DOE Office of Scientific and Technical Information (OSTI.GOV)
George, Kevin W.; Thompson, Mitchell; Kim, Joonhoon
Isopentenyl pyrophosphate (IPP) toxicity presents a challenge in engineered microbial systems since its formation is unavoidable in terpene biosynthesis. Here in this work, we develop an experimental platform to study IPP toxicity in isoprenol-producing Escherichia coli. We first characterize the physiological response to IPP accumulation, demonstrating that elevated IPP levels are linked to growth inhibition, reduced cell viability, and plasmid instability. We show that IPP toxicity selects for pathway “breakage”, using proteomics to identify a reduction in phosphomevalonate kinase (PMK) as a probable recovery mechanism. Next, using multi-omics data, we demonstrate that endogenous E. coli metabolism is globally impacted bymore » IPP accumulation, which slows nutrient uptake, decreases ATP levels, and perturbs nucleotide metabolism. We also observe the extracellular accumulation of IPP and present preliminary evidence that IPP can be transported by E. coli, findings that might be broadly relevant for the study of isoprenoid biosynthesis. Finally, we discover that IPP accumulation leads to the formation of ApppI, a nucleotide analog of IPP that may contribute to observed toxicity phenotypes. This comprehensive assessment of IPP stress suggests potential strategies for the alleviation of prenyl diphosphate toxicity and highlights possible engineering targets for improved IPP flux and high titer isoprenoid production.« less
George, Kevin W.; Thompson, Mitchell; Kim, Joonhoon; ...
2018-03-09
Isopentenyl pyrophosphate (IPP) toxicity presents a challenge in engineered microbial systems since its formation is unavoidable in terpene biosynthesis. Here in this work, we develop an experimental platform to study IPP toxicity in isoprenol-producing Escherichia coli. We first characterize the physiological response to IPP accumulation, demonstrating that elevated IPP levels are linked to growth inhibition, reduced cell viability, and plasmid instability. We show that IPP toxicity selects for pathway “breakage”, using proteomics to identify a reduction in phosphomevalonate kinase (PMK) as a probable recovery mechanism. Next, using multi-omics data, we demonstrate that endogenous E. coli metabolism is globally impacted bymore » IPP accumulation, which slows nutrient uptake, decreases ATP levels, and perturbs nucleotide metabolism. We also observe the extracellular accumulation of IPP and present preliminary evidence that IPP can be transported by E. coli, findings that might be broadly relevant for the study of isoprenoid biosynthesis. Finally, we discover that IPP accumulation leads to the formation of ApppI, a nucleotide analog of IPP that may contribute to observed toxicity phenotypes. This comprehensive assessment of IPP stress suggests potential strategies for the alleviation of prenyl diphosphate toxicity and highlights possible engineering targets for improved IPP flux and high titer isoprenoid production.« less
USDA-ARS?s Scientific Manuscript database
All products of isoprenoid metabolism originate with the C5 non-allylic substrate, isopentenyl pyrophosphate (IPP). IPP is produced in plants by two distinct pathways, the mevalonate pathway (MEV) in the cytosol and the 2 C methyl-D-erythritol 4 phosphate (MEP) pathway in plastids. A multi-gene a...
Thibodeaux, Christopher J.; Mansoorabadi, Steven O.; Kittleman, William; Chang, Wei-chen; Liu, Hung-wen
2011-01-01
The type II isopentenyl diphosphate/dimethylallyl diphosphate isomerase (IDI-2) is a flavin mononucleotide (FMN)-dependent enzyme that catalyzes the reversible isomerization of isopentenyl pyrophosphate (IPP) to dimethylallyl pyrophosphate (DMAPP), a reaction with no net change in redox state of the coenzyme or substrate. Here, UV-vis spectral analysis of the IDI-2 reaction revealed the accumulation of a reduced neutral dihydroflavin intermediate when the reduced enzyme was incubated with IPP or DMAPP. When IDI-2 was reconstituted with 1-deazaFMN and 5-deazaFMN, similar reduced neutral forms of the deazaflavin analogues were observed in the presence of IPP. Single turnover stopped-flow absorbance experiments indicated that this flavin intermediate formed and decayed at kinetically competent rates in the pre-steady-state and, thus, most likely represents a true intermediate in the catalytic cycle. UV-vis spectra of the reaction mixtures reveal trace amounts of a neutral semiquinone, but evidence for the presence of IPP-based radicals could not be obtained by EPR spectroscopy. Rapid-mix chemical quench experiments show no burst in DMAPP formation, suggesting that the rate determining step in the forward direction (IPP to DMAPP) occurs prior to DMAPP formation. A solvent deuterium kinetic isotope effect (D2OVmax = 1.5) was measured on vo in steady-state kinetic experiments at saturating substrate concentrations. A substrate deuterium kinetic isotope effect was also measured on the initital velocity (DVmax = 1.8) and on the decay rate of the flavin intermediate (Dks = 2.3) in single-turnover stopped-flow experiments using (R)-[2-2H]-IPP. Taken together, these data suggest that the C2–H bond of IPP is cleaved in the rate determining step and that general acid/base catalysis may be involved during turnover. Possible mechanisms for the IDI-2 catalyzed reaction are presented and discussed in terms of the available X-ray crystal structures. PMID:18229948
Ma, Dongming; Li, Gui; Alejos-Gonzalez, Fatima; Zhu, Yue; Xue, Zhen; Wang, Aimin; Zhang, Hui; Li, Xing; Ye, Hechun; Wang, Hong; Liu, Benye; Xie, De-Yu
2017-08-01
We recently characterized a gene-terpene network that is associated with artemisinin biosynthesis in self-pollinated (SP) Artemisia annua, an effective antimalarial plant. We hypothesize that an alteration of gene expression in the network may improve the production of artemisinin and its precursors. In this study, we cloned an isopentenyl pyrophosphate isomerase (IPPI) cDNA, AaIPPI1, from Artemisia annua (Aa). The full-length cDNA encodes a type-I IPPI containing a plastid transit peptide (PTP) at its amino terminus. After the removal of the PTP, the recombinant truncated AaIPPI1 isomerized isopentenyl pyrophosphate (IPP) to dimethyl allyl pyrophosphate (DMAPP) and vice versa. The steady-state equilibrium ratio of IPP/DMAPP in the enzymatic reactions was approximately 1:7. The truncated AaIPPI1 was overexpressed in the cytosol of the SP A. annua variety. The leaves of transgenic plants produced approximately 4% arteannuin B (g g -1 , dry weight, dw) and 0.17-0.25% artemisinin (g g -1 , dw), the levels of which were significantly higher than those in the leaves of wild-type plants. In addition, transgenic plants showed an increase in artemisinic acid production of more than 1% (g g -1 , dw). In contrast, isoprene formation was significantly reduced in transgenic plants. These results provide evidence that overexpression of AaIPPI1 in the cytosol can lead to metabolic alterations of terpenoid biosynthesis, and show that these transgenic plants have the potential to yield high production levels of arteannuin B as a new precursor source for artemisinin. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.
Laurent, Agneta J.; Bindslev, Niels; Johansson, Björn; Berg, Louise
2014-01-01
Low to moderate ethanol consumption has been associated with protective effects in autoimmune diseases such as rheumatoid arthritis, RA. An expansion of γδ T cells induced by isopentenyl pyrophosphate, IPP, likewise seems to have a protective role in arthritis. The aim of this project was to test the hypothesis that low doses of ethanol can enhance IPP-induced expansion of synovial fluid γδ T cells from patients with arthritis and may thereby potentially account for the beneficial effects of ethanol on symptoms of the arthritic process. Thus, mononuclear cells from synovial fluid (SF) from 15 patients with arthritis and from peripheral blood (PB) from 15 healthy donors were stimulated with low concentrations of ethanol and IPP for 7 days in vitro. IPP in combination with ethanol 0.015%, 2.5 mM, equivalent to the decrease per hour in blood ethanol concentration due to metabolism, gave a significantly higher fractional expansion of SF γδ T cells compared with IPP alone after 7 days (ratio 10.1+/−4.0, p<0.0008, n = 12) in patients with arthritis. Similar results were obtained for PB γδ T cells from healthy controls (ratio 2.0+/−0.4, p<0.011, n = 15). The augmented expansion of γδ T cells in SF is explained by a higher proliferation (p = 0.0034, n = 11) and an increased survival (p<0.005, n = 11) in SF cultures stimulated with IPP plus ethanol compared to IPP alone. The synergistic effects of IPP and ethanol indicate a possible allosteric effect of ethanol. Similar effects could be seen when stimulating PB with ethanol in presence of risedronate, which has the ability to increase endogenous levels of IPP. We conclude that expansion of γδ T cells by combinatorial drug effects, possibly in fixed-dose combination, FDC, of ethanol in the presence of IPP might give a protective role in diseases such as arthritis. PMID:25090614
Xiang, Lin; Zhao, Kaige; Chen, Longqing
2010-01-01
Farnesyl pyrophosphate (FPP) synthase catalyzes the biosynthesis of FPP, which is the precursors of sesquiterpenoids such as floral scent volatiles, from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). cDNA encoding wintersweet (Chimonanthus praecox L.) FPP synthase was isolated by the RT-PCR and RACE methods. The deduced amino acid sequence showed a high identity to plant FPP synthases. Expression of the gene in Escherichia coli yielded FPPS activity that catalyzed the synthesis of FPP as a main product. Tissue-specific and developmental analyses of the mRNA levels of CpFPPS and volatile sesquiterpenoids levels in C. praecox flowers revealed that the FPPS may play a regulatory role in floral volatile sesquiterpenoids of wintersweet. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Vγ9Vδ2 T cell activation by strongly agonistic nucleotidic phosphoantigens.
Moulin, Morgane; Alguacil, Javier; Gu, Siyi; Mehtougui, Asmaa; Adams, Erin J; Peyrottes, Suzanne; Champagne, Eric
2017-12-01
Human Vγ9Vδ2 T cells can sense through their TCR tumor cells producing the weak endogenous phosphorylated antigen isopentenyl pyrophosphate (IPP), or bacterially infected cells producing the strong agonist hydroxyl dimethylallyl pyrophosphate (HDMAPP). The recognition of the phosphoantigen is dependent on its binding to the intracellular B30.2 domain of butyrophilin BTN3A1. Most studies have focused on pyrophosphate phosphoantigens. As triphosphate nucleotide derivatives are naturally co-produced with IPP and HDMAPP, we analyzed their specific properties using synthetic nucleotides derived from HDMAPP. The adenylated, thymidylated and uridylated triphosphate derivatives were found to activate directly Vγ9Vδ2 cell lines as efficiently as HDMAPP in the absence of accessory cells. These antigens were inherently resistant to terminal phosphatases, but apyrase, when added during a direct stimulation of Vγ9Vδ2 cells, abrogated their stimulating activity, indicating that their activity required transformation into strong pyrophosphate agonists by a nucleotide pyrophosphatase activity which is present in serum. Tumor cells can be sensitized with nucleotide phosphoantigens in the presence of apyrase to become stimulatory, showing that this can occur before their hydrolysis into pyrophosphates. Whereas tumors sensitized with HDMAPP rapidly lost their stimulatory activity, sensitization with nucleotide derivatives, in particular with the thymidine derivative, induced long-lasting stimulating ability. Using isothermal titration calorimetry, binding of some nucleotide derivatives to BTN3A1 intracellular domain was found to occur with an affinity similar to that of IPP, but much lower than that of HDMAPP. Thus, nucleotide phosphoantigens are precursors of pyrophosphate antigens which can deliver strong agonists intracellularly resulting in prolonged and strengthened activity.
Castella, Barbara; Kopecka, Joanna; Sciancalepore, Patrizia; Mandili, Giorgia; Foglietta, Myriam; Mitro, Nico; Caruso, Donatella; Novelli, Francesco; Riganti, Chiara; Massaia, Massimo
2017-01-01
Vγ9Vδ2 T cells are activated by phosphoantigens, such as isopentenyl pyrophosphate (IPP), which is generated in the mevalonate pathway of antigen-presenting cells. IPP is released in the extracellular microenvironment via unknown mechanisms. Here we show that the ATP-binding cassette transporter A1 (ABCA1) mediates extracellular IPP release from dendritic cells (DC) in cooperation with apolipoprotein A-I (apoA-I) and butyrophilin-3A1. IPP concentrations in the supernatants are sufficient to induce Vγ9Vδ2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA). ZA treatment increases ABCA1 and apoA-I expression via IPP-dependent LXRα nuclear translocation and PI3K/Akt/mTOR pathway inhibition. These results close the mechanistic gap in our understanding of extracellular IPP release from DC and provide a framework to fine-tune Vγ9Vδ2 T cell activation via mevalonate and PI3K/Akt/mTOR pathway modulation. PMID:28580927
You, Shengping; Yin, Qingdian; Zhang, Jianye; Zhang, Chengyu; Qi, Wei; Gao, Lan; Tao, Zhiping; Su, Rongxin; He, Zhimin
2017-11-01
Farnesene has been identified as suitable jet fuel substitutes and metabolic engineering for microbial production of farnesene is an alternative and attractive route. In this study, due to accumulation of toxic intermediate isopentenyl pyrophosphate (IPP), an engineered Escherichia coli strain harboring heterologous mevalonate pathway produced only 4.11mg/L β-farnesene. Through higher-level expression of isopentenyl diphosphate isomerase and farnesyl diphosphate synthase to minimize the accumulated IPP, another engineered strain with relatively balanced mevalonate pathway was constructed and had the highest production of β-farnesene to date (8.74g/L) by Escherichia coli in a lab bioreactor. Furthermore, this is the first report on utilization of biodiesel by-product (simple purification) as substrate for high-production of β-farnesene by the engineered strain optimized and β-farnesene concentration reached 2.83g/L in a lab bioreactor. Therefore, the engineered strain optimized could be used as a platform host for high-production of other terpenoids using biodiesel by-product as substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.
Heider, Sabine A E; Peters-Wendisch, Petra; Wendisch, Volker F; Beekwilder, Jules; Brautaset, Trygve
2014-05-01
Carotenoids, a subfamily of terpenoids, are yellow- to red-colored pigments synthesized by plants, fungi, algae, and bacteria. They are ubiquitous in nature and take over crucial roles in many biological processes as for example photosynthesis, vision, and the quenching of free radicals and singlet oxygen. Due to their color and their potential beneficial effects on human health, carotenoids receive increasing attention. Carotenoids can be classified due to the length of their carbon backbone. Most carotenoids have a C40 backbone, but also C30 and C50 carotenoids are known. All carotenoids are derived from isopentenyl pyrophosphate (IPP) as a common precursor. Pathways leading to IPP as well as metabolic engineering of IPP synthesis and C40 carotenoid production have been reviewed expertly elsewhere. Since C50 carotenoids are synthesized from the C40 carotenoid lycopene, we will summarize common strategies for optimizing lycopene production and we will focus our review on the characteristics, biosynthesis, glycosylation, and overproduction of C50 carotenoids.
Molecular regulation of santalol biosynthesis in Santalum album L.
Rani, Arti; Ravikumar, Puja; Reddy, Manjunatha Damodara; Kush, Anil
2013-09-25
Santalum album L. commonly known as East-Indian sandal or chandan is a hemiparasitic tree of family santalaceae. Santalol is a bioprospecting molecule present in sandalwood and any effort towards metabolic engineering of this important moiety would require knowledge on gene regulation. Santalol is a sesquiterpene synthesized through mevalonate or non-mevalonate pathways. First step of santalol biosynthesis involves head to tail condensation of isopentenyl pyrophosphate (IPP) with its allylic co-substrate dimethyl allyl pyrophosphate (DMAPP) to produce geranyl pyrophosphate (GPP; C10 - a monoterpene). GPP upon one additional condensation with IPP produces farnesyl pyrophosphate (FPP; C15 - an open chain sesquiterpene). Both the reactions are catalyzed by farnesyl diphosphate synthase (FDS). Santalene synthase (SS), a terpene cyclase catalyzes cyclization of open ring FPP into a mixture of cyclic sesquiterpenes such as α-santalene, epi-β-santalene, β-santalene and exo bergamotene, the main constituents of sandal oil. The objective of the present work was to generate a comprehensive knowledge on the genes involved in santalol production and study their molecular regulation. To achieve this, sequences encoding farnesyl diphosphate synthase and santalene synthase were isolated from sandalwood using suppression subtraction hybridization and 2D gel electrophoresis technology. Functional characterization of both the genes was done through enzyme assays and tissue-specific expression of both the genes was studied. To our knowledge, this is the first report on studies on molecular regulation, and tissue-specific expression of the genes involved in santalol biosynthesis. © 2013.
Nishino, T; Rudney, H
1977-02-22
The properties of 4-hydroxybenzoate:polyprenyl transferase and the system synthesizing polyprenyl pyrophosphate have been studied in mitochondria from rat and guinea pig livers. With solanesyl pyrophosphate and 4-hydroxybenzoate as substrates the formation of 3-nonaprenyl-4-hydroxybenzoate was linear with time, concentration of protein, and concentration of solanesyl pyrophosphate. Solanesyl monophosphate is inactive as a substrate and is noninhibitory. Conversion of solanesyl monophosphate to the pyrophosphate could not be detected. Detergents such as Triton X-100, Tween-80, and sodium deoxycholate activated the enzyme in mitochondria which were aged by freezing at -20 degrees C for periods ranging from 1 h to several days. Maximum activation also required Mg2+. In agreement with previous observation the effect of Mg2+ and Triton X-100 on fresh mitochondria was quite variable; however, activation with aged preparations was very consistent. Treatment with TritonX-100 causes al alteration in the biosynthetic pattern of rat liver mitochondria so that rather than nonaprenyl, decaprenyl, pyrophosphate is preferentially made in the presence of solanesyl pyrophosphate and isopentenyl pyrophosphate. In the presence of Triton X-100 and added pool of solanesyl pyrophosphate appears to exert a feedback inhibition on the incorporation of isopentenyl pyrophosphate into solanesyl pyrophosphate. In the case of guinea pig liver mitochondria a different pattern is observed with Triton X-100 in contrast to the rat. The de novo formation of decaprenyl pyrophosphate from isopentenyl pyrophosphate appears to be inhibited by Triton X-100, but the synthesis of decaprenyl pyrophosphate from isopentenyl pyrophosphate and nonaprenyl pyrophosphate is not inhibited. The data also indicate that in guinea pig liver in a system synthesizing decaprenyl pyrophosphate from isopentenyl pyrophosphate, there does not appear to be a detectable pool of nonaprenyl pyrophosphate. These results show that detergents can affect the specificity of the mitochondrial system synthesizing polyprenyl pyrophosphates.
Anti-fibrotic characteristics of Vγ9+ γδ T cells in systemic sclerosis.
Markovits, Noa; Bendersky, Anna; Loebstein, Ronen; Brusel, Marina; Kessler, Efrat; Bank, Ilan
2016-01-01
γδ T cells of the Vγ9Vδ2 subtype secrete anti-fibrotic cytokines upon isopentenyl pyrophosphate (IPP) stimulation. In this study, we sought to compare IPP and Zoledronate, an up-regulator of IPP, effects on proliferation and cytokine secretion of Vγ9+ T cells from systemic sclerosis (SSc) patients and healthy controls (HCs). We also examined the effect of IPP-triggered peripheral blood mononuclear cells (PBMC) on fibroblast procolla- gen secretion. PBMC from SSc patients and HCs were stimulated by increasing concentrations of Zoledronate, with or without IPP, and Vγ9+ T cell percentages were calculated using FACScan analysis. Subsequently, PBMC were cultured with IPP or toxic shock syndrome toxin-1 (TSST-1), and contents of the anti-fibrotic cytokines tumour necrosis factor (TNF)-α and interferon (IFN)-γ were measured by ELISA kits. Finally, supernatants of IPP-triggered Vγ9+ T cells from SSc patients were added to fibroblast cultures, and relative intensities of procollagen α1 chains were determined by densinometry. Higher concentrations of Zoledronate were required for maximal proliferation of Vγ9+ T cells in 9 SSc patients compared to 9 HCs, irrespective of exogenous IPP. When compared to stimulation by TSST-1, a non-Vγ9+ selective reagent, secretion of the anti-fibrotic cytokines TNF-α and IFN-γ in response to IPP was relatively diminished in SSc but not in HCs. Reduction of procollagen secretion by fibroblasts cultured with supernatants of IPP-stimulated PBMC was observed only in some SSc patients. Activated Vγ9+ T cells could act as anti-fibrotic mediators in SSc, although decreased responsiveness to IPP may play a role in the pathological fibrosis of this disease.
Ariyawutthiphan, Orapin; Ose, Toyoyuki; Minami, Atsushi; Shinde, Sandip; Sinde, Sandip; Tsuda, Muneya; Gao, Yong-Gui; Yao, Min; Oikawa, Hideaki; Tanaka, Isao
2012-11-01
In the typical isoprenoid-biosynthesis pathway, condensation of the universal C(5)-unit precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) occurs via the common intermediates prenyl pyrophosphates (C(10)-C(20)). The diversity of isoprenoids reflects differences in chain length, cyclization and further additional modification after cyclization. In contrast, the biosynthesis of 2-methylisonorneol (2-MIB), which is responsible for taste and odour problems in drinking water, is unique in that it primes the enzymatic methylation of geranyl pyrophosphate (GPP) before cyclization, which is catalyzed by an S-adenosyl-L-methionine-dependent methyltransferase (GPPMT). The substrate of GPPMT contains a nonconjugated olefin and the reaction mechanism is expected to be similar to that of the steroid methyltransferase (SMT) family. Here, structural analysis of GPPMT in complex with its cofactor and substrate revealed the mechanisms of substrate recognition and possible enzymatic reaction. Using the structures of these complexes, methyl-group transfer and the subsequent proton-abstraction mechanism are discussed. GPPMT and SMTs contain a conserved glutamate residue that is likely to play a role as a general base. Comparison with the reaction mechanism of the mycolic acid cyclopropane synthase (MACS) family also supports this result. This enzyme represented here is the first model of the enzymatic C-methylation of a nonconjugated olefin in the isoprenoid-biosynthesis pathway. In addition, an elaborate system to avoid methylation of incorrect substrates is proposed.
USDA-ARS?s Scientific Manuscript database
Isoprenoids are a large class of compounds that are present in all living organisms. They are derived from the 5C building blocks isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). In plants, IPP is synthesized in the cytoplasm from mevalonic acid via the “MVA pathway” a...
Chaves, Julie E; Romero, Paloma Rueda; Kirst, Henning; Melis, Anastasios
2016-12-01
Heterologous production of isoprene (C 5 H 8 ) hydrocarbons in cyanobacteria, emanating from sunlight, CO 2 , and water, is now attracting increasing attention. The concept entails application of an isoprene synthase transgene from terrestrial plants, heterologously expressed in cyanobacteria, aiming to reprogram carbon flux in the terpenoid biosynthetic pathway toward formation and spontaneous release of this volatile chemical from the cell and liquid culture. However, flux manipulations and carbon-partitioning reactions between isoprene (the product) and native terpenoid biosynthesis for cellular needs are not yet optimized for isoprene yield. The primary reactant for isoprene biosynthesis is dimethylallyl diphosphate (DMAPP), whereas both DMAPP and its isopentenyl diphosphate (IPP) isomer are needed for cellular terpenoid biosynthesis. The present work addressed the function of an isopentenyl diphosphate (IPP) isomerase in cyanobacteria and its role in carbon partitioning between IPP and DMAPP, both of which serve, in variable ratios, as reactants for the synthesis of different cellular terpenoids. The work was approached upon the heterologous expression in Synechocystis of the "isopentenyl diphosphate isomerase" gene (FNI) from Streptococcus pneumoniae, using isoprene production as a "reporter process" for substrate partitioning between DMAPP and IPP. It is shown that transgenic expression of the FNI gene in Synechocystis resulted in a 250 % increase in the "reporter isoprene" rate and yield, suggesting that the FNI isomerase shifted the endogenous DMAPP-IPP steady-state pool size toward DMAPP, thereby enhancing rates and yield of isoprene production. The work provides insight into the significance and functional role of the IPP isomerase in these photosynthetic microorganisms.
Chou, Howard H [Berkeley, CA; Keasling, Jay D [Berkeley, CA
2011-07-26
The invention provides for a method for producing a 5-carbon alcohol in a genetically modified host cell. In one embodiment, the method comprises culturing a genetically modified host cell which expresses a first enzyme capable of catalyzing the dephosphorylation of an isopentenyl pyrophosphate (IPP) or dimethylallyl diphosphate (DMAPP), such as a Bacillus subtilis phosphatase (YhfR), under a suitable condition so that 5-carbon alcohol is 3-methyl-2-buten-1-ol and/or 3-methyl-3-buten-1-ol is produced. Optionally, the host cell may further comprise a second enzyme capable of reducing a 3-methyl-2-buten-1-ol to 3-methyl-butan-1-ol, such as a reductase.
Hoeffler, Jean-François; Hemmerlin, Andréa; Grosdemange-Billiard, Catherine; Bach, Thomas J; Rohmer, Michel
2002-01-01
In the bacterium Escherichia coli, the mevalonic-acid (MVA)-independent 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway is characterized by two branches leading separately to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The signature of this branching is the retention of deuterium in DMAPP and the deuterium loss in IPP after incorporation of 1-[4-(2)H]deoxy-d-xylulose ([4-(2)H]DX). Feeding tobacco BY-2 cell-suspension cultures with [4-(2)H]DX resulted in deuterium retention in the isoprene units derived from DMAPP, as well as from IPP in the plastidial isoprenoids, phytoene and plastoquinone, synthesized via the MEP pathway. This labelling pattern represents direct evidence for the presence of the DMAPP branch of the MEP pathway in a higher plant, and shows that IPP can be synthesized from DMAPP in plant plastids, most probably via a plastidial IPP isomerase. PMID:12010124
van Deenen, Nicole; Bachmann, Anne-Lena; Schmidt, Thomas; Schaller, Hubert; Sand, Jennifer; Prüfer, Dirk; Schulze Gronover, Christian
2012-04-01
Taraxacum brevicorniculatum is known to produce high quality rubber. The biosynthesis of rubber is dependent on isopentenyl pyrophosphate (IPP) precursors derived from the mevalonate (MVA) pathway. The cDNA sequences of seven MVA pathway genes from latex of T. brevicorniculatum were isolated, including three cDNA sequences encoding for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductases (TbHMGR1-3). Expression analyses indicate an important role of TbHMGR1 as well as for the HMG-CoA synthase (TbHMGS), the diphosphomevalonate decarboxylase and the mevalonate kinase in the provision of precursors for rubber biosynthesis. The amino acid sequences of the TbHMGRs show the typical motifs described for plant HMGRs such as two transmembrane domains and a catalytic domain containing two HMG-CoA and two NADP(H) binding sites. The functionality of the HMGRs was demonstrated by complementation assay using an IPP auxotroph mutant of Escherichia coli. Furthermore, the transient expression of the catalytic domains of TbHMGR1 and TbHMGR2 in Nicotiana benthamiana resulted in a strong accumulation of sterol precursors, one of the major groups of pathway end-products.
Type 1 Responses of Human Vγ9Vδ2 T Cells to Influenza A Viruses▿
Qin, Gang; Liu, Yinping; Zheng, Jian; Ng, Iris H. Y.; Xiang, Zheng; Lam, Kwok-Tai; Mao, Huawei; Li, Hong; Peiris, J. S. Malik; Lau, Yu-Lung; Tu, Wenwei
2011-01-01
γδ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells participated in anti-influenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs) in vitro. However, little is known about the noncytolytic responses and trafficking program of γδ T cells to influenza virus. In this study, we found that Vγ9Vδ2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-γ). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated γδ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-γ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in Vγ9Vδ2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of Vγ9Vδ2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human Vγ9Vδ2 T cells against influenza virus infection. PMID:21752902
USDA-ARS?s Scientific Manuscript database
Natural rubber biosynthesis occurs in laticifers of Ficus elastica and Hevea brasiliensis, and in parenchyma cells of Parthenium argentatum. Natural rubber is synthesized by rubber transferase using allylic pyrophosphates as initiators, isopentenyl pyrophosphate as monomeric substrate and magnesium ...
Grabińska, Kariona A; Park, Eon Joo; Sessa, William C
2016-08-26
cis-Prenyltransferases (cis-PTs) constitute a large family of enzymes conserved during evolution and present in all domains of life. cis-PTs catalyze consecutive condensation reactions of allylic diphosphate acceptor with isopentenyl diphosphate (IPP) in the cis (Z) configuration to generate linear polyprenyl diphosphate. The chain lengths of isoprenoid carbon skeletons vary widely from neryl pyrophosphate (C10) to natural rubber (C>10,000). The homo-dimeric bacterial enzyme, undecaprenyl diphosphate synthase (UPPS), has been structurally and mechanistically characterized in great detail and serves as a model for understanding the mode of action of eukaryotic cis-PTs. However, recent experiments have revealed that mammals, fungal, and long-chain plant cis-PTs are heteromeric enzymes composed of two distantly related subunits. In this review, the classification, function, and evolution of cis-PTs will be discussed with a special emphasis on the role of the newly described NgBR/Nus1 subunit and its plants' orthologs as essential, structural components of the cis-PTs activity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Methods for increasing production of 3-methyl-2-butenol using fusion proteins
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chou, Howard; Keasling, Jay D.
The present invention relates to methods and compositions for increasing production of 3-methyl-2-butenol in a de novo synthetic pathway in a genetically modified host cell using isopentenyl disphosphate (IPP) as a substrate.
Synthesis and Evaluation of Chlorinated Substrate Analogues for Farnesyl Diphosphate Synthase
Heaps, Nicole A.; Poulter, C. Dale
2011-01-01
Substrate analogues for isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), where the C3 methyl groups were replaced by chlorine, were synthesized and evaluated as substrates for avian farnesyl diphosphate synthase (FPPase). The IPP analogue (3-ClIPP) was a co-substrate when incubated with dimethylallyl diphosphate (DMAPP) or geranyl diphosphate (GPP) to give the corresponding chlorinated analogues of geranyl diphosphate (3-ClGPP) and farnesyl diphosphate (3-ClFPP), respectively. No products were detected in incubations of 3-ClIPP with 3-ClDMAPP. Incubation of IPP with 3-ClDMAPP gave 11-ClFPP as the sole product. Values of KM3-ClIPP (with DMAPP) and KM3-ClDMAPP (with IPP) were similar to those for IPP and DMAPP, however values of kcat for both analogues were substantially lower. These results are consistent with a dissociative electrophilic alkylation mechanism where the rate-limiting step changes from heterolytic cleavage of the carbon-oxygen bond in the allylic substrate to alkylation of the double bond of the homoallylic substrate. PMID:21344952
Metabolic routes affecting rubber biosynthesis in Hevea brasiliensis latex
Chow, Keng-See; Mat-Isa, Mohd.-Noor; Bahari, Azlina; Ghazali, Ahmad-Kamal; Alias, Halimah; Mohd.-Zainuddin, Zainorlina; Hoh, Chee-Choong; Wan, Kiew-Lian
2012-01-01
The cytosolic mevalonate (MVA) pathway in Hevea brasiliensis latex is the conventionally accepted pathway which provides isopentenyl diphosphate (IPP) for cis-polyisoprene (rubber) biosynthesis. However, the plastidic 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway may be an alternative source of IPP since its more recent discovery in plants. Quantitative RT-PCR (qRT-PCR) expression profiles of genes from both pathways in latex showed that subcellular compartmentalization of IPP for cis-polyisoprene synthesis is related to the degree of plastidic carotenoid synthesis. From this, the occurrence of two schemes of IPP partitioning and utilization within one species is proposed whereby the supply of IPP for cis-polyisoprene from the MEP pathway is related to carotenoid production in latex. Subsequently, a set of latex unique gene transcripts was sequenced and assembled and they were then mapped to IPP-requiring pathways. Up to eight such pathways, including cis-polyisoprene biosynthesis, were identified. Our findings on pre- and post-IPP metabolic routes form an important aspect of a pathway knowledge-driven approach to enhancing cis-polyisoprene biosynthesis in transgenic rubber trees. PMID:22162870
Metabolic routes affecting rubber biosynthesis in Hevea brasiliensis latex.
Chow, Keng-See; Mat-Isa, Mohd-Noor; Bahari, Azlina; Ghazali, Ahmad-Kamal; Alias, Halimah; Mohd-Zainuddin, Zainorlina; Hoh, Chee-Choong; Wan, Kiew-Lian
2012-03-01
The cytosolic mevalonate (MVA) pathway in Hevea brasiliensis latex is the conventionally accepted pathway which provides isopentenyl diphosphate (IPP) for cis-polyisoprene (rubber) biosynthesis. However, the plastidic 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway may be an alternative source of IPP since its more recent discovery in plants. Quantitative RT-PCR (qRT-PCR) expression profiles of genes from both pathways in latex showed that subcellular compartmentalization of IPP for cis-polyisoprene synthesis is related to the degree of plastidic carotenoid synthesis. From this, the occurrence of two schemes of IPP partitioning and utilization within one species is proposed whereby the supply of IPP for cis-polyisoprene from the MEP pathway is related to carotenoid production in latex. Subsequently, a set of latex unique gene transcripts was sequenced and assembled and they were then mapped to IPP-requiring pathways. Up to eight such pathways, including cis-polyisoprene biosynthesis, were identified. Our findings on pre- and post-IPP metabolic routes form an important aspect of a pathway knowledge-driven approach to enhancing cis-polyisoprene biosynthesis in transgenic rubber trees.
Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kang, Aram; George, Kevin W.; Wang, George
Branched C 5 alcohols are promising biofuels with excellent combustion properties. A mevalonate (MVA)-based isoprenoid biosynthetic pathway for C 5 alcohols was constructed in Escherichia coli using genes from several organisms, and the pathway was optimized to achieve over 50% theoretical yield. Although the MVA pathway is energetically less efficient than the native methylerythritol 4-phosphate (MEP) pathway, implementing the MVA pathway in bacterial hosts such as E. coli is advantageous due to its lack of endogenous regulation. The MVA and MEP pathways intersect at isopentenyl diphosphate (IPP), the direct precursor to isoprenoid-derived C 5 alcohols and initial precursor to longermore » chain terpenes, which makes independent regulation of the pathways difficult. In pursuit of the complete "decoupling" of the MVA pathway from native cellular regulation, we designed novel IPP-bypass MVA pathways for C 5 alcohol production by utilizing promiscuous activities of two enzymes, phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA). These bypass pathways have reduced energetic requirements, are further decoupled from intrinsic regulation, and are free from IPP-related toxicity. In addition to these benefits, we demonstrate that reduced aeration rate has less impact on the bypass pathway than the original MVA pathway. Finally, we showed that performance of the bypass pathway was primarily determined by the activity of PMD. We designed PMD mutants with improved activity and demonstrated titer increases in the mutant strains. These modified pathways would be a good platform for industrial production of isopentenol and related chemicals such as isoprene.« less
Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production
Kang, Aram; George, Kevin W.; Wang, George; ...
2015-12-17
Branched C 5 alcohols are promising biofuels with excellent combustion properties. A mevalonate (MVA)-based isoprenoid biosynthetic pathway for C 5 alcohols was constructed in Escherichia coli using genes from several organisms, and the pathway was optimized to achieve over 50% theoretical yield. Although the MVA pathway is energetically less efficient than the native methylerythritol 4-phosphate (MEP) pathway, implementing the MVA pathway in bacterial hosts such as E. coli is advantageous due to its lack of endogenous regulation. The MVA and MEP pathways intersect at isopentenyl diphosphate (IPP), the direct precursor to isoprenoid-derived C 5 alcohols and initial precursor to longermore » chain terpenes, which makes independent regulation of the pathways difficult. In pursuit of the complete "decoupling" of the MVA pathway from native cellular regulation, we designed novel IPP-bypass MVA pathways for C 5 alcohol production by utilizing promiscuous activities of two enzymes, phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA). These bypass pathways have reduced energetic requirements, are further decoupled from intrinsic regulation, and are free from IPP-related toxicity. In addition to these benefits, we demonstrate that reduced aeration rate has less impact on the bypass pathway than the original MVA pathway. Finally, we showed that performance of the bypass pathway was primarily determined by the activity of PMD. We designed PMD mutants with improved activity and demonstrated titer increases in the mutant strains. These modified pathways would be a good platform for industrial production of isopentenol and related chemicals such as isoprene.« less
Banthorpe, Derek V.; Le Patourel, Geoffrey N. J.; Francis, Martin J. O.
1972-01-01
1. 3R-[2-14C]Mevalonate was incorporated into geranyl and neryl β-d-glucosides in petals of Rosa dilecta in up to 10.6% yield, and the terpenoid part was specifically and equivalently labelled in the moieties derived from isopentenyl pyrophosphate and 3,3-dimethylallyl pyrophosphate. A similar labelling pattern, with incorporations of 0.06–0.1% was found for geraniol or nerol formed in leaves of Pelargonium graveolens The former results provide the best available evidence for the mevalonoid route to regular monoterpenes in higher plants. 2. Incorporation studies with 3RS-[2-14C,(4R)-4-3H1]-mevalonate and its (4S)-isomer showed that the pro-4R hydrogen atom of the precursor was retained and the pro-4S hydrogen atom was eliminated in both alcohols and both glucosides. These results suggest that the correlation of retention of the pro-4S hydrogen atom of mevalonate with formation of a cis-substituted double bond, such as has been found in certain higher terpenoids, does not apply to the biosynthesis of monoterpenes. It is proposed that either nerol is derived from isomerization of geraniol or the two alcohols are directly formed by different prenyltransferases. Possible mechanisms for these processes are discussed. 3. The experiments with [14C,3H]mevalonate also show that in these higher plants, as has been previously found in animal tissue and yeast, the pro-4S hydrogen atom of mevalonate was lost in the conversion of isopentenyl pyrophosphate into 3,3-dimethylallyl pyrophosphate. PMID:4348258
USDA-ARS?s Scientific Manuscript database
The 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway leads to the synthesis of isopentenyl-phosphate (IPP) in plastids. It is a major branch point providing precursors for the synthesis of carotenoids, tocopherols, plastoquinone and the phytyl chain of chlorophylls, as well as the hormones abscisi...
Sakamoto, Hirokazu; Suzuki, Shigeo; Nagamune, Kisaburo; Kita, Kiyoshi; Matsuzaki, Motomichi
2017-07-01
Some organisms have retained plastids even after they have lost the ability to photosynthesize. Several studies of nonphotosynthetic plastids in apicomplexan parasites have shown that the isopentenyl pyrophosphate biosynthesis pathway in the organelle is essential for their survival. A phytohormone, abscisic acid, one of several compounds biosynthesized from isopentenyl pyrophosphate, regulates the parasite cell cycle. Thus, it is possible that the phytohormone is universally crucial, even in nonphotosynthetic plastids. Here, we examined this possibility using the oyster parasite Perkinsus marinus, which is a plastid-harboring cousin of apicomplexan parasites and has independently lost photosynthetic ability. Fluridone, an inhibitor of abscisic acid biosynthesis, blocked parasite growth and induced cell clustering. Nevertheless, abscisic acid and its intermediate carotenoids did not affect parasite growth or rescue the parasite from inhibition. Moreover, abscisic acid was not detected from the parasite using liquid chromatography mass spectrometry. Our findings show that abscisic acid does not play any significant roles in P. marinus. © 2016 The Authors. Journal of Eukaryotic Microbiology published by Wiley Periodicals, Inc. on behalf of International Society of Protistologists.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heider, Sabine A. E.; Wolf, Natalie; Hofemeier, Arne
The biotechnologically relevant bacterium Corynebacterium glutamicum, currently used for the million ton-scale production of amino acids for the food and feed industries, is pigmented due to synthesis of the rare cyclic C50 carotenoid decaprenoxanthin and its glucosides. The precursors of carotenoid biosynthesis, isopenthenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate, are synthesized in this organism via the methylerythritol phosphate (MEP) or non-mevalonate pathway. Terminal pathway engineering in recombinant C. glutamicum permitted the production of various non-native C50 and C40 carotenoids. Here, the role of engineering isoprenoid precursor supply for lycopene production by C. glutamicum was characterized. Overexpression of dxs encodingmore » the enzyme that catalyzes the first committed step of the MEP-pathway by chromosomal promoter exchange in a prophage-cured, genome-reduced C. glutamicum strain improved lycopene formation. Similarly, an increased IPP supply was achieved by chromosomal integration of two artificial operons comprising MEP pathway genes under the control of a constitutive promoter. Combined overexpression of dxs and the other six MEP pathways genes in C. glutamicum strain LYC3-MEP was not synergistic with respect to improving lycopene accumulation. Based on C. glutamicum strain LYC3-MEP, astaxanthin could be produced in the milligrams per gram cell dry weight range when the endogenous genes crtE, crtB, and crtI for conversion of geranylgeranyl pyrophosphate to lycopene were coexpressed with the genes for lycopene cyclase and β-carotene hydroxylase from Pantoea ananatis and carotene C(4) oxygenase from Brevundimonas aurantiaca.« less
Engprasert, Surang; Taura, Futoshi; Kawamukai, Makoto; Shoyama, Yukihiro
2004-01-01
Background Isopentenyl diphosphate (IPP), a common biosynthetic precursor to the labdane diterpene forskolin, has been biosynthesised via a non-mevalonate pathway. Geranylgeranyl diphosphate (GGPP) synthase is an important branch point enzyme in terpenoid biosynthesis. Therefore, GGPP synthase is thought to be a key enzyme in biosynthesis of forskolin. Herein we report the first confirmation of the GGPP synthase gene in Coleus forskohlii Briq. Results The open reading frame for full-length GGPP synthase encodes a protein of 359 amino acids, in which 1,077 nucleotides long with calculated molecular mass of 39.3 kDa. Alignments of C. forskohlii GGPP synthase amino acid sequences revealed high homologies with other plant GGPP synthases. Several highly conserved regions, including two aspartate-rich motifs were identified. Transient expression of the N-terminal region of C. forskohlii GGPP synthase-GFP fusion protein in tobacco cells demonstrated subcellular localization in the chloroplast. Carotenoid production was observed in Escherichia coli harboring pACCAR25ΔcrtE from Erwinia uredovora and plasmid carrying C. forskohlii GGPP synthase. These results suggested that cDNA encoded functional GGPP synthase. Furthermore, C. forskohlii GGPP synthase expression was strong in leaves, decreased in stems and very little expression was observed in roots. Conclusion This investigation proposed that forskolin was synthesised via a non-mevalonate pathway. GGPP synthase is thought to be involved in the biosynthesis of forskolin, which is primarily synthesised in the leaves and subsequently accumulates in the stems and roots. PMID:15550168
Kang, Aram; Meadows, Corey W.; Canu, Nicolas; ...
2017-04-05
Isopentenol (or isoprenol, 3-methyl-3-buten-1-ol) is a drop-in biofuel and a precursor for commodity chemicals such as isoprene. Biological production of isopentenol via the mevalonate pathway has been optimized extensively in Escherichia coli, yielding 70% of its theoretical maximum. However, high ATP requirements and isopentenyl diphosphate (IPP) toxicity pose immediate challenges for engineering bacterial strains to overproduce commodities utilizing IPP as an intermediate. To overcome these limitations, we developed an “IPP-bypass” isopentenol pathway using the promiscuous activity of a mevalonate diphosphate decarboxylase (PMD) and demonstrated improved performance under aeration-limited conditions. However, relatively low activity of PMD toward the non-native substrate (mevalonatemore » monophosphate, MVAP) was shown to limit flux through this new pathway. By inhibiting all IPP production from the endogenous non-mevalonate pathway, we developed a high-throughput screening platform that correlated promiscuous PMD activity toward MVAP with cellular growth. Successful identification of mutants that altered PMD activity demonstrated the sensitivity and specificity of the screening platform. Strains with evolved PMD mutants and the novel IPP-bypass pathway increased titers up to 2.4-fold. Further enzymatic characterization of the evolved PMD variants suggested that higher isopentenol titers could be achieved either by altering residues directly interacting with substrate and cofactor or by altering residues on nearby α-helices. These altered residues could facilitate the production of isopentenol by tuning either k cat or K i of PMD for the non-native substrate. The synergistic modification made on PMD for the IPP-bypass mevalonate pathway is expected to significantly facilitate the industrial scale production of isopentenol.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kang, Aram; Meadows, Corey W.; Canu, Nicolas
Isopentenol (or isoprenol, 3-methyl-3-buten-1-ol) is a drop-in biofuel and a precursor for commodity chemicals such as isoprene. Biological production of isopentenol via the mevalonate pathway has been optimized extensively in Escherichia coli, yielding 70% of its theoretical maximum. However, high ATP requirements and isopentenyl diphosphate (IPP) toxicity pose immediate challenges for engineering bacterial strains to overproduce commodities utilizing IPP as an intermediate. To overcome these limitations, we developed an “IPP-bypass” isopentenol pathway using the promiscuous activity of a mevalonate diphosphate decarboxylase (PMD) and demonstrated improved performance under aeration-limited conditions. However, relatively low activity of PMD toward the non-native substrate (mevalonatemore » monophosphate, MVAP) was shown to limit flux through this new pathway. By inhibiting all IPP production from the endogenous non-mevalonate pathway, we developed a high-throughput screening platform that correlated promiscuous PMD activity toward MVAP with cellular growth. Successful identification of mutants that altered PMD activity demonstrated the sensitivity and specificity of the screening platform. Strains with evolved PMD mutants and the novel IPP-bypass pathway increased titers up to 2.4-fold. Further enzymatic characterization of the evolved PMD variants suggested that higher isopentenol titers could be achieved either by altering residues directly interacting with substrate and cofactor or by altering residues on nearby α-helices. These altered residues could facilitate the production of isopentenol by tuning either k cat or K i of PMD for the non-native substrate. The synergistic modification made on PMD for the IPP-bypass mevalonate pathway is expected to significantly facilitate the industrial scale production of isopentenol.« less
Tashiro, Miki; Fujii, Akira; Kawai-Noma, Shigeko; Saito, Kyoichi; Umeno, Daisuke
2017-11-17
To achieve an efficient production of geraniol and its derivatives in Escherichia coli, we aimed to improve the activity of geraniol synthase (GES) through a single round of mutagenesis and screening for higher substrate consumption. We isolated GES variants that outperform their parent in geraniol production. The analysis of GES variants indicated that the expression level of GES was the bottleneck for geraniol synthesis. Over-expression of the mutant GES M53 with a 5'-untranslated sequence designed for high translational efficiency, along with the additional expression of mevalonate pathway enzymes, isopentenyl pyrophosphate isomerase, and geranyl pyrophosphate synthase, yielded 300 mg/L/12 h geraniol and its derivatives (>1000 mg/L/42 h in total) in a shaking flask.
The effect of phloretin on human γδ T cells killing colon cancer SW-1116 cells.
