome in an easy and fast way through a copy-and-paste approach. The "index cutback technique" is a complementary variant of the "index technique" for class IV direct restorations. After the casts have been generated, the technician creates a full wax-up of the tooth to be restored. A transparent silicone key of the full wax-up provides the full enamel index that is then cut with a blade along the incisal edge to achieve two enamel indexes, one palatal and one buccal. Then, the required amount of wax is removed from the full wax-up through a cutback step. The aim of this step is to remove a suitable amount of wax to leave a predetermined space for the composite enamel layers, both on the palatal and buccal surfaces. A second transparent silicone key is built on the cutback wax-up to achieve the cutback dentin index, which is then used to press the composite dentin onto the prepared tooth.

PEROXOTITANATE- AND MONOSODIUM METAL-TITANATE COMPOUNDS AS INHIBITORS OF BACTERIAL GROWTH

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

Hobbs, D.

2011-01-19

Sodium titanates are ion-exchange materials that effectively bind a variety of metal ions over a wide pH range. Sodium titanates alone have no known adverse biological effects but metal-exchanged titanates (or metal titanates) can deliver metal ions to mammalian cells to alter cell processes in vitro. In this work, we test a hypothesis that metal-titanate compounds inhibit bacterial growth; demonstration of this principle is one prerequisite to developing metal-based, titanate-delivered antibacterial agents. Focusing initially on oral diseases, we exposed five species of oral bacteria to titanates for 24 h, with or without loading of Au(III), Pd(II), Pt(II), and Pt(IV), andmore » measuring bacterial growth in planktonic assays through increases in optical density. In each experiment, bacterial growth was compared with control cultures of titanates or bacteria alone. We observed no suppression of bacterial growth by the sodium titanates alone, but significant (p < 0.05, two-sided t-tests) suppression was observed with metal-titanate compounds, particularly Au(III)-titanates, but with other metal titanates as well. Growth inhibition ranged from 15 to 100% depending on the metal ion and bacterial species involved. Furthermore, in specific cases, the titanates inhibited bacterial growth 5- to 375-fold versus metal ions alone, suggesting that titanates enhanced metal-bacteria interactions. This work supports further development of metal titanates as a novel class of antibacterials.« less

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis

PubMed Central

Twarog, Nathaniel R.; Low, Jonathan A.; Currier, Duane G.; Miller, Greg; Chen, Taosheng; Shelat, Anang A.

2016-01-01

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2’-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used. PMID:26886014

Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis.

PubMed

Twarog, Nathaniel R; Low, Jonathan A; Currier, Duane G; Miller, Greg; Chen, Taosheng; Shelat, Anang A

2016-01-01

Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2'-deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used.

A comprehensive evaluation of three microfluidic chemiluminescence methods for the determination of the total phenolic contents in fruit juices.

PubMed

Al Haddabi, Buthaina; Al Lawati, Haider A J; Suliman, FakhrEldin O

2017-01-01

Three recently reported microfluidic chemiluminescence (MF-CL) methods (based on reactions with acidic permanganate enhanced by formaldehyde (KMnO4-COH), acidic cerium (IV) and rhodamine B (Ce-RB), and acidic cerium (IV) and rhodamine 6G (Ce-R6G) enhanced by SDS) for the determination of the total phenolic content (TPC) in juices were critically evaluated in terms of their selectivity. The evaluation was carried out using 86 analytes, including 22 phenolic compounds (phenolic acids and polyphenols), 6 known non-phenolic antioxidants, 9 amino acids and a number of proteins, carbohydrates, nucleotide bases, inorganic salts and other compounds. Each method was sensitive toward phenolic compounds (PCs). However, the KMnO4-COH CL system showed a higher sensitivity toward phenolic acids and also responded to non-phenolic antioxidants. The other two systems showed higher sensitivity toward polyphenolic compounds than to phenolic acids and did not responded to all other compounds including non-phenolic antioxidants. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Study on chemical constituents from the roots and rhizomes of Sinopodophyllum emodi].

PubMed

Sun, Yan-Jun; Li, Zhan-Lin; Chen, Hong; Zhou, Wei; Hua, Hui-Ming

2012-10-01

To investigate the chemical constituents in the roots and rhizomes of Sinopodophyllum emodi. The compounds were isolated by many different chromatographic methods such as silica gel, Sephadex LH-20, and ODS column. Their structures were identified by their physicochemical properties and spectrascopic data. Nine compounds were isolated and identified as isopicrodeoxypodophyllotoxin(I), 3beta-hydroxy-7alpha-methoxy-24beta-ethyl-cholest-5-ene(II), 5alpha, 8alpha-epidioxy-(22E,24R)-erg-osta-6,22-dien-3beta-ol(III), 7beta-hydroxysitosterol (IV), beta-sitosterol (V), daucosterol (VI), alpha-glyceryl palmitate (VII), alpha-D-glucose (VIII), 5-hydromethyl furaldehyde (IX). Compounds I - IV, VII - IX are obtained from this genus for the first time.

Exploration of a Series of 5-Arylidene-2-thioxoimidazolidin-4-ones as Inhibitors of the Cytolytic Protein Perforin

PubMed Central

2013-01-01

A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming protein perforin. Structure–activity relationships were explored through variation of an isoindolinone or 3,4-dihydroisoquinolinone subunit on a fixed 2-thioxoimidazolidin-4-one/thiophene core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perforin protein and perforin delivered in situ by natural killer cells was determined. A number of compounds showed excellent activity at concentrations that were nontoxic to the killer cells, and several were a significant improvement on previous classes of inhibitors, being substantially more potent and soluble. Representative examples showed rapid and reversible binding to immobilized mouse perforin at low concentrations (≤2.5 μM) by surface plasmon resonance and prevented formation of perforin pores in target cells despite effective target cell engagement, as determined by calcium influx studies. Mouse PK studies of two analogues showed T1/2 values of 1.1–1.2 h (dose of 5 mg/kg iv) and MTDs of 60–80 mg/kg (ip). PMID:24195776

Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents

PubMed Central

Fedorova, Elena V.; Buryakina, Anna V.; Zakharov, Alexey V.; Filimonov, Dmitry A.; Lagunin, Alexey A.; Poroikov, Vladimir V.

2014-01-01

Based on the data about structure and antidiabetic activity of twenty seven vanadium and zinc coordination complexes collected from literature we developed QSAR models using the GUSAR program. These QSAR models were applied to 10 novel vanadium coordination complexes designed in silico in order to predict their hypoglycemic action. The five most promising substances with predicted potent hypoglycemic action were selected for chemical synthesis and pharmacological evaluation. The selected coordination vanadium complexes were synthesized and tested in vitro and in vivo for their hypoglycemic activities and acute rat toxicity. Estimation of acute rat toxicity of these five vanadium complexes was performed using a freely available web-resource (http://way2drug.com/GUSAR/acutoxpredict.html). It has shown that the selected compounds belong to the class of moderate toxic pharmaceutical agents, according to the scale of Hodge and Sterner. Comparison with the predicted data has demonstrated a reasonable correspondence between the experimental and predicted values of hypoglycemic activity and toxicity. Bis{tert-butyl[amino(imino)methyl]carbamato}oxovanadium (IV) and sodium(2,2′-Bipyridyl)oxo-diperoxovanadate(V) octahydrate were identified as the most potent hypoglycemic agents among the synthesized compounds. PMID:25057899

Polymers for electronics and spintronics.

PubMed

Bujak, Piotr; Kulszewicz-Bajer, Irena; Zagorska, Malgorzata; Maurel, Vincent; Wielgus, Ireneusz; Pron, Adam

2013-12-07

This critical review is devoted to semiconducting and high spin polymers which are of great scientific interest in view of further development of the organic electronics and the emerging organic spintronic fields. Diversified synthetic strategies are discussed in detail leading to high molecular mass compounds showing appropriate redox (ionization potential (IP), electron affinity (EA)), electronic (charge carrier mobility, conductivity), optoelectronic (electroluminescence, photoconductivity) and magnetic (magnetization, ferromagnetic spin interactions) properties and used as active components of devices such as n- and p-channel field effect transistors, ambipolar light emitting transistors, light emitting diodes, photovoltaic cells, photodiodes, magnetic photoswitches, etc. Solution processing procedures developed with the goal of depositing highly ordered and oriented films of these polymers are also described. This is completed by the description of principal methods that are used for characterizing these macromolecular compounds both in solution and in the solid state. These involve various spectroscopic methods (UV-vis-NIR, UPS, pulse EPR), electrochemistry and spectroelectrochemistry, magnetic measurements (SQUID), and structural and morphological investigations (X-ray diffraction, STM, AFM). Finally, four classes of polymers are discussed in detail with special emphasis on the results obtained in the past three years: (i) high IP, (ii) high |EA|, (iii) low band gap and (iv) high spin ones.

First-principles calculations of phonons and Raman and infrared spectra in Cd-IV-N2 compounds

NASA Astrophysics Data System (ADS)

Lyu, Sai; Lambrecht, Walter R. L.

2018-05-01

A first-principles study of the phonons at the zone center in Cd-IV-N2 compounds is presented with IV = Si, Ge, Sn. The calculations are performed for the most likely Pbn21 crystal structure, after showing that it is indeed lower in total energy compared to the closely related Pmc21 structure. The normal mode frequencies are calculated using density functional perturbation theory and symmetry labeled. The longitudinal optical-transverse optical splittings are determined using the Born effective charges which are also reported. These are used to simulate polarized Raman spectra for different scattering configurations as well as the infrared absorption and reflection spectra. The mode frequencies are found to decrease from Si to Ge to Sn as group-IV cation. The spectra show a wide variety of number of prominent peaks and relative intensities in spite of the great similarities of these three materials. Phonon densities of states and their analysis in atom by atom contributions are also reported.

40 CFR 721.775 - Brominated aromatic com-pound (generic name).

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Requirements as specified in § 721.80 (j) (use as an additive flame retardant for plastics) and (q). (iv... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Brominated aromatic com-pound (generic... Specific Chemical Substances § 721.775 Brominated aromatic com-pound (generic name). (a) Chemical...

40 CFR 721.775 - Brominated aromatic com-pound (generic name).

Code of Federal Regulations, 2014 CFR

2014-07-01

.... Requirements as specified in § 721.80 (j) (use as an additive flame retardant for plastics) and (q). (iv... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Brominated aromatic com-pound (generic... Specific Chemical Substances § 721.775 Brominated aromatic com-pound (generic name). (a) Chemical...

40 CFR 721.775 - Brominated aromatic com-pound (generic name).

Code of Federal Regulations, 2012 CFR

2012-07-01

.... Requirements as specified in § 721.80 (j) (use as an additive flame retardant for plastics) and (q). (iv... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Brominated aromatic com-pound (generic... Specific Chemical Substances § 721.775 Brominated aromatic com-pound (generic name). (a) Chemical...

Overlapping and Divergent Actions of Structurally Distinct Histone Deacetylase Inhibitors in Cardiac Fibroblasts.

PubMed

Schuetze, Katherine B; Stratton, Matthew S; Blakeslee, Weston W; Wempe, Michael F; Wagner, Florence F; Holson, Edward B; Kuo, Yin-Ming; Andrews, Andrew J; Gilbert, Tonya M; Hooker, Jacob M; McKinsey, Timothy A

2017-04-01

Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly affect cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II, and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiologic and pathophysiological processes. For example, the benzamide class I HDAC-selective inhibitor, MGCD0103 [ N -(2-aminophenyl)-4-[[(4-pyridin-3-ylpyrimidin-2-yl)amino]methyl] benzamide], was shown to block cardiac fibrosis, a process involving excess extracellular matrix deposition, which often results in heart dysfunction. Here, we compare the mechanisms of action of structurally distinct HDAC inhibitors in isolated primary cardiac fibroblasts, which are the major extracellular matrix-producing cells of the heart. TSA, MGCD0103, and the cyclic peptide class I HDAC inhibitor, apicidin, exhibited a common ability to enhance histone acetylation, and all potently blocked cardiac fibroblast cell cycle progression. In contrast, MGCD0103, but not TSA or apicidin, paradoxically increased expression of a subset of fibrosis-associated genes. Using the cellular thermal shift assay, we provide evidence that the divergent effects of HDAC inhibitors on cardiac fibroblast gene expression relate to differential engagement of HDAC1- and HDAC2-containing complexes. These findings illustrate the importance of employing multiple compounds when pharmacologically assessing HDAC function in a cellular context and during HDAC inhibitor drug development. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

2D and 3D T2-weighted MR sequences for the assessment of neurovascular bundle changes after nerve-sparing radical retropubic prostatectomy with erectile function correlation.

PubMed

Panebianco, Valeria; Sciarra, Alessandro; Osimani, Marcello; Lisi, Danilo; Ciccariello, Mauro; Salciccia, Stefano; Gentile, Vincenzo; Di Silverio, Franco; Passariello, Roberto

2009-01-01

The aim of this study was to assess the capability of a 3D isotropic MRI T2-weighted sequence (3D T2 ISO) in the depiction of changes of neurovascular bundles (NVBs) after bilateral nerve-sparing radical retropubic prostatectomy (RRP). Furthermore, our aim was also to introduce a new MRI classification score of the NVB alteration patterns using the International Index Erectile Function Five-Item (IIEF-5) score as standard of reference. Fifty-three consecutive patients were postoperatively submitted to two MR examinations, including both 2D TSE T2-weighted (2D T2) and 3D T2 ISO sequences. Image findings were scored using a relative five-point classification and correlated with the postoperative IIEF-5 score. Radiologists attributed 13.2% of patients to class 0, 11.3% to class I, 34% to class II, 24.5% to class III, and 16.9% to class IV. With 3D T2 ISO images, the same radiologists determined 43.3% class 0, 32% class I, 11.4% class II, 7.5% class III, and 5.7% class IV. In all cases, the correlation and regression analysis between the 3D T2 ISO and IIEF-5 score resulted in higher coefficients values. The 3D sequence correlated most closely with patients' grading of erectile function.

Antitumoral effect of vanadium compounds in malignant melanoma cell lines.

PubMed

Rozzo, Carla; Sanna, Daniele; Garribba, Eugenio; Serra, Maria; Cantara, Alessio; Palmieri, Giuseppe; Pisano, Marina

2017-09-01

In this study we evaluated the anticancer activity against malignant melanoma (MM) of four different vanadium species: the inorganic anion vanadate(V) (indicated with VN), and three oxidovanadium(IV) complexes, [V IV O(dhp) 2 ] where dhp - is the anion 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS2), [V IV O(mpp) 2 ] where mpp - is 1-methyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS3), and [V IV O(ppp) 2 ] where ppp - is 1-phenyl-2-methyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS4). The antitumor effects of these compounds were studied against two different MM cell lines (A375 and CN-mel) and a fibroblast cell line (BJ) as normal control. All tested V compounds exert antiproliferative activity on MM cells in a dose dependent manner (IC 50 ranges from 2.4μM up to 14μM) being A375 the most sensitive cell line. VN and VS2 were the two most active compounds against A375 (IC 50 of 4.7 and 2.6μM, respectively), causing apoptosis and cell cycle block. The experimental data indicate that the cell cycle arrest occurs at different phases for the two V species analyzed (G2 checkpoint for VN and G0/G1 for VS2), showing the importance of the chemical form in determining their mechanism of action. These results add more insights into the landscape of vanadium versatility in biological systems and into its role as a potential cancer therapeutic agent. Copyright © 2017 Elsevier Inc. All rights reserved.

40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...

40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...

40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...

40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...

40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...

76 FR 56833 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Notice of Filing of Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... respective voting rights and of Class A and Class B common stock, (iv) setting forth certain limitations on... Incorporation, shares of Non-Voting Common Stock possess the same rights, preferences, powers, privileges... B Common Stock. Except for voting rights and certain conversion features, as described below, Class...

76 FR 56840 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... respective voting rights and of Class A and Class B common stock, (iv) setting forth certain limitations on... Incorporation, shares of Non-Voting Common Stock possess the same rights, preferences, powers, privileges...-Voting Class B Common Stock. Except for voting rights and certain conversion features, as described below...

77 FR 24978 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah. AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act (Pub. L. 97-451...

76 FR 14686 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-17

... Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act (Pub. L. 97-451...

Is the full potential of the biopharmaceutics classification system reached?

PubMed

Bergström, Christel A S; Andersson, Sara B E; Fagerberg, Jonas H; Ragnarsson, Gert; Lindahl, Anders

2014-06-16

In this paper we analyse how the biopharmaceutics classification system (BCS) has been used to date. A survey of the literature resulted in a compilation of 242 compounds for which BCS classes were reported. Of these, 183 compounds had been reported to belong to one specific BCS class whereas 59 compounds had been assigned to multiple BCS classes in different papers. Interestingly, a majority of the BCS class 2 compounds had fraction absorbed (FA) values >85%, indicating that they were completely absorbed after oral administration. Solubility was computationally predicted at pH 6.8 for BCS class 2 compounds to explore the impact of the pH of the small intestine, where most of the absorption occurs, on the solubility. In addition, the solubilization capacity of lipid aggregates naturally present in the intestine was studied computationally and experimentally for a subset of 12 compounds. It was found that all acidic compounds with FA>85% were completely dissolved in the pH of the small intestine. Further, lipids at the concentration used in fasted state simulated intestinal fluid (FaSSIF) dissolved the complete dose given of the most lipophilic (logD6.5>3) compounds studied. Overall, biorelevant dissolution media (pure buffer of intestinal pH or FaSSIF) identified that for 20 of the 29 BCS class 2 compounds with FA>85% the complete dose given orally would be dissolved. These results indicate that a more relevant pH restriction for acids and/or dissolution medium with lipids present better forecast solubility-limited absorption in vivo than the presently used BCS solubility criterion. The analysis presented herein further strengthens the discussion on the requirement of more physiologically relevant dissolution media for the in vitro solubility classification performed to reach the full potential of the BCS. Copyright © 2013 Elsevier B.V. All rights reserved.

Triaryl Benzimidazoles as a New Class of Antibacterial Agents against Resistant Pathogenic Microorganisms.

PubMed

Picconi, Pietro; Hind, Charlotte; Jamshidi, Shirin; Nahar, Kazi; Clifford, Melanie; Wand, Matthew E; Sutton, J Mark; Rahman, Khondaker Miraz

2017-07-27

A new class of nontoxic triaryl benzimidazole compounds, derived from existing classes of DNA minor groove binders, were designed, synthesized, and evaluated for their antibacterial activity against multidrug resistant (MDR) Gram-positive and Gram-negative species. Molecular modeling experiments suggest that the newly synthesized class cannot be accommodated within the minor groove of DNA due to a change in the shape of the molecules. Compounds 8, 13, and 14 were found to be the most active of the series, with MICs in the range of 0.5-4 μg/mL against the MDR Staphylococci and Enterococci species. Compound 13 showed moderate activity against the MDR Gram-negative strains, with MICs in the range of 16-32 μg/mL. Active compounds showed a bactericidal mode of action, and a mechanistic study suggested the inhibition of bacterial gyrase as the mechanism of action (MOA) of this chemical class. The MOA was further supported by the molecular modeling study.

Multidisciplinary and multisetting team management programme in heart failure patients affects hospitalisation and costing.

PubMed

Piepoli, M F; Villani, G Q; Aschieri, D; Bennati, S; Groppi, F; Pisati, M S; Rosi, A; Capucci, A

2006-08-28

We evaluated whether multidisciplinary disease management programme developed with collaboration of physicians and nurses inside and outside general district hospital settings can affect clinical outcomes in heart failure population over a 12-month period. 571 patients hospitalised with CHF were referred to our unit and 509 patients agreed to participation. The intervention team included physicians and nurses from Internal Medicine and Cardiac Dept., and the patient's general practitioners. Contacts were on a pre-specified schedule, included a computerised programme of hospital visits and phone calls; in case of NYHA functional class III and IV patients, home visits were also planned. The median age of patients was 77.7+/-9 years (43.3% women). At baseline the percentage of patients with NYHA class III and IV was 56.0% vs. 26.0% after 12 months (P<0.05). Programme enrolment reduced total hospital admissions (82 vs. 190, -56%, P<0.05), number of patients hospitalised (62 vs. 146, 57%, P<0.05). All NYHA functional class benefited (class I=75%, class IV=67%), with reduction in the costing (-48%, P<0.05). Improvement in symptoms (-9.0+/-3.2) and signs (-5.2+/-3.1) scores was measured (P<0.01). Therapy optimisation was obtained by 20.5% increase in patients taking betablockade and 21.0% increase in those on anti-aldosterone drugs. Multidisciplinary approach to CHF management can improve clinical management, reducing hospitalisation rate and costing.

Repellent and Anti-quorum Sensing Activity of Six Aromatic Plants Occurring in Colombia.

PubMed

Cervantes-Ceballos, Leonor; Caballero-Gallardo, Karina; Olivero-Verbel, Jesus

2015-10-01

Essential oils (EOs) are widely used as biopesticides and to control bacterial infections. This study describes the ability of six EOs isolated from plants cultivated in Colombia to perform as repellents against Ulomoides dermestoides and as quorum sensing (QS) inhibitors. EOs from Aloysia triphylla, Cymbopogon nardus, Lippia origanoides, Hyptis suaveolens, Swinglea glutinosa and Eucalyptus globulus were repellents classified as Class IV, IV, IV, III, II, and II, respectively, whereas the commercial repellent IR3535 only reached Class II after 2 h exposure. All EOs presented small, but significant inhibitory properties against the QS system in Escherichia coli (pJBA132) at 25 μg/mL after 4 h exposure. These data suggest evaluated EOs from Colombia are sustainable, promising new sources of natural repellents and could be important as anti-quorum sensing molecules.

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... (iii) Glider. (iv) Lighter-than-air. (v) Powered-lift. (vi) Powered parachute. (vii) Weight-shift...—Airplane. (ii) Instrument—Helicopter. (iii) Instrument—Powered-lift. (c) The following ratings are placed.... (iii) Glider. (iv) Powered-lift. (2) Airplane class ratings— (i) Single-engine. (ii) Multiengine. (3...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... (iii) Glider. (iv) Lighter-than-air. (v) Powered-lift. (vi) Powered parachute. (vii) Weight-shift...—Airplane. (ii) Instrument—Helicopter. (iii) Instrument—Powered-lift. (c) The following ratings are placed.... (iii) Glider. (iv) Powered-lift. (2) Airplane class ratings— (i) Single-engine. (ii) Multiengine. (3...

Structure of 7,12-dimethylbenz(a)anthracene-guanosine adducts.

PubMed

Jeffrey, A M; Blobstein, S H; Weinstein, I B; Beland, F A; Harvey, R G; Kasai, H; Nakanishi, K

1976-07-01

Arene oxides have been proposed as the reactive intermediates in the process of carcinogenesis induced by polycyclic aromatic hydrocarbons. The present study defines the structures of four guanosine adducts formed by the reaction of 7,12-dimethylbenz[a]anthracene-5,6-oxide with polyguanylic acid. The modified polymer was hydrolyzed to nucleotides and the hydrophobic guanosine adducts separated from unmodified guanosine by LH-20 column chromatograhy. The adducts were further resolved into four components (I-IV) by reverse phase high pressure liquid chromatography. Analysis of the ultraviolet, circular dichroism, mass, and proton magnetic resonance spectra of these compounds, or their acetate and free base derivatives, indicates that in all four compounds the aromatic hydrocarbon is present on the 2 amino group of guanine. Compounds I and IV, and II and III constitute diastereoisomeric pairs, respectively. In the I and IV pair, the adducts result from addition at the 6 position of the original dimethylbenz[a]anthracene oxide, whereas in the II and III pair, the addition occurs at the 5 position. Indirect evidence suggests that trans opening of the oxide occurred in all cases but this remains to be established.

Iron(IV)hydroxide pK(a) and the role of thiolate ligation in C-H bond activation by cytochrome P450.

PubMed

Yosca, Timothy H; Rittle, Jonathan; Krest, Courtney M; Onderko, Elizabeth L; Silakov, Alexey; Calixto, Julio C; Behan, Rachel K; Green, Michael T

2013-11-15

Cytochrome P450 enzymes activate oxygen at heme iron centers to oxidize relatively inert substrate carbon-hydrogen bonds. Cysteine thiolate coordination to iron is posited to increase the pK(a) (where K(a) is the acid dissociation constant) of compound II, an iron(IV)hydroxide complex, correspondingly lowering the one-electron reduction potential of compound I, the active catalytic intermediate, and decreasing the driving force for deleterious auto-oxidation of tyrosine and tryptophan residues in the enzyme's framework. Here, we report on the preparation of an iron(IV)hydroxide complex in a P450 enzyme (CYP158) in ≥90% yield. Using rapid mixing technologies in conjunction with Mössbauer, ultraviolet/visible, and x-ray absorption spectroscopies, we determine a pK(a) value for this compound of 11.9. Marcus theory analysis indicates that this elevated pK(a) results in a >10,000-fold reduction in the rate constant for oxidations of the protein framework, making these processes noncompetitive with substrate oxidation.

Coordination chemistry and insulin-enhancing behavior of vanadium complexes with maltol C6H6O3 structural isomers.

PubMed

Saatchi, Katayoun; Thompson, Katherine H; Patrick, Brian O; Pink, Maren; Yuen, Violet G; McNeill, John H; Orvig, Chris

2005-04-18

Syntheses of vanadium complexes using the naturally occurring ligands isomaltol (Hima) and allomaltol (Hama), as well as a newly synthesized, potentially tetradentate diaminodipyrone [H(2)(en(ama)(2)], are reported. Complete characterization of the resulting compounds [trans-VO(ima)(2)(H(2)O), VO(ama)(2), V(ima)(3), V(ama)(3) and VO(en(ama)(2))], including X-ray crystallography analyses for trans-VO(ima)(2)(H(2)O) and V(ima)(3), are presented herein. Potentiometric titrations (25 degrees C, I = 0.16 M NaCl) were used to measure stability constants in the V(IV)-Hima system; these data were compared to previous data collected on the V(IV)-L (L = Hma, Hama) systems. The in vivo efficacy of these compounds to lower the blood glucose levels of STZ-diabetic rats was tested; all but VO(en(ama)(2)) produced significant decreases in plasma glucose levels. The results were compared to those of the benchmark compound BMOV [VO(ma)(2), bis(maltolato)oxovanadium(IV)], a known insulin-enhancing agent.

Nature and prevalence of non-additive toxic effects in industrially relevant mixtures of organic chemicals.

PubMed

Parvez, Shahid; Venkataraman, Chandra; Mukherji, Suparna

2009-06-01

The concentration addition (CA) and the independent action (IA) models are widely used for predicting mixture toxicity based on its composition and individual component dose-response profiles. However, the prediction based on these models may be inaccurate due to interaction among mixture components. In this work, the nature and prevalence of non-additive effects were explored for binary, ternary and quaternary mixtures composed of hydrophobic organic compounds (HOCs). The toxicity of each individual component and mixture was determined using the Vibrio fischeri bioluminescence inhibition assay. For each combination of chemicals specified by the 2(n) factorial design, the percent deviation of the predicted toxic effect from the measured value was used to characterize mixtures as synergistic (positive deviation) and antagonistic (negative deviation). An arbitrary classification scheme was proposed based on the magnitude of deviation (d) as: additive (< or =10%, class-I) and moderately (10< d < or =30 %, class-II), highly (30< d < or =50%, class-III) and very highly (>50%, class-IV) antagonistic/synergistic. Naphthalene, n-butanol, o-xylene, catechol and p-cresol led to synergism in mixtures while 1, 2, 4-trimethylbenzene and 1, 3-dimethylnaphthalene contributed to antagonism. Most of the mixtures depicted additive or antagonistic effect. Synergism was prominent in some of the mixtures, such as, pulp and paper, textile dyes, and a mixture composed of polynuclear aromatic hydrocarbons. The organic chemical industry mixture depicted the highest abundance of antagonism and least synergism. Mixture toxicity was found to depend on partition coefficient, molecular connectivity index and relative concentration of the components.

Exploring new classification criteria for the earliest type stars: the 3400 Aregion

NASA Astrophysics Data System (ADS)

Morrell, Nidia I.; Walborn, Nolan R.; Arias, Julia I.

2002-02-01

We propose spectroscopic observations of a sample of standard O2-O4 stars in the wavelength region containing the N IV 3479-83-85 Aand O IV 3381-85-3412 Alines, in order to analyze the behavior of these spectral features as a function of the spectral type. We aim to define new classification criteria for the hottest stars, evaluating these N IV and O IV lines near 3400 Aas possible temperature and luminosity discriminators. The former spectral class O3 has just been split into three different classes: O2, O3 and O3.5 (Walborn et al. 2001). The paucity of classification criteria at these types in the traditional wavelength domain (4000 - 4700 Å), makes clear the need to explore other spectral ranges in order to define additional constraints on the determination of spectral types and luminosity classes. The wavelength range around 3400 Ahas been observed in many faint, crowded early O-type stars by HST/FOS, the corresponding data being available from the HST archive. This enhances our interest in observing this spectral range in the classification standards for the early O-type stars in order to make these existing HST observations even more useful, allowing the determination of accurate spectral types for unknown objects from them, once the behavior of the new criteria in the standards has been charted.

Coordination Chemistry of Homoleptic Actinide(IV)-Thiocyanate Complexes

DOE PAGES

Carter, Tyler J.; Wilson, Richard E.

2015-09-10

Here, the synthesis, X-ray crystal structure, vibrational and optical spectroscopy for the eight-coordinate thiocyanate compounds, [Et 4N] 4[Pu IV(NCS) 8], [Et 4N] 4[Th IV(NCS) 8], and [Et 4N] 4[Ce III(NCS) 7(H 2O)] are reported. Thiocyanate was found to rapidly reduce plutonium to Pu III in acidic solutions (pH<1) in the presence of NCS –. The optical spectrum of [Et 4N][SCN] containing Pu III solution was indistinguishable from that of aquated Pu III suggesting that inner-sphere complexation with [Et 4N][SCN] does not occur in water. However, upon concentration, the homoleptic thiocyanate complex [Et 4N] 4[Pu IV(NCS) 8] was crystallized when amore » large excess of [Et 4N][NCS] was present. This compound, along with its U IV analogue, maintains inner-sphere thiocyanate coordination in acetonitrile based on the observation of intense ligand-to-metal charge-transfer bands. Spectroscopic and crystallographic data do not support the interaction of the metal orbitals with the ligand π system, but support an enhanced An IV–NCS interaction, as the Lewis acidity of the metal ion increases from Th to Pu.« less

Investigating the Effect of Emetic Compounds on Chemotaxis in Dictyostelium Identifies a Non-Sentient Model for Bitter and Hot Tastant Research

PubMed Central

Robery, Steven; Mukanowa, Janina; Percie du Sert, Nathalie; Andrews, Paul L. R.; Williams, Robin S. B.

2011-01-01

Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence reduce adverse animal experimentation in this area. Twenty eight emetic or taste aversive compounds were employed to investigate the acute (10 min) effect of compounds on Dictyostelium cell behaviour (shape, speed and direction of movement) in a shallow chemotaxic gradient (Dunn chamber). Compound concentrations were chosen based on those previously reported to be emetic or aversive in in vivo studies and results were recorded and quantified by automated image analysis. Dictyostelium cell motility was rapidly and strongly inhibited by four structurally distinct tastants (three bitter tasting compounds - denatonium benzoate, quinine hydrochloride, phenylthiourea, and the pungent constituent of chilli peppers - capsaicin). In addition, stomach irritants (copper chloride and copper sulphate), and a phosphodiesterase IV inhibitor also rapidly blocked movement. A concentration-dependant relationship was established for five of these compounds, showing potency of inhibition as capsaicin (IC50 = 11.9±4.0 µM) > quinine hydrochloride (IC50 = 44.3±6.8 µM) > denatonium benzoate (IC50 = 129±4 µM) > phenylthiourea (IC50 = 366±5 µM) > copper sulphate (IC50 = 1433±3 µM). In contrast, 21 compounds within the cytotoxic and receptor agonist/antagonist classes did not affect cell behaviour. Further analysis of bitter and pungent compounds showed that the effect on cell behaviour was reversible and not cytotoxic, suggesting an uncharacterised molecular mechanism of action for these compounds. These results therefore demonstrate that Dictyostelium has potential as a non-sentient model in the analysis of the molecular effects of tastants, although it has limited utility in identification of emetic agents in general. PMID:21931717

Intravenous alcohol self-administration in the P rat.