Zhu, Sheng-Ping; Liu, Gang; Wu, Xiao-Ting; Chen, Fu-Xing; Liu, Jun-Quan; Zhou, Zhong-Hai; Zhang, Jian-Fu; Fei, Su-Juan
2013-01-01
To explore the effect and mechanism of Phloretin on human γδ T cells killing colon cancer SW-1116 cells. γδ T cells were amplified in vitro from human peripheral blood mononuclear cells through isopentenyl pyrophosphate method (IPP). After cocultured different concentrations of Phloretin with γδ T cells or SW-1116 cells for 48h respectively, MTT assay was used to test the growth curve of these two cells; Flow cytometry to test the expression of Granzyme B (GraB), perforin (PFP), CD107a and IFN-γ of γδ T cells; Lactate dehydrogenase (LDH) release assay to test the cytotoxic activity of the γδ T cells on SW-1116 cells; and Western blot to test the Wnt3a expression of the γδ T cells. After cultured with IPP for ten days, the percentage of γδ T cells increased from 3.31±3.00% to 78.40±10.30%. Compared to the control group, when the concentration of Phloretin increased from 2.35μg/ml to 18.75μg/ml, it could significantly proliferate the γδ T cell growth (P<0.05) and inhibit the growth of SW-1116 cells in dose-response, and the expression of GraB, PFP, CD107a and Wnt3a significantly increased (P<0.05). Significant positive relationships were observed among CD107a and PFP, GraB, cytotoxicity (P<0.05). The percentage of IFN-γ producing γδ T cells treated with Phloretin was significantly higher than control group. Phloretin can enhance the killing effect of γδ T cells on SW-1116 cells; the mechanism may be that Phloretin could proliferate the γδ T cell growth, increase the expression of PFP and GraB, activate the Wnt signaling pathway, and produce higher level of IFN-γ. Indeed CD107a expression probably correlates quite well with antitumor activity. Copyright © 2012 Elsevier B.V. All rights reserved.
Sensor Function for Butyrophilin 3A1 in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells
Wang, Hong; Morita, Craig T.
2016-01-01
Vγ2Vδ2 T cells play important roles in human immunity to pathogens and in cancer immunotherapy by responding to isoprenoid metabolites, such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and isopentenyl pyrophosphate. The Ig superfamily protein butyrophilin (BTN)3A1 was shown to be required for prenyl pyrophosphate stimulation. We proposed that the intracellular B30.2 domain of BTN3A1 binds prenyl pyrophosphates, resulting in a change in the extracellular BTN3A1 dimer that is detected by Vγ2Vδ2 TCRs. Such B30.2 binding was demonstrated recently. However, other investigators reported that the extracellular BTN3A1 IgV domain binds prenyl pyrophosphates, leading to the proposal that the Vγ2Vδ2 TCR recognizes the complex. To distinguish between these mechanisms, we mutagenized residues in the two binding sites and tested the mutant BTN3A1 proteins for their ability to mediate prenyl pyrophosphate stimulation of Vγ2Vδ2 T cells to proliferate and secrete TNF-α. Mutagenesis of residues in the IgV site had no effect on Vγ2Vδ2 T cell proliferation or secretion of TNF-α. In contrast, mutagenesis of residues within the basic pocket and surrounding V regions of the B30.2 domain abrogated prenyl pyrophosphate-induced proliferation. Mutations of residues making hydrogen bonds to the pyrophosphate moiety also abrogated TNF-α secretion, as did mutation of aromatic residues making contact with the alkenyl chain. Some mutations further from the B30.2 binding site also diminished stimulation, suggesting that the B30.2 domain may interact with a second protein. These findings support intracellular sensing of prenyl pyrophosphates by BTN3A1 rather than extracellular presentation. PMID:26475929
Olson, Robert J.; Trumble, Thomas E.; Gamble, Wilbert
1974-01-01
2,4-Dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid inhibited the incorporation of [2-14C]mevalonate into cholesterol and non-saponifiable lipids. Both compounds inhibited the conversion of [1-14C]isopentenyl pyrophosphate into cholesterol and the synthesis of cholesterol and fatty acids from [2-14C]acetate. There was no inhibition of the conversion of [1-14C]mevalonate into CO2. At low concentrations (0.5mm) of the compounds there was a stimulation of acetate incorporation into fatty acids. PMID:4441387
Withers, Sydnor T.; Gottlieb, Shayin S.; Lieu, Bonny; Newman, Jack D.; Keasling, Jay D.
2007-01-01
We have developed a novel method to clone terpene synthase genes. This method relies on the inherent toxicity of the prenyl diphosphate precursors to terpenes, which resulted in a reduced-growth phenotype. When these precursors were consumed by a terpene synthase, normal growth was restored. We have demonstrated that this method is capable of enriching a population of engineered Escherichia coli for those clones that express the sesquiterpene-producing amorphadiene synthase. In addition, we enriched a library of genomic DNA from the isoprene-producing bacterium Bacillus subtilis strain 6051 in E. coli engineered to produce elevated levels of isopentenyl diphosphate and dimethylallyl diphosphate. The selection resulted in the discovery of two genes (yhfR and nudF) whose protein products acted directly on the prenyl diphosphate precursors and produced isopentenol. Expression of nudF in E. coli engineered with the mevalonate-based isopentenyl pyrophosphate biosynthetic pathway resulted in the production of isopentenol. PMID:17693564
Karunakaran, Mohindar M.; Herrmann, Thomas
2014-01-01
Most circulating human gamma delta T cells are Vγ9Vδ2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains show a Vγ9-JP (Vγ2-Jγ1.2) rearrangement and are paired with Vδ2-containing δ-chains, a dominant TCR configuration, which until recently seemed to occur in primates only. Vγ9Vδ2 T cells respond to phosphoantigens (PAg) such as (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is produced by many pathogens and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. A prerequisite for PAg-induced activation is the contact of Vγ9Vδ2 T cells with cells expressing butyrophilin-3 A1 (BTN3A1). We will first critically review models of how BTN3 might act in PAg-mediated Vγ9Vδ2 T cell activation and then address putative co-evolution of Vγ9, Vδ2, and BTN3 genes. In those rodent and lagomorphs used as animal models, all three genes are lost but a data-base analysis showed that they emerged together with placental mammals. A strong concomitant conservation of functional Vγ9, Vδ2, and BTN3 genes in other species suggests co-evolution of these three genes. A detailed analysis was performed for the new world camelid alpaca (Vicugna pacos). It provides an excellent candidate for a non-primate species with presumably functional Vγ9Vδ2 T cells since TCR rearrangements share features characteristic for PAg-reactive primate Vγ9Vδ2 TCR and proposed PAg-binding sites of BTN3A1 have been conserved. Finally, we analyze the possible functional relationship between the butyrophilin-family member Skint1 and the γδ TCR-V genes used by murine dendritic epithelial T cells (DETC). Among placental mammals, we identify five rodents, the cow, a bat, and the cape golden mole as the only species concomitantly possessing potentially functional homologs of murine Vγ3, Vδ4 genes, and Skint1 gene and suggest to search for DETC like cells in these species. PMID:25566259
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Chuan-Hsiang; Gabelli, Sandra B.; Oldfield, Eric
Bisphosphonates (BPs) are a class of compounds that have been used extensively in the treatment of osteoporosis and malignancy-related hypercalcemia. Some of these compounds act through inhibition of farnesyl diphosphate synthase (FPPS), a key enzyme in the synthesis of isoprenoids. Recently, nitrogen-containing bisphosphonates (N-BPs) used in bone resorption therapy have been shown to be active against Trypanosoma cruzi, the parasite that causes American trypanosomiasis (Chagas disease), suggesting that they may be used as anti-trypanosomal agents. The crystal structures of TcFPPS in complex with substrate (isopentenyl diphosphate, IPP) and five N-BP inhibitors show that the C-1 hydroxyl and the nitrogen-containing groupsmore » of the inhibitors alter the binding of IPP and the conformation of two TcFPPS residues, Tyr94 and Gln167. Isothermal titration calorimetry experiments suggest that binding of the first N-BPs to the homodimeric TcFPPS changes the binding properties of the second site. This mechanism of binding of N-BPs to TcFPPS is different to that reported for the binding of the same compounds to human FPPS.« less
Wen, Zewen; Liu, Zhiyong; Hou, Yuyong; Liu, Chenfeng; Gao, Feng; Zheng, Yubin; Chen, Fangjian
2015-10-01
Haematococcus pluvialis is one of the most promising natural sources of astaxanthin. However, inducing the accumulation process has become one of the primary obstacles in astaxanthin production. In this study, the effect of ethanol on astaxanthin accumulation was investigated. The results demonstrated that astaxanthin accumulation occurred with ethanol addition even under low-light conditions. The astaxanthin productivity could reach 11.26 mg L(-1) d(-1) at 3% (v/v) ethanol, which was 2.03 times of that of the control. The transcriptional expression patterns of eight carotenogenic genes were evaluated using real-time PCR. The results showed that ethanol greatly enhanced transcription of the isopentenyl diphosphate (IPP) isomerase genes (ipi-1 and ipi-2), which were responsible for isomerization reaction of IPP and dimethylallyl diphosphate (DMAPP). This finding suggests that ethanol induced astaxanthin biosynthesis was up-regulated mainly by ipi-1 and ipi-2 at transcriptional level, promoting isoprenoid synthesis and substrate supply to carotenoid formation. Thus ethanol has the potential to be used as an effective reagent to induce astaxanthin accumulation in H. pluvialis. Copyright © 2015 Elsevier Inc. All rights reserved.
Cipriani, B; Borsellino, G; Knowles, H; Tramonti, D; Cavaliere, F; Bernardi, G; Battistini, L; Brosnan, C F
2001-09-15
Curcumin, in addition to its role as a spice, has been used for centuries to treat inflammatory disorders. Although the mechanism of action remains unclear, it has been shown to inhibit the activation of NF-kappaB and AP-1, transcription factors required for induction of many proinflammatory mediators. Due to its low toxicity it is currently under consideration as a broad anti-inflammatory, anti-tumor cell agent. In this study we investigated whether curcumin inhibited the response of gammadelta T cells to protease-resistant phosphorylated derivatives found in the cell wall of many pathogens. The results showed that curcumin levels > or =30 microM profoundly inhibited isopentenyl pyrophosphate-induced release of the chemokines macrophage inflammatory protein-1alpha and -1beta and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-kappaB and AP-1. Commencing around 16 h, treatment with curcumin lead to the induction of cell death that could not be reversed by APC, IL-15, or IL-2. This cytotoxicity was associated with increased annexin V reactivity, nuclear expression of active caspase-3, cleavage of poly(ADP-ribose) polymerase, translocation of apoptosis-inducing factor to the nucleus, and morphological evidence of nuclear disintegration. However, curcumin led to only large scale DNA chromatolysis, as determined by a combination of TUNEL staining and pulse-field and agarose gel electrophoresis, suggesting a predominantly apoptosis-inducing factor-mediated cell death process. We conclude that gammadelta T cells activated by these ubiquitous Ags are highly sensitive to curcumin, and that this effect may contribute to the anti-inflammatory properties of this compound.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aripirala, Srinivas; Gonzalez-Pacanowska, Dolores; Oldfield, Eric
Structural insights into L. major farnesyl diphosphate synthase, a key enzyme in the mevalonate pathway, are described. Farnesyl diphosphate synthase (FPPS) is an essential enzyme involved in the biosynthesis of sterols (cholesterol in humans and ergosterol in yeasts, fungi and trypanosomatid parasites) as well as in protein prenylation. It is inhibited by bisphosphonates, a class of drugs used in humans to treat diverse bone-related diseases. The development of bisphosphonates as antiparasitic compounds targeting ergosterol biosynthesis has become an important route for therapeutic intervention. Here, the X-ray crystallographic structures of complexes of FPPS from Leishmania major (the causative agent of cutaneousmore » leishmaniasis) with three bisphosphonates determined at resolutions of 1.8, 1.9 and 2.3 Å are reported. Two of the inhibitors, 1-(2-hydroxy-2,2-diphosphonoethyl)-3-phenylpyridinium (300B) and 3-butyl-1-(2,2-diphosphonoethyl)pyridinium (476A), co-crystallize with the homoallylic substrate isopentenyl diphosphate (IPP) and three Ca{sup 2+} ions. A third inhibitor, 3-fluoro-1-(2-hydroxy-2,2-diphosphonoethyl)pyridinium (46I), was found to bind two Mg{sup 2+} ions but not IPP. Calorimetric studies showed that binding of the inhibitors is entropically driven. Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. The asymmetric structure of the LmFPPS–46I homodimer indicates that binding of the allylic substrate to both monomers of the dimer results in an asymmetric dimer with one open and one closed homoallylic site. It is proposed that IPP first binds to the open site, which then closes, opening the site on the other monomer, which closes after binding the second IPP, leading to the symmetric fully occupied FPPS dimer observed in other structures.« less
Fowler, Daniel W; Copier, John; Dalgleish, Angus G; Bodman-Smith, Mark D
2017-09-01
Vδ2 + T cells are a subpopulation of γδ T cells in humans that are cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen-containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to Vδ2 + T cell cytotoxicity. However, little is known about whether ZA renders other, non-malignant cell types susceptible. In this study we focussed on macrophages (Mϕs), as these cells have been shown to take up ZA. We differentiated peripheral blood monocytes from healthy donors into Mϕs and then treated them with IFN-γ or IL-4 to generate M1 and M2 Mϕs, respectively. We characterised these Mϕs based on their phenotype and cytokine production and then tested whether ZA rendered them susceptible to Vδ2 + T cell cytotoxicity. Consistent with the literature, IFN-γ-treated Mϕs expressed higher levels of the M1 markers CD64 and IL-12p70, whereas IL-4-treated Mϕs expressed higher levels of the M2 markers CD206 and chemokine (C-C motif) ligand 18. When treated with ZA, both M1 and M2 Mϕs became susceptible to Vδ2 + T cell cytotoxicity. Vδ2 + T cells expressed perforin and degranulated in response to ZA-treated Mϕs as shown by mobilisation of CD107a and CD107b to the cell surface. Furthermore, cytotoxicity towards ZA-treated Mϕs was sensitive-at least in part-to the perforin inhibitor concanamycin A. These findings suggest that ZA can render M1 and M2 Mϕs susceptible to Vδ2 + T cell cytotoxicity in a perforin-dependent manner, which has important implications regarding the use of ZA in cancer immunotherapy.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gabelli,S.; McLellan, J.; Montalvetti, A.
2006-01-01
Typanosoma cruzi, the causative agent of Chagas disease, has recently been shown to be sensitive to the action of the bisphosphonates currently used in bone resorption therapy. These compounds target the mevalonate pathway by inhibiting farnesyl diphosphate synthase (farnesyl pyrophosphate synthase, FPPS), the enzyme that condenses the diphosphates of C{sub 5} alcohols (isopentenyl and dimethylallyl) to form C{sub 10} and C{sub 15} diphosphates (geranyl and farnesyl). The structures of the T. cruzi FPPS (TcFPPS) alone and in two complexes with substrates and inhibitors reveal that following binding of the two substrates and three Mg2+ ions, the enzyme undergoes a conformationalmore » change consisting of a hinge-like closure of the binding site. In this conformation, it would be possible for the enzyme to bind a bisphosphonate inhibitor that spans the sites usually occupied by dimethylallyl diphosphate (DMAPP) and the homoallyl moiety of isopentenyl diphosphate. This observation may lead to the design of new, more potent anti-trypanosomal bisphosphonates, because existing FPPS inhibitors occupy only the DMAPP site. In addition, the structures provide an important mechanistic insight: after its formation, geranyl diphosphate can swing without leaving the enzyme, from the product site to the substrate site to participate in the synthesis of farnesyl diphosphate.« less
Dynamics of Monoterpene Formation in Spike Lavender Plants.
Mendoza-Poudereux, Isabel; Kutzner, Erika; Huber, Claudia; Segura, Juan; Arrillaga, Isabel; Eisenreich, Wolfgang
2017-12-19
The metabolic cross-talk between the mevalonate (MVA) and the methylerythritol phosphate (MEP) pathways was analyzed in spike lavender ( Lavandula latifolia Med) on the basis of 13 CO₂-labelling experiments using wildtype and transgenic plants overexpressing the 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), the first and key enzyme of the MVA pathway. The plants were labelled in the presence of 13 CO₂ in a gas chamber for controlled pulse and chase periods of time. GC/MS and NMR analysis of 1,8-cineole and camphor, the major monoterpenes present in their essential oil, indicated that the C5-precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) of both monoterpenes are predominantly biosynthesized via the MEP pathway. Surprisingly, overexpression of HMGR did not have significant impact upon the crosstalk between the MVA and MEP pathways indicating that the MEP route is the preferred pathway for the synthesis of C5 monoterpene precursors in spike lavender.
Unknown components of the plastidial permeome
Pick, Thea R.; Weber, Andreas P. M.
2014-01-01
Beyond their role in photosynthesis plastids provide a plethora of additional metabolic functions to plant cells. For example, they harbor complete biosynthetic pathways for the de novo synthesis of carotenoids, fatty acids, and amino acids. Furthermore plastids contribute important reactions to multi-compartmentalized pathways, such as photorespiration or plant hormone syntheses, and they depend on the import of essential molecules that they cannot synthesize themselves, such as ascorbic acid. This causes a high traffic of metabolites across the plastid envelope. Although it was recently shown that non-polar substrates could be exchanged between the plastid and the ER without involving transporters, various essential transport processes are mediated by highly selective but still unknown metabolite transporters. This review focuses on selected components of the plastidial permeome that are predicted to exist but that have not yet been identified as molecular entities, such as the transporters for isopentenyl diphosphate (IPP) or ascorbic acid. PMID:25191333
An Enzymatic Platform for the Synthesis of Isoprenoid Precursors
Rodriguez, Sofia B.; Leyh, Thomas S.
2014-01-01
The isoprenoid family of compounds is estimated to contain ∼65,000 unique structures including medicines, fragrances, and biofuels. Due to their structural complexity, many isoprenoids can only be obtained by extraction from natural sources, an inherently risky and costly process. Consequently, the biotechnology industry is attempting to genetically engineer microorganisms that can produce isoprenoid-based drugs and fuels on a commercial scale. Isoprenoid backbones are constructed from two, five-carbon building blocks, isopentenyl 5-pyrophosphate and dimethylallyl 5-pyrophosphate, which are end-products of either the mevalonate or non-mevalonate pathways. By linking the HMG-CoA reductase pathway (which produces mevalonate) to the mevalonate pathway, these building block can be synthesized enzymatically from acetate, ATP, NAD(P)H and CoA. Here, the enzymes in these pathways are used to produce pathway intermediates and end-products in single-pot reactions and in remarkably high yield, ∼85%. A strategy for the regio-specific incorporation of isotopes into isoprenoid backbones is developed and used to synthesize a series of isotopomers of diphosphomevalonate, the immediate end-product of the mevalonate pathway. The enzymatic system is shown to be robust and capable of producing quantities of product in aqueous solutions that meet or exceed the highest levels achieved using genetically engineered organisms in high-density fermentation. PMID:25153179
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Chun-Liang; Mermoud, James C.; Paul, Lake N.
The mevalonate pathway produces isopentenyl diphosphate (IPP), a building block for polyisoprenoid synthesis, and is a crucial pathway for growth of the human bacterial pathogen Enterococcus faecalis. The final enzyme in this pathway, mevalonate diphosphate decarboxylase (MDD), acts on mevalonate diphosphate (MVAPP) to produce IPP while consuming ATP. This essential enzyme has been suggested as a therapeutic target for the treatment of drug-resistant bacterial infections. Here, we report functional and structural studies on the mevalonate diphosphate decarboxylase from E. faecalis (MDDEF). The MDDEF crystal structure in complex with ATP (MDDEF–ATP) revealed that the phosphate-binding loop (amino acids 97–105) is notmore » involved in ATP binding and that the phosphate tail of ATP in this structure is in an outward-facing position pointing away from the active site. This suggested that binding of MDDEF to MVAPP is necessary to guide ATP into a catalytically favorable position. Enzymology experiments show that the MDDEF performs a sequential ordered bi-substrate reaction with MVAPP as the first substrate, consistent with the isothermal titration calorimetry (ITC) experiments. On the basis of ITC results, we propose that this initial prerequisite binding of MVAPP enhances ATP binding. In summary, our findings reveal a substrate-induced substrate-binding event that occurs during the MDDEF-catalyzed reaction. The disengagement of the phosphate-binding loop concomitant with the alternative ATP-binding configuration may provide the structural basis for antimicrobial design against these pathogenic enterococci.« less
Dynamics of Monoterpene Formation in Spike Lavender Plants
Kutzner, Erika; Huber, Claudia; Segura, Juan; Arrillaga, Isabel
2017-01-01
The metabolic cross-talk between the mevalonate (MVA) and the methylerythritol phosphate (MEP) pathways was analyzed in spike lavender (Lavandula latifolia Med) on the basis of 13CO2-labelling experiments using wildtype and transgenic plants overexpressing the 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), the first and key enzyme of the MVA pathway. The plants were labelled in the presence of 13CO2 in a gas chamber for controlled pulse and chase periods of time. GC/MS and NMR analysis of 1,8-cineole and camphor, the major monoterpenes present in their essential oil, indicated that the C5-precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) of both monoterpenes are predominantly biosynthesized via the MEP pathway. Surprisingly, overexpression of HMGR did not have significant impact upon the crosstalk between the MVA and MEP pathways indicating that the MEP route is the preferred pathway for the synthesis of C5 monoterpene precursors in spike lavender. PMID:29257083
Metabolic engineering for the high-yield production of isoprenoid-based C 5 alcohols in E. coli
DOE Office of Scientific and Technical Information (OSTI.GOV)
George, Kevin W.; Thompson, Mitchell G.; Kang, Aram
2015-06-08
Branched five carbon (C 5) alcohols are attractive targets for microbial production due to their desirable fuel properties and importance as platform chemicals. In this study, we engineered a heterologous isoprenoid pathway in E. coli for the high-yield production of 3-methyl-3-buten-1-ol, 3-methyl-2-buten-1-ol, and 3-methyl-1-butanol, three C 5 alcohols that serve as potential biofuels. We first constructed a pathway for 3-methyl-3-buten-1-ol, where metabolite profiling identified NudB, a promiscuous phosphatase, as a likely pathway bottleneck. We achieved a 60% increase in the yield of 3-methyl-3-buten-1-ol by engineering the Shine-Dalgarno sequence of nudB, which increased protein levels by 9-fold and reduced isopentenyl diphosphatemore » (IPP) accumulation by 4-fold. To further optimize the pathway, we adjusted mevalonate kinase (MK) expression and investigated MK enzymes from alternative microbes such as Methanosarcina mazei. Next, we expressed a fusion protein of IPP isomerase and the phosphatase (Idi1~NudB) along with a reductase (NemA) to diversify production to 3-methyl-2-buten-1-ol and 3-methyl-1-butanol. Lastly, we used an oleyl alcohol overlay to improve alcohol recovery, achieving final titers of 2.23 g/L of 3-methyl-3-buten-1-ol (~70% of pathway-dependent theoretical yield), 150 mg/L of 3-methyl-2-buten-1-ol, and 300 mg/L of 3-methyl-1-butanol.« less
Metabolic engineering for the high-yield production of isoprenoid-based C5 alcohols in E. coli
George, Kevin W.; Thompson, Mitchell G.; Kang, Aram; Baidoo, Edward; Wang, George; Chan, Leanne Jade G.; Adams, Paul D.; Petzold, Christopher J.; Keasling, Jay D.; Soon Lee, Taek
2015-01-01
Branched five carbon (C5) alcohols are attractive targets for microbial production due to their desirable fuel properties and importance as platform chemicals. In this study, we engineered a heterologous isoprenoid pathway in E. coli for the high-yield production of 3-methyl-3-buten-1-ol, 3-methyl-2-buten-1-ol, and 3-methyl-1-butanol, three C5 alcohols that serve as potential biofuels. We first constructed a pathway for 3-methyl-3-buten-1-ol, where metabolite profiling identified NudB, a promiscuous phosphatase, as a likely pathway bottleneck. We achieved a 60% increase in the yield of 3-methyl-3-buten-1-ol by engineering the Shine-Dalgarno sequence of nudB, which increased protein levels by 9-fold and reduced isopentenyl diphosphate (IPP) accumulation by 4-fold. To further optimize the pathway, we adjusted mevalonate kinase (MK) expression and investigated MK enzymes from alternative microbes such as Methanosarcina mazei. Next, we expressed a fusion protein of IPP isomerase and the phosphatase (Idi1~NudB) along with a reductase (NemA) to diversify production to 3-methyl-2-buten-1-ol and 3-methyl-1-butanol. Finally, we used an oleyl alcohol overlay to improve alcohol recovery, achieving final titers of 2.23 g/L of 3-methyl-3-buten-1-ol (~70% of pathway-dependent theoretical yield), 150 mg/L of 3-methyl-2-buten-1-ol, and 300 mg/L of 3-methyl-1-butanol. PMID:26052683
Bentley, Fiona K; Zurbriggen, Andreas; Melis, Anastasios
2014-01-01
Heterologous expression of the isoprene synthase gene in the cyanobacterium Synechocystis PCC 6803 conferred upon these microorganisms the property of photosynthetic isoprene (C₅H₈) hydrocarbons production. Continuous production of isoprene from CO₂ and H₂O was achieved in the light, occurring via the endogenous methylerythritol-phosphate (MEP) pathway, in tandem with the growth of Synechocystis. This work addressed the issue of photosynthetic carbon partitioning between isoprene and biomass in Synechocystis. Evidence is presented to show heterologous genomic integration and cellular expression of the mevalonic acid (MVA) pathway genes in Synechocystis endowing a non-native pathway for carbon flux amplification to isopentenyl-diphosphate (IPP) and dimethylallyl-diphosphate (DMAPP) precursors of isoprene. Heterologous expression of the isoprene synthase in combination with the MVA pathway enzymes resulted in photosynthetic isoprene yield improvement by approximately 2.5-fold, compared with that measured in cyanobacteria transformed with the isoprene synthase gene only. These results suggest that the MVA pathway introduces a bypass in the flux of endogenous cellular substrate in Synechocystis to IPP and DMAPP, overcoming flux limitations of the native MEP pathway. The work employed a novel chromosomal integration and expression of synthetic gene operons in Synechocystis, comprising up to four genes under the control of a single promoter, and expressing three operons simultaneously. This is the first time an entire biosynthetic pathway with seven recombinant enzymes has been heterologously expressed in a photosynthetic microorganism. It constitutes contribution to the genetic engineering toolkit of photosynthetic microorganisms and a paradigm in the pursuit of photosynthetic approaches for the renewable generation of high-impact products.
Orlova, Irina; Nagegowda, Dinesh A.; Kish, Christine M.; Gutensohn, Michael; Maeda, Hiroshi; Varbanova, Marina; Fridman, Eyal; Yamaguchi, Shinjiro; Hanada, Atsushi; Kamiya, Yuji; Krichevsky, Alexander; Citovsky, Vitaly; Pichersky, Eran; Dudareva, Natalia
2009-01-01
Geranyl diphosphate (GPP), the precursor of many monoterpene end products, is synthesized in plastids by a condensation of dimethylallyl diphosphate and isopentenyl diphosphate (IPP) in a reaction catalyzed by homodimeric or heterodimeric GPP synthase (GPPS). In the heterodimeric enzymes, a noncatalytic small subunit (GPPS.SSU) determines the product specificity of the catalytic large subunit, which may be either an active geranylgeranyl diphosphate synthase (GGPPS) or an inactive GGPPS-like protein. Here, we show that expression of snapdragon (Antirrhinum majus) GPPS.SSU in tobacco (Nicotiana tabacum) plants increased the total GPPS activity and monoterpene emission from leaves and flowers, indicating that the introduced catalytically inactive GPPS.SSU found endogenous large subunit partner(s) and formed an active snapdragon/tobacco GPPS in planta. Bimolecular fluorescence complementation and in vitro enzyme analysis of individual and hybrid proteins revealed that two of four GGPPS-like candidates from tobacco EST databases encode bona fide GGPPS that can interact with snapdragon GPPS.SSU and form a functional GPPS enzyme in plastids. The formation of chimeric GPPS in transgenic plants also resulted in leaf chlorosis, increased light sensitivity, and dwarfism due to decreased levels of chlorophylls, carotenoids, and gibberellins. In addition, these transgenic plants had reduced levels of sesquiterpene emission, suggesting that the export of isoprenoid intermediates from the plastids into the cytosol was decreased. These results provide genetic evidence that GPPS.SSU modifies the chain length specificity of phylogenetically distant GGPPS and can modulate IPP flux distribution between GPP and GGPP synthesis in planta. PMID:20028839
Nucleic acid molecules encoding isopentenyl monophosphate kinase, and methods of use
Croteau, Rodney B.; Lange, Bernd M.
2001-01-01
A cDNA encoding isopentenyl monophosphate kinase (IPK) from peppermint (Mentha x piperita) has been isolated and sequenced, and the corresponding amino acid sequence has been determined. Accordingly, an isolated DNA sequence (SEQ ID NO:1) is provided which codes for the expression of isopentenyl monophosphate kinase (SEQ ID NO:2), from peppermint (Mentha x piperita). In other aspects, replicable recombinant cloning vehicles are provided which code for isopentenyl monophosphate kinase, or for a base sequence sufficiently complementary to at least a portion of isopentenyl monophosphate kinase DNA or RNA to enable hybridization therewith. In yet other aspects, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding isopentenyl monophosphate kinase. Thus, systems and methods are provided for the recombinant expression of the aforementioned recombinant isopentenyl monophosphate kinase that may be used to facilitate its production, isolation and purification in significant amounts. Recombinant isopentenyl monophosphate kinase may be used to obtain expression or enhanced expression of isopentenyl monophosphate kinase in plants in order to enhance the production of isopentenyl monophosphate kinase, or isoprenoids derived therefrom, or may be otherwise employed for the regulation or expression of isopentenyl monophosphate kinase, or the production of its products.
Characterization of rubber particles and rubber chain elongation in Taraxacum koksaghyz
2010-01-01
Background Natural rubber is a biopolymer with exceptional qualities that cannot be completely replaced using synthetic alternatives. Although several key enzymes in the rubber biosynthetic pathway have been isolated, mainly from plants such as Hevea brasiliensis, Ficus spec. and the desert shrub Parthenium argentatum, there have been no in planta functional studies, e.g. by RNA interference, due to the absence of efficient and reproducible protocols for genetic engineering. In contrast, the Russian dandelion Taraxacum koksaghyz, which has long been considered as a potential alternative source of low-cost natural rubber, has a rapid life cycle and can be genetically transformed using a simple and reliable procedure. However, there is very little molecular data available for either the rubber polymer itself or its biosynthesis in T. koksaghyz. Results We established a method for the purification of rubber particles - the active sites of rubber biosynthesis - from T. koksaghyz latex. Photon correlation spectroscopy and transmission electron microscopy revealed an average particle size of 320 nm, and 13C nuclear magnetic resonance (NMR) spectroscopy confirmed that isolated rubber particles contain poly(cis-1,4-isoprene) with a purity >95%. Size exclusion chromatography indicated that the weight average molecular mass (w) of T. koksaghyz natural rubber is 4,000-5,000 kDa. Rubber particles showed rubber transferase activity of 0.2 pmol min-1 mg-1. Ex vivo rubber biosynthesis experiments resulted in a skewed unimodal distribution of [1-14C]isopentenyl pyrophosphate (IPP) incorporation at a w of 2,500 kDa. Characterization of recently isolated cis-prenyltransferases (CPTs) from T. koksaghyz revealed that these enzymes are associated with rubber particles and are able to produce long-chain polyprenols in yeast. Conclusions T. koksaghyz rubber particles are similar to those described for H. brasiliensis. They contain very pure, high molecular mass poly(cis-1,4-isoprene) and the chain elongation process can be studied ex vivo. Because of their localization on rubber particles and their activity in yeast, we propose that the recently described T. koksaghyz CPTs are the major rubber chain elongating enzymes in this species. T. koksaghyz is amenable to genetic analysis and modification, and therefore could be used as a model species for the investigation and comparison of rubber biosynthesis. PMID:20170509
Baadhe, Rama Raju; Mekala, Naveen Kumar; Palagiri, Satwik Reddy; Parcha, Sreenivasa Rao
2012-07-01
In this case study, we designed a farnesyl pyrophosphate (FPP) biosynthetic network using hybrid functional Petri net with extension (HFPNe) which is derived from traditional Petri net theory and allows easy modeling with graphical approach of various types of entities in the networks together. Our main objective is to improve the production of FPP in yeast, which is further converted to amorphadiene (AD), a precursor of artemisinin (antimalarial drug). Natively, mevalonate (MEV) pathway is present in yeast. Methyl erythritol phosphate pathways (MEP) are present only in higher plant plastids and eubacteria, but not present in yeast. IPP and DAMP are common isomeric intermediate in these two pathways, which immediately yields FPP. By integrating these two pathways in yeast, we augmented the FPP synthesis approximately two folds higher (431.16 U/pt) than in MEV pathway alone (259.91 U/pt) by using HFPNe technique. Further enhanced FPP levels converted to AD by amorphadiene synthase gene yielding 436.5 U/pt of AD which approximately two folds higher compared to the AD (258.5 U/pt) synthesized by MEV pathway exclusively. Simulation and validation processes performed using these models are reliable with identified biological information and data.
Johnson, L. Jeffrey
2012-01-01
Isoprenoid biosynthesis is essential for survival of all living organisms. More than 50,000 unique isoprenoids occur naturally, with each constructed from two simple five-carbon precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Two pathways for the biosynthesis of IPP and DMAPP are found in nature. Humans exclusively use the mevalonate (MVA) pathway, while most bacteria, including all Gram-negative and many Gram-positive species, use the unrelated methylerythritol phosphate (MEP) pathway. Here we report the development of a novel, whole-cell phenotypic screening platform to identify compounds that selectively inhibit the MEP pathway. Strains of Salmonella enterica serovar Typhimurium were engineered to have separately inducible MEP (native) and MVA (nonnative) pathways. These strains, RMC26 and CT31-7d, were then used to differentiate MVA pathway- and MEP pathway-specific perturbation. Compounds that inhibit MEP pathway-dependent bacterial growth but leave MVA-dependent growth unaffected represent MEP pathway-selective antibacterials. This screening platform offers three significant results. First, the compound is antibacterial and is therefore cell permeant, enabling access to the intracellular target. Second, the compound inhibits one or more MEP pathway enzymes. Third, the MVA pathway is unaffected, suggesting selectivity for targeting the bacterial versus host pathway. The cell lines also display increased sensitivity to two reported MEP pathway-specific inhibitors, further biasing the platform toward inhibitors selective for the MEP pathway. We demonstrate development of a robust, high-throughput screening platform that combines phenotypic and target-based screening that can identify MEP pathway-selective antibacterials simply by monitoring optical density as the readout for cell growth/inhibition. PMID:22777049
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barta, Michael L.; McWhorter, William J.; Miziorko, Henry M.
2012-09-17
Mevalonate diphosphate decarboxylase (MDD) catalyzes the final step of the mevalonate pathway, the Mg{sup 2+}-ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP), producing isopentenyl diphosphate (IPP). Synthesis of IPP, an isoprenoid precursor molecule that is a critical intermediate in peptidoglycan and polyisoprenoid biosynthesis, is essential in Gram-positive bacteria (e.g., Staphylococcus, Streptococcus, and Enterococcus spp.), and thus the enzymes of the mevalonate pathway are ideal antimicrobial targets. MDD belongs to the GHMP superfamily of metabolite kinases that have been extensively studied for the past 50 years, yet the crystallization of GHMP kinase ternary complexes has proven to be difficult. To further ourmore » understanding of the catalytic mechanism of GHMP kinases with the purpose of developing broad spectrum antimicrobial agents that target the substrate and nucleotide binding sites, we report the crystal structures of wild-type and mutant (S192A and D283A) ternary complexes of Staphylococcus epidermidis MDD. Comparison of apo, MVAPP-bound, and ternary complex wild-type MDD provides structural information about the mode of substrate binding and the catalytic mechanism. Structural characterization of ternary complexes of catalytically deficient MDD S192A and D283A (k{sub cat} decreased 10{sup 3}- and 10{sup 5}-fold, respectively) provides insight into MDD function. The carboxylate side chain of invariant Asp{sup 283} functions as a catalytic base and is essential for the proper orientation of the MVAPP C3-hydroxyl group within the active site funnel. Several MDD amino acids within the conserved phosphate binding loop ('P-loop') provide key interactions, stabilizing the nucleotide triphosphoryl moiety. The crystal structures presented here provide a useful foundation for structure-based drug design.« less
Zhou, Jia; Yang, Liyang; Wang, Chonglong; Choi, Eui-Sung; Kim, Seon-Won
2017-04-20
The 2C-methyl-D-erythritol 4-phosphate (MEP) pathway is a carbon-efficient route for synthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the building blocks of isoprenoids. However, practical application of a native or recombinant MEP pathway for the mass production of isoprenoids in Escherichia coli has been unsatisfactory. In this study, the entire recombinant MEP pathway was established with plasmids and used for the production of an isoprenoid, protoilludene. E. coli harboring the recombinant MEP pathway plasmid (ME) and a protoilludene synthesis pathway plasmid (AO) produced 10.4mg/L of protoilludene after 48h of culture. To determine the rate-limiting gene on plasmid ME, each constituent gene of the MEP pathway was additionally overexpressed on the plasmid AO. The additional overexpression of IPP isomerase (IDI) enhanced protoilludene production to 67.4mg/L. Overexpression of the Fpr and FldA protein complex, which could mediate electron transfer from NADPH to Fe-S cluster proteins such as IspG and IspH of the MEP pathway, increased protoilludene production to 318.8mg/L. Given that it is required for IspC as well as IspG/H, the MEP pathway has high demand for NADPH. To increase the supply of NADPH, a NADH kinase from Saccharomyces cerevisiae (tPos5p) that converts NADH to NADPH was introduced along with the deletion of a promiscuous NADPH-dependent aldehyde reductase (YjgB) that consumes NADPH. This resulted in a protoilludene production of 512.7mg/L. The results indicate that IDI, Fpr-FldA redox proteins, and NADPH regenerators are key engineering points for boosting the metabolic flux toward a recombinant MEP pathway. Copyright © 2017 Elsevier B.V. All rights reserved.
Pan, Jian-Jung; Ramamoorthy, Gurusankar; Poulter, C. Dale
2013-01-01
Long-chain E-polyprenyl diphosphate synthases (E-PDS) catalyze repetitive addition of isopentenyl diphosphate (IPP) to the growing prenyl chain of an allylic diphosphate. The polyprenyl diphosphate products are required for the biosynthesis of ubiquinones and menaquinones required for electron transport during oxidative phosphorylation to generate ATP. In vitro, the long-chain PDSs require addition of phospholipids or detergents to the assay buffer to enhance product release and maintain efficient turnover. During preliminary assays of product chain-length with anionic, zwitterionic, and non-ionic detergents, we discovered considerable variability. Examination of a series of non-ionic PEG detergents with several long-chain E-PDSs from different organisms revealed that in vitro incubations with nonaethylene glycol monododecyl ether or Triton X-100 typically gave chain lengths that corresponded to those of the isoprenoid moieties in respiratory quinones synthesized in vivo. In contrast incubations in buffer with n-butanol, CHAPS, DMSO, n-octyl-β-glucopyranoside, or β-cyclodextrin or in buffer without detergent typically proceeded more slowly and gave a broad range of chain lengths. PMID:23802587
Garg, Aprajita; Wesolowski, Donna; Alonso, Dulce; Deitsch, Kirk W; Ben Mamoun, Choukri; Altman, Sidney
2015-09-22
Identification and genetic validation of new targets from available genome sequences are critical steps toward the development of new potent and selective antimalarials. However, no methods are currently available for large-scale functional analysis of the Plasmodium falciparum genome. Here we present evidence for successful use of morpholino oligomers (MO) to mediate degradation of target mRNAs or to inhibit RNA splicing or translation of several genes of P. falciparum involved in chloroquine transport, apicoplast biogenesis, and phospholipid biosynthesis. Consistent with their role in the parasite life cycle, down-regulation of these essential genes resulted in inhibition of parasite development. We show that a MO conjugate that targets the chloroquine-resistant transporter PfCRT is effective against chloroquine-sensitive and -resistant parasites, causes enlarged digestive vacuoles, and renders chloroquine-resistant strains more sensitive to chloroquine. Similarly, we show that a MO conjugate that targets the PfDXR involved in apicoplast biogenesis inhibits parasite growth and that this defect can be rescued by addition of isopentenyl pyrophosphate. MO-based gene regulation is a viable alternative approach to functional analysis of the P. falciparum genome.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Byres, Emma; Martin, David M. A.; Hunter, William N., E-mail: w.n.hunter@dundee.ac.uk
2005-06-01
The gene encoding the putative mevalonate diphosphate decarboxylase, an enzyme from the mevalonate pathway of isoprenoid precursor biosynthesis, has been cloned from T. brucei. Recombinant protein has been expressed, purified and highly ordered crystals obtained and characterized to aid the structure–function analysis of this enzyme. Mevalonate diphosphate decarboxylase catalyses the last and least well characterized step in the mevalonate pathway for the biosynthesis of isopentenyl pyrophosphate, an isoprenoid precursor. A gene predicted to encode the enzyme from Trypanosoma brucei has been cloned, a highly efficient expression system established and a purification protocol determined. The enzyme gives monoclinic crystals in spacemore » group P2{sub 1}, with unit-cell parameters a = 51.5, b = 168.7, c = 54.9 Å, β = 118.8°. A Matthews coefficient V{sub M} of 2.5 Å{sup 3} Da{sup −1} corresponds to two monomers, each approximately 42 kDa (385 residues), in the asymmetric unit with 50% solvent content. These crystals are well ordered and data to high resolution have been recorded using synchrotron radiation.« less
An enzyme-coupled continuous fluorescence assay for farnesyl diphosphate synthases
Dozier, Jonathan K; Distefano, Mark D
2012-01-01
Farnesyl diphosphate synthase (FDPS) catalyzes the conversion of isopentenyl diphosphate and dimethylallyl diphosphate to farnesyl diphosphate, a crucial metabolic intermediate in the synthesis of cholesterol, ubiquinone and prenylated proteins; consequently, much effort has gone into developing inhibitors that target FDPS. Currently most FDPS assays use either radiolabeled substrates and are discontinuous, or monitor pyrophosphate release and not farnesyl diphosphate (FPP) creation. Here we report the development of a continuous coupled enzyme assay for FDPS activity that involves the subsequent incorporation of the FPP product of that reaction into a peptide via the action of protein farnesyltransferase (PFTase). By using a dansylated peptide whose fluorescence quantum yield increases upon farnesylation, the rate of FDPS-catalyzed FPP production can be measured. We show that this assay is more sensitive than existing coupled assays, that it can be used to conveniently monitor FDPS activity in a 96-well plate format and that it can reproduce IC50 values for several previously reported FDPS inhibitors. This new method offers a simple, safe and continuous method to assay FDPS activity that should greatly facilitate the screening of inhibitors of this important target. PMID:22085443
Identification of natural rubber and characterization of rubber biosynthetic activity in fig tree.
Kang, H; Kang, M Y; Han, K H
2000-07-01
Natural rubber was extracted from the fig tree (Ficus carica) cultivated in Korea as part of a survey of rubber producing plants. Fourier transform infrared and (13)C nuclear magnetic resonance analysis of samples prepared by successive extraction with acetone and benzene confirmed that the benzene-soluble residues are natural rubber, cis-1,4-polyisoprene. The rubber content in the latex of fig tree was about 4%, whereas the rubber content in the bark, leaf, and fruit was 0.3%, 0.1%, and 0.1%, respectively. Gel-permeation chromatography revealed that the molecular size of the natural rubber from fig tree is about 190 kD. Similar to rubber tree (Hevea brasiliensis) and guayule (Parthenium argentatum Gray), rubber biosynthesis in fig tree is tightly associated with rubber particles. The rubber transferase in rubber particles exhibited a higher affinity for farnesyl pyrophosphate than for isopentenyl pyrophosphate, with apparent K(m) values of 2.8 and 228 microM, respectively. Examination of latex serum from fig tree by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed major proteins of 25 and 48 kD in size, and several proteins with molecular mass below 20 and above 100 kD. Partial N-terminal amino acid sequencing and immunochemical analyses revealed that the 25- and 48-kD proteins were novel and not related to any other suggested rubber transferases. The effect of EDTA and Mg(2+) ion on in vitro rubber biosynthesis in fig tree and rubber tree suggested that divalent metal ion present in the latex serum is an important factor in determining the different rubber biosynthetic activities in fig tree and rubber tree.
Identification of Natural Rubber and Characterization of Rubber Biosynthetic Activity in Fig Tree1
Kang, Hunseung; Kang, Min Young; Han, Kyung-Hwan
2000-01-01
Natural rubber was extracted from the fig tree (Ficus carica) cultivated in Korea as part of a survey of rubber producing plants. Fourier transform infrared and 13C nuclear magnetic resonance analysis of samples prepared by successive extraction with acetone and benzene confirmed that the benzene-soluble residues are natural rubber, cis-1,4-polyisoprene. The rubber content in the latex of fig tree was about 4%, whereas the rubber content in the bark, leaf, and fruit was 0.3%, 0.1%, and 0.1%, respectively. Gel-permeation chromatography revealed that the molecular size of the natural rubber from fig tree is about 190 kD. Similar to rubber tree (Hevea brasiliensis) and guayule (Parthenium argentatum Gray), rubber biosynthesis in fig tree is tightly associated with rubber particles. The rubber transferase in rubber particles exhibited a higher affinity for farnesyl pyrophosphate than for isopentenyl pyrophosphate, with apparent Km values of 2.8 and 228 μm, respectively. Examination of latex serum from fig tree by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed major proteins of 25 and 48 kD in size, and several proteins with molecular mass below 20 and above 100 kD. Partial N-terminal amino acid sequencing and immunochemical analyses revealed that the 25- and 48-kD proteins were novel and not related to any other suggested rubber transferases. The effect of EDTA and Mg2+ ion on in vitro rubber biosynthesis in fig tree and rubber tree suggested that divalent metal ion present in the latex serum is an important factor in determining the different rubber biosynthetic activities in fig tree and rubber tree. PMID:10889262
Cai, Zhiqiang; Wang, Jing; Ma, Jiangtao; Zhu, Xiaolin; Cai, Jinyan; Yang, Guanghua
2015-08-19
To comprehensively understand anaerobic degradation of the novel cis-nitromethylene neonicotinoid insecticide Paichongding (IPP) and its impacts on microbial communities in anaerobic soils, we investigated IPP degradation characteristics, kinetics, and pathway in four different soils. The bacterial community in response to the application of IPP using pyrosequencing of 16S rRNA gene amplicons was also studied. The removal ratio of IPP stereoisomers (RR-IPP, SS-IPP, RS-IPP, and SR-IPP) reached >90% at 60 days after IPP treatment (DAT) in yellow loam soil (F) and paddy field on desalting muddy polder (C), whereas the degradation ratios of RR-IPP and SS-IPP were <30% at 60 DAT in Huangshi soil (J) and yellow paddy soil (H). The results showed that the anaerobic degradation rate of IPP and its stereoisomers was strongly affected by soil physical-chemical characteristics. Furthermore, on the basis of the six metabolites (M1-M6) identified by LC-MS/MS and their behavior, the anaerobic degradation pathway of IPP in soils was proposed. Biodegradation of IPP involved continuous biocatalytic reactions such as nitro reduction and elimination, hydrolysis, demethyl, and ether cleavage reactions. A higher richness of operational taxonomic units (OTUs) was found in soils without IPP application than in soils with IPP application. Both the rarefaction curves and Shannon-Wiener diversity index in anaerobic soils had significant difference after IPP application, and the community composition also differed at both the phyla and genus levels.