PubMed

Windisch, Kyle A; Kosobud, Ann E K; Czachowski, Cristine L

2014-08-01

Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally "relevant" effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding "non-pharmacological" effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol's effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol self-administration methodology cannot overcome the aversive properties of ethanol via this route in the rat. Copyright © 2014 Elsevier Inc. All rights reserved.

URANIUM EXTRACTION PROCESS USING SYNERGISTIC REAGENTS

DOEpatents

Schmitt, J.M.; Blake, C.A. Jr.; Brown, K.B.; Coleman, C.F.

1958-11-01

Improved methods are presented for recovering uranium values from aqueous solutions by organic solvent extraction. The improvement lies in the use, in combination, of two classes of organic compounds so that their extracting properties are enhanced synergistically. The two classes of organic compounds are dialkylphosphoric acid and certain neutral organophosphorus compounds such as trialkylphosphates, trialkylphosphonates, trlalkylphosphinates and trialkylphosphine oxides.

A Dinitroaniline-Resistant Mutant of Eleusine indica Exhibits Cross-Resistance and Supersensitivity to Antimicrotubule Herbicides and Drugs 1

PubMed Central

Vaughn, Kevin C.; Marks, M. David; Weeks, Donald P.

1987-01-01

A dinitroaniline-resistant (R) biotype of Eleusine indica (L.) Gaertner. (goosegrass) is demonstrated to be cross-resistant to a structurally non-related herbicide, amiprophosmethyl, and supersensitive to two other classes of compounds which disrupt mitosis. These characteristics of the R biotype were discovered in a comparative test of the effects of 24 different antimitotic compounds on the R biotype and susceptible (S) wild-type Eleusine. The compounds tested could be classified into three groups based upon their effects on mitosis in root tips of the susceptible (S) biotype. Class I compounds induced effects like the well known mitotic disrupter colchicine: absence of cortical and spindle microtubules, mitosis arrested at prometaphase, and the formation of polymorphic nuclei after arrested mitosis. The R biotype was resistant to treatment with some class I inhibitors (all dinitroaniline herbicides and amiprophosmethyl) but not all (e.g. colchicine, podophyllotoxin, vinblastine, and pronamide). Roots of the R biotype, when treated with either dinitroaniline herbicides or amiprophosmethyl, exhibited no or only small increases in the mitotic index nor were the spindle and cortical microtubules affected. Compounds of class II (carbamate herbicides and griseofulvin) cause misorientation of microtubules which results in multinucleated cells. Compounds of class III (caffeine and structually related alkaloids) cause imcomplete cell walls to form at telophase. Each of these last two classes of compounds affected the R biotype more than the S biotype (supersensitivity). The cross-resistance and high levels of resistance of the R biotype of Eleusine to the dinitroaniline herbicides and the structurally distinct herbicide, amiprophosmethyl, indicate that a mechanism of resistance based upon metabolic modification, translocation, or compartmentation of the herbicides is probably not operative. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 Fig. 6 PMID:16665371

A Dinitroaniline-Resistant Mutant of Eleusine indica Exhibits Cross-Resistance and Supersensitivity to Antimicrotubule Herbicides and Drugs.

PubMed

Vaughn, K C; Marks, M D; Weeks, D P

1987-04-01

A dinitroaniline-resistant (R) biotype of Eleusine indica (L.) Gaertner. (goosegrass) is demonstrated to be cross-resistant to a structurally non-related herbicide, amiprophosmethyl, and supersensitive to two other classes of compounds which disrupt mitosis. These characteristics of the R biotype were discovered in a comparative test of the effects of 24 different antimitotic compounds on the R biotype and susceptible (S) wild-type Eleusine. The compounds tested could be classified into three groups based upon their effects on mitosis in root tips of the susceptible (S) biotype. Class I compounds induced effects like the well known mitotic disrupter colchicine: absence of cortical and spindle microtubules, mitosis arrested at prometaphase, and the formation of polymorphic nuclei after arrested mitosis. The R biotype was resistant to treatment with some class I inhibitors (all dinitroaniline herbicides and amiprophosmethyl) but not all (e.g. colchicine, podophyllotoxin, vinblastine, and pronamide). Roots of the R biotype, when treated with either dinitroaniline herbicides or amiprophosmethyl, exhibited no or only small increases in the mitotic index nor were the spindle and cortical microtubules affected. Compounds of class II (carbamate herbicides and griseofulvin) cause misorientation of microtubules which results in multinucleated cells. Compounds of class III (caffeine and structually related alkaloids) cause imcomplete cell walls to form at telophase. Each of these last two classes of compounds affected the R biotype more than the S biotype (supersensitivity). The cross-resistance and high levels of resistance of the R biotype of Eleusine to the dinitroaniline herbicides and the structurally distinct herbicide, amiprophosmethyl, indicate that a mechanism of resistance based upon metabolic modification, translocation, or compartmentation of the herbicides is probably not operative.

Structure activity relationship of C-2 ether substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-5).

PubMed

Singh, Sheo B; Kaelin, David E; Meinke, Peter T; Wu, Jin; Miesel, Lynn; Tan, Christopher M; Olsen, David B; Lagrutta, Armando; Fukuda, Hideyuki; Kishii, Ryuta; Takei, Masaya; Takeuchi, Tomoko; Takano, Hisashi; Ohata, Kohei; Kurasaki, Haruaki; Nishimura, Akinori; Shibata, Takeshi; Fukuda, Yasumichi

2015-09-01

Oxabicyclooctane linked novel bacterial topoisomerase inhibitors (NBTIs) are new class of recently reported broad-spectrum antibacterial agents. They target bacterial DNA gyrase and topoisomerase IV and bind to a site different than quinolones. They show no cross-resistance to known antibiotics and provide opportunity to combat drug-resistant bacteria. A structure activity relationship of the C-2 substituted ether analogs of 1,5-naphthyridine oxabicyclooctane-linked NBTIs are described. Synthesis and antibacterial activities of a total of 63 analogs have been summarized representing alkyl, cyclo alkyl, fluoro alkyl, hydroxy alkyl, amino alkyl, and carboxyl alkyl ethers. All compounds were tested against three key strains each of Gram-positive and Gram-negative bacteria as well as for hERG binding activities. Many key compounds were also tested for the functional hERG activity. Six compounds were evaluated for efficacy in a murine bacteremia model of Staphylococcus aureus infection. Significant tolerance for the ether substitution (including polar groups such as amino and carboxyl) at C-2 was observed for S. aureus activity however the same was not true for Enterococcus faecium and Gram-negative strains. Reduced clogD generally showed reduced hERG activity and improved in vivo efficacy but was generally associated with decreased overall potency. One of the best compounds was hydroxy propyl ether (16), which mainly retained the potency, spectrum and in vivo efficacy of AM8085 associated with the decreased hERG activity and improved physical property. Copyright © 2015 Elsevier Ltd. All rights reserved.

Triphasic blood pressure responses to cannabinoids: do we understand the mechanism?

PubMed Central

Malinowska, Barbara; Baranowska-Kuczko, Marta; Schlicker, Eberhard

2012-01-01

The cannabinoids comprise three major classes of substances, including compounds derived from the cannabis plant (e.g. Δ9-tetrahydrocannabinol and the chemically related substances CP55940 and HU210), endogenously formed (e.g. anandamide) and synthetic compounds (e.g. WIN55212-2). Beyond their psychotropic effects, cannabinoids have complex effects on blood pressure, including biphasic changes of Δ9-tetrahydrocannabinol and WIN55212-2 and an even triphasic effect of anandamide. The differing pattern of blood pressure changes displayed by the three types of compounds is not really surprising since, although they share an agonistic effect at cannabinoid CB1 and CB2 receptors, some compounds have additional effects. In particular, anandamide is known for its pleiotropic effects, and there is overwhelming evidence that anandamide influences blood pressure via (i) CB1 receptors, (ii) TRPV1 receptors, (iii) endothelial cannabinoid receptors and (iv) degradation products. This review is dedicated to the description of the effects of externally added cannabinoids on cardiovascular parameters in vivo. First, the cardiovascular effects of cannabinoids in anaesthetized animals will be highlighted since most data have been generated in experiments of that type. The text will follow the three phases of anandamide on blood pressure, and we will check to which extent cardiovascular changes elicited by other cannabinoids show overlap with those effects or differ. The second part will be dedicated to the cardiovascular effects of the cannabinoids in conscious animals. In the third part, cardiovascular effects in humans will be discussed, and similarities and differences with respect to the data from animals will be examined. PMID:22022923

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Sloan, M A; Alexandrov, A V; Tegeler, C H; Spencer, M P; Caplan, L R; Feldmann, E; Wechsler, L R; Newell, D W; Gomez, C R; Babikian, V L; Lefkowitz, D; Goldman, R S; Armon, C; Hsu, C Y; Goodin, D S

2004-05-11

To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia

PubMed Central

Huang, David T.; Weissfeld, Lisa A.; Kellum, John A.; Yealy, Donald M.; Kong, Lan; Martino, Michael; Angus, Derek C.

2009-01-01

Objective The Pneumonia Severity Index (PSI) and CURB-65 predict outcomes in community acquired pneumonia (CAP), but have limitations. Procalcitonin, a biomarker of bacterial infection, may provide prognostic information in CAP. Our objective was to describe the pattern of procalcitonin in CAP, and determine if procalcitonin provides prognostic information beyond PSI and CURB-65. Methods We conducted a multi-center prospective cohort study in 28 community and teaching emergency departments. Patients presenting with a clinical and radiographic diagnosis of CAP were enrolled. We stratified procalcitonin levels a priori into four tiers – I: < 0.1; II: ≥ 0.1 to <0.25; III: ≥ 0.25 to < 0.5; and IV: ≥ 0.5 ng/ml. Primary outcome was 30d mortality. Results 1651 patients formed the study cohort. Procalcitonin levels were broadly spread across tiers: 32.8% (I), 21.6% (II), 10.2% (III), 35.4% (IV). Used alone, procalcitonin had modest test characteristics: specificity (35%), sensitivity (92%), positive likelihood ratio (LR) (1.41), and negative LR (0.22). Adding procalcitonin to PSI in all subjects minimally improved performance. Adding procalcitonin to low risk PSI subjects (Class I–III) provided no additional information. However, subjects in procalcitonin tier I had low 30d mortality regardless of clinical risk, including those in higher risk classes (1.5% vs. 1.6% for those in PSI Class I–III vs. Class IV/V). Among high risk PSI subjects (Class IV/V), one quarter (126/546) were in procalcitonin tier I, and the negative LR of procalcitonin tier I was 0.09. Procalcitonin tier I was also associated with lower burden of other adverse outcomes. Similar results were seen with CURB-65 stratification. Conclusions Selective use of procalcitonin as an adjunct to existing rules may offer additional prognostic information in high risk patients. PMID:18342993

Bis(N-ethyl-N-methyl-dithio-carbamato-κS,S')diphenyl-tin(IV).

PubMed

Muthalib, Amirah Faizah; Baba, Ibrahim; Ng, Seik Weng

2010-03-03

The dithio-carbamate anions in the title compound, [Sn(C(6)H(5))(2)(C(4)H(8)NS(2))(2)], chelate to the Sn(IV) atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol-ecule lies across a twofold rotation axis.

Bis(N-isopropyl-N-methyl-dithio-carbamato-κS,S')diphenyl-tin(IV).

PubMed

Muthalib, Amirah Faizah; Baba, Ibrahim; Farina, Yang; Ng, Seik Weng

2010-03-03

The dithio-carbamate anions in the title compound, [Sn(C(6)H(5))(2)(C(5)H(10)NS(2))(2)], chelate to the Sn(IV) atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol-ecule lies across a twofold rotation axis.

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction).

PubMed

Pizarro, Gonzalo; Fernández-Friera, Leticia; Fuster, Valentin; Fernández-Jiménez, Rodrigo; García-Ruiz, José M; García-Álvarez, Ana; Mateos, Alonso; Barreiro, María V; Escalera, Noemí; Rodriguez, Maite D; de Miguel, Antonio; García-Lunar, Inés; Parra-Fuertes, Juan J; Sánchez-González, Javier; Pardillos, Luis; Nieto, Beatriz; Jiménez, Adriana; Abejón, Raquel; Bastante, Teresa; Martínez de Vega, Vicente; Cabrera, José A; López-Melgar, Beatriz; Guzman, Gabriela; García-Prieto, Jaime; Mirelis, Jesús G; Zamorano, José Luis; Albarrán, Agustín; Goicolea, Javier; Escaned, Javier; Pocock, Stuart; Iñiguez, Andrés; Fernández-Ortiz, Antonio; Sánchez-Brunete, Vicente; Macaya, Carlos; Ibanez, Borja

2014-06-10

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Reactivity and O2 Formation by Mn(IV)- and Mn(V)-Hydroxo Species Stabilized within a Polyfluoroxometalate Framework.

PubMed

Schreiber, Roy E; Cohen, Hagai; Leitus, Gregory; Wolf, Sharon G; Zhou, Ang; Que, Lawrence; Neumann, Ronny

2015-07-15

Manganese(IV,V)-hydroxo and oxo complexes are often implicated in both catalytic oxygenation and water oxidation reactions. Much of the research in this area is designed to structurally and/or functionally mimic enzymes. On the other hand, the tendency of such mimics to decompose under strong oxidizing conditions makes the use of molecular inorganic oxide clusters an enticing alternative for practical applications. In this context it is important to understand the reactivity of conceivable reactive intermediates in such an oxide-based chemical environment. Herein, a polyfluoroxometalate (PFOM) monosubstituted with manganese, [NaH2(Mn-L)W17F6O55](q-), has allowed the isolation of a series of compounds, Mn(II, III, IV and V), within the PFOM framework. Magnetic susceptibility measurements show that all the compounds are high spin. XPS and XANES measurements confirmed the assigned oxidation states. EXAFS measurements indicate that Mn(II)PFOM and Mn(III)PFOM have terminal aqua ligands and Mn(V)PFOM has a terminal hydroxo ligand. The data are more ambiguous for Mn(IV)PFOM where both terminal aqua and hydroxo ligands can be rationalized, but the reactivity observed more likely supports a formulation of Mn(IV)PFOM as having a terminal hydroxo ligand. Reactivity studies in water showed unexpectedly that both Mn(IV)-OH-PFOM and Mn(V)-OH-PFOM are very poor oxygen-atom donors; however, both are highly reactive in electron transfer oxidations such as the oxidation of 3-mercaptopropionic acid to the corresponding disulfide. The Mn(IV)-OH-PFOM compound reacted in water to form O2, while Mn(V)-OH-PFOM was surprisingly indefinitely stable. It was observed that addition of alkali cations (K(+), Rb(+), and Cs(+)) led to the aggregation of Mn(IV)-OH-PFOM as analyzed by electron microscopy and DOSY NMR, while addition of Li(+) and Na(+) did not lead to aggregates. Aggregation leads to a lowering of the entropic barrier of the reaction without changing the free energy barrier. The observation that O2 formation is fastest in the presence of Cs(+) and ∼fourth order in Mn(IV)-OH-PFOM supports a notion of a tetramolecular Mn(IV)-hydroxo intermediate that is viable for O2 formation in an oxide-based chemical environment. A bimolecular reaction mechanism involving a Mn(IV)-hydroxo based intermediate appears to be slower for O2 formation.

Solid-to-solid oxidation of a vanadium(IV) to a vanadium(V) compound: chemisty of a sulfur-containing siderophore.

PubMed

Chatterjee, Pabitra B; Crans, Debbie C

2012-09-03

Visible light facilitates a solid-to-solid photochemical aerobic oxidation of a hunter-green microcrystalline oxidovanadium(IV) compound (1) to form a black powder of cis-dioxidovanadium(V) (2) at ambient temperature. The siderophore ligand pyridine-2,6-bis(thiocarboxylic acid), H(2)L, is secreted by a microorganism from the Pseudomonas genus. This irreversible transformation of a metal monooxo to a metal dioxo complex in the solid state in the absence of solvent is unprecedented. It serves as a proof-of-concept reaction for green chemistry occurring in solid matrixes.

Synthesis and Biological Evaluation of Ginsenoside Compound K Derivatives as a Novel Class of LXRα Activator.

PubMed

Huang, Yan; Liu, Hongmei; Zhang, Yingxian; Li, Jin; Wang, Chenping; Zhou, Li; Jia, Yi; Li, Xiaohui

2017-07-24

Compound K is one of the active metabolites of Panaxnotoginseng saponins, which could attenuate the formation of atherosclerosis in mice modelsvia activating LXRα. We synthesized and evaluated a series of ginsenoside compound K derivatives modified with short chain fatty acids. All of the structures of this class of ginsenoside compound K derivative exhibited comparable or better biological activity than ginsenoside compound K. Especially structure 1 exhibited the best potency (cholesteryl ester content: 41.51%; expression of ABCA1 mRNA: 319%) and low cytotoxicity.

Investigating the Capability of IRS-P6-LISS IV Satellite Image for Pistachio Forests Density Mapping (case Study: Northeast of Iran)

NASA Astrophysics Data System (ADS)

Hoseini, F.; Darvishsefat, A. A.; Zargham, N.

2012-07-01

In order to investigate the capability of satellite images for Pistachio forests density mapping, IRS-P6-LISS IV data were analyzed in an area of 500 ha in Iran. After geometric correction, suitable training areas were determined based on fieldwork. Suitable spectral transformations like NDVI, PVI and PCA were performed. A ground truth map included of 34 plots (each plot 1 ha) were prepared. Hard and soft supervised classifications were performed with 5 density classes (0-5%, 5-10%, 10-15%, 15-20% and > 20%). Because of low separability of classes, some classes were merged and classifications were repeated with 3 classes. Finally, the highest overall accuracy and kappa coefficient of 70% and 0.44, respectively, were obtained with three classes (0-5%, 5-20%, and > 20%) by fuzzy classifier. Considering the low kappa value obtained, it could be concluded that the result of the classification was not desirable. Therefore, this approach is not appropriate for operational mapping of these valuable Pistachio forests.

State laser regulations: Arizona's approach and experience

NASA Astrophysics Data System (ADS)

Barat, Kenneth L.

1992-06-01

Approximately a dozen states have regulatory or statutory authority in the area of nonionizing radiation. With only half that number having established laser regulations. Examples are Texas, Florida, Arizona, Mass. many more are considering establishing such rules, such as N.J., Il., Neb. On the federal level, the Food and Drug Administration has been the most active entity. OSHA has just recently established laser safety guidelines for its inspection staff. In March of 1990 the State of Arizona enacted rules for the control of Nonionizing radiation. This fell under Article 14 of Tittle 12 of the Arizona Administrative Code, which is under the authority of the Arizona Radiation Regulatory Agency. The rules cover a wide range of nonionizing sources, but the major emphasis is in the area of laser devices. While all class lasers fall under Article 14, only Class IIIb and Class IV laser use facilities are required to be registered and inspected by the agency. The rules apply to all Class IIIb and Class IV laser users, meaning medical, industrial, entertainment, and also research facilities.

75 FR 27785 - Final Effect of Designation of a Class of Employees for Addition to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Final Effect of Designation of a Class of Employees for Addition to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health... concerning the final effect of the decision to designate a class of employees from Area IV of the Santa...

Determination of total antioxidant capacity by a new spectrofluorometric method based on Ce(IV) reduction: Ce(III) fluorescence probe for CERAC assay.

PubMed

Ozyurt, Dilek; Demirata, Birsen; Apak, Resat

2011-11-01

A Ce(IV)-based reducing capacity (CERAC) assay was developed to measure the total antioxidant capacity (TAC) of foods, in which Ce(IV) would selectively oxidize antioxidant compounds but not citric acid and reducing sugars which are not classified as antioxidants. The method is based on the electron-transfer (ET) reaction between Ce(IV) ion and antioxidants in optimized acidic sulphate medium (i.e., 0.3 M H(2)SO(4) and 0.7 M Na(2)SO(4)) and subsequent determination of the produced Ce(III) ions by a fluorometric method. The fluorescent product, Ce(III), exhibited strong fluorescence at 360 nm with an excitation wavelength of 256 nm, the fluorescence intensity being correlated to antioxidant power of the original sample. The linear concentration range for most antioxidants was quite wide, e.g., 5.0 × 10(-7)-1.0 × 10(-5) M for quercetin. The developed procedure was successfully applied to the TAC assay of antioxidant compounds such as trolox, quercetin, gallic acid, ascorbic acid, catechin, naringin, naringenin, caffeic acid, ferulic acid, glutathione, and cysteine. The proposed method was reproducible, additive in terms of TAC values of constituents of complex mixtures, and the trolox equivalent antioxidant capacities (TEAC coefficients) of the tested antioxidant compounds gave good correlations with those found by reference methods such as ABTS and CUPRAC.

Impact of Sterile Compounding Batch Frequency on Pharmaceutical Waste.

PubMed

Abbasi, Ghalib; Gay, Evan

2017-01-01

Purpose: To measure the impact of increasing sterile compounding batch frequency on pharmaceutical waste as it relates to cost and quantity. Methods: Pharmaceutical IV waste at a tertiary care hospital was observed and recorded for 7 days. The batching frequency of compounded sterile products (CSPs) was then increased from twice daily to 4 times daily. After a washout period, pharmaceutical IV waste was then recorded for another 7 days. The quantity of units wasted and the cost were compared between both phases to determine the impact that batching frequency has on IV waste, specifically among high- and low-cost drugs. Results: Patient days increased from 2,459 during phase 1 to 2,617 during phase 2. The total number of CSPs wasted decreased from 3.6 to 2.7 doses per 100 patient days. Overall cost was reduced from $4,585.36 in phase 1 to $4,453.88 in phase 2. The value of wasted high-cost drugs per 100 patient days increased from $146 in phase 1 to $149 in phase 2 ( p > .05). The value of wasted low cost drugs per 100 patient days decreased from $41 in phase 1 to $21 in phase 2 ( p < .05). Conclusion: Lean batch IV methodology reduced overall waste quantity and cost. The highest impact of the intervention was observed among low-cost CSPs.

[Evaluation of a chronic fatigue in patients with moderate-to-severe chronic heart failure].

PubMed

Jasiukeviciene, Lina; Vasiliauskas, Donatas; Kavoliūniene, Ausra; Marcinkeviciene, Jolanta; Grybauskiene, Regina; Grizas, Vytautas; Tumyniene, Vida

2008-01-01

To evaluate the chronic fatigue and its relation to the function of hypothalamus-pituitary-adrenal axis in patients with New York Heart Association (NYHA) functional class III-IV chronic heart failure. A total of 170 patients with NYHA functional class III-IV chronic heart failure completed MFI-20L, DUFS, and DEFS questionnaires assessing chronic fatigue and underwent echocardiography. Blood cortisol concentration was assessed at 8:00 am and 3:00 pm, and plasma N-terminal brain natriuretic pro-peptide (NT-proBNP) concentration was measured at 8:00 am. Neurohumoral investigations were repeated before cardiopulmonary exercise test and after it. The results of all questionnaires showed that 100% of patients with NYHA functional class III-IV heart failure complained of chronic fatigue. The level of overall fatigue was 54.5+/-31.5 points; physical fatigue - 56.8+/-24.6 points. Blood cortisol concentration at 8:00 am was normal (410.1+/-175.1 mmol/L) in majority of patients. Decreased concentration was only in four patients (122.4+/-15.5 mmol/L); one of these patients underwent heart transplantation. In the afternoon, blood cortisol concentration was insufficiently decreased (355.6+/-160.3 mmol/L); reaction to a physical stress was attenuated (Delta 92.9 mmol/L). Plasma NT-proBNP concentration was 2188.9+/-1852.2 pg/L; reaction to a physical stress was diminished (Delta 490.3 pg/L). All patients with NYHA class III-IV heart failure complained of daily chronic fatigue. Insufficiently decreased blood cortisol concentration in the afternoon showed that in the presence of chronic fatigue in long-term cardiovascular organic disease, disorder of a hypothalamus-pituitary-adrenal axis is involved.

Multi-class Mode of Action Classification of Toxic Compounds Using Logic Based Kernel Methods.

PubMed

Lodhi, Huma; Muggleton, Stephen; Sternberg, Mike J E

2010-09-17

Toxicity prediction is essential for drug design and development of effective therapeutics. In this paper we present an in silico strategy, to identify the mode of action of toxic compounds, that is based on the use of a novel logic based kernel method. The technique uses support vector machines in conjunction with the kernels constructed from first order rules induced by an Inductive Logic Programming system. It constructs multi-class models by using a divide and conquer reduction strategy that splits multi-classes into binary groups and solves each individual problem recursively hence generating an underlying decision list structure. In order to evaluate the effectiveness of the approach for chemoinformatics problems like predictive toxicology, we apply it to toxicity classification in aquatic systems. The method is used to identify and classify 442 compounds with respect to the mode of action. The experimental results show that the technique successfully classifies toxic compounds and can be useful in assessing environmental risks. Experimental comparison of the performance of the proposed multi-class scheme with the standard multi-class Inductive Logic Programming algorithm and multi-class Support Vector Machine yields statistically significant results and demonstrates the potential power and benefits of the approach in identifying compounds of various toxic mechanisms. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Contextual control using a go/no-go procedure with compound abstract stimuli.

PubMed

Modenesi, Rafael Diego; Debert, Paula

2015-05-01

Contextual control has been described as (1) a five-term contingency, in which the contextual stimulus exerts conditional control over conditional discriminations, and (2) allowing one stimulus to be a member of different equivalence classes without merging them into one. Matching-to-sample is the most commonly employed procedure to produce and study contextual control. The present study evaluated whether the go/no-go procedure with compound stimuli produces equivalence classes that share stimuli. This procedure does not allow the identification of specific stimulus functions (e.g., contextual, conditional, or discriminative functions). If equivalence classes were established with this procedure, then only the latter part of the contextual control definition (2) would be met. Six undergraduate students participated in the present study. In the training phases, responses to AC, BD, and XY compounds with stimuli from the same classes were reinforced, and responses to AC, BD, and XY compounds with stimuli from different classes were not. In addition, responses to X1A1B1, X1A2B2, X2A1B2, and X2A2B1 compounds were reinforced and responses to the other combinations were not. During the tests, the participants had to respond to new combinations of stimuli compounds YCD to indicate the formation of four equivalence classes that share stimuli: X1A1B1Y1C1D1, X1A2B2Y1C2D2, X2A1B2Y2C1D2, and X2A2B1Y2C2D1. Four of the six participants showed the establishment of these classes. These results indicate that establishing contextual stimulus functions is unnecessary to produce equivalence classes that share stimuli. Therefore, these results are inconsistent with the first part of the definition of contextual control. © Society for the Experimental Analysis of Behavior.

Antimicrobial peptide inhibition of fungalysin proteases that target plant type 19 Family IV defense chitinases

USDA-ARS?s Scientific Manuscript database

Cereal crops and other plants produce secreted seed chitinases that reduce pathogenic infection, most likely by targeting the fungal chitinous cell wall. We have shown that corn (Zea mays) produces three GH family 19, plant class IV chitinases, that help in protecting the plant against Fusarium and ...

PTP1B, α-glucosidase, and DPP-IV inhibitory effects for chromene derivatives from the leaves of Smilax china L.

PubMed

Zhao, Bing Tian; Le, Duc Dat; Nguyen, Phi Hung; Ali, Md Yousof; Choi, Jae-Sue; Min, Byung Sun; Shin, Heung Mook; Rhee, Hae Ik; Woo, Mi Hee

2016-06-25

Two new flavonoids, bismilachinone (11) and smilachinin (14), were isolated from the leaves of Smilax china L. together with 14 known compounds. Their structures were elucidated using spectroscopic methods. The PTP1B, α-glucosidase, and DPP-IV inhibitory activities of compounds 1-16 were evaluated at the molecular level. Among them, compounds 4, 7, and 10 showed moderate DPP-IV inhibitory activities with IC50 values of 20.81, 33.12, and 32.93 μM, respectively. Compounds 3, 4, 6, 11, 12, and 16 showed strong PTP1B inhibitory activities, with respective IC50 values of 7.62, 10.80, 0.92, 2.68, 9.77, and 24.17 μM compared with the IC50 value for the positive control (ursolic acid: IC50 = 1.21 μM). Compounds 2-7, 11, 12, 15, and 16 showed potent α-glucosidase inhibitory activities, with respective IC50 values of 8.70, 81.66, 35.11, 35.92, 7.99, 26.28, 11.28, 62.68, 44.32, and 70.12 μM. The positive control, acarbose, displayed an IC50 value of 175.84 μM. In the kinetic study for the PTP1B enzyme, compounds 6, 11, and 12 displayed competitive inhibition with Ki values of 3.20, 8.56, and 5.86 μM, respectively. Compounds 3, 4, and 16 showed noncompetitive inhibition with Ki values of 18.75, 5.95, and 22.86 μM, respectively. Molecular docking study for the competitive inhibitors (6, 11, and 12) radically corroborates the binding affinities and inhibition of PTP1B enzymes. These results indicated that the leaves of Smilax china L. may contain compounds with anti-diabetic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

chs-4, a class IV chitin synthase gene from Neurospora crassa.

PubMed

Din, A B; Specht, C A; Robbins, P W; Yarden, O

1996-02-05

In Saccharomyces cerevisiae, most of the cellular chitin is produced by chitin synthase III, which requires the product encoded by the CSD2/CAL1/DIT101/KT12 gene. We have identified, isolated and structurally characterized as CSD2/CAL1/DIT101/KT12 homologue in the filamentous ascomycete Neurospora crassa and have used a "reverse genetics" approach to determine its role in vivo. The yeast gene was used as a heterologous probe for the isolation of a N. crassa gene(designated chs-4) encoding a polypeptide belonging to a class of chitin synthases which we have designated class IV. The predicted polypeptide encoded by this gene is highly similar to those of S. cerevisiae and Candida albicans. N. crassa strains in which chs-4 had been inactivated by the Repeat-Induced point mutation (RIP) process grew and developed in a normal manner under standard growth conditions. However, when grown in the presence of sorbose (a carbon source which induces morphological changes accompanied by elevated chitin content), chitin levels in the chs-4RIP strain were significantly lower than those observed in the wild type. We suggest that CHS4 may serve as an auxiliary enzyme in N. crassa and that, in contrast to yeasts, it is possible that filamentous fungi may have more than one class IV chitin synthase.

Identification of branched-chain amino acid aminotransferases active towards (R)-(+)-1-phenylethylamine among PLP fold type IV transaminases.

PubMed

Bezsudnova, Ekaterina Yu; Dibrova, Daria V; Nikolaeva, Alena Yu; Rakitina, Tatiana V; Popov, Vladimir O

2018-04-10

New class IV transaminases with activity towards L-Leu, which is typical of branched-chain amino acid aminotransferases (BCAT), and with activity towards (R)-(+)-1-phenylethylamine ((R)-PEA), which is typical of (R)-selective (R)-amine:pyruvate transaminases, were identified by bioinformatics analysis, obtained in recombinant form, and analyzed. The values of catalytic activities in the reaction with L-Leu and (R)-PEA are comparable to those measured for characteristic transaminases with the corresponding specificity. Earlier, (R)-selective class IV transaminases were found to be active, apart from (R)-PEA, only with some other (R)-primary amines and D-amino acids. Sequences encoding new transaminases with mixed type of activity were found by searching for changes in the conserved motifs of sequences of BCAT by different bioinformatics tools. Copyright © 2018 Elsevier B.V. All rights reserved.

Redox shuttles for high voltage cathodes

DOEpatents

Zhang, Lu; Zhang, Zhengcheng; Amine, Khalil; Chen, Zonghai

2015-03-03

A compound has general Formula I, II, III, or IV: ##STR00001## where X and Y are independently a group of Formula (A): ##STR00002## and Z a group of Formula (B): ##STR00003## The compounds may be used in electrolytes and electrochemical devices.

Development of "one-pot" method for multi-class compounds in porcine formula feed by multi-function impurity adsorption cleaning followed ultra-performance liquid chromatography-tandem mass spectrometry detection.

PubMed

Wang, Peilong; Wang, Xiao; Zhang, Wei; Su, Xiaoou

2014-02-01

A novel and efficient determination method for multi-class compounds including β-agonists, sedatives, nitro-imidazoles and aflatoxins in porcine formula feed based on a fast "one-pot" extraction/multifunction impurity adsorption (MFIA) clean-up procedure has been developed. 23 target analytes belonging to four different class compounds could be determined simultaneously in a single run. Conditions for "one-pot" extraction were studied in detail. Under the optimized conditions, the multi-class compounds in porcine formula feed samples were extracted and purified with methanol contained ammonia and absorbents by one step. The compounds in extracts were purified by using multi types of absorbent based on MFIA in one pot. The multi-walled carbon nanotubes were employed to improved clean-up efficiency. Shield BEH C18 column was used to separate 23 target analytes, followed by tandem mass spectrometry (MS/MS) detection using an electro-spray ionization source in positive mode. Recovery studies were done at three fortification levels. Overall average recoveries of target compounds in porcine formula feed at each levels were >51.6% based on matrix fortified calibration with coefficients of variation from 2.7% to 13.2% (n=6). The limit of determination (LOD) of these compounds in porcine formula feed sample matrix was <5.0 μg/kg. This method was successfully applied in screening and confirmation of target drugs in >30 porcine formula feed samples. It was demonstrated that the integration of the MFIA protocol with the MS/MS instrument could serve as a valuable strategy for rapid screening and reliable confirmatory analysis of multi-class compounds in real samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Relative Incidence of Acute Adverse Events with Ferumoxytol Compared to Other Intravenous Iron Compounds: A Matched Cohort Study.

PubMed

Wetmore, James B; Weinhandl, Eric D; Zhou, Jincheng; Gilbertson, David T

2017-01-01

Concerns persist about adverse reactions to intravenous (IV) iron. We aimed to determine the relative safety of ferumoxytol compared to other IV iron compounds. This retrospective cohort study with propensity-score matching for patients and drug doses used the Medicare 20% random sample to identify patients (1) without chronic kidney disease (non-CKD) and (2) with non-dialysis-dependent chronic kidney disease (NDD-CKD) who received a first dose of IV iron in 2010-2012. Exposures were ferumoxytol, iron sucrose, sodium ferric gluconate, or iron dextran. Outcomes were hypersensitivity symptoms, anaphylaxis, emergency department (ED) encounters, hospitalizations, and death after acute IV iron exposure. In the primary analysis for reactions on the day of or following exposure, there was no difference in hypersensitivity symptoms (hazard ratio 1.04, 95% confidence interval 0.94-1.16) or hypotension (0.83, 0.52-1.34) between 4289 non-CKD ferumoxytol users and an equal number of users of other compounds; results were similar for 7358 NDD-CKD patients and an equal number of controls. All-cause ED encounters or hospitalizations were less common in both the non-CKD (0.56, 0.45-0.70) and NDD-CKD ferumoxytol-treated patients (0.83, 0.71-0.95). Fewer than 10 deaths occurred in both the non-CKD and NDD-CKD ferumoxytol users and in matched controls; the hazard for death did not differ significantly between ferumoxytol users and controls in the non-CKD patients (2.00, 0.33-11.97) or in the NDD-CKD patients (0.25, 0.04-1.52). Multiple sensitivity analyses showed similar results. Ferumoxytol did not appear to be associated with more adverse reactions than other compounds for the treatment of iron-deficiency anemia in both non-CKD and NDD-CKD patients.

Discovery of Potent and Selective Dipeptidyl Peptidase IV Inhibitors Derived from [beta]-Aminoamides Bearing Subsituted Triazolopiperazines

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

Kim, Dooseop; Kowalchick, Jennifer E.; Brockunier, Linda L.

2008-06-30

A series of {beta}-aminoamides bearing triazolopiperazines have been discovered as potent, selective, and orally active dipeptidyl peptidase IV (DPP-4) inhibitors by extensive structure-activity relationship (SAR) studies around the triazolopiperazine moiety. Among these, compound 34b with excellent in vitro potency (IC{sub 50} = 4.3 nM) against DPP-4, high selectivity over other enzymes, and good pharmacokinetic profiles exhibited pronounced in vivo efficacy in an oral glucose tolerance test (OGTT) in lean mice. On the basis of these properties, compound 34b has been profiled in detail. Further refinement of the triazolopiperazines resulted in the discovery of a series of extremely potent compounds withmore » subnanomolar activity against DPP-4 (42b-49b), that is, 4-fluorobenzyl-substituted compound 46b, which is notable for its superior potency (IC{sub 50} = 0.18 nM). X-ray crystal structure determination of compounds 34b and 46b in complex with DPP-4 enzyme revealed that (R)-stereochemistry at the 8-position of triazolopiperazines is strongly preferred over (S) with respect to DPP-4 inhibition.« less

Outcome of bipolar electrocoagulation with lesionectomy in the treatment of epilepsy involving eloquent areas.

PubMed

Zhai, Feng; Zhou, Jian; Li, Tianfu; Cui, Zhiqiang; Luan, Guoming

2015-01-01

We have demonstrated previously that bipolar electrocoagulation on functional cortex (BCFC) is a safe and effective approach for epilepsy involving eloquent areas. Here, we report the results of BCFC with lesionectomy for patients with epileptogenic foci partially overlapping eloquent areas. Forty patients who had been treated with lesionectomy with BCFC were retrospectively reviewed with regard to seizure outcome and neurological deficits. Ten similar patients who had received lesionectomy with multiple subpial transections (MST) were examined as a control group. In the lesionectomy group with BCFC, Engel class I was achieved in 18 (45%) patients, class II in 8 (20%) patients, class III in 8 (20%) patients and class IV in 6 (15%) patients. Five (12.5%) patients developed mild hemiparesis and 1 (2.5%) patient mild sensory dysphasia. In the lesionectomy group with MST, Engel class I was achieved in 3 (30%) patients, class II in 2 (20%) patients, class III in 3 (30%) patients and class IV in 2 (20%) patients. Two (20%) patients developed mild hemiparesis and 1 (10%) patient moderate hemiparesis. All these complications recovered within 1-12 months. Compared with MST, the outcome of BCFC with lesionectomy is similar. But since MST leads to mechanical injury, while BCFC causes thermal injury, the complications of BCFC seem less severe. © 2014 S. Karger AG, Basel.

Heterogonous expression and characterization of a plant class IV chitinase from the pitcher of the carnivorous plant Nepenthes alata.

PubMed

Ishisaki, Kana; Honda, Yuji; Taniguchi, Hajime; Hatano, Naoya; Hamada, Tatsuro

2012-03-01

A class IV chitinase belonging to the glycoside hydrolase 19 family from Nepenthes alata (NaCHIT1) was expressed in Escherichia coli. The enzyme exhibited weak activity toward polymeric substrates and significant activity toward (GlcNAc)(n) [β-1,4-linked oligosaccharide of GlcNAc with a polymerization degree of n (n = 4-6)]. The enzyme hydrolyzed the third and fourth glycosidic linkages from the non-reducing end of (GlcNAc)(6). The pH optimum of the enzymatic reaction was 5.5 at 37°C. The optimal temperature for activity was 60°C in 50 mM sodium acetate buffer (pH 5.5). The anomeric form of the products indicated that it was an inverting enzyme. The k(cat)/K(m) of the (GlcNAc)(n) hydrolysis increased with an increase in the degree of polymerization. Amino acid sequence alignment analysis between NaCHIT1 and a class IV chitinase from a Picea abies (Norway spruce) suggested that the deletion of four loops likely led the enzyme to optimize the (GlcNAc)(n) hydrolytic reaction rather than the hydrolysis of polymeric substrates.

Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals

PubMed Central

Bhogal, Balpreet; Plaza-Jennings, Amara

2016-01-01

Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. PMID:27256879

Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals.

PubMed

Bhogal, Balpreet; Plaza-Jennings, Amara; Gavis, Elizabeth R

2016-06-15

Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. © 2016. Published by The Company of Biologists Ltd.

Characterization of toluene and ethylbenzene biodegradation under nitrate-, iron(III)- and manganese(IV)-reducing conditions by compound-specific isotope analysis.

PubMed

Dorer, Conrad; Vogt, Carsten; Neu, Thomas R; Stryhanyuk, Hryhoriy; Richnow, Hans-Hermann

2016-04-01

Ethylbenzene and toluene degradation under nitrate-, Mn(IV)-, or Fe(III)-reducing conditions was investigated by compound specific stable isotope analysis (CSIA) using three model cultures (Aromatoleum aromaticum EbN1, Georgfuchsia toluolica G5G6, and a Azoarcus-dominated mixed culture). Systematically lower isotope enrichment factors for carbon and hydrogen were observed for particulate Mn(IV). The increasing diffusion distances of toluene or ethylbenzene to the solid Mn(IV) most likely caused limited bioavailability and hence resulted in the observed masking effect. The data suggests further ethylbenzene hydroxylation by ethylbenzene dehydrogenase (EBDH) and toluene activation by benzylsuccinate synthase (BSS) as initial activation steps. Notably, significantly different values in dual isotope analysis were detected for toluene degradation by G. toluolica under the three studied redox conditions, suggesting variations in the enzymatic transition state depending on the available TEA. The results indicate that two-dimensional CSIA has significant potential to assess anaerobic biodegradation of ethylbenzene and toluene at contaminated sites. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides.

PubMed

Bercu, J P; Galloway, S M; Parris, P; Teasdale, A; Masuda-Herrera, M; Dobo, K; Heard, P; Kenyon, M; Nicolette, J; Vock, E; Ku, W; Harvey, J; White, A; Glowienke, S; Martin, E A; Custer, L; Jolly, R A; Thybaud, V

2018-04-01

This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common by-products that are potential impurities in drug substances. In addition, a 15 μg/day class-specific limit was developed for monofunctional alkyl bromides, aligning this with the class-specific limit previously defined for monofunctional alkyl chlorides. Both the compound- and class-specific toxicology limits assume a lifetime chronic exposure for the general population (including sensitive subpopulations) by all routes of exposure for pharmaceuticals. Inhalation-specific toxicology limits were also derived for acrolein, formaldehyde, and methyl bromide because of their localized toxicity via that route. Mode of action was an important consideration for a compound-specific toxicology limit. Acceptable intake (AI) calculations for certain mutagenic carcinogens assumed a linear dose-response for tumor induction, and permissible daily exposure (PDE) determination assumed a non-linear dose-response. Several compounds evaluated have been previously incorrectly assumed to be mutagenic, or to be mutagenic carcinogens, but the evidence reported here for such compounds indicates a lack of mutagenicity, and a non-mutagenic mode of action for tumor induction. For non-mutagens with insufficient data to develop a toxicology limit, the ICH Q3A qualification thresholds are recommended. The compound- and class-specific toxicology limits described here may be adjusted for an individual drug substance based on treatment duration, dosing schedule, severity of the disease and therapeutic indication. Copyright © 2018. Published by Elsevier Inc.

A Connectionist Model of Stimulus Class Formation with a Yes/No Procedure and Compound Stimuli

ERIC Educational Resources Information Center

Tovar, Angel E.; Chavez, Alvaro Torres

2012-01-01

We analyzed stimulus class formation in a human study and in a connectionist model (CM) with a yes/no procedure, using compound stimuli. In the human study, the participants were six female undergraduate students; the CM was a feed-forward back-propagation network. Two 3-member stimulus classes were trained with a similar procedure in both the…

Neutral six-coordinate bis(dithiocarbamato)silicon(iv) complexes with an SiCl2S4 skeleton.

PubMed

Baus, Johannes A; Tacke, Reinhold

2017-07-11

Treatment of SiCl 4 with lithium dithiocarbamates of the formula type Li[R 2 NCS 2 ] (R = Ph, iPr) in a molar ratio of 1 : 2 afforded the respective six-coordinate silicon(iv) complexes [Ph 2 NCS 2 ] 2 SiCl 2 (3) and [iPr 2 NCS 2 ] 2 SiCl 2 (4), which were isolated as the solvates 3·MeCN and 4·MeCN. Compounds 3·MeCN and 4·MeCN were structurally characterised by single-crystal X-ray diffraction and multinuclear NMR spectroscopic studies in the solid state and in solution. In this study, dithiocarbamato ligands were implemented in silicon coordination chemistry for the first time. Compounds 3 and 4 represent the first six-coordinate silicon(iv) complexes with an SiCl 2 S 4 skeleton.

A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects

PubMed Central

Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

2009-01-01

AIMS To evaluate the pharmacokinetics (PK) of five H1 receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). METHODS Five H1 receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. RESULTS The median clearance (CL), apparent volume of distribution (Vd) and apparent terminal elimination half-life (t1/2) of diphenhydramine after an i.v. microdose were 24.7 l h−1, 302 l and 9.3 h, and the oral Cmax and AUC0–∞ were 0.195 ng ml−1 and 1.52 ng h ml−1, respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. CONCLUSIONS Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection. PMID:19523012

A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.

PubMed

Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

2009-03-01

To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

Characterization and synthesis of volatile compounds from the defensive secretions of some "daddy longlets" (Arachnida: Opiliones: Leiobunum spp.).

PubMed

Jones, T H; Meinwald, J; Hicks, K; Eisner, T

1977-02-01

Analyses of the chief volatile constituents of the defensive secretions of three oplionids were carried out. Leiobunum nigripalpi produces three closely related C7 compounds: E-4-methyl-4-hexen-3-one(I), 4-methylhexan-3-one(II), and 4-methylhexan-3-ol(III), along with E-4-methyl-4-hepten-3-one(IV), E,E-2,4-dimethylhexa-2,4-dienal(IX), and a minor, unidentified component. L. leiopenis secretion contains E-4-methyl-4-hepten-3-one(IV), 4-methylheptan-3-one(V), E,E-2,4-dimethylhexa-2,4-dien-1-ol(VII), and E,E-2,4-dimethylhepta-2,4-dien-1-ol(VIII). L. calcar yields chiefly E-4,6-dimethyl-6-octen-3-one(VI) and E,E-2,4-dimethylhexa-2,4-dien-1-ol(VII). Six of these compounds are new natural products. The structures of these compounds, which can be regarded either as polyketide-derived or as modified isoprenoids, raise interesting biosynthetic questions.

Characterization and synthesis of volatile compounds from the defensive secretions of some "daddy longlets" (Arachnida: Opiliones: Leiobunum spp.).

PubMed Central

Jones, T H; Meinwald, J; Hicks, K; Eisner, T

1977-01-01

Analyses of the chief volatile constituents of the defensive secretions of three oplionids were carried out. Leiobunum nigripalpi produces three closely related C7 compounds: E-4-methyl-4-hexen-3-one(I), 4-methylhexan-3-one(II), and 4-methylhexan-3-ol(III), along with E-4-methyl-4-hepten-3-one(IV), E,E-2,4-dimethylhexa-2,4-dienal(IX), and a minor, unidentified component. L. leiopenis secretion contains E-4-methyl-4-hepten-3-one(IV), 4-methylheptan-3-one(V), E,E-2,4-dimethylhexa-2,4-dien-1-ol(VII), and E,E-2,4-dimethylhepta-2,4-dien-1-ol(VIII). L. calcar yields chiefly E-4,6-dimethyl-6-octen-3-one(VI) and E,E-2,4-dimethylhexa-2,4-dien-1-ol(VII). Six of these compounds are new natural products. The structures of these compounds, which can be regarded either as polyketide-derived or as modified isoprenoids, raise interesting biosynthetic questions. PMID:265514

Synthesis and radical scavenging activity of 6-hydroxyl-4-methylcoumarin and its derivatives

NASA Astrophysics Data System (ADS)

Jumal, Juliana; Ayomide, Adetunji Fridaos

2018-06-01

Four compounds of coumarin derivatives namely 6-hydroxyl-4-methylcoumarin (I), 6-hydroxyl-4-methyl-5-(p-nitrophenyl azocoumarin) (II), 6-hydroxyl-4-methyl-5,7-(bis-p-nitrophenyl azocoumarin) (III) and 6-hydroxyl-4-methyl-5,7-(bis-p-chlorophenyl azocoumarin) (IV) were successfully synthesized. These compounds were prepared by reacting hydroquinone with ethylacetoacetate and selected anilines which are chloro and nitro aniline. All synthesized compounds were characterized by CHN micro-elemental analysis, 1H Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared (FTIR) spectroscopic methods. The infrared spectra of these compounds exhibited five important stretching vibrations: ʋ(-OH), ʋ(C=O), ʋ(C=C), ʋ(C-O) and ʋ(C-N) at 3441-3359 cm-1, 1604-1632 cm-1, 1581-1496 cm-1, 1331-1225 cm-1, 1251-1109 cm-1, respectively. 1H NMR spectra of these compounds show the presence of proton aromatic, proton methyl and proton pyrone ring with the chemical shift at δH 7.00-8.70 ppm, δH 2.20-2.50 ppm and δH 6.10-6.90 ppm, respectively. CHN analysis results of all compounds are in good agreement with the calculated values. All the synthesized compounds were evaluated for their antioxidant activity using DPPH method and ascorbic acid used as the standard. UV-Vis spectroscopic technique was used to investigate the absorbance of these compounds. Compound (II) shows high antioxidant activities compared to compound (I), (III) and (IV) which show moderate to low activities.

Therapeutic cure against human tumor xenografts in nude mice by a microtubule stabilization agent, fludelone, via parenteral or oral route.

PubMed

Chou, Ting-Chao; Dong, Huajin; Zhang, Xiuguo; Tong, William P; Danishefsky, Samuel J

2005-10-15

Epothilones, 16-membered macrolides isolated from a myxobacterium in soil, exert their antitumor effect, like Taxol, by induction of microtubule polymerization and microtubule stabilization. They are effective against tumor cells that are resistant to Taxol or vinblastine. We recently designed, via molecular editing and total synthesis, a new class of epothilones represented by 26-trifluoro-(E)-9,10-dehydro-12,13-desoxy-epothilone B (Fludelone), which has emerged as a lead candidate for clinical development. Treatment of nude mice bearing MX-1 human mammary carcinoma xenografts (as large as 3.4% body weight) with Fludelone (6-hour i.v. infusion, 25 mg/kg, q3d x 5, q3d x 4) led to complete disappearance and de facto "cure" (i.e., remission without a relapse for over 15% of the average life span of 2 years). The toxicities induced by bolus i.v. injection could be avoided through prolonged i.v. infusion, which allowed for a 10-fold increase in maximal tolerated dose. Complete remission of MX-1 xenografts was achieved with only one third of this maximal tolerated dose. Parallel studies with Taxol and Fludelone [20 mg/kg, 6-hour i.v. infusion (q2d x 4) x3] against HCT-116 human colon carcinoma xenografts revealed that both drugs achieved tumor remission; however, all Taxol-treated mice relapsed in approximately 1.3 months, whereas the Fludelone-treated mice were cured without any relapse for over 7 months. Furthermore, tumor remission was achieved by Fludelone against SK-OV-3 (ovary), PC-3 (prostate), and the Taxol-resistant CCRF-CEM/Taxol (leukemia) xenograft tumors. Most remarkably, p.o. administration of Fludelone (30 mg/kg, q2d x 7, q2d x 9, q2d x 5) against MX-1 xenografts achieved a nonrelapsing cure for as long as 8.4 months. The above results indicate that Fludelone is a highly promising compound for cancer chemotherapeutics.

SNRB{trademark} air toxics monitoring. Final report

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

Not Available

1994-01-01

Babcock & Wilcox (B&W) is currently conducting a project under the DOE`s Clean Coal Technology (CCT II) Program to demonstrate its SO{sub x}NO{sub x}-Rox Box{trademark} (SNRB{trademark}) process in a 5 MWe Field Demonstration Unit at Ohio Edison`s R. E. Burger Plant near Shadyside, Ohio. The objective of the SNRB{trademark} Air Toxics Monitoring Project was to provide data on SNRB{trademark} air toxics emissions control performance to B&W and to add to the DOE/EPRI/EPA data base by quantifying the flow rates of selected hazardous substances (or air toxics) in all of the major input and output streams of the SNRB{trademark} process asmore » well as the power plant. Work under the project included the collection and analysis of representative samples of all major input and output streams of the SNRB{trademark} demonstration unit and the power plant, and the subsequent laboratory analysis of these samples to determine the partitioning of the hazardous substances between the various process streams. Material balances for selected air toxics were subsequently calculated around the SNRB{trademark} and host boiler systems, including the removal efficiencies across each of the major air pollution control devices. This report presents results of the SNRB{trademark} Air Toxics Monitoring Project. In addition to the Introduction, a brief description of the test site, including the Boiler No. 8 and the SNRB{trademark} process, is included in Section H. The concentrations of air toxic emissions are presented in Section II according to compound class. Material balances are included in Section IV for three major systems: boiler, electrostatic precipitator, and SNRB{trademark}. Emission factors and removal efficiencies are also presented according to compound class in Sections V and VI, respectively. A data evaluation is provided in Section VII.« less

Selection of a discriminant and biorelevant in vitro dissolution test for the development of fenofibrate self-emulsifying lipid-based formulations.

PubMed

Pestieau, Aude; Krier, Fabrice; Brouwers, Adeline; Streel, Bruno; Evrard, Brigitte

2016-09-20

Fenofibrate, a BCS class II compound, has a low bioavailability especially when taken orally on an empty stomach. The challenge to find a new formulation for providing bioavailability, independent of food, is still ongoing. If the development of a suitable oral delivery formulation of BCS class II compounds is a frequent and great challenge to formulation scientists, the in vitro evaluation of these new formulations is also a great challenge. The purpose of this study was therefore to select an in vitro dissolution test that would be useful and as biorelevant as possible for the development of fenofibrate self-emulsifying lipid-based formulations. In this context, three different fenofibrate formulations, for which in vivo data are available in the literature, were tested using different dissolution tests until we found the one that was the most suitable. As part of this approach, we started with the simplest in vitro dissolution tests and progressed to tests that were increasingly more complex. The first tests were different single phase dissolution tests: a test under sink conditions based on the USP monograph, and different tests under non-sink conditions in non-biorelevant and biorelevant media. Given the inconclusive results obtained with these tests, biphasic dissolution systems were then tested: one with USP apparatus type II alone and another which combined USP apparatus types II and IV. This last combined test seemed the most suitable in vitro dissolution test for the development of the future fenofibrate lipid-based formulations we intend to develop in our own laboratory. Copyright © 2016 Elsevier B.V. All rights reserved.

Printed-Circuit-Board Soldering Training for Group IV Personnel.

ERIC Educational Resources Information Center

Hooprich, E. A.; Matlock, E. W.

As part of a larger program to determine which Navy skills can be learned by lower aptitude personnel, and which methods and techniques would be most effective, an experimental course in printed circuit board soldering was given to 186 Group IV students in 13 classes. Two different training approaches--one stressing instructor guidance and the…

Highly soluble 3,4-(dimethoxyphenylthio) substituted phthalocyanines: Synthesis, photophysical and photochemical studies

NASA Astrophysics Data System (ADS)

Öztürk, Cansu; Erdoğmuş, Ali; Durmuş, Mahmut; Uğur, Ahmet Lütfi; Kılıçarslan, Fatma Aytan; Erden, İbrahim

2012-02-01

The synthesis of a new 3,4-(dimethoxyphenylthio) substituted phthalonitrile ( 1) and its soluble metal free ( 2), zinc (II) ( 3), oxo-titanium (IV) ( 4) and nickel (II) ( 5) phthalocyanine derivatives are reported for the first time. The new compounds have been characterized by elemental analysis, FT-IR, 1H NMR, UV-Vis, fluorescence spectroscopies and mass spectra. General trends are described for fluorescence, photodegradation and singlet oxygen quantum yields and fluorescence lifetimes of oxo-titanium (IV) and zinc (II) phthalocyanine compounds in dimethylsulfoxide (DMSO). The effects of the metal ion on the photophysical and photochemical parameters for these phthalocyanines ( 3 and 4) are also reported.

Comparative erythropoietic effects of three vanadium compounds.

PubMed

Hogan, G R

2000-07-10

The biotoxic effects of vanadium are variable depending upon a number of factors including the oxidation state of the test compound. This study reports the effects of three vanadium compounds on peripheral erythrocytes. On day 0 female ICR mice received a single injection of vanadium chloride (V-III), vanadyl sulfate (V-IV), or sodium orthovandate (V-V). At scheduled intervals post-injection, the number of circulating erythrocytes [red blood cells per millimeter cubed (RBC/mm3)], reticulocyte percentages, and radioiron uptake percentages were determined and compared to mice receiving saline only. Data show that all three test substances promoted a significant lowering of RBC/mm3 beginning on day 1 for V-IV and V-V and on day 2 for V-III through day 4. The reticulocyte percentages increase followed the same time course as that of the peripheral RBC decrease. Peak reticulocytosis was noted on days 2 and 4 for all three vanadium-treated groups; for V-IV and V-V the increase continued to day 6. Radioiron data showed an erythropoietic stimulation by a significant increase in uptake percentages on days 4-6 after vanadium injections compared to saline-treated controls.

Structure of 7,12-dimethylbenz(a)anthracene-guanosine adducts.

PubMed Central

Jeffrey, A M; Blobstein, S H; Weinstein, I B; Beland, F A; Harvey, R G; Kasai, H; Nakanishi, K

1976-01-01

Arene oxides have been proposed as the reactive intermediates in the process of carcinogenesis induced by polycyclic aromatic hydrocarbons. The present study defines the structures of four guanosine adducts formed by the reaction of 7,12-dimethylbenz[a]anthracene-5,6-oxide with polyguanylic acid. The modified polymer was hydrolyzed to nucleotides and the hydrophobic guanosine adducts separated from unmodified guanosine by LH-20 column chromatograhy. The adducts were further resolved into four components (I-IV) by reverse phase high pressure liquid chromatography. Analysis of the ultraviolet, circular dichroism, mass, and proton magnetic resonance spectra of these compounds, or their acetate and free base derivatives, indicates that in all four compounds the aromatic hydrocarbon is present on the 2 amino group of guanine. Compounds I and IV, and II and III constitute diastereoisomeric pairs, respectively. In the I and IV pair, the adducts result from addition at the 6 position of the original dimethylbenz[a]anthracene oxide, whereas in the II and III pair, the addition occurs at the 5 position. Indirect evidence suggests that trans opening of the oxide occurred in all cases but this remains to be established. PMID:821053

Natural chalcones as dual inhibitors of HDACs and NF-κB

PubMed Central

ORLIKOVA, B.; SCHNEKENBURGER, M.; ZLOH, M.; GOLAIS, F.; DIEDERICH, M.; TASDEMIR, D.

2012-01-01

Histone deacetylase enzymes (HDACs) are emerging as a promising biological target for cancer and inflammation. Using a fluorescence assay, we tested the in vitro HDAC inhibitory activity of twenty-one natural chalcones, a widespread group of natural products with well-known anti-inflammatory and antitumor effects. Since HDACs regulate the expression of the transcription factor NF-κB, we also evaluated the inhibitory potential of the compounds on NF-κB activation. Only four chalcones, isoliquiritigenin (no. 10), butein (no. 12), homobutein (no. 15) and the glycoside marein (no. 21) showed HDAC inhibitory activity with IC50 values of 60–190 μM, whereas a number of compounds inhibited TNFα-induced NF-κB activation with IC50 values in the range of 8–41 μM. Interestingly, three chalcones (nos. 10, 12 and 15) inhibited both TNFα-induced NF-κB activity and total HDAC activity of classes I, II and IV. Molecular modeling and docking studies were performed to shed light into dual activity and to draw structure-activity relationships among chalcones (nos. 1–21). To the best of our knowledge this is the first study that provides evidence for HDACs as potential drug targets for natural chalcones. The dual inhibitory potential of the selected chalcones on NF-κB and HDACs was investigated for the first time. This study demonstrates that chalcones can serve as lead compounds in the development of dual inhibitors against both targets in the treatment of inflammation and cancer. PMID:22710558

Multi-Targeting Andrographolide, a Novel NF-κB Inhibitor, as a Potential Therapeutic Agent for Stroke

PubMed Central

Yang, Chih-Hao; Yen, Ting-Lin; Hsu, Chia-Yuan; Thomas, Philip-Aloysius; Sheu, Joen-Rong; Jayakumar, Thanasekaran

2017-01-01

A key focus in the field of drug discovery has been motivated by the neuroprotection of natural compounds. Cerebral ischemia is a multifaceted pathological process with a series of mechanisms, and a perspective for the development of neuroprotectants from traditional herbal medicine or natural products is a promising treatment for this disease. Natural compounds with the effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional regulation exhibit therapeutic effects on experimental ischemic brain injury. Conferring to the pharmacological mechanisms underlying neuroprotection, a study found that androgapholide, a diterpene lactone compound, exhibits varying degrees of neuroprotective activities in both in vitro and in vivo experimental models of stroke. The neuroprotective mechanisms of andrographolide are suggested as: (I) increasing nuclear factor E2-related factor 2-heme oxygenase (Nrf2-HO-1) expression through p38-mitogen activated protein kinase (MAPK) regulation, (II) inducing cerebral endothelial cells (CEC) apoptosis and caspase-3 activation, (III) down regulating Bax, inducible nitric oxide synthase (iNOS), and (IV) inhibiting hydroxyl radical (OH−) formation, and activating transcription factor NF-κB signaling pathways. Recently, several researchers have also been trying to unveil the principal mechanisms involved in the neuroprotective effects of andrographolide. Therefore, this review aims to summarize an overview on the neuroprotective effects of andrographolide and exemplifies the essential mechanisms involved. This paper can provide information that andrographolide drug discovery may be a promising strategy for the development of a novel class of neuroprotective drug. PMID:28749412

Carboxylate derivatives of tributyltin (IV) complexes as anticancer and antileishmanial agents.

PubMed

Waseem, Durdana; Butt, Arshad Farooq; Haq, Ihsan-Ul; Bhatti, Moazzam Hussain; Khan, Gul Majid

2017-04-04

Tributyltin (IV) compounds are promising candidates for drug development. In the current study, we evaluated in-vitro and in-silico profile of carboxylate derivatives of tributyltin (IV) complexes. ADMET and drug-likeliness properties were predicted using MetaPrint2D React, preADMET, SwissADME and Molsoft tools. SwissTargetPrediction predicted molecular targets for compounds. In-vitro bioactivity was evaluated by quantifying cytotoxicity against HepG2, THP-1 cell lines, isolated lymphocytes and leishmania promastigotes as well as measuring protein kinase (PK) inhibition activity. Results indicate partial compliance of compounds with drug-likeliness rules. Ch-409 complies with WDI and Lipinski rules. ADMET profile prediction shows strong plasma protein binding except for Ch-409, low to high GI absorption and BBB penetration (C brain /C blood  = 0.942-11; caco-2 cells permeability 20.13-26.75 nm/sec), potential efflux by P-glycoprotein, metabolism by CYP3A4, medium inhibition of hERG, mutagenicity and capacity to be detoxified by glutathionation and glucuronidation. Molecular targets include proteases, enzymes, membrane receptors, transporters and ion channels where Ch-409 targets membrane receptors only. Compounds are significantly (p < 0.05) cytotoxic against HepG2 cell line and leishmania as compared with normal isolated lymphocytes. Ch-459 indicates highest toxicity against leishmania (mortality 97.9 ± 3.99%; LC50 0.323 ± 0.002 μg/mL) whereas Ch-409 possesses maximum cytotoxicity against HepG2 cell line (IC50 0.08 ± 0.001 μg/mL) as well as 97.5 ± 1.98% (LC50 0.954 ± 0.158 μg/mL) mortality of leishmania promastigotes. It was observed that antileishmanial effect was reduced by 16.38%-34.38% and 15-38.2% in the presence of NaN 3 and mannitol respectively. PK inhibition and reactive oxygen species production are possible mechanisms for cytotoxicity. Selected carboxylate derivatives of tributyltin (IV) complexes possess significant antileishmanial and cytotoxic potential. These are promising compounds for the development of antileishmanial and anticancer drugs. Graphical Abstract Carboxylate derivatives of tributyltin (IV) complexes as anticancer and antileishmanial agents.