Synthetic Routes to Methylerythritol Phosphate Pathway Intermediates and Downstream Isoprenoids
Jarchow-Choy, Sarah K; Koppisch, Andrew T; Fox, David T
2014-01-01
Isoprenoids constitute the largest class of natural products with greater than 55,000 identified members. They play essential roles in maintaining proper cellular function leading to maintenance of human health, plant defense mechanisms against predators, and are often exploited for their beneficial properties in the pharmaceutical and nutraceutical industries. Most impressively, all known isoprenoids are derived from one of two C5-precursors, isopentenyl diphosphate (IPP) or dimethylallyl diphosphate (DMAPP). In order to study the enzyme transformations leading to the extensive structural diversity found within this class of compounds there must be access to the substrates. Sometimes, intermediates within a biological pathway can be isolated and used directly to study enzyme/pathway function. However, the primary route to most of the isoprenoid intermediates is through chemical catalysis. As such, this review provides the first exhaustive examination of synthetic routes to isoprenoid and isoprenoid precursors with particular emphasis on the syntheses of intermediates found as part of the 2C-methylerythritol 4-phosphate (MEP) pathway. In addition, representative syntheses are presented for the monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), triterpenes (C30) and tetraterpenes (C40). Finally, in some instances, the synthetic routes to substrate analogs found both within the MEP pathway and downstream isoprenoids are examined. PMID:25009443
Ohto, C; Ishida, C; Nakane, H; Muramatsu, M; Nishino, T; Obata, S
1999-05-01
Prenyltransferases (prenyl diphosphate synthases), which are a broad group of enzymes that catalyze the consecutive condensation of homoallylic diphosphate of isopentenyl diphosphates (IPP, C5) with allylic diphosphates to synthesize prenyl diphosphates of various chain lengths, have highly conserved regions in their amino acid sequences. Based on the above information, three prenyltransferase homologue genes were cloned from a thermophilic cyanobacterium, Synechococcus elongatus. Through analyses of the reaction products of the enzymes encoded by these genes, it was revealed that one encodes a thermolabile geranylgeranyl (C20) diphosphate synthase, another encodes a farnesyl (C15) diphosphate synthase whose optimal reaction temperature is 60 degrees C, and the third one encodes a prenyltransferase whose optimal reaction temperature is 75 degrees C. The last enzyme could catalyze the synthesis of five prenyl diphosphates of farnesyl, geranylgeranyl, geranylfarnesyl (C25), hexaprenyl (C30), and heptaprenyl (C35) diphosphates from dimethylallyl (C5) diphosphate, geranyl (C10) diphosphate, or farnesyl diphosphate as the allylic substrates. The product specificity of this novel kind of enzyme varied according to the ratio of the allylic and homoallylic substrates. The situations of these three S. elongatus enzymes in a phylogenetic tree of prenyltransferases are discussed in comparison with a mesophilic cyanobacterium of Synechocystis PCC6803, whose complete genome has been reported by Kaneko et al. (1996).
Perez-Castineira, Jose R; Lopez-Marques, Rosa L; Villalba, Jose M; Losada, Manuel; Serrano, Aurelio
2002-12-10
Two types of proteins that hydrolyze inorganic pyrophosphate (PPi), very different in both amino acid sequence and structure, have been characterized to date: soluble and membrane-bound proton-pumping pyrophosphatases (sPPases and H(+)-PPases, respectively). sPPases are ubiquitous proteins that hydrolyze PPi releasing heat, whereas H+-PPases, so far unidentified in animal and fungal cells, couple the energy of PPi hydrolysis to proton movement across biological membranes. The budding yeast Saccharomyces cerevisiae has two sPPases that are located in the cytosol and in the mitochondria. Previous attempts to knock out the gene coding for a cytosolic sPPase (IPP1) have been unsuccessful, thus suggesting that this protein is essential for growth. Here, we describe the generation of a conditional S. cerevisiae mutant (named YPC-1) whose functional IPP1 gene is under the control of a galactose-dependent promoter. Thus, YPC-1 cells become growth arrested in glucose but they regain the ability to grow on this carbon source when transformed with autonomous plasmids bearing diverse foreign H+-PPase genes under the control of a yeast constitutive promoter. The heterologously expressed H+-PPases are distributed among different yeast membranes, including the plasma membrane, functional complementation by these integral membrane proteins being consistently sensitive to external pH. These results demonstrate that hydrolysis of cytosolic PPi is essential for yeast growth and that this function is not substantially affected by the intrinsic characteristics of the PPase protein that accomplishes it. Moreover, this is, to our knowledge, the first direct evidence that H+-PPases can mediate net hydrolysis of PPi in vivo. YPC-1 mutant strain constitutes a convenient expression system to perform studies aimed at the elucidation of the structure-function relationships of this type of proton pumps.
Parker, Vicki; McNeil, Karen; Higgins, Isabel; Mitchell, Rebecca; Paliadelis, Penelope; Giles, Michelle; Parmenter, Glenda
2013-12-01
Although interprofessional practice (IPP) offers the potential to enhance rural health services and provide support to rural clinicians, IPP may itself be problematic due to workforce limitations and service fragmentation. Differing socioeconomic and geographic characteristics of rural communities means that the way that IPP occurs in rural contexts will necessarily differ from that occurring in metropolitan contexts. The aim of this study was to investigate the factors contributing to effective IPP in rural contexts, to examine how IPP happens and to identify barriers and enablers. Using Realistic Evaluation as a framework, semi-structured interviews were conducted with health professionals in a range of rural healthcare contexts in NSW, Australia. Independent thematic analysis was undertaken by individual research team members, which was then integrated through consensus to achieve a qualitative description of rural IPP practice. There was clear evidence of diversity and complexity associated with IPP in the rural settings that was supported by descriptions of collaborative integrated practice. There were instances where IPP doesn't and could happen. There were a number of characteristics identified that significantly impacted on IPP including the presence of a shared philosophical position and valuing of IPP and recognition of the benefits, funding to support IPP, pivotal roles, proximity and workforce resources. The nature of IPP in rural contexts is diverse and determined by a number of critical factors. This study goes some of the way towards unravelling the complexity of IPP in rural contexts, highlighting the strong motivating factors that drive IPP. However, it has also identified significant structural and relational barriers related to workload, workforce, entrenched hierarchies and ways of working and service fragmentation. Further research is required to explicate the mechanisms that drive successful IPP across a range of diverse rural contexts in order to inform the implementation of robust flexible strategies that will support sustainable models of rural IPP.
2013-01-01
Background Although interprofessional practice (IPP) offers the potential to enhance rural health services and provide support to rural clinicians, IPP may itself be problematic due to workforce limitations and service fragmentation. Differing socioeconomic and geographic characteristics of rural communities means that the way that IPP occurs in rural contexts will necessarily differ from that occurring in metropolitan contexts. The aim of this study was to investigate the factors contributing to effective IPP in rural contexts, to examine how IPP happens and to identify barriers and enablers. Methods Using Realistic Evaluation as a framework, semi-structured interviews were conducted with health professionals in a range of rural healthcare contexts in NSW, Australia. Independent thematic analysis was undertaken by individual research team members, which was then integrated through consensus to achieve a qualitative description of rural IPP practice. Results There was clear evidence of diversity and complexity associated with IPP in the rural settings that was supported by descriptions of collaborative integrated practice. There were instances where IPP doesn’t and could happen. There were a number of characteristics identified that significantly impacted on IPP including the presence of a shared philosophical position and valuing of IPP and recognition of the benefits, funding to support IPP, pivotal roles, proximity and workforce resources. Conclusions The nature of IPP in rural contexts is diverse and determined by a number of critical factors. This study goes some of the way towards unravelling the complexity of IPP in rural contexts, highlighting the strong motivating factors that drive IPP. However, it has also identified significant structural and relational barriers related to workload, workforce, entrenched hierarchies and ways of working and service fragmentation. Further research is required to explicate the mechanisms that drive successful IPP across a range of diverse rural contexts in order to inform the implementation of robust flexible strategies that will support sustainable models of rural IPP. PMID:24289815
[Protective Effect of S-isopentenyl-L-cysteine against DNA Damage in Irradiated Mice].
Zheng, Qi-sheng; Yu, Guang-yun; He, Xin; Jiang, Ming; Chu, Xiao-fei; Zhao, Shu-yi; Fan, Sai-jun; Liu, Pei-xun
2015-10-01
To evaluate the protective effect of S-isopentenyl-L-cysteine,a new cysteine derivative,on DNA damage induced by radiation by using acute radiation injury animal models. Forty ICR mice were randomly divided into five groups:the control group,1.0Gy gamma irradiation group,1.0Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,7.2Gy gamma irradiation group,and 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,with 8 mice in each group.The comet assay and bone marrow polychromatic micronucleus experiments were performed to evaluate the double-strand DNA breaks in ICR mice exposed to 1.0 and 7.2Gy gamma-ray, respectively. The tail DNA percentage,tail length,tail moment,and olive tail moment of peripheral blood lymphocytes in 7.2Gy gamma irradiation group were significantly higher than that of the control group (P<0.01).And it was also observed that above experimental indexes of 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group was significantly less than that of 7.2Gy gamma irradiation group (P<0.05). In addition,the micronucleus rate of 1.0Gy gamma irradiation group and 7.2Gy gamma irradiation group were both significantly higher than in the control group (P<0.01). In addition,in mice given S-isopentenyl-L-cysteine before irradiation,the micronucleus rate of ICR mice exposed to 1.0 and 7.2Gy gamma-ray decreased from (39.5000 ± 3.3141)‰ to (28.1667±4.1345)‰ (P=0.033) and from (76.5000 ± 4.6242)‰ to (22.8333 ± 3.6553)‰(P=0.000),respectively. The bone marrow polychromatic micronucleus experiment indicated that the value of polychromatic erythrocyte (PCE)/normochromatic erythrocyte(NCE) of ICR mice exposed to 1.0 and 7.2Gy gamma-ray was less than the control group(P<0.05). Meanwhile,after irradiating by certain dose,the value of PCE/NCE in mice given S-isopentenyl-L-cysteine before irradiation was significantly higher than the corresponding groups (P<0.05). S-isopentenyl-L-cysteine has a good protective effect against DNA damage induced by radiation.
Murphy, Timothy V; Kanagarajah, Arjna; Toemoe, Sianne; Bertrand, Paul P; Grayson, T Hilton; Britton, Fiona C; Leader, Leo; Senadheera, Sevvandi; Sandow, Shaun L
2016-08-01
This study investigated the expression and function of transient receptor potential vanilloid type-3 ion channels (TRPV3) in uterine radial arteries isolated from non-pregnant and twenty-day pregnant rats. Immunohistochemistry (IHC) suggested TRPV3 is primarily localized to the smooth muscle in arteries from both non-pregnant and pregnant rats. IHC using C' targeted antibody, and qPCR of TRPV3 mRNA, suggested pregnancy increased arterial TRPV3 expression. The TRPV3 activator carvacrol caused endothelium-independent dilation of phenylephrine-constricted radial arteries, with no difference between vessels from non-pregnant and pregnant animals. Carvacrol-induced dilation was reduced by the TRPV3-blockers isopentenyl pyrophosphate and ruthenium red, but not by the TRPA1 or TRPV4 inhibitors HC-030031 or HC-067047, respectively. In radial arteries from non-pregnant rats only, inhibition of NOS and sGC, or PKG, enhanced carvacrol-mediated vasodilation. Carvacrol-induced dilation of arteries from both non-pregnant and pregnant rats was prevented by the IKCa blocker TRAM-34. TRPV3 caused an endothelium-independent, IKCa-mediated dilation of the uterine radial artery. NO-PKG-mediated modulation of TRPV3 activity is lost in pregnancy, but this did not alter the response to carvacrol. Copyright © 2016 Elsevier Inc. All rights reserved.
Malhotra, Karan; Subramaniyan, Mayavan; Rawat, Khushboo; Kalamuddin, Md.; Qureshi, M. Irfan; Malhotra, Pawan; Mohmmed, Asif; Cornish, Katrina; Daniell, Henry; Kumar, Shashi
2017-01-01
Artemisinin is highly effective against drug-resistant malarial parasites, which affects nearly half of the global population and kills >500 000 people each year. The primary cost of artemisinin is the very expensive process used to extract and purify the drug from Artemisia annua. Elimination of this apparently unnecessary step will make this potent antimalarial drug affordable to the global population living in endemic regions. Here we reported the oral delivery of a non-protein drug artemisinin biosynthesized (~0.8 mg/g dry weight) at clinically meaningful levels in tobacco by engineering two metabolic pathways targeted to three different cellular compartments (chloroplast, nucleus, and mitochondria). The doubly transgenic lines showed a three-fold enhancement of isopentenyl pyrophosphate, and targeting AACPR, DBR2, and CYP71AV1 to chloroplasts resulted in higher expression and an efficient photo-oxidation of dihydroartemisinic acid to artemisinin. Partially purified extracts from the leaves of transgenic tobacco plants inhibited in vitro growth progression of Plasmodium falciparum-infected red blood cells. Oral feeding of whole intact plant cells bioencapsulating the artemisinin reduced the parasitemia levels in challenged mice in comparison with commercial drug. Such novel synergistic approaches should facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants. PMID:27773616
Atkins, Craig A; Emery, R J Neil; Smith, Penelope M C
2011-12-01
Phenotypes of five transgenic lines of narrow-leafed lupin (Lupinus angustifolius [L] cv Merrit) stably transformed with the isopentenyl pyrophosphate transferase (ipt) gene from Agrobacterium tumefaciens coupled to a flower-specific promoter (TP12) from Nicotiana tabacum [L.] are described. Expression of the transgene was detected in floral tissues and in shoot apical meristems on all orders of inflorescence. In each transgenic line there was significant axillary bud outgrowth at all nodes on the main stem with pronounced branch development from the more basal nodes in three of the lines. The lowest basal branches developed in a manner similar to the upper stem axillary branches on cv Merrit and bore fruits, which, in two lines, contained a significant yield of filled seeds at maturity. Senescence of the cotyledons was delayed in all lines with green cotyledons persisting beyond anthesis in one case. IPT expression increased cytokinin (CK) levels in flowers, meristem tissues and phloem exudates in a form specific manner, which was suggestive of localized flower and meristem production with significant long-distance re-distribution in phloem. The total number of fruits formed (pod set) on some transgenic lines was increased compared to cv Merrit. Grain size compared to cv Merrit was not significantly altered in transgenic lines.
An adaptation to life in acid through a novel mevalonate pathway
Vinokur, Jeffrey M.; Cummins, Matthew C.; Korman, Tyler P.; ...
2016-12-22
Here, extreme acidophiles are capable of growth at pH values near zero. Sustaining life in acidic environments requires extensive adaptations of membranes, proton pumps, and DNA repair mechanisms. Here we describe an adaptation of a core biochemical pathway, the mevalonate pathway, in extreme acidophiles. Two previously known mevalonate pathways involve ATP dependent decarboxylation of either mevalonate 5-phosphate or mevalonate 5-pyrophosphate, in which a single enzyme carries out two essential steps: (1) phosphorylation of the mevalonate moiety at the 3-OH position and (2) subsequent decarboxylation. We now demonstrate that in extreme acidophiles, decarboxylation is carried out by two separate steps: previouslymore » identified enzymes generate mevalonate 3,5-bisphosphate and a new decarboxylase we describe here, mevalonate 3,5-bisphosphate decarboxylase, produces isopentenyl phosphate. Why use two enzymes in acidophiles when one enzyme provides both functionalities in all other organisms examined to date? We find that at low pH, the dual function enzyme, mevalonate 5-phosphate decarboxylase is unable to carry out the first phosphorylation step, yet retains its ability to perform decarboxylation. We therefore propose that extreme acidophiles had to replace the dual-purpose enzyme with two specialized enzymes to efficiently produce isoprenoids in extremely acidic environments.« less
An adaptation to life in acid through a novel mevalonate pathway
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vinokur, Jeffrey M.; Cummins, Matthew C.; Korman, Tyler P.
Here, extreme acidophiles are capable of growth at pH values near zero. Sustaining life in acidic environments requires extensive adaptations of membranes, proton pumps, and DNA repair mechanisms. Here we describe an adaptation of a core biochemical pathway, the mevalonate pathway, in extreme acidophiles. Two previously known mevalonate pathways involve ATP dependent decarboxylation of either mevalonate 5-phosphate or mevalonate 5-pyrophosphate, in which a single enzyme carries out two essential steps: (1) phosphorylation of the mevalonate moiety at the 3-OH position and (2) subsequent decarboxylation. We now demonstrate that in extreme acidophiles, decarboxylation is carried out by two separate steps: previouslymore » identified enzymes generate mevalonate 3,5-bisphosphate and a new decarboxylase we describe here, mevalonate 3,5-bisphosphate decarboxylase, produces isopentenyl phosphate. Why use two enzymes in acidophiles when one enzyme provides both functionalities in all other organisms examined to date? We find that at low pH, the dual function enzyme, mevalonate 5-phosphate decarboxylase is unable to carry out the first phosphorylation step, yet retains its ability to perform decarboxylation. We therefore propose that extreme acidophiles had to replace the dual-purpose enzyme with two specialized enzymes to efficiently produce isoprenoids in extremely acidic environments.« less
A novel plant enzyme with dual activity: an atypical Nudix hydrolase and a dipeptidyl peptidase III
Karačić, Zrinka; Vukelić, Bojana; Ho, Gabrielle H.; Jozić, Iva; Sučec, Iva; Salopek-Sondi, Branka; Kozlović, Marija; Brenner, Steven E.; Ludwig-Müller, Jutta; Abramić, Marija
2017-01-01
In a search for plant homologues of dipeptidyl peptidase III (DPP III) family, we found a predicted protein from the moss Physcomitrella patens (UniProt entry: A9TLP4), which shared 61% sequence identity with the Arabidopsis thaliana uncharacterized protein, designated Nudix hydrolase 3. Both proteins contained all conserved regions of the DPP III family, but instead of the characteristic hexapeptide HEXXGH zinc-binding motif, they possessed a pentapeptide HEXXH, and at the N-terminus, a Nudix box, a hallmark of Nudix hydrolases, known to act upon a variety of nucleoside diphosphate derivatives. To investigate their biochemical properties, we expressed heterologously and purified Physcomitrella (PpND) and Arabidopsis (AtND) protein. Both hydrolyzed, with comparable catalytic efficiency, the isopentenyl diphosphate (IPP), a universal precursor for the biosynthesis of isoprenoid compounds. In addition, PpND dephosphorylated four purine nucleotides (ADP, dGDP, dGTP, and 8-oxo-dATP) with strong preference for oxidized dATP. Furthermore, PpND and AtND showed DPP III activity against dipeptidyl-2-arylamide substrates, which they cleaved with different specificity. This is the first report of a dual activity enzyme, highly conserved in land plants, which catalyses the hydrolysis of a peptide bond and of a phosphate bond, acting both as a dipeptidyl peptidase III and an atypical Nudix hydrolase. PMID:27467751
Bostwick, Jolene R; Leung, Gillian P; Smith, Tawny L; Ahmed, Uzma; Bainbridge, Jacquelyn L; Peyronnet, Jean-Xavier
2018-01-01
Introductory pharmacy practice experiences (IPPEs) are 1 requirement schools and colleges of pharmacy must fulfill to meet accreditation standards. The purpose of this manuscript is to report existing IPPEs in psychiatry and neurology across the United States. Two separate electronic surveys were administered to individual College of Psychiatric and Neurologic Pharmacists members with board certification in psychiatric pharmacy with an academic affiliation and academic institutions in the 2014-15 academic year to assess the neuropsychiatric curriculum in pharmacy programs. Results focusing on IPPEs were summarized using descriptive statistics. Academic institutional data reveal only 37.3% offered IPPEs in psychiatry, and 6.7% offered neurology. The number of available IPPEs is low even if a program offered an available rotation. The majority of College of Psychiatric and Neurologic Pharmacists member respondents (69.9%) did not offer IPPEs in psychiatry in the 2014-15 academic year, and none offered an IPPE in neurology. More than half of individual respondents feel their institution should increase IPPEs in psychiatry and neurology in order to enhance their curriculum. To expand IPPE availability, pharmacy programs should increase early exposure of pharmacy students to patients with psychiatric and neurologic conditions. Longitudinal experiences may allow students to engage in hands-on experiences, which may impact future career aspirations and reduce stigma. Current example IPPEs at the authors' institutions are included to stimulate discussion and action among readers on how IPPEs in these practice areas may be developed. Implementation of IPPEs in psychiatry and neurology is needed for students to gain experience working with these patients.
The Lead Crack Fatigue Lifting Framework
2010-04-01
15000 20000 25000 30000 35000 40000 F-WELD Test Hours C ra ck d ep th (m m ) IPP (1) IPP (2) IPP (3) IPP ( 4 ) IPP (5) IPP ( 6 ) IPP (6_A) FASS 226 (2...FASS 226 ( 4 ) FASS 226 (5) FASS 226 (5L) FASS 226 ( 6 ) FASS 226 (6R) SIH_OBD_SPLICE SIH_FS238/239 (1) SIH_FS238/239 (2) SIH_FS238/239 (3) SIH_FS238/239...conservative. 0.001 0.01 0.1 1 10 0 1 2 3 4 5 6 CB9 RHS CB8 LHS CB12 LHS CB12 RHS CB1 LHS FT55 LHS FT55 RHS ST16 LHS ST16 RHS Log average FLEI Virtual test
Antiproliferative effect of isopentenylated coumarins on several cancer cell lines.
Kawaii, S; Tomono, Y; Ogawa, K; Sugiura, M; Yano, M; Yoshizawa, Y; Ito, C; Furukawa, H
2001-01-01
33 coumarins, mainly the simple isopentenylated coumarins and derived pyrano- and furanocoumarins, were examined for their antiproliferative activity towards several cancer and normal human cell lines. The pyrano- and furanocoumarins showed strong activity against the cancer cell lines, whereas they had weak antiproliferative activity against the normal human cell lines. The decreasing rank order of potency was osthenone (10), clausarin (25), clausenidin (26), dentatin (24), nordentatin (23), imperatorin (29), seselin (27), xanthyletin (21), suberosin (17), phebalosin (8) and osthol (12). The structure-activity relationship established from the results revealed that the 1,1-dimethylallyl and isopentenyl groups have an important role for antiproliferative activity.
2018-01-01
Introduction: Introductory pharmacy practice experiences (IPPEs) are 1 requirement schools and colleges of pharmacy must fulfill to meet accreditation standards. The purpose of this manuscript is to report existing IPPEs in psychiatry and neurology across the United States. Methods: Two separate electronic surveys were administered to individual College of Psychiatric and Neurologic Pharmacists members with board certification in psychiatric pharmacy with an academic affiliation and academic institutions in the 2014-15 academic year to assess the neuropsychiatric curriculum in pharmacy programs. Results focusing on IPPEs were summarized using descriptive statistics. Results: Academic institutional data reveal only 37.3% offered IPPEs in psychiatry, and 6.7% offered neurology. The number of available IPPEs is low even if a program offered an available rotation. The majority of College of Psychiatric and Neurologic Pharmacists member respondents (69.9%) did not offer IPPEs in psychiatry in the 2014-15 academic year, and none offered an IPPE in neurology. More than half of individual respondents feel their institution should increase IPPEs in psychiatry and neurology in order to enhance their curriculum. Discussion: To expand IPPE availability, pharmacy programs should increase early exposure of pharmacy students to patients with psychiatric and neurologic conditions. Longitudinal experiences may allow students to engage in hands-on experiences, which may impact future career aspirations and reduce stigma. Current example IPPEs at the authors' institutions are included to stimulate discussion and action among readers on how IPPEs in these practice areas may be developed. Implementation of IPPEs in psychiatry and neurology is needed for students to gain experience working with these patients. PMID:29955538
The Use of Capacity Ratios in Introductory Pharmacy Practice Experiences
Haswell, Jamie L.; Byrd, Debbie C.; Foster, Stephan
2012-01-01
Objective. To describe the use of capacity ratios following the assignment of introductory pharmacy practice experiences (IPPEs) to a rising third-year pharmacy (P3) class. Methods. Practice experience availability for IPPEs was collected by means of preceptor response to requests. Following assignment of IPPEs to the rising P3 class, capacity ratios from the IPPEs available across the entire state and within each of 4 geographic zones were calculated. Capacity ratios for both community pharmacy and institutional pharmacy also were calculated. Results. The capacity ratio for IPPEs across the entire state was 2.11, which documents solvency. When the capacity ratios were calculated individually for community pharmacy and institutional pharmacy, solvency was also achieved. Likewise, IPPE capacity ratios were solvent in all 4 geographic zones. Conclusions. Capacity ratios are helpful in evaluating IPPE availability as they can be used to determine practice experience need in either type of practice experience or geographic zone. PMID:23193336
Lim, Kok Bin; Ho, Henry; Foo, Keong Tatt; Wong, Michael Yuet Chen; Fook-Chong, Stephanie
2006-12-01
The aims of this study were to define the relationship between intravesical prostatic protrusion (IPP), prostate-specific antigen (PSA) and prostate volume (PV) and to determine which one of them is the best predictor of bladder outlet obstruction (BOO) due to benign prostatic enlargement. A prospective study of 114 male patients older than 50 years examined between November 2001 and 2002 was performed. They were evaluated with digital rectal examination, International Prostate Symptoms Score, PSA, uroflowmetry, postvoid residual urine measurement, IPP and PV using transabdominal ultrasound scan. Statistical analysis included scatter plot with Spearman's correlation coefficients and nominal logistic regression Prostate volume, IPP and PSA showed parallel correlation. Although all three indices had good correlation with BOO index, IPP was the best. The Spearman rho correlation coefficients were 0.314, 0.408 and 0.507 for PV, PSA and IPP, respectively. Using receiver-operator characteristic curves, the areas under the curve for PV, PSA and IPP were 0.637, 0.703 and 0.772, respectively. The positive predictive values of PV, PSA and IPP were 65%, 68% and 72%, respectively. Using a nominal regression model, IPP remained the most significant independent index to determine BOO. All three non-invasive indices correlate with one another. The study showed that IPP is a better predictor for BOO than PSA or PV.
Boutin, Lola; Scotet, Emmanuel
2018-01-01
Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg), such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277) molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset.
Boutin, Lola; Scotet, Emmanuel
2018-01-01
Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg), such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277) molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset. PMID:29731756
Malhotra, Karan; Subramaniyan, Mayavan; Rawat, Khushboo; Kalamuddin, Md; Qureshi, M Irfan; Malhotra, Pawan; Mohmmed, Asif; Cornish, Katrina; Daniell, Henry; Kumar, Shashi
2016-11-07
Artemisinin is highly effective against drug-resistant malarial parasites, which affects nearly half of the global population and kills >500 000 people each year. The primary cost of artemisinin is the very expensive process used to extract and purify the drug from Artemisia annua. Elimination of this apparently unnecessary step will make this potent antimalarial drug affordable to the global population living in endemic regions. Here we reported the oral delivery of a non-protein drug artemisinin biosynthesized (∼0.8 mg/g dry weight) at clinically meaningful levels in tobacco by engineering two metabolic pathways targeted to three different cellular compartments (chloroplast, nucleus, and mitochondria). The doubly transgenic lines showed a three-fold enhancement of isopentenyl pyrophosphate, and targeting AACPR, DBR2, and CYP71AV1 to chloroplasts resulted in higher expression and an efficient photo-oxidation of dihydroartemisinic acid to artemisinin. Partially purified extracts from the leaves of transgenic tobacco plants inhibited in vitro growth progression of Plasmodium falciparum-infected red blood cells. Oral feeding of whole intact plant cells bioencapsulating the artemisinin reduced the parasitemia levels in challenged mice in comparison with commercial drug. Such novel synergistic approaches should facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.
Bacopa monniera recombinant mevalonate diphosphate decarboxylase: Biochemical characterization.
Abbassi, Shakeel J; Vishwakarma, Rishi K; Patel, Parth; Kumari, Uma; Khan, Bashir M
2015-08-01
Mevalonate diphosphate decarboxylase (MDD; EC 4.1.1.33) is an important enzyme in the mevalonic acid pathway catalyzing the Mg(2+)-ATP dependant decarboxylation of mevalonate 5-diphosphate (MVAPP) to isopentenyl diphosphate (IPP). Bacopa monniera recombinant MDD (BmMDD) protein was overexpressed in Escherichia coli BL21 (DE3) strain and purified to apparent homogeneity. Km and Vmax for MVAPP were 144 μM and 52 U mg(-1) respectively. The values of turnover (kcat) and kcat/Km for mevalonate 5-diphosphate were determined to be 40s(-1) and 2.77×10(5) M(-1) s(-1) and kcat and kcat/Km values for ATP were found to be 30 s(-1) and 2.20×10(4) M(-1) s(-1), respectively. pH activity profile indicated the involvement of carboxylate ion, lysine and arginine for the activity of enzyme. The apparent activation energy for the BmMDD catalyzed reaction was 12.7 kJ mol(-1). Optimum pH and temperature for the forward reaction was found to be 8.0 and 45 °C. The enzyme was most stable at pH 7 at 20 °C with the deactivation rate constant (Kd(*)) of 1.69×10(-4) and half life (t1/2) of 68 h. The cation studies suggested that BmMDD is a cation dependant enzyme and optimum activity was achieved in the presence of Mg(2+). Copyright © 2015 Elsevier B.V. All rights reserved.
Kuo, Tricia L C; Teo, Jonathan S M; Foo, K T
2016-04-01
Intravesical prostatic protrusion (IPP) may be an underutilized modality for the assessment of bladder outlet obstruction (BOO). Pressure flow studies or urodynamics have long been the gold standard for the evaluation of lower urinary tract symptoms (LUTS) in men but are invasive, time-consuming and costly. Potentially, IPP may be a useful adjunct prior to performing urodynamics. Measurement of IPP is taken in the sagittal view, using the transabdominal ultrasound. It is the vertical height from the tip of the protrusion to the base of the prostate. This technique was previously described. We reviewed previous publications that studied the accuracy, positive predictive value and clinical use of IPP. In addition, we noted the comments regarding the challenges of using this technique. IPP has been shown to have a positive predictive value of 72% for BOO. It has been calculated to have an area under curve (AUC) value of 0.71 and 0.84 in some stuies. Clinically, it may be used to predict the outcome of a trial without catheter following acute retention of urine. Patients with higher IPP grade were noted to have a higher risk of clinical progression. Studies have also shown that men with higher IPP are poorer responders to medical treatment such as α-blockers. Compared to other modalities, the advantage of IPP in assessing BOO may be its easy applicability and non-invasive nature. Therefore, there is a consideration for a larger role of IPP in bedside assessment and management of BOO in daily practice. Neurourol. Urodynam. 35:535-537, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
Ohto, Chikara; Muramatsu, Masayoshi; Obata, Shusei; Sakuradani, Eiji; Shimizu, Sakayu
2009-01-01
Isopentenyl diphosphate isomerase (idi) and farnesyl diphosphate synthase (ispA) genes were overexpressed in Escherichia coli. The resulting transformant showed 6.8-fold higher production of farnesol (389 microg/l). In a similar manner, overexpression of idi and mutated ispA led to high production of geranylgeraniol (128 microg/l).
Unno, Hideaki; Yamashita, Satoshi; Ikeda, Yosuke; Sekiguchi, Shin-ya; Yoshida, Norie; Yoshimura, Tohru; Kusunoki, Masami; Nakayama, Toru; Nishino, Tokuzo; Hemmi, Hisashi
2009-01-01
Using FMN and a reducing agent such as NAD(P)H, type 2 isopentenyl-diphosphate isomerase catalyzes isomerization between isopentenyl diphosphate and dimethylallyl diphosphate, both of which are elemental units for the biosynthesis of highly diverse isoprenoid compounds. Although the flavin cofactor is expected to be integrally involved in catalysis, its exact role remains controversial. Here we report the crystal structures of the substrate-free and complex forms of type 2 isopentenyl-diphosphate isomerase from the thermoacidophilic archaeon Sulfolobus shibatae, not only in the oxidized state but also in the reduced state. Based on the active-site structures of the reduced FMN-substrate-enzyme ternary complexes, which are in the active state, and on the data from site-directed mutagenesis at highly conserved charged or polar amino acid residues around the active site, we demonstrate that only reduced FMN, not amino acid residues, can catalyze proton addition/elimination required for the isomerase reaction. This discovery is the first evidence for this long suspected, but previously unobserved, role of flavins just as a general acid-base catalyst without playing any redox roles, and thereby expands the known functions of these versatile coenzymes. PMID:19158086
Unno, Hideaki; Yamashita, Satoshi; Ikeda, Yosuke; Sekiguchi, Shin-Ya; Yoshida, Norie; Yoshimura, Tohru; Kusunoki, Masami; Nakayama, Toru; Nishino, Tokuzo; Hemmi, Hisashi
2009-04-03
Using FMN and a reducing agent such as NAD(P)H, type 2 isopentenyl-diphosphate isomerase catalyzes isomerization between isopentenyl diphosphate and dimethylallyl diphosphate, both of which are elemental units for the biosynthesis of highly diverse isoprenoid compounds. Although the flavin cofactor is expected to be integrally involved in catalysis, its exact role remains controversial. Here we report the crystal structures of the substrate-free and complex forms of type 2 isopentenyl-diphosphate isomerase from the thermoacidophilic archaeon Sulfolobus shibatae, not only in the oxidized state but also in the reduced state. Based on the active-site structures of the reduced FMN-substrate-enzyme ternary complexes, which are in the active state, and on the data from site-directed mutagenesis at highly conserved charged or polar amino acid residues around the active site, we demonstrate that only reduced FMN, not amino acid residues, can catalyze proton addition/elimination required for the isomerase reaction. This discovery is the first evidence for this long suspected, but previously unobserved, role of flavins just as a general acid-base catalyst without playing any redox roles, and thereby expands the known functions of these versatile coenzymes.
Jones, Kim M; Blumenthal, Donald K; Burke, John M; Condren, Michelle; Hansen, Richard; Holiday-Goodman, Monica; Peterson, Charles D
2012-06-18
To assess the extent to which US colleges and schools of pharmacy are incorporating interprofessional education into their introductory pharmacy practice experiences (IPPEs), and to identify barriers to implementation; characterize the format, structure, and assessment; and identify factors associated with incorporating interprofessional education in IPPEs. An electronic survey of 116 US colleges and schools of pharmacy was conducted from March 2011 through May 2011. Interprofessional education is a stated curricular goal in 78% of colleges and schools and consistently occurred in IPPEs in 55%. Most colleges and schools that included interprofessional education in IPPEs (70%) used subjective measures to assess competencies, while 17.5% used standardized outcomes assessment instruments. Barriers cited by respondents from colleges and schools that had not implemented interprofessional education in IPPEs included a lack of access to sufficient healthcare facilities with interprofessional education opportunities (57%) and a lack of required personnel resources (52%). Many US colleges and schools of pharmacy have incorporated interprofessional education into their IPPEs, but there is a need for further expansion of interprofessional education and better assessment related to achievement of interprofessional education competencies in IPPEs.
Phase separation of DMDBS from iPP, and controlled crystalline orientation
NASA Astrophysics Data System (ADS)
Sreenivas, K.; Kumaraswamy, Guruswamy; Basargekar, R. S.
2012-02-01
We report an unexpected dependence of DMDBS phase separation temperature on the molecular weight of the matrix isotactic polypropylene (iPP). DMDBS crystallizes out at lower temperatures for iPP with decreasing molecular weight (and correspondingly lower tacticity). This molecular weight dependence is unique to iPP, and is not observed for either syndiotactic PP or for random ethylene-PP copolymers. We show that thermodynamic Flory-type arguments are unable to rationalize the observed results. We also results on extrusion film casting of iPP containing DMDBS and show that flow-alignment of DMDBS networks template the orientation of PP crystals. The modulus and yield strength increase on addition of DMDBS, relative to the neat iPP. Tensile modulus and yield stress of drawn films increase with the degree of orientation, and we are able to achieve a substantial increase even at relatively low draw ratios.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Street, I.P.; Poulter, C.D.
1990-08-14
Isopentenyldiphosphate:dimethylallyldiphosphate isomerase (IPP isomerase) is an enzyme in isoprene metabolism which catalyzes the interconversion of the fundamental five-carbon homoallylic and allylic diphosphate building blocks for the pathway. The gene encoding IPP isomerase has recently been isolated from Saccharomyces cerevisiae. A heterologous expression system was constructed for the gene and used to overexpress IPP isomerase in Escherichia coli. In transformants carrying the expression vector, IPP isomerase activity was increased by over 100,000-fold relative to that of the untransformed host strain. The overexpressed enzyme constitutes 30-35% of the total soluble cell protein and can be purified to homogeneity in two steps. Recombinantmore » IPP isomerase was indistinguishable from that purified from yeast. 3-(Fluoromethyl)-3-butenyl diphosphate (FIPP) is a specific active-site-directed inhibitor of IPP isomerase from Claviceps purpurea. Inactivation of yeast IPP isomerase by FIPP was active-site-directed, and inhibition resulted in formation of a stoichiometric enzyme-inhibitor complex. The site of covalent attachment in the enzyme-inhibitor complex was determined by inactivating IPP isomerase with (4-{sup 3}H)FIPP, followed by digestion of the labeled enzyme with trypsin and purification of the resulting radioactive peptides by reversed-phase high-performance liquid chromatography. The primary site of attachment was Cys-139.« less
Blumenthal, Donald K.; Burke, John M.; Condren, Michelle; Hansen, Richard; Holiday-Goodman, Monica; Peterson, Charles D.
2012-01-01
Objective. To assess the extent to which US colleges and schools of pharmacy are incorporating interprofessional education into their introductory pharmacy practice experiences (IPPEs), and to identify barriers to implementation; characterize the format, structure, and assessment; and identify factors associated with incorporating interprofessional education in IPPEs. Methods. An electronic survey of 116 US colleges and schools of pharmacy was conducted from March 2011 through May 2011. Results. Interprofessional education is a stated curricular goal in 78% of colleges and schools and consistently occurred in IPPEs in 55%. Most colleges and schools that included interprofessional education in IPPEs (70%) used subjective measures to assess competencies, while 17.5% used standardized outcomes assessment instruments. Barriers cited by respondents from colleges and schools that had not implemented interprofessional education in IPPEs included a lack of access to sufficient healthcare facilities with interprofessional education opportunities (57%) and a lack of required personnel resources (52%). Conclusions. Many US colleges and schools of pharmacy have incorporated interprofessional education into their IPPEs, but there is a need for further expansion of interprofessional education and better assessment related to achievement of interprofessional education competencies in IPPEs. PMID:22761521
Intra-vesical Prostatic Protrusion (IPP) Can Be Reduced by Prostatic Artery Embolization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Yen-Ting, E-mail: ymerically@gmail.com; Amouyal, Grégory, E-mail: gregamouyal@hotmail.com; Thiounn, Nicolas, E-mail: nicolas.thiounn@egp.aphp.fr
BackgroundProstate artery embolization (PAE) is a new approach to improve lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia. PAE results in global reduction of prostate volume (PV). There are no data available on the efficacy of PAE in reducing intra-vesical prostatic protrusion (IPP), an anatomic feature that is clinically related with bladder outlet obstruction and LUTS.ObjectiveTo assess the results of PAE in patients with significant IPP due to median lobe hyperplasia and to compare the IPSS decrease and IPP change.Material and MethodsProspective analysis of 18 consecutive patients with significant IPP (>5 mm) related to median lobe hyperplasia undergoing PAEmore » using 30–500-μm-calibrated trisacryl microspheres. We measured IPP on sagittal T2-weighted images before and 3 months after PAE. IPSS and clinical results were also evaluated at 3 months.ResultsPAE resulted in significant IPP reduction (1.57 cm ± 0.55 before PAE and 1.30 cm ± 0.46 after PAE, p = 0.0005) (Fig. 1) with no complication. IPSS, quality of life (QoL), total prostate-specific antigen (PSA) level, and PV showed significant reduction after PAE, and maximum urinary flow rate (Q{sub max}) showed significant increase after PAE. No significant change of International Index of Erectile Function (IIEF) for clinical evaluation after PAE. A significant correlation was found between the IPP change and the IPSS change (r = 0.636, p = 0.0045).ConclusionPatients had significant IPP reduction as well as significant symptomatic improvement after PAE, and these improvements were positively correlated.« less
Chung, Eric; Solomon, Matthew; DeYoung, Ling; Brock, Gerald B
2013-11-01
The implantation of inflatable penile prosthesis (IPP) with simultaneous manual penile remodeling allows for men to undergo a single procedure aimed at correcting both the penile deformity/curvature and erectile dysfunction (ED). To evaluate the clinical outcomes and patient satisfaction in men with Peyronie's disease (PD) and ED who underwent AMS 700™ CX and the newer Coloplast™ Titan inflatable penile prosthesis (IPP) implant. Patient demographics, type of IPP, clinical outcomes, post-implant sexual characteristics, and overall patient satisfaction. A single-center retrospective review of clinical database and prospective telephone survey were conducted in all men with PD who underwent IPP between January 2006 and November 2010. A total of 138 patients with an average age of 57.7 (32 to 80) underwent AMS 700 CX (88 patients) and Coloplast Titans (50 patients) IPP implantation during the 5-year period. The majority of patients (91%) had only one IPP implantation. The IPP clinical outcomes include eight (6%) revision surgery for device malfunction and three (2%) device explantation for prosthesis infection. While there was no statistically significance in device survival between the two devices, the trend favored AMS 700 CX over Titan (5-year Kaplan-Meier estimates of mechanical survival were 91% vs. 87%, P>0.05) and both IPPs provided similar penile straightening without the need for revision surgery. Most men (79%) reported great satisfaction following CX or Titan implants with greater than two thirds of men reported greater self-confidence and 82% of patients would undergo the same operation again. AMS 700™ CX and Coloplast™ Titan IPP implantation and penile remodeling appeared to provide permanent penile straightening and high patient satisfaction without an increase risk of revision surgery. © 2012 International Society for Sexual Medicine.
Barnett, Tony; Hoang, Ha; Cross, Merylin; Bridgman, Heather
2015-01-01
Few studies have examined interprofessional practice (IPP) from a mental health service perspective. This study applied a mixed-method approach to examine the IPP and learning occurring in a youth mental health service in Tasmania, Australia. The aims of the study were to investigate the extent to which staff were networked, how collaboratively they practiced and supported student learning, and to elicit the organisation's strengths and opportunities regarding IPP and learning. Six data sets were collected: pre- and post-test readiness for interprofessional learning surveys, Social Network survey, organisational readiness for IPP and learning checklist, "talking wall" role clarification activity, and observations of participants working through a clinical case study. Participants (n = 19) were well-networked and demonstrated a patient-centred approach. Results confirmed participants' positive attitudes to IPP and learning and identified ways to strengthen the organisation's interprofessional capability. This mixed-method approach could assist others to investigate IPP and learning.
Stimulation of inorganic pyrophosphate elaboration by cultured cartilage and chondrocytes.
Ryan, L M; Kurup, I; Rosenthal, A K; McCarty, D J
1989-08-01
Inorganic pyrophosphate elaboration by articular cartilage may favor calcium pyrophosphate dihydrate crystal deposition. Frequently crystal deposits form in persons affected with metabolic diseases. The cartilage organ culture system was used to model these metabolic conditions while measuring the influence on extracellular pyrophosphate elaboration. Alterations of ambient pH, thyroid stimulating hormone levels, and parathyroid hormone levels did not change pyrophosphate accumulation in the media. However, subphysiologic ambient calcium concentrations (25, 100, 500 microM) increased pyrophosphate accumulation about chondrocytes 3- to 10-fold. Low calcium also induced release of [14C]adenine-labeled nucleotides from chondrocytes, potential substrates for generation of extracellular pyrophosphate by ectoenzymes. Exposing cartilage to 10% fetal bovine serum also enhanced by 50% the egress of inorganic pyrophosphate from the tissue.
NASA Astrophysics Data System (ADS)
Yan, Jingming
2002-09-01
In recent years, there have been efforts at both the federal and state level to introduce greater competition and markets into the US electricity industry through regulatory restructuring. A key to the success of such efforts is the ability of the restructuring to attract investment from non-utility, independent power producers (IPPs). The two essays in this dissertation examine empirically the investment behavior of IPPs under the regulatory restructuring between 1996 and 2000. In both essays, the effects of restructuring on a firm's investment decision are decomposed into the effects that work through the investment cost and that through the expected profit from the investment. The first essay studies the entry behavior of IPPs under the restructuring. The main finding of the essay is that the restructuring has done little to lower the entry barrier faced by IPPs-high fixed cost to entry is still a main factor that hinders IPP investment. The second essay studies IPPs' decisions between investing through building new power plants ("make") and investing through acquiring divested plants ("buy"). It finds that the availability of the "buy" option does not "squeeze" out investment on new capacities. IPPs that chose to "buy" did so because they expected a lower return from "make" and hence would not have switched their investment to new capacities even if the "buy" option were not available. Therefore, divestiture is a viable policy tool for state regulators to attract more IPP investment.
Hall, Stephen J.; Eastham, Graham; Licence, Peter; Stephens, Gill
2015-01-01
Mevalonate diphosphate decarboxylase (MVD) is an ATP-dependent enzyme that catalyzes the phosphorylation/decarboxylation of (R)-mevalonate-5-diphosphate to isopentenyl pyrophosphate in the mevalonate (MVA) pathway. MVD is a key enzyme in engineered metabolic pathways for bioproduction of isobutene, since it catalyzes the conversion of 3-hydroxyisovalerate (3-HIV) to isobutene, an important platform chemical. The putative homologue from Picrophilus torridus has been identified as a highly efficient variant in a number of patents, but its detailed characterization has not been reported. In this study, we have successfully purified and characterized the putative MVD from P. torridus. We discovered that it is not a decarboxylase per se but an ATP-dependent enzyme, mevalonate-3-kinase (M3K), which catalyzes the phosphorylation of MVA to mevalonate-3-phosphate. The enzyme's potential in isobutene formation is due to the conversion of 3-HIV to an unstable 3-phosphate intermediate that undergoes consequent spontaneous decarboxylation to form isobutene. Isobutene production rates were as high as 507 pmol min−1 g cells−1 using Escherichia coli cells expressing the enzyme and 2,880 pmol min−1 mg protein−1 with the purified histidine-tagged enzyme, significantly higher than reported previously. M3K is a key enzyme of the novel MVA pathway discovered very recently in Thermoplasma acidophilum. We suggest that P. torridus metabolizes MVA by the same pathway. PMID:25636853
Exploring individual adaptations to an anterior cruciate ligament injury prevention programme.
Fox, Aaron S; Bonacci, Jason; McLean, Scott G; Saunders, Natalie
2018-01-01
Individual responses to anterior cruciate ligament injury prevention programmes (ACL IPPs) have received little attention. This study examined the effects of an ACL IPP on neuromuscular control and lower limb biomechanics during landing at the group and individual levels. Sixteen female athletes were randomly allocated to training (n=8) or control (n=8) groups. Electromyography, and three-dimensional kinematic and kinetic data were collected during landing at two testing sessions. Repeated measures ANOVA and effect sizes (Cohen's d) examined the effect of the IPP at the group and individual levels. A sub-group analysis comparing the effect of the IPP on 'high-' (i.e. large peak knee abduction moment at baseline) versus 'low-risk' individuals was also conducted. At the group level; the IPP increased activation of the medial hamstrings prior to landing (p<0.001; d=0.264) and the medial gastrocnemius at landing (p<0.001; d=0.426), and increased hip external rotation early after initial contact (p<0.001; d=0.476). Variable adaptations were seen across individuals within the training group for all variables (p<0.001). The IPP had a large effect in reducing frontal plane knee moments for 'high-risk' individuals (d>0.91), however these results did not reach statistical significance (p>0.05). The IPP induced adaptations during landing, however, individual data revealed dissimilar responses to the programme. Individuals displaying a pre-existing high-risk strategy may incur greater benefits from IPPs, yet only if the programme targets the relevant high-risk strategy. Copyright © 2017 Elsevier B.V. All rights reserved.