[Studies on the chemical constituents of Gueldenstaedtia stenophylla].

PubMed

Wei, You-xia; Chen, Li; Wang, Jun-xian

2007-08-01

To study the chemical constituents of Gueldenstaeditia stenophylla. The constituents were isolated by alcohol extraction, column chromatography on silica gel. Their structures were elucidated by chemical and spectroscopic methods. Six compounds were obtained, and five of them were identified as n-hexadecanioc acid (I), beta-sitosterol (II), daucosterol (III), apigenin (IV), D-fructose (VI). Compound V was being determined. Five compounds are isolated from Gueldenstaedtia stenophylla and compounds I, III are extracted from Gueldenstaedtia Fisch for the first time.

19 CFR Appendix to Part 146 - Guidelines for Determining Producibility and Relative Values for Oil Refinery Zones

Code of Federal Regulations, 2012 CFR

2012-04-01

... × .20). Likewise, the class IV crude oil could produce aviation gasoline in an amount up to 8,500 pounds... Class III PF Crude 35,000 24,500 31,850 14,000 31,150 10,150 Class III D Crude 20,000 14,000 18,200 8,000 17,800 5,800 Class III NPF Crude 20,000 14,000 18,200 8,000 17,800 5,800 Feedstock factors are...

19 CFR Appendix to Part 146 - Guidelines for Determining Producibility and Relative Values for Oil Refinery Zones

Code of Federal Regulations, 2014 CFR

2014-04-01

... × .20). Likewise, the class IV crude oil could produce aviation gasoline in an amount up to 8,500 pounds... Class III PF Crude 35,000 24,500 31,850 14,000 31,150 10,150 Class III D Crude 20,000 14,000 18,200 8,000 17,800 5,800 Class III NPF Crude 20,000 14,000 18,200 8,000 17,800 5,800 Feedstock factors are...

Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review.

PubMed

Magoulas, Pilar L; El-Hattab, Ayman W; Roy, Angshumoy; Bali, Deeksha S; Finegold, Milton J; Craigen, William J

2012-06-01

Glycogen storage disease type IV is a rare autosomal recessive disorder of glycogen metabolism caused by mutations in the GBE1 gene that encodes the 1,4-alpha-glucan-branching enzyme 1. Its clinical presentation is variable, with the most common form presenting in early childhood with primary hepatic involvement. Histologic manifestations in glycogen storage disease type IV typically consist of intracytoplasmic non-membrane-bound inclusions containing abnormally branched glycogen (polyglucosan bodies) within hepatocytes and myocytes. We report a female infant with classic hepatic form of glycogen storage disease type IV who demonstrated diffuse reticuloendothelial system involvement with the spleen, bone marrow, and lymph nodes infiltrated by foamy histiocytes with intracytoplasmic polyglucosan deposits. Sequence analysis of the GBE1 gene revealed compound heterozygosity for a previously described frameshift mutation (c.1239delT) and a novel missense mutation (c.1279G>A) that is predicted to alter a conserved glycine residue. GBE enzyme analysis revealed no detectable activity. A review of the literature for glycogen storage disease type IV patients with characterized molecular defects and deficient enzyme activity reveals most GBE1 mutations to be missense mutations clustering in the catalytic enzyme domain. Individuals with the classic hepatic form of glycogen storage disease type IV tend to be compound heterozygotes for null and missense mutations. Although the extensive reticuloendothelial system involvement that was observed in our patient is not typical of glycogen storage disease type IV, it may be associated with severe enzymatic deficiency and a poor outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

Bioactive compounds from culinary herbs inhibit a molecular target for type 2 diabetes management, dipeptidyl peptidase IV.

PubMed

Bower, Allyson M; Real Hernandez, Luis M; Berhow, Mark A; de Mejia, Elvira Gonzalez

2014-07-02

Greek oregano (Origanum vulgare), marjoram (Origanum majorana), rosemary (Rosmarinus officinalis), and Mexican oregano (Lippia graveolens) are concentrated sources of bioactive compounds. The aims were to characterize and examine extracts from greenhouse-grown or commercially purchased herbs for their ability to inhibit dipeptidyl peptidase IV (DPP-IV) and protein tyrosine phosphatase 1B (PTP1B), enzymes that play a role in insulin secretion and insulin signaling, respectively. Greenhouse herbs contained more polyphenols (302.7-430.1 μg of gallic acid equivalents/mg of dry weight of extract (DWE)) and flavonoids (370.1-661.4 μg of rutin equivalents/mg of DWE) compared to the equivalent commercial herbs. Greenhouse rosemary, Mexican oregano, and marjoram extracts were the best inhibitors of DPP-IV (IC₅₀=16, 29, and 59 μM, respectively). Commercial rosemary, Mexican oregano, and marjoram were the best inhibitors of PTP1B (32.4-40.9% at 500 μM). The phytochemicals eriodictyol, naringenin, hispidulin, cirsimaritin, and carnosol were identified by LC-ESI-MS as being present in greenhouse-grown Mexican oregano and rosemary. Computational modeling indicated that hispidulin, carnosol, and eriodictyol would have the best binding affinities for DPP-IV. Biochemically, the best inhibitors of DPP-IV were cirsimaritin (IC₅₀=0.43±0.07 μM), hispidulin (IC₅₀=0.49±0.06 μM), and naringenin (IC₅₀=2.5±0.29 μM). Overall, herbs contain several flavonoids that inhibit DPP-IV and should be investigated further regarding their potential in diabetes management.

Precursors to radiopharmaceutical agents for tissue imaging

DOEpatents

Srivastava, Prem C.; Knapp, Jr., Furn F.

1988-01-01

A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

Better End-Cap Processing for Oxidation-Resistant Polyimides

NASA Technical Reports Server (NTRS)

Meador, Mary Ann B.; Frimer, Aryeh A.

2004-01-01

A class of end-cap compounds that increase the thermo-oxidative stab ility of polyimides of the polymerization of monomeric reactants (PM R) type has been extended. In addition, an improved processing proto col for this class of end-cap compounds has been invented.

Expanding the Therapeutic Potential of the Iron Chelator Deferasirox in the Development of Aqueous Stable Ti(IV) Anticancer Complexes.

PubMed

Loza-Rosas, Sergio A; Vázquez-Salgado, Alexandra M; Rivero, Kennett I; Negrón, Lenny J; Delgado, Yamixa; Benjamín-Rivera, Josué A; Vázquez-Maldonado, Angel L; Parks, Timothy B; Munet-Colón, Charlene; Tinoco, Arthur D

2017-07-17

The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV). This metal affinity preference drives deferasirox to facilitate the release of cytotoxic Ti(IV) intracellularly in exchange for Fe(III). An aqueous speciation study performed by potentiometric titration from pH 4 to 8 with micromolar levels of Ti(IV) deferasirox at a 1:2 ratio reveals exclusively Ti(deferasirox) 2 in solution. The predominant complex at pH 7.4, [Ti(deferasirox) 2 ] 2- , exhibits the one of the highest aqueous stabilities observed for a potent cytotoxic Ti(IV) species, demonstrating little dissociation even after 1 month in cell culture media. UV-vis and 1 H NMR studies show that the stability is unaffected by the presence of biomolecular Ti(IV) binders such as citrate, STf, and albumin, which have been shown to induce dissociation or regulate cellular uptake and can alter the activity of other antiproliferative Ti(IV) complexes. Kinetic studies on [Ti(deferasirox) 2 ] 2- transmetalation with Fe(III) show that a labile Fe(III) source is required to induce this process. The initial step of this process occurs on the time scale of minutes, and equilibrium for the complete transmetalation is reached on a time scale of hours to a day. This work reveals a mechanism to deliver Ti(IV) compounds into cells and trigger Ti(IV) release by a labile Fe(III) species. Cellular studies including other cTfm ligands confirm the Fe(III) depletion mechanism of these compounds and show their ability to induce early and late apoptosis.

Pain: Systematic Review of Pharmacy Compounding of Pain Medication.

PubMed

Shawaqfeh, Mohammad S; Harrington, Catherine

2018-01-01

There are limited resources available for pharmacists and doctors to reference proper compounded formulas for pain medications. The systematic review discussed within this article provides the foundation for a searchable database, allowing users to find various compounded formulations. It also provides data about the safety and efficacy of the preparations. Compounding information about several drug classes was reviewed. Those drug classes included, but were not limited to, opioids, non-steroidal anti-inflammatory drugs, central nervous system agents, and anesthetics, with evidence that of the various drugs that could be compounded for pain, anesthetics, non-steroidal anti-inflammatory drugs, and opioids ranked highest within the articles researched. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Is scaffold hopping a reliable indicator for the ability of computational methods to identify structurally diverse active compounds?

NASA Astrophysics Data System (ADS)

Dimova, Dilyana; Bajorath, Jürgen

2017-07-01

Computational scaffold hopping aims to identify core structure replacements in active compounds. To evaluate scaffold hopping potential from a principal point of view, regardless of the computational methods that are applied, a global analysis of conventional scaffolds in analog series from compound activity classes was carried out. The majority of analog series was found to contain multiple scaffolds, thus enabling the detection of intra-series scaffold hops among closely related compounds. More than 1000 activity classes were found to contain increasing proportions of multi-scaffold analog series. Thus, using such activity classes for scaffold hopping analysis is likely to overestimate the scaffold hopping (core structure replacement) potential of computational methods, due to an abundance of artificial scaffold hops that are possible within analog series.

BCI Competition IV – Data Set I: Learning Discriminative Patterns for Self-Paced EEG-Based Motor Imagery Detection

PubMed Central

Zhang, Haihong; Guan, Cuntai; Ang, Kai Keng; Wang, Chuanchu

2012-01-01

Detecting motor imagery activities versus non-control in brain signals is the basis of self-paced brain-computer interfaces (BCIs), but also poses a considerable challenge to signal processing due to the complex and non-stationary characteristics of motor imagery as well as non-control. This paper presents a self-paced BCI based on a robust learning mechanism that extracts and selects spatio-spectral features for differentiating multiple EEG classes. It also employs a non-linear regression and post-processing technique for predicting the time-series of class labels from the spatio-spectral features. The method was validated in the BCI Competition IV on Dataset I where it produced the lowest prediction error of class labels continuously. This report also presents and discusses analysis of the method using the competition data set. PMID:22347153

Self-organized perturbations enhance class IV behavior and 1/f power spectrum in elementary cellular automata.

PubMed

Nakajima, Kohei; Haruna, Taichi

2011-09-01

In this paper, we propose a new class of cellular automata based on the modification of its state space. It is introduced to model a computation which is exposed to an environment. We formalized the computation as extension and projection processes of its state space and resulting misidentifications of the state. This is motivated to embed the role of an environment into the system itself, which naturally induces self-organized internal perturbations rather than the usual external perturbations. Implementing this structure into the elementary cellular automata, we characterized its effect by means of input entropy and power spectral analysis. As a result, the cellular automata with this structure showed robust class IV behavior and a 1/f power spectrum in a wide range of rule space comparative to the notion of the edge of chaos. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Bis(N-ethyl-N-methyl­dithio­carbamato-κ2 S,S′)diphenyl­tin(IV)

PubMed Central

Muthalib, Amirah Faizah; Baba, Ibrahim; Ng, Seik Weng

2010-01-01

The dithio­carbamate anions in the title compound, [Sn(C6H5)2(C4H8NS2)2], chelate to the SnIV atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol­ecule lies across a twofold rotation axis. PMID:21580470

Bis(N-isopropyl-N-methyl­dithio­carbamato-κ2 S,S′)diphenyl­tin(IV)

PubMed Central

Muthalib, Amirah Faizah; Baba, Ibrahim; Farina, Yang; Ng, Seik Weng

2010-01-01

The dithio­carbamate anions in the title compound, [Sn(C6H5)2(C5H10NS2)2], chelate to the SnIV atom, which is six-coordinated in a skew-trapezoidal-bipyramidal geometry. The mol­ecule lies across a twofold rotation axis. PMID:21580469

[Studies on the chemical constituents from Cissus pteroclada].

PubMed

Chi, Cui-Yun; Wang, Feng; Lei, Ting; Xu, Shao-Yu; Hong, Ai-Hua; Cen, Ying-Zhou

2010-10-01

To study the chemical constituents of Yao Medicine Cissus pteroclada. The compounds were isolated and purified by column chromatography with silica gel, TLC and recrystallization. Their structures were elucidated on the basis of physicochemical properties and spectra analysis. Six compounds were isolated and identified as beta-sitosterol (I), bergenin (II), 11-O-galloylbergenin (III), 11-O-(4-hydroxy benzoyl) bergenin (IV), gallic acid (V), daucosterol (VI). Compounds III and NIV are obtained from the genus for the first time. All the compounds are isolated from this plant for the first time except the compound II.

Provision of Atraumatic Restorative Treatment (ART) restorations to Chinese pre-school children--a 30-month evaluation.

PubMed

Lo, E C; Holmgren, C J

2001-01-01

The objectives of this study were: to provide restorations using the ART approach to pre-school children in Southern China in a kindergarten environment, using a high-strength glass-ionomer restorative material; to assess the acceptability of this approach and to evaluate on a longitudinal basis the restorations placed. A total of 170 ART restorations were placed in 95 children, aged 5.1 +/- 0.7 years, by seven final-year dental students using standard ART procedures and hand instruments. The restorations were evaluated every six months thereafter by two calibrated independent examiners using explorers and mouth-mirrors. 93% of the children reported that they did not feel pain during treatment and 86% were willing to receive ART restorations again. The cumulative 12- and 30-month survival rates of Class I restorations were 91% and 79%, respectively. The corresponding figures for Class V restorations were 79% and 70%, while those for Class II restorations were 75% and 51%. The failure rates of Class III and IV restorations were high with more than half of them scored as missing within the first year. The ART approach was shown to be acceptable to Chinese pre-school children for providing restorative dental care outside the traditional clinical setting. The success rates were high for Class I and V restorations in primary teeth, modest for Class II, and low for Class III and IV restorations.

Bioactive compounds from culinary herbs inhibit a molecular target for type 2 diabetes management, dipeptidyl peptidase IV

USDA-ARS?s Scientific Manuscript database

Greek oregano (Origanum vulgare), marjoram (Origanum majorana), rosemary (Rosmarinus officinalis) and Mexican oregano (Lippia graveolens) are concentrated sources of bioactive compounds. The aims of this study were to characterize extracts from greenhouse grown or commercially purchased herbs for th...

Dual targeting of GyrB and ParE by a novel aminobenzimidazole class of antibacterial compounds.

PubMed

Grossman, Trudy H; Bartels, Douglas J; Mullin, Steve; Gross, Christian H; Parsons, Jonathan D; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Olson, Eric R; Charifson, Paul S; Mani, Nagraj

2007-02-01

A structure-guided drug design approach was used to optimize a novel series of aminobenzimidazoles that inhibit the essential ATPase activities of bacterial DNA gyrase and topoisomerase IV and that show potent activities against a variety of bacterial pathogens. Two such compounds, VRT-125853 and VRT-752586, were characterized for their target specificities and preferences in bacteria. In metabolite incorporation assays, VRT-125853 inhibited both DNA and RNA synthesis but had little effect on protein synthesis. Both compounds inhibited the maintenance of negative supercoils in plasmid DNA in Escherichia coli at the MIC. Sequencing of DNA corresponding to the GyrB and ParE ATP-binding regions in VRT-125853- and VRT-752586-resistant mutants revealed that their primary target in Staphylococcus aureus and Haemophilus influenzae was GyrB, whereas in Streptococcus pneumoniae it was ParE. In Enterococcus faecalis, the primary target of VRT-125853 was ParE, whereas for VRT-752586 it was GyrB. DNA transformation experiments with H. influenzae and S. aureus proved that the mutations observed in gyrB resulted in decreased susceptibilities to both compounds. Novobiocin resistance-conferring mutations in S. aureus, H. influenzae, and S. pneumoniae were found in gyrB, and these mutants showed little or no cross-resistance to VRT-125853 or VRT-752586 and vice versa. Furthermore, gyrB and parE double mutations increased the MICs of VRT-125853 and VRT-752586 significantly, providing evidence of dual targeting. Spontaneous frequencies of resistance to VRT-752586 were below detectable levels (<5.2x10(-10)) for wild-type E. faecalis but were significantly elevated for strains containing single and double target-based mutations, demonstrating that dual targeting confers low levels of resistance emergence and the maintenance of susceptibility in vitro.

Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators.

PubMed

Zhang, Hai-Chun; Hu, Rong-Fei; Zhu, Ting; Tong, Ling; Zhang, Qiu-Qin

2016-06-14

To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators. One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve. LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83.3%). The diagnostic value of PBC cirrhosis degree in liver cirrhosis degree assessment by ARFI combined with the four indicators of serum liver fibrosis is of satisfactory effectiveness and has important clinical application value.

Joint Tactical Information Distribution System (JTIDS). Class 3 Terminal Conceptual Study. Volume 4. Appendix A. Mission Profile Detail. Appendix B. Moments of the Decision Variable for preamble Detection

DTIC Science & Technology

1978-07-07

i on CM . ’ oil ■ «) rH H O W CO rH 0) H H <: o I »d • •o H i ! • M CO X -H | i iQ M 4> m u...referred to Electronic Systems Division, Hanscom AFB, MA. Document partially illegible. AFGL ltr 15 May 1981 A I ’ ESD-ra-7B-l6l, Vol. IV V,^^7 -J...BEPORE COMPLETING FORM ESD-TR-78-161, Vol. IV 2 COVT ACCESSION NO I RCCIFICNT’S CATALOG NUMBCn 4. TITLE (mid Submit) JTIDS Class

Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus

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

Wener, M.H.; Mannik, M.; Schwartz, M.M.

1987-03-01

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) ormore » proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc).« less

Heat generated by Er:YAG laser in the pulp chamber of teeth submitted to removal of dental tissue and composite resin

NASA Astrophysics Data System (ADS)

Zanin, Fatima; Brugnera, Aldo, Jr.; Pecora, Jesus D.; Pinheiro, Antonio; Spano, Julio; Barbin, Eduardo; Marchesan, Melissa A.

2004-05-01

The knowledge about and control of thermal energy produced by Er:YAG laser after irradiating hard dental tissues and compound resin is important because the pulp, like all vital biological tissue, has a certain capacity for supporting stimulus. The objective of this study was to analyze the thermal variation generated by Er:YAG laser (λ=2.94μm) during the preparation of a Class I cavity in the dental structure and in the removal of microhybrid Z100 (3M) compound resin. An evaluation was made of 30 maxillary human pre-molar teeth from the bank of the Endodontic Laboratory Center of Ribeirao Preto Dental School, Brasil. The sample was divided into 6 groups of 5 teeth each: Group 1, preparation of Class I cavity with Er:YAG laser (350mJ, 3Hz, 343 impulses, 120J, 113 seconds); Group 2, preparation of Class I cavity with Er:YAG laser (350mJ, 4Hz, 343 impulses, 120J, 81 seconds); Group 3, preparation of Class I cavity with Er:YAG laser (350mJ, 6Hz, 343 impulses, 120J, 58 seconds); Group 4, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 3Hz, 258 impulses, 90J, 85 seconds); Group 5, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 4Hz, 258 impulses, 90J, 67 seconds); Group 6, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 6Hz, 258 impulses, 42 seconds). The laser used was KaVo Key 2 (Biberach, Germany), λ=2,94μm, P=3 Watts, pulse duration of 250μs, with air-water cooling. The increase in temperature during dental preparation and the removal of the compound resin was evaluated by means of a Tektronix DMM916 Thermocouple (Consitec, Brasil). The results showed that the application of laser for the removal of the hard dental tissues and for the removal of compound resins with the pulse frequencies 3, 4 and 6 Hz did not generate heating greater than 3.1°C and remained within the histopathological limits permitted for pulp tissue (5.5°C) and there was a significant statistical difference between the heat generated by the application of laser in the removal of the hard dental tissues and in the removal of compound resins (p<0.01). The average increase in temperature of the compound resin component was greater than the tooth.

Inflammatory mediators in chronic heart failure in North India.

PubMed

Fedacko, Jan; Singh, Ram B; Gupta, Aditya; Hristova, Krasimira; Toda, Eri; Kumar, Adarsh; Saxena, Manoj; Baby, Anjum; Singh, Ranjana; Toru, Takahashi; Wilson, Douglas W

2014-08-01

Recent evidence shows that pro-inflammatory cytokines may be important in the assessment of severity and prognosis in congestive heart failure (CHF). In the present study, we examine the association of cytokines with causes, grade and prognosis of CHF patients. Of 127 patients with CHF, 11 were excluded and the remaining 116 patients with different aetiologies of CHF, and 250 age- and sex-matched control subjects, were evaluated in this case study. Severity of disease based on the New York Heart Association (NYHA) standards, fell within functional classes II to IV. The diagnosis of HF was based on clinical manifestations as well as on echocardiographic heart enlargement. Cytokines were measured by chemiluminescence. Causes of death were assessed based on death certificates. Multivariate logistic regression analysis was used to determine the risk factors of heart failure. Echocardiographic ejection fraction was 39.1 +/- 8.2% (mean +/- SD) in the study group indicating class II-IV heart failure. Laboratory data showed increase in biomarkers of oxidative stress, among HF patients compared to healthy subjects. Pro-inflammatory cytokines; IL-6 and TNF-alpha were significantly higher among HF patients compared to healthy subjects. TNF-alpha and IL-6, showed significant increase among patients with CHF due to ischaemic heart disease and cardiomyopathy compared to levels among CHF patients with valvular heart disease and hypertensive heart diseases. The levels of the cytokines were significantly higher among patients with class III and IV heart failure and those who died, compared to patients with class II heart failure. Multivariate logistic regression analysis revealed that CAD, cardiomyopathy, and IL-6 were strongly associated--and low ejection fraction and TNF-alpha--weakly associated with HF. Of 116 patients, 20 (17.2%) died during a follow-up of two years, and the deaths were mainly among NYHA class III and IV patients in whom the cause of CHF was CAD (10.9%) and cardiomyopathy (6.9%) which had greater levels of cytokines. The findings indicated that pro-inflammatory cytokines may be important indicators of causes, severity of CHF and prognosis among these patients.

The Generation of Diazo Compounds in Continuous-Flow.

PubMed

Hock, Katharina J; Koenigs, Rene M

2018-03-25

Toxic, cancerogenic and explosive - these attributes are typically associated with diazo compounds. Nonetheless, diazo compounds are nowadays a highly demanded class of reagents for organic synthesis, yet the concerns with regards to safe and scalable transformations of these compounds are still exceptionally high. Lately, the research area of the continuous-flow synthesis of diazo compounds attracted significant interest and a whole variety of protocols for their "on-demand" preparation have been realized to date. This concept article focuses on the recent developments using continuous-flow technologies to access diazo compounds; thus minimizing risks and hazards when working with this particular class of compounds. In this article we discuss these concepts and highlight different pre-requisites to access and to perform downstream functionalization reaction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

Understanding the tolerance of the industrial yeast Saccharomyces cerevisiae against a major class of toxic aldehyde compounds

USDA-ARS?s Scientific Manuscript database

Development of the next-generation biocatalyst is vital for fermentation-based industrial applications and a sustainable bio-based economy. Overcoming the major class of toxic compounds associated with lignocellulose-to-biofuels conversion is one of the significant challenges for new strain developm...

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable evolving flammable vapor and Plastic...

49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable evolving flammable vapor and Plastic...

Keto-acids in Carbonaceous Meteorites

NASA Technical Reports Server (NTRS)

Cooper, G.; Chang, P. M.; Dugas, A.; Byrd, A.; Chang, P. M.; Washington, N.

2005-01-01

The Murchison and Murray meteorites are the best-characterized carbonaceous meteorites with respect to organic chemistry and are generally used as references for organic compounds in extraterrestrial material. Among the classes of organic compounds found in these meteorites are amino acids, carboxylic acids, hydroxy acids, purines, and pyrimidines. Such compounds, important in contemporary biochemistry, are thought to have been delivered to the early Earth in asteroids and comets and may have played a role in early life and/or the origin of life. Absent among (today's) critically important biological compounds reported in carbonaceous meteorites are keto acids, i.e., pyruvic acid, acetoacetic acid, and higher homologs. These compounds are key intermediates in such critical processes as glycolysis and the citric acid cycle. In this study several individual meteoritic keto acids were identified by gas chromatography-mass spectrometry (GC-MS) (see figure below). All compounds were identified as their trimethylsilyl (TMS), isopropyl ester (ISP), and tert-butyldimethylsilyl (tBDMS) derivatives. In general, the compounds follow the abiotic synthesis pattern of other known meteorite classes of organic compounds [1,2]: a general decrease in abundance with increasing carbon number within a class of compounds and many, if not all, possible isomers present at a given carbon number. The majority of the shown compounds was positively identified by comparison of their mass spectra to commercially available standards or synthesized standards.

Computational Analysis of Gynura bicolor Bioactive Compounds as Dipeptidyl Peptidase-IV Inhibitor

PubMed Central

Abdullah Zawawi, Muhammad Redha; Ahmad, Muhamad Aizuddin; Jaganath, Indu Bala

2017-01-01

The inhibition of dipeptidyl peptidase-IV (DPPIV) is a popular route for the treatment of type-2 diabetes. Commercially available gliptin-based drugs such as sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin were specifically developed as DPPIV inhibitors for diabetic patients. The use of Gynura bicolor in treating diabetes had been reported in various in vitro experiments. However, an understanding of the inhibitory actions of G. bicolor bioactive compounds on DPPIV is still lacking and this may provide crucial information for the development of more potent and natural sources of DPPIV inhibitors. Evaluation of G. bicolor bioactive compounds for potent DPPIV inhibitors was computationally conducted using Lead IT and iGEMDOCK software, and the best free-binding energy scores for G. bicolor bioactive compounds were evaluated in comparison with the commercial DPPIV inhibitors, sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin. Drug-likeness and absorption, distribution, metabolism, and excretion (ADME) analysis were also performed. Based on molecular docking analysis, four of the identified bioactive compounds in G. bicolor, 3-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, and trans-5-p-coumaroylquinic acid, resulted in lower free-binding energy scores when compared with two of the commercially available gliptin inhibitors. The results revealed that bioactive compounds in G. bicolor are potential natural inhibitors of DPPIV. PMID:28932239

Study of Default Options in Advance Directives

ClinicalTrials.gov

2015-06-29

COPD; Severe or Very Severe Airflow Obstruction and/or Receiving or Eligible to Receive Long-term Oxygen Therapy; Idiopathic Pulmonary Fibrosis; Other Interstitial Lung Disease Without Curative Therapy; Congestive Heart Failure; NYHA Class IV or NYHA Class III Plus 1 Hospitalization in the Past Year; Malignancy; Any Stage 3B or 4 Solid Tumor

78 FR 56732 - Submission of Information Collection Extensions Under the Paperwork Reduction Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... Control Number 3141-0006; and (iv) issuance to tribes of certificates of self- regulation for Class II... the Commission for a certificate of self-regulation for its Class II gaming operation(s). The... to issue the certificate of self- regulation. Once a certificate of self-regulation has been issued...

78 FR 40766 - Renewals of Information Collections Under the Paperwork Reduction Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... Control Number 3141-0006; and (iv) issuance to tribes of certificates of self-regulation for Class II.... Estimated Total Non-hour Cost Burden: $14,846,686. Title: Issuance of Certificates of Self-Regulation to... Commission for a certificate of self-regulation for its Class II gaming operation(s). The Commission will...

40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM: CRITERIA AND STANDARDS General... of drinking water. The Director may allow Class III wells to use other plugging materials if the... sources of drinking water. (2) Placement of the cement plugs shall be accomplished by one of the following...

40 CFR 147.751 - EPA-administered program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I, III, IV, and V wells on non-Indian lands in the State of Indiana is administered by the EPA. The...

40 CFR 147.751 - EPA-administered program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I, III, IV, and V wells on non-Indian lands in the State of Indiana is administered by the EPA. The...

40 CFR 147.101 - EPA-administered program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.101 EPA-administered program. (a) Contents. The UIC program in the State of Alaska for Class I, III, IV, and V wells, and for all classes of wells on Indian lands, is administered by EPA. This program consists of the UIC...

Working Smarter, Not Harder (Part IV).

ERIC Educational Resources Information Center

LaBelle, Sandy

2003-01-01

Discusses ways of improving student attitudes and motivation, such as changing the focus of tests, making students responsible for their work, using a grid to show test results, instituting in-class breaks, using a personal grade book, discussing with students the effects of sleep deprivation, and using separate folders for papers of each class.…

The social class gradient in health in Spain and the health status of the Spanish Roma.

PubMed

La Parra Casado, Daniel; Gil González, Diana; de la Torre Esteve, María

2016-10-01

To determine the social class gradient in health in general Spain population and the health status of the Spanish Roma. The National Health Survey of Spanish Roma 2006 (sample size = 993 people; average age: 33.6 years; 53.1% women) and the National Health Surveys for Spain 2003 (sample size: 21,650 people; average age: 45.5 years; 51.2% women) and 2006 (sample size: 29,478 people; average age: 46 years; 50.7% women) are compared. Several indicators were chosen: self-perceived health, activity limitation, chronic diseases, hearing and sight problems, caries, and obesity. Analysis was based on age-standardised rates and logistic regression models. According to most indicators, Roma's health is worse than that of social class IV-V (manual workers). Some indicators show a remarkable difference between Roma and social class IV-V: experiencing three or more health problems, sight problems, and caries, in both sexes, and hearing problems and obesity, in women. Roma people are placed on an extreme position on the social gradient in health, a situation of extreme health inequality.

Pea Chaperones under Centrifugation

NASA Astrophysics Data System (ADS)

Talalaiev, Oleksandr

2008-06-01

Etiolated Pisum sativum seedlings were subjected to altered g-forces by centrifugation (3-14g). By using semiquantitative RT-PCR, we studied transcripts of pea genes coding for chaperones that are representatives of small heat shock proteins (sHsps) family. Four members from the different classes of sHsps: cytosolic Hsp17.7 and Hsp18.1 (class I and class II accordingly), chloroplast Hsp21 (class III) and endoplasmic reticulum Hsp22.7 (class IV) were investigated. We conclude that exposure to 3, 7, 10 and 14g for 1h did not affect the level of sHsp transcripts.

2005 NDIA Combat Vehicles Conference. Volume 2- Thursday Presentations and Videos

DTIC Science & Technology

2005-09-22

Mounted Combat System MULE: (Countermine) MULE: (Transport) Class II Class III Class IV Armed Robotic Vehicle ARV RSTA ARV Assault FCS Recovery and...Vehicles – Infantry Carrier Vehicle (ICV) – Armed Robotic Vehicle - Assault (ARV (A)) – Recon & Surveillance Vehicle (RSV)  Training Ammo for AP & AB...Holtz and Mr. Dick Williams, Boeing Mr. Dean Vanderstelt, General Dynamics Land Systems ( GDLS ) Mr. Mike Zoltoski, TARDEC Mr. Peter DeMasi, Program

Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit.

PubMed

Backes, Bradley J; Longenecker, Kenton; Hamilton, Gregory L; Stewart, Kent; Lai, Chunqiu; Kopecka, Hana; von Geldern, Thomas W; Madar, David J; Pei, Zhonghua; Lubben, Thomas H; Zinker, Bradley A; Tian, Zhenping; Ballaron, Stephen J; Stashko, Michael A; Mika, Amanda K; Beno, David W A; Kempf-Grote, Anita J; Black-Schaefer, Candace; Sham, Hing L; Trevillyan, James M

2007-04-01

A novel series of pyrrolidine-constrained phenethylamines were developed as dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2 diabetes. The cyclohexene ring of lead-like screening hit 5 was replaced with a pyrrolidine to enable parallel chemistry, and protein co-crystal structural data guided the optimization of N-substituents. Employing this strategy, a >400x improvement in potency over the initial hit was realized in rapid fashion. Optimized compounds are potent and selective inhibitors with excellent pharmacokinetic profiles. Compound 30 was efficacious in vivo, lowering blood glucose in ZDF rats that were allowed to feed freely on a mixed meal.

(3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone: A potent, selective, orally active dipeptidyl peptidase IV inhibitor

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

Ammirati, Mark J.; Andrews, Kim M.; Boyer, David D.

2010-10-01

A series of 4-substituted proline amides was synthesized and evaluated as inhibitors of dipeptidyl pepdidase IV for the treatment of type 2 diabetes. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone (5) emerged as a potent (IC{sub 50} = 13 nM) and selective compound, with high oral bioavailability in preclinical species and low plasma protein binding. Compound 5, PF-00734200, was selected for development as a potential new treatment for type 2 diabetes.

Microwave assisted synthesis of novel acridine-acetazolamide conjugates and investigation of their inhibition effects on human carbonic anhydrase isoforms hCA I, II, IV and VII.

PubMed

Ulus, Ramazan; Aday, Burak; Tanç, Muhammet; Supuran, Claudiu T; Kaya, Muharrem

2016-08-15

4-Amino-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)benzamide was condensed with cyclic-1,3-diketones (dimedone and cyclohexane-1,3-dione) and aromatic aldehydes under microwave irradiation, leading to a series of acridine-acetazolamide conjugates. The new compounds were investigated as inhibitors of carbonic anhydrases (CA, EC 4.2.1.1), and more precisely cytosolic isoforms hCA I, II, VII and membrane-bound one hCA IV. All investigated isoforms were inhibited in low micromolar and nanomolar range by the new compounds. hCA IV and VII were inhibited with KIs in the range of 29.7-708.8nM (hCA IV), and of 1.3-90.7nM (hCA VII). For hCA I and II the KIs were in the range of 6.7-335.2nM (hCA I) and of 0.5-55.4nM (hCA II). The structure-activity relationships (SAR) for the inhibition of these isoforms with the acridine-acetazolamide conjugates reported here were delineated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical features and histological patterns of lupus nephritis in a single center of South India.

PubMed

Devadass, Clement Wilfred; Mysorekar, Vijaya Viswanath; Eshwarappa, Mahesh; Mekala, Lakshminarayanan; Siddaiah, M Gireesh; Channabasappa, K Gurudev

2016-01-01

Renal involvement occurs in up to 60% of patients with systemic lupus erythematosus (SLE) and signifies a poor prognosis. The class of lupus nephritis (LN), determined on renal biopsy evaluation, guides the therapeutic management and has prognostic connotations. Our aim is to determine the clinicolaboratory features and histopathological patterns of LN at presentation in our local (South Indian) population. The study was conducted in a tertiary care hospital in South India between 2009 and 2014 on SLE patients with clinical evidence of LN. The renal biopsies were examined by light and immunofluorescence microscopy and were classified according to the International Society of Nephrology/Renal Pathology Society Classification of LN. A total of 46 patients were included, with age range of 12-60 years and a female to male ratio of 8.2:1. Arthritis, dermatological manifestations, and fever occurred, respectively, in 43.5%, 39.1%, and 30.4% of the cases. Class IV LN was present in 17 (37.1%), Class III LN in ten (21.7%), Class II LN in nine (19.5%), Class V LN in eight (17.4%), Class I LN in one (2.2%), and Class VI LN in one (2.2%) patients. Antinuclear antibody (ANA) and dsDNA positivity were present, respectively, in 82.6% and 65.2% of the patients. The most common pattern of LN was Class IV LN followed by Class III LN. Relatively higher proportions of ANA and anti-dsDNA positivity were present in proliferative LN, and there was a high frequency of arthritis at presentation in our LN patients.

Latent classes of emotional and behavioural problems in epidemiological and referred samples and their relations to DSM-IV diagnoses.

PubMed

Bianchi, Valentina; Brambilla, Paolo; Garzitto, Marco; Colombo, Paola; Fornasari, Livia; Bellina, Monica; Bonivento, Carolina; Tesei, Alessandra; Piccin, Sara; Conte, Stefania; Perna, Giampaolo; Frigerio, Alessandra; Castiglioni, Isabella; Fabbro, Franco; Molteni, Massimo; Nobile, Maria

2017-05-01

Researchers' interest have recently moved toward the identification of recurrent psychopathological profiles characterized by concurrent elevations on different behavioural and emotional traits. This new strategy turned to be useful in terms of diagnosis and outcome prediction. We used a person-centred statistical approach to examine whether different groups could be identified in a referred sample and in a general-population sample of children and adolescents, and we investigated their relation to DSM-IV diagnoses. A latent class analysis (LCA) was performed on the Child Behaviour Checklist (CBCL) syndrome scales of the referred sample (N = 1225), of the general-population sample (N = 3418), and of the total sample. Models estimating 1-class through 5-class solutions were compared and agreement in the classification of subjects was evaluated. Chi square analyses, a logistic regression, and a multinomial logistic regression analysis were used to investigate the relations between classes and diagnoses. In the two samples and in the total sample, the best-fitting models were 4-class solutions. The identified classes were Internalizing Problems (15.68%), Severe Dysregulated (7.82%), Attention/Hyperactivity (10.19%), and Low Problems (66.32%). Subsequent analyses indicated a significant relationship between diagnoses and classes as well as a main association between the severe dysregulated class and comorbidity. Our data suggested the presence of four different psychopathological profiles related to different outcomes in terms of psychopathological diagnoses. In particular, our results underline the presence of a profile characterized by severe emotional and behavioural dysregulation that is mostly associated with the presence of multiple diagnosis.

Microleakage in conservative cavities varying the preparation method and surface treatment

PubMed Central

ATOUI, Juliana Abdallah; CHINELATTI, Michelle Alexandra; PALMA-DIBB, Regina Guenka; CORONA, Silmara Aparecida Milori

2010-01-01

Objective To assess microleakage in conservative class V cavities prepared with aluminum-oxide air abrasion or turbine and restored with self-etching or etch-and-rinse adhesive systems. Material and Methods Forty premolars were randomly assigned to 4 groups (I and II: air abrasion; III and IV: turbine) and class V cavities were prepared on the buccal surfaces. Conditioning approaches were: groups I/III - 37% phosphoric acid; groups II/IV -self-priming etchant (Tyrian-SPe). Cavities were restored with One Step Plus/Filtek Z250. After finishing, specimens were thermocycled, immersed in 50% silver nitrate, and serially sectioned. Microleakage at the occlusal and cervical interfaces was measured in mm and calculated by a software. Data were subjected to ANOVA and Tukey’s test (α=0.05). Results Forty premolars were randomly assigned to 4 groups (I and II: air abrasion; III and IV: turbine) and class V cavities were prepared on the buccal surfaces. Conditioning approaches were: groups I/III - 37% phosphoric acid; groups II/IV -self-priming etchant (Tyrian-SPe). Cavities were restored with One Step Plus/Filtek Z250. After finishing, specimens were thermocycled, immersed in 50% silver nitrate, and serially sectioned. Microleakage at the occlusal and cervical interfaces was measured in mm and calculated by a software. Data were subjected to ANOVA and Tukey’s test (α=0.05). Conclusion Marginal seal of cavities prepared with aluminum-oxide air abrasion was different from that of conventionally prepared cavities, and the etch-and-rinse system promoted higher marginal seal at both enamel and dentin margins. PMID:20835580

A new, empirically established hypochondriasis diagnosis.

PubMed

Fink, Per; Ørnbøl, Eva; Toft, Tomas; Sparle, Kaj Christensen; Frostholm, Lisbeth; Olesen, Frede

2004-09-01

The narrow ICD-10 and DSM-IV definition of hypochondriasis makes it rarely used yet does not prevent extensive diagnosis overlap. This study identified a distinct hypochondriasis symptom cluster and defined diagnostic criteria. Consecutive patients (N=1,785) consulting primary care physicians for new illness were screened for somatization, anxiety, depression, and alcohol abuse. A stratified subgroup of 701 patients were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and questions addressing common hypochondriasis symptoms. Symptom patterns were analyzed by latent class analysis. Patients fell into three classes based on six symptoms: preoccupation with the idea of harboring an illness or with bodily function, rumination about illness, suggestibility, unrealistic fear of infection, fascination with medical information, and fear of prescribed medication. All symptoms, particularly rumination, were frequent in one of the classes. Classification allowed definition of new diagnostic criteria for hypochondriasis and division of the cases into "mild" and "severe." The weighted prevalence of severe cases was 9.5% versus 5.8% for DSM-IV hypochondriasis. Compared with DSM-IV hypochondriasis, this approach produced less overlap with other somatoform disorders, similar overlap with nonsomatoform psychiatric disorders, and similar assessments by primary care physicians. Severe cases of the new hypochondriasis lasted 2 or more years in 54.3% of the subjects and 1 month or less in 27.2%. These results suggest that rumination about illness plus at least one of five other symptoms form a distinct diagnostic entity performing better than the current DSM-IV hypochondriasis diagnosis. However, these criteria are preliminary, awaiting cross-validation in other subject groups.

Stabilization of higher-valent states of iron porphyrin by hydroxide and methoxide ligands: electrochemical generation of iron(IV)-oxo porphyrins.

PubMed Central

Lee, W A; Calderwood, T S; Bruice, T C

1985-01-01

An electrochemical study of hydroxide- and methoxide-ligated iron(III) tetraphenylporphyrins possessing ortho-phenyl substituents that block mu-oxo dimer formation has been carried out. Ligation by these strongly basic oxyanions promotes the formation of iron(IV)-oxo porphyrins upon one-electron oxidation. Further one-electron oxidation of the latter provides the iron(IV)-oxo porphyrin pi-cation radical. These results are discussed in terms of chemical model studies and the enzymatic intermediate compounds I and II of the peroxidases. PMID:3859865

Acute bioassays and hazard evaluation of representative contaminants detected in Great Lakes fish

USGS Publications Warehouse

Passino, Dora R. May; Smith, Stephen B.

1987-01-01

We have provided a hazard ranking for 19 classes of compounds representing many of the nearly 500 organic compounds identified by gas chromatography-mass spectrometry in lake trout (Salvelinus namaycush) and walleye (Stizostedion vitreum vitreum) from the Great Lakes and Lake St. Clair. We initially made a provisional hazard ranking based on available published and unpublished information on aquatic toxicity, bioaccumulation, occurrence and sources. Acute toxicity tests with Daphnia pulex at 17A°C in reconstituted hard water were performed with 30 compounds representative of the 19 classes that were highest in the provisional ranking. The resulting toxicity data, along with information on the compounds' occurrence in Great Lakes fish and their sources, were ranked and weighted and then used in calculating the revised hazard ranking. The 10 most hazardous classes, in descending order, are as follows (values shown are mean 48-h EC50s, in μ/ml): arene halides (e.g., polychlorinated biphenyls, DDT), 0.0011; phthalate esters, 0.133; chlorinated camphenes (toxaphene), 0.0082; polyaromatic hydrocarbons (PAHs; e.g., dimethylnaphthalene) and reduced derivatives, 1.01; chlorinated fused polycyclics (e.g., trans-nonachlor), 0.022; nitrogen-containing compounds (e.g., O-methylhydroxyl-amine), 1.35; alkyl halides (e.g., (bromomethyl)cyclohexene), 10.1; cyclic alkanes (e.g., cyclododecane), 20.9; silicon-containing compounds (e.g., dimethyldiethoxy silane), 1.25; and heterocyclic nitrogen compounds (e.g., nicotine), 2.48. We recommend that chronic bioassays be conducted with fish and invertebrates to determine the sublethal effects of the following classes of compounds, for which few toxicity data are available: PAHs, heterocyclic nitrogen compounds, other nitrogen-containing compounds, alkyl halides, cyclic alkanes and silicon-containing compounds. Information from these types of studies will aid researchers in determining the possible causal role these contaminants play in the decline and reproductive impairment of Great Lakes fish.

Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules.

PubMed

Dave, Vivek S; Gupta, Deepak; Yu, Monica; Nguyen, Phuong; Varghese Gupta, Sheeba

2017-02-01

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.

Phenolic root exudate and tissue compounds vary widely among temperate forest tree species and have contrasting effects on soil microbial respiration.

PubMed

Zwetsloot, Marie J; Kessler, André; Bauerle, Taryn L

2018-04-01

Root-soil interactions fundamentally affect the terrestrial carbon (C) cycle and thereby ecosystem feedbacks to climate change. This study addressed the question of whether the secondary metabolism of different temperate forest tree species can affect soil microbial respiration. We hypothesized that phenolics can both increase and decrease respiration depending on their function as food source, mobilizer of other soil resources, signaling compound, or toxin. We analyzed the phenolic compounds from root exudates and root tissue extracts of six tree species grown in a glasshouse using high-performance liquid chromatography. We then tested the effect of individual phenolic compounds, representing the major identified phenylpropanoid compound classes, on microbial respiration through a 5-d soil incubation. Phenolic root profiles were highly species-specific. Of the eight classes identified, flavonoids were the most abundant, with flavanols being the predominating sub-class. Phenolic effects on microbial respiration ranged from a 26% decrease to a 46% increase, with reduced respiration occurring in the presence of compounds possessing a catechol ring. Tree species variation in root phenolic composition influences the magnitude and direction of root effects on microbial respiration. Our data support the hypothesis that functional group rather than biosynthetic class determines the root phenolic effect on soil C cycling. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Levofloxacin 750-mg for 5 days for the treatment of hospitalized Fine Risk Class III/IV community-acquired pneumonia patients.

PubMed

Shorr, Andrew F; Khashab, Mohammed M; Xiang, Jim X; Tennenberg, Alan M; Kahn, James B

2006-12-01

The efficacy and safety of 750-mg, 5-day levofloxacin was recently shown to be comparable to 500-mg, 10-day levofloxacin in a randomized, double-blind, multicentre clinical trial for mild-to-severe community-acquired pneumonia (CAP). This subgroup analysis attempted to compare the safety and efficacy of a short-course levofloxacin regimen with traditional levofloxacin dosing for PSI Class III/IV patients. This retrospective, subgroup analysis focused on Pneumonia Severity Index Class III and IV patients enrolled in the study. Measurements included clinical and microbiological success rates, adverse events, and symptom resolution by day 3 of therapy. Of the 528 patients in the ITT population, 219 (41.5%) were categorized as PSI Class III/IV and included in this analysis. Among the clinically evaluable patients, 90.8% (69/76) of patients treated with the 750-mg regimen achieved clinical success, compared with 85.5% (71/83) treated with 500-mg levofloxacin (95% CI,-15.9 to 5.4). Eradication rates in the microbiologically evaluable population were comparable for the 750- and 500-mg regimens (88.9% vs 87.5%, respectively; 95% CI,-18.3 to 15.6). Both regimens were well tolerated and had comparable safety profiles. A greater proportion of patients in the 750-mg treatment group experienced resolution of fever (48.4% vs 34.0%; P=.046) and purulent sputum (48.4% vs 27.5%; P=.007) by day 3 of therapy. The 750-mg, 5-day levofloxacin course achieved comparable clinical and microbiologic efficacy to the 500-mg, 10-day regimen. By day 3 of therapy, a greater proportion of patients in the 750-mg group had objective and subjective resolution of fever. Further research is needed to determine the economic significance of short-course levofloxacin therapy.

Evaluation of a technique for color correction in restoring anterior teeth.

PubMed

Rauber, Gabrielle Branco; Bernardon, Jussara Karina; Vieira, Luiz Clovis Cardoso; Baratieri, Luiz Narciso

2017-09-01

This study aimed to evaluate the ability of the proposed technique in producing restorations that exhibit mimesis with tooth structure and to define a restorative clinical protocol. For this study a typodont was used. The right upper central incisor with Class IV lesion was restored with the layering technique (reference tooth, RT). For the left upper central incisor with Class IV lesion, six teeth were restored monochromatically (test teeth, TT), using DA3.5 (n = 3) and DA4 (n = 3) composite resins-resulting in six unsatisfactory color restorations. TT were divided into six groups depending on the color of unsatisfactory restoration and preparation depth. First, a preparation was realized on the labial surface with 0.5 mm, 0.7 mm or 1.0 mm of depth. A second preparation was then performed to reproduce the dentinal mamelons. Next, adhesive procedures were performed and the teeth restored. Opaque halo, opalescent halo and vestibular enamel were then reproduced by the addition of different composite resins. The RT and TT were photographed side by side in typodont to obtain six photographic prints. The photographs of the groups were subjected to visual evaluation by 120 volunteers via a questionnaire. Data were analyzed by the prevalence of answers, and Chi-square test was used to investigate the association between variables at .05 significance. Furthermore, ΔE of groups was evaluated in comparison RT. The results demonstrated that the moderate intensity restorations (DA3.5) with depths of 0.5 mm and 0.7 mm had the highest prevalence of acceptance. For severe intensity restorations (DA4), the preparation depth of 1.0 mm obtained better acceptance. The technique was able to modify the final color of Class IV restorations, producing satisfactory color restorations. This technique can be used for color correction in cases of Class IV restorations, in situations where there is no time for immediate layered restoration, and as a restorative technique. © 2017 Wiley Periodicals, Inc.

The Genome Sequence of the Obligately Chemolithoautotrophic, Facultatively Anaerobic Bacterium Thiobacillus denitrificans

PubMed Central

Beller, Harry R.; Chain, Patrick S. G.; Letain, Tracy E.; Chakicherla, Anu; Larimer, Frank W.; Richardson, Paul M.; Coleman, Matthew A.; Wood, Ann P.; Kelly, Donovan P.

2006-01-01

The complete genome sequence of Thiobacillus denitrificans ATCC 25259 is the first to become available for an obligately chemolithoautotrophic, sulfur-compound-oxidizing, β-proteobacterium. Analysis of the 2,909,809-bp genome will facilitate our molecular and biochemical understanding of the unusual metabolic repertoire of this bacterium, including its ability to couple denitrification to sulfur-compound oxidation, to catalyze anaerobic, nitrate-dependent oxidation of Fe(II) and U(IV), and to oxidize mineral electron donors. Notable genomic features include (i) genes encoding c-type cytochromes totaling 1 to 2 percent of the genome, which is a proportion greater than for almost all bacterial and archaeal species sequenced to date, (ii) genes encoding two [NiFe]hydrogenases, which is particularly significant because no information on hydrogenases has previously been reported for T. denitrificans and hydrogen oxidation appears to be critical for anaerobic U(IV) oxidation by this species, (iii) a diverse complement of more than 50 genes associated with sulfur-compound oxidation (including sox genes, dsr genes, and genes associated with the AMP-dependent oxidation of sulfite to sulfate), some of which occur in multiple (up to eight) copies, (iv) a relatively large number of genes associated with inorganic ion transport and heavy metal resistance, and (v) a paucity of genes encoding organic-compound transporters, commensurate with obligate chemolithoautotrophy. Ultimately, the genome sequence of T. denitrificans will enable elucidation of the mechanisms of aerobic and anaerobic sulfur-compound oxidation by β-proteobacteria and will help reveal the molecular basis of this organism's role in major biogeochemical cycles (i.e., those involving sulfur, nitrogen, and carbon) and groundwater restoration. PMID:16452431

Intravenous Chemotherapy Compounding Errors in a Follow-Up Pan-Canadian Observational Study.

PubMed

Gilbert, Rachel E; Kozak, Melissa C; Dobish, Roxanne B; Bourrier, Venetia C; Koke, Paul M; Kukreti, Vishal; Logan, Heather A; Easty, Anthony C; Trbovich, Patricia L

2018-05-01

Intravenous (IV) compounding safety has garnered recent attention as a result of high-profile incidents, awareness efforts from the safety community, and increasingly stringent practice standards. New research with more-sensitive error detection techniques continues to reinforce that error rates with manual IV compounding are unacceptably high. In 2014, our team published an observational study that described three types of previously unrecognized and potentially catastrophic latent chemotherapy preparation errors in Canadian oncology pharmacies that would otherwise be undetectable. We expand on this research and explore whether additional potential human failures are yet to be addressed by practice standards. Field observations were conducted in four cancer center pharmacies in four Canadian provinces from January 2013 to February 2015. Human factors specialists observed and interviewed pharmacy managers, oncology pharmacists, pharmacy technicians, and pharmacy assistants as they carried out their work. Emphasis was on latent errors (potential human failures) that could lead to outcomes such as wrong drug, dose, or diluent. Given the relatively short observational period, no active failures or actual errors were observed. However, 11 latent errors in chemotherapy compounding were identified. In terms of severity, all 11 errors create the potential for a patient to receive the wrong drug or dose, which in the context of cancer care, could lead to death or permanent loss of function. Three of the 11 practices were observed in our previous study, but eight were new. Applicable Canadian and international standards and guidelines do not explicitly address many of the potentially error-prone practices observed. We observed a significant degree of risk for error in manual mixing practice. These latent errors may exist in other regions where manual compounding of IV chemotherapy takes place. Continued efforts to advance standards, guidelines, technological innovation, and chemical quality testing are needed.

Synthesis and crystal structures of nitratocobaltates Na2[Co(NO3)4], K2[Co(NO3)4], and Ag[Co(NO3)3] and potassium nitratonickelate K2[Ni(NO3)4

NASA Astrophysics Data System (ADS)

Morozov, I. V.; Fedorova, A. A.; Albov, D. V.; Kuznetsova, N. R.; Romanov, I. A.; Rybakov, V. B.; Troyanov, S. I.

2008-03-01

The cobalt(II) and nickel(II) nitrate complexes with an island structure (Na2[Co(NO3)4] ( I) and K2[Co(NO3)4] ( II)] and a chain structure [Ag[Co(NO3)3] ( III) and K2[Ni(NO3)4] ( IV)] are synthesized and investigated using X-ray diffraction. In the anionic complex [Co(NO3)4]2- of the crystal structure of compound I, the Co coordination polyhedron is a twisted tetragonal prism formed by the O atoms of four asymmetric bidentate nitrate groups. In the anion [Co(NO3)4]2- of the crystal structure of compound II, one of the four NO3 groups is monodentate and the other NO3 groups are bidentate (the coordination number of the cobalt atom is equal to seven, and the cobalt coordination polyhedron is a monocapped trigonal prism). The crystal structures of compounds III and IV contain infinite chains of the compositions [Co(NO3)2(NO3)2/2]- and [Ni(NO3)3(NO3)2/2]2-, respectively. In the crystal structure of compound III, seven oxygen atoms of one monodentate and three bidentate nitrate groups form a dodecahedron with an unoccupied vertex of the A type around the Co atom. In the crystal structure of compound IV, the octahedral polyhedron of the Ni atom is formed by five nitrate groups, one of which is terminal bidentate. The data on the structure of Co(II) coordination polyhedra in the known nitratocobaltates are generalized.

Berry Phenolic Compounds Increase Expression of Hepatocyte Nuclear Factor-1α (HNF-1α) in Caco-2 and Normal Colon Cells Due to High Affinities with Transcription and Dimerization Domains of HNF-1α

PubMed Central

Real Hernandez, Luis M.; Fan, Junfeng; Johnson, Michelle H.; Gonzalez de Mejia, Elvira

2015-01-01

Hepatocyte nuclear factor-1α (HNF-1α) is found in the kidneys, spleen, thymus, testis, skin, and throughout the digestive organs. It has been found to promote the transcription of various proteins involved in the management of type II diabetes, including dipeptidyl peptidase-IV (DPP-IV). Phenolic compounds from berries and citrus fruits are known to inhibit DPP-IV, but have not been tested for their interactions with wild-type HNF-1α. By studying the interactions of compounds from berries and citrus fruits have with HNF-1α, pre-transcriptional mechanisms that inhibit the expression of proteins such as DPP-IV may be elucidated. In this study, the interactions of berry phenolic compounds and citrus flavonoids with the dimerization and transcriptional domains of HNF-1α were characterized using the molecular docking program AutoDock Vina. The anthocyanin delphinidin-3-O-arabinoside had the highest binding affinity for the dimerization domain as a homodimer (-7.2 kcal/mol) and transcription domain (-8.3 kcal/mol) of HNF-1α. Anthocyanins and anthocyanidins had relatively higher affinities than resveratrol and citrus flavonoids for both, the transcription domain and the dimerization domain as a homodimer. The flavonoid flavone had the highest affinity for a single unit of the dimerization domain (-6.5 kcal/mol). Nuclear expression of HNF-1α was measured in Caco-2 and human normal colon cells treated with blueberry and blackberry anthocyanin extracts. All extracts tested increased significantly (P < 0.05) the nuclear expression of HNF-1α in Caco-2 cells by 85.2 to 260% compared to a control. The extracts tested increased significantly (P < 0.02) the nuclear expression of HNF-1α in normal colon cells by 48.6 to 243%. It was confirmed that delphinidin-3-O-glucoside increased by 3-fold nuclear HNF-1α expression in Caco-2 cells (P < 0.05). Anthocyanins significantly increased nuclear HNF-1α expression, suggesting that these compounds might regulate the genes HNF-1α promotes. PMID:26413797

Deposit formation in liquid fuels. II - The effect of selected compounds on the storage stability of Jet A turbine fuel

NASA Technical Reports Server (NTRS)

Worstell, J. H.; Daniel, S. R.

1981-01-01

The influence of substituted pyridines, pyrroles, indoles, and quinolines on the storage stability of conventional Jet A turbine fuel is evaluated. Significant increases in the amount of deposit formed in accelerated storage tests are found upon addition of these compounds at levels as low as one ppm nitrogen. While the effect is correlated with basicity of the nitrogen compound within a given compound class, the correlation does not hold between classes (pyridines, quinolines, etc.). Steric hindrance at the nitrogen atom greatly inhibits deposit promotion. The characteristics, but not the elemental composition, of deposits vary with the identity of the added nitrogen compound and with deposition temperature.

Design of Glucagon-Like Peptide-1 Receptor Agonist for Diabetes Mellitus from Traditional Chinese Medicine

PubMed Central

Tang, Hsin-Chieh; Chen, Calvin Yu-Chian

2014-01-01

Glucagon-like peptide-1 (GLP-1) is a promising target for diabetes mellitus (DM) therapy and reduces the occurrence of diabetes due to obesity. However, GLP-1 will be hydrolyzed soon by the enzyme dipeptidyl peptidase-4 (DPP-4). We tried to design small molecular drugs for GLP-1 receptor agonist from the world's largest traditional Chinese medicine (TCM) Database@Taiwan. According to docking results of virtual screening, we selected 2 TCM compounds, wenyujinoside and 28-deglucosylchikusetsusaponin IV, for further molecular dynamics (MD) simulation. GLP-1 was assigned as the control compound. Based on the results of root mean square deviation (RMSD), solvent accessible surface (SAS), mean square deviation (MSD), Gyrate, total energy, root mean square fluctuation (RMSF), matrices of smallest distance of residues, database of secondary structure assignment (DSSP), cluster analysis, and distance of H-bond, we concluded that all the 3 compounds could bind and activate GLP-1 receptor by computational simulation. Wenyujinoside and 28-deglucosylchikusetsusaponin IV were the TCM compounds that could be GLP-1 receptor agonists. PMID:24891870

Design of glucagon-like Peptide-1 receptor agonist for diabetes mellitus from traditional chinese medicine.

PubMed

Tang, Hsin-Chieh; Chen, Calvin Yu-Chian

2014-01-01

Glucagon-like peptide-1 (GLP-1) is a promising target for diabetes mellitus (DM) therapy and reduces the occurrence of diabetes due to obesity. However, GLP-1 will be hydrolyzed soon by the enzyme dipeptidyl peptidase-4 (DPP-4). We tried to design small molecular drugs for GLP-1 receptor agonist from the world's largest traditional Chinese medicine (TCM) Database@Taiwan. According to docking results of virtual screening, we selected 2 TCM compounds, wenyujinoside and 28-deglucosylchikusetsusaponin IV, for further molecular dynamics (MD) simulation. GLP-1 was assigned as the control compound. Based on the results of root mean square deviation (RMSD), solvent accessible surface (SAS), mean square deviation (MSD), Gyrate, total energy, root mean square fluctuation (RMSF), matrices of smallest distance of residues, database of secondary structure assignment (DSSP), cluster analysis, and distance of H-bond, we concluded that all the 3 compounds could bind and activate GLP-1 receptor by computational simulation. Wenyujinoside and 28-deglucosylchikusetsusaponin IV were the TCM compounds that could be GLP-1 receptor agonists.

II-I2-IV-VI4 (II = Sr,Ba; I = Cu,Ag; IV = Ge,Sn; VI = S,Se): Earth-Abundant Chalcogenides for Thin Film Photovoltaics

NASA Astrophysics Data System (ADS)

Zhu, Tong; Huhn, William P.; Shin, Donghyeop; Mitzi, David B.; Blum, Volker; Saparov, Bayrammurad

Chalcogenides such as CdTe, CIGSSe, and CZTSSe are successful for thin film photovoltaics (PV) but contain elements that are rare, toxic, or prone to the formation of detrimental antisite disorder. Recently, the BaCu2SnS4-xSex system has been shown to offer a prospective path to circumvent these problems. While early prototypes show efficiencies of a few percent, many avenues remain to optimize the materials, including the underlying chemical composition. In this work, we explore 16 compounds II-I2-IV-VI4 to help identify new candidate materials for PV, with predictions based on both known experimental and computationally derived structures that belong to five different space groups. We employ hybrid density functional theory (HSE06) to explore the band gap tunability by substituting different elements, and other characteristics such as the effective mass and the absorption coefficient. Compounds containing Cu (rather than Ag) are found to have direct or nearly direct band gaps. Depending on the compound, replacing S with Se leads to a decrease of the predicted band gaps by 0.2-0.8 eV and to somewhat decreasing hole effective masses.

Structures of plutonium coordination compounds: A review of past work, recent single crystal x-ray diffraction results, and what we're learning about plutonium coordination chemistry

NASA Astrophysics Data System (ADS)

Neu, M. P.; Matonic, J. H.; Smith, D. M.; Scott, B. L.

2000-07-01

The compounds we have isolated and characterized include plutonium(III) and plutonium(IV) bound by ligands with a range of donor types and denticity (halide, phosphine oxide, hydroxamate, amine, sulfide) in a variety of coordination geometries. For example, we have obtained the first X-ray structure of Pu(III) complexed by a soft donor ligand. Using a "one pot" synthesis beginning with Pu metal strips and iodine in acetonitrile and adding trithiacyclononane we isolated the complex, PuI3(9S3)(MeCN)2 (Figure 1). On the other end of the coordination chemistry spectrum, we have obtained the first single crystal structure of the Pu(IV) hexachloro anion (Figure 2). Although this species has been used in plutonium purification via anion exchange chromatography for decades, the bond distances and exact structure were not known. We have also characterized the first plutonium-biomolecule complex, Pu(IV) bound by the siderophore desferrioxamine E.In this presentation we will review the preparation, structures, and importance of previously known coordination compounds and of those we have recently isolated. We will show the coordination chemistry of plutonium is rich and varied, well worth additional exploration.

Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

PubMed Central

Gajanan Khanage, Shantaram; Raju, Appala; Baban Mohite, Popat; Bhanudas Pandhare, Ramdas

2013-01-01

Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives containing 1,2,4-triazole ring were subjected to study their in vivo analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted derivatives showed excellent analgesic activity and dimethylamino, furan and phenyl substituted derivatives showed moderate analgesic activity in both of the methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj IV3a and IIj were found to be superior analgesic agents after screening by Acetic acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb, IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after screening of Hot plate method. Conclusion: All tested compounds containing 1,2,4-triazole were found to be promising analgesic agents, for this activity pyrazole, tetrazole, isoxazole and pyrimidine leads might be supported. PMID:24312806

Equatorial Ligand Perturbations Influence the Reactivity of Manganese(IV)-Oxo Complexes.