Asymmetrical intrapleural pressure distribution: a cause for scoliosis? A computational analysis.
Schlager, Benedikt; Niemeyer, Frank; Galbusera, Fabio; Wilke, Hans-Joachim
2018-04-13
The mechanical link between the pleural physiology and the development of scoliosis is still unresolved. The intrapleural pressure (IPP) which is distributed across the inner chest wall has yet been widely neglected in etiology debates. With this study, we attempted to investigate the mechanical influence of the IPP distribution on the shape of the spinal curvature. A finite element model of pleura, chest and spine was created based on CT data of a patient with no visual deformities. Different IPP distributions at a static end of expiration condition were investigated, such as the influence of an asymmetry in the IPP distribution between the left and right hemithorax. The results were then compared to clinical data. The application of the IPP resulted in a compressive force of 22.3 N and a flexion moment of 2.8 N m at S1. An asymmetrical pressure between the left and right hemithorax resulted in lateral deviation of the spine towards the side of the reduced negative pressure. In particular, the pressure within the dorsal section of the rib cage had a strong influence on the vertebral rotation, while the pressure in medial and ventral region affected the lateral displacement. An asymmetrical IPP caused spinal deformation patterns which were comparable to deformation patterns seen in scoliotic spines. The calculated reaction forces suggest that the IPP contributes in counterbalancing the weight of the intrathoracic organs. The study confirms the potential relevance of the IPP for spinal biomechanics and pathologies, such as adolescent idiopathic scoliosis.
Liu, Qiang; Zhu, Yunkai; Liu, Jianping; Qi, Jun; Kang, Jian
2017-03-01
Intravesical prostatic protrusion (IPP) is a type of benign prostatic hyperplasia (BPH) adenoma, and it plays a critical role in the pathogenesis of bladder outlet obstruction in patients with lower urinary tract syndromes (LUTS/BPH). The goal of this study was to investigate the effect of a combination therapy with finasteride and doxazosin on IPP in BPU/LUTS patients. A total of 322 BPH patients with enlarged prostatic volume as well as moderate to severe symptom scores were enrolled and divided into four groups according to the degree of IPP (IPP > 10 mm, 5-10 mm, <5 mm and no IPP) in this study. Aggravated International Prostatic Symptom Score (IPSS), acute urinary retention or relevant urinary complications were considered as failure of the therapy. The degrees of IPP were recorded before and after 6 months of treatment. Student's t test and χ 2 were performed between the baseline and endpoint of the therapy. The results showed that the total prostate volume (TPV) and transition zone volume (TZV) of the prostate decreased significantly after 6-month combination therapy (P < 0.05), while no significant changes in IPP were observed at that point (P > 0.05). Failure rates of the medication differed significantly among the four groups. The study indicated that the combination therapy using finasteride and doxazosin could not reduce the degree of IPP. LUTS/BPH patients with IPP which contributes to the failure of medication tend to have a higher risk of progression.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-01
... proceeding Black Hills Colorado IPP, LLC's application for market-based rate authority, with an accompanying... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER11-2724-000] Black Hills Colorado IPP, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for Blanket...
Polarimetric imaging of biological tissues based on the indices of polarimetric purity.
Van Eeckhout, Albert; Lizana, Angel; Garcia-Caurel, Enric; Gil, José J; Sansa, Adrià; Rodríguez, Carla; Estévez, Irene; González, Emilio; Escalera, Juan C; Moreno, Ignacio; Campos, Juan
2018-04-01
We highlight the interest of using the indices of polarimetric purity (IPPs) to the inspection of biological tissues. The IPPs were recently proposed in the literature and they result in a further synthetization of the depolarizing properties of samples. Compared with standard polarimetric images of biological samples, IPP-based images lead to larger image contrast of some biological structures and to a further physical interpretation of the depolarizing mechanisms inherent to the samples. In addition, unlike other methods, their calculation do not require advanced algebraic operations (as is the case of polar decompositions), and they result in 3 indicators of easy implementation. We also propose a pseudo-colored encoding of the IPP information that leads to an improved visualization of samples. This last technique opens the possibility of tailored adjustment of tissues contrast by using customized pseudo-colored images. The potential of the IPP approach is experimentally highlighted along the manuscript by studying 3 different ex-vivo samples. A significant image contrast enhancement is obtained by using the IPP-based methods, compared to standard polarimetric images. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Rai, Avanish; Smita, Shachi S; Singh, Anup Kumar; Shanker, Karuna; Nagegowda, Dinesh A
2013-09-01
Catharanthus roseus is the sole source of two most important monoterpene indole alkaloid (MIA) anti-cancer agents: vinblastine and vincristine. MIAs possess a terpene and an indole moiety derived from terpenoid and shikimate pathways, respectively. Geranyl diphosphate (GPP), the entry point to the formation of terpene moiety, is a product of the condensation of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) by GPP synthase (GPPS). Here, we report three genes encoding proteins with sequence similarity to large subunit (CrGPPS.LSU) and small subunit (CrGPPS.SSU) of heteromeric GPPSs, and a homomeric GPPSs. CrGPPS.LSU is a bifunctional enzyme producing both GPP and geranyl geranyl diphosphate (GGPP), CrGPPS.SSU is inactive, whereas CrGPPS is a homomeric enzyme forming GPP. Co-expression of both subunits in Escherichia coli resulted in heteromeric enzyme with enhanced activity producing only GPP. While CrGPPS.LSU and CrGPPS showed higher expression in older and younger leaves, respectively, CrGPPS.SSU showed an increasing trend and decreased gradually. Methyl jasmonate (MeJA) treatment of leaves significantly induced the expression of only CrGPPS.SSU. GFP localization indicated that CrGPPS.SSU is plastidial whereas CrGPPS is mitochondrial. Transient overexpression of AmGPPS.SSU in C. roseus leaves resulted in increased vindoline, immediate monomeric precursor of vinblastine and vincristine. Although C. roseus has both heteromeric and homomeric GPPS enzymes, our results implicate the involvement of only heteromeric GPPS with CrGPPS.SSU regulating the GPP flux for MIA biosynthesis.
Lopes, Thiago Jambo Alves; Simic, Milena; Myer, Gregory D; Ford, Kevin R; Hewett, Timothy E; Pappas, Evangelos
2018-05-01
Anterior cruciate ligament (ACL) tear is a common injury in sports and often occurs during landing from a jump. To synthesize the evidence on the effects of injury prevention programs (IPPs) on landing biomechanics as they relate to the ligament, quadriceps, trunk, and leg dominance theories associated with ACL injury risk. Meta-analysis. Six electronic databases were searched for studies that investigated the effect of IPPs on landing task biomechanics. Prospective studies that reported landing biomechanics at baseline and post-IPP were included. Results from trunk, hip, and knee kinematics and kinetics related to the ACL injury theories were extracted, and meta-analyses were performed when possible. The criteria were met by 28 studies with a total of 466 participants. Most studies evaluated young females, bilateral landing tasks, and recreational athletes, while most variables were related to the ligament and quadriceps dominance theories. An important predictor of ACL injury, peak knee abduction moment, decreased ( P = .01) after the IPPs while other variables related to the ligament dominance theory did not change. Regarding the quadriceps dominance theory, after the IPPs, angles of hip flexion at initial contact ( P = .009), peak hip flexion ( P = .002), and peak knee flexion ( P = .007) increased, while knee flexion at initial contact did not change ( P = .18). Moreover, peak knee flexion moment decreased ( P = .005) and peak vertical ground-reaction force did not change ( P = .10). The exercises used in IPPs might have the potential to improve landing task biomechanics related to the quadriceps dominance theory, especially increasing peak knee and hip flexion angles. Importantly, peak knee abduction moment decreased, which indicates that IPPs influence a desired movement strategy to help athletes overcome dangerous ligament dominance loads arising from lack of frontal plane control during dynamic tasks. The lack of findings for some biomechanical variables suggests that future IPPs may be enhanced by targeting participants' baseline profile deficits, highlighting the need to deliver an individualized and task-specific IPP.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Z Xu; C Chen; Y Wang
Combined effects of graphene nanosheets (GNSs) and shear flow on the crystallization behavior of isotactic polypropylene (iPP) were investigated by in-situ synchrotron wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS) techniques. For crystallization under quiescent condition (at 145 C), the half-crystallization time (t{sub 1/2}) of nanocomposites containing 0.05 and 0.1 wt % GNSs was reduced to at least 50% compared to that of neat iPP, indicating the high nucleation ability of GNSs. The crystallization rate of iPP was directly proportional to the GNS content. Under a relatively weak shear flow (at a rate of 20 s{sup -1} for 5more » s duration) and a low degree of supercooling, the neat iPP exhibited an isotropic structure due to the relaxation of row nuclei. However, visible antisotropic crystals appeared in sheared iPP/GNSs nanocomposites, indicating that GNSs induced a network structure hindering the mobility of iPP chains and allowing the survival of oriented row nuclei for a long period of time. The presence of GNSs clearly enhanced the effects of shear-induced nucleation as well as orientation of iPP crystals. Two kinds of nucleating origins coexisted in the sheared nanocomposite melt: heterogeneous nucleating sites initiated by GNSs and homogeneous nucleating sites (row nuclei) induced by shear. The difference of t{sub 1/2} of nanocomposites with and without shear was significantly larger than that of neat iPP. The presence of GNSs and shear flow exhibited a synergistic interaction on promoting crystallization kinetics of iPP, although the effect of GNS concentration was not apparent. From WAXD results of isothermal and nonisothermal crystallization of sheared iPP, it was found that the appearance of {beta}-crystals depended on the preservation of row nuclei, where the {alpha}-crystals were predominant in the iPP/GNSs nanocomposites, indicating that GNSs could directly induce {alpha}-crystals of iPP.« less
Henry, Gerard D; Carrion, Rafael; Jennermann, Caroline; Wang, Run
2015-05-01
The most prevalent long-term complaint after successful inflatable penile prosthesis (IPP) surgery is reduction of penile length. The purpose of this study was to evaluate penile measurements in patients whose implantation experience included the aggressive new length measurement technique (NLMT) coupled with postoperative IPP rehabilitation (daily inflation) of the implant for 1 year. Moreover, we aimed to document objective data concerning dimensional changes of the phallus over time. Postoperative IPP rehabilitation has been discussed and presented at meetings, but no multi-institutional prospective data have been published. Our goal was to assess results using the Coloplast Titan IPP, with NLMT, and postoperative rehabilitation. After IRB approval, we conducted a prospective, three-center study of 40 patients who underwent IPP placement, with NLMT for end organ failure erectile dysfunction with the Coloplast Titan IPP. The patient was instructed to inflate daily for 6 months and then inflate maximally for 1-2 hours daily for 6-12 months. Fifteen penile measurements were taken before and immediately after surgery and at follow-up visits. Penile length measurements after implantation compared with 12 months postimplantation. Penile measurement changes were statistically significantly improved at 12 months as compared with immediately postoperative and at 6 months. A total of 64.5% of subjects were satisfied with their length at 1 year, and 74.2% had perceived penile length that was longer (29%) or the same (45.2%) as prior to the surgery; 61.3% and 16.1% of subjects had increased and unchanged satisfaction, respectively, with penile length as compared with prior to IPP surgery. All but two subjects (93.4%) were satisfied with the overall function and dimensions of their IPP. This study suggests using the Coloplast Titan IPP with aggressive cylinder sizing, and a postoperative penile rehabilitation inflation protocol may help optimize patient satisfaction and erectile penile measurements. © 2015 International Society for Sexual Medicine.
Treatment with pyrophosphate inhibits uremic vascular calcification
O’Neill, W. Charles; Lomashvili, Koba A.; Malluche, Hartmut H.; Faugere, Marie-Claude; Riser, Bruce L.
2011-01-01
Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone. PMID:21124302
Treatment with pyrophosphate inhibits uremic vascular calcification.
O'Neill, W Charles; Lomashvili, Koba A; Malluche, Hartmut H; Faugere, Marie-Claude; Riser, Bruce L
2011-03-01
Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone.
National trends in IPPE programs at US schools of pharmacy from 2008-2013.
Devine, Patricia S; Darbishire, Patricia L
2015-04-25
To determine trends and challenges in introductory pharmacy practice experience (IPPE) programs from 2008-2013. In 2013, a web-based survey was sent to IPPE program administrators at 107 fully accredited colleges and schools of pharmacy. The survey addressed administrative personnel, program structure, and quality assurance issues. Sixty-nine IPPE administrators responded to the survey (64.5% response rate). Within the past 5 years, 4 significant trends occurred in the area of administrative personnel, 7 trends in program structure, and 6 in quality assurance. Clarifications of ACPE Standards through new guidelines and policy statements likely influence many of the 17 trends. Understaffed programs, competition for institutional sites, difficulty conducting site visits, preceptor training, program assessment, documentation maintenance, and individual site requirements are all challenges. The results of this study can be used as a stimulus to address ongoing issues and to enhance the quality of IPPE programs.
Idiopathic precocious puberty in girls: Psychosexual development.
Meyer-Bahlburg, H F; Ehrhardt, A A; Bell, J J; Cohen, S F; Healey, J M; Feldman, J F; Morishima, A; Baker, S W; New, M I
1985-08-01
A promising model syndrome for the examination of the role of physical maturation in the development of female sexuality is idiopathic precocious puberty (IPP). In this first controlled study of psychosexual development in IPP females, 16 females between 13 and 20 years of age with a history of IPP were compared to 16 control subjects with a history of normal puberty pair-matched to the index subjects on the basis of sex, race, age, socioeconomic level, and menarcheal status. The psychosexual history and the current psychosexual status were assessed by a systematic half-structured interview. The IPP females on average passed the psychosexual milestones at an earlier age than their normal maturing peers, with a particularly early onset of masturbation. Those who were sociosexually active tended to report a higher total orgasmic outlet and a higher sex drive. There was no increase in homosexuality among IPP girls. The timing of puberty has a (modest) influence on psychosexual development in females.
IMMR Phase 1 Prototyping Plan Inputs
NASA Technical Reports Server (NTRS)
Vowell, C. W.; Johnson-Throop, Kathy; Smith, Bryon; Darcy, Jeannette
2006-01-01
This viewgraph presentation reviews the phase I plan of the prototype of the IMMR by the Multilateral Medical Operations Panel (MMOP) Medical Informatics & Technology (MIT) Working Group. It reviews the Purpose of IMMR Prototype Phase 1 (IPP1); the IPP1 Plan Overview, the IMMR Prototype Phase 1 Plan for PDDs and MIC and MIC-DDs, Plan for MICs, a nd the IPP1 objectives
McNaughton, Susan
2017-12-22
Several recent high-quality systematic reviews have identified the importance of measuring outcomes in evaluating the effectiveness of interprofessional education (IPE) in healthcare, but also the process- and context-dependent nature of these outcomes. This paper presents a scoping review, the objectives of which were to evaluate the evidence for the long-term impact of undergraduate IPE on graduate interprofessional practice (IPP) and to identify areas for further research in the specific context of practice-based IPE. An initial search identified 596 potentially relevant titles published between 2008 and 2016. Screening for inclusion of documented IPE with IPP evaluation reduced this to 130. Abstract reading excluded 99 studies that were not longitudinal. Full reading of the remaining 31 articles identified 23 original studies which were analysed descriptively and tabulated. The main findings were synthesised around three themes: undergraduate evidence for a long-term impact of IPE on IPP; graduate evidence for a long-term impact of IPE on IPP; and barriers to an impact of IPE on graduate IPP. Drawing on these findings, research areas likely to produce further evidence for the impact of practice-based IPE on graduate IPP are discussed, along with some suitable methodologies.
21 CFR 182.8223 - Calcium pyrophosphate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223... FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use. This substance is generally recognized...
21 CFR 182.8223 - Calcium pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pyrophosphate. 182.8223 Section 182.8223... FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use. This substance is generally recognized...
21 CFR 582.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...
21 CFR 182.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Conditions of use. This substance is...
21 CFR 582.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...
21 CFR 182.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Conditions of use. This substance is...
21 CFR 182.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Conditions of use. This substance is...
21 CFR 182.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Conditions of use. This substance is...
21 CFR 582.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...
21 CFR 582.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...
21 CFR 582.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium pyrophosphate. 582.6787 Section 582.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Sodium pyrophosphate. (a) Product. Sodium pyrophosphate. (b) Condition of use. This substance is...
21 CFR 182.6789 - Tetra sodium pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tetra sodium pyrophosphate. 182.6789 Section 182.6789 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6789 Tetra sodium pyrophosphate. (a) Product. Tetra sodium pyrophosphate. (b) Conditions of use. This...
21 CFR 182.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium acid pyrophosphate. 182.1087 Section 182.1087 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b...
21 CFR 182.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium acid pyrophosphate. 182.1087 Section 182...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally...
21 CFR 582.6789 - Tetra sodium pyrophosphate.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Tetra sodium pyrophosphate. 582.6789 Section 582.6789 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6789 Tetra sodium pyrophosphate. (a) Product. Tetra sodium pyrophosphate. (b) Conditions of use. This...
21 CFR 182.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium acid pyrophosphate. 182.1087 Section 182.1087 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b...
21 CFR 182.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium acid pyrophosphate. 182.1087 Section 182.1087 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b...
Chen, Chen; Zhang, Ning; He, Yulu; Liang, Bo; Ma, Renzhi; Liu, Xiaohe
2016-09-07
Incorporation of two transition metals offers an effective method to enhance the electrochemical performance in supercapacitors for transition metal compound based electrodes. However, such a configuration is seldom concerned in pyrophosphates. Here, amorphous phase Co-Ni pyrophosphates are fabricated as electrodes in supercapacitors. Through controllably adjusting the ratios of Co and Ni as well as the calcination temperature, the electrochemical performance can be tuned. An optimized amorphous Ni-Co pyrophosphate exhibits much higher specific capacitance than monometallic Ni and Co pyrophosphates and shows excellent cycling ability. When employing Ni-Co pyrophosphates as positive electrode and activated carbon as a negative electrode, the fabricated asymmetric supercapacitor cell exhibits favorable capacitance and cycling ability. This study provides facile methods to improve the transition metal pyrophosphate electrodes for efficient electrodes in electrochemical energy storage devices.
21 CFR 582.5306 - Ferric sodium pyrophosphate.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Dietary Supplements 1 § 582.5306 Ferric sodium pyrophosphate. (a) Product. Ferric sodium pyrophosphate. (b...
21 CFR 182.6789 - Tetra sodium pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Tetra sodium pyrophosphate. 182.6789 Section 182...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6789 Tetra sodium pyrophosphate. (a) Product. Tetra sodium pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when...
NASA Astrophysics Data System (ADS)
Ikotun, Oluwatayo (Tayo) F.
The multidentate nature of pyrophosphate makes it an attractive ligand for complexation of metal cations. The participation of pyrophosphate in a variety of biological pathways and its metal catalyzed hydrolysis has driven our investigation into its coordination chemistry. We have successfully synthesized a library of binuclear pyrophosphate bridge coordination complexes. The problem of pyrophosphate hydrolysis to phosphate in the presence of divalent metal ions was overcome by incorporating capping ligands such as 1,10-phenanthroline and 2,2'-bipyridine prior to the addition of the pyrophosphate. The magnetic properties of these complexes was investigated and magneto-structural analysis was conducted. The biological abundance of pyrophosphate and the success of metal based drugs such as cisplatin, prompted our investigation of the cytotoxic properties of M(II) pyrophosphate dimeric complexes (where M(II) is CoII, CuII, and NiII) in adriamycin resistant human ovarian cancer cells. Thess compounds were found to exhibit toxicity in the nanomolar to picomolar range. We conducted in vitro stability studies and the mechanism of cytoxicity was elucidated by performing DNA mobility and binding assays, enzyme inhibition assays, and in vitro oxidative stress studies.
NASA Astrophysics Data System (ADS)
Baohong, Gao; Yuling, Liu; Chenwei, Wang; Yadong, Zhu; Shengli, Wang; Qiang, Zhou; Baimei, Tan
2010-10-01
This paper presents a new cleaning process using boron-doped diamond (BDD) film anode electrochemical oxidation for metallic contaminants on polished silicon wafer surfaces. The BDD film anode electrochemical oxidation can efficiently prepare pyrophosphate peroxide, pyrophosphate peroxide can oxidize organic contaminants, and pyrophosphate peroxide is deoxidized into pyrophosphate. Pyrophosphate, a good complexing agent, can form a metal complex, which is a structure consisting of a copper ion, bonded to a surrounding array of two pyrophosphate anions. Three polished wafers were immersed in the 0.01 mol/L CuSO4 solution for 2 h in order to make comparative experiments. The first one was cleaned by pyrophosphate peroxide, the second by RCA (Radio Corporation of America) cleaning, and the third by deionized (DI) water. The XPS measurement result shows that the metallic contaminants on wafers cleaned by the RCA method and by pyrophosphate peroxide is less than the XPS detection limits of 1 ppm. And the wafer's surface cleaned by pyrophosphate peroxide is more efficient in removing organic carbon residues than RCA cleaning. Therefore, BDD film anode electrochemical oxidation can be used for microelectronics cleaning, and it can effectively remove organic contaminants and metallic contaminants in one step. It also achieves energy saving and environmental protection.
And deregulation shall lead me to lie down in green pastures
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weidinger, G.
1995-06-01
This presentation briefly reviews the history of the IPP industry, the current state of competition, and potential opportunities for IPPs in a deregulated environment. Since the beginning of the PURPA created IPP industry, we have experienced many market phases. These began with {open_quotes}beat avoided cost,{close_quotes} followed by {open_quotes}find a need and fill it,{close_quotes} followed by {open_quotes}the bid fest,{close_quotes} to today`s {open_quotes}anything goes.{close_quotes} During this time, market clearing prices have declined from over 80/KwHr to 2-40/KwHr. Today`s partially deregulated electric market includes fierce competition and several new players in the game. Where surplus capacity exists, IPPs must compete with subsidized power.more » Long-term contracts are no longer widely available. Access to markets is constrained by less than open transmission. Even with these challenges, opportunities remain for the IPP supplier. Opportunities for advanced coal-fired power systems will be explored.« less
Dinkins, Melissa M; Haltom, Wesley R
2018-04-01
Objective. To characterize weekly student reflections in an introductory pharmacy practice experience (IPPE) discussion course meeting concurrently with IPPE rotations in institutional pharmacy. Methods. A qualitative analysis was conducted to identify themes within weekly reflective statements submitted by second year pharmacy students (P2) enrolled in an IPPE rotation and concurrent discussion course. Weekly reflections from the 2015-2016 offering of the course were reviewed by investigators to identify common themes via an iterative process. Subsequently, investigators coded each submission into one of the identified categories. Initial agreement between investigators was assessed using the Cohen kappa coefficient. Discrepancies between coding were resolved through discussion to reach consensus. Results. A total of 402 reflection assignments were reviewed from 85 P2 students enrolled in the IPPE course. Ten themes were identified, with the most common themes being interprofessional teamwork, pharmacist and technician roles and responsibilities, and policies and procedures. Substantial initial agreement between investigators was found, with the most discrepancies arising within the themes of medication distribution and pharmacy administration/organizational structure. Conclusion. Student reflections on IPPEs centered on 10 key topics, primarily related to distributive, legal, and regulatory functions of institutional pharmacy practice. Structuring an IPPE rotation longitudinally in an academic term, with a concurrent discussion course, builds a framework for regular student reflection.
Lovell, R; Whalan, M; Marshall, P W M; Sampson, J A; Siegler, J C; Buchheit, M
2018-05-24
Scheduling eccentric-based injury prevention programs (IPP) during the common 6-day micro-cycle in soccer is challenged by recovery and tapering phases. This study profiled muscle damage, neuromuscular performance, and perceptual responses to a lower limb eccentric-based IPP administered 1 (MD+1) vs 3 days (MD+3) postmatch. A total of 18 semi-professional players were monitored daily during 3 in-season 6-day micro-cycles, including weekly competitive fixtures. Capillary creatine kinase concentration (CK), posterior lower limb isometric peak force (PF), counter-movement jump (CMJ) performance, and muscle soreness were assessed 24 hours prior to match-day (baseline), and every 24 hours up to 120 hours postmatch. The IPP consisted of lunges, single stiff leg dead-lifts, single leg-squats, and Nordic hamstring exercises. Performing the IPP on MD+1 attenuated the decline in CK normally observed following match play (CON: 142%; MD+3: 166%; small differences). When IPP was delivered on MD+3, CK was higher vs CON and MD+1 trials on both MD+4 (MD+3: 260%; CON: 146%; MD+1: 151%; moderate differences) and MD+5 (MD+3: 209%; CON: 125%; MD+1: 127%; small differences). Soreness ratings were not exacerbated when the IPP was delivered on MD+1, but when prescribed on MD+3, hamstring soreness ratings remained higher on MD+4 and MD+5 (small differences). No between-trial differences were observed for PF and CMJ. Administering the IPP in the middle of the micro-cycle (MD+3) increased measures of muscle damage and soreness, which remained elevated on the day prior to the next match (MD+5). Accordingly, IPP should be scheduled early in the micro-cycle, to avoid compromising preparation for the following match. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Alphs, Hannah H; Navai, Neema; Köhler, Tobias S; McVary, Kevin T
2010-03-01
Penile vascular abnormalities occur in a high proportion of patients with Peyronie's disease (PD). Penile duplex ultrasonography (PDU) and dynamic infusion cavernosometry and cavernosography (DICC) are tools that can be used to help tailor individualized treatment for patients undergoing surgical intervention for their PD. However, precisely which parameters can be used to predict those patients with PD at risk for developing erectile dysfunction (ED) after intervention without inflatable penile prosthesis (IPP) has not been previously elucidated. To evaluate preoperative vascular parameters that predispose PD patients for developing ED after intervention without IPP. Twenty-six patients receiving surgical intervention for their PD at a single center were retrospectively identified. Of these, 11 (42.3%) opted for primary repair without placement of an IPP. Three (27.2%) of these 11 patients went on to develop ED postoperatively. We compared various demographic, PDU, and DICC parameters between patients who did and did not fail primary repair of their PD. Mean age and follow-up of patients who went on to develop ED after repair of PD without IPP were not significantly different (P < 0.05). Resistive index (RI) and end diastolic volume were significantly different between these two groups (P < 0.05), while peak systolic volume, flow to maintain, and pressure decay were not significantly different. An RI cutoff of <0.80 was found to identify all patients who would later develop ED and fail primary repair without IPP. Penile vascular assessment can aid in counseling patients about their risk of developing delayed ED after primary repair of PD. In our cohort of patients, PDU provided preoperative risk stratification for postoperative erectile dysfunction in men undergoing Peyronie's repair without IPP. We propose the prospective study of an RI cutoff to identify patients at risk of failing primary PD repair without IPP.
Formation of pyrophosphate on hydroxyapatite with thioesters as condensing agents
NASA Technical Reports Server (NTRS)
Weber, A. L.
1982-01-01
'Energy-rich' thioesters are shown to act as condensing agents in the formation of pyrophosphate on hydroxyapatite in the presence of water at ambient temperature. The yield of pyrophosphate based on thioester ranges from 2.5% to 11.4% and depends upon the pH and concentration of reactants. Reaction of 0.130 M hydroxyapatite suspended in a solution of 0.08 M sodium phosphate and 0.20 M imidazole hydrochloride (pH 7.0) with 0.10 M N,S-diacetylcysteamine for 6 days gives the highest yield of pyrophosphate (11.4%). Pyrophosphate formation requires the presence of hydroxyapatite, sodium phosphate and the thioester, N,S-diacetylcysteamine. The related thioester, N,S-diacetylcysteine, also yields pyrophosphate in reactions on hydroxyapatite.
Integrated Personnel and Pay System-Army Increment 2 (IPPS-A Inc 2)
2016-03-01
2016 Major Automated Information System Annual Report Integrated Personnel and Pay System-Army Increment 2 (IPPS-A Inc 2) Defense Acquisition...703-325-3747 DSN Phone: 865-2915 DSN Fax: 221-3747 Date Assigned: May 2, 2014 Program Information Program Name Integrated Personnel and Pay System...Program Description The Integrated Personnel and Pay System-Army (IPPS-A) will provide the Army with an integrated, multi-Component (Active, National
21 CFR 582.5223 - Calcium pyrophosphate.
Code of Federal Regulations, 2012 CFR
2012-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...
21 CFR 582.5223 - Calcium pyrophosphate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...
21 CFR 582.5223 - Calcium pyrophosphate.
Code of Federal Regulations, 2013 CFR
2013-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...
21 CFR 582.5223 - Calcium pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...
21 CFR 582.5223 - Calcium pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5223 Calcium pyrophosphate. (a) Product. Calcium pyrophosphate. (b) Conditions of use...
Addlesee, Hugh A.; Fiedor, Leszek; Hunter, C. Neil
2000-01-01
The purple photosynthetic bacterium Rhodobacter sphaeroides has within its genome a cluster of photosynthesis-related genes approximately 41 kb in length. In an attempt to identify genes involved in the terminal esterification stage of bacteriochlorophyll biosynthesis, a previously uncharacterized 5-kb region of this cluster was sequenced. Four open reading frames (ORFs) were identified, and each was analyzed by transposon mutagenesis. The product of one of these ORFs, bchG, shows close homologies with (bacterio)chlorophyll synthetases, and mutants in this gene were found to accumulate bacteriopheophorbide, the metal-free derivative of the bacteriochlorophyll precursor bacteriochlorophyllide, suggesting that bchG is responsible for the esterification of bacteriochlorophyllide with an alcohol moiety. This assignment of function to bchG was verified by the performance of assays demonstrating the ability of BchG protein, heterologously synthesized in Escherichia coli, to esterify bacteriochlorophyllide with geranylgeranyl pyrophosphate in vitro, thereby generating bacteriochlorophyll. This step is pivotal to the assembly of a functional photosystem in R. sphaeroides, a model organism for the study of structure-function relationships in photosynthesis. A second gene, orf177, is a member of a large family of isopentenyl diphosphate isomerases, while sequence homologies suggest that a third gene, orf427, may encode an assembly factor for photosynthetic complexes. The function of the remaining ORF, bchP, is the subject of a separate paper (H. Addlesee and C. N. Hunter, J. Bacteriol. 181:7248–7255, 1999). An operonal arrangement of the genes is proposed. PMID:10809697
Shea, Patrick R; Virtaneva, Kimmo; Kupko, John J; Porcella, Stephen F; Barry, William T; Wright, Fred A; Kobayashi, Scott D; Carmody, Aaron; Ireland, Robin M; Sturdevant, Daniel E; Ricklefs, Stacy M; Babar, Imran; Johnson, Claire A; Graham, Morag R; Gardner, Donald J; Bailey, John R; Parnell, Michael J; Deleo, Frank R; Musser, James M
2010-03-09
Relatively little is understood about the dynamics of global host-pathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven biological pathways were differentially expressed throughout the entire 32-day infection cycle. GAS infection produced an initial widespread significant decrease in expression of many host genes, including those involved in cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic capsule production and host endocytic vesicle formation, GAS GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host gammadelta T cells and genes in the GAS mevalonic acid synthesis pathway responsible for production of isopentenyl-pyrophosphate, a short-chain phospholipid that stimulates these T cells. Taken together, our results are unique in providing a comprehensive understanding of the host-pathogen interactome during mucosal infection by a bacterial pathogen.
Efficient searching and annotation of metabolic networks using chemical similarity
Pertusi, Dante A.; Stine, Andrew E.; Broadbelt, Linda J.; Tyo, Keith E.J.
2015-01-01
Motivation: The urgent need for efficient and sustainable biological production of fuels and high-value chemicals has elicited a wave of in silico techniques for identifying promising novel pathways to these compounds in large putative metabolic networks. To date, these approaches have primarily used general graph search algorithms, which are prohibitively slow as putative metabolic networks may exceed 1 million compounds. To alleviate this limitation, we report two methods—SimIndex (SI) and SimZyme—which use chemical similarity of 2D chemical fingerprints to efficiently navigate large metabolic networks and propose enzymatic connections between the constituent nodes. We also report a Byers–Waterman type pathway search algorithm for further paring down pertinent networks. Results: Benchmarking tests run with SI show it can reduce the number of nodes visited in searching a putative network by 100-fold with a computational time improvement of up to 105-fold. Subsequent Byers–Waterman search application further reduces the number of nodes searched by up to 100-fold, while SimZyme demonstrates ∼90% accuracy in matching query substrates with enzymes. Using these modules, we have designed and annotated an alternative to the methylerythritol phosphate pathway to produce isopentenyl pyrophosphate with more favorable thermodynamics than the native pathway. These algorithms will have a significant impact on our ability to use large metabolic networks that lack annotation of promiscuous reactions. Availability and implementation: Python files will be available for download at http://tyolab.northwestern.edu/tools/. Contact: k-tyo@northwestern.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25417203
Efficient searching and annotation of metabolic networks using chemical similarity.
Pertusi, Dante A; Stine, Andrew E; Broadbelt, Linda J; Tyo, Keith E J
2015-04-01
The urgent need for efficient and sustainable biological production of fuels and high-value chemicals has elicited a wave of in silico techniques for identifying promising novel pathways to these compounds in large putative metabolic networks. To date, these approaches have primarily used general graph search algorithms, which are prohibitively slow as putative metabolic networks may exceed 1 million compounds. To alleviate this limitation, we report two methods--SimIndex (SI) and SimZyme--which use chemical similarity of 2D chemical fingerprints to efficiently navigate large metabolic networks and propose enzymatic connections between the constituent nodes. We also report a Byers-Waterman type pathway search algorithm for further paring down pertinent networks. Benchmarking tests run with SI show it can reduce the number of nodes visited in searching a putative network by 100-fold with a computational time improvement of up to 10(5)-fold. Subsequent Byers-Waterman search application further reduces the number of nodes searched by up to 100-fold, while SimZyme demonstrates ∼ 90% accuracy in matching query substrates with enzymes. Using these modules, we have designed and annotated an alternative to the methylerythritol phosphate pathway to produce isopentenyl pyrophosphate with more favorable thermodynamics than the native pathway. These algorithms will have a significant impact on our ability to use large metabolic networks that lack annotation of promiscuous reactions. Python files will be available for download at http://tyolab.northwestern.edu/tools/. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
21 CFR 582.5304 - Ferric pyrophosphate.
Code of Federal Regulations, 2013 CFR
2013-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...
21 CFR 582.5304 - Ferric pyrophosphate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...
21 CFR 582.5304 - Ferric pyrophosphate.
Code of Federal Regulations, 2012 CFR
2012-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...
21 CFR 582.5304 - Ferric pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...
21 CFR 582.5304 - Ferric pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5304 Ferric pyrophosphate. (a) Product. Ferric pyrophosphate. (b) Conditions of use. This...
Ciaglia, Elena; Pisanti, Simona; Picardi, Paola; Laezza, Chiara; Malfitano, Anna Maria; D'Alessandro, Alba; Gazzerro, Patrizia; Vitale, Mario; Carbone, Ennio; Bifulco, Maurizio
2013-12-01
iPA is a naturally occurring nucleoside with an isopentenyl moiety derived from the mevalonate pathway and a well-established anti-tumor activity. In analogy to the unique specificity for phosphoantigens, such as IPP, shown by human Vγ9Vδ2 T cells, here, we report for the first time the ability of iPA to selectively expand and directly target human NK cells. Interestingly, submicromolar doses of iPA stimulate resting human NK cells and synergize with IL-2 to induce a robust activation ex vivo with significant secretion of CCL5 and CCL3 and a large increase in TNF-α and IFN-γ production when compared with IL-2 single cytokine treatment. Moreover, iPA promotes NK cell proliferation and up-regulates the expression of specific NK cell-activating receptors, as well as CD69 and CD107a expression. Accordingly, this phenotype correlates with significantly greater cytotoxicity against tumor targets. At the molecular level, iPA leads to a selective, potent activation of MAPK signaling intermediaries downstream of the IL-2R. The effect results, at least in part, from the fine modulation of the FDPS activity, the same enzyme implicated in the stimulation of the human γδ T cells. The iPA-driven modulation of FDPS can cause an enhancement of post-translational prenylation essential for the biological activity of key proteins in NK signaling and effector functions, such as Ras. These unanticipated properties of iPA provide an additional piece of evidence of the immunoregulatory role of the intermediates of the mevalonate pathway and open novel therapeutic perspectives for this molecule as an immune-modulatory drug.
Microbial Production of Isoprene
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ray Fall
2007-07-29
Isoprene is a volatile hydrocarbon of unknown function, produced by certain bacteria, plants and animals, sometimes in huge amounts—the Earth’s forests are estimated to emit >500 x 106 tons of isoprene per year. With funding from this program we explored the biochemistry and regulation of isoprene formation in the model bacterial system, Bacillus subtilis, with the goals of explaining the biological rationale for isoprene biogenesis and constructing an isoprene-overproducing microbial system. Although the role for isoprene formation in B. subtilis is still uncertain, our current model for regulation of this hydrocarbon’s synthesis is that isoprene production in B. subtilis ismore » controlled by a combination of i) rapid regulation of isoprene synthase activity and ii) supply of the substrate for isoprene synthase, dimethyallyl diphosphate (DMAPP). This model parallels our current thinking about the control of isoprene formation in plant chloroplasts. In this reporting period we have been working to test part ii) of this model; this work has produced new results using genetic and analytical approaches. For examples, we have developed an analytical method to resolve DMAPP and its isomer, isopentenyl diphosphate, from each other in bacteria and plants. We have also shown that the IPP isomerase (type 2) of B. subtilis is not the source of “isoprene synthase” activity, and discovered that B. subtilis releases C5 isoprenoid alcohols to the medium, suggesting that isoprene plus other C5 isoprenoids may be common by-products of metabolism. In addition, we have continued to work on our discovery that wild type B. subtilis strains form prolific biofilms, are normal components of plant root microflora, and are testing the idea that B. subtilis growing in biofilms uses isoprene to induce plant root exudation.« less
Hypolito, Octavio; Azevedo, João Luiz; Gama, Fernanda; Azevedo, Otavio; Miyahira, Susana Abe; Pires, Oscar César; Caldeira, Fabiana Alvarenga; Silva, Thamiris
2014-01-01
to evaluate the clinical, hemodynamic, gas analysis and metabolic repercussions of high transient pressures of pneumoperitoneum for a short period of time to ensure greater security for introduction of the first trocar. sixty-seven patients undergoing laparoscopic procedures were studied and randomly distributed in P12 group: n=30 (intraperitoneal pressure [IPP] 12mmHg) and P20 group: n=37 (IPP of 20mmHg). Mean arterial pressure (MAP) was evaluated by catheterization of the radial artery; and through gas analysis, pH, partial pressure of oxygen (PaO2), partial pressure of CO2 (PaCO2), bicarbonate (HCO3) and alkalinity (BE) were evaluated. These parameters were measured in both groups at time zero before pneumoperitoneum (TP0); at time 1 (TP1) when IPP reaches 12mmHg in both groups; at time 2 (TP2) after five min with IPP=12mmHg in P12 and after 5min with IPP=20mmHg at P20; and at time 3 (TP3) after 10min with IPP=12mmHg in P12 and with return of IPP from 20 to 12mmHg, starting 10min after TP1 in P20. Different values from those considered normal for all parameters assessed, or the appearance of atypical organic phenomena, were considered as clinical changes. there were statistically significant differences in P20 group in MAP, pH, HCO3 and BE, but within normal limits. No clinical and pathological changes were observed. high and transient intra-abdominal pressure causes changes in MAP, pH, HCO3 and BE, but without any clinical impact on the patient. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Sheikh, Mashhood Ahmed
2018-05-01
The aim of this study was to assess the mediating role of dissatisfaction with friendships in adulthood in the associations between psychological abuse in childhood, substance abuse distress in childhood, and incident psychiatric problems (IPPs) in adulthood over 13 years of follow-up. We used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 9502), a representative, longitudinal, prospective cohort study. Poisson regression analysis was used to assess the associations between psychological abuse, substance abuse distress, dissatisfaction with friendships in adulthood, and IPPs in adulthood. Indirect effects and proportion mediated (%) were assessed with the difference-in-coefficients method. Psychological abuse (relative risk [RR] = 1.66, 95% confidence interval [CI]: 1.45-1.89) and substance abuse distress in childhood (RR = 1.38, 95% CI: 1.18-1.62) were associated with an increased risk of dissatisfaction with friendships in adulthood. Dissatisfaction with friendships in adulthood was associated with an increased risk of IPPs in adulthood (RR = 1.71, 95% CI: 1.33-2.20). Moreover, dissatisfaction with friendships in adulthood mediated 9.31% (95% CI: 4.25-14.57) of the association between psychological abuse in childhood and IPPs in adulthood, and 9.17% (95% CI: 4.35-16.33) of the association between substance abuse distress in childhood and IPPs in adulthood. Dissatisfaction with friendships in adulthood mediates a minor proportion of the associations between psychological abuse, substance abuse distress, and IPPs in adulthood. Interventions aimed at decreasing dissatisfaction with friendships may dampen some of the effect of psychological abuse and substance abuse distress in childhood on IPPs in adulthood. Copyright © 2018 Elsevier Inc. All rights reserved.
Shah, Nirali M; Brieger, William R; Peters, David H
2011-07-01
BACKGROUND There is a growing interest in the role of private health providers in low- and middle-income countries (LMICs). Informal private providers (IPPs) provide a significant portion of health care in many LMICs, but they have not received training in allopathic medicine. Interventions have been developed to take advantage of their potential to expand access to essential health services, although their success is not well measured. This paper addresses this information gap through a review of interventions designed to improve the quality, coverage, or costs of health services provided by IPPs in LMICs. METHODS A search for published literature in the last 15 years for any intervention dealing with IPPs in a LMIC, where at least one outcome was measured, was conducted through electronic databases PubMed and Global Health, as well as Google for grey literature from the Internet. RESULTS A total of 1272 articles were retrieved, of which 70 separate studies met inclusion criteria. The majority (70%) of outcomes measured proximate indicators such as provider knowledge (61% were positive) and behaviour (56% positive). Training IPPs was the most common intervention tested (77% of studies), but the more effective strategies did not involve training alone. Interventions that changed the institutional relationships and contributed to changing the incentives and accountability environment were most successful, and often required combinations of interventions. CONCLUSION Although there are documented interventions among IPPs, there are few good quality studies. Strategies that change the market conditions for IPPs-by changing incentives and accountability-appear more likely to succeed than those that depend on building individual capacities of IPPs. Understanding the effectiveness of these and other strategies will also require more rigorous research designs that assess contextual factors and document outcomes over longer periods.
Schefft, Matthew R; Swaffar, Caitlan; Newlin, Jennifer; Noda, Cady; Sisler, India
2018-06-01
Vaso-occlusive crisis (VOC) is frequent in children with sickle cell disease (SCD) creating significant burden on patients, families, and emergency departments (ED). The objective of the project was to reduce the admission rate for children with SCD presenting to our ED with VOC by >20% within 6 months of initiating individualized pain plans (IPP). A multi-disciplinary quality improvement team was assembled. A Plan-Do-Study-Act (PDSA) format was employed. The IPP document was created in a unique folder within the electronic medical record. IPPs were created through retrospective chart review for our 80 highest resource users. Pediatric residents, ED residents, and ED attending physicians were instructed on use of the IPPs. Our study measured the presence of an IPP, adherence to the IPP, and time to opiate administration. Our primary outcome was admission rate. Length of stay and 72-hr return to the ED were assessed as balancing measures. Overall, admission rate decreased by 24% following implementation compared with the previous 5 years (P = 0.046). IPPs were created for 78% of patients and followed by ED staff in 86% of visits. Admission rate was significantly lower for patients receiving a second opiate dose within 45 min of the first dose (P < 0.01). There was no difference in readmission rate or 72-hr return rate to ED. This study presents an effective strategy to reduce admission rate for children with SCD presenting with VOC. Shorter time to second opiate dosing was also associated with reduced risk of admission. © 2018 Wiley Periodicals, Inc.
DOD Business Systems Modernization: Additional Action Needed to Achieve Intended Outcomes
2015-07-01
including greater operational efficiencies and cost savings. View GAO-15-627. For more information, contact Carol R. Cha at (202) 512-4456 or chac @gao.gov...report, please contact me at (202) 512-4456 or chac @gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs may be found...Personnel and Pay System - Army (IPPS-A), Integrated Personnel and Pay System - Navy (IPPS- N ), Air Force Integrated Personnel and Pay System (AF-IPPS
21 CFR 582.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...
21 CFR 582.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...
21 CFR 582.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2012 CFR
2012-04-01
... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...
21 CFR 582.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...
21 CFR 582.1087 - Sodium acid pyrophosphate.
Code of Federal Regulations, 2013 CFR
2013-04-01
... Additives § 582.1087 Sodium acid pyrophosphate. (a) Product. Sodium acid pyrophosphate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...
Indices of polarimetric purity for biological tissues inspection
NASA Astrophysics Data System (ADS)
Van Eeckhout, Albert; Lizana, Angel; Garcia-Caurel, Enric; Gil, José J.; Sansa, Adrià; Rodríguez, Carla; Estévez, Irene; González, Emilio; Escalera, Juan C.; Moreno, Ignacio; Campos, Juan
2018-02-01
We highlight the interest of using the Indices of Polarimetric Purity (IPPs) for the biological tissue inspection. These are three polarimetric metrics focused on the study of the depolarizing behaviour of the sample. The IPPs have been recently proposed in the literature and provide different and synthetized information than the commonly used depolarizing indices, as depolarization index (PΔ) or depolarization power (Δ). Compared with the standard polarimetric images of biological samples, IPPs enhance the contrast between different tissues of the sample and show differences between similar tissues which are not observed using the other standard techniques. Moreover, they present further physical information related to the depolarization mechanisms inherent to different tissues. In addition, the algorithm does not require advanced calculations (as in the case of polar decompositions), being the indices of polarimetric purity fast and easy to implement. We also propose a pseudo-coloured image method which encodes the sample information as a function of the different indices weights. These images allow us to customize the visualization of samples and to highlight certain of their constitutive structures. The interest and potential of the IPP approach are experimentally illustrated throughout the manuscript by comparing polarimetric images of different ex-vivo samples obtained with standard polarimetric methods with those obtained from the IPPs analysis. Enhanced contrast and retrieval of new information are experimentally obtained from the different IPP based images.
Girgih, Abraham T; Chao, Dongfang; Lin, Lin; He, Rong; Jung, Stephanie; Aluko, Rotimi E
2015-12-01
Isolated pea protein (IPP) dispersions (1%, w/v) were pretreated with high pressure (HP) of 200, 400, or 600 MPa for 5 min at 24 °C or high temperature (HT) for 30 min at 100 °C prior to hydrolysis with 1% (w/w) Alcalase. HP pretreatment of IPP at 400 and 600 MPa levels led to significantly (P<0.05) improved (>40%) oxygen radical absorption capacity (ORAC) of hydrolysates. 2,2-Diphenyl-1-picrylhydrazyl, superoxide radical and hydroxyl radical scavenging activities of pea protein hydrolysates were also significantly (P<0.05) improved (25%, 20%, and 40%, respectively) by HP pretreatment of IPP. Protein hydrolysates from HT IPP showed no ORAC, superoxide or hydroxyl scavenging activity but had significantly (P<0.05) improved (80%) ferric reducing antioxidant power. The protein hydrolysates had weaker antioxidant properties than glutathione but overall, the HP pretreatment was superior to HT pretreatment in facilitating enzymatic release of antioxidant peptides from IPP. Copyright © 2015 Elsevier Ltd. All rights reserved.
Naffakh, Mohammed; Marco, Carlos; Ellis, Gary
2012-02-16
The isothermal crystallization and subsequent melting behavior of isotactic polypropylene (iPP) nucleated with different nucleating agents (NAs) are investigated. Tungsten disulfide (IF-WS(2)) and N,N'-dicyclohexyl-2,6-naphthalene (NJ) and dual-additive mixtures are introduced into an iPP matrix to generate new materials that exhibit variable α- and β-polymorphism. As shown in previous work, small amounts of IF-WS(2) or NJ have a nucleating effect during the crystallization of iPP. However, the isothermal crystallization and melting behavior of iPP nucleated by dual α(IF-WS(2))/β(NJ) additive systems are dependent on both the NA composition balance and the crystallization temperature. In particular, our results demonstrate that it is possible to obtain any α-phase to β-phase content ratio by controlling the composition of NAs under appropriate isothermal crystallization conditions. The nucleating behavior of the additives can be illustrated by competitive nucleation, and the correlation between crystallization and melting temperatures and relative α- and β-crystals content in iPP in the nanocomposites is discussed.
Immunomodulatory constituents from an ascomycete, Microascus tardifaciens.
Fujimoto, H; Fujimaki, T; Okuyama, E; Yamazaki, M
1999-10-01
Fractionation guided by the immunosuppressive activity of the defatted AcOEt extract of an Ascomycete, Microascus tardifaciens, afforded eight constituents, questin (emodin 8-O-methylether) (1), rubrocristin (2), 5,7-dihydroxy-4-methylphthalide (3), cladosporin (asperentin) (4), cladosporin 8-O-methylether (5), tradioxopiperazine A [cyclo-L-alanyl-5-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (6), tradioxopiperazine B [cyclo-L-alanyl-7-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (7), and asperflavin (8), among which 6 and 7 were new compounds. Compounds 1 and 2 showed considerably high immunosuppressive activity, 6 was moderate and, 3, 4, 5, 7 and 8 showed low activity.
Landing Technique and Performance in Youth Athletes After a Single Injury-Prevention Program Session
Root, Hayley; Trojian, Thomas; Martinez, Jessica; Kraemer, William; DiStefano, Lindsay J.
2015-01-01
Context Injury-prevention programs (IPPs) performed as season-long warm-ups improve injury rates, performance outcomes, and jump-landing technique. However, concerns regarding program adoption exist. Identifying the acute benefits of using an IPP compared with other warm-ups may encourage IPP adoption. Objective To examine the immediate effects of 3 warm-up protocols (IPP, static warm-up [SWU], or dynamic warm-up [DWU]) on jump-landing technique and performance measures in youth athletes. Design Randomized controlled clinical trial. Setting Gymnasiums. Patients or Other Participants Sixty male and 29 female athletes (age = 13 ± 2 years, height = 162.8 ± 12.6 cm, mass = 37.1 ± 13.5 kg) volunteered to participate in a single session. Intervention(s) Participants were stratified by age, sex, and sport and then were randomized into 1 protocol: IPP, SWU, or DWU. The IPP consisted of dynamic flexibility, strengthening, plyometric, and balance exercises and emphasized proper technique. The SWU consisted of jogging and lower extremity static stretching. The DWU consisted of dynamic lower extremity flexibility exercises. Participants were assessed for landing technique and performance measures immediately before (PRE) and after (POST) completing their warm-ups. Main Outcome Measure(s) One rater graded each jump-landing trial using the Landing Error Scoring System. Participants performed a vertical jump, long jump, shuttle run, and jump-landing task in randomized order. The averages of all jump-landing trials and performance variables were used to calculate 1 composite score for each variable at PRE and POST. Change scores were calculated (POST − PRE) for all measures. Separate 1-way (group) analyses of variance were conducted for each dependent variable (α < .05). Results No differences were observed among groups for any performance measures (P > .05). The Landing Error Scoring System scores improved after the IPP (change = −0.40 ± 1.24 errors) compared with the DWU (0.27 ± 1.09 errors) and SWU (0.43 ± 1.35 errors; P = .04). Conclusions An IPP did not impair sport performance and may have reduced injury risk, which supports the use of these programs before sport activity. PMID:26523663
Byakika-Kibwika, Pauline; Kutesa, Annet; Baingana, Rhona; Muhumuza, Christine; Kitutu, Freddy Eric; Mwesigwa, Catherine; Chalo, Rose Nabirye; Sewankambo, Nelson K
2015-10-23
Students at Makerere University College of Health Sciences (MakCHS) are introduced to ethics and professionalism using the inter-professional education (IPE) model. Ethics and professionalism should be running themes throughout succeeding years of study during which students are expected to develop qualities and skills for future inter-professional practice (IPP). We performed a situation analysis of IPE and IPP among students and teaching health professionals at MakCHS to guide development of a relevant training curriculum of ethics and professionalism. A cross sectional study with quantitative and qualitative methods which included questionnaires, focus group discussions and key informant interviews. We interviewed 236 undergraduate students (148, 63 % male) and 32 teaching health professionals (25, 78 % male). Two hundred fifteen (91 %) students indicated they had joint learning activities with students of other professions and 166 (70 %) stated there was benefit in having an IPE model training curriculum. Most students (140, 59 %) strongly agreed that learning with other students will make them more effective members of the health team. Whereas the respondents reported inter professionalism as being well articulated in their course curricula, more than half said IPE is only implemented in the pre-clinical years of study. They noted that IPE and IPP concepts were not well programmed, health professionals engaged in teaching had poor attitudes towards IPE and IPP, there were limited numbers of skilled health care workers to implement IPP and there was poor communication between students and teaching health professionals. Majority of teaching health professionals noted challenges in implementation of IPE such as poor coordination and large student population and major factors influencing ethics and professionalism in healthcare such as limited government support, low pay for the health care workers, disrespect and lack of appreciation of the health workers by the public. Our findings demonstrate that IPE, IPP, ethics and professionalism are not emphasized in the clinical years of study at MakCHS. We recommend increased sensitization on the concepts of IPE and IPP plus enhanced mentorship for both students and teaching health professionals. Innovative strategies of implementation of IPE and IPP for training in ethics and professionalism must be introduced.
Palmisano, Franco; Boeri, Luca; Cristini, Cristiano; Antonini, Gabriele; Spinelli, Matteo Giulio; Franco, Giorgio; Longo, Fabrizio; Gadda, Franco; Colombo, Fulvio; Montanari, Emanuele
2018-05-02
The 3-piece inflatable penile prosthesis (IPP) is the gold standard treatment for male erectile dysfunction when other less invasive approaches are contra-indicated or unacceptable for the patient. There are currently 2 surgical approaches for IPP implantation: the penoscrotal (PS) and the infrapubic (IP) incision. To assess the most recent evidence on the impact of surgical approach for 3-piece IPP implantation in patients with erectile dysfunction. A systematic literature review was performed using the MEDLINE (PubMed) and Cochrane Libraries databases in November 2017 to identify all studies investigating 3-piece IPP with a specified surgical access. The following key words were used in combination: "infrapubic," "transcrotal," "penoscrotal," "peno-scrotal," and "penile prosthesis." Additional references were obtained from the reference lists of full-text manuscripts. We used a narrative synthesis for the analyses of the studies. 22 Studies reporting data on 3-piece IPP implantation with a specified surgical approach were found in the literature. While IPPs are most commonly positioned through a PS incision, the IP approach is a faster procedure. No cases of glans hypoesthesia after IPP placement with an IP approach were reported, and the overall peri-prosthetic infection rate was 3.3% or less. Patient satisfaction rates were higher than 80% in both groups. Both the IP and PS approaches are viable and effective strategies for a 3-piece IPP placement, and result in high satisfaction rates. To date there is no evidence that an incision strategy may reduce infection rates. Penile sensory loss following an IP approach remains a virtual risk. It is recommended that the surgeon executing the implant have knowledge of both accesses and be capable of tailoring the incision strategy for complex cases. The chosen method should be based on the patient's specific anatomy, surgical history, and surgeon experience. Palmisano F, Boeri L, Cristini C, et al. Comparison of Infrapubic vs Penoscrotal Approaches for 3-Piece Inflatable Penile Prosthesis Placement: Do We Have a Winner? Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Trembacz, H; Jezewska, M M
1990-01-01
Spontaneous decomposition of 5-phosphoribosyl 1-pyrophosphate at pH 5.5 was established to occur as follows: 5-Phosphoribosyl 1-pyrophosphate----5-phosphoribosyl 1,2-(cyclic)phosphate----ribose 1-phosphate----ribose Enzymic degradation of 5-phosphoribosyl 1-pyrophosphate by alkaline phosphatase from calf intestine and by acid phosphatases from potato and Aspergillus niger was found to proceed according to this pathway within the pH range 2.5-7.4 with accumulation of ribose 1-phosphate. In the case of alkaline phosphatase, Mg2+ ions inhibit the pyrophosphorolysis of 5-phosphoribosyl 1-pyrophosphate and stimulate the hydrolysis of ribose 1-phosphate. PMID:1700897
Enhanced Photolysis of Nucleic Acid Monomers by Pyrophosphate in the Simulated Primitive Soup
NASA Astrophysics Data System (ADS)
Kongjiang, Wang; Zhifang, Chai; Xianming, Pan
1999-05-01
In our simulation of the photochemistry of the primitive soup, it was found that yield of chromophore loss of some nucleic acid bases, nucleosides and nucleotides [NA] undergoing ultraviolet radiation by medium pressure mercury lamp [MPML] was enhanced by pyrophosphate and triphosphate whether O2 is present or not. The yield of chromophore loss of guanosine, uracil, 5' CMP, and the derivatives of adenine and thymine was observed to rise with the increase of molar concentration of pyrophosphate in N2-saturated systems. In air-saturated samples, increase in yield of chromophore loss was observed when the concentration of pyrophosphate reaches 5×10-4 M, relative yield of chromophore loss (CLrel) coming to maximum in the range from 0.01 to 0.1 M, followed by a slight decline with the further increase of pyrophosphate concentration. The enhancement of photolysis of NA by pyrophosphate was due to the interaction between NA and pyrophosphate radicals photoionized by UV quanta of wavelength less than about 210 nm in the emission spectrum of a MPML. The relevance of this phenomenon to the origin of life has been discussed as well.
Meyer, J; Bütikofer, U; Walther, B; Wechsler, D; Sieber, R
2009-03-01
The angiotensin-converting enzyme (ACE) inhibitory activity and the concentration of the 2 ACE-inhibiting tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) were studied during cheese ripening in 7 Swiss cheese varieties. The semi-hard cheeses Tilsiter, Appenzeller 1/4 fat, Tête de Moine, and Vacherin fribourgeois and the extra-hard and hard cheeses Berner Hobelkäse, Le Gruyère, and Emmentaler were investigated. Three loaves of each variety manufactured in different cheese factories were purchased at the beginning of commercial ripeness and investigated at constant intervals until the end of the usual sale period. Good agreement was found between ACE-inhibitory activity and the total concentration of VPP and IPP at advanced ripening stages. In most of the investigated varieties ACE-inhibitory activity and the concentration of the 2 tripeptides initially increased during the study period. A decline in the concentration of VPP and IPP was obtained toward the end of the investigated period for Tilsiter and Gruyère. The ratio of VPP/IPP decreased during ripening in all varieties with the exception of Emmentaler. However, large variations were observed among the cheese varieties as well as the individual loaves of the same variety. Chemical characterization of the investigated cheeses revealed that qualitative differences in the proteolysis pattern, not quantitative differences in the degree of proteolysis, are responsible for the observed variations in the concentrations of VPP and IPP. The presence of Lactobacillus helveticus in the starter culture was associated with elevated concentrations of VPP and IPP. The results of the present study show that concentrations of VPP and IPP above 100 mg/kg are attainable in semi-hard cheese varieties after ripening periods of about 4 to 7 mo and that stable concentrations of the 2 antihypertensive tripeptides can be expected over several weeks of cheese ripening.
Influence of Ice-phase of Hydrometeors on Moist-Convection
NASA Technical Reports Server (NTRS)
Sud, Y. C.; Walker, G. K.
2003-01-01
Climate models often ignore the influence of ice-phase physics (IPP) of hydrometeors as a second order effect. This has also been true for McRAS (Microphysics of clouds with Relaxed Arakawa Schubert Scheme) developed by the authors. Recognizing that the temperature sounding is critical for moist-convection, and, that IPP would modify it, we investigated the influence of introducing IPP into McRAS coupled to FvGCM (finite volume General Circulation Model with NCAR physics). We analyzed three 3-yr long simulations; the first called Control Case, CC and had no IPP; the other two called Experiments El and E2 had IPP introduced with two different in-cloud freezing assumptions. Simulation El assumed that all hydrometeors remain liquid in the updraft and freeze upon detrainment. Simulation E2 invoked the in-cloud freezing of new condensate generated at subfreezing temperatures in the updraft while old cloud water continued to ascend as liquid. Upon detrainment, this cloud water also froze like in E1. With these assumptions, about 50% of hydrometeors froze in the tower and the rest froze in the anvil. However, in both El and E2, the frozen hydrometeors melted during fall at the first encounter of above freezing ambient temperature. Comparative analysis revealed that El simulated far more mid-level and far less deep clouds while E2 had modified deep and more mid-level clouds as compared to CC along with some major changes around the melt-level. We infer that IPP produced a more realistic response in E2. At the basic level, the results show that ice-phase processes influence convective detrainment at mid- and deep levels in accord with TOGAGOARE observations. The results suggest that IPP can help to mitigate less-than-observed mid-level and over-abundance of deep convective clouds in McRAS.
The melt-recrystallization behavior of highly oriented α-iPP fibers embedded in a HIPS matrix.
Ye, Liwei; Li, Huihui; Qiu, Zhaobin; Yan, Shouke
2015-03-21
The melt-recrystallization behavior of α-iPP fibers embedded in an amorphous HIPS matrix has been studied by means of optical microscopy. The amorphous HIPS serving as a supporter of iPP fibers does not become involved in the nucleation and crystallization process of the molten highly oriented iPP fibers. It also does not provide any birefringence under the optical microscope with crossed polarizers. This enables the study of orientation-induced β-iPP crystallization through a control of the melting status of the fibers. Through melting the fibers at different temperatures above 175 °C and subsequent recrystallization, some β-iPP crystals were always produced. The content of the β-iPP crystal depends strongly on the melting temperature and melting time of the iPP fibers. It was confirmed that melting the iPP fibers at relatively lower temperature, e.g. 176 °C, less amount of β-iPP crystals were observed. The content of β-iPP crystal enhances first with increasing melting temperature and then decreases with further increase of the fiber melting temperature. The β-iPP crystallization is found to be most favorable upon melting the fibers at 178 °C for 2 min. This demonstrates the requirement of a certain chain or chain segment orientation for generating β-iPP crystallization on the one hand, while higher orientation of the iPP chains or chain segments encourages the growth of iPP crystals in the α-form on the other hand. This has been further confirmed by varying the melting time of the fiber at different temperatures, since relaxation of the iPP molecular chains at a fixed temperature is time dependent. Moreover, the complete transformation of α-iPP fibers in some local places into β-iPP crystals implies that the αβ-transition may not be required for the orientation-induced β-iPP crystallization.
Russo, Giorgio I; Regis, Federica; Spatafora, Pietro; Frizzi, Jacopo; Urzì, Daniele; Cimino, Sebastiano; Serni, Sergio; Carini, Marco; Gacci, Mauro; Morgia, Giuseppe
2018-05-01
To investigate the association between metabolic syndrome (MetS) and morphological features of benign prostatic enlargement (BPE), including total prostate volume (TPV), transitional zone volume (TZV) and intravesical prostatic protrusion (IPP). Between January 2015 and January 2017, 224 consecutive men aged >50 years presenting with lower urinary tract symptoms (LUTS) suggestive of BPE were recruited to this multicentre cross-sectional study. MetS was defined according to International Diabetes Federation criteria. Multivariate linear and logistic regression models were performed to verify factors associated with IPP, TZV and TPV. Patients with MetS were observed to have a significant increase in IPP (P < 0.01), TPV (P < 0.01) and TZV (P = 0.02). On linear regression analysis, adjusted for age and metabolic factors of MetS, we found that high-density lipoprotein (HDL) cholesterol was negatively associated with IPP (r = -0.17), TPV (r = -0.19) and TZV (r = -0.17), while hypertension was positively associated with IPP (r = 0.16), TPV (r = 0.19) and TZV (r = 0.16). On multivariate logistic regression analysis adjusted for age and factors of MetS, hypertension (categorical; odds ratio [OR] 2.95), HDL cholesterol (OR 0.94) and triglycerides (OR 1.01) were independent predictors of TPV ≥ 40 mL. We also found that HDL cholesterol (OR 0.86), hypertension (OR 2.0) and waist circumference (OR 1.09) were significantly associated with TZV ≥ 20 mL. On age-adjusted logistic regression analysis, MetS was significantly associated with IPP ≥ 10 mm (OR 34.0; P < 0.01), TZV ≥ 20 mL (OR 4.40; P < 0.01) and TPV ≥ 40 mL (OR 5.89; P = 0.03). We found an association between MetS and BPE, demonstrating a relationship with IPP. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.
Spencer, Judy; Woodroffe, Jessica; Cross, Merylin; Allen, Penny
2015-01-01
Little is known about interprofessional practice (IPP) and interprofessional learning (IPL) in rural health services, despite national funding and continuing emphasis on increasing students' clinical placements in rural areas. This short paper outlines a study in Tasmania, Australia, which investigated how and under what contexts and conditions IPP and IPL occur in rural clinical settings, and the enabling factors and strategies that promote this learning and practice. This study employed a mixed method design comprising focus group discussions and a survey involving health professionals from two rural health services. The findings demonstrate that formal and informal arrangements, the collaborative nature of small, close-knit healthcare teams and patient-centred models of care employed in rural practice settings, provide ideal contexts for IPP and IPL. The study has implications for promoting organisational readiness for IPP and IPL and harnessing the potential of rural services to promote and develop students' interprofessional capability.
Kadar, Gena E; Vosko, Andrew; Sackett, Michael; Thompson, H Garrett Rush
2015-01-01
A survey of the constituents of a complementary and alternative medicine (CAM) institution was conducted to identify perceptions of interprofessional education (IPE) and practice (IPP). A 22 question survey was developed and administered to: chiropractic students, acupuncture and oriental medicine students, faculty and alumni of both professions, staff and administrators. The majority of the 321 respondents demonstrated positive perceptions of IPE and IPP, however many reported a lack of understanding of the distinct roles of select healthcare professions. The study also suggested that the campus community is not homogenous in its understanding of CAM or allopathic professions, or is it homogenous in its understanding of IPE and IPP. While the overall positive attitudes toward IPE and IPP imply a willingness to improve collaboration between these groups, the lack of understanding of profession-specific roles must be addressed to support effective implementation of IPE.
Enhancing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through pulse zoledronate stimulation.
Nada, Mohanad H; Wang, Hong; Workalemahu, Grefachew; Tanaka, Yoshimasa; Morita, Craig T
2017-01-01
Human γδ T cells expressing Vγ2Vδ2 T cell receptors monitor foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis to mediate immunity to microbes and tumors. Adoptive immunotherapy with Vγ2Vδ2 T cells has been used to treat cancer patients with partial and complete remissions. Most clinical trials and preclinical studies have used continuous zoledronate exposure to expand Vγ2Vδ2 cells where zoledronate is slowly diluted over the course of the culture. Zoledronate inhibits farnesyl diphosphate synthase (FDPS) in monocytes causing isopentenyl pyrophosphate to accumulate that then stimulates Vγ2Vδ2 cells. Because zoledronate inhibition of FDPS is also toxic for T cells, we hypothesized that a short period of exposure would reduce T cell toxicity but still be sufficient for monocytes uptake. Additionally, IL-15 increases the anti-tumor activity of murine αβ T cells in mice but its effect on the in vivo anti-tumor activity of human Vγ2Vδ2 cells has not been assessed. Human Vγ2Vδ2 T cells were expanded by pulse or continuous zoledronate stimulation with IL-2 or IL-15. Expanded Vγ2Vδ2 cells were tested for their expression of effector molecules and killing of tumor cells as well as their in vivo control of human prostate cancer tumors in immunodeficient NSG mice. Pulse zoledronate stimulation with either IL-2 or IL-15 resulted in more uniform expansion of Vγ2Vδ2 cells with higher purity and cell numbers as compared with continuous exposure. The Vγ2Vδ2 cells had higher levels of CD107a and perforin and increased tumor cytotoxicity. Adoptive immunotherapy with Vγ2Vδ2 cells derived by pulse stimulation controlled human PC-3 prostate cancer tumors in NSG mice significantly better than those derived by continuous stimulation, halting tumor growth. Although pulse zoledronate stimulation with IL-15 preserved early memory subsets, adoptive immunotherapy with IL-15-derived Vγ2Vδ2 cells equally inhibited PC-3 tumor growth as those derived with IL-2. Pulse zoledronate stimulation maximizes the purity, quantity, and quality of expanded Vγ2Vδ2 cells for adoptive immunotherapy but there is no advantage to using IL-15 over IL-2 in our humanized mouse model. Pulse zoledronate stimulation is a simple modification to existing protocols that will enhance the effectiveness of adoptively transferred Vγ2Vδ2 cells by increasing their numbers and anti-tumor activity.
Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters
Rhodes, David A.; Chen, Hung-Chang; Williamson, James C.; Hill, Alfred; Yuan, Jack; Smith, Sam; Rhodes, Harriet; Trowsdale, John; Lehner, Paul J.; Herrmann, Thomas; Eberl, Matthias
2018-01-01
Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR) transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC) transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with efficiency of T cell activation by cytokine secretion, although direct evidence of a functional role was not obtained by knockdown experiments. Our findings indicate a link between members of the ABC protein superfamily and the BTN3A-dependent activation of γδ T cells by endogenous and exogenous pAg. PMID:29670629
Two inositol hexakisphosphate kinases drive inositol pyrophosphate synthesis in plants
USDA-ARS?s Scientific Manuscript database
Inositol pyrophosphates are novel cellular signaling molecules with newly discovered roles in energy sensing and metabolic control. Studies in eukaryotes have revealed that these compounds turn over rapidly, and thus only small amounts accumulate. Inositol pyrophosphates have not been the subject of...
21 CFR 182.8223 - Calcium pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium pyrophosphate. (a) Product. Calcium...
21 CFR 182.6787 - Sodium pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium pyrophosphate. 182.6787 Section 182.6787 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6787 Sodium pyrophosphate. (a) Product. Sodium...
Steidle, Elizabeth A; Chong, Lucy S; Wu, Mingxuan; Crooke, Elliott; Fiedler, Dorothea; Resnick, Adam C; Rolfes, Ronda J
2016-03-25
Inositol pyrophosphates are high energy signaling molecules involved in cellular processes, such as energetic metabolism, telomere maintenance, stress responses, and vesicle trafficking, and can mediate protein phosphorylation. Although the inositol kinases underlying inositol pyrophosphate biosynthesis are well characterized, the phosphatases that selectively regulate their cellular pools are not fully described. The diphosphoinositol phosphate phosphohydrolase enzymes of the Nudix protein family have been demonstrated to dephosphorylate inositol pyrophosphates; however, theSaccharomyces cerevisiaehomolog Ddp1 prefers inorganic polyphosphate over inositol pyrophosphates. We identified a novel phosphatase of the recently discovered atypical dual specificity phosphatase family as a physiological inositol pyrophosphate phosphatase. Purified recombinant Siw14 hydrolyzes the β-phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5or IP7)in vitro. In vivo,siw14Δ yeast mutants possess increased IP7levels, whereas heterologousSIW14overexpression eliminates IP7from cells. IP7levels increased proportionately whensiw14Δ was combined withddp1Δ orvip1Δ, indicating independent activity by the enzymes encoded by these genes. We conclude that Siw14 is a physiological phosphatase that modulates inositol pyrophosphate metabolism by dephosphorylating the IP7isoform 5PP-IP5to IP6. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Chiba, Masatoshi; Hirotani, Hiroaki; Takahashi, Tetsu
2018-01-01
First bite syndrome, characterized by pain in the parotid region after the first bite of each meal, predominantly develops in patients who have had head and neck surgery. Idiopathic parotid pain (IPP) that mimics first bite syndrome may present in patients without a history of surgery or evidence of an underlying tumor, but its clinical features are unclear. This study characterized the clinical characteristics of IPP in patients with diabetes. A retrospective case review involving the clinical findings and pain characteristics of nine patients with IPP and diabetes who presented to our department between 2013 and 2016. All the patients were men diagnosed with type 2 diabetes (median age, 43 years). IPP developed unilaterally in seven patients and bilaterally in two. The median intensity of the first bite pain was 8 on a numerical rating scale of 0-10. The trigger factor was gustatory stimuli, and the trigger area was the posterior section of the tongue. Postprandial pain occurred within 1-10 min after meals in six patients. IPP may be considered a separate disorder, in which the pain characteristics are similar to those of first bite syndrome but the clinical features and pathophysiology are different.
Hirotani, Hiroaki; Takahashi, Tetsu
2018-01-01
Objective First bite syndrome, characterized by pain in the parotid region after the first bite of each meal, predominantly develops in patients who have had head and neck surgery. Idiopathic parotid pain (IPP) that mimics first bite syndrome may present in patients without a history of surgery or evidence of an underlying tumor, but its clinical features are unclear. This study characterized the clinical characteristics of IPP in patients with diabetes. Study Design A retrospective case review involving the clinical findings and pain characteristics of nine patients with IPP and diabetes who presented to our department between 2013 and 2016. Results All the patients were men diagnosed with type 2 diabetes (median age, 43 years). IPP developed unilaterally in seven patients and bilaterally in two. The median intensity of the first bite pain was 8 on a numerical rating scale of 0–10. The trigger factor was gustatory stimuli, and the trigger area was the posterior section of the tongue. Postprandial pain occurred within 1–10 min after meals in six patients. Conclusions IPP may be considered a separate disorder, in which the pain characteristics are similar to those of first bite syndrome but the clinical features and pathophysiology are different. PMID:29796314
Zhu, Xiaolin; Zhou, Shaomin; Guo, Jing; Zhao, Xiyue; Yang, Guanghua; Cai, Zhiqiang
2018-04-18
Paichongding (IPP) is a neonicotinoid chiral insecticide with independent intellectual property in China. IPP application can increase crop yield, and also lead to insecticide residue and pollution in soils, which will affect microbial population and community composition in soils. In this study, four different types of soils were employed to inquire into the impact of IPP on eukaryal community and species-group through pyrosequencing of 18S rRNA gene amplicons. Fungal population differed in different soils at different days after IPP treatment (DAT). Eukaryal community species in CK (control check) groups were more rich than that with Paichongding sprayed at 5 DAT, while eukaryal species in CK soils at 60 DAT was relatively slight. Shannon's H' analysis indicated fungal species in CK soils were also higher at 5 DAT and relative lower at 60 DAT, except in soil C. There are also differences in the phyla and genus levels of the eukaryotic communities in the soil. After IPP application, the relative abundance of Nectriaceae increased 3-4 times in soil C. In soil F, Phaeosphaeriaceae increased to 57.3% at 5 DAT. The genus of Guehomyces, Aspergillus and Alternaria increased from 3.1 to 9.7, 1.1 to 4.6, 1.5 to 6.7% in soil H, respectively.
Khodamoradi, Abdolvahed; Ghaffari, Mohammad Payam; Daryabeygi-Khotbehsara, Reza; Sajadi, Haniye Sadat; Majdzadeh, Reza
2018-01-01
Informal patients' payments (IPPs) is a sensitive subject. The aim of current study was to assess the trends in informal payment studies and explore methods of IPPs measurement, prevalence, and features (payment type, volume, and receiver) in various contexts. A search strategy was developed to identify peer-reviewed articles addressing informal payments on PubMed, Science Direct, Web of Science, Scopus, and CINAHL. A total of 1252 studies were identified initially. After screening process, 38 studies were included in the systematic review. The selected studies were appraised, and findings were synthesized. Among selected studies, quantitative approaches were mostly used for measuring IPPs from general public and patients' perspective, and qualitative methods mainly targeted health care providers. Reported IPP prevalence in selected articles ranges between 2% and 80%, more prevalent in the inpatient sector than in outpatient. There are a number of strategies for the measurement of IPPs with different strengths and weaknesses. Most applied strategies for general public were quantitative surveys recruiting more than 1000 participants using a face-to-face structured interview, and then qualitative studies on less than 150 health care providers, with focus group discussion. This review provides a comprehensive picture of current informal patients' payments measurement tools, which helps researchers in future investigations. Copyright © 2017 John Wiley & Sons, Ltd.
Faude, Oliver; Rössler, Roland; Petushek, Erich J.; Roth, Ralf; Zahner, Lukas; Donath, Lars
2017-01-01
Objective: Neuromuscular injury prevention programs (IPP) can reduce injury rate by about 40% in youth sport. Multimodal IPP include, for instance, balance, strength, power, and agility exercises. Our systematic review and meta-analysis aimed to evaluate the effects of multimodal IPP on neuromuscular performance in youth sports. Methods: We conducted a systematic literature search including selected search terms related to youth sports, injury prevention, and neuromuscular performance. Inclusion criteria were: (i) the study was a (cluster-)randomized controlled trial (RCT), and (ii) investigated healthy participants, up to 20 years of age and involved in organized sport, (iii) an intervention arm performing a multimodal IPP was compared to a control arm following a common training regime, and (iv) neuromuscular performance parameters (e.g., balance, power, strength, sprint) were assessed. Furthermore, we evaluated IPP effects on sport-specific skills. Results: Fourteen RCTs (comprising 704 participants) were analyzed. Eight studies included only males, and five only females. Seventy-one percent of all studies investigated soccer players with basketball, field hockey, futsal, Gaelic football, and hurling being the remaining sports. The average age of the participants ranged from 10 years up to 19 years and the level of play from recreational to professional. Intervention durations ranged from 4 weeks to 4.5 months with a total of 12 to 57 training sessions. We observed a small overall effect in favor of IPP for balance/stability (Hedges' g = 0.37; 95%CI 0.17, 0.58), leg power (g = 0.22; 95%CI 0.07, 0.38), and isokinetic hamstring and quadriceps strength as well as hamstrings-to-quadriceps ratio (g = 0.38; 95%CI 0.21, 0.55). We found a large overall effect for sprint abilities (g = 0.80; 95%CI 0.50, 1.09) and sport-specific skills (g = 0.83; 95%CI 0.34, 1.32). Subgroup analyses revealed larger effects in high-level (g = 0.34–1.18) compared to low-level athletes (g = 0.22–0.75), in boys (g = 0.27–1.02) compared to girls (g = 0.09–0.38), in older (g = 0.32–1.16) compared to younger athletes (g = 0.18–0.51), and in studies with high (g = 0.35–1.16) compared to low (g = 0.12–0.38) overall number of training sessions. Conclusion: Multimodal IPP beneficially affect neuromuscular performance. These improvements may substantiate the preventative efficacy of IPP and may support the wide-spread implementation and dissemination of IPP. The study has been a priori registered in PROSPERO (CRD42016053407). PMID:29075200
Cyclase inhibitor tripropylamine significantly enhanced lycopene accumulation in Blakeslea trispora.
Wang, Yanlong; Chen, Xiwen; Hong, Xiao; Du, Shipeng; Liu, Chunxiao; Gong, Wenfang; Chen, Defu
2016-11-01
Lycopene is a member of carotenoids that exhibits strong antioxidant activity. In this study, on the basis of screening suitable strain combination [ATCC 14271(+) and ATCC 14272(-)] and establishing the optimal inoculation proportion of mated culture (1/2, +/-, w/w) for carotenoid production, the efficiency of compounds, mainly tertiary amines, on enhancing the lycopene content of Blakeslea trispora was systematically assessed. Of these compounds, tripropylamine showed the best enhancing effect, and then sequentially followed by triethylamine, tributylamine, trimethylamine, diisopropylamine, and isopropylamine. After treated with 1.8 g/L tripropylamine for two days, the lycopene proportion was increased from 1.7% to 90.1%, while the β-carotene proportion was decreased from 91.1% to 6.4% of the total carotenoids. In this case, the lycopene and total carotenoid contents were increased to 83.2 and 92.4 mg/gDW, which were 315.8- and 5.9-fold of that of the untreated control, respectively; while the growth of mycelia was only decreased at 6.0 g/L tripropylamine. Gene expression analysis showed that all the tested genes, especially genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgr) and isopentenyl pyrophosphate isomerase (ipi) in mevalonate pathway, as well as phytoene desaturase (carB) in carotenoid biosynthesis process were upregulated. Therefore, tripropylamine enhanced lycopene content of B. trispora by inhibiting the cyclase activity, and by upregulating the expression of genes associated with terpenoid biosynthesis. Besides, a possible association between the structure and the lycopene-enhancing capability of these compounds was also discussed. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
A Non-photosynthetic Diatom Reveals Early Steps of Reductive Evolution in Plastids.
Kamikawa, Ryoma; Moog, Daniel; Zauner, Stefan; Tanifuji, Goro; Ishida, Ken-Ichiro; Miyashita, Hideaki; Mayama, Shigeki; Hashimoto, Tetsuo; Maier, Uwe G; Archibald, John M; Inagaki, Yuji
2017-09-01
Nonphotosynthetic plastids retain important biological functions and are indispensable for cell viability. However, the detailed processes underlying the loss of plastidal functions other than photosynthesis remain to be fully understood. In this study, we used transcriptomics, subcellular localization, and phylogenetic analyses to characterize the biochemical complexity of the nonphotosynthetic plastids of the apochlorotic diatom Nitzschia sp. NIES-3581. We found that these plastids have lost isopentenyl pyrophosphate biosynthesis and ribulose-1,5-bisphosphate carboxylase/oxygenase-based carbon fixation but have retained various proteins for other metabolic pathways, including amino acid biosynthesis, and a portion of the Calvin-Benson cycle comprised only of glycolysis/gluconeogenesis and the reductive pentose phosphate pathway (rPPP). While most genes for plastid proteins involved in these reactions appear to be phylogenetically related to plastid-targeted proteins found in photosynthetic relatives, we also identified a gene that most likely originated from a cytosolic protein gene. Based on organellar metabolic reconstructions of Nitzschia sp. NIES-3581 and the presence/absence of plastid sugar phosphate transporters, we propose that plastid proteins for glycolysis, gluconeogenesis, and rPPP are retained even after the loss of photosynthesis because they feed indispensable substrates to the amino acid biosynthesis pathways of the plastid. Given the correlated retention of the enzymes for plastid glycolysis, gluconeogenesis, and rPPP and those for plastid amino acid biosynthesis pathways in distantly related nonphotosynthetic plastids and cyanobacteria, we suggest that this substrate-level link with plastid amino acid biosynthesis is a key constraint against loss of the plastid glycolysis/gluconeogenesis and rPPP proteins in multiple independent lineages of nonphotosynthetic algae/plants. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Tian, Tian; Blanco, Elena; Smoukov, Stoyan K; Velev, Orlin D; Velikov, Krassimir P
2016-10-01
Ferric pyrophosphate (FePP) is a widely used iron source in food fortification and in nutritional supplements, due to its white colour, that is very uncommon for insoluble Fe salts. Although its dissolution is an important determinant of Fe adsorption in human body, the solubility characteristics of FePP are complex and not well understood. This report is a study on the solubility of FePP as a function of pH and excess of pyrophosphate ions. FePP powder is sparingly soluble in the pH range of 3-6 but slightly soluble at pH<2 and pH>8. In the presence of pyrophosphate ions the solubility of FePP strongly increases at pH 5-8.5 due to formation a soluble complex between Fe(III) and pyrophosphate ions, which leads to an 8-10-fold increase in the total ionic iron concentration. This finding is beneficial for enhancing iron bioavailability, which important for the design of fortified food, beverages, and nutraceutical products. Copyright © 2016 Elsevier Ltd. All rights reserved.
Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Falk, R.H.; Lee, V.W.; Rubinow, A.
1983-03-01
To determine the value of technetium-99m-pyrophosphate myocardial scintigraphy in the diagnosis of amyloid heart disease this procedure was prospectively performed in 20 consecutive patients with biopsy-proven primary amyloidosis. Eleven patients had echocardiographic abnormalities compatible with amyloid cardiomyopathy, 9 of whom had congestive heart failure. Diffuse myocardial pyrophosphate uptake was of equal or greater intensity than that of the ribs in 9 of the 11 patients with echocardiograms suggestive of amyloidosis, but in only 2 of the 9 with normal echocardiograms, despite abnormal electrocardiograms (p less than 0.01). Increased wall thickness measured by M-mode echocardiography correlated with myocardial pyrophosphate uptake (rmore » . 0.68, p less than 0.01). None of 10 control patients with nonamyloid, nonischemic heart disease had a strongly positive myocardial pyrophosphate uptake. Thus, myocardial technetium-99m-pyrophosphate scanning is a sensitive and specific test for the diagnosis of cardiac amyloidosis in patients with congestive heart failure of obscure origin. It does not appear to be of value for the early detection of cardiac involvement in patients with known primary amyloidosis without echocardiographic abnormalities.« less
Bickford, Justin S; Nick, Harry S
2013-12-01
Isoprenoid lipid carriers are essential in protein glycosylation and bacterial cell envelope biosynthesis. The enzymes involved in their metabolism (synthases, kinases and phosphatases) are therefore critical to cell viability. In this review, we focus on two broad groups of isoprenoid pyrophosphate phosphatases. One group, containing phosphatidic acid phosphatase motifs, includes the eukaryotic dolichyl pyrophosphate phosphatases and proposed recycling bacterial undecaprenol pyrophosphate phosphatases, PgpB, YbjB and YeiU/LpxT. The second group comprises the bacterial undecaprenol pyrophosphate phosphatase, BacA/UppP, responsible for initial formation of undecaprenyl phosphate, which we predict contains a tyrosine phosphate phosphatase motif resembling that of the tumour suppressor, phosphatase and tensin homologue (PTEN). Based on protein sequence alignments across species and 2D structure predictions, we propose catalytic and lipid recognition motifs unique to BacA/UppP enzymes. The verification of our proposed active-site residues would provide new strategies for the development of substrate-specific inhibitors which mimic both the lipid and pyrophosphate moieties, leading to the development of novel antimicrobial agents.
Luijsterburg, B J; Jobse, P S; Spoelstra, A B; Goossens, J G P
2016-08-01
Post-consumer plastic waste obtained via mechanical recycling is usually applied in thick-walled products, because of the low mechanical strength due to the presence of contaminants. In fact, sorted post-consumer isotactic poly(propylene) (i-PP) can be considered as a blend of 95% i-PP and 5% poly(ethylene), with traces of poly(ethylene terephthalate) (PET). By applying a treatment such as solid-state drawing (SSD) after melt extrusion, the polymer chains can be oriented in one direction, thereby improving the stiffness and tensile strength. In this research, molecular processes such as crystal break-up and chain orientation of these complex blends were monitored as a function of draw ratio. The melt filter mesh size - used to exclude rigid PET particles - and the addition of carbon black (CB) - often added for coloration in the recycling industry - were varied to investigate their influence on the SSD process. This research shows that despite the blend complexity, the molecular processes during SSD compare to virgin i-PP and that similar draw ratios can be obtained (λmax=20), albeit at reduced stiffness and strength as a result of the foreign polymers present in post-consumer i-PP. It is observed that the process stability improves with decreasing mesh size and that higher draw ratios can be obtained. The addition of carbon black, which resides in the dispersed PE phase, also stabilizes the SSD process. Compared to isotropic post-consumer i-PP, the stiffness can be improved by a factor 10 to over 11GPa, while the tensile strength can be improved by a factor 15-385MPa, which is approx. 70% of the maximum tensile strength achieved for virgin i-PP. Copyright © 2016 Elsevier Ltd. All rights reserved.
Tubing erosion of an inflatable penile prosthesis long after implantation.
Morales, Alvaro
2014-06-01
Erosion through skin of connecting tubing of an inflatable penile prosthesis (IPP) has not been previously reported. The aim of this study was to present a case of tubing erosion, review the pertinent literature, and discuss the possible causes and management options, including preservation of the device and its components. A 42-year-old male failing to respond to medical treatment for erectile dysfunction underwent insertion of an AMS 700 IPP in 1986. Six years later, a revision was necessary because of a leak in the right cylinder and 4 years after, the pump was replaced. Fourteen years after the original implant, he presented with a portion of the tube connecting the pump to the right cylinder eroding through the skin. There was no infection. The skin area involved was resected and the original pump and tubing were buried in a new scrotal pocket after thorough irrigation. The IPP remained in place, allowing vaginal penetration and without infection for another 11 years. Three years later, it was de-functionalized, converted into a fixed volume device. It eventually was replaced 25 years after originally implanted with a semirigid prosthesis because it did not provide sufficient rigidity and because of concerns about the presence of "screws" detected during pelvic imaging. Mechanical failures in the early IPP models, as illustrated in this case, were expected. However, the long survival of the device is remarkable. Erosion of the connecting tubing through the skin is unique and, under exceptional circumstances, may be managed conservatively without replacing components of the IPP. Clinicians unfamiliar with procedures involving inflatable devices need to be aware of "foreign bodies" visible in radiological examinations in men who have had revisions of an IPP. Morales A. Tubing erosion of an inflatable penile prosthesis long after implantation. Sex Med 2014;2:103-106.
Wang, X; Shu, X; Li, Z; Huo, W; Zou, L; Tang, Y; Li, L
2018-01-27
Skin imaging analysis, acting as a supplement to noninvasive bioengineering devices, has been widely used in medical cosmetology and cosmetic product evaluation. The main aim of this study is to assess the differences and correlations in measuring skin spots, wrinkles, vascular features, porphyrin, and pore between two commercially available image analysis software. Seventy healthy women were included in the study. Before taking pictures, the dermatologist evaluated subjects' skin conditions. Test sites included the forehead, cheek, and periorbital skin. A 2 × 2 cm cardboard was used to make a mark on the skin surface. Pictures were taken using VISIA ® under three kinds light conditions and analyzed using VISIA ® and IPP ® respectively. (1) Skin pore, red area, ultraviolet spot, brown spot, porphyrin, and wrinkle measured with VISIA ® were correlated with those measured with IPP ® (P < .01). (2) Spot, wrinkle, fine line, brown spot, and red area analyzed with VISIA ® were correlated with age on the forehead and periorbital skin (P < .05). L-value, Crow's feet, ultraviolet spot, brown spot, and red area analyzed with IPP ® were correlated with age on the periorbital skin (P < .05). (3) L-value, spot, wrinkle, fine line, porphyrin, red area, and pore analyzed with VISIA ® and IPP ® showed correlations with the subjective evaluation scores (P < .05). VISIA ® and IPP ® showed acceptable correlation in measuring various skin conditions. VISIA ® showed a high sensibility when measured on the forehead skin. IPP ® is available as an alternative software program to evaluate skin features. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
NASA's Impact in Florida: A Tech Transfer Perspective
NASA Technical Reports Server (NTRS)
Dunn, Carol
2009-01-01
The Innovative Partnerships Program (IPP) Office at NASA's Kennedy Space Center is dedicated to forming partnerships that can positively contribute to -- and benefit from -- NASA's research and development (R&D) and technology innovations. This document discusses the IPP-driven impacts of NASA in Florida.
Wall, Geoff C.; Soltis, Denise A.
2013-01-01
Objective. To implement an introductory pharmacy practice experience (IPPE) involving discharge counseling on postpartum pertussis immunization recommendations and evaluate its impact on student learning and patient immunization rates. Design. Seventeen pharmacy students provided verbal and written information based on Centers for Disease Control and Prevention (CDC) recommendations regarding pertussis immunization for mothers and caregivers of newborns. Assessment. Educational and clinical outcomes were evaluated using student documentation and pharmacy records. Students completed 615 IPPE hours and provided 1,263 consultations. Students reported that 52% of mothers requested immunization, 27% were undecided, 11% had previously been immunized, and 10% declined. Following counseling, immunization rates, as a percentage of total births, significantly increased by 18.5%. Learning objectives of enhanced counseling and documentation skills were achieved. Conclusions. IPPE students provided patient counseling in an institutional setting that contributed to healthcare team efforts to increase pertussis immunization rates in mothers of newborns. This IPPE may serve as a potential model for additional student involvement in discharge counseling. PMID:23519719
Clarke, Cheryl; Wall, Geoff C; Soltis, Denise A
2013-03-12
To implement an introductory pharmacy practice experience (IPPE) involving discharge counseling on postpartum pertussis immunization recommendations and evaluate its impact on student learning and patient immunization rates. Seventeen pharmacy students provided verbal and written information based on Centers for Disease Control and Prevention (CDC) recommendations regarding pertussis immunization for mothers and caregivers of newborns. Educational and clinical outcomes were evaluated using student documentation and pharmacy records. Students completed 615 IPPE hours and provided 1,263 consultations. Students reported that 52% of mothers requested immunization, 27% were undecided, 11% had previously been immunized, and 10% declined. Following counseling, immunization rates, as a percentage of total births, significantly increased by 18.5%. Learning objectives of enhanced counseling and documentation skills were achieved. IPPE students provided patient counseling in an institutional setting that contributed to healthcare team efforts to increase pertussis immunization rates in mothers of newborns. This IPPE may serve as a potential model for additional student involvement in discharge counseling.
Frébortová, Jitka; Greplová, Marta; Seidl, Michael F; Heyl, Alexander; Frébort, Ivo
2015-01-01
Cytokinins, a class of phytohormones, are adenine derivatives common to many different organisms. In plants, these play a crucial role as regulators of plant development and the reaction to abiotic and biotic stress. Key enzymes in the cytokinin synthesis and degradation in modern land plants are the isopentyl transferases and the cytokinin dehydrogenases, respectively. Their encoding genes have been probably introduced into the plant lineage during the primary endosymbiosis. To shed light on the evolution of these proteins, the genes homologous to plant adenylate isopentenyl transferase and cytokinin dehydrogenase were amplified from the genomic DNA of cyanobacterium Nostoc sp. PCC 7120 and expressed in Escherichia coli. The putative isopentenyl transferase was shown to be functional in a biochemical assay. In contrast, no enzymatic activity was detected for the putative cytokinin dehydrogenase, even though the principal domains necessary for its function are present. Several mutant variants, in which conserved amino acids in land plant cytokinin dehydrogenases had been restored, were inactive. A combination of experimental data with phylogenetic analysis indicates that adenylate-type isopentenyl transferases might have evolved several times independently. While the Nostoc genome contains a gene coding for protein with characteristics of cytokinin dehydrogenase, the organism is not able to break down cytokinins in the way shown for land plants.