PubMed

Massie, Allyssa A; Denler, Melissa C; Cardoso, Luísa Thiara; Walker, Ashlie N; Hossain, M Kamal; Day, Victor W; Nordlander, Ebbe; Jackson, Timothy A

2017-04-03

Manganese(IV)-oxo complexes are often invoked as intermediates in Mn-catalyzed C-H bond activation reactions. While many synthetic Mn IV -oxo species are mild oxidants, other members of this class can attack strong C-H bonds. The basis for these reactivity differences is not well understood. Here we describe a series of Mn IV -oxo complexes with N5 pentadentate ligands that modulate the equatorial ligand field of the Mn IV center, as assessed by electronic absorption, electron paramagnetic resonance, and Mn K-edge X-ray absorption methods. Kinetic experiments show dramatic rate variations in hydrogen-atom and oxygen-atom transfer reactions, with faster rates corresponding to weaker equatorial ligand fields. For these Mn IV -oxo complexes, the rate enhancements are correlated with both 1) the energy of a low-lying 4 E excited state, which has been postulated to be involved in a two-state reactivity model, and 2) the Mn III/IV reduction potentials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relationship of serum uric acid and Killip class on mortality after acute ST-segment elevation myocardial infarction and primary percutaneous coronary intervention.

PubMed

Liu, Cheng-Wei; Liao, Pen-Chih; Chen, Kuo-Chin; Chiu, Yu-Wei; Liu, Yuan-Hung; Ke, Shin-Rong; Wu, Yen-Wen

2017-01-01

There is conflicting information regarding the association between hyperuricemia and survival in STEMI patients. Our study examined the interaction between hyperuricemia and Killip class on mortality of STEMI patients. We analyzed 951 consecutive STEMI patients between February 2006 and September 2012. Hyperuricemia was defined as SUA of at least 7mg/dL in males and 6mg/dL in females. Killip class I patients were divided into hyperuricemia and normouricemia groups. The Killip class I hyperuricemia and normouricemia groups had similar baseline and procedural characteristics, but the hyperuricemia group had significantly greater BMI, serum creatinine, and SUA, and a lower TIMI risk score (2, IQR: 1-4 vs. 3, IQR: 2-4, p=0.019). The hyperuricemia group also had greater 30-day and 1-year mortality rates (2.9% vs. 0.3%, p=0.022; 6.5% vs. 1.1%, p=0.002, respectively). However, hyperuricemia was not associated with mortality of patients in Killip classes II-IV or in the overall study population. Hyperuricemia was associated with increased mortality in subgroups of patients who were at least 65years-old, male, had BMI of 25kg/m 2 or less, were in Killip class I, without diabetes, and who did not receive intra-aortic balloon pump support. Hyperuricemia interacted with Killip class I in increasing the risk for 1-year mortality (p for interaction=0.038). Hyperuricemia increased the 1-year mortality of STEMI patients in Killip class I, but not of patients in Killip classes II-IV. An interaction of hyperuricemia and Killip class significantly affects the mortality of STEMI patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bayesian probability of success for clinical trials using historical data

PubMed Central

Ibrahim, Joseph G.; Chen, Ming-Hui; Lakshminarayanan, Mani; Liu, Guanghan F.; Heyse, Joseph F.

2015-01-01

Developing sophisticated statistical methods for go/no-go decisions is crucial for clinical trials, as planning phase III or phase IV trials is costly and time consuming. In this paper, we develop a novel Bayesian methodology for determining the probability of success of a treatment regimen on the basis of the current data of a given trial. We introduce a new criterion for calculating the probability of success that allows for inclusion of covariates as well as allowing for historical data based on the treatment regimen, and patient characteristics. A new class of prior distributions and covariate distributions is developed to achieve this goal. The methodology is quite general and can be used with univariate or multivariate continuous or discrete data, and it generalizes Chuang-Stein’s work. This methodology will be invaluable for informing the scientist on the likelihood of success of the compound, while including the information of covariates for patient characteristics in the trial population for planning future pre-market or post-market trials. PMID:25339499

Bayesian probability of success for clinical trials using historical data.

PubMed

Ibrahim, Joseph G; Chen, Ming-Hui; Lakshminarayanan, Mani; Liu, Guanghan F; Heyse, Joseph F

2015-01-30

Developing sophisticated statistical methods for go/no-go decisions is crucial for clinical trials, as planning phase III or phase IV trials is costly and time consuming. In this paper, we develop a novel Bayesian methodology for determining the probability of success of a treatment regimen on the basis of the current data of a given trial. We introduce a new criterion for calculating the probability of success that allows for inclusion of covariates as well as allowing for historical data based on the treatment regimen, and patient characteristics. A new class of prior distributions and covariate distributions is developed to achieve this goal. The methodology is quite general and can be used with univariate or multivariate continuous or discrete data, and it generalizes Chuang-Stein's work. This methodology will be invaluable for informing the scientist on the likelihood of success of the compound, while including the information of covariates for patient characteristics in the trial population for planning future pre-market or post-market trials. Copyright © 2014 John Wiley & Sons, Ltd.

Prenatal diagnosis of fetal glutaric aciduria type 1 with rare compound heterozygous mutations in GCDH gene.

PubMed

Peng, Hsiu-Huei; Shaw, Sheng-Wen; Huang, Kuan-Gen

2018-02-01

Glutaric aciduria type 1 is a rare disease, with the estimated prevalence about 1 in 100,000 newborns. GCDH gene mutation can lead to glutaric acid and 3- OH glutaric acid accumulation, with clinical manifestation of neuronal damage, brain atrophy, microencephalic macrocephaly, decreased coordination of swallowing, poor muscle coordination, spasticity, and severe dystonic movement disorder. A 22-year-old female, Gravida 4 Para 2, is pregnancy at 13 weeks of gestational age. Her first child is normal, however, the second child was diagnosed as glutaric aciduria type I after birth. She came to our hospital for prenatal genetic counselling of her fetus at 13 weeks of gestational age. We performed GCDH gene mutation analysis of maternal blood showed IVS 3 + 1 G > A heterozygous mutation, GCDH gene mutation analysis of paternal blood showed c. 1240 G > A heterozygous mutation, and the second child has compound heterozygous IVS 3 + 1 G > A and c. 1240 G > A mutations. Later, we performed amniocentesis at 16 weeks of gestational age for chromosome study and GCDH gene mutation analysis for the fetus. The fetal chromosome study showed normal karyotype, however, GCDH gene mutation analysis showed compound heterozygous IVS 3 + 1 G > A and c. 1240 G > A mutations. The couple decided to termination of pregnancy thereafter. Glutaric acidemia type 1 is an autosomal recessive disorder because of pathogenic mutations in the GCDH gene. Early diagnosis and therapy of glutaric acidemia type 1 can reduce the risk of neuronal damage and acute dystonia. We report a case of prenatal diagnosis of fetal glutaric aciduria type 1 with rare compound heterozygous GCDH gene mutation at IVS 3 + 1 G > A and c. 1240 G > A mutations, which provide better genetic counselling for the couples. Copyright © 2018. Published by Elsevier B.V.

Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon–Metal Bond Cleavage

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

Wahba, Haytham M.; Stevenson, Michael J.; Mansour, Ahmed

2017-01-03

The organomercurial lyase MerB has the unique ability to cleave carbon–Hg bonds, and structural studies indicate that three residues in the active site (C96, D99, and C159 in E. coli MerB) play important roles in the carbon–Hg bond cleavage. However, the role of each residue in carbon–metal bond cleavage has not been well-defined. To do so, we have structurally and biophysically characterized the interaction of MerB with a series of organotin and organolead compounds. Studies with two known inhibitors of MerB, dimethyltin (DMT) and triethyltin (TET), reveal that they inhibit by different mechanisms. In both cases the initial binding ismore » to D99, but DMT subsequently binds to C96, which induces a conformation change in the active site. In contrast, diethyltin (DET) is a substrate for MerB and the SnIV product remains bound in the active site in a coordination similar to that of HgII following cleavage of organomercurial compounds. The results with analogous organolead compounds are similar in that trimethyllead (TML) is not cleaved and binds only to D99, whereas diethyllead (DEL) is a substrate and the PbIV product remains bound in the active site. Binding and cleavage is an exothermic reaction, while binding to D99 has negligible net heat flow. These results show that initial binding of organometallic compounds to MerB occurs at D99 followed, in some cases, by cleavage and loss of the organic moieties and binding of the metal ion product to C96, D99, and C159. The N-terminus of MerA is able to extract the bound PbVI but not the bound SnIV. These results suggest that MerB could be utilized for bioremediation applications, but certain organolead and organotin compounds may present an obstacle by inhibiting the enzyme.« less

NEW FRONTIERS IN DRUGGABILITY

PubMed Central

Kozakov, Dima; Hall, David R.; Napoleon, Raeanne L.; Yueh, Christine; Whitty, Adrian; Vajda, Sandor

2016-01-01

A powerful early approach to evaluating the druggability of proteins involved determining the hit rate in NMR-based screening of a library of small compounds. Here we show that a computational analog of this method, based on mapping proteins using small molecules as probes, can reliably reproduce druggability results from NMR-based screening, and can provide a more meaningful assessment in cases where the two approaches disagree. We apply the method to a large set of proteins. The results show that, because the method is based on the biophysics of binding rather than on empirical parameterization, meaningful information can be gained about classes of proteins and classes of compounds beyond those resembling validated targets and conventionally druglike ligands. In particular, the method identifies targets that, while not druggable by druglike compounds, may become druggable using compound classes such as macrocycles or other large molecules beyond the rule-of-five limit. PMID:26230724

Structural Basis for Assembly of the MnIV/FeIII Cofactor in the Class Ic Ribonucleotide Reductase from Chlamydia trachomatis‡

PubMed Central

Dassama, Laura M.K.; Krebs, Carsten; Bollinger, J. Martin; Rosenzweig, Amy C.; Boal, Amie K.

2013-01-01

The class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis (Ct) employs a MnIV/FeIII cofactor in each monomer of its β2 subunit to initiate nucleotide reduction. The cofactor forms by reaction of MnII/FeII-β2 with O2. Previously, in vitro cofactor assembly from apo β2 and divalent metal ions produced a mixture of two forms, with Mn in site 1 (MnIV/FeIII) or site 2 (FeIII/MnIV), of which the more active MnIV/FeIII product predominates. Here we have addressed the basis for metal site-selectivity by solving X-ray crystal structures of apo, MnII, and MnII/FeII complexes of Ct β2. A structure obtained anaerobically with equimolar MnII, FeII, and apo protein reveals exclusive incorporation of MnII in site 1 and FeII in site 2, in contrast to the more modest site-selectivity achieved previously. Site-specificity is controlled thermodynamically by the apo protein structure, as only minor adjustments of ligands occur upon metal binding. Additional structures imply that, by itself, MnII binds in either site. Together the structures are consistent with a model for in vitro cofactor assembly in which FeII specificity for site 2 drives assembly of the appropriately configured heterobimetallic center, provided that FeII is substoichiometric. This model suggests that use of an MnIV/FeIII cofactor in vivo could be an adaptation to FeII limitation. A 1.8 Å resolution model of the MnII/FeII-β2 complex reveals additional structural determinants for activation of the cofactor, including a proposed site for side-on (η2) addition of O2 to FeII and a short (3.2 Å) MnII-FeII interionic distance, promoting formation of the MnIV/FeIV activation intermediate. PMID:23924396

Chemical Space Mapping and Structure-Activity Analysis of the ChEMBL Antiviral Compound Set.

PubMed

Klimenko, Kyrylo; Marcou, Gilles; Horvath, Dragos; Varnek, Alexandre

2016-08-22

Curation, standardization and data fusion of the antiviral information present in the ChEMBL public database led to the definition of a robust data set, providing an association of antiviral compounds to seven broadly defined antiviral activity classes. Generative topographic mapping (GTM) subjected to evolutionary tuning was then used to produce maps of the antiviral chemical space, providing an optimal separation of compound families associated with the different antiviral classes. The ability to pinpoint the specific spots occupied (responsibility patterns) on a map by various classes of antiviral compounds opened the way for a GTM-supported search for privileged structural motifs, typical for each antiviral class. The privileged locations of antiviral classes were analyzed in order to highlight underlying privileged common structural motifs. Unlike in classical medicinal chemistry, where privileged structures are, almost always, predefined scaffolds, privileged structural motif detection based on GTM responsibility patterns has the decisive advantage of being able to automatically capture the nature ("resolution detail"-scaffold, detailed substructure, pharmacophore pattern, etc.) of the relevant structural motifs. Responsibility patterns were found to represent underlying structural motifs of various natures-from very fuzzy (groups of various "interchangeable" similar scaffolds), to the classical scenario in medicinal chemistry (underlying motif actually being the scaffold), to very precisely defined motifs (specifically substituted scaffolds).

Metabolomics and Ionomics of Potato Tuber Reveals an Influence of Cultivar and Market Class on Human Nutrients and Bioactive Compounds

PubMed Central

Chaparro, Jacqueline M.; Holm, David G.; Broeckling, Corey D.; Prenni, Jessica E.; Heuberger, Adam L.

2018-01-01

Potato (Solanum tuberosum L.) is an important global food crop that contains phytochemicals with demonstrated effects on human health. Understanding sources of chemical variation of potato tuber can inform breeding for improved health attributes of the cooked food. Here, a comprehensive metabolomics (UPLC- and GC-MS) and ionomics (ICP-MS) analysis of raw and cooked potato tuber was performed on 60 unique potato genotypes that span 5 market classes including russet, red, yellow, chip, and specialty potatoes. The analyses detected 2,656 compounds that included known bioactives (43 compounds), nutrients (42), lipids (76), and 23 metals. Most nutrients and bioactives were partially degraded during cooking (44 out of 85; 52%), however genotypes with high quantities of bioactives remained highest in the cooked tuber. Chemical variation was influenced by genotype and market class. Specifically, ~53% of all detected compounds from cooked potato varied among market class and 40% varied by genotype. The most notable metabolite profiles were observed in yellow-flesh potato which had higher levels of carotenoids and specialty potatoes which had the higher levels of chlorogenic acid as compared to the other market classes. Variation in several molecules with known association to health was observed among market classes and included vitamins (e.g., pyridoxal, ~2-fold variation), bioactives (e.g., chlorogenic acid, ~40-fold variation), medicinals (e.g., kukoamines, ~6-fold variation), and minerals (e.g., calcium, iron, molybdenum, ~2-fold variation). Furthermore, more metabolite variation was observed within market class than among market class (e.g., α-tocopherol, ~1-fold variation among market class vs. ~3-fold variation within market class). Taken together, the analysis characterized significant metabolite and mineral variation in raw and cooked potato tuber, and support the potential to breed new cultivars for improved health traits. PMID:29876353

Compounds affecting cholesterol absorption

NASA Technical Reports Server (NTRS)

Koo, Sung I. (Inventor); Noh, Sang K. (Inventor); Hua, Duy H. (Inventor)

2004-01-01

A class of novel compounds is described for use in affecting lymphatic absorption of cholesterol. Compounds of particular interest are defined by Formula I: ##STR1## or a pharmaceutically acceptable salt thereof.

Reactivity of nitrido complexes of ruthenium(VI), osmium(VI), and manganese(V) bearing Schiff base and simple anionic ligands.

PubMed

Man, Wai-Lun; Lam, William W Y; Lau, Tai-Chu

2014-02-18

Nitrido complexes (M≡N) may be key intermediates in chemical and biological nitrogen fixation and serve as useful reagents for nitrogenation of organic compounds. Osmium(VI) nitrido complexes bearing 2,2':6',2″-terpyridine (terpy), 2,2'-bipyridine (bpy), or hydrotris(1-pyrazolyl)borate anion (Tp) ligands are highly electrophilic: they can react with a variety of nucleophiles to generate novel osmium(IV)/(V) complexes. This Account describes our recent results studying the reactivity of nitridocomplexes of ruthenium(VI), osmium(VI), and manganese(V) that bear Schiff bases and other simple anionic ligands. We demonstrate that these nitrido complexes exhibit rich chemical reactivity. They react with various nucleophiles, activate C-H bonds, undergo N···N coupling, catalyze the oxidation of organic compounds, and show anticancer activities. Ruthenium(VI) nitrido complexes bearing Schiff base ligands, such as [Ru(VI)(N)(salchda)(CH3OH)](+) (salchda = N,N'-bis(salicylidene)o-cyclohexyldiamine dianion), are highly electrophilic. This complex reacts readily at ambient conditions with a variety of nucleophiles at rates that are much faster than similar reactions using Os(VI)≡N. This complex also carries out unique reactions, including the direct aziridination of alkenes, C-H bond activation of alkanes and C-N bond cleavage of anilines. The addition of ligands such as pyridine can enhance the reactivity of [Ru(VI)(N)(salchda)(CH3OH)](+). Therefore researchers can tune the reactivity of Ru≡N by adding a ligand L trans to nitride: L-Ru≡N. Moreover, the addition of various nucleophiles (Nu) to Ru(VI)≡N initially generate the ruthenium(IV) imido species Ru(IV)-N(Nu), a new class of hydrogen-atom transfer (HAT) reagents. Nucleophiles also readily add to coordinated Schiff base ligands in Os(VI)≡N and Ru(VI)≡N complexes. These additions are often stereospecific, suggesting that the nitrido ligand has a directing effect on the incoming nucleophile. M≡N is also a potential platform for the design of new oxidation catalysts. For example, [Os(VI)(N)Cl4](-) catalyzes the oxidation of alkanes by a variety of oxidants, and the addition of Lewis acids greatly accelerates these reactions. [Mn(V)(N)(CN)4]2(-) is another highly efficient oxidation catalyst, which facilitates the epoxidation of alkenes and the oxidation of alcohols to carbonyl compounds using H2O2. Finally, M≡N can potentially bind to and exert various effects on biomolecules. For example, a number of Os(VI)≡N complexes exhibit novel anticancer properties, which may be related to their ability to bind to DNA or other biomolecules.

Classifying environmental pollutants: Part 3. External validation of the classification system.

PubMed

Verhaar, H J; Solbé, J; Speksnijder, J; van Leeuwen, C J; Hermens, J L

2000-04-01

In order to validate a classification system for the prediction of the toxic effect concentrations of organic environmental pollutants to fish, all available fish acute toxicity data were retrieved from the ECETOC database, a database of quality-evaluated aquatic toxicity measurements created and maintained by the European Centre for the Ecotoxicology and Toxicology of Chemicals. The individual chemicals for which these data were available were classified according to the rulebase under consideration and predictions of effect concentrations or ranges of possible effect concentrations were generated. These predictions were compared to the actual toxicity data retrieved from the database. The results of this comparison show that generally, the classification system provides adequate predictions of either the aquatic toxicity (class 1) or the possible range of toxicity (other classes) of organic compounds. A slight underestimation of effect concentrations occurs for some highly water soluble, reactive chemicals with low log K(ow) values. On the other end of the scale, some compounds that are classified as belonging to a relatively toxic class appear to belong to the so-called baseline toxicity compounds. For some of these, additional classification rules are proposed. Furthermore, some groups of compounds cannot be classified, although they should be amenable to predictions. For these compounds additional research as to class membership and associated prediction rules is proposed.

25 CFR 547.12 - What are the minimum technical standards for downloading on a Class II gaming system?

Code of Federal Regulations, 2013 CFR

2013-04-01

... limited to software, files, data, and prize schedules. (2) Downloads must use secure methodologies that... date of the completion of the download; (iii) The Class II gaming system components to which software was downloaded; (iv) The version(s) of download package and any software downloaded. Logging of the...

25 CFR 547.12 - What are the minimum technical standards for downloading on a Class II gaming system?

Code of Federal Regulations, 2014 CFR

2014-04-01

... limited to software, files, data, and prize schedules. (2) Downloads must use secure methodologies that... date of the completion of the download; (iii) The Class II gaming system components to which software was downloaded; (iv) The version(s) of download package and any software downloaded. Logging of the...

Wisconsin Technical College System Board Equity Staff Development Workshops and Services--Phase IV. Final Report.

ERIC Educational Resources Information Center

Baldus, Lorayne

A staff development program on gender equity was conducted for personnel in Wisconsin's technical colleges using the train-the-trainer method. The training took two approaches: a class for college personnel and career challenge training for project directors of single parent and displaced homemaker grants. The inservice class resulted in increased…

76 FR 46838 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-03

... Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty... petition for reinstatement of oil and gas leases UTU-85226 and UTU-85230 lands in Uintah County, Utah, and...

77 FR 76069 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

... Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act, Quinex Energy Corporation timely filed a petition for reinstatement of oil and gas lease...

76 FR 66080 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act, Bro Energy LLC timely filed a petition for reinstatement of oil and gas lease UTU85562 lands...

The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization.

PubMed

Tokusumi, Yumiko; Tokusumi, Tsuyoshi; Schulz, Robert A

2017-05-13

In vertebrates, interaction between the nervous system and immune system is important to protect a challenged host from stress inputs from external sources. In this study, we demonstrate that sensory neurons are involved in the cellular immune response elicited by wasp infestation of Drosophila larvae. Multidendritic class IV neurons sense contacts from external stimuli and induce avoidance behaviors for host defense. Our findings show that inactivation of these sensory neurons impairs the cellular response against wasp parasitization. We also demonstrate that the nociception genes encoding the mechanosensory receptors Painless and Piezo, both expressed in class IV neurons, are essential for the normal cellular immune response to parasite challenge. Copyright © 2017. Published by Elsevier Inc.

[Evaluation of view points in forest park based on landscape sensitivity].

PubMed

Zhou, Rui; Li, Yue-hui; Hu, Yuan-man; Liu, Miao

2008-11-01

Based on topographical characteristics, five factors including comparative slope, comparative distance, mutual visibility, vision probability, and striking degree were chosen to assess the landscape sensitivity of major view points in Houshi National Forest Park. Spatial analysis in GIS was used for exploring the theory and method of landscape sensitivity of view points. The results showed that in the Park, there were totally 23 view points, but none of them reached up to class I. Among the 23 points, 10 were of class II , accounting for 43.5% of the total, 8 were of class III, accounting for 34.8%, and 5 were of classes IV and V, accounting for 21.7%. Around the view points of class II, the landscape should be strictly protected to maintain their natural feature; around the view points of class III, human-made landscape points should be developed according to the natural landscape feature, and wide tourism roads and small-size buildings could be constructed but the style of the buildings should be harmonious with surrounding nature landscape; while around the view points of classes IV and V, large-size multifunctional items and roads could be built to perfect the natural landscape. Through the multi-perspective and quantitative evaluation of landscape sensitivity, this study enriched the theory of landscape visual assessment and landscape apperception, and provided scientific base and direction for the planning and management of forest parks and other tourism areas.

Recalcitrant Carbonaceous Material: A Source of Electron Donors for Anaerobic Microbial Metabolisms in the Subsurface?

NASA Astrophysics Data System (ADS)

Nixon, S. L.; Montgomery, W.; Sephton, M. A.; Cockell, C. S.

2014-12-01

More than 90% of organic material on Earth resides in sedimentary rocks in the form of kerogens; fossilized organic matter formed through selective preservation of high molecular weight biopolymers under anoxic conditions. Despite its prevalence in the subsurface, the extent to which this material supports microbial metabolisms is unknown. Whilst aerobic microorganisms are known to derive energy from kerogens within shales, utilization in anaerobic microbial metabolisms that proliferate in the terrestrial subsurface, such as microbial iron reduction, has yet to be demonstrated. Data are presented from microbial growth experiments in which kerogens and shales were supplied as the sole electron donor source for microbial iron reduction by an enrichment culture. Four well-characterized kerogens samples (representative of Types I-IV, classified by starting material), and two shale samples, were assessed. Organic analysis was carried out to investigate major compound classes present in each starting material. Parallel experiments were conducted to test inhibition of microbial iron reduction in the presence of each material when the culture was supplied with a full redox couple. The results demonstrate that iron-reducing microorganisms in this culture were unable to use kerogens and shales as a source of electron donors for energy acquisition, despite the presence of compound classes known to support this metabolism. Furthermore, the presence of these materials was found to inhibit microbial iron reduction to varying degrees, with some samples leading to complete inhibition. These results suggest that recalcitrant carbonaceous material in the terrestrial subsurface is not available for microbial iron reduction and similar metabolisms, such as sulphate-reduction. Further research is needed to investigate the inhibition exerted by these materials, and to assess whether these findings apply to other microbial consortia. These results may have significant implications for the role of anaerobic microbial metabolisms in the subsurface terrestrial carbon cycle. Kerogens are chemically similar to organic material in carbonaceous chondrites. As such, further study may provide insight into the potential availability of organic compounds for microbial metabolisms operating in the subsurface of Mars.

SPECIATION OF SELENIUM AND ARSENIC COMPOUNDS BY CAPILLARY ELECTROPHORESIS WITH HYDRODYNAMICALLY MODIFIED ELECTROOSMOTIC FLOW AND ON-LINE REDUCTION OF SELENIUM(VI) TO SELENIUM(IV) WITH HYDRIDE GENERATION INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRIC DETECTION

EPA Science Inventory

Capillary electrophoresis (CE) with hydride generation inductively coupled plasma mass spectrometry was used to determine four arsenicals and two selenium species. Selenate (SeVI) was reduced on-line to selenite (SeIV') by mixing the CE effluent with concentrated HCl. A microporo...

The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

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

Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.

Background: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods: Three TNBCmore » cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. - Highlights: • TNBC cells are sensitive to sigma-2 receptor targeted drug conjugate SW IV-134. • MDA-MB-231 displayed the highest amount of sigma-2 receptors and corresponded well with sensitivity. • The sigma-2 receptor is a potential biomarker in TNBC for prognosis and therapy.« less

[Chemical constituents of Cocculus orbiculatus var. mollis root].

PubMed

Liao, Jing; Lei, Yu; Wang, Jian-Zhong

2014-02-01

To study the chemical constituents in the root of Cocculus orbiculatus var. mollis. The compounds were isolated by silica gel chromatography, their structures were established by spectroscopic methods. Eleven compounds were isolated and identified as wattisine A (I), O-methylcocsoline (II), (+) cocsoline (III), (+) cocsuline (IV), magnoflorine (V), sino-coculine (VI), isosinococuline (VII), (-) coclaurine (VIII), daucosterol (IX), beta-sitosterol (X) and 1-oleioyl-3-(9Z, 12Z-arachoyl) glycerol (XI). Compound I is isolated from this genus for the first time,and compound II - XI are isolated from this plant for the first time.

Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes.

PubMed

Madar, David J; Kopecka, Hana; Pireh, Daisy; Yong, Hong; Pei, Zhonghua; Li, Xiaofeng; Wiedeman, Paul E; Djuric, Stevan W; Von Geldern, Thomas W; Fickes, Michael G; Bhagavatula, Lakshmi; McDermott, Todd; Wittenberger, Steven; Richards, Steven J; Longenecker, Kenton L; Stewart, Kent D; Lubben, Thomas H; Ballaron, Stephen J; Stashko, Michael A; Long, Michelle A; Wells, Heidi; Zinker, Bradley A; Mika, Amanda K; Beno, David W A; Kempf-Grote, Anita J; Polakowski, James; Segreti, Jason; Reinhart, Glenn A; Fryer, Ryan M; Sham, Hing L; Trevillyan, James M

2006-10-19

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.

Prediction of future uniform milk prices in Florida federal milk marketing order 6 from milk futures markets.

PubMed

De Vries, A; Feleke, S

2008-12-01

This study assessed the accuracy of 3 methods that predict the uniform milk price in Federal Milk Marketing Order 6 (Florida). Predictions were made for 1 to 12 mo into the future. Data were from January 2003 to May 2007. The CURRENT method assumed that future uniform milk prices were equal to the last announced uniform milk price. The F+BASIS and F+UTIL methods were based on the milk futures markets because the futures prices reflect the market's expectation of the class III and class IV cash prices that are announced monthly by USDA. The F+BASIS method added an exponentially weighted moving average of the difference between the class III cash price and the historical uniform milk price (also known as basis) to the class III futures price. The F+UTIL method used the class III and class IV futures prices, the most recently announced butter price, and historical utilizations to predict the skim milk prices, butterfat prices, and utilizations in all 4 classes. Predictions of future utilizations were made with a Holt-Winters smoothing method. Federal Milk Marketing Order 6 had high class I utilization (85 +/- 4.8%). Mean and standard deviation of the class III and class IV cash prices were $13.39 +/- 2.40/cwt (1 cwt = 45.36 kg) and $12.06 +/- 1.80/cwt, respectively. The actual uniform price in Tampa, Florida, was $16.62 +/- 2.16/cwt. The basis was $3.23 +/- 1.23/cwt. The F+BASIS and F+UTIL predictions were generally too low during the period considered because the class III cash prices were greater than the corresponding class III futures prices. For the 1- to 6-mo-ahead predictions, the root of the mean squared prediction errors from the F+BASIS method were $1.12, $1.20, $1.55, $1.91, $2.16, and $2.34/cwt, respectively. The root of the mean squared prediction errors ranged from $2.50 to $2.73/cwt for predictions up to 12 mo ahead. Results from the F+UTIL method were similar. The accuracies of the F+BASIS and F+UTIL methods for all 12 fore-cast horizons were not significantly different. Application of the modified Mariano-Diebold tests showed that no method included all the information contained in the other methods. In conclusion, both F+BASIS and F+UTIL methods tended to more accurately predict the future uniform milk prices than the CURRENT method, but prediction errors could be substantial even a few months into the future. The majority of the prediction error was caused by the inefficiency of the futures markets to predict the class III cash prices.

Permanent work incapacity, mortality and survival without work incapacity among occupations and social classes: a cohort study of ageing men in Geneva.

PubMed

Gubéran, E; Usel, M

1998-12-01

The objective of this retrospective cohort study was to investigate the burden of disability and death in men, from middle age to age of retirement, among occupational groups and classes in Geneva. Men were included if they resided in the Canton of Geneva, were 45 years of age in 1970-1972, and were not receiving a disability pension at the start of the follow-up. The cohort of 5137 men was followed up for 20 years and linked to national registers of disability pension allowance and of causes of death. There was a steep upward trend in incidence of permanent work incapacity with lower social class for all causes as well as for the seven causes of disability studied. Compared with professional occupations (social class I), the relative risk (RR) of permanent work incapacity was 11.4 for partly skilled and unskilled occupations (class IV+V) (95% confidence interval [CI]: 5.2-28.0). The social class gradient in mortality was in the same direction as that in work incapacity although much less steep (RR class IV+V to class I = 1.6, 95% CI : 1.1-2.2). Survival without work incapacity at the time of the 65th birthday ranged from only 57% in construction workers and labourers to 89% in science and related professionals. Unemployment in Geneva was below 1.5% during almost all the study period. Medically-ascertained permanent work incapacity and survival without work incapacity have shown considerably greater socioeconomic differentials than the mortality differentials.

Evaluation of the ex vivo antimalarial activity of organotin (IV) ethylphenyldithiocarbamate on erythrocytes infected with Plasmodium berghei NK 65.

PubMed

Awang, Normah; Jumat, Hafizah; Ishak, Shafariatul Akmar; Kamaludin, Nurul Farahana

2014-06-01

Malaria is the most destructive and dangerous parasitic disease. The commonness of this disease is getting worse mainly due to the increasing resistance of Plasmodium falciparum against antimalarial drugs. Therefore, the search for new antimalarial drug is urgently needed. This study was carried out to evaluate the effects of dibutyltin (IV) ethylphenyldithiocarbamate (DBEP), diphenyltin (IV) ethylphenyldithiocarbamate (DPEP) and triphenyltin (IV) ethylphenyldithiocarbamate (TPEP) compounds as antimalarial agents. These compounds were evaluated against erythrocytes infected with Plasmodium berghei NK65 via ex vivo. Organotin (IV) ethylphenyldithiocarbamate, [R(n)Sn(C9H10NS2)(4-n)] with R = C4H9 and C6H5 for n = 2; R = C6H5 for n = 3 is chemically synthesised for its potential activities. pLDH assay was employed for determination of the concentration that inhibited 50% of the Plasmodium's activity (IC50) after 24 h treatment at concentration range of 10-0.0000001 mg mL(-1). Plasmodium berghei NK65 was cultured in vitro to determine the different morphology of trophozoite and schizont. Only DPEP and TPEP compounds have antimalarial activity towards P. berghei NK65 at IC50 0.094±0.011 and 0.892±0.088 mg mL(-1), respectively. The IC50 of DPEP and TPEP were lowest at 30% parasitemia with IC50 0.001±0.00009 and 0.0009±0.0001 mg mL(-1), respectively. In vitro culture showed that TPEP was effective towards P. berghei NK65 in trophozoite and schizont morphology with IC50 0.0001±0.00005 and 0.00009±0.00003 μg mL(-1), respectively. In conclusion, DPEP and TPEP have antimalarial effect on erythrocytes infected with P. berghei NK65 and have potential as antimalarial and schizonticidal agents.