Frébortová, Jitka; Greplová, Marta; Seidl, Michael F.; Heyl, Alexander; Frébort, Ivo
2015-01-01
Cytokinins, a class of phytohormones, are adenine derivatives common to many different organisms. In plants, these play a crucial role as regulators of plant development and the reaction to abiotic and biotic stress. Key enzymes in the cytokinin synthesis and degradation in modern land plants are the isopentyl transferases and the cytokinin dehydrogenases, respectively. Their encoding genes have been probably introduced into the plant lineage during the primary endosymbiosis. To shed light on the evolution of these proteins, the genes homologous to plant adenylate isopentenyl transferase and cytokinin dehydrogenase were amplified from the genomic DNA of cyanobacterium Nostoc sp. PCC 7120 and expressed in Escherichia coli. The putative isopentenyl transferase was shown to be functional in a biochemical assay. In contrast, no enzymatic activity was detected for the putative cytokinin dehydrogenase, even though the principal domains necessary for its function are present. Several mutant variants, in which conserved amino acids in land plant cytokinin dehydrogenases had been restored, were inactive. A combination of experimental data with phylogenetic analysis indicates that adenylate-type isopentenyl transferases might have evolved several times independently. While the Nostoc genome contains a gene coding for protein with characteristics of cytokinin dehydrogenase, the organism is not able to break down cytokinins in the way shown for land plants. PMID:26376297
Maroilley, T; Berri, M; Lemonnier, G; Esquerré, D; Chevaleyre, C; Mélo, S; Meurens, F; Coville, J L; Leplat, J J; Rau, A; Bed'hom, B; Vincent-Naulleau, S; Mercat, M J; Billon, Y; Lepage, P; Rogel-Gaillard, C; Estellé, J
2018-06-13
The epithelium of the intestinal mucosa and the gut-associated lymphoid tissues (GALT) constitute an essential physical and immunological barrier against pathogens. In order to study the specificities of the GALT transcriptome in pigs, we compared the transcriptome profiles of jejunal and ileal Peyer's patches (PPs), mesenteric lymph nodes (MLNs) and peripheral blood (PB) of four male piglets by RNA-Seq. We identified 1,103 differentially expressed (DE) genes between ileal PPs (IPPs) and jejunal PPs (JPPs), and six times more DE genes between PPs and MLNs. The master regulator genes FOXP3, GATA3, STAT4, TBX21 and RORC were less expressed in IPPs compared to JPPs, whereas the transcription factor BCL6 was found more expressed in IPPs. In comparison between IPPs and JPPs, our analyses revealed predominant differential expression related to the differentiation of T cells into Th1, Th2, Th17 and iTreg in JPPs. Our results were consistent with previous reports regarding a higher T/B cells ratio in JPPs compared to IPPs. We found antisense transcription for respectively 24%, 22% and 14% of the transcripts detected in MLNs, PPs and PB, and significant positive correlations between PB and GALT transcriptomes. Allele-specific expression analyses revealed both shared and tissue-specific cis-genetic control of gene expression.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-06
... Hospital IPPS Inpatient prospective payment system MS-DRG Diagnosis-related group NCA National coverage... based on the ``inpatient prospective payment system'' (IPPS) described in section 1886(d) of the Act... and procedures, and payment systems. We reviewed various articles, reports, summaries, and data bases...
Calcium pyrophosphate dihydrate gout and other crystal deposition diseases.
Reginato, A J
1991-08-01
The number of crystal or birefringent particles associated with arthritis is increasing, and a uniform taxonomy is needed. The term gout has been proposed as a generic term for these diseases based on historical, clinical, and crystallographic reasons. Calcium pyrophosphate dihydrate gout follows monosodium urate gout in frequency, and its spectrum of clinical manifestations continues to grow. Familial calcium pyrophosphate dihydrate gout was described for the first time in kindreds studied in England and Tunisia; new Jewish and Spanish kindreds were also reported. Type I collagen was shown to nucleate nativelike calcium pyrophosphate dihydrate crystals, and pyrophosphate elaboration was explored in cartilage explants in an attempt to reproduce the in vivo metabolic or endocrine disorders associated with calcium pyrophosphate dihydrate gout. The effect of pyrophosphatase and different cofactors such as magnesium in dissolving calcium pyrophosphate dihydrate crystals was investigated. High-resolution electron microscopy was used to study the interrelation between apatite and other basic calcium phosphate crystals in apatite gout. Raman microscopy was applied for the first time to identify crystals in biologic specimens. A simple and specific technique for basic calcium phosphate crystal identification is necessary to understand the relationship between different calcium phosphate crystals and osteoarthritis. Several reports about children and young patients with primary oxalate gout described the effect of oxalate on eyes, periodontal tissues, and bone. Multicenter studies showed poor results of renal transplantation, but favored combined liver and renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
ALKYL PYROPHOSPHATE METAL SOLVENT EXTRACTANTS AND PROCESS
Long, R.L.
1958-09-30
A process is presented for the recovery of uranium from aqueous mineral acidic solutions by solvent extraction. The extractant is a synmmetrical dialkyl pyrophosphate in which the alkyl substituents have a chain length of from 4 to 17 carbon atoms. Mentioned as a preferred extractant is dioctyl pyrophosphate. The uranium is precipitated irom the organic extractant phase with an agent such as HF, fluoride salts. alcohol, or ammonia.
Morphology Evolution of Polypropylene in Immiscible Polymer Blends for Fabrication of Nanofibers
USDA-ARS?s Scientific Manuscript database
Immiscible blends of cellulose acetate butyrate (CAB) and isotactic polypropylenes (iPPs) with different melting index were extruded through a two-strand rod die. The extrudates were hot-drawn at the die exit at different draw ratios by controlling the drawing speed. The morphologies of iPP fibers e...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-23
... services and technologies under the hospital inpatient prospective payment system (IPPS). Interested parties are invited to this meeting to present their comments, recommendations, and data regarding whether... technologies under the hospital inpatient prospective payment system (IPPS). In addition, section 1886(d)(5)(K...
Geriatric Care as an Introductory Pharmacy Practice Experience
Boyce, Eric; Patel, Rajul A.
2011-01-01
Objective. To describe the design, delivery, and impact of a geriatric introductory pharmacy practice experience (IPPE) to develop students’ skills related to consultant pharmacists’ roles and patient care responsibilities. Design. A required 2-unit geriatric IPPE, involving 40 hours in a geriatric-care facility, 5 reflection hours, and 12 classroom-discussion hours, was developed for first- and second-year pharmacy students. Students interviewed patients and caregivers, reviewed patient charts, triaged patient needs, prepared care plans, and performed quality-assurance functions. Assessment. After completing the IPPE, students’ geriatric- and patient-care abilities were enhanced, based on review of their interactions, care plans, reflections, and examinations, and they demonstrated cognitive, affective, and psychomotor-domain learning skills. Students’ care plans and quality assurance activities revealed positive patient outcomes, opportunities for measurable patient health improvement, and a positive impact on quality assurance activities. Student evaluations and feedback from health workers at the facilities also were positive. Conclusions. This geriatric IPPE in which students cared for a specific patient and interacted with other health care providers is an innovative approach to enhancing students’ abilities to serve the growing geriatric population. PMID:21931453
Mendes, Paula; Nunes, Luis Miguel; Teixeira, Margarida Ribau
2014-09-01
This article demonstrates how decision-makers can be guided in the process of defining performance target values in the balanced scorecard system. We apply a method based on sensitivity analysis with Monte Carlo simulation to the municipal solid waste management system in Loulé Municipality (Portugal). The method includes two steps: sensitivity analysis of performance indicators to identify those performance indicators with the highest impact on the balanced scorecard model outcomes; and sensitivity analysis of the target values for the previously identified performance indicators. Sensitivity analysis shows that four strategic objectives (IPP1: Comply with the national waste strategy; IPP4: Reduce nonrenewable resources and greenhouse gases; IPP5: Optimize the life-cycle of waste; and FP1: Meet and optimize the budget) alone contribute 99.7% of the variability in overall balanced scorecard value. Thus, these strategic objectives had a much stronger impact on the estimated balanced scorecard outcome than did others, with the IPP1 and the IPP4 accounting for over 55% and 22% of the variance in overall balanced scorecard value, respectively. The remaining performance indicators contribute only marginally. In addition, a change in the value of a single indicator's target value made the overall balanced scorecard value change by as much as 18%. This may lead to involuntarily biased decisions by organizations regarding performance target-setting, if not prevented with the help of methods such as that proposed and applied in this study. © The Author(s) 2014.
NASA Astrophysics Data System (ADS)
Zhang, Yu; Wang, Xinzhi; Tang, Jianguo; Wang, Wei; Wang, Jinping; Belfiore, Laurence A.
2017-04-01
In this contribution, we obtained the strong enhancement effect of silver nanowires(AgNWs) on fluorescent property of Eu3+-antenna complexes through the function of the surface plasmon resonance(SPR) effect. The key structural characteristics are: (1) AgNWs are covered by the Eu3+-ligand complex and spaced by SiO2 nano-layer between AgNWs and Eu3+-ligand complex (this structure is marked as AgNWs@SiO2@EuTP), and (2) AgNWs as nano-material with large ratio of length to diameter show their good dispersion and processability in isotactic polypropylene (iPP). We obtained the important data about the optimal spacer thickness of SiO2 is 15 nm that was not found in previous publications. The enhanced intensity of fluorescence of EuTP by AgNWs in AgNWs@SiO2@EuTP is 9 times compared with that of EuTP. All of these outstanding properties and fine structures were characterized by TEM, FT-IR, XRD, and fluorescence spectrophotometer. On the other hand, the desired fluorescent iPP composite material was obtained through blending AgNWs@SiO2@EuTP into iPP host. Very importantly, the enhancement effect of AgNWs on EuTP fluorescence in AgNWs@SiO2@EuTP is refrained from the quenching caused by host polymer of iPP.
Xu, Ding; Yu, Yongjiang; Zhu, Yunkai; Huang, Tao; Chen, Yaqing; Qi, Jun
2014-04-01
The Prostate-specific antigen (PSA) level is largely used to diagnose prostate cancer (PCa) in last decades. However, its specificity is low in patients with a PSA level ranging from 4.0 to 10.0 ng/ml. This study aims to define the correlation between intravesical prostatic protrusion (IPP) and PSA and to establish a new model to predict PCa. A total of 339 patients order than 45 years examined between October 2010 and June 2012 were enrolled. Eligible patients were recommended for transrectal ultrasonography (TRUS)-guided prostate biopsies after measuring total prostate volume (TPV), tranzisional zone volume (TZV) and IPP. The levels of total PSA (tPSA), free PSA (fPSA) were analyzed by using Hybritech calibrated Access tPSA and fPSA assays. A new mathematical model, named IPP removed PCa predicting score (IRPPS), consists of tPSA, TZV and IPP was established. The predictive accuracy of IRPPS, PSA density (PSAD), %PSA and tPSA were compared using receiver-operator characteristic (ROC) analysis. Eighty-six patients had PSA levels of 4.0-10.0 ng/ml. Twenty of them were diagnosed as PCa. Using ROC curves, the areas under the curve for IRPPS, PSAD and %PSA and tPSA were 0.786, 0.768 and 0.664 and 0.585, respectively. We suggested IPP grade had a significant relationship with serum tPSA levels. The predictive accuracy of IRPPS was higher than the other 3 indictors.
Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Huanchen; Falck, J.R.; Hall, Traci M. Tanaka
2012-01-11
Inositol pyrophosphates (such as IP7 and IP8) are multifunctional signaling molecules that regulate diverse cellular activities. Inositol pyrophosphates have 'high-energy' phosphoanhydride bonds, so their enzymatic synthesis requires that a substantial energy barrier to the transition state be overcome. Additionally, inositol pyrophosphate kinases can show stringent ligand specificity, despite the need to accommodate the steric bulk and intense electronegativity of nature's most concentrated three-dimensional array of phosphate groups. Here we examine how these catalytic challenges are met by describing the structure and reaction cycle of an inositol pyrophosphate kinase at the atomic level. We obtained crystal structures of the kinase domainmore » of human PPIP5K2 complexed with nucleotide cofactors and either substrates, product or a MgF{sub 3}{sup -} transition-state mimic. We describe the enzyme's conformational dynamics, its unprecedented topological presentation of nucleotide and inositol phosphate, and the charge balance that facilitates partly associative in-line phosphoryl transfer.« less
Heightened Avidity for Trisodium Pyrophosphate in Mice Lacking Tas1r3
Aleman, Tiffany R.; McCaughey, Stuart A.
2015-01-01
Laboratory rats and mice prefer some concentrations of tri- and tetrasodium pyrophosphate (Na3HP2O7 and Na4P2O7) to water, but how they detect pyrophosphates is unknown. Here, we assessed whether T1R3 is involved. We found that relative to wild-type littermate controls, Tas1r3 knockout mice had stronger preferences for 5.6–56mM Na3HP2O7 in 2-bottle choice tests, and they licked more 17.8–56mM Na3HP2O7 in brief-access tests. We hypothesize that pyrophosphate taste in the intact mouse involves 2 receptors: T1R3 to produce a hedonically negative signal and an unknown G protein-coupled receptor to produce a hedonically positive signal; in Tas1r3 knockout mice, the hedonically negative signal produced by T1R3 is absent, leading to a heightened avidity for pyrophosphate. PMID:25452580
NASA Astrophysics Data System (ADS)
Chen, Dongxing; He, Lei; Liu, Fenfen; Yin, Kedong
2017-07-01
Typhoons play an important role in the regulation of phytoplankton biomass and carbon fixation in the ocean. Data from the moderate-resolution imaging spectroradiometer (MODIS) on 35 typhoon events during 2002-2011 are analyzed to examine the effects of typhoon events on variations in sea surface temperature (SST), chlorophyll-a (Chl-a), and depth-integrated primary productivity (IPP) in the East China Sea (ECS). For all 35 typhoon cases, the average SST drops by 0.1 °C in the typhoon influenced regions, and the maximal decrease is 2.2 °C. During the same period, average Chl-a increases by 0.1 mg m-3, with the maximal increase reaching up to 1 mg m-3, and average IPP increases by 32.9 mg C m-2·d-1, with the largest increase being 221 mg C m-2·d-1. The IPP are significantly correlated with SST and Chl-a data, and the correlations become stronger after typhoon passage. On average, nearly one-third of the ECS is affected by typhoons during the 10 year period, and the resident time of the typhoons in the area reach to 38.2 h. Effects of the typhoon events on SST, Chl-a, and IPP manifest differently in the three key sea areas, namely, the coastal water (depths <50 m), continental shelf (depths 50-200 m), and open sea (depths >200 m) regions in the ECS. Specifically, stronger responses are observed in shallow water than in deeper depths. The comparisons between the pre- and post-typhoon periods show that IPP in the post-typhoon period increases by 19.7% and 12.2% in the coastal and continental shelf regions, respectively, but it decreases by 9.4% in the open sea region. Overall, our results reveal that there is a close coupling between Chl-a, SST, and IPP in shallow areas and that typhoon events can have strong effects on carbon fixation in coastal regions.
Reaction Mechanism of Isopentenyl Phosphate Kinase: A QM/MM Study.
McClory, James; Timson, David J; Singh, Warispreet; Zhang, Jian; Huang, Meilan
2017-12-14
Isopentenyl phosphate kinase (IPK) catalyzes the Mg 2+ -ATP dependent phosphorylation reactions to produce isopentenyl diphosphate, an important precursor in the synthesis of isopentenols. However, the position of the divalent metal ion in the crystal structures of IPK in complex with ATP and its native substrate IP has not been definitively resolved, and as a result ambiguity surrounds the catalytic mechanism of IP, limiting its exploitation as a biofuel and in drug design. Here we report the catalytically competent structure in complex with the metal ion Mg 2+ and elucidate the phosphorylation reaction mechanism using molecular dynamic simulations and density functional theory-based quantum mechanics/molecular mechanics calculations (B97d/AMBER99). Comparing the substrate-bound and substrate-free IPK complexes, we observed that substrate binding results in significant conformational change of three residues Lys204, Glu207, and Lys211 located on the αG helix to form a strong salt bridge network with Asp145, which in turn tethers the invariant Ser142 via H-bond interaction. The conformational change shuts the subtrate entrance channel formed between the αG and αE helices. Further, we demonstrate the phosphorylation reaction occurs with a reaction barrier of 17.58 kcal/mol, which is in agreement with the previous experimental kinetic data. We found that a highly conserved Gly8 on a glycine-rich loop, together with Lys14, stabilizes the transition state.
Individualized Program Planning (IPP): ECS to Grade 12. Programming for Students with Special Needs
ERIC Educational Resources Information Center
Online Submission, 2006
2006-01-01
This resource is a revision of the teaching resource Individualized Program Plans (1995), Book 3 (ED392232) in the Programming for Students with Special Needs series. It aims to create a bridge between the product, the process and the underlying vision of Individualized Program Planning (IPP). The Standards for Special Education (Amended June…
[Individual Progress Program for the Extremely Gifted Student in the Greater Seattle Area.
ERIC Educational Resources Information Center
Norsen, Barbara G.; Wick, Christine
The Individual Progress Program (IPP) is an approach designed to serve extremely advanced gifted students (grades 1 through 9) in the Seattle area. IPP is intended to meet students' unmet educational needs by allowing them to progress at their own accelerated pace through a broadly based curriculum while also pursuing interest areas. The program…
Familial pyrophosphate arthropathy. Occurrence and Crystal Identification.
Bjelle, A
1981-01-01
Hereditary pyrophosphate arthropathy has been observed in three Swedish families and in a few other caucasian populations. The inheritance is most probably autosomal dominant with a variable penetrance. The most severe cases have been found in homozygotes among isolates of immigrants in Slovakia and Chile. Studies on genetic and etio-pathogenetic factors in hereditary pyrophosphate arthropathy, and the utilization of new diagnostic techniques for crystal identification, are important approaches towards a further understanding of the disease.
Pradeep, A R; Agarwal, Esha; P, Arjun Raju; Rao, M S Narayana; Faizuddin, Mohamed
2011-03-01
A large amount of calculus may hamper the efficacy of daily oral hygiene and thereby accelerate plaque formation. Salivary concentrations of orthophosphate and pyrophosphate are important in preventing calculus formation. Activity of orthophosphate, pyrophosphate, and pyrophosphatase was studied in whole saliva in calculus-forming groups and plaque-forming groups. The material for this study consists of 60 healthy individuals (age range: 15 to 30 years; mean age: 22 years). Depending on calculus index score, individuals were divided into four groups, each of 15 patients: Group 1, calculus index score 0 to 0.6; Group 2, calculus index score 0.7 to 1.8; Group 3, calculus index score 1.9 to 3; and Group 4, plaque group where index varied from 0 to 3. The saliva was collected and biochemically analyzed for concentration of orthophosphate, pyrophosphate, and pyrophosphatase. The mean values of orthophosphate in Groups 1, 2, 3, and 4 were 0.2559, 1.3639, 1.7311, and 0.1868 mM, respectively. The mean values of pyrophosphate in Groups 1, 2, 3, and 4 were 0.3258, 0.1091, 0.0314, and 0.3860 mM, respectively. The mean values of pyrophosphatase in Groups 1, 2, 3, and 4 were 10.7937, 15.4249, 27.2900, and 7.5427 units/ml, respectively. A holistic approach toward the control of periodontal disease should include antiplaque and anticalculus agents. The results are conclusive that the components orthophosphate, pyrophosphate, and pyrophosphatase present in saliva have a very significant role to play in formation and inhibition of calculus. This study reinforces the idea of using pyrophosphate and newer bisphosphonates as potential anticalculus agents.
Jani, Kavina; Smith, Christopher; Delk, John R; Carson, Culley C; Donatucci, Craig F; Cleves, Mario A; Wilson, Steven K; Henry, Gerard D
2018-06-09
To investigate patients for positive culture rates with or without IRC PPs and to examine changes in culture positive isolates found in patients presenting overt clinical infection. Cultures were obtained from PPs immediately upon surgical exposure of the pump. 236 patients were broken down into 2 groups, with each further divided into 2 groups. The non-infected group included 208 patients: 133 with uncoated PPs and 75 with IRC implants. The infected group included 28 patients: 16 with uncoated PP and 12 with IRC IPP. Additionally, sensitivity to the combination of tetracycline and rifampin were evaluated on all cultures. In the non-infected group, culture positive isolates were found in 85 patients with uncoated PP's and in 32 patients with IRC implants [p-value = 0.0003]. Cultures positive for Staphylococcus genus were found in 75 uncoated PP patients, while 20 patients with IRC implants had an isolate of this genus. In the infected group, culture positive isolates were found in 7 patients with uncoated PP and 6 patients with IRC IPPs [p-value = 1.000]. Positive cultures for Staphylococcus genus were found in 6 patients with uncoated PP, while 3 patients with IRC IPP had an isolate of this genus. All bacterial isolates were sensitive to the combination of tetracycline and rifampin. Positive bacterial cultures have been shown to be present on clinically uninfected IPPs at time of revision surgery. Culture isolates grown from patients with IRC IPPs reveal a non-traditional bacterial profile: fewer cultured isolates of Staphylococcus genus. Copyright © 2018. Published by Elsevier Inc.
Terenteva, E A; Apyari, V V; Dmitrienko, S G; Garshev, A V; Volkov, P A; Zolotov, Yu A
2018-04-01
Positively charged polyhexamethylene guanidine hydrochloride-stabilized silver nanoparticles (PHMG-AgNPs) were prepared and applied as a colorimetric probe for single-step determination of pyrophosphate and sulfate. The approach is based on the nanoparticles aggregation leading to change in their absorption spectra and color of the solution. Due to both electrostatic and steric stabilization these nanoparticles show decreased sensitivity relatively to many common anions, which allows for simple and rapid direct single-step determination of pyrophosphate and sulfate. Effects of different factors (time of interaction, pH, concentrations of anions and the nanoparticles) on aggregation of PHMG-AgNPs and analytical performance of the procedure were investigated. The method allows for the determination of pyrophosphate and sulfate in the range of 0.16-2μgmL -1 and 20-80μgmL -1 with RSD of 2-5%, respectively. The analysis can be performed using either spectrophotometry or naked-eye detection. Practical application of the method was shown by the example of pyrophosphate determination in baking powder sample. Copyright © 2017 Elsevier B.V. All rights reserved.
Heightened avidity for trisodium pyrophosphate in mice lacking Tas1r3.
Tordoff, Michael G; Aleman, Tiffany R; McCaughey, Stuart A
2015-01-01
Laboratory rats and mice prefer some concentrations of tri- and tetrasodium pyrophosphate (Na3HP2O7 and Na4P2O7) to water, but how they detect pyrophosphates is unknown. Here, we assessed whether T1R3 is involved. We found that relative to wild-type littermate controls, Tas1r3 knockout mice had stronger preferences for 5.6-56mM Na3HP2O7 in 2-bottle choice tests, and they licked more 17.8-56mM Na3HP2O7 in brief-access tests. We hypothesize that pyrophosphate taste in the intact mouse involves 2 receptors: T1R3 to produce a hedonically negative signal and an unknown G protein-coupled receptor to produce a hedonically positive signal; in Tas1r3 knockout mice, the hedonically negative signal produced by T1R3 is absent, leading to a heightened avidity for pyrophosphate. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Sangyeob Lee; Todd F. Shupe; Chung Y. Hse
2008-01-01
The objective of this study was to improve interfacial adhesion properties at the interface of thermomechanical pulp (TMP) fiber and isotactic polypropylene (iPP) using thermoset adhesives such as phenol formaldehyde (PF) and urea formaldehyde (UF). This study also attempted to achieve fiber-to-fiber adhesion using thermoset adhesives before the molten iPP would flow...
RF Negative Ion Source Development at IPP Garching
NASA Astrophysics Data System (ADS)
Kraus, W.; McNeely, P.; Berger, M.; Christ-Koch, S.; Falter, H. D.; Fantz, U.; Franzen, P.; Fröschle, M.; Heinemann, B.; Leyer, S.; Riedl, R.; Speth, E.; Wünderlich, D.
2007-08-01
IPP Garching is heavily involved in the development of an ion source for Neutral Beam Heating of the ITER Tokamak. RF driven ion sources have been successfully developed and are in operation on the ASDEX-Upgrade Tokamak for positive ion based NBH by the NB Heating group at IPP Garching. Building on this experience a RF driven H- ion source has been under development at IPP Garching as an alternative to the ITER reference design ion source. The number of test beds devoted to source development for ITER has increased from one (BATMAN) by the addition of two test beds (MANITU, RADI). This paper contains descriptions of the three test beds. Results on diagnostic development using laser photodetachment and cavity ringdown spectroscopy are given for BATMAN. The latest results for long pulse development on MANITU are presented including the to date longest pulse (600 s). As well, details of source modifications necessitated for pulses in excess of 100 s are given. The newest test bed RADI is still being commissioned and only technical details of the test bed are included in this paper. The final topic of the paper is an investigation into the effects of biasing the plasma grid.
Cluster randomised control trial for cricket injury prevention programme (CIPP): a protocol paper.
Soomro, Najeebullah; Chua, Nina; Freeston, Jonathan; Ferdinands, Rene E D; Sanders, Ross
2017-09-28
Injury prevention programmes (IPPs) are effective in reducing injuries among adolescent team sports. However, there is no validated cricket-specific IPP despite the high incidence of musculoskeletal injuries among amateur cricketers. To evaluate whether a cricket injury prevention programme (CIPP) as a pretraining warm-up or post-training cool-down can reduce injury rates in amateur cricket players. CIPP is a cluster randomised controlled trial which includes 36 male amateur club teams having cricket players aged 14-40 years to be randomly assigned to three study arms: warm-up, cool-down and control (n=12 teams, 136 players in each arm). The intervention groups will perform 15 min CIPP either as a pretraining warm-up or a post-training cool-down. The primary outcome measure will be injury incidence per 1000 player hours and the secondary outcome measures will be whether IPP as a warm-up is better than IPP as a cool-down, and the adherence to the intervention. ACTRN 1261700047039. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
A simple model for heterogeneous nucleation of isotactic polypropylene
NASA Astrophysics Data System (ADS)
Howard, Michael; Milner, Scott
2013-03-01
Flow-induced crystallization (FIC) is of interest because of its relevance to processes such as injection molding. It has been suggested that flow increases the homogeneous nucleation rate by reducing the melt state entropy. However, commercial polypropylene (iPP) exhibits quiescent nucleation rates that are much too high to be consistent with homogeneous nucleation in carefully purified samples. This suggests that heterogeneous nucleation is dominant for typical samples used in FIC experiments. We describe a simple model for heterogeneous nucleation of iPP, in terms of a cylindrical nucleus on a flat surface with the critical size and barrier set by the contact angle. Analysis of quiescent crystallization data with this model gives reasonable values for the contact angle. We have also employed atomistic simulations of iPP crystals to determine surface energies with vacuum and with Hamaker-matched substrates, and find values consistent with the contact angles inferred from heterogeneous nucleation experiments. In future work, these results combined with calculations from melt rheology of entropy reduction due to flow can be used to estimate the heterogeneous nucleation barrier reduction due to flow, and hence the increase in nucleation rate due to FIC for commecial iPP.
Method of synthesis of proton conducting materials
Garzon, Fernando Henry; Einsla, Melinda Lou; Mukundan, Rangachary
2010-06-15
A method of producing a proton conducting material, comprising adding a pyrophosphate salt to a solvent to produce a dissolved pyrophosphate salt; adding an inorganic acid salt to a solvent to produce a dissolved inorganic acid salt; adding the dissolved inorganic acid salt to the dissolved pyrophosphate salt to produce a mixture; substantially evaporating the solvent from the mixture to produce a precipitate; and calcining the precipitate at a temperature of from about 400.degree. C. to about 1200.degree. C.
SEPARATION OF PLUTONIUM IONS FROM SOLUTION BY ADSORPTION ON ZIRCONIUM PYROPHOSPHATE
Stoughton, R.W.
1961-01-31
A method is given for separating plutonium in its reduced, phosphate- insoluble state from other substances. It involves contacting a solution containing the plutonium with granular zirconium pyrophosphate.
"India Population Projects" in Karnataka.
Reddy, P H; Badari, V S
1991-12-01
An overview, objectives, implementation, and research and evaluation studies of 2 India Population Projects in Karnataka are presented. The India Population Project I (IPP-I) was conducted in Karnataka and Uttar Pradesh. India Population Project III (IPP-III) took place between 1984-92 in 6 districts of Karnataka: Belgaum, Bijapur, Dharwad, Bidar, Gulbarga, and Raichur, and 4 districts in Kerala. The 6 districts in Karnataka accounted for 36% (13.2 million) of the total national population. The project cost was Rs. 713.1 million which was shared by the World Bank, and the Indian national and regional government. Due to poor past performance, these projects were undertaken to improve health and family welfare status. Specific project objectives are outlined. IPP-I included an urban component, and optimal Government of India program, and an intensive rural initiative. The urban program aimed to improved pre- and postnatal services and facilities, and the family planning (FP) in Bangalore city. The rural program was primarily to provide auxiliary nurse-midwives and hospitals and clinics, and also supplemental feeding program for pregnant and nursing mothers and children up to 2 years. The government program provided FP staff and facilities. IPP-I had 3 units to oversee building construction, to recruit staff and provide supplies and equipment, and to establish a Population Center. IPP-III was concerned with service delivery; information, education, and communication efforts (IEC) and population education; research and evaluation; and project management. Both projects contributed significantly to improving the infrastructure. A brief account of the types and kinds of studies undertaken is given. Studies were grouped into longitudinal studies of fertility, mortality, and FP; management information and evaluation systems for health and family welfare programs; experimental strategies; and other studies. Research and evaluation studies in IPP-III encompassed studies in gaps in knowledge, skills, and practice of health and FP personnel; baseline and endline surveys; and operational evaluation of the management information and evaluation system; factors affecting primary health care in Gulbarga district; evaluation of radio health lessons and the impact of the Kalyana Matha Program; and studies of vaccination and child survival and maternal mortality. Training programs were also undertaken.
The Efficacy of Injury Prevention Programs in Adolescent Team Sports: A Meta-analysis.
Soomro, Najeebullah; Sanders, Ross; Hackett, Daniel; Hubka, Tate; Ebrahimi, Saahil; Freeston, Jonathan; Cobley, Stephen
2016-09-01
Intensive sport participation in childhood and adolescence is an established cause of acute and overuse injury. Interventions and programs designed to prevent such injuries are important in reducing individual and societal costs associated with treatment and recovery. Likewise, they help to maintain the accrual of positive outcomes from participation, such as cardiovascular health and skill development. To date, several studies have individually tested the effectiveness of injury prevention programs (IPPs). To determine the overall efficacy of structured multifaceted IPPs containing a combination of warm-up, neuromuscular strength, or proprioception training, targeting injury reduction rates according to risk exposure time in adolescent team sport contexts. Systematic review and meta-analysis. With established inclusion criteria, studies were searched in the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, SPORTDiscus, Web of Science, EMBASE, CINAHL, and AusSportMed. The keyword search terms (including derivations) included the following: adolescents, sports, athletic injuries, prevention/warm-up programs. Eligible studies were then pooled for meta-analysis with an invariance random-effects model, with injury rate ratio (IRR) as the primary outcome. Heterogeneity among studies and publication bias were tested, and subgroup analysis examined heterogeneity sources. Across 10 studies, including 9 randomized controlled trials, a pooled overall point estimate yielded an IRR of 0.60 (95% CI = 0.48-0.75; a 40% reduction) while accounting for hours of risk exposure. Publication bias assessment suggested an 8% reduction in the estimate (IRR = 0.68, 95% CI = 0.54-0.84), and the prediction interval intimated that any study estimate could still fall between 0.33 and 1.48. Subgroup analyses identified no significant moderators, although possible influences may have been masked because of data constraints. Compared with normative practices or control, IPPs significantly reduced IRRs in adolescent team sport contexts. The underlying explanations for IPP efficacy remain to be accurately identified, although they potentially relate to IPP content and improvements in muscular strength, proprioceptive balance, and flexibility. Clinical practitioners (eg, orthopaedics, physical therapists) and sports practitioners (eg, strength and conditioners, coaches) can respectively recommend and implement IPPs similar to those examined to help reduce injury rates in adolescent team sports contexts. © 2015 The Author(s).
Active-site-directed irreversible inhibitors of isopentenyl diphosphate isomerase
DOE Office of Scientific and Technical Information (OSTI.GOV)
Muhlbacher, M.
1987-01-01
Seven analogues of isopentenyl diphosphate, containing fluorine, epoxy, or ammonium functionalities were found to irreversibly inhibit isopentenyl diphosphate:dimethylallyl diphosphate isomerase isolated from the mold Claviceps purpurea. The mechanism of their inhibition of isomerase was studied. Syntheses of 3-(fluoromethyl)-3-buten-1-yl diphosphate, 2-dimethylamino-1-ethyl diphosphate, 3,4-epoxy-3-methyl-1-butyl diphosphate, 3,4,-epoxy-1-butyl diphosphate, and 2,3-epoxy-3-methyl-1-butyl diphosphate were developed and carried out in high overall yield affording 100 mg quantities of the triammonium diphosphate salts. Radiolabeled materials of these analogues with {sup 3}H, {sup 14}C, and {sup 32}P at appropriate positions were also prepared. Inactivation kinetics, substrate protection studies, and labeling experiments demonstrated that the analogues interact stoichiometrically withmore » the active-site of isomerase. Radioactive enzyme-inactivator complexes were isolated, that are stable to extended dialysis and chaotropic reagents. The complexes resulting from inactivation of the enzyme by 3-(fluoromethyl)-3-buten-1-yl diphosphate and 3,4-epoxy-3-methyl-1-butyl diphosphate are stable to ion exchange chromatography and gel electrophoresis. Stoichiometric fluoride ion release occurs during inactivation of isomerase with 3-(fluoromethyl)-3-buten-1-yl diphosphate. The complexes are not stable to high concentrations of mixtures of 2-mercaptoethanol-sodium dodecyl sulfate. The radiolabeled 2-dimethylamino-1-ethyl diphosphate isomerase complex loses radioactivity almost instantaneously when treated with base. Partial fragmentation of the inactivator molecule was observed.« less
NASA Technical Reports Server (NTRS)
Nan, R.; Carman, J. G.; Salisbury, F. B.
1999-01-01
Wheat (Triticum aestivum L.) plants were grown under four irradiance levels: 1,400, 400, 200, and 100 micromol m-2 s-1. Leaves and roots were sampled before, during, and after the boot stage, and levels of abscisic acid (ABA), indole-3-acetic acid (IAA), zeatin, zeatin riboside, dihydrozeatin, dihydrozeatin riboside, isopentenyl adenine, and isopentenyl adenosine were quantified using noncompetitive indirect ELISA systems. Levels of IAA in leaves and roots of plants exposed to 100 micromol m-2 s-1 of irradiance were 0.7 and 2.9 micromol kg-1 dry mass (DM), respectively. These levels were 0.2 and 1.0 micromol kg-1 DM, respectively, when plants were exposed to 1,400 micromol m-2 s-1. Levels of ABA in leaves and roots of plants exposed to 100 micromol m-2 s-1 were 0.65 and 0.55 micromol kg-1 DM, respectively. They were 0.24 micromol kg-1 DM (both leaves and roots) when plants were exposed to 1,400 micromol m-2 s-1. Levels of isopentenyl adenosine in leaves (24.3 nmol kg-1 DM) and roots (29.9 nmol kg-1 DM) were not affected by differences in the irradiance regime. Similar values were obtained in a second experiment. Other cytokinins could not be detected (<10 nmol kg 1 DM) in either experiment with the sample sizes used (150-600 mg DM for roots and shoots, respectively).
Risk factors for bladder calculi in patients with benign prostatic hyperplasia.
Huang, Wei; Cao, Jun-Jie; Cao, Min; Wu, Hong-Shen; Yang, Yong-Yi; Xu, Zi-Meng; Jin, Xiao-Dong
2017-08-01
We aim to find the risk factors that influence the formation of bladder calculi in patients with benign prostate hyperplasia (BPH) and to reduce the surgical intervention related to bladder calculi.Between January 2015 and October 2016, 332 patients with BPH underwent surgical therapy were retrospectively evaluated. Patients with BPH were categorized into 2 groups: 94 patients with bladder calculi in group 1 and 238 patients without bladder calculi in group 2. Medical history, age, body mass index (BMI), total prostate specific antigen, total prostate volume (TPV), International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), urodynamic parameters, and urine culture were compared between groups.There was no significant difference in the age, BMI, peak flow rate, and total IPSS between groups. TPV, total prostate specific antigen, and duration of BPH were significantly lower in group 1 than those in group 2. In addition, IPP was significantly higher in group 1 than group 2 (P < .001). Besides, after exclusion of patients with urinary retention and indwelling catheter, group 1 associated with a significantly higher preoperative positive rate of urine culture than that of group 2 (P = .046). Multivariate analysis indicated that IPP was a significant independent risk factor for the presence of bladder calculi.The incidence of bladder calculi in patients with BPH was proved to be closely associated with preoperative positive urine culture and longer IPP in our study. Furthermore, the IPP was presented to be an independent risk factor for the formation of bladder calculi. And early antibacterial therapy of urinary tract infection (UTI) may help to prevent the presence of bladder calculi in patients with BPH.
Ren, Zhou-Xin; Yu, Hai-Bin; Shen, Jun-Ling; Li, Ya; Li, Jian-Sheng
2015-06-01
To establish a preprocessing method for cell morphometry in microscopic images of A549 cells in epithelial-mesenchymal transition (EMT). Adobe Photoshop CS2 (Adobe Systems, Inc.) was used for preprocessing the images. First, all images were processed for size uniformity and high distinguishability between the cell and background area. Then, a blank image with the same size and grids was established and cross points of the grids were added into a distinct color. The blank image was merged into a processed image. In the merged images, the cells with 1 or more cross points were chosen, and then the cell areas were enclosed and were replaced in a distinct color. Except for chosen cellular areas, all areas were changed into a unique hue. Three observers quantified roundness of cells in images with the image preprocess (IPP) or without the method (Controls), respectively. Furthermore, 1 observer measured the roundness 3 times with the 2 methods, respectively. The results between IPPs and Controls were compared for repeatability and reproducibility. As compared with the Control method, among 3 observers, use of the IPP method resulted in a higher number and a higher percentage of same-chosen cells in an image. The relative average deviation values of roundness, either for 3 observers or 1 observer, were significantly higher in Controls than in IPPs (p < 0.01 or 0.001). The values of intraclass correlation coefficient, both in Single Type or Average, were higher in IPPs than in Controls both for 3 observers and 1 observer. Processed with Adobe Photoshop, a chosen cell from an image was more objective, regular, and accurate, creating an increase of reproducibility and repeatability on morphometry of A549 cells in epithelial to mesenchymal transition.
The Pan-STARRS PS1 Image Processing Pipeline
NASA Astrophysics Data System (ADS)
Magnier, E.
The Pan-STARRS PS1 Image Processing Pipeline (IPP) performs the image processing and data analysis tasks needed to enable the scientific use of the images obtained by the Pan-STARRS PS1 prototype telescope. The primary goals of the IPP are to process the science images from the Pan-STARRS telescopes and make the results available to other systems within Pan-STARRS. It also is responsible for combining all of the science images in a given filter into a single representation of the non-variable component of the night sky defined as the "Static Sky". To achieve these goals, the IPP also performs other analysis functions to generate the calibrations needed in the science image processing, and to occasionally use the derived data to generate improved astrometric and photometric reference catalogs. It also provides the infrastructure needed to store the incoming data and the resulting data products. The IPP inherits lessons learned, and in some cases code and prototype code, from several other astronomy image analysis systems, including Imcat (Kaiser), the Sloan Digital Sky Survey (REF), the Elixir system (Magnier & Cuillandre), and Vista (Tonry). Imcat and Vista have a large number of robust image processing functions. SDSS has demonstrated a working analysis pipeline and large-scale databasesystem for a dedicated project. The Elixir system has demonstrated an automatic image processing system and an object database system for operational usage. This talk will present an overview of the IPP architecture, functional flow, code development structure, and selected analysis algorithms. Also discussed is the HW highly parallel HW configuration necessary to support PS1 operational requirements. Finally, results are presented of the processing of images collected during PS1 early commissioning tasks utilizing the Pan-STARRS Test Camera #3.
Reinforcing Cultural Competency Concepts During Introductory Pharmacy Practice Experiences
Caligiuri, Frank J
2010-01-01
Objectives To incorporate cultural competency concepts into various introductory pharmacy practice experiences (IPPE) at the University of Missouri - Kansas City, School of Pharmacy. Design A 6-week series, titled “Becoming a Culturally Competent Provider” was developed to provide IPPE students with the opportunity to apply theory regarding cultural competency in a clinical context. Assessment Pre- and post-intervention attitude survey instruments were administered to 25 students in the spring semester of 2009. Several activities within the series were associated with reflection exercises. Student presentations were evaluated and formal feedback was provided by faculty members. A course evaluation was administered to evaluate the series and determine areas of improvement. Conclusion A special series on cultural competency resulted in positive changes in students' attitudes, highlighting the importance of reinforcing cultural competency concepts during IPPEs. PMID:21088735
Penbegul, Necmettin; Utangac, Mehmet Mazhar; Daggulli, Mansur; Dede, Onur; Bozkurt, Yasar; Bodakci, Mehmet Nuri; Atar, Murat
2016-06-01
Micropercutaneous nephrolithotomy (microperc) is a recently introduced percutaneous nephrolithotomy (PNL) technique that has the smallest tract size. The absence of an amplatz sheath during the microperc technique is a fundamental difference that distinguishes it from all other types of PNL (standard, mini, ultramini). Increasing of the intrarenal pelvic pressure (IPP) was demonstrated by the authors in adult patients but this problem may be even more serious in pediatric patients. Previously, the authors defined the use of a 14 gauge angiocath needle and sheath (microsheath) during microperc surgery for pediatric patient to reduce the IPP. In this novel technique, a second angiocath is used to access the renal collecting system to drain fluid during surgery. This technique is more effective in reducing IPP during microperc, especially in pediatric patients. Copyright © 2016 Elsevier Inc. All rights reserved.
Permeation study through bacterial cellulose membrane.
Wu, Chengdong; Murtaza, Ghulam; Yameen, Muhammad Arfat; Aamir, Muhammad Naeem; Akhtar, Muhammad; Zhao, Yuhao
2014-01-01
Abstract: The objective of this study was to fabricate topical formulations of diclofenac diethylamine (DD) using isopropyl myristate (IPM) and isopropyl palmitate (IPP) as permeation enhancers. Franz cell and bacterial cellulose were used as analytical instrument and diffusion membrane, respectively. Permeation enhancers exhibited significant effect on the permeation characteristics of DD. It was concluded from the results that improved permeation of DD was observed when IPP was used as enhancer.
Variation in Payment Rates under Medicare's Inpatient Prospective Payment System.
Krinsky, Sam; Ryan, Andrew M; Mijanovich, Tod; Blustein, Jan
2017-04-01
To measure variation in payment rates under Medicare's Inpatient Prospective Payment System (IPPS) and identify the main payment adjustments that drive variation. Medicare cost reports for all Medicare-certified hospitals, 1987-2013, and Dartmouth Atlas geographic files. We measure the Medicare payment rate as a hospital's total acute inpatient Medicare Part A payment, divided by the standard IPPS payment for its geographic area. We assess variation using several measures, both within local markets and nationally. We perform a factor decomposition to identify the share of variation attributable to specific adjustments. We also describe the characteristics of hospitals receiving different payment rates and evaluate changes in the magnitude of the main adjustments over time. Data downloaded from the Centers for Medicare and Medicaid Services, the National Bureau of Economic Research, and the Dartmouth Atlas. In 2013, Medicare paid for acute inpatient discharges at a rate 31 percent above the IPPS base. For the top 10 percent of discharges, the mean rate was double the IPPS base. Variations were driven by adjustments for medical education and care to low-income populations. The magnitude of variation has increased over time. Adjustments are a large and growing share of Medicare hospital payments, and they create significant variation in payment rates. © Health Research and Educational Trust.
Svane, Simon; Kjeldsen, Frank; McKee, Vickie; McKenzie, Christine J
2015-07-14
The three dimetallic compounds [Ga2(bpbp)(OH)2(H2O)2](ClO4)3, [In2(bpbp)(CH3CO2)2](ClO4)3 and [Zn2(bpbp)(HCO2)2](ClO4) (bpbp(-) = 2,6-bis((N,N'-bis(2-picolyl)amino)methyl)-4-tertbutylphenolate) were evaluated as stable solid state precursors for reactive solution state receptors to use for the recognition of the biologically important anion pyrophosphate in water at neutral pH. Indicator displacement assays using in situ generated complex-pyrocatechol violet adducts, {M2(bpbp)(HxPV)}(n+) M = Ga(3+), In(3+), Zn(2+), were tested for selectivity in their reactions with a series of common anions: pyrophosphate, phosphate, ATP, arsenate, nitrate, perchlorate, chloride, sulfate, formate, carbonate and acetate. The receptor employing Ga(3+) showed a slow but visually detectable response (blue to yellow) in the presence of one equivalent of pyrophosphate but no response to any other anion, even when they were present in much higher concentrations. The systems based on In(3+) or Zn(2+) show less selectivity in accord with visibly discernible responses to several of the anions. These results demonstrate a facile method for increasing anion selectivity without modification of an organic dinucleating ligand scaffold. The comfortable supramolecular recognition of pyrophosphate by the dimetallic complexes is demonstrated by the single crystal X-ray structure of [Ga2(bpbp)(HP2O7)](ClO4)2 in which the pyrophosphate is coordinated to the two gallium ions via four of its oxygen atoms.
Injection molding of iPP samples in controlled conditions and resulting morphology
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sessa, Nino, E-mail: ninosessa.ns@gmail.com; De Santis, Felice, E-mail: fedesantis@unisa.it; Pantani, Roberto, E-mail: rpantani@unisa.it
2015-12-17
Injection molded parts are driven down in size and weight especially for electronic applications. In this work, an investigation was carried out on the process of injection molding of thin iPP samples and on the morphology of these parts. Melt flow in the mold cavity was analyzed and described with a mathematical model. Influence of mold temperature and injection pressure was analyzed. Samples orientation was studied using optical microscopy.
Blacker, Susan; Head, Barbara A; Jones, Barbara L; Remke, Stacy S; Supiano, Katherine
2016-01-01
The importance of interprofessional collaboration in achieving high quality outcomes, improving patient quality of life, and decreasing costs has been growing significantly in health care. Palliative care has been viewed as an exemplary model of interprofessional care delivery, yet best practices in both interprofessional education (IPE) and interprofessional practice (IPP) in the field are still developing. So, too, is the leadership of hospice and palliative care social workers within IPE and IPP. Generating evidence regarding best practices that can prepare social work professionals for collaborative practice is essential. Lessons learned from practice experiences of social workers working in hospice and palliative care can inform educational efforts of all professionals. The emergence of interprofessional education and competencies is a development that is relevant to social work practice in this field. Opportunities for hospice and palliative social workers to demonstrate leadership in IPE and IPP are presented in this article.
Russian-US collaboration on implementation of the active well coincidence counter (AWCC)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mozhajev, V.; Pshakin, G.; Stewart, J.
The feasibility of using a standard AWCC at the Obninsk IPPE has been demonstrated through active measurements of single UO{sub 2} (36% enriched) disks and through passive measurements of plutonium metal disks used for simulating reactor cores. The role of the measurements is to verify passport values assigned to the disks by the facility, and thereby facilitate the mass accountability procedures developed for the very large inventory of fuel disks at the facility. The AWCC is a very flexible instrument for verification measurements of the large variety of nuclear material items at the Obninsk IPPE and other Russian facilities. Futuremore » work at the IPPE will include calibration and verification measurements for other materials, both in individual disks and in multi-disk storage tubes; it will also include training in the use of the AWCC.« less
NASA Technical Reports Server (NTRS)
Cody, Dennis J.; Concepcion, Allan G.; Watras, Edward C., III
1995-01-01
This project, conducted in cooperation with the NASA Advanced Space Design Program, is part of an ongoing effort to place an experiment package into space. The goal of this project is to build and test flight-ready hardware that can be launched from the Space Shuttle. Get Away Special Canister 2 (GASCan 2) consists of three separate experiments. The Ionospheric Properties and Propagation Experiment (IPPE) determines effects of the ionosphere on radio wave propagation. The Microgravity Ignition experiment (MGI) tests the effects of combustion in a microgravity environment. The Rotational Fluid Flow experiment (RFF) examines fluid behavior under varying levels of gravity. This year the following tasks were completed: design of the IPPE antenna, X- and J-cell battery boxes, J-cell battery box enclosure, and structural bumpers; construction of the MGI canisters, MGI mounting brackets, IPPE antenna, and battery boxes; and the selection of the RFF's operating fluid and the analysis of the fluid behavior under microgravity test conditions.
LEFPS1, a Tomato Farnesyl Pyrophosphate Gene Highly Expressed during Early Fruit Development1
Gaffe, Joel; Bru, Jean-Philippe; Causse, Mathilde; Vidal, Alain; Stamitti-Bert, Linda; Carde, Jean-Pierre; Gallusci, Philippe
2000-01-01
Farnesyl pyrophosphate synthase (FPS) catalyzes the synthesis of farnesyl pyrophosphate, a key intermediate in sterol and sesquiterpene biosynthesis. Using a polymerase chain reaction-based approach, we have characterized LeFPS1, a tomato (Lycoperscion esculentum cv Wva 106) fruit cDNA, which encodes a functional FPS. We demonstrate that tomato FPSs are encoded by a small multigenic family with genes located on chromosomes 10 and 12. Consistent with farnesyl pyrophosphate requirement in sterol biosynthesis, FPS genes are ubiquitously expressed in tomato plants. Using an LeFPS1 specific probe, we show that the corresponding gene can account for most of FPS mRNA in most plant organs, but not during young seedling development, indicating a differential regulation of FPS genes in tomato. FPS gene expression is also under strict developmental control: FPS mRNA was mainly abundant in young organs and decreased as organs matured with the exception of fruits that presented a biphasic accumulation pattern. In this latter case in situ hybridization studies have shown that FPS mRNA is similarly abundant in all tissues of young fruit. Taken together our results suggest that several FPS isoforms are involved in tomato farnesyl pyrophosphate metabolism and that FPS genes are mostly expressed in relation to cell division and enlargement. PMID:10938353
Photoaffinity-labeled Cytokinins
Theiler, Jane B.; Leonard, Nelson J.; Schmitz, Ruth Y.; Skoog, Folke
1976-01-01
Two new azidopurine derivatives, 2-azido-N6-(Δ2-isopentenyl)adenine and 2-azido-N6-benzyladenine, have been synthesized as potential photoaffinity labels for probing cytokinin-binding sites. The preparation and the biological activity of these compounds are described. PMID:16659772
Giant geode (subchondrial cyst) in calcium pyrophosphate deposition disease on the curist.
Weinberg, S; Scott, R A
1981-09-01
It is important to be aware of the radiographic features of pyrophosphate arthropathy with or without associated chondrocalcinosis. Accordingly, when appropriate structural joint changes are present an extraordinarily large subchondral cyst should not prompt a misdiagnosis of cystic tumor.
Preoperative counseling and expectation management for inflatable penile prosthesis implantation.
Narang, Gopal L; Figler, Bradley D; Coward, Robert M
2017-11-01
The inflatable penile prosthesis (IPP) is the gold standard surgical treatment for medical refractory erectile dysfunction (ED). While the modern IPP has enjoyed high satisfaction rates as a product of its continued innovation, reliability, and performance, patient dissatisfaction can still occur. IPP implantation restores physiologic function with cosmetic and psychological consequences, both of which place inherent emphasis on preoperative counseling and expectation management. This review aims to highlight the complex nature of such counseling and provide practitioners with a roadmap to navigate the landscape. Preoperative counseling begins with appropriate patient selection and identification of those patients who are at risk for dissatisfaction as a result of personality characteristics. The informed consent provides a natural framework to discuss the host of complications and risks that are associated with surgery, including infection, device malfunction, damage to nearby structures, and device erosion. Device selection is a nuanced process that merges patient preference with clinical factors and consideration. We address device selection through a description of cylinder construction, pump design, and reservoir placement in the context of preoperative counseling. Lastly, we draw attention to expectation management with a specific focus on possible post-operative changes to penile length and sensation as well as partner involvement. The modern IPP provides excellent results with high patient and partner satisfaction. Ultimately, satisfaction is dependent on multiple factors, but providing accurate, realistic counseling and expectation management prepares patients for the best possible outcomes.
Pérez-Medina, Juan C.; Waldo-Mendoza, Miguel A.; Cruz-Delgado, Víctor J.; Quiñones-Jurado, Zoe V.; González-Morones, Pablo; Ziolo, Ronald F.; Martínez-Colunga, Juan G.; Soriano-Corral, Florentino; Avila-Orta, Carlos A.
2016-01-01
Metamaterial behavior of polymer nanocomposites (NCs) based on isotactic polypropylene (iPP) and multi-walled carbon nanotubes (MWCNTs) was investigated based on the observation of a negative dielectric constant (ε′). It is demonstrated that as the dielectric constant switches from negative to positive, the plasma frequency (ωp) depends strongly on the ultrasound-assisted fabrication method, as well as on the melt flow index of the iPP. NCs were fabricated using ultrasound-assisted extrusion methods with 10 wt % loadings of MWCNTs in iPPs with different melt flow indices (MFI). AC electrical conductivity (σ(AC)) as a function of frequency was determined to complement the electrical classification of the NCs, which were previously designated as insulating (I), static-dissipative (SD), and conductive (C) materials. It was found that the SD and C materials can also be classified as metamaterials (M). This type of behavior emerges from the negative dielectric constant observed at low frequencies although, at certain frequencies, the dielectric constant becomes positive. Our method of fabrication allows for the preparation of metamaterials with tunable ωp. iPP pure samples show only positive dielectric constants. Electrical conductivity increases in all cases with the addition of MWCNTs with the largest increases observed for samples with the highest MFI. A relationship between MFI and the fabrication method, with respect to electrical properties, is reported. PMID:28774042
Demiryilmaz, Ismail; Sener, Ebru; Cetin, Nihal; Altuner, Durdu; Suleyman, Bahadir; Albayrak, Fatih; Akcay, Fatih; Suleyman, Halis
2012-01-01
Summary Background Oxidative liver injury occurring with methotrexate restricts its use in the desired dose. Therefore, whether or not thiamine and thiamine pyrophosphate, whose antioxidant activity is known, have protective effects on oxidative liver injury generated with methotrexate was comparatively researched in rats using biochemical and histopathological approaches. Material/Methods Thiamine pyrophosphate+methotrexate, thiamine+methotrexate, and methotrexate were injected intraperitoneally in rats for 7 days. After this period, all animals’ livers were excised, killing them with high-dose anesthesia, and histopathologic and biochemical investigations were made. Result Biochemical results demonstrated a significant elevation in level of oxidant parameters such as MDA and MPO, and a reduction in antioxidant parameters such as GSH and SOD in the liver tissue of the methotrexate group. Also, the quantity of 8-OHdG/dG, a DNA injury product, was higher in the methotrexate group with high oxidant levels and low antioxidant levels, and the quantity of 8-OHdG/dG was in the thiamine pyrophosphate group with low oxidant levels and high antioxidant levels. In the thiamine and control groups, the 8-OHdG/dG rate was 1.48±0.35 pmol/L (P>0.05) and 0.55±0.1 pmol/L (P<0.0001). Thiamine pyrophosphate significantly decreased blood AST, ALT and LDH, but methotrexate and thiamine did not decrease the blood levels of AST, ALT and LDH. Histopathologically, although centrilobular necrosis, apoptotic bodies and inflammation were monitored in the methotrexate group, the findings in the thiamine pyrophosphate group were almost the same as in the control group. Conclusions Thiamine pyrophosphate was found to be effective in methotrexate hepatotoxicity, but thiamine was ineffective. PMID:23197226
NASA Technical Reports Server (NTRS)
Ciszak, Ewa M.; Korotchkina, Lioubov G.; Dominiak, Paulina M.; Sidhu, Sukdeep; Patel, Mulchand S.
2003-01-01
The derivative of vitamin B1, thiamin pyrophosphate, is a cofactor of enzymes performing catalysis in pathways of energy production. In alpha (sub 2) beta (sub 2)-heterotetrameric human pyruvate dehydrogenase, this cofactor is used to cleave the C(sup alpha) -C(=O) bond of pyruvate followed by reductive acetyl transfer to lipoyl-dihydrolipoamide acetyltransferase. The dynamic nonequivalence of two, otherwise chemically equivalent, catalytic sites has not yet been understood. To understand the mechanism of action of this enzyme, we determined the crystal structure of the holo-form of human pyruvate dehydrogenase at 1.95-Angstrom resolution. We propose a model for the flip-flop action of this enzyme through a concerted approximately 2-Angstrom shuttle-like motion of its heterodimers. Similarity of thiamin pyrophosphate binding in human pyruvate dehydrogenase with functionally related enzymes suggests that this newly defined shuttle-like motion of domains is common to the family of thiamin pyrophosphate-dependent enzymes.
Kowalczyk, S
1987-01-01
Three different molecular forms of pyrophosphate-dependent phosphofructokinase have been isolated: one from Sansevieria trifasciata leaves and two from Phaseolus coccineus stems. The form isolated from S. trifasciata has the molecular weight of about 115,000. The apparent molecular weights for the two forms from mung bean were approximately 220,000 and 450,000. All three forms have the same pH optima, an absolute requirement for Mg2+ ions both in the forward and reverse reaction, but differ in their sensitivity toward fructose 2,6-bisphosphate. Kinetic properties of the partially purified enzymes have been investigated in the presence and absence of fructose 2,6-bisphosphate. Pyrophosphate-dependent phosphofructokinase from S. trifasciata exhibited hyperbolic kinetics with all substrates tested. The saturation curves of the enzyme (form A) from mung bean for pyrophosphate, fructose 6-phosphate and fructose 1,6-bisphosphate were sigmoidal in the absence of fructose 2,6-bisphosphate. In the presence of fructose 2,6-bisphosphate these kinetics became hyperbolic.
Penile Lengthening, Girth, and Size Preservation at the Time of Penile Prosthesis Insertion.
Tran, Henry; Goldfarb, Robert; Ackerman, Anika; Valenzuela, Robert J
2017-07-01
Penile prosthetic devices are the gold standard treatment of medication-refractory erectile dysfunction. Inflatable penile prosthetic (IPP) devices have been available and used for more than four decades. Oftentimes, medical conditions causing erectile dysfunction also cause penile shortening, causing decreased patient quality of life. To identify and review all available penile lengthening procedures that can be performed at time of IPP insertion. An extensive, systematic literature review was performed using PubMed searching for key terms penile lengthening, inflatable penile prosthesis, penile girth, corporoplasty, glans augmentation, and penile enhancement; all articles with subjective and/or objective penile length outcomes were reviewed. A review of various techniques for penile length and girth preservation and enhancement during penile prosthesis insertion. Several advanced and novel techniques were found for penile length preservation and enhancement at time of IPP insertion, including the sub-coronal IPP insertion technique, and adjuvant maneuvers during insertion, such as the sliding technique, modified sliding technique, multiple slice technique, and circumferential incision and grafting. Other adjuvant techniques that can enhance perception of increased length include ventral phalloplasty, suprapubic lipectomy, and suspensory ligament release. Further enhancement can be obtained using augmentation corporoplasty and glans augmentation with hyaluronic acid and other fillers. The different techniques vary in complexity and could require specialized training and experience. Maximum length gain appears to be limited by the length of the neurovascular bundles. Overall, surgical penile lengthening procedures at time of IPP insertion appear safe and effective for treatment of patients with penile shortening and severe erectile dysfunction. These therapies can significantly improve patient self-esteem and quality of life in properly selected patients. Tran H, Goldfarb R, Ackerman A, Valenxuela RJ. Penile Lengthening, Girth and Size Preservation at the Time of Penile Prosthesis Insertion. Sex Med Rev 2017;5:403-412. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Promotion of Influenza Prevention Beliefs and Behaviors through Primary School Science Education
Koep, TH; Jenkins, S; M Hammerlund, ME; Clemens, C; Fracica, E; Ekker, SC; Enders, FT; Huskins, WC; Pierret, C
2016-01-01
Background School-based campaigns to improve student health have demonstrated short-term success across various health topics. However, evidence of the effectiveness of programs in promoting healthy beliefs and behaviors is limited. We hypothesized that educational curricula teaching the science behind health promotion would increase student knowledge, beliefs and adherence to healthy behaviors, in this case related to influenza. Methods Integrated Science Education Outreach is a successful education intervention in Rochester, Minnesota public schools that has demonstrated improvements in student learning. Within this program, we designed novel curricula and assessments to determine if gains in knowledge extended to influenza prevention. Further, we coupled InSciEd Out programming with a clinical intervention, Influenza Prevention Prescription Education (IPPE), to compare students' attitudes, intentions and healthy behaviors utilizing surveys and hand hygiene monitoring equipment. Results 95 students participated in (IPPE) in the intervention school. Talking drawings captured improvement in influenza prevention understanding related to hand washing [pre n=17(43%); post n=30(77%)] and vaccination [pre n=2(5%); post n=15(38%)]. Findings from 1024 surveys from 566 students revealed strong baseline understanding and attitudes related to hand washing and cough etiquette (74% or greater positive responses). Automated hand hygiene monitoring in school bathrooms and classrooms estimated compliance for both soap (overall median 63%, IQR 38% to 100%) and hand sanitizer use (0.04 to 0.24 uses per student per day) but did not show significant pre/ post IPPE differences. Conclusions Student understanding of principles of influenza prevention was reasonably high. Even with this baseline, InSciEd Out and IPPE improved students’ unprompted knowledge of behaviors to prevent influenza, as reflected by talking drawings. This novel metric may be more sensitive in capturing knowledge among students than traditional assessment methods. However, IPPE did not produce further significant differences in student attitudes and behaviors regarding the flu. PMID:27525193
Promotion of Influenza Prevention Beliefs and Behaviors through Primary School Science Education.
Koep, T H; Jenkins, S; M Hammerlund, M E; Clemens, C; Fracica, E; Ekker, S C; Enders, F T; Huskins, W C; Pierret, C
2016-06-01
School-based campaigns to improve student health have demonstrated short-term success across various health topics. However, evidence of the effectiveness of programs in promoting healthy beliefs and behaviors is limited. We hypothesized that educational curricula teaching the science behind health promotion would increase student knowledge, beliefs and adherence to healthy behaviors, in this case related to influenza. Integrated Science Education Outreach is a successful education intervention in Rochester, Minnesota public schools that has demonstrated improvements in student learning. Within this program, we designed novel curricula and assessments to determine if gains in knowledge extended to influenza prevention. Further, we coupled InSciEd Out programming with a clinical intervention, Influenza Prevention Prescription Education (IPPE), to compare students' attitudes, intentions and healthy behaviors utilizing surveys and hand hygiene monitoring equipment. 95 students participated in (IPPE) in the intervention school. Talking drawings captured improvement in influenza prevention understanding related to hand washing [pre n=17(43%); post n=30(77%)] and vaccination [pre n=2(5%); post n=15(38%)]. Findings from 1024 surveys from 566 students revealed strong baseline understanding and attitudes related to hand washing and cough etiquette (74% or greater positive responses). Automated hand hygiene monitoring in school bathrooms and classrooms estimated compliance for both soap (overall median 63%, IQR 38% to 100%) and hand sanitizer use (0.04 to 0.24 uses per student per day) but did not show significant pre/ post IPPE differences. Student understanding of principles of influenza prevention was reasonably high. Even with this baseline, InSciEd Out and IPPE improved students' unprompted knowledge of behaviors to prevent influenza, as reflected by talking drawings. This novel metric may be more sensitive in capturing knowledge among students than traditional assessment methods. However, IPPE did not produce further significant differences in student attitudes and behaviors regarding the flu.
Estimation of crystallinity in isotropic isotactic polypropylene with Raman spectroscopy.
Minogianni, Chrysa; Gatos, Konstantinos G; Galiotis, Costas
2005-09-01
The Raman spectrum of isotactic polypropylene (iPP) has been found to exhibit vibrational peaks in the region of 750 to 880 cm(-1) that are sensitive to the degree of crystallinity. These features are broadly assigned to various modes of methyl group rocking, rho(CH2), and there have been various attempts to assess crystallinity based on the integrated intensities of these bands. Various vibrational analyses performed in the past in combination with experimental studies have concluded that the presence of crystalline order with trans-gauche conformation gives rise to a peak at 809 cm(-1), which is assigned to a rho(CH2) mode coupled with the skeletal stretching mode. However, the presence of additional peaks at 830 cm(-1), 841 cm(-1), and 854 cm(-1), within the same envelope, have been the subject of controversy. In this work isotropic films of iPP derived from the same precursor of identical tacticity have been subjected to various degrees of annealing and the integrated intensities of the Raman bands were measured. The results showed that true 3d crystallinity in isotropic iPP can only be expressed by the 809 cm(-1) band whereas the band at 841 cm(-1) corresponds to an uncoupled rho(CH2) fundamental mode and thus is a measure of the amorphous content. The less intense satellite bands at 830 cm(-1) and 854 cm(-1) of solid iPP cannot be distinguished from the 841 cm(-1) band in the melt and are generally considered as intermediate phases possibly related to non-crystalline components with 3(1)-helical conformations. Independent differential scanning calorimetry (DSC) crystallinity measurements were in broad agreement with the Raman measurements based on the normalized intensity of the 809 cm(-1) Raman band. By comparing the Raman with the DSC data a new value for the theoretical heat of fusion for the 100% crystalline iPP has been proposed.
Gleeson, John P; Frías, Jesús M; Ryan, Sinéad M; Brayden, David J
2018-04-20
The tripeptides, Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP), inhibit angiotensin-converting enzyme (ACE) resulting in lowered blood pressure. Our hypothesis was that the medium chain fatty acid permeation enhancer, sodium caprate (C 10 ), may prevent the decrease in permeability of the tripeptides when PepT1 is inhibited by glycyl-sarcosine (Gly-Sar), a situation that may occur in the presence of food hydrolysates. Using Caco-2 monolayers and isolated rat jejunal tissue, the apparent permeability coefficients (P app ) of [ 3 H]-IPP and [ 3 H]-LKP were assessed in the presence of Gly-Sar with and without C 10 . Gly-Sar decreased the P app of both tripeptides across monolayers and isolated jejunal tissue, but C 10 restored it. C 10 likely increased the paracellular permeability of the tripeptides, as indicated by immunofluorescence changes in tight junction proteins in Caco-2 monolayers accompanied by a concentration-dependent decrease in transepithelial electrical resistance (TEER). [ 3 H]-IPP and [ 3 H]-LKP were orally-gavaged to normal rats with Gly-Sar, C 10 , or with a mixture. Plasma levels of both peptides were reduced by Gly-Sar to less than half that of the levels detected in its absence, but were restored when C 10 was co-administered. In spontaneously hypertensive rats (SHRs), unlabelled IPP and LKP lowered blood pressure when delivered either by i.v. or oral routes. Oral gavage of Gly-Sar reduced the hypotensive action of peptides in SHRs, but the effect was restored in the presence of C 10 . In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C 10 may circumvent this by enhancing paracellular permeability. Copyright © 2018 Elsevier B.V. All rights reserved.
Vogel, Christian; Adam, Christian; Sekine, Ryo; Schiller, Tara; Lipiec, Ewelina; McNaughton, Don
2013-10-01
The reaction mechanisms of phosphate-bearing mineral phases from sewage sludge ash-based fertilizers in soil were determined by Raman and synchrotron infrared microspectroscopy. Different reaction mechanisms in wet soil were found for calcium and magnesium (pyro-) phosphates. Calcium orthophosphates were converted over time to hydroxyapatite. Conversely, different magnesium phosphates were transformed to trimagnesium phosphate. Since the magnesium phosphates are unable to form an apatite structure, the plant-available phosphorus remains in the soil, leading to better growth results observed in agricultural pot experiments. The pyrophosphates also reacted very differently. Calcium pyrophosphate is unreactive in soil. In contrast, magnesium pyrophosphate quickly formed plant-available dimagnesium phosphate.
21 CFR 182.8223 - Calcium pyrophosphate.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium...
21 CFR 582.5306 - Ferric sodium pyrophosphate.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...
21 CFR 182.8223 - Calcium pyrophosphate.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium pyrophosphate. 182.8223 Section 182.8223 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8223 Calcium...
21 CFR 582.5306 - Ferric sodium pyrophosphate.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...
21 CFR 582.5306 - Ferric sodium pyrophosphate.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...
21 CFR 582.5306 - Ferric sodium pyrophosphate.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ferric sodium pyrophosphate. 582.5306 Section 582.5306 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...
Stuknytė, Milda; Cattaneo, Stefano; Masotti, Fabio; De Noni, Ivano
2015-02-01
The occurrence of the casein-derived angiotensin converting enzyme-inhibitor (ACE-I) peptides VPP, IPP, RYLGY, RYLG, AYFYPEL, AYFYPE, LHLPLP and HLPLP were investigated in 12 different cheese samples by Ultra Performance Liquid Chromatography/High-Resolution Mass Spectrometry. The total amount of ACE-I peptides was in the range 0.87-331mgkg(-1). VPP and IPP largely prevailed in almost all cheeses. Following in vitro static gastrointestinal digestion of Cheddar, Gorgonzola, Maasdam and Grana Padano cheeses, type and amount of ACE-I peptides changed, and only VPP, IPP, HLPLP and LHLPLP were detected in the intestinal digestates. The results evidenced that the degree of proteolysis itself cannot be regarded as a promoting or hindering factor for ACE-I peptide release during cheese digestion. Moreover, the data indicated that the ACE-I potential of cheeses cannot be inferred based on the type and amount of ACE-I peptides present in undigested samples. Copyright © 2014 Elsevier Ltd. All rights reserved.
Power plant allocation in East Kalimantan considering total cost and emissions
NASA Astrophysics Data System (ADS)
Muslimin; Utomo, D. S.
2018-04-01
The fulfillment of electricity need in East Kalimantan is the responsibility of State Electricity Company/Perusahaan Listrik Negara (PLN). But PLN faces constraints in the lack of generating capacity it has. So the allocation of power loads in East Kalimantan has its own challenges. Additional power supplies from other parties are required. In this study, there are four scenarios tested to meet the electricity needs in East Kalimantan with the goal of minimizing costs and emissions. The first scenario is only by using PLN power plant. The second scenario is by combining PLN + Independent Power Producer (IPP) power plants. The third scenario is by using PLN + Rented power plants. The fourth scenario is by using PLN + Excess capacity generation. Numerical experiment using nonlinear programming is conducted with the help of the solver. The result shows that in the peak load condition, the best combination is scenario 2 (PLN + IPP). While at the lowest load condition, the cheapest scenario is PLN + IPP while the lowest emission is PLN + Rent.
Implementation of the Pan-STARRS Image Processing Pipeline
NASA Astrophysics Data System (ADS)
Fang, Julia; Aspin, C.
2007-12-01
Pan-STARRS, or Panoramic Survey Telescope and Rapid Response System, is a wide-field imaging facility that combines small mirrors with gigapixel cameras. It surveys the entire available sky several times a month, which ultimately requires large amounts of data to be processed and stored right away. Accordingly, the Image Processing Pipeline--the IPP--is a collection of software tools that is responsible for the primary image analysis for Pan-STARRS. It includes data registration, basic image analysis such as obtaining master images and detrending the exposures, mosaic calibration when applicable, and lastly, image sum and difference. In this paper I present my work of the installation of IPP 2.1 and 2.2 on a Linux machine, running the Simtest, which is simulated data to test your installation, and finally applying the IPP to two different sets of UH 2.2m Tek data. This work was conducted by a Research Experience for Undergraduates (REU) position at the University of Hawaii's Institute for Astronomy and funded by the NSF.
Nuffer, Wesley; Botts, Sheila; Franson, Kari; Gilliam, Eric; Knutsen, Randy; Nuffer, Monika; O'Brien, Elizabeth; Saseen, Joseph; Thompson, Megan; Vande Griend, Joseph; Willis, Robert
2017-11-01
The University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) used the opportunity of curriculum renewal to integrate knowledge and skills learned from didactic courses into the introductory pharmacy practice experiences (IPPEs) occurring simultaneously. This paper describes and evaluates the meaningful application of course content into IPPEs, and evaluates the success using qualitative feedback. Students entering the renewed curriculum starting in fall 2012 were provided a list of pharmacy skills and activities from didactic course directors that reinforced course content for that semester. The skills and activities were to be completed during the students' IPPE visits in the community or health systems settings, depending on the program year and semester. Students successfully completed course assignments during their IPPE course program. Not all activities could be completed as designed, and many required modification, including simulated experiences. Feedback from faculty and preceptor members of the school's experiential education committee demonstrated that these activities were valuable and improved learning of course material, but were challenging to implement. A renewed curriculum that mapped course assignments for completion in experiential settings was successfully established, after some modifications. The program was modified at regular intervals to improve the ability of preceptors to complete these activities in their individual practice environment. A balance between the school providing guidance on what activities students should perform and allowing unstructured independent learning with the preceptor is needed for an optimal experience. Copyright © 2017 Elsevier Inc. All rights reserved.
Enhancing an introductory Pharmacy Practice Experience at free medical clinics.
Morello, Candis M; Singh, Renu F; Chen, Karen J; Best, Brookie M
2010-02-01
The aim of the study was to assess and improve first-year student pharmacists' satisfaction and learning experience in a Student-Run Free Medical Clinic Project (SFMCP) providing medical care to an underserved population. Two consecutive classes of first-year student pharmacists at the University of California San Diego (UCSD) Skaggs School of Pharmacy and Pharmaceutical Sciences participated in an Introductory Pharmacy Practice Experience (IPPE) at the UCSD SFMCP. This IPPE involved two inter-professional evening free clinics which provide medical care to an underserved population and opportunities for healthcare professional training and service. Year 1 students completed a self-assessment survey instrument and year 2 students completed the survey instrument plus a new competency checklist tool. Average scores from the self-assessment survey instrument were compared between years 1 and 2. Initial survey results showed that students felt the SFMCP was worthwhile; however, they did not experience enough involvement in the patient assistance programme or non-pharmacy-related clinic activities. After the competency checklist tool implementation, overall student pharmacist satisfaction of the SFMCP IPPE remained high (88%), participation in identified weak areas improved and students agreed that the tool helped focus their clinic experience. Areas of improvement were identified with the survey instrument and the competency checklist tool increased achievement of learning objectives. Overall, student pharmacists felt the SFMCP IPPE was a good learning experience. Practising pharmacists can employ these or similar tools in specific practice settings, to evaluate and help ensure that student pharmacists or interns are achieving applicable learning objectives.
In silico profiling of Escherichia coli and Saccharomyces cerevisiae as terpenoid factories
2013-01-01
Background Heterologous microbial production of rare plant terpenoids of medicinal or industrial interest is attracting more and more attention but terpenoid yields are still low. Escherichia coli and Saccharomyces cerevisiae are the most widely used heterologous hosts; a direct comparison of both hosts based on experimental data is difficult though. Hence, the terpenoid pathways of E. coli (via 1-deoxy-D-xylulose 5-phosphate, DXP) and S. cerevisiae (via mevalonate, MVA), the impact of the respective hosts metabolism as well as the impact of different carbon sources were compared in silico by means of elementary mode analysis. The focus was set on the yield of isopentenyl diphosphate (IPP), the general terpenoid precursor, to identify new metabolic engineering strategies for an enhanced terpenoid yield. Results Starting from the respective precursor metabolites of the terpenoid pathways (pyruvate and glyceraldehyde-3-phosphate for the DXP pathway and acetyl-CoA for the MVA pathway) and considering only carbon stoichiometry, the two terpenoid pathways are identical with respect to carbon yield. However, with glucose as substrate, the MVA pathway has a lower potential to supply terpenoids in high yields than the DXP pathway if the formation of the required precursors is taken into account, due to the carbon loss in the formation of acetyl-CoA. This maximum yield is further reduced in both hosts when the required energy and reduction equivalents are considered. Moreover, the choice of carbon source (glucose, xylose, ethanol or glycerol) has an effect on terpenoid yield with non-fermentable carbon sources being more promising. Both hosts have deficiencies in energy and redox equivalents for high yield terpenoid production leading to new overexpression strategies (heterologous enzymes/pathways) for an enhanced terpenoid yield. Finally, several knockout strategies are identified using constrained minimal cut sets enforcing a coupling of growth to a terpenoid yield which is higher than any yield published in scientific literature so far. Conclusions This study provides for the first time a comprehensive and detailed in silico comparison of the most prominent heterologous hosts E. coli and S. cerevisiae as terpenoid factories giving an overview on several promising metabolic engineering strategies paving the way for an enhanced terpenoid yield. PMID:24059635
DOE Office of Scientific and Technical Information (OSTI.GOV)
Timofeev, V. I., E-mail: inna@ns.crys.ras.ru; Abramchik, Yu. A., E-mail: tostars@mail.ru; Zhukhlistova, N. E., E-mail: ugama@yandex.ru
2015-09-15
Enzymes of the phosphoribosyl pyrophosphate synthetase family (PRPPS, EC 2.7.6.1) catalyze the formation of 5-phosphoribosyl pyrophosphate (5-PRPP) from adenosine triphosphate and ribose 5-phosphate. 5-Phosphoribosyl pyrophosphate is an important intermediate in the synthesis of purine, pyrimidine, and pyridine nucleotides, as well as of the amino acids histidine and tryptophan. The crystallization conditions for E. coli PRPPS were found by the vapor-diffusion technique and were optimized to apply the capillary counter-diffusion technique. The X-ray diffraction data set was collected from the crystals grown by the counter-diffusion technique using a synchrotron radiation source to 3.1-Å resolution. The crystals of PRPPS belong to sp.more » gr. P6{sub 3}22 and have the following unit-cell parameters: a = b = 104.44 Å, c = 124.98 Å, α = β = 90°, γ = 120°. The collected X-ray diffraction data set is suitable for the solution of the three-dimensional structure of PRPPS at 3.1-Å resolution.« less
Kleber, C J; Putt, M S; Milleman, J L; Harris, M
1998-01-01
This clinical study compared the effect of a dental floss containing 0.25 mg tetrasodium pyrophosphate per cm and a placebo floss on supragingival calculus formation using a 6-week, partial-mouth toothshield model. The six lower anterior teeth were scaled and polished before each 2-week period (i.e., pre-trial, washout, trial). During both the pre-trial and trial periods, subjects brushed twice daily with a non-tartar control dentifrice, while a toothshield protected the six test teeth from brushing. After rinsing with water and removing the shield, they flossed the test teeth. All subjects used placebo floss during the pre-trial period in order to determine the baseline Volpe-Manhold Index (VMI) calculus formation scores, which were used to balance groups for the trial period. During the trial period, one group used the placebo floss, while the second group used the pyrophosphate floss. The final results demonstrated that the pyrophosphate floss significantly inhibited calculus formation between teeth (mesial-distal scores) by 21%, and on labial surfaces by 37% relative to the placebo floss.
A specialized plug-in software module for computer-aided quantitative measurement of medical images.
Wang, Q; Zeng, Y J; Huo, P; Hu, J L; Zhang, J H
2003-12-01
This paper presents a specialized system for quantitative measurement of medical images. Using Visual C++, we developed a computer-aided software based on Image-Pro Plus (IPP), a software development platform. When transferred to the hard disk of a computer by an MVPCI-V3A frame grabber, medical images can be automatically processed by our own IPP plug-in for immunohistochemical analysis, cytomorphological measurement and blood vessel segmentation. In 34 clinical studies, the system has shown its high stability, reliability and ease of utility.
2014-06-17
This document announces changes to the payment adjustment for low-volume hospitals and to the Medicare-dependent hospital (MDH) program under the hospital inpatient prospective payment systems (IPPS) for the second half of FY 2014 (April 1, 2014 through September 30, 2014) in accordance with sections 105 and 106, respectively, of the Protecting Access to Medicare Act of 2014 (PAMA).
Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1
Rao, Feng; Xu, Jing; Fu, Chenglai; Cha, Jiyoung Y.; Gadalla, Moataz M.; Xu, Risheng; Barrow, James C.; Snyder, Solomon H.
2015-01-01
The inositol pyrophosphates, molecular messengers containing an energetic pyrophosphate bond, impact a wide range of biologic processes. They are generated primarily by a family of three inositol hexakisphosphate kinases (IP6Ks), the principal product of which is diphosphoinositol pentakisphosphate (IP7). We report that IP6K2, via IP7 synthesis, is a major mediator of cancer cell migration and tumor metastasis in cell culture and in intact mice. IP6K2 acts by enhancing cell-matrix adhesion and decreasing cell–cell adhesion. This action is mediated by IP7-elicited nuclear sequestration and inactivation of the tumor suppressor liver kinase B1 (LKB1). Accordingly, inhibitors of IP6K2 offer promise in cancer therapy. PMID:25617365
DOE Office of Scientific and Technical Information (OSTI.GOV)
Timofeev, V. I., E-mail: inna@ns.crys.ras.ru, E-mail: tostars@mail.ru, E-mail: ugama@yandex.ru; Abramchik, Yu. A.; Zhukhlistova, N. E.
2016-01-15
Phosphoribosyl pyrophosphate synthetase from Escherichia coli was cloned, purified, and crystallized. Single crystals of the enzyme were grown under microgravity. The X-ray diffraction data set was collected at the Spring-8 synchrotron facility and used to determine the three-dimensional structure of the enzyme by the molecular-replacement method at 2.71 Å resolution. The active and regulatory sites in the molecule of E. coli phosphoribosyl pyrophosphate synthetase were revealed by comparison with the homologous protein from Bacillus subtilis, the structure of which was determined in a complex with functional ligands. The conformations of polypeptide-chain fragments surrounding and composing the active and regulatory sitesmore » were shown to be identical in both proteins.« less
Skropeta, C Margaret; Colvin, Alf; Sladen, Shannon
2014-10-08
Intergenerational playgroups in aged care are limited and little is known about the perceptions of individuals who have participated in such programs. Most research is focused on intergenerational programs that involved two generations of people--young people and older people or young people and people with dementia reported the significant outcomes for each group of participants. In this study a number of generations participated in the intergenerational playgroup intervention that included older people, child carers who were parents, grandparents or nannies and children aged 0-4 years old. The objective of this study was to explore the benefits of participating in an intergenerational playgroup program IPP in an aged care facility. This mixed methods quantitative and qualitative design explored the benefits of participating in an intergenerational playgroup program IPP in aged care settings. The intervention is an intergenerational playgroup program (IPP) offered in the aged care facility where intergenerational socialisation and interaction occurred between different generations. The SF36 and Geriatric Depression Scale (GDS) were used to collect pre-test post test data. The qualitative interpretive research approach used semi-structured interviews to develop the descriptive interpretation of the intergenerational playgroup experience. Interviews were conducted with aged care residents and child carers. The pre-test post-test results for the SF36 revealed a declining trend in one scale only energy/fatigue and no significant differences on the Geriatric Depression Scale GDS. The interview analyses revealed the following themes (1) intergenerational experiences, (2) two-way contributions, (3) friendships work, (4) personal growth, and (5) environmental considerations and nineteen subthemes were extracted to provide meanings. The IPP provided a successful innovative intergenerational program intervention where older people and people with dementia interacted and connected with a number of people from different generations. The IPP provided meaningful engagement for all participants considered important for self-esteem and the ability to participate fully in society. This allowed people to develop a sense of connectedness and friendships in a safe and secure environment. This increased the dignity of older people and people with dementia within the community and increased public awareness about the existing care and support services available to them.
Jacobs, Sara R; Weiner, Bryan J; Reeve, Bryce B; Hofmann, David A; Christian, Michael; Weinberger, Morris
2015-01-22
The failure rates for implementing complex innovations in healthcare organizations are high. Estimates range from 30% to 90% depending on the scope of the organizational change involved, the definition of failure, and the criteria to judge it. The innovation implementation framework offers a promising approach to examine the organizational factors that determine effective implementation. To date, the utility of this framework in a healthcare setting has been limited to qualitative studies and/or group level analyses. Therefore, the goal of this study was to quantitatively examine this framework among individual participants in the National Cancer Institute's Community Clinical Oncology Program using structural equation modeling. We examined the innovation implementation framework using structural equation modeling (SEM) among 481 physician participants in the National Cancer Institute's Community Clinical Oncology Program (CCOP). The data sources included the CCOP Annual Progress Reports, surveys of CCOP physician participants and administrators, and the American Medical Association Physician Masterfile. Overall the final model fit well. Our results demonstrated that not only did perceptions of implementation climate have a statistically significant direct effect on implementation effectiveness, but physicians' perceptions of implementation climate also mediated the relationship between organizational implementation policies and practices (IPP) and enrollment (p <0.05). In addition, physician factors such as CCOP PI status, age, radiological oncologists, and non-oncologist specialists significantly influenced enrollment as well as CCOP organizational size and structure, which had indirect effects on implementation effectiveness through IPP and implementation climate. Overall, our results quantitatively confirmed the main relationship postulated in the innovation implementation framework between IPP, implementation climate, and implementation effectiveness among individual physicians. This finding is important, as although the model has been discussed within healthcare organizations before, the studies have been predominately qualitative in nature and/or at the organizational level. In addition, our findings have practical applications. Managers looking to increase implementation effectiveness of an innovation should focus on creating an environment that physicians perceive as encouraging implementation. In addition, managers should consider instituting specific organizational IPP aimed at increasing positive perceptions of implementation climate. For example, IPP should include specific expectations, support, and rewards for innovation use.
On the relation between GNSS phase scintillation and auroral brightness around satellite's IPP
NASA Astrophysics Data System (ADS)
Spanswick, E.; Mushini, S. C.; Skone, S.; Donovan, E.
2017-12-01
Aurora occurs in different well-known morphologies, or types, including arcs and patchy-pulsating aurora (PPA). Previous observational studies have demonstrated that global navigation satellite system (GNSS) signals transiting the ionosphere in regions of aurora can contain varying levels of scintillation. These scintillations are often attributed to the ionospheric disturbances associated with auroral precipitation, which in extreme cases can affect the accuracy of these systems. One question that remains unanswered is whether a satellite's line of sight transmission through the aurora is a sufficient condition for signal scintillation. Previous studies have used "level" or "strength" of auroral emission as a proxy indicator for scintillation using limited datasets. In general, these results are mixed and inconclusive. In this study, we use a large data set (700 Auroral arc events) to statistically study the relationship between aurora and scintillation of GPS signals. This is one of the largest datasets used in this type of studies. We utilize the THEMIS (Time History of Events and Macroscale Interactions during Substorms) All-Sky Imagers (ASIs) located at Fort Smith (59.9 N, 248.1 E geog.) and Gillam (56.5 N, 265.4 E geog.), Canada. Corresponding GPS data were obtained from CHAIN (Canadian High Arctic Ionospheric Network) GPS receivers collocated with the ASIs. These GPS receivers are custom made receivers capable of providing high rate GPS signal power and phase observations as well as scintillation indices. To obtain information how aurora is affecting the signal, brightness around satellite's Ionospheric Pierce Point (IPP) was calculated and correlated with sigma phi from the satellite's signal. A very low correlation of 0.003 was observed between them. Correlation between the rate of change of brightness around the satellite's IPP and sigma phi was also calculated and a correlation coefficient of 0.7 was observed between them. These results indicate that GPS signal scintillation is not a direct function of overall luminosity but instead related to the rate of change of brightness around the satellite's IPP. Spectral analysis was also performed on this data set to observe if there are any dominant frequencies in the brightness around the satellite signal's IPP when that signal is scintillated.
Facciuolo, Antonio; Gonzalez-Cano, Patricia; Napper, Scott; Griebel, Philip J.
2016-01-01
In cattle, Mycobacterium avium subsp. paratuberculosis infection is primarily mediated through M cells overlying Peyer’s patches (PP) in the ileum. The capacity of M. avium subsp. paratuberculosis to invade ileal PP (IPP) versus discrete PP in the jejunum (JPP) and subsequent differences in mucosal immune responses were investigated. Intestinal segments were surgically prepared in both mid-jejunum, containing two JPPs, and in terminal small intestine containing continuous IPP. M. avium subsp. paratuberculosis (109 CFU) was injected into the lumen of half of each intestinal segment when calves were 10–14 days-old and infection confirmed 1–2 months later by PCR and immunohistochemistry. Thirteen recombinant M. avium subsp. paratuberculosis proteins, previously identified as immunogenic, were used to analyze pathogen-specific B- and T-cell responses in PP and mesenteric lymph nodes. IgA plasma cell responses to 9 of 13 recombinant proteins were detected in JPP but not in IPP. Secretory IgA reacting in ELISA with 9 of the 13 recombinant proteins was detected in luminal contents from both jejunal and ileal segments. These observations support the conclusion that pathogen-specific IgA B cells were induced in JPP but not IPP early after a primary infection. The presence of secretory IgA in intestinal contents is consistent with dissemination of IgA plasma cells from the identified mucosa-associated immune induction sites. This is the first direct evidence for M. avium subsp. paratuberculosis uptake by bovine JPP and for local induction of pathogen-specific IgA plasma cell responses after enteric infection. We also provide evidence that bacterial invasion of IPP, a primary B lymphoid tissue, provides a novel strategy to evade induction of mucosal immune responses. Over 60% of PPs in the newborn calf small intestine is primary lymphoid tissue, which has significant implications when designing oral vaccines or diagnostic tests to detect early M. avium subsp. paratuberculosis infections. PMID:27387969
Jacques, Olivier; Bouchard, Frédéric; MacDonald, Lauren A; Hall, Roland I; Wolfe, Brent B; Pienitz, Reinhard
2016-07-01
The hydrology of shallow lakes (and ponds) located in the western Hudson Bay Lowlands (HBL) is sensitive to climate warming and associated permafrost thaw. However, their biological characteristics are poorly known, which hampers effective aquatic ecosystem monitoring. Located in northern Manitoba along the southwestern coast of Hudson Bay, Wapusk National Park (WNP) encompasses numerous shallow lakes representative of the subarctic zone. We analyzed the distribution and diversity of diatom (microscopic algae; class Bacillariophyceae) assemblages in surficial sediments of 33 lakes located in three different ecozones spanning a vegetation gradient, from NE to SW: the Coastal Fen (CF), the Interior Peat Plateau (IPP), and the Boreal Spruce Forest (BSF). We found significant differences (P < 0.05) in diatom community composition between CF and IPP lakes, and CF and BSF lakes, but not between IPP and BSF lakes. These results are consistent with water chemistry measurements, which indicated distinct limnological conditions for CF lakes. Diatom communities in CF lakes were generally dominated by alkaliphilous taxa typical of waters with medium to high conductivity, such as Nitzschia denticula. In contrast, several IPP and BSF lakes were dominated by acidophilous and circumneutral diatom taxa with preference for low conductivity (e.g., Tabellaria flocculosa, Eunotia mucophila, E. necompacta var. vixcompacta). This exploratory survey provides a first detailed inventory of the diatom assemblages in the WNP region needed for monitoring programs to detect changes in shallow lake ecosystems and ecozonal shifts in response to climate variations.
Hinson, Jessica L; Garofoli, Gretchen K; Elswick, Betsy M
To determine the impact of a comprehensive medication synchronization program in an independent community pharmacy by (1) evaluating changes in Electronic Quality Improvement Platform for Plans and Pharmacies (EQuIPP) scores and (2) examining the change in monthly prescription volume. Independent community pharmacy in Morgantown, WV. Waterfront Family Pharmacy is a single-location independent community pharmacy located in Morgantown, WV. The pharmacy consists of four full-time pharmacists and is the primary practice site for one community pharmacy PGY-1 resident. The pharmacy provides a variety of clinical services, including vaccine administration, medication therapy management, and diabetes education services. In September 2014, Waterfront Family Pharmacy started a comprehensive medication synchronization program. Change in Electronic Quality Improvement Platform for Plans and Pharmacies (EQuIPP) scores and change in monthly prescription volume. At the end of 6 months there was improvement in all targeted EQuIPP scores. There was a 7% improvement in proportion of days covered (PDC) for cholesterol-reducing agents, a 9.5% improvement in PDC for oral glycemic agents, a 1.2% improvement in PDC for renin-angiotensin system antagonists, and a 1.8% reduction in the use of high-risk medications in the elderly. There was also an average increase in monthly prescription volume of 4.8% over the first 6 months after the implementation of the comprehensive medication synchronization program. The implementation of a comprehensive medication synchronization program in an independent community pharmacy may result in benefits including improved EQuIPP scores and increased prescription volume. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Frencher, James T.; Shen, Hongbo; Yan, Lin; Wilson, Jessica O.; Freitag, Nancy E.; Rizzo, Alicia N.; Chen, Crystal Y.; Chen, Zheng W.
2014-01-01
Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactAΔgcpE prfA* mutant. The HMBPP-deficient ΔgcpE mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention. PMID:25114162
Capuno, Joseph J; Kraft, Aleli D; Quimbo, Stella; Tan, Carlos R; Wagstaff, Adam
2016-06-01
A cluster randomized experiment was undertaken testing two sets of interventions encouraging enrollment in the Individually Paying Program (IPP), the voluntary component of the Philippines' social health insurance program. In early 2011, 1037 unenrolled IPP-eligible families in 179 randomly selected intervention municipalities were given an information kit and offered a 50% premium subsidy valid until the end of 2011; 383 IPP-eligible families in 64 control municipalities were not. In February 2012, the 787 families in the intervention sites who were still IPP-eligible but had not enrolled had their vouchers extended, were resent the enrollment kits and received SMS reminders. Half the group also received a 'handholding' intervention: in the endline interview, the enumerator offered to help complete the enrollment form, deliver it to the insurer's office in the provincial capital, and mail the membership cards. The main intervention raised the enrollment rate by 3 percentage points (ppts) (p = 0.11), with an 8 ppt larger effect (p < 0.01) among city-dwellers, consistent with travel time to the insurance office affecting enrollment. The handholding intervention raised enrollment by 29 ppts (p < 0.01), with a smaller effect (p < 0.01) among city-dwellers, likely because of shorter travel times, and higher education levels facilitating unaided completion of the enrollment form. Copyright © The World Bank Health Economics © 2015 John Wiley & Sons, Ltd. Copyright © The World Bank Health Economics © 2015 John Wiley & Sons, Ltd.