Computational and experimental study of the interactions between ionic liquids and volatile organic compounds.

PubMed

Gao, Tingting; Andino, Jean M; Alvarez-Idaboy, J Raul

2010-09-07

Computational chemistry calculations were performed to investigate the interactions of ionic liquids with different classes of volatile organic compounds (VOCs), including alcohols, aldehydes, ketones, alkanes, alkenes, alkynes and aromatic compounds. At least one VOC was studied to represent each class. Initially, 1-butyl-3-methylimindazolium chloride (abbreviated as C(4)mimCl) was used as the test ionic liquid compound. Calculated interaction lengths between atoms in the ionic liquid and the VOC tested as well as thermodynamic data suggest that C(4)mimCl preferentially interacts with alcohols as compared to other classes of volatile organic compounds. The interactions of methanol with different kinds of ionic liquids, specifically 1-butyl-3-methylimidazolium bromine (C(4)mimBr) and 1-butyl-3-methylimidazolium tetrafluoroborate (C(4)mimBF(4)) were also studied. In comparing C(4)mimCl, C(4)mimBr, and C(4)mimBF(4), the computational results suggest that C(4)mimCl is more likely to interact with methanol. Laboratory experiments were performed to provide further evidence for the interaction between C(4)mimCl and different classes of VOCs. Fourier transform infrared spectroscopy was used to probe the ionic liquid surface before and after exposure to the VOCs that were tested. New spectral features were detected after exposure of C(4)mimCl to various alcohols. The new features are characteristic of the alcohols tested. No new IR features were detected after exposure of the C(4)mimCl to the aldehyde, ketone, alkane, alkene, alkyne or aromatic compounds studied. In addition, after exposing the C(4)mimCl to a multi-component mixture of various classes of compounds (including an alcohol), the only new peaks that were detected were characteristic of the alcohol that was tested. These experimental results demonstrated that C(4)mimCl is selective to alcohols, even in complex mixtures. The findings in this work provide information for future gas-phase alcohol sensor design.

Assessment of feasibility and efficacy of Class IV laser therapy for postoperative pain relief in off-pump coronary artery bypass surgery patients: A pilot study

PubMed Central

Karlekar, Anil; Bharati, Saswata; Saxena, Ravindra; Mehta, Kanchan

2015-01-01

Background: Laser therapy, for its established analgesic properties with minimal side effects, has been used for the treatment of chronic pain. However, it has not been used for the treatment of acute postoperative pain. This pilot study was designed to assess the feasibility and efficacy of Class IV laser on postoperative pain relief following off-pump coronary artery bypass graft (OPCABG) surgery, as a component of multimodal analgesia (MMA) technique. Methods: This open observational prospective study comprised of 100 adult patients (84 male, 16 female) who underwent OPCABG through sternotomy. For postoperative analgesia, they were subjected to laser therapy subjected to laser therapy in addition to the standard institutional pain management protocol comprising of IV infusion/bolus of tramadol and paracetamol and fentanyl bolus as rescue analgesic. Pain intensity was measured by Verbal Rating Scale (VRS). The laser therapy was scheduled as once a day regime for three consecutive postoperative days (PODs) starting on POD 1, 30 min following tracheal extubation. The subsequent laser applications were also scheduled at the same time of the day as on day 1 if VRS was ≥5. 10 W Class IV laser was applied over 150 cm2 sternal wound area for 150 s. VRS was used to assess pain severity and was recorded for statistical analysis using Friedman Test. Results: The mean (standard deviation [SD]) VRS of all the 100 patients just before application of the first dose of laser was 7.31 (0.94) while on MMT; the same fell to 4.0 (1.279) and 3.40 (2.697) at 1 h and 24 h respectively following first dose of laser. The change of VRS over first 24 h among all the 100 patients was statistically significant (P = 0.000). Laser was re-applied in 40 patients whose VRS was ≥5 (mean [SD] – 6.38 [0.868]) at 24th h. After receiving the 2nd dose of laser the VRS scores fell significantly (P = 0.000) and became 0 at 54th h. No patients required 3rd dose of the laser. No patient required rescue analgesic while on laser therapy. Conclusion: Class IV laser can be an effective technique for postoperative analgesia following OPCABG surgery through sternotomy when included as a component of MMA technique. PMID:26139735

PEALD grown high-k ZrO{sub 2} thin films on SiC group IV compound semiconductor

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

Khairnar, A. G., E-mail: agkhairnar@gmail.com; Patil, V. S.; Agrawal, K. S.

The study of ZrO{sub 2} thin films on SiC group IV compound semiconductor has been studied as a high mobility substrates. The ZrO{sub 2} thin films were deposited using the Plasma Enhanced Atomic Layer Deposition System. The thickness of the thin films were measured using ellipsometer and found to be 5.47 nm. The deposited ZrO{sub 2} thin films were post deposition annealed in rapid thermal annealing chamber at temperature of 400°Ð¡. The atomic force microscopy and X-гау photoelectron spectroscopy has been carried out to study the surface topography, roughness and chemical composition of thin film, respectively.

Discovery of Rigidified α,β-Unsaturated Imines as New Resistance-breaking Insecticides for Malaria Vector Control.

PubMed

Arlt, Alexander; Böhnke, Niels; Horstmann, Sebastian; Vermeer, Arnoldus W P; Werner, Stefan; Velten, Robert

2016-10-01

During our continuous search for new resistance-breaking insecticides applicable to malaria vector control, a new class of α,β-unsaturated imines was identified by applying the principle of conformational rigidification as a powerful tool for compound optimisation. Herein we describe the successful synthesis of these compounds and their biological test results. Our lead compound 16 from this insecticidal class outperforms market standards, notably for the control of mosquito strains that exhibit either metabolic or target-site resistance to these established insecticides. In our model system for insecticide-treated mosquito nets the compound reveals long-lasting efficacy for up to several months.

Synchroton and Simulations Techniques Applied to Problems in Materials Science: Catalysts and Azul Maya Pigments

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

Chianelli, R.

2005-01-12

Development of synchrotron techniques for the determination of the structure of disordered, amorphous and surface materials has exploded over the past twenty years due to the increasing availability of high flux synchrotron radiation and the continuing development of increasingly powerful synchrotron techniques. These techniques are available to materials scientists who are not necessarily synchrotron scientists through interaction with effective user communities that exist at synchrotrons such as the Stanford Synchrotron Radiation Laboratory (SSRL). In this article we review the application of multiple synchrotron characterization techniques to two classes of materials defined as ''surface compounds.'' One class of surface compounds aremore » materials like MoS{sub 2-x}C{sub x} that are widely used petroleum catalysts used to improve the environmental properties of transportation fuels. These compounds may be viewed as ''sulfide supported carbides'' in their catalytically active states. The second class of ''surface compounds'' is the ''Maya Blue'' pigments that are based on technology created by the ancient Maya. These compounds are organic/inorganic ''surface complexes'' consisting of the dye indigo and palygorskite, a common clay. The identification of both surface compounds relies on the application of synchrotron techniques as described in this report.« less

Social class inequalities in the use of and access to health services in Catalonia, Spain: what is the influence of supplemental private health insurance?

PubMed

Borrell, C; Fernandez, E; Schiaffino, A; Benach, J; Rajmil, L; Villalbi, J R; Segura, A

2001-04-01

To analyse social class inequalities in the access to and utilization of health services in Catalonia (Spain), and the influence of having private health insurance supplementing the National Health System (NHS) coverage. 1994 Catalan Health Interview Survey, a cross-sectional survey conducted in 1994. Catalonia (Spain). The participants were a representative sample of people aged over 14 years from the non-institutionalized population of Catalonia (n = 12,245). Health services utilization, perceived health, having only NHS or NHS plus a private health insurance, and social class. Although one-quarter of the population of Catalonia had a supplemental private health insurance, percentages were very different according to social class, ranging from almost 50% for classes I and II to 16% for classes IV and V in both sexes. No inequalities by social class were observed for the utilization of non-preventive health care services (consultation with a health professional in the last 2 weeks and hospitalization in the last year) among persons with poor self-perceived health status, i.e. those in most need. However, social inequalities still remain in the use of health services provided only partially by the NHS, and when characteristics of last consultation are taken into account. Subjects who paid for a private service waited an average of 18.8 minutes less than those attending the NHS. Within the NHS, social classes IV and V waited longer (35.5 minutes) than social classes I and II (28.4 minutes). The NHS in Catalonia, Spain, has reduced inequalities in the use of health services. Social inequalities remain in the use of those health services provided only partially by the NHS.

Synthesis, molecular structure and magnetic properties of a rhenium(IV) compound with catechol

NASA Astrophysics Data System (ADS)

Cuevas, A.; Geis, L.; Pintos, V.; Chiozzone, R.; Sanchíz, J.; Hummert, M.; Schumann, H.; Kremer, C.

2009-03-01

A novel Re(IV) complex containing catechol as ligand has been prepared and characterized. The crystal structure of (HNEt 3)(NBu 4)[ReCl 4(cat)]·H 2cat was determined. The rhenium ion presents a distorted octahedral geometry, being bonded to a bidentate catecholate group and four chloride anions. The magnetic properties of the complex were studied, a /2 D/ (the energy gap between ±3/2 and ±1/2 Kramers doublets) value of 190(10) cm -1. This is the largest /2 D/ value reported for Re(IV) up to now.

Dynein-Dependent Transport of nanos RNA in Drosophila Sensory Neurons Requires Rumpelstiltskin and the Germ Plasm Organizer Oskar

PubMed Central

Xu, Xin; Brechbiel, Jillian L.

2013-01-01

Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts. PMID:24027279

Dynein-dependent transport of nanos RNA in Drosophila sensory neurons requires Rumpelstiltskin and the germ plasm organizer Oskar.

PubMed

Xu, Xin; Brechbiel, Jillian L; Gavis, Elizabeth R

2013-09-11

Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts.

Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators

PubMed Central

Zhang, Hai-Chun; Hu, Rong-Fei; Zhu, Ting; Tong, Ling; Zhang, Qiu-Qin

2016-01-01

AIM: To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators. METHODS: One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve. RESULTS: LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83.3%). CONCLUSION: The diagnostic value of PBC cirrhosis degree in liver cirrhosis degree assessment by ARFI combined with the four indicators of serum liver fibrosis is of satisfactory effectiveness and has important clinical application value. PMID:27298571

49 CFR 232.205 - Class I brake test-initial terminal inspection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... § 232.205 Class I brake test-initial terminal inspection. (a) Each train and each car in the train shall... tested solid block of cars to the train; (iii) Changing motive power; (iv) Removing or changing the... conduct a brake test pursuant to § 232.209 on those cars added to the train. (B) [Reserved] (b) Except as...

Assessment of the Treatability of Toxic Organics by Overland Flow,

DTIC Science & Technology

1983-01-01

Tab’ I . Occunrence of organic chemsicals in household products . (After Hathaway 1980.1 Product Classter of organ iCs Product Classe of organirs...volatilization. the various classes of organics and their presence in Another important property of organic chemicals household products are given in Table 1...23 iv TABLES Table Page I. Occurrence of organic chemicals in household

78 FR 24334 - Milk in the Northeast and Other Marketing Areas; Order Amending the Orders

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

...) allowances for cheese, butter, nonfat dry milk (NFDM) and dry whey contained in the Class III and Class IV....1715 per pound); NFDM ($0.1678 per pound); and dry whey ($0.1991 per pound). In addition, the butterfat... dry whey continues to be $0.1991 per pound (initially increased from $0.1956 per pound). Finally, the...

40 CFR 144.28 - Requirements for Class I, II, and III wells authorized by rule.

Code of Federal Regulations, 2010 CFR

2010-07-01

... proposed test or measurement to be made; (D) The amount, size, and location (by depth) of casing to be left..., internal pressure, and axial loading; (iv) Hole size; (v) Size and grade of all casing strings; and (vi... Class III wells the owner or operator shall provide to the Director a qualitative analysis and ranges in...

40 CFR 90.410 - Engine test cycle.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Engine test cycle. 90.410 Section 90... Procedures § 90.410 Engine test cycle. (a) Follow the appropriate 6-mode test cycle for Class I, I-B and II engines and 2-mode test cycle for Class I-A, III, IV, and V engines when testing spark-ignition engines...

Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha.

PubMed

Corral, L G; Haslett, P A; Muller, G W; Chen, R; Wong, L M; Ocampo, C J; Patterson, R T; Stirling, D I; Kaplan, G

1999-07-01

TNF-alpha mediates both protective and detrimental manifestations of the host immune response. Our previous work has shown thalidomide to be a relatively selective inhibitor of TNF-alpha production in vivo and in vitro. Additionally, we have recently reported that thalidomide exerts a costimulatory effect on T cell responses. To develop thalidomide analogues with increased anti-TNF-alpha activity and reduced or absent toxicities, novel TNF-alpha inhibitors were designed and synthesized. When a selected group of these compounds was examined for their immunomodulatory activities, different patterns of cytokine modulation were revealed. The tested compounds segregated into two distinct classes: one class of compounds, shown to be potent phosphodiesterase 4 inhibitors, inhibited TNF-alpha production, increased IL-10 production by LPS-induced PBMC, and had little effect on T cell activation; the other class of compounds, similar to thalidomide, were not phosphodiesterase 4 inhibitors and markedly stimulated T cell proliferation and IL-2 and IFN-gamma production. These compounds inhibited TNF-alpha, IL-1beta, and IL-6 and greatly increased IL-10 production by LPS-induced PBMC. Similar to thalidomide, the effect of these agents on IL-12 production was dichotomous; IL-12 was inhibited when PBMC were stimulated with LPS but increased when cells were stimulated by cross-linking the TCR. The latter effect was associated with increased T cell CD40 ligand expression. The distinct immunomodulatory activities of these classes of thalidomide analogues may potentially allow them to be used in the clinic for the treatment of different immunopathological disorders.

Imido-pyridine Ti(IV) compounds: synthesis of unusual imido-amido heterobimetallic derivatives.

PubMed

Pedrosa, Sergio; Vidal, Fernando; Lee, Lucia Myongwon; Vargas-Baca, Ignacio; Gómez-Sal, Pilar; Mosquera, Marta E G

2015-06-28

The reaction of lithiated picolines and [TiCl3(η(5)-C5Me5)] leads to several bridging or terminal imido compounds, each of which can be selectively formed by controlling the stoichiometry and temperature. Specifically, the dinuclear imido-bridged [TiCl(η(5)-C5Me5)(μ-NR)]2 (1a, NR = 2-imido-3-picoline; 1b, NR = 2-imido-5-picoline) species and the unusual Ti-Li imido-amido heterobimetallic complex [{Li(THF)}{Ti(η(5)-C5Me5)(NR)(NHR)2}] (2a, NR = 2-imido-3-picoline; 2b, NR = 2-imido-5-picoline) were isolated. Compounds 2 are in effect the first structurally characterized examples of titanium(IV) coordinated to terminal imido-pyridines. DFT-D calculations for 2a denote a multiple bond character between titanium and the imido ligand and a strong polarization of the electron density by the alkali cation in spite of the lack of intermetallic bonding.

Syntheses and characterization of one-dimensional alkali metal antimony(III) thiostannates(IV), A{sub 2}Sb{sub 2}Sn{sub 3}S{sub 10} (A=K, Rb, Cs)

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

Yohannan, Jinu P.; Vidyasagar, Kanamaluru, E-mail: kvsagar@iitm.ac.in

2015-01-15

Three new isostructural quaternary antimony(III) thiostannates(IV), A{sub 2}Sb{sub 2}Sn{sub 3}S{sub 10} (A=K, Rb, Cs) have been synthesized by using alkali metal thiosulfate flux and structurally characterized by X-ray diffraction. Their structures contain A{sup +} ions around the [Sb{sub 2}Sn{sub 3}S{sub 10}]{sup 2−} chains, which are built from SbS{sub 3} pyramids, SnS{sub 6} octahedra and SnS{sub 4} tetrahedra. Raman and Mössbauer spectroscopic measurements corroborate the oxidation states and coordination environments of Sb(III) and Sn(IV). All three compounds are wide band gap semiconductors. Potassium compound undergoes partial exchange with strontium, cadmium and lead ions. - Graphical abstract: Syntheses, crystal structure, spectroscopic andmore » partial ion-exchange studies of new one-dimensional alkali metal antimony(III) thiostannates(IV), A{sub 2}Sb{sub 2}Sn{sub 3}S{sub 10} (A=K, Rb, Cs) are described. - Highlights: • Syntheses of new alkali metal antimony(III) thiostannates(IV), A{sub 2}Sb{sub 2}Sn{sub 3}S{sub 10} (A=K, Rb, Cs). • Wide band gap semiconductors with one-dimensional structure. • Topotactic partial exchange of K{sup +} ions of K{sub 2}Sb{sub 2}Sn{sub 3}S{sub 10} with Sr{sup 2+}, Cd{sup 2+} and Pb{sup 2+} ions.« less

Di-pentyl phthalate dosing during sexual differentiation disrupts fetal testis function and postnatal development of the male Sprague dawley rat with greater relative potency than other phthalates

EPA Science Inventory

Phthalate esters (PEs) constitute a large class of plasticizer compounds that are widely used for many consumer product applications. Ten or more members of the PE class of compounds have been shown to induce male fetal endocrine toxicity and postnatal reproductive malformations ...

Identification and hit-to-lead optimization of a novel class of CB1 antagonists.

PubMed

Letourneau, Jeffrey J; Jokiel, Patrick; Olson, John; Riviello, Christopher M; Ho, Koc-Kan; McAleer, Lihong; Yang, Jingchun; Swanson, Robert N; Baker, James; Cowley, Phillip; Edwards, Darren; Ward, Nick; Ohlmeyer, Michael H J; Webb, Maria L

2010-09-15

The discovery, synthesis and preliminary structure-activity relationships (SARs) of a novel class of CB1 antagonists is described. Initial optimization of benzimidazole-based screening hit 4 led to the identification of 'inverted' indole-based lead compound 18c with improved properties versus compound 4 including reduced AlogP, improved microsomal stability and improved aqueous solubility. Compound 18c demonstrates in vivo CB1 antagonist efficacy (CB1 agonist induced hypothermia model) and is orally bioavailable in rat. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes

PubMed Central

Darwich, Adam S; Henderson, Kathryn; Burgin, Angela; Ward, Nicola; Whittam, Janet; Ammori, Basil J; Ashcroft, Darren M; Rostami-Hodjegan, Amin

2012-01-01

AIMS To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. METHODS A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. RESULTS No significant difference in the ‘post/pre surgery oral drug exposure ratio’ (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as ‘solubility limited’ displayed an overall reduction as compared with ‘freely soluble’ compounds, as well as an unaltered and increased ppR. CONCLUSION Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance. PMID:22463107

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

Varga, Tamas

Despite the fact that all chemical bonds expand on heating, a small class of materials shrinks when heated. These, so called negative thermal expansion (NTE) materials, are a unique class of materials with some exotic properties. The present chapter offers insight into the structural aspects of pressure- (or temperature-) induced phase transformations, and the energetics of those changes in these fascinating materials, in particular NTE compound cubic ZrW2O8, orthorhombic Sc2W3O12 and Sc2Mo3O12, as well as other members of the 'scandium tungstate family'. In subsequent sections, (i) combined in situ high-pressure synchrotron XRD and XAS studies of NTE material ZrW2O8; (ii)more » an in situ high-pressure synchrotron XRD study of Sc2W3O12, Sc2Mo3O12, and Al2W3O12; and (iii) thermochemical studies of the above materials are presented and discussed. In all of these studies, chemical bonds change, sometimes break and new ones form. Correlations between structure, chemistry, and energetics are revealed. It is also shown that (iv) NTE materials are good candidates as precursors to make novel solid state materials, such as the conducting Sc0.67WO4, using high-pressure, high-temperature synthesis, through modification of bonding and electronic structure, and thus provide vast opportunities for scientific exploration.« less

New and old roles of the peripheral and brain renin-angiotensin-aldosterone system (RAAS): Focus on cardiovascular and neurological diseases.

PubMed

Mascolo, A; Sessa, M; Scavone, C; De Angelis, A; Vitale, C; Berrino, L; Rossi, F; Rosano, G; Capuano, A

2017-01-15

It is commonly accepted that the renin-angiotensin-aldosterone system (RAAS) is a cardiovascular circulating hormonal system that plays also an important role in the modulation of several patterns in the brain. The pathway of the RAAS can be divided into two classes: the traditional pathway of RAAS, also named classic RAAS, and the non-classic RAAS. Both pathways play a role in both cardiovascular and neurological diseases through a peripheral or central control. In this regard, renewed interest is growing in the last years for the consideration that the brain RAAS could represent a new important therapeutic target to regulate not only the blood pressure via central nervous control, but also neurological diseases. However, the development of compounds able to cross the blood-brain barrier and to act on the brain RAAS is challenging, especially if the metabolic stability and the half-life are taken into consideration. To date, two drug classes (aminopeptidase type A inhibitors and angiotensin IV analogues) acting on the brain RAAS are in development in pre-clinical or clinical stages. In this article, we will present an overview of the biological functions played by peripheral and brain classic and non-classic pathways of the RAAS in several clinical conditions, focusing on the brain RAAS and on the new pharmacological targets of the RAAS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Phenolic Compounds from Fermented Berry Beverages Modulated Gene and Protein Expression To Increase Insulin Secretion from Pancreatic β-Cells in Vitro.

PubMed

Johnson, Michelle H; de Mejia, Elvira Gonzalez

2016-03-30

Berries are a rich source of bioactive phenolic compounds that are able to bind and inhibit the enzyme dipeptidyl peptidase-IV (DPP-IV), a current target for type-2 diabetes therapy. The objectives were to determine the role of berry phenolic compounds to modulate incretin-cleaving DPP-IV and its substrate glucagon-like peptide-1 (GLP-1), insulin secretion from pancreatic β-cells, and genes and proteins involved in the insulin secretion pathway using cell culture. Anthocyanins (ANC) from 50% blueberry-50% blackberry (Blu-Bla) and 100% blackberry (Bla) fermented beverages at 50 μM cyanidin-3-glucoside equivalents increased (p < 0.05) glucose-stimulated insulin secretion from pancreatic β-cells (iNS-1E) both when applied directly and following simulated absorption through Caco-2 cells (by 233 and 100 μIU insulin/mL, respectively). ANC 50%Blu-Bla and ANC 100%Bla upregulated the gene for incretin hormone GLP-1 (fold-change 3.0 ± 1.4 and 2.0 ± 0.3, respectively) and genes in the insulin secretory pathway including insulin-like growth factor 1 receptor (iGF1R, 2.3 ± 0.6 and 1.6 ± 0.3, respectively), and increased (p < 0.05) the protein expression of insulin-like growth factor 2 (IGF-II), insulin-like growth factor binding proteins (IGFBP-2 and 3), and vascular endothelial growth factor (VEGF) in iNS-1E cells. Taken together, anthocyanins, predominantly delphinidin-3-arabinoside, from fermented berry beverages have the potential to modulate DPP-IV and its substrate GLP-1, to increase insulin secretion, and to upregulate expression of mRNA of insulin-receptor associated genes and proteins in pancreatic β-cells.

A Perturbation Based Decomposition of Compound-Evoked Potentials for Characterization of Nerve Fiber Size Distributions.

PubMed

Szlavik, Robert B

2016-02-01

The characterization of peripheral nerve fiber distributions, in terms of diameter or velocity, is of clinical significance because information associated with these distributions can be utilized in the differential diagnosis of peripheral neuropathies. Electro-diagnostic techniques can be applied to the investigation of peripheral neuropathies and can yield valuable diagnostic information while being minimally invasive. Nerve conduction velocity studies are single parameter tests that yield no detailed information regarding the characteristics of the population of nerve fibers that contribute to the compound-evoked potential. Decomposition of the compound-evoked potential, such that the velocity or diameter distribution of the contributing nerve fibers may be determined, is necessary if information regarding the population of contributing nerve fibers is to be ascertained from the electro-diagnostic study. In this work, a perturbation-based decomposition of compound-evoked potentials is proposed that facilitates determination of the fiber diameter distribution associated with the compound-evoked potential. The decomposition is based on representing the single fiber-evoked potential, associated with each diameter class, as being perturbed by contributions, of varying degree, from all the other diameter class single fiber-evoked potentials. The resultant estimator of the contributing nerve fiber diameter distribution is valid for relatively large separations in diameter classes. It is also useful in situations where the separation between diameter classes is small and the concomitant single fiber-evoked potentials are not orthogonal.

In vitro and in vivo antitumor effects of the VO-chrysin complex on a new three-dimensional osteosarcoma spheroids model and a xenograft tumor in mice.

PubMed

León, Ignacio E; Cadavid-Vargas, Juan F; Resasco, Agustina; Maschi, Fabricio; Ayala, Miguel A; Carbone, Cecilia; Etcheverry, Susana B

2016-12-01

Osteosarcoma (OS) is the most common primary tumor of bone, occurring predominantly in the second decade of life. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for patients with localized disease. Vanadium is an ultra-trace element that after being absorbed accumulates in bone. Besides, vanadium compounds have been studied during recent years to be considered as representative of a new class of non-platinum antitumor agents. Moreover, flavonoids are a wide family of polyphenolic compounds that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, the in vitro and in vivo effects of an oxidovanadium(IV) complex with the flavonoid chrysin on the new 3D human osteosarcoma and xenograft osteosarcoma mice models. The pharmacological results show that VOchrys inhibited the cell viability affecting the shape and volume of the spheroids and VOchrys suppressed MG-63 tumor growth in the nude mice without inducing toxicity and side effects. As a whole, the results presented herein demonstrate that the antitumor action of the complex was very promissory on human osteosarcoma models, whereby suggesting that VOchrys is a potentially good candidate for future use in alternative antitumor treatments.

Artificial ribonucleases inactivate a wide range of viruses using their ribonuclease, membranolytic, and chaotropic-like activities.

PubMed

Fedorova, Antonina A; Goncharova, Elena P; Koroleva, Lyudmila S; Burakova, Ekatherina A; Ryabchikova, Elena I; Bichenkova, Elena V; Silnikov, Vladimir N; Vlassov, Valentin V; Zenkova, Marina A

2016-09-01

Artificial ribonucleases (aRNases) are small compounds catalysing RNA cleavage. Recently we demonstrated that aRNases readily inactivate various viruses in vitro. Here, for three series of aRNases (1,4-diazabicyclo [2.2.2]octane-based and peptide-like compounds) we show that apart from ribonuclease activity the aRNases display chaotropic-like and membranolytic activities. The levels of membranolytic and chaotropic-like activities correlate well with the efficiency of various viruses inactivation (enveloped, non-enveloped, RNA-, DNA-containing). We evaluated the impact of these activities on the efficiency of virus inactivation and found: i) the synergism between membranolytic and chaotropic-like activities is sufficient for the inactivation of enveloped viruses (influenza A, encephalitis, vaccinia viruses) for 1,4-diazabicyclo [2.2.2]octane based aRNases, ii) the inactivation of non-enveloped viruses (encephalomyocarditis, acute bee paralysis viruses) is totally dependent on the synergism of chaotropic-like and ribonuclease activities, iii) ribonuclease activity plays a leading role in the inactivation of RNA viruses by aRNases Dp12F6, Dtr12 and K-D-1, iv) peptide-like aRNases (L2-3, K-2) being effective virus killers have a more specific mode of action. Obtained results clearly demonstrate that aRNases represent a new class of broad-spectrum virus-inactivating agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Antiproliferative and apoptosis-inducing activity of an oxidovanadium(IV) complex with the flavonoid silibinin against osteosarcoma cells.

PubMed

Leon, I E; Porro, V; Di Virgilio, A L; Naso, L G; Williams, P A M; Bollati-Fogolín, M; Etcheverry, S B

2014-01-01

Flavonoids are a large family of polyphenolic compounds synthesized by plants. They display interesting biological effects mainly related to their antioxidant properties. On the other hand, vanadium compounds also exhibit different biological and pharmacological effects in cell culture and in animal models. Since coordination of ligands to metals can improve or change the pharmacological properties, we report herein, for the first time, a detailed study of the mechanisms of action of an oxidovanadium(IV) complex with the flavonoid silibinin, Na2[VO(silibinin)2]·6H2O (VOsil), in a model of the human osteosarcoma derived cell line MG-63. The complex inhibited the viability of osteosarcoma cells in a dose-dependent manner with a greater potency than that of silibinin and oxidovanadium(IV) (p < 0.01), demonstrating the benefit of complexation. Cytotoxicity and genotoxicity studies also showed a concentration effect for VOsil. The increase in the levels of reactive oxygen species and the decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of the complex. Besides, the complex caused cell cycle arrest and activated caspase 3, triggering apoptosis as determined by flow cytometry. As a whole, these results show the main mechanisms of the deleterious effects of VOsil in the osteosarcoma cell line, demonstrating that this complex is a promising compound for cancer treatments.

Phosphorescent heterobimetallic complexes involving platinum(iv) and rhenium(vii) centers connected by an unsupported μ-oxido bridge.

PubMed

Molaee, Hajar; Nabavizadeh, S Masoud; Jamshidi, Mahboubeh; Vilsmeier, Max; Pfitzner, Arno; Samandar Sangari, Mozhgan

2017-11-28

Heterobimetallic compounds [(C^N)LMe 2 Pt(μ-O)ReO 3 ] (C^N = ppy, L = PPh 3 , 2a; C^N = ppy, L = PMePh 2 , 2b; C^N = bhq, L = PPh 3 , 2c; C^N = bhq, L = PMePh 2 , 2d) containing a discrete unsupported Pt(iv)-O-Re(vii) bridge have been synthesized through a targeted synthesis route. The compounds have been prepared by a single-pot synthesis in which the Pt(iv) precursor [PtMe 2 I(C^N)L] complexes are allowed to react easily with AgReO 4 in which the iodide ligand of the starting Pt(iv) complex is replaced by an ReO 4 - anion. In these Pt-O-Re complexes, the Pt(iv) centers have an octahedral geometry, completed by a cyclometalated bidentate ligand (C^N), two methyl groups and a phosphine ligand, while the Re(vii) centers have a tetrahedral geometry. Elemental analysis, single crystal X-ray diffraction analysis and multinuclear NMR spectroscopy are used to establish their identities. The new complexes exhibit phosphorescence emission in the solid and solution states at 298 and 77 K, which is an uncommon property of platinum complexes with an oxidation state of +4. According to DFT calculations, we found that this emission behavior in the new complexes originates from ligand centered 3 LC (C^N) character with a slight amount of metal to ligand charge transfer ( 3 MLCT). The solid-state emission data of the corresponding cycloplatinated(iv) precursor complexes [PtMe 2 I(C^N)L], 1a-1d, pointed out that the replacement of I - by an ReO 4 - anion helps enhancing the emission efficiency besides shifting the emission wavelengths.

Synthesis, spectral characterization and biological studies of some organotin(IV) complexes of L-proline, trans-hydroxy- L-proline and L-glutamine

NASA Astrophysics Data System (ADS)

Nath, Mala; Jairath, Ruchi; Eng, George; Song, Xueqing; Kumar, Ashok

2005-12-01

New organotin(IV) complexes of the general formula R 3Sn(L) (where R = Me, n-Bu and HL = L-proline; R = Me, Ph and HL = trans-hydroxy- L-proline and L-glutamine) and R 2Sn(L) 2 (where R = n-Bu, Ph and HL = L-proline; R = Ph, HL = trans-hydroxy- L-proline) have been synthesized by the reaction of R nSnCl 4- n (where n = 2 or 3) with sodium salt of the amino acid (HL). n-Bu 2Sn(Pro) 2 was synthesized by the reaction of n-Bu 2SnO with L-proline under azeotropic removal of water. The bonding and coordination behavior in these complexes have been discussed on the basis of IR and 119Sn Mössbauer spectroscopic studies in the solid-state. Their coordination behavior in solution has been discussed with the help of multinuclear ( 1H, 13C and 119Sn) NMR spectral studies. The 119Sn Mössbauer and IR studies indicate that L-proline and trans-hydroxy- L-proline show similar coordination behavior towards organotin(IV) compounds. Pentacoordinate trigonal-bipyramidal and hexacoordinate octahedral structures, respectively, have been proposed for the tri- and diorganotin(IV) complexes of L-proline and trans-hydroxy- L-proline, in which the carboxylate group acts as bidentate group. L-Glutamine shows different coordination behavior towards organotin(IV) compounds, it acts as monoanionic bidentate ligand coordinating through carboxylate and amino group. The triorganotin(IV) complexes of L-glutamine have been proposed to have trigonal-bipyramidal environment around tin. The newly synthesized complexes have been tested for their antiinflammatory and cardiovascular activities. Their LD 50 values are >1000 mg kg -1.

Predicting DPP-IV inhibitors with machine learning approaches

NASA Astrophysics Data System (ADS)

Cai, Jie; Li, Chanjuan; Liu, Zhihong; Du, Jiewen; Ye, Jiming; Gu, Qiong; Xu, Jun

2017-04-01

Dipeptidyl peptidase IV (DPP-IV) is a promising Type 2 diabetes mellitus (T2DM) drug target. DPP-IV inhibitors prolong the action of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), improve glucose homeostasis without weight gain, edema, and hypoglycemia. However, the marketed DPP-IV inhibitors have adverse effects such as nasopharyngitis, headache, nausea, hypersensitivity, skin reactions and pancreatitis. Therefore, it is still expected for novel DPP-IV inhibitors with minimal adverse effects. The scaffolds of existing DPP-IV inhibitors are structurally diversified. This makes it difficult to build virtual screening models based upon the known DPP-IV inhibitor libraries using conventional QSAR approaches. In this paper, we report a new strategy to predict DPP-IV inhibitors with machine learning approaches involving naïve Bayesian (NB) and recursive partitioning (RP) methods. We built 247 machine learning models based on 1307 known DPP-IV inhibitors with optimized molecular properties and topological fingerprints as descriptors. The overall predictive accuracies of the optimized models were greater than 80%. An external test set, composed of 65 recently reported compounds, was employed to validate the optimized models. The results demonstrated that both NB and RP models have a good predictive ability based on different combinations of descriptors. Twenty "good" and twenty "bad" structural fragments for DPP-IV inhibitors can also be derived from these models for inspiring the new DPP-IV inhibitor scaffold design.

Outcome of nonsurgical intervention in patients with perforated peptic ulcers.

PubMed

Lay, Ping-Lien; Huang, Hsin-Hung; Chang, Wei-Kuo; Hsieh, Tsai-Yuan; Huang, Tien-Yu; Lin, Hsuan-Hwai

2016-08-01

Although surgical intervention is the favorable treatment modality for perforated peptic ulcer, nonsurgical treatment is another option. The aim of this study is to analyze the results of conservative treatment for perforated peptic ulcer. Between 2003 and 2014, 403 patients were admitted to our hospital for perforated peptic ulcer, and 383 patients underwent surgery, whereas 20 were allocated to conservative treatment. The results of nonsurgical intervention in these patients were analyzed retrospectively. The overall mortality rate of conservative treatment was 40%. Eleven patients remained hospitalized less than 2 weeks; among them, patients with a high (≥IV) American Society of Anesthesiologists class at admission had higher mortality than those with a low (

[Study on chemical constituents of Orobanche coerulescens].

PubMed

Zhao, Jun; Yan, Ming; Huang, Yi; He, Wen-yi; Zhao, Yu

2007-10-01

Six compounds were isolated and purified from Orobanche coerulescens by extraction and different kinds of column chromatography. The structures were determined on the basis of spectral analysis. The structures were elucidated as D-mannitol(I), beta-sitosterol(II), succinic acid(III), caffeic acid(IV), protocatechuic aldehyde(V) and daucosterol(VI). All compounds are obtained from this plant for the first time.

Phytochemical study of the headspace volatile organic compounds of fresh algae and seagrass from the Adriatic Sea (single point collection)

PubMed Central

Marijanović, Zvonimir; Roje, Marin; Kuś, Piotr M.; Jokić, Stela; Čož-Rakovac, Rozelinda

2018-01-01

Performed phytochemical study contributes to the knowledge of volatile organic compounds (VOCs) of Halopteris filicina (Grateloup) Kützing, Dictyota dichotoma (Hudson) J. V. Lamouroux, Posidonia oceanica (L.) Delile and Flabellia petiolata (Turra) Nizamuddin from the Adriatic Sea (single point collection). VOCs were investigated by headspace solid-phase microextraction (HS-SPME) and analysed by gas chromatography and mass spectrometry (GC-MS/FID). H. filicina headspace contained dimethyl sulfide (DMS; 12.8%), C8-compounds (e.g. fucoserratene (I; 9.5%)), benzaldehyde (II; 8.7%), alkane C17, dictyopterene D and C (III, IV), tribromomethane (V), 1-iodopentane, others. F. petiolata headspace was characterized by DMS (22.2%), 6-methylhept-5-en-2-one (9.5%), C17 (9.1%), II (6.5%), compounds I-V. DMS (59.3%), C15 (14.5%), C17 (7.2%) and C19 (6.3%) dominated in P. oceanica headspace. Sesquiterpenes were found in D. dichotoma, predominantly germacrene D (28.3%) followed by other cadinenyl (abundant), muurolenyl and amorphenyl structures. Determined VOCs may be significant for chemosystematics and chemical communications in marine ecosystem. PMID:29738535

[Studies on the chemical constituents of ethyl acetate extract from the roots of Actinidia chrysantha].

PubMed

Meng, Li-Li; Huang, Chu-Sheng; Liu, Hong-Xing; Chen, Xi-Hui

2009-10-01

To study the chemical constituents of ethyl acetate extract from the roots of Actinidia chrysantha. Chromatographic methods were used to isolate the compounds from ethyl acetate extract from the roots of Actinidia chrysantha and chemical and spectral methods were used to elucidate the structures of the isolated compounds. Five compounds were identified as stigmast-3, 6-dione (I), beta-sitosterol (II), ursolicacid (III), beta-daucosterol (IV), 2alpha, 3beta, 23-triol-12-en-28-ursolic acid (V). Those compounds are obtained from the plant for the first time.

[Study on the chemical constituents from Melicope ptelefolia].

PubMed

Xie, Yu-Feng; Liang, Yue; Du, Qing-Tao; Guo, Li-Bing

2011-03-01

To study the chemical constituents from Melicope ptelefolia. Several chromatographic methods were applied to isolate and purify compounds. Their structures were identified on the basis of physicochemical properties and spectroscopic data. Seven compounds were isolated and elucidated as n-octadecanyl palmitate (I), beta-sitosterol (II), palmitic acid (III), 3, 5,3'-trihydroxy-8,4'-dimethoxy-7-(3-methylbut-2-enyloxy) flavone (IV), daucosterol (V), salylic acid (VI), kaempferol-3-O-alpha-D-arabinpyranoside (VII). Compound VII is isolated from the genus for the first time, Compounds V and VI are isolated from Melicope ptelefolia for the first time.

[Clinical policy for management and risk stratification of community-acquired pneumonia in patients hospitalized on the basis of conventional admission criteria].

PubMed

Putinati, Stefano; Ballerin, Licia; Piattella, Marco; Ritrovato, Lucia; Zabini, Franco; Potena, Alfredo

2003-05-01

To identify discrepancies between Pneumonia Severity Index (PSI) risk class and the conventional criteria for deciding the site of care we performed a prospective observational study on 229 patients hospitalized for community-acquired pneumonia. PSI classes and corresponding mortality rates were as following: class I, 41 patients (0%); class II, 20 (0%); class III, 58 (1.7%); class IV, 86 (8.1%); class V, 24 (33.3%). Overall, 119 patients (52%) who were hospitalized according to conventional criteria were assigned to low-risk classes (I-III). Among these low risk patients, 58 (49%) had complications as respiratory failure, pleural effusion, hypotension or shock; among remaining patients, no reasons for admission were found. This latter group deserves prospective evaluation in randomized studies comparing in-hospital versus outpatient management.

Initial Interpretation and Evaluation of a Profile-Based Classification System for the Anxiety and Mood Disorders: Incremental Validity Compared to DSM-IV Categories

PubMed Central

Rosellini, Anthony J.; Brown, Timothy A.

2014-01-01

Limitations in anxiety and mood disorder diagnostic reliability and validity due to the categorical approach to classification used by the Diagnostic and Statistical Manual of Mental Disorders (DSM) have been long recognized. Although these limitations have led researchers to forward alternative classification schemes, few have been empirically evaluated. In a sample of 1,218 outpatients with anxiety and mood disorders, the present study examined the validity of Brown and Barlow's (2009) proposal to classify the anxiety and mood disorders using an integrated dimensional-categorical approach based on transdiagnostic emotional disorder vulnerabilities and phenotypes. Latent class analyses of seven transdiagnostic dimensional indicators suggested that a six-class (i.e., profile) solution provided the best model fit and was the most conceptually interpretable. Interpretation of the classes was further supported when compared with DSM-IV diagnoses (i.e., within-class prevalence of diagnoses, using diagnoses to predict class membership). In addition, hierarchical multiple regression models were used to demonstrate the incremental validity of the profiles; class probabilities consistently accounted for unique variance in anxiety and mood disorder outcomes above and beyond DSM diagnoses. These results provide support for the potential development and utility of a hybrid dimensional-categorical profile approach to anxiety and mood disorder classification. In particular, the availability of dimensional indicators and corresponding profiles may serve as a useful complement to DSM diagnoses for both researchers and clinicians. PMID:25265416

Synthesis, structure, and optoelectronic properties of II-IV-V 2 materials

DOE PAGES

Martinez, Aaron D.; Fioretti, Angela N.; Toberer, Eric S.; ...

2017-03-07

II-IV-V 2 materials offer the promise of enhanced functionality in optoelectronic devices due to their rich ternary chemistry. In this review, we consider the potential for new optoelectronic devices based on nitride, phosphide, and arsenide II-IV-V 2 materials. As ternary analogs to the III-V materials, these compounds share many of the attractive features that have made the III-Vs the basis of modern optoelectronic devices (e.g. high mobility, strong optical absorption). Control of cation order parameter in the II-IV-V 2 materials can produce significant changes in optoelectronic properties at fixed chemical composition, including decoupling band gap from lattice parameter. Recent progressmore » has begun to resolve outstanding questions concerning the structure, dopability, and optical properties of the II-IV-V 2 materials. Furthermore, remaining research challenges include growth optimization and integration into heterostructures and devices.« less

Hit-to-Lead Optimization of a Novel Class of Potent, Broad-Spectrum Trypanosomacides.

PubMed

Russell, Stephanie; Rahmani, Raphaël; Jones, Amy J; Newson, Harriet L; Neilde, Kevin; Cotillo, Ignacio; Rahmani Khajouei, Marzieh; Ferrins, Lori; Qureishi, Sana; Nguyen, Nghi; Martinez-Martinez, Maria S; Weaver, Donald F; Kaiser, Marcel; Riley, Jennifer; Thomas, John; De Rycker, Manu; Read, Kevin D; Flematti, Gavin R; Ryan, Eileen; Tanghe, Scott; Rodriguez, Ana; Charman, Susan A; Kessler, Albane; Avery, Vicky M; Baell, Jonathan B; Piggott, Matthew J

2016-11-10

The parasitic trypanosomes Trypanosoma brucei and T. cruzi are responsible for significant human suffering in the form of human African trypanosomiasis (HAT) and Chagas disease. Drugs currently available to treat these neglected diseases leave much to be desired. Herein we report optimization of a novel class of N-(2-(2-phenylthiazol-4-yl)ethyl)amides, carbamates, and ureas, which rapidly, selectively, and potently kill both species of trypanosome. The mode of action of these compounds is unknown but does not involve CYP51 inhibition. They do, however, exhibit clear structure-activity relationships, consistent across both trypanosome species. Favorable physicochemical parameters place the best compounds in CNS drug-like chemical space but, as a class, they exhibit poor metabolic stability. One of the best compounds (64a) cleared all signs of T. cruzi infection in mice when CYP metabolism was inhibited, with sterile cure achieved in one mouse. This family of compounds thus shows significant promise for trypanosomiasis drug discovery.

A Comparison of the Effects of Intraosseous and Intravenous 5% Albumin on Infusion Time and Hemodynamic Measures in a Swine Model of Hemorrhagic Shock.

PubMed

Muir, Stacy L; Sheppard, Lance B; Maika-Wilson, Anne; Burgert, James M; Garcia-Blanco, Jose; Johnson, Arthur D; Coyner, Jennifer L

2016-08-01

Introduction Obtaining intravenous (IV) access in patients in hemorrhagic shock is often difficult and prolonged. Failed IV attempts delay life-saving treatment. Intraosseous (IO) access may often be obtained faster than IV access. Albumin (5%) is an option for prehospital volume expansion because of the absence of interference with coagulation and platelet function. Hypothesis/Problem There are limited data comparing the performance of IO and IV administered 5% albumin. The aims of this study were to compare the effects of tibial IO (TIO) and IV administration of 500 mL of 5% albumin on infusion time and hemodynamic measurements of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) in a swine model of hemorrhagic shock. Sixteen male swine were divided into two groups: TIO and IV. All subjects were anesthetized and a Class III hemorrhage was achieved by exsanguination of 31% of estimated blood volume (EBV) from a femoral artery catheter. Following exsanguination, 500 mL of 5% albumin was administered under pressurized infusion (300 mmHg) by the TIO or IV route and infusion time was recorded. Hemodynamic measurements of HR, MAP, CO, and SV were collected before and after exsanguination and every 20 seconds for 180 seconds during 5% albumin infusion. An independent t-test determined that IV 5% albumin infusion was significantly faster compared to IO (P=.01). Mean infusion time for TIO was seven minutes 35 seconds (SD=two minutes 44 seconds) compared to four minutes 32 seconds (SD=one minute 08 seconds) in the IV group. Multivariate Analysis of Variance was performed on hemodynamic data collected during the 5% albumin infusion. Analyses indicated there were no significant differences between the TIO and IV groups relative to MAP, CO, HR, or SV (P>.05). While significantly longer to infuse 5% albumin by the TIO route, the longer TIO infusion time may be negated as IO devices can be placed more quickly compared to repeated IV attempts. The lack of significant difference between the TIO and IV routes relative to hemodynamic measures indicate the TIO route is a viable route for the infusion of 5% albumin in a swine model of Class III hemorrhage. Muir SL , Sheppard LB , Maika-Wilson A , Burgert JM , Garcia-Blanco J , Johnson AD , Coyner JL . A comparison of the effects of intraosseous and intravenous 5% albumin on infusion time and hemodynamic measures in a swine model of hemorrhagic shock. Prehosp Disaster Med. 2016;31(4):436-442.

Distribution of Trauma Care Facilities in Oman in Relation to High-Incidence Road Traffic Injury Sites: Pilot study.

PubMed

Al-Kindi, Sara M; Naiem, Ahmed A; Taqi, Kadhim M; Al-Gheiti, Najla M; Al-Toobi, Ikhtiyar S; Al-Busaidi, Nasra Q; Al-Harthy, Ahmed Z; Taqi, Alaa M; Ba-Alawi, Sharif A; Al-Qadhi, Hani A

2017-11-01

Road traffic injuries (RTIs) are considered a major public health problem worldwide. In Oman, high numbers of RTIs and RTI-related deaths are frequently registered. This study aimed to evaluate the distribution of trauma care facilities in Oman with regards to their proximity to RTI-prevalent areas. This descriptive pilot study analysed RTI data recorded in the national Royal Oman Police registry from January to December 2014. The distribution of trauma care facilities was analysed by calculating distances between areas of peak RTI incidence and the closest trauma centre using Google Earth and Google Maps software (Google Inc., Googleplex, Mountain View, California, USA). A total of 32 trauma care facilities were identified. Four facilities (12.5%) were categorised as class V trauma centres. Of the facilities in Muscat, 42.9% were ranked as class IV or V. There were no class IV or V facilities in Musandam, Al-Wusta or Al-Buraimi. General surgery, orthopaedic surgery and neurosurgery services were available in 68.8%, 59.3% and 12.5% of the centres, respectively. Emergency services were available in 75.0% of the facilities. Intensive care units were available in 11 facilities, with four located in Muscat. The mean distance between a RTI hotspot and the nearest trauma care facility was 34.7 km; however, the mean distance to the nearest class IV or V facility was 83.3 km. The distribution and quality of trauma care facilities in Oman needs modification. It is recommended that certain centres upgrade their levels of trauma care in order to reduce RTI-associated morbidity and mortality in Oman.

Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Reduced Ejection Fraction.

PubMed

Sandhu, Alexander T; Ollendorf, Daniel A; Chapman, Richard H; Pearson, Steven D; Heidenreich, Paul A

2016-11-15

Sacubitril-valsartan therapy reduces cardiovascular mortality compared with enalapril therapy in patients with heart failure with reduced ejection fraction. To evaluate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor therapy in patients with chronic heart failure. Markov decision model. Clinical trials, observational analyses, reimbursement data from the Centers for Medicare & Medicaid Services, drug pricing databases, and Centers for Disease Control and Prevention life tables. Patients at an average age of 64 years, New York Heart Association (NYHA) class II to IV heart failure, and left ventricular ejection fraction of 0.40 or less. Lifetime. Societal. Treatment with sacubitril-valsartan or lisinopril. Life-years, quality-adjusted life-years (QALYs), costs, heart failure hospitalizations, and incremental cost-effectiveness ratios. The sacubitril-valsartan group experienced 0.08 fewer heart failure hospitalization, 0.69 additional life-year, 0.62 additional QALY, and $29 203 in incremental costs, equating to a cost per QALY gained of $47 053. The cost per QALY gained was $44 531 in patients with NYHA class II heart failure and $58 194 in those with class III or IV heart failure. Sacubitril-valsartan treatment was most sensitive to the duration of improved outcomes, with a cost per QALY gained of $120 623 if the duration was limited to the length of the trial (median, 27 months). No variations in other parameters caused the cost to exceed $100 000 per QALY gained. The benefit of sacubitril-valsartan is based on a single clinical trial. Treatment with sacubitril-valsartan provides reasonable value in reducing cardiovascular mortality and morbidity in patients with NYHA class II to IV heart failure. U.S. Department of Veterans Affairs and Institute for Clinical and Economic Review.

ACUTE TOXICITY OF SELECTED ORGANIC COMPOUNDS TO FATHEAD MINNOWS

EPA Science Inventory

Static nonrenewal laboratory bioassays were conducted with 26 organic compounds commonly used by industry. The selected compounds represented the five following chemical classes: acids, alcohols, hydrocarbons, ketones and aldehydes, and phenols. Juvenile fathead minnows (Pimephal...

Ontology-based content analysis of US patent applications from 2001-2010.

PubMed

Weber, Lutz; Böhme, Timo; Irmer, Matthias

2013-01-01

Ontology-based semantic text analysis methods allow to automatically extract knowledge relationships and data from text documents. In this review, we have applied these technologies for the systematic analysis of pharmaceutical patents. Hierarchical concepts from the knowledge domains of chemical compounds, diseases and proteins were used to annotate full-text US patent applications that deal with pharmacological activities of chemical compounds and filed in the years 2001-2010. Compounds claimed in these applications have been classified into their respective compound classes to review the distribution of scaffold types or general compound classes such as natural products in a time-dependent manner. Similarly, the target proteins and claimed utility of the compounds have been classified and the most relevant were extracted. The method presented allows the discovery of the main areas of innovation as well as emerging fields of patenting activities - providing a broad statistical basis for competitor analysis and decision-making efforts.

From the Test Tube to the Treatment Room: Fundamentals of Boron-containing Compounds and their Relevance to Dermatology.

PubMed

Del Rosso, James Q; Plattner, Jacob J

2014-02-01

The development of new drug classes and novel molecules that are brought to the marketplace has been a formidable challenge, especially for dermatologic drugs. The relative absence of new classes of antimicrobial agents is also readily apparent. Several barriers account for slow drug development, including regulatory changes, added study requirements, commercial pressures to bring drugs to market quickly by developing new generations of established compounds, and the greater potential for failure and higher financial risk when researching new drug classes. In addition, the return on investment is usually much lower with dermatologic drugs as compared to the potential revenue from "blockbuster" drugs for cardiovascular or gastrointestinal disease, hypercholesterolemia, and mood disorders. Nevertheless, some researchers are investigating new therapeutic platforms, one of which is boron-containing compounds. Boron-containing compounds offer a wide variety of potential applications in dermatology due to their unique physical and chemical properties, with several in formal phases of development. Tavaborole, a benzoxaborole compound, has been submitted to the United States Food and Drug Administration for approval for treatment of onychomycosis. This article provides a thorough overview of the history of boron-based compounds in medicine, their scientific rationale, physiochemical and pharmacologic properties, and modes of actions including therapeutic targets. A section dedicated to boron-based compounds in development for treatment of various skin disorders is also included.

Compound Heterozygosity for Hb Alperton (HBB: c.407C>T) and IVS-I-5 (G>C) (HBB: c.92+5G>C) Mutations Presenting as a Moderate Anemia in an Indian Family.

PubMed

Godbole, Koumudi G; Ramachandran, Angelina; Karkamkar, Ashwini S; Dalal, Ashwin B

2018-04-13

While knowledge of HBB gene mutations is necessary for offering prenatal diagnosis (PND) of β-thalassemia (β-thal), a genotype-phenotype correlation may not always be available for rare variants. We present for the first time, genotype-phenotype correlation for a compound heterozygous status with IVS-I-5 (G>C) (HBB: c.92+5G>C) and HBB: c.407C>T (Hb Alperton) mutations on the HBB gene in an Indian family. Hb Alperton is a very rare hemoglobin (Hb) variant with scant published information about its clinical presentation, especially when accompanied with another HBB gene mutation. Here we provide biochemical as well as clinical details of this variant.

Assessment of Multiple Solvents for Extraction and Direct GC-MS Determination of the Phytochemical Inventory of Sansevieria Extrafoliar Nectar Droplets.

PubMed

Gaylor, Michael O; Juntunen, Hope L; Hazelwood, Donna; Videau, Patrick

2018-04-01

Considerable effort has been devoted to analytical determinations of sugar and amino acid constituents of plant nectars, with the primary aim of understanding their ecological roles, yet few studies have reported more exhaustive organic compound inventories of plant nectars or extrafoliar nectars. This work evaluated the efficacy of four solvents (ethyl acetate, dichloromethane, toluene and hexane) to extract the greatest number of organic compound classes and unique compounds from extrafoliar nectar drops produced by Sansevieria spp. Aggregation of the results from each solvent revealed that 240 unique compounds were extracted in total, with 42.5% of those detected in multiple extracts. Aliphatic hydrocarbons dominated in all but the ethyl acetate extracts, with 44 unique aliphatic hydrocarbons detected in dichloromethane (DCM) extracts, followed by 41, 19 and 8 in hexane, toluene and ethyl acetate extracts, respectively. Hexane extracted the most unique compounds (79), followed by DCM (73), ethyl acetate (56) and toluene (32). Integrated total ion chromatographic peak areas of extracted compound classes were positively correlated with numbers of unique compounds detected within those classes. In addition to demonstrating that multi-solvent extraction with direct GC-MS detection is a suitable analytical approach for determining secondary nectar constituents, to the best of our knowledge, this study also represents: (i) the first attempt to inventory the secondary phytochemical constituents of Sansevieria spp. extrafoliar nectar secretions and (ii) the largest organic solvent extractable compound inventory reported for any plant matrix to date.

Anti-trypanosomal activities and structural chemical properties of selected compound classes.

PubMed

Ponte-Sucre, Alicia; Bruhn, Heike; Schirmeister, Tanja; Cecil, Alexander; Albert, Christian R; Buechold, Christian; Tischer, Maximilian; Schlesinger, Susanne; Goebel, Tim; Fuß, Antje; Mathein, Daniela; Merget, Benjamin; Sotriffer, Christoph A; Stich, August; Krohne, Georg; Engstler, Markus; Bringmann, Gerhard; Holzgrabe, Ulrike

2015-02-01

Potent compounds do not necessarily make the best drugs in the market. Consequently, with the aim to describe tools that may be fundamental for refining the screening of candidates for animal and preclinical studies and further development, molecules of different structural classes synthesized within the frame of a broad screening platform were evaluated for their trypanocidal activities, cytotoxicities against murine macrophages J774.1 and selectivity indices, as well as for their ligand efficiencies and structural chemical properties. To advance into their modes of action, we also describe the morphological and ultrastructural changes exerted by selected members of each compound class on the parasite Trypanosoma brucei. Our data suggest that the potential organelles targeted are either the flagellar pocket (compound 77, N-Arylpyridinium salt; 15, amino acid derivative with piperazine moieties), the endoplasmic reticulum membrane systems (37, bisquaternary bisnaphthalimide; 77, N-Arylpyridinium salt; 68, piperidine derivative), or mitochondria and kinetoplasts (88, N-Arylpyridinium salt; 68, piperidine derivative). Amino acid derivatives with fumaric acid and piperazine moieties (4, 15) weakly inhibiting cysteine proteases seem to preferentially target acidic compartments. Our results suggest that ligand efficiency indices may be helpful to learn about the relationship between potency and chemical characteristics of the compounds. Interestingly, the correlations found between the physico-chemical parameters of the selected compounds and those of commercial molecules that target specific organelles indicate that our rationale might be helpful to drive compound design toward high activities and acceptable pharmacokinetic properties for all compound families.

Outdoor passive air monitoring of semi volatile organic compounds (SVOCs): a critical evaluation of performance and limitations of polyurethane foam (PUF) disks.

PubMed

Bohlin, P; Audy, O; Škrdlíková, L; Kukučka, P; Přibylová, P; Prokeš, R; Vojta, Š; Klánová, J

2014-03-01

The most commonly used passive air sampler (PAS) (i.e. polyurethane foam (PUF) disk) is cheap, versatile, and capable of accumulating compounds present both in gas and particle phases. Its performance for particle associated compounds is however disputable. In this study, twelve sets of triplicate PUF-PAS were deployed outdoors for exposure periods of 1-12 weeks together with continuously operated active samplers, to characterize sampling efficiency and derive sampling rates (RS) for compounds belonging to 7 SVOC classes (including particle associated compounds). PUF-PAS efficiently and consistently sampled polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs), and eight novel brominated flame retardant (nBFR) compounds. Low accuracy and lack of sensitivity was observed for most polychlorinated dibenzo-p-dioxins/furans PCDD/Fs and polybrominated diphenyl ethers (PBDEs) (under the conditions of this study), with the exception of some congeners which may be used as qualitative markers for their respective classes. Application of compound specific RS was found crucial for all compounds except PCBs. Sampling efficiency of the particle associated compounds was often low.

ION COMPOSITION ELUCIDATION (ICE): A HIGH ...

EPA Pesticide Factsheets

Unidentified Organic Compounds. For target analytes, standards are purchased, extraction and clean-up procedures are optimized, and mass spectra and retention times for the chromatographic separation are obtained for comparison to the target compounds in environmental sample extracts. This is an efficient approach and selective extraction and clean-up can decrease detection limits for the target compounds relative to analyzing a raw extract containing compounds that yield mass interferences. But selection of a class of compounds for study ignores many potentially toxic compounds. All compounds should be considered, because even trace amounts of compounds found to be endocrine disrupting chemicals might influence embryonic development. Before the toxicology of the hundreds of compounds found in sewage treatment effluents and water reservoirs can be studied alone and in mixtures, they must first be identified. A given compound might be one of the 3800 high production volume chemicals used commercially, a human or microorganism metabolite of such a compound, a photochemical degradation, hydrolysis, or thermal decomposition product, a chlorination or ozonolysis byproduct for drinking water samples, or a naturally occurring compound. Numerous researchers targeting assorted classes of analytes could easily overlook or be unable to identify many of these compounds. Most non-targeted compounds will not be in mass spectral libraries and can seldom be tentatively identifi

Institutional Research, Fiscal Year 1977: Report on Publicity Activities. Research Monograph IV.

ERIC Educational Resources Information Center

South Oklahoma City Junior Coll., OK.

During the first week of December, a 10% random sample of day classes and a 10% sample of night classes at South Oklahoma City Junior College were given a questionnaire dealing with the publicity activities used prior to and during the fall 1976 enrollment period. A total of 314 students responded, 179 night and 135 day students. Day students were…

Tri-city study of Ecstasy use problems: a latent class analysis.

PubMed

Scheier, Lawrence M; Ben Abdallah, Arbi; Inciardi, James A; Copeland, Jan; Cottler, Linda B

2008-12-01

This study used latent class analysis to examine distinctive subtypes of Ecstasy users based on 24 abuse and dependence symptoms underlying standard DSM-IV criteria. Data came from a three site, population-based, epidemiological study to examine diagnostic nosology for Ecstasy use. Subject inclusion criteria included lifetime Ecstasy use exceeding five times and once in the past year, with participants ranging in age between 16 and 47 years of age from St. Louis, Miami, U.S. and Sydney, Australia. A satisfactory model typified four latent classes representing clearly differentiated diagnostic clusters including: (1) a group of sub-threshold users endorsing few abuse and dependence symptoms (negatives), (2) a group of 'diagnostic orphans' who had characteristic features of dependence for a select group of symptoms (mild dependent), (3) a 'transitional group' mimicking the orphans with regard to their profile of dependence also but reporting some abuse symptoms (moderate dependent), and (4) a 'severe dependent' group with a distinct profile of abuse and dependence symptoms. A multinomial logistic regression model indicated that certain latent classes showed unique associations with external non-diagnostic markers. Controlling for demographic characteristics and lifetime quantity of Ecstasy pill use, criminal behavior and motivational cues for Ecstasy use were the most efficient predictors of cluster membership. This study reinforces the heuristic utility of DSM-IV criteria applied to Ecstasy but with a different collage of symptoms that produced four distinct classes of Ecstasy users.

40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...

40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...

40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...

40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...

40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...

21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2010 CFR

2010-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...

21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2012 CFR

2012-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...

21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2013 CFR

2013-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...

21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2011 CFR

2011-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...

21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2014 CFR

2014-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...

The Crystal and Molecular Structure of Acetatochlorobis(4-methylpyridine)oxovanadium (IV)

NASA Technical Reports Server (NTRS)

Schupp, John D.; Hepp, Aloysius F.; Duraj, Stan A.; Richman, Robert M.; Fanwick, Phillip E.; Hakimzadeh, Roshanak (Technical Monitor)

2001-01-01

The crystal and molecular structure of the title compound, VOCl(O2CCH3)(4-CH3C5H4N)2, has been determined by single-crystal x-ray diffraction. The material crystallizes in the space group P 1(bar) (#2) with a = 7.822(2), b = 8.023(l), c = 14.841(2) Angstroms, alpha = 99.73(l), beta = 91.41(l), and gamma = 117.13(l). The coordination geometry around the vanadium is a highly distorted octahedron. The molecule is remarkable for being a monomeric oxovanadium (IV) carboxylate. A generalized synthetic strategy is proposed for the preparation of oxovanadium (IV) monomers.

Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels

PubMed Central

Zhang, Miao; Pascal, John M.; Schumann, Marcel; Armen, Roger S.; Zhang, Ji-fang

2012-01-01

Small- and intermediate-conductance Ca2+-activated potassium channels, activated by Ca2+-bound calmodulin, play an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potentials for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-EBIO class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class. PMID:22929778