Hwangbo, Cheol; Park, Juhee; Lee, Jeong-Hyung
2011-09-23
The integrin-linked kinase (ILK)-PINCH1-α-parvin (IPP) complex functions as a signaling platform for integrins that modulates various cellular processes. ILK functions as a central adaptor for the assembly of IPP complex. We report here that mda-9/syntenin, a positive regulator of cancer metastasis, regulates the activation of Akt (also known as protein kinase B) by facilitating ILK adaptor function during adhesion to type I collagen (COL-I) in human breast cancer cells. COL-I stimulation induced the phosphorylation and plasma membrane translocation of Akt. Inhibition of mda-9/syntenin or expression of mutant ILK (E359K) significantly blocked the translocation of both ILK and Akt to the plasma membrane. mda-9/syntenin associated with ILK, and this association was increased at the plasma membrane by COL-I stimulation. Knockdown of mda-9/syntenin impaired COL-I-induced association of ILK with Akt and plasma membrane targeting of ILK-Akt complex. These results demonstrated that mda-9/syntenin regulates the activation of Akt by controlling the plasma membrane targeting of Akt via a mechanism that facilitates the association of Akt with ILK at the plasma membrane during adhesion to COL-I. On a striking note, inhibition of mda-9/syntenin impaired COL-I-induced plasma membrane translocation of the IPP complex and assembly of integrin β1-IPP signaling complexes. Thus, our study defines the role of mda-9/syntenin in ILK adaptor function and describes a new mechanism of mda-9/syntenin for regulation of cell migration.
Pseudo-malfunction of the Coloplast Titan Inflatable Penile Prosthesis One-Touch Release Pump.
Garber, Bruce B; Khurgin, Jacob L; Stember, Doron S; Perito, Paul E
2014-10-01
To define and describe a type of pseudo-malfunction of the Coloplast Titan Inflatable Penile Prosthesis (IPP) One-Touch Release (OTR) pump (Coloplast Corp, Minneapolis, MN). We retrospectively reviewed a consecutive series of 550 patients with refractory organic erectile dysfunction who were implanted with a Coloplast Titan IPP with the OTR pump during a period of approximately 4 years. All patients were implanted using standard techniques through an infrapubic or penoscrotal approach. Twenty-nine patients (5.3%) complained that their IPP would not inflate and that the pump bulb felt "hard." Examination revealed that their IPP was working normally; however, the inflate/deflate valve disc had become stuck in the deflate position. Very firm pressure had to be applied to the pump bulb to move the valve disc into the inflate position. Once this was accomplished, the device inflated and deflated normally. Another 14 patients (2.5%) reported this phenomenon to us but were able to apply enough pressure on the pump bulb to rectify it. The inflate/deflate valve disc in the Coloplast Titan OTR pump can occasionally become stuck in the deflate position (7.8% of patients in our experience). Patients may be unable to inflate the device and return for evaluation. In all cases we have encountered, firm pressure on the pump bulb caused the valve to shift into the inflate position, and the device worked properly thereafter. Patients and implanting urologists should be aware of this issue and of the way in which it can be rectified. Copyright © 2014 Elsevier Inc. All rights reserved.
High submuscular placement of urologic prosthetic balloons and reservoirs via transscrotal approach.
Morey, Allen F; Cefalu, Christopher A; Hudak, Steven J
2013-02-01
Traditional placement of inflatable penile prosthesis (IPP) reservoirs and/or artificial urinary sphincter (AUS) balloons into the space of Retzius may be challenging following major pelvic surgery. The aim of this study is to report our 1-year experience using a novel technique for high balloon/reservoir placement beneath the rectus abdominus muscle, thus completely obviating deep pelvic dissection during prosthetic urologic surgery. A retrospective review of all patients who underwent IPP and/or AUS placement between June 2011 and June 2012 was performed. All had AUS balloons and/or IPP reservoirs placed in a submuscular location by bluntly tunneling through the external inguinal ring into a potential space between the transversalis fascia and the rectus abdominus muscle using a long, angled, lung grasping clamp. Patient demographics, perioperative outcomes, and initial follow-up patient-reported outcomes were reviewed. During the study period, 120 submuscular balloons/reservoirs were inserted in 107 consecutive patients who underwent placement of an IPP (61 patients), AUS (33 patients), or both (13 patients). Among our 48 most recent patients, 41 (85%) reported they were totally unable to feel their balloon/reservoir, and all but two patients reported no bother from the submuscular balloon/reservoir placement. Of the 120 total submuscular balloons and reservoirs, surgical time and outcomes of the prosthetic procedures appeared similar to those placed using traditional methods; two reservoirs required revision surgery for repositioning. High submuscular placement of genitourinary prosthetic balloons and reservoirs via a transscrotal approach is both safely and effective, while avoiding deep retropubic dissection. © 2012 International Society for Sexual Medicine.
Chung, Eric
2017-02-01
Despite introduction of oral phosphodiesterase type 5 inhibitors and intracavernosal vasoactive agents, penile prosthesis implant remains a relevant and desired option with sales of penile prostheses continue to stay high, as many men became refractory to medical therapy and/or seeking a more effective and permanent therapy. There are two types of penile prosthesis implants: inflatable and non-inflatable types, and the inflatable penile implants can be subdivided into single-, two- and three-piece devices. Non-inflatable penile prosthesis (non-IPP) may be referred to as semi-rigid rod or malleable prosthesis. IPP is considered a superior option to malleable prosthesis as it produces penile rigidity and flaccidity that closely replicates a normal penile erectile function. Since the introduction of IPP by Scott in 1973, surgical landscape for penile prosthesis implantation has changed dramatically. Advances in prosthesis design, device technologies and surgical techniques have made penile prosthesis implant a more natural, durable and reliable device. The following article reviews the scientific advances and technological innovation in modern penile prosthesis implants over the last four decades.
2017-01-01
Despite introduction of oral phosphodiesterase type 5 inhibitors and intracavernosal vasoactive agents, penile prosthesis implant remains a relevant and desired option with sales of penile prostheses continue to stay high, as many men became refractory to medical therapy and/or seeking a more effective and permanent therapy. There are two types of penile prosthesis implants: inflatable and non-inflatable types, and the inflatable penile implants can be subdivided into single-, two- and three-piece devices. Non-inflatable penile prosthesis (non-IPP) may be referred to as semi-rigid rod or malleable prosthesis. IPP is considered a superior option to malleable prosthesis as it produces penile rigidity and flaccidity that closely replicates a normal penile erectile function. Since the introduction of IPP by Scott in 1973, surgical landscape for penile prosthesis implantation has changed dramatically. Advances in prosthesis design, device technologies and surgical techniques have made penile prosthesis implant a more natural, durable and reliable device. The following article reviews the scientific advances and technological innovation in modern penile prosthesis implants over the last four decades. PMID:28217449
Induratio penis plastica (IPP) and laser: a review
NASA Astrophysics Data System (ADS)
Longo, Leonardo; Mancini, S.; Postiglione, M. G.
2002-10-01
The first employments of Laser therapy for I.P.P. came from back to more than twenty years ago. At the beginning it was employed only in the acute forms as analgesic laser laser was used also as anti-inflammatory following the doses of Low Level Laser Therapy. Than the science tried to use the laser effect remodelling phase of the scars, to make the fibrosis regrade in the chronic forms. Tunable laser in small optical fiber was used for ablation of calcified zones with very good results. For the slight forms were used diode laser 660 and 904 nm, alone ir coupling with CO2 laser with large spot. At first some Author used helium-Neon laser 632. Some of these lasers were combined wtih microiontophoresis and ultrasounds therapy in teh same treatment. Now we use 810 nm surgical diode laser in almost all induratio forms. The immediate results and follow up will be discussed. Thanks to these results we could conclude that IPP laser therapy can be effective in most of the clinic forms. Although the used procedure is subject to improvement.
Estimating sectoral pollution load in Lagos by Industrial Pollution Projection System (IPPS).
Oketola, A A; Osibanjo, O
2007-05-15
Sensitivity to environmental issues brought about increasing pressure from local community, groups, environmental organizations and government regulators on industries to reduce their pollutant emissions. In this study, Industrial Pollution Projection System (IPPS), which was developed by the Infrastructure and Environment Team of the World Bank, was used to estimate pollution load in ton/yr (with respect to employment) of industrial sectors in Lagos. The IPPS was developed to exploit the fact that the scale of industrial activity, its sectorial composition, and the process technologies, employed in production, heavily affect industrial pollution. Available data, from Manufacturer's Association of Nigeria (M.A.N.) for the years 1997-2002 was used for the estimation. From the cumulative ranking of the pollution load (ton/yr) estimate to all media (i.e. air, land, and water), Chemical and Pharmaceutical (CPH) sector is the highest polluting sector, followed by Basic Metal (BML), Domestic and Industrial Plastics (DIP), and Food, Beverage and Tobacco (FBT) sectors. Some of these sectors have the highest number of employees, and also appeared as the most polluting sectors in Lagos.
Contemporary Patient Satisfaction Rates for Three-Piece Inflatable Penile Prostheses
Bernal, Raymond M.; Henry, Gerard D.
2012-01-01
Among the many treatments for erectile dysfunction, implantation of a penile prosthesis has been associated with high patient satisfaction rates. Specifically, the placement of a three-piece inflatable penile prosthesis (IPP) confers the highest rates of satisfaction. We reviewed the literature over the past 20 years regarding satisfaction rates for penile prostheses, with a focus on patients who had undergone an initial IPP implantation for erectile dysfunction. In all, 194 articles were reviewed, and of these, nine met inclusion criteria for analysis and data collation. We determined contemporary satisfaction rates to reflect patients' experiences with newer products and surgical approaches. Of importance, we noted that varied metrics were used to determine patient satisfaction, and overall satisfaction could not be precisely determined. Nevertheless, we found that patients in general were quite satisfied with their three-piece IPPs and restoration of sexual function. We also identified reasons for patient dissatisfaction and reviewed the literature to find ways by which satisfaction could be improved. Given the various means by which patient satisfaction was determined, future efforts should include standardized and validated questionnaires. PMID:22899909
Filippucci, E; Riveros, M Gutierrez; Georgescu, D; Salaffi, F; Grassi, W
2009-02-01
The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference. A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow. Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity=99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity=97.6%). The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.
USDA-ARS?s Scientific Manuscript database
This paper presents a model for predicting relative growth of C. perfringens in ground beef products at different percentages of salt (0%, 1%, 2% and 3%) and nitrite (0 and 200 ppm). Included in the experiments were different levels of sodium pyrophosphate (SPP). The results of the experiments indic...
NASA Technical Reports Server (NTRS)
Willerson, J. T.; Parkey, R. W.; Bonte, F. J.; Stokely, E. M.; Buja, E. M.
1975-01-01
The ability of technetium-99m stannous pyrophosphate myocardial scintigrams to aid diagnostically in recognizing, localizing, and identifying extension of acute myocardial infarction in patients was evaluated. The present study is an extension of previous animal and patient evaluations that were recently performed utilizing this myocardial imaging agent.
A pyrophosphate-responsive gadolinium(III) MRI contrast agent.
Surman, Andrew J; Bonnet, Célia S; Lowe, Mark P; Kenny, Gavin D; Bell, Jimmy D; Tóth, Eva; Vilar, Ramon
2011-01-03
This study shows that the relaxivity and optical properties of functionalised lanthanide-DTPA-bis-amide complexes (lanthanide=Gd(3+) and Eu(3+) , DTPA=diethylene triamine pentaacetic acid) can be successfully modulated by addition of specific anions, without direct Ln(3+) /anion coordination. Zinc(II)-dipicolylamine moieties, which are known to bind strongly to phosphates, were introduced in the amide "arms" of these ligands, and the interaction of the resulting Gd-Zn(2) complexes with a range of anions was screened by using indicator displacement assays (IDAs). Considerable selectivity for polyphosphorylated species (such as pyrophosphate and adenosine-5'-triphosphate (ATP)) over a range of other anions (including monophosphorylated anions) was apparent. In addition, we show that pyrophosphate modulates the relaxivity of the gadolinium(III) complex, this modulation being sufficiently large to be observed in imaging experiments. To establish the binding mode of the pyrophosphate and gain insight into the origin of the relaxometric modulation, a series of studies including UV/Vis and emission spectroscopy, luminescence lifetime measurements in H(2) O and D(2) O, (17) O and (31) P NMR spectroscopy and nuclear magnetic resonance dispersion (NMRD) studies were carried out. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ievleva, J.I.; Kolesnikov, V.P.; Mezhertisky, G.S.
1996-04-01
The main direction of science investigations for creation of efficient solid oxide fuel cells (SOFC) in IPPE are considered in this work. The development program of planar SOFC with thin-film electrolyte is shown. General design schemes of experimental SOFC units are presented. The flow design schemes of processes for initial materials and electrodes fabrication are shown. The results of investigations for creation thin-film solid oxide electrolyte at porous cathode by magnetron sputtering from complex metal target in oxidative environment are presented.
Credo, Grace M; Su, Xing; Wu, Kai; Elibol, Oguz H; Liu, David J; Reddy, Bobby; Tsai, Ta-Wei; Dorvel, Brian R; Daniels, Jonathan S; Bashir, Rashid; Varma, Madoo
2012-03-21
We introduce a label-free approach for sensing polymerase reactions on deoxyribonucleic acid (DNA) using a chelator-modified silicon-on-insulator field-effect transistor (SOI-FET) that exhibits selective and reversible electrical response to pyrophosphate anions. The chemical modification of the sensor surface was designed to include rolling-circle amplification (RCA) DNA colonies for locally enhanced pyrophosphate (PPi) signal generation and sensors with immobilized chelators for capture and surface-sensitive detection of diffusible reaction by-products. While detecting arrays of enzymatic base incorporation reactions is typically accomplished using optical fluorescence or chemiluminescence techniques, our results suggest that it is possible to develop scalable and portable PPi-specific sensors and platforms for broad biomedical applications such as DNA sequencing and microbe detection using surface-sensitive electrical readout techniques.
USDA-ARS?s Scientific Manuscript database
Response to the Letter to the Editor: We have received with great satisfaction that our article “Modelling the effect of pH, sodium chloride and sodium pyrophosphate on the thermal resistance of Escherichia coli O157:H7 in ground beef” (Food Research International, 69:289-304; 2015) has awaken inte...
Pintar, Paula A
2013-01-01
Hospital quality and financial sustainability rely on reducing healthcare-associated events/infections, length of stay, and readmissions. This project focused on designing an integrated role for the clinical nurse specialist (CNS) and the infection prevention professional (IPP) to proactively manage the delivery of evidence-based practice to high-risk surgical patients. The healthcare industry is in the midst of a paradigm shift driven by changing health policy focusing on quality indicators, patient satisfaction, and lowering costs. Coupled with these indicators is the expectation and responsibility to provide evidence-based practice at all levels of the healthcare continuum. This paradigm shift places healthcare facilities in a very competitive atmosphere as they rally for the revenue of a fixed payer mix. A literature search using CINHAL, PubMed, and the CNS national listserve databases was completed to identify if there was any previously written information available on an integrated role of the CNS/IPP. An online business plan template was used to communicate the significance, implications, and return on organizational investment to practice with establishing this role. Chronic health conditions such as diabetes, hypertension, congestive heart failure, and colonization with multidrug-resistant organisms can place patients at an increased risk for developing a surgical site infection or complications. The CNS/IPP will proactively manage these risk factors, including the patient and family in a preventive care model to manage the acute inpatient high-risk surgical patient. Care management will include coordinated, collaborative, and consultative follow-up by the CNS/IPP in the acute care, long-term care facilities, and home settings. The infection prevention skill set brings a level of clinical expertise that makes a unique CNS. The IPP is immersed in using epidemiological principles that examine the impact of comorbidities and the added risk that can contribute to developing a surgical site infection. This CNS/IPP incorporates the CNS Spheres of Influence Model and the Association of Professionals in Infection Prevention Competency Model. This combination advanced practice nurse uses a nurse-managed model of care focused on patient/family education, prevention, and self-care management. Therefore, this specific and specialized practice will bring value to the organization by improving financial outcomes through reducing infections, readmission rates, and length of stay. By providing this level of focused care, patient satisfaction will improve and system financial stability will be supported by decreasing hospital readmissions, length of stay, and other hospital-acquired conditions that the surgical candidate is prone to developing. The critical juncture in healthcare is providing opportunities for innovation by examining the CNS role and considering the feasibility of pairing it with the infection preventionist skills. This pairing provides an unprecedented opportunity to improve patient outcomes across the continuum of care. This provider has the ability to influence the Centers for Medicare and Medicaid Services quality indicators in a positive way by using implementation science to partner with system/organization stakeholders that focuses on prevention rather than reactive care processes. The dynamic trends in healthcare continue to drive "intrepreneurial," innovative, and creative ways of thinking; provide clinical practice that has the ability to perform nimbly; and maintain a proactive vision to provide quality care to a diverse patient population. This CNS/IPP role meets the dynamic proactive planning that will shift with patient, system, and nursing needs to deliver cost-effective managed care to improve the health of our patients.
Wu, Feng-Li; Shi, Liang; Yao, Jian; Ren, Ang; Zhou, Chao; Mu, Da-Shuai; Zhao, Ming-Wen
2013-01-01
An isopentenyl diphosphate isomerase (IDI) gene, GlIDI, was isolated from Ganoderma lucidum, which produces triterpenes through the mevalonate pathway. The open reading frame of GlIDI encodes a 252 amino acid polypeptide with a theoretical molecular mass of 28.71 kDa and a theoretical isoelectric point of 5.36. GlIDI is highly homologous to other fungal IDIs and contains conserved active residues and nudix motifs shared by the IDI protein family. The color complementation assay indicated that GlIDI can accelerate the accumulation of β-carotene and confirmed that the cloned complementary DNA encoded a functional GlIDI protein. Gene expression analysis showed that the GlIDI transcription level was relatively low in the mycelia and reached a relatively high level in the mushroom primordia. In addition, its expression level could be up-regulated by 254 µM methyl jasmonate. Our results suggest that this enzyme may play an important role in triterpene biosynthesis.
Taban, A Huma; Tittiger, Claus; Blomquist, Gary J; Welch, William H
2009-06-01
Farnesyl diphosphate synthase (FPPS) catalyzes the consecutive condensation of two molecules of isopentenyl diphosphate with dimethylallyl diphosphate to form farnesyl diphosphate (FPP). In insects, FPP is used for the synthesis of ubiquinones, dolicols, protein prenyl groups, and juvenile hormone. A full-length cDNA of FPPS was cloned from the cotton boll weevil, Anthonomus grandis (AgFPPS). AgFPPS cDNA consists of 1,835 nucleotides and encodes a protein of 438 amino acids. The deduced amino acid sequence has high similarity to previously isolated insect FPPSs and other known FPPSs. Recombinant AgFPPS expressed in E. coli converted labeled isopentenyl diphosphate in the presence of dimethylallyl diphosphate to FPP. Southern blot analysis indicated the presence of a single copy gene. Using molecular modeling, the three-dimensional structure of coleopteran FPPS was determined and compared to the X-ray crystal structure of avian FPPS. The alpha-helical fold is conserved in AgFPPS and the size of the active site cavity is consistent with the enzyme being a FPPS. (c) 2009 Wiley Periodicals, Inc.
Bütikofer, U; Meyer, J; Sieber, R; Walther, B; Wechsler, D
2008-01-01
The contents of the 2 antihypertensive peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) were determined in 101 samples from 10 different Swiss cheese varieties using HPLC with subsequent triple mass spectrometry. In the category of extra hard and hard cheeses, the Protected Denomination of Origin cheeses Berner Alpkäse and Berner Hobelkäse, L'Etivaz à rebibes, Le Gruyère, Sbrinz, Emmentaler (organic and conventional) and in the category of semihard cheeses, the varieties Tilsiter, Appenzeller 1/4 fat and full fat, Tête de Moine, and Vacherin fribourgeois were screened in the study. The average concentration of the sum of VPP and IPP in the screened cheese varieties varied to a large extent, and substantial variations were obtained for individual samples within the cheese varieties. The lowest average concentration of the 2 tri-petides was found in L'Etivaz à rebibes (n = 3) at 19.1 mg/kg, whereas Appenzeller 1/4 fat (n = 4) contained the greatest concentration at 182.2 mg/kg. In individual samples, the total concentration of VPP and IPP varied between 1.6 and 424.5 mg/kg. With the exception of a 10-yr-old cheese, VPP was always present at greater concentrations than IPP. Milk pretreatment, cultures, scalding conditions, and ripening time were identified as the key factors influencing the concentration of these 2 naturally occurring bioactive peptides in cheese. The results of the present study show that various traditional cheese varieties contain, on average, similar concentrations of the 2 antihypertensive peptides to the recently developed fermented milk products with blood pressure-lowering property. This may serve as a basis for the development of a functional cheese with blood pressure-lowering property.
Park, Gun Wook; Hwang, Heeyoun; Kim, Kwang Hoe; Lee, Ju Yeon; Lee, Hyun Kyoung; Park, Ji Yeong; Ji, Eun Sun; Park, Sung-Kyu Robin; Yates, John R; Kwon, Kyung-Hoon; Park, Young Mok; Lee, Hyoung-Joo; Paik, Young-Ki; Kim, Jin Young; Yoo, Jong Shin
2016-11-04
In the Chromosome-Centric Human Proteome Project (C-HPP), false-positive identification by peptide spectrum matches (PSMs) after database searches is a major issue for proteogenomic studies using liquid-chromatography and mass-spectrometry-based large proteomic profiling. Here we developed a simple strategy for protein identification, with a controlled false discovery rate (FDR) at the protein level, using an integrated proteomic pipeline (IPP) that consists of four engrailed steps as follows. First, using three different search engines, SEQUEST, MASCOT, and MS-GF+, individual proteomic searches were performed against the neXtProt database. Second, the search results from the PSMs were combined using statistical evaluation tools including DTASelect and Percolator. Third, the peptide search scores were converted into E-scores normalized using an in-house program. Last, ProteinInferencer was used to filter the proteins containing two or more peptides with a controlled FDR of 1.0% at the protein level. Finally, we compared the performance of the IPP to a conventional proteomic pipeline (CPP) for protein identification using a controlled FDR of <1% at the protein level. Using the IPP, a total of 5756 proteins (vs 4453 using the CPP) including 477 alternative splicing variants (vs 182 using the CPP) were identified from human hippocampal tissue. In addition, a total of 10 missing proteins (vs 7 using the CPP) were identified with two or more unique peptides, and their tryptic peptides were validated using MS/MS spectral pattern from a repository database or their corresponding synthetic peptides. This study shows that the IPP effectively improved the identification of proteins, including alternative splicing variants and missing proteins, in human hippocampal tissues for the C-HPP. All RAW files used in this study were deposited in ProteomeXchange (PXD000395).
Trujillo-Pozo, Isabel; Martín-Monzón, Isabel; Rodríguez-Romero, Rafael
2013-01-01
The use of intracarotid propofol procedure (IPP) when assessing musical lateralization has not been reported in literature up to now. This procedure (similar to Wada Test) has provided the opportunity to investigate not only lateralization of language and memory functions on epileptic patients but also offers a functional mapping approach with superior spatial and temporal resolution to analyze the lateralization of musical abilities. Findings in literature suggest that musical training modifies functional and structural brain organization. We studied hemispheric lateralization in a professional musician, a 33 years old woman with refractory left medial temporal lobe (MTL) epilepsy (TLE). A longitudinal neuropsychological study was performed over a period of 21 months. Before epilepsy surgery, musical abilities, language and memory were tested during IPP by means of a novel and exhaustive neuropsychological battery focusing on the processing of music. We used a selection of stimuli to analyze listening, score reading, and tempo discrimination. Our results suggested that IPP is an excellent method to determine not only language, semantic, and episodic memory, but also musical dominance in a professional musician who may be candidate for epilepsy surgery. Neuropsychological testing revealed that right hemisphere's patient is involved in semantic and episodic musical memory processes, whereas her score reading and tempo processing require contribution from both hemispheres. At one-year follow-up, outcome was excellent with respect to seizures and professional skills, meanwhile cognitive abilities improved. These findings indicate that IPP helps to predict who might be at risk for postoperative musical, language, and memory deficits after epilepsy surgery. Our research suggests that musical expertise and epilepsy critically modifies long-term memory processes and induces brain structural and functional plasticity. PMID:24367312
Yu, Cheng-Ju; Wu, Su-Mei; Tseng, Wei-Lung
2013-09-17
We report that magnetite nanoparticles (Fe3O4 NPs) act as an efficient quencher for boron dipyrromethene-conjugated adenosine 5'-triphosphate (BODIPY-ATP) that is highly fluorescent in bulk solution. BODIPY-ATP molecules attached to the surface of Fe3O4 NPs through the coordination between the triphosphate group of BODIPY-ATP and Fe(3+)/Fe(2+) on the NP surface. The formed complexes induced an apparent reduction in the BODIPY-ATP fluorescence resulting from an oxidative-photoinduced electron transfer (PET) from the BODIPY-ATP excited state to an unfilled d shell of Fe(3+)/Fe(2+) on the NP surface. A comparison of the Stern-Volmer quenching constant between Fe(3+) and Fe(2+) suggests that Fe(3+) on the NP surface dominantly controls this quenching process. The efficiency for Fe3O4 NP-induced fluorescence quenching of the BODIPY-ATP was enhanced by increasing the concentration of Fe3O4 NPs and lowering the pH of the solution to below 6.0. We found that pyrophosphate and ATP compete with BODIPY-ATP for binding to Fe3O4 NPs. Thus, we amplified BODIPY-ATP fluorescence in the presence of increasing the pyrophosphate and ATP concentration; the detection limits at a signal-to-noise ratio of 3 for pyrophosphate and ATP were determined to be 7 and 30 nM, respectively. The Fe3O4 NP-based competitive binding assay detected ATP and pyrophosphate in only 5 min. The selectivity of this assay for ATP over metal ions, amino acids, and adenosine analogues is particularly high. The practicality of using the developed method to determine ATP in a single drop of blood is also validated.
Micali, E; Chehade, K A; Isaacs, R J; Andres, D A; Spielmann, H P
2001-10-16
Farnesylation is a posttranslational lipid modification in which a 15-carbon farnesyl isoprenoid is linked via a thioether bond to specific cysteine residues of proteins in a reaction catalyzed by protein farnesyltransferase (FTase). We synthesized the benzyloxyisoprenyl pyrophosphate (BnPP) series of transferable farnesyl pyrophosphate (FPP) analogues (1a-e) to test the length dependence of the isoprenoid substrate on the FTase-catalyzed transfer of lipid to protein substrate. Kinetic analyses show that pyrophosphates 1a-e and geranyl pyrophosphate (GPP) transfer with a lower efficiency than FPP whereas geranylgeranyl pyrophosphate (GGPP) does not transfer at all. While a correlation was found between K(m) and analogue hydrophobicity and length, there was no correlation between k(cat) and these properties. Potential binding geometries of FPP, GPP, GGPP, and analogues 1a-e were examined by modeling the molecules into the active site of the FTase crystal structure. We found that analogue 1d displaces approximately the same volume of the active site as does FPP, whereas GPP and analogues 1a-c occupy lesser volumes and 1e occupies a slightly larger volume. Modeling also indicated that GGPP adopts a different conformation than the farnesyl chain of FPP, partially occluding the space occupied by the Ca(1)a(2)X peptide in the ternary X-ray crystal structure. Within the confines of the FTase pocket, the double bonds and branched methyl groups of the geranylgeranyl chain significantly restrict the number of possible conformations relative to the more flexible lipid chain of analogues 1a-e. The modeling results also provide a molecular explanation for the observation that an aromatic ring is a good isostere for the terminal isoprene of FPP.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ni, Shuisong; Robinson, Howard; Marsing, Gregory C.
2004-11-01
1. Introduction Enzymes in the non-mevalonate pathway for isoprenoid synthesis have gained recent attention because of their potential value as targets for antibiotic drug development. 2C-methyl-D-erythritol-2,4 cyclophosphate (MECDP) synthase is the fifth enzyme in the seven enzyme non-mevalonate pathway for synthesis of isopentenyl diphosphate. Four groups have published structures of MECDP synthase at resolutions varying from 1.6Å to 2.8Å, either in the presence or absence of substrate from Escherichia coli (Richard et al., 2002; Kemp et al., 2002; Steinbacher et al., 2002) or from Thermus thermophilus (Kishida et al., 2003). Among these structures, the protein always exists as a homotrimermore » either with a crystallographic or a non-crystallographic three-fold symmetry axis and an active site formed in a cleft between adjacent monomers. While the overall shape of the proteins is highly similar among these structures, each of the four reported structures contain different combinations of metal ions in the active site including a Zn2+ ion only (Steinbacher et al., 2002), a Mn2+ ion only (Richard et al., 2002), Zn2+ and Mn2+ ions (Kemp et al., 2002) or two Mg2+ ions (Kishida et al., 2003). Furthermore, two of the structures are reported to contain a hydrophobic channel along the three-fold symmetry axis that is capped by a cluster of three arginine side chains (one from each monomer) at one end of the cavity and a cluster of three glutamic acid side chains (one from each monomer) at the other side of the cavity. In a 1.8Å resolution structure, Kemp et al. (2002) reported a sulfate ion coordinated to the arginine cap and solvent trapped in a hydrophobic cavity. In a lower 2.8Å resolution structure, Richard et al. (2002) concluded that geranyl diphosphate, GPP, was most likely trapped by the arginine cap and hydrophobic cavity (Richard et al., 2002), however, the low resolution of the data together with the presence of the crystallographic symmetry axis prohibited a definitive analysis of the identity and mode of binding of the bound molecule. Kishida et al. (2003) reported that no cavity existed in a 1.6Å structure of the SO3437 homolog from Thermus thermophilus, presumably due to tighter packing of the protein from the thermophilic organism. Steinbacher et al. (2002) make no description of a hydrophobic cavity in a lower resolution (2.5-3.2Å) of the Escherichia coli protein. Here, we report a high-resolution (1.6Å) structure of MECDP synthase from Shewanella oneidensis in the absence of substrate in the active site. We provide unambiguous data that confirms the presence of Zn2+ in one of the metal binding sites and observe what appears to be farnesyl diphosphate (FPP) bound in the hydrophobic cavity along the non-crystallographic three-fold symmetry axis of the homotrimer. The high-resolution structure clarifies the mode of binding of the pyrophosphate of FPP in the arginine cluster that caps the hydrophobic cavity.« less
Bioactive calcium pyrophosphate glasses and glass-ceramics.
Kasuga, Toshihiro
2005-01-01
Calcium phosphate glass-based materials in the pyrophosphate region are briefly reviewed. Calcium pyrophosphate glasses can be prepared by including a small amount of TiO(2) (
Radioisotope scanning in osseous sarcoidosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rohatgi, P.K.
1980-01-01
Technetium-99m (/sup 99m/Tc)-labeled pyrophosphate or diphosphonate compounds and gallium-67 citrate (/sup 67/Ga) are two radionuclide scanning agents that are in widespread use in clinical practice. Technetium-99m pyrophosphate is used extensively for bone scanning to detect metastatic bone disease, benign bone tumors, osteomyelitis, benign hypertrophic osteoarthropathy, and Paget's disease. Only two reports describe abnormal /sup 99m/Tc/ pyrophosphate bone scans in four patients with osseous sarcoidosis. Gallium-67 scans are used primarily to localize neoplastic or inflammatory lesions anywhere in the body. In recent years /sup 67/Ga scans have also been used to detect the presence of both pulmonary and extrapulmonary sarcoidosis, butmore » there are no reports describing abnormal uptake of gallium in patients with osseous sarcoidosis. This report describes experience with radioisotope scanning in two patients with osseous sarcoidosis.« less
González-Caballero, Natalia; Valenzuela, Jesus G; Ribeiro, José M C; Cuervo, Patricia; Brazil, Reginaldo P
2013-03-07
Molecules involved in pheromone biosynthesis may represent alternative targets for insect population control. This may be particularly useful in managing the reproduction of Lutzomyia longipalpis, the main vector of the protozoan parasite Leishmania infantum in Latin America. Besides the chemical identity of the major components of the L. longipalpis sex pheromone, there is no information regarding the molecular biology behind its production. To understand this process, obtaining information on which genes are expressed in the pheromone gland is essential. In this study we used a transcriptomic approach to explore the pheromone gland and adjacent abdominal tergites in order to obtain substantial general sequence information. We used a laboratory-reared L. longipalpis (one spot, 9-Methyl GermacreneB) population, captured in Lapinha Cave, state of Minas Gerais, Brazil for this analysis. From a total of 3,547 cDNA clones, 2,502 high quality sequences from the pheromone gland and adjacent tissues were obtained and assembled into 1,387 contigs. Through blast searches of public databases, a group of transcripts encoding proteins potentially involved in the production of terpenoid precursors were identified in the 4th abdominal tergite, the segment containing the pheromone gland. Among them, protein-coding transcripts for four enzymes of the mevalonate pathway such as 3-hydroxyl-3-methyl glutaryl CoA reductase, phosphomevalonate kinase, diphosphomevalonate descarboxylase, and isopentenyl pyrophosphate isomerase were identified. Moreover, transcripts coding for farnesyl diphosphate synthase and NADP+ dependent farnesol dehydrogenase were also found in the same tergite. Additionally, genes potentially involved in pheromone transportation were identified from the three abdominal tergites analyzed. This study constitutes the first transcriptomic analysis exploring the repertoire of genes expressed in the tissue containing the L. longipalpis pheromone gland as well as the flanking tissues. Using a comparative approach, a set of molecules potentially present in the mevalonate pathway emerge as interesting subjects for further study regarding their association to pheromone biosynthesis. The sequences presented here may be used as a reference set for future research on pheromone production or other characteristics of pheromone communication in this insect. Moreover, some matches for transcripts of unknown function may provide fertile ground of an in-depth study of pheromone-gland specific molecules.
Castano-Duque, Lina; Helms, Anjel; Ali, Jared Gregory; Luthe, Dawn S
2018-06-21
In this study we examined global changes in protein expression in both roots and leaves of maize plants attacked by the root herbivore, Western corn rootworm (WCR, Diabrotica virgifera virgifera). The changes in protein expression Are indicative of metabolic changes during WCR feeding that enable the plant to defend itself. This is one of the first studies to look above- and below-ground at global protein expression patterns of maize plants grown in soil and infested with a root herbivore. We used advanced proteomic and network analyses to identify metabolic pathways that contribute to global defenses deployed by the insect resistant maize genotype, Mp708, infested with WCR. Using proteomic analysis, 4878 proteins in roots and leaves were detected and of these 863 showed significant changes of abundance during WCR infestation. Protein abundance patterns were analyzed using hierarchical clustering, protein correlation and protein-protein interaction networks. All three data analysis pipelines showed that proteins such as jasmonic acid biosynthetic enzymes, serine proteases, protease inhibitors, proteins involved in biosynthesis and signaling of ethylene, and enzymes producing reactive oxygen species and isopentenyl pyrophosphate, a precursor for volatile production, were upregulated in roots during WCR infestation. In leaves, highly abundant proteins were involved in signal perception suggesting activation of systemic signaling. We conclude that these protein networks contribute to the overall herbivore defense mechanisms in Mp708. Because the plants were grown in potting mix and not sterilized sand, we found that both microbial and insect defense-related proteins were present in the roots. The presence of the high constitutive levels of reduced ascorbate in roots and benzothiazole in the root volatile profiles suggest a tight tri-trophic interaction among the plant, soil microbiomes and WCR-infested roots suggesting that defenses against insects coexist with defenses against bacteria and fungi due to the interaction between roots and soil microbiota. In this study, which is one of the most complete descriptions of plant responses to root-feeding herbivore, we established an analysis pipeline for proteomics data that includes network biology that can be used with different types of "omics" data from a variety of organisms.
USDA-ARS?s Scientific Manuscript database
Ground beef products are susceptible contamination with Escherichia coli O157:H7. The objective of this study was to examine the effect of salt, sodium pyrophosphate (SPP) and sodium lactate on the probability of growth of E. coli O157:H7 in ground beef after storage for 15 days at 10 degree centig...
Tc-99m pyrophosphate myocardial scanning in Chagas' disease
DOE Office of Scientific and Technical Information (OSTI.GOV)
da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.
1981-04-01
Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.
Tc-99m pyrophosphate myocardial scanning in Chagas' disease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Goncalves da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.
1981-04-01
Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas's disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.
NASA Technical Reports Server (NTRS)
Hanner, M. S.; Weinberg, J. L.; Beeson, D. E.; Sparrow, J. G.
1976-01-01
Sky maps made by the Pioneer 10 Imaging Photopolarimeter (IPP) at sun-spacecraft distances from 1 to 3 AU have been analyzed to derive the brightness of the zodiacal light near the ecliptic at elongations greater than 90 degrees. The change in zodiacal light brightness with heliocentric distance is compared with models of the spatial distribution of the dust. Use of background starlight brightnesses derived from IPP measurements beyond the asteroid belt, where the zodiacal light is not detected, and, especially, use of a corrected calibration lead to considerably lower values for zodiacal light than those reported by us previously.
Fiore, Lorenzo; Lorenzetti, Walter; Ratti, Giovannino
2005-11-30
A procedure is proposed to compare single-unit spiking activity elicited in repetitive cycles with an inhomogeneous Poisson process (IPP). Each spike sequence in a cycle is discretized and represented as a point process on a circle. The interspike interval probability density predicted for an IPP is computed on the basis of the experimental firing probability density; differences from the experimental interval distribution are assessed. This procedure was applied to spike trains which were repetitively induced by opening-closing movements of the distal article of a lobster leg. As expected, the density of short interspike intervals, less than 20-40 ms in length, was found to lie greatly below the level predicted for an IPP, reflecting the occurrence of the refractory period. Conversely, longer intervals, ranging from 20-40 to 100-120 ms, were markedly more abundant than expected; this provided evidence for a time window of increased tendency to fire again after a spike. Less consistently, a weak depression of spike generation was observed for longer intervals. A Monte Carlo procedure, implemented for comparison, produced quite similar results, but was slightly less precise and more demanding as concerns computation time.
Quantum chemical study on gas phase pyrolysis of p-isopropenylphenol.
Mohan Verma, Anand; Kawale, Harshal D; Agrawal, Kushagra; Kishore, Nanda
2018-05-01
In the pyrolysis of Sphagnum moss species, p-isopropenylphenol (p-IPP) is a major product which has been considered in this density functional theory based computational study for its conversion to various products such as benzene, phenol, 4-propenylphenol, indan-5-ol, 4-propylcyclohexanone, 4-cyclopropylphenol, etc. In order to achieve these products, eight different reaction schemes are performed using B3LYP/6-311 + g (d,p) level of theory. Further, thermodynamic properties such as reaction free energies and reaction enthalpies associated with these eight reaction schemes are developed in the temperature range of 298-898 K. The reaction schemes that include partial hydrogenation of the aromatic carbon followed by elimination of functional groups are found to demand low activation energy. The production of benzene from p-IPP with isopropenylbenzene as an intermediate product requiring only 19.83 kcal/mol of activation energy is the rate limiting reaction step. Indan-5-ol produced from p-IPP is validated with the literature results and found excellent agreement between two results. Furthermore, the temperature is found to have phenomenal effect in each reaction scheme. Copyright © 2018 Elsevier Inc. All rights reserved.
Halpert, Madeleine-Thérèse; Chappell, M. Jahi
2017-01-01
In principle, intellectual property protections (IPPs) promote and protect important but costly investment in research and development. However, the empirical reality of IPPs has often gone without critical evaluation, and the potential of alternative approaches to lend equal or greater support for useful innovation is rarely considered. In this paper, we review the mounting evidence that the global intellectual property regime (IPR) for germplasm has been neither necessary nor sufficient to generate socially beneficial improvements in crop plants and maintain agrobiodiversity. Instead, based on our analysis, the dominant global IPR appears to have contributed to consolidation in the seed industry while failing to genuinely engage with the potential of alternatives to support social goods such as food security, adaptability, and resilience. The dominant IPR also constrains collaborative and cumulative plant breeding processes that are built upon the work of countless farmers past and present. Given the likely limits of current IPR, we propose that social goods in agriculture may be better supported by alternative approaches, warranting a rapid move away from the dominant single-dimensional focus on encouraging innovation through ensuring monopoly profits to IPP holders. PMID:28529703
Forman, Dawn; Nicol, Pam; Nicol, Paul
2015-01-01
Adapting to interprofessional education and practice requires a change of perspective for many health professionals. We aimed to explore the potential of scenario planning to bridge the understanding gap and framing strategic planning for interprofessional education (IPE) and practice (IPP), as well as to implement innovative techniques and technology for large-group scenario planning. A full-day scenario planning workshop incorporating innovative methodology was designed and offered to participants. The 71 participants included academics from nine universities, as well as service providers, government, students and consumer organisations. The outcomes were evaluated by statistical and thematic analysis of a mixed method survey questionnaire. The scenario planning method resulted in a positive response as a means of collaboratively exploring current knowledge and broadening entrenched attitudes. It was perceived to be an effective instrument for framing strategy for the implementation of IPE/IPP, with 81 percent of respondents to a post-workshop survey indicating they would consider using scenario planning in their own organisations. The scenario planning method can be used by tertiary academic institutions as a strategy in developing, implementing and embedding IPE, and for the enculturation of IPP in practice settings.
Halpert, Madeleine-Thérèse; Chappell, M Jahi
2017-01-01
In principle, intellectual property protections (IPPs) promote and protect important but costly investment in research and development. However, the empirical reality of IPPs has often gone without critical evaluation, and the potential of alternative approaches to lend equal or greater support for useful innovation is rarely considered. In this paper, we review the mounting evidence that the global intellectual property regime (IPR) for germplasm has been neither necessary nor sufficient to generate socially beneficial improvements in crop plants and maintain agrobiodiversity. Instead, based on our analysis, the dominant global IPR appears to have contributed to consolidation in the seed industry while failing to genuinely engage with the potential of alternatives to support social goods such as food security, adaptability, and resilience. The dominant IPR also constrains collaborative and cumulative plant breeding processes that are built upon the work of countless farmers past and present. Given the likely limits of current IPR, we propose that social goods in agriculture may be better supported by alternative approaches, warranting a rapid move away from the dominant single-dimensional focus on encouraging innovation through ensuring monopoly profits to IPP holders.
NASA Astrophysics Data System (ADS)
Yuan, Y.; Tscherning, C. C.; Knudsen, P.; Xu, G.; Ou, J.
2008-01-01
A new method for modeling the ionospheric delay using global positioning system (GPS) data is proposed, called the ionospheric eclipse factor method (IEFM). It is based on establishing a concept referred to as the ionospheric eclipse factor (IEF) λ of the ionospheric pierce point (IPP) and the IEF’s influence factor (IFF) bar{λ}. The IEF can be used to make a relatively precise distinction between ionospheric daytime and nighttime, whereas the IFF is advantageous for describing the IEF’s variations with day, month, season and year, associated with seasonal variations of total electron content (TEC) of the ionosphere. By combining λ and bar{λ} with the local time t of IPP, the IEFM has the ability to precisely distinguish between ionospheric daytime and nighttime, as well as efficiently combine them during different seasons or months over a year at the IPP. The IEFM-based ionospheric delay estimates are validated by combining an absolute positioning mode with several ionospheric delay correction models or algorithms, using GPS data at an international Global Navigation Satellite System (GNSS) service (IGS) station (WTZR). Our results indicate that the IEFM may further improve ionospheric delay modeling using GPS data.
Bornstein, Jacob; Goldstein, Andrew T; Stockdale, Colleen K; Bergeron, Sophie; Pukall, Caroline; Zolnoun, Denniz; Coady, Deborah
2016-04-01
In 2014, the Executive Council of the International Society for the Study of Vulvovaginal Disease (ISSVD), the Boards of Directors of the International Society for the Study of Women's Sexual Health (ISSWSH), and the International Pelvic Pain Society (IPPS) acknowledged the need to revise the current terminology of vulvar pain, based on the significant increase in high quality etiologic studies published in the last decade. The new terminology was achieved in four steps. The first involved a terminology consensus conference with representatives of the three societies, held in April 2015. Then, an analysis of the relevant published studies was used to establish a level of evidence for each factor associated with vulvodynia. The terminology was amended based on feedback from members of the societies. Finally, each society's board accepted the new terminology. In 2015, the ISSVD, ISSWSH, and IPPS adopted a new vulvar pain and vulvodynia terminology that acknowledges the complexity of the clinical presentation and pathophysiology involved in vulvar pain and vulvodynia, and incorporates new information derived from evidence-based studies conducted since the last terminology published in 2003. Copyright © 2016 International Society for Sexual Medicine. All rights reserved.
Hatzichristodoulou, Georgios
2018-03-01
Correction of residual curvature during inflatable penile prosthesis (IPP) implantation in patients with Peyronie's disease (PD) by plaque incision and grafting is a common approach. To present a novel technique for residual curvature correction during IPP implantation using collagen fleece (TachoSil, Baxter Healthcare Corp, Deerfield, IL, USA). After the IPP (Titan Touch, Coloplast, Minneapolis, MN, USA) is placed, the implant is inflated maximally. When residual curvature exceeds 40°, the PICS (penile implant in combination with the Sealing technique) technique is performed. The device is deflated, and a circumcising skin incision and penile degloving are performed. After elevation of the neurovascular bundle, the device is reinflated maximally. Plaque incision is performed at the point of maximum curvature using electrocautery. This leads to penile straightening because the tension is removed. In the next step, the defect of the tunica is closed with collagen fleece, which sticks to the tunica and defect without any sutures needed. The neurovascular bundle is reapproximated and the Buck fascia is closed. This is followed by closure of penile skin. Primary outcome measurements were straightening rates, operative times, 5-item International Index of Erectile Function (IIEF-5) scores at follow-up, immediate and late complications, and patient satisfaction. The PICS technique was applied to 15 patients. Mean patient age was 61.7 years (52-79 years). Mean residual curvature after IPP was 66.7° (50-90°). Mean operative time was 117.3 minutes (100-140 minutes). Mean follow-up was 15.1 months (1-29 months). 12 of 15 patients (80%) showed a totally straight penis. 3 patients (20%) had residual curvature of 10° at follow-up, which did not interfere with sexual intercourse. Mean IIEF-5 score at follow-up was 24.2 (22-25). No immediate or late complications occurred. All patients were satisfied with the surgical outcomes. This novel technique prevents puncture or injury of the device, because the collagen fleece does not require suture fixation into the defect after plaque incision. This technique can be applied to patients with severe PD who display residual curvature greater than 40° after IPP placement. It is a fast approach with low complication rates. Limitations include the small patient population and short follow-up. The PICS technique represents a safe and time-saving approach for residual curvature correction during IPP placement in patients with PD and prevents device puncture. Hatzichristodoulou G. The PICS Technique: A Novel Approach for Residual Curvature Correction During Penile Prosthesis Implantation in Patients With Severe Peyronie's Disease Using the Collagen Fleece TachoSil. J Sex Med 2018;15:416-421. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Microclonal Multipication of Wild Cherry (Prunus Avium L.) from Shoot Tips and Root Sucker Buds
Branka Pevalek-Kozlina; Charles H. Michler; Sibila Jelaska
1994-01-01
The effects of different combinations and concentrations of the growth regulators: 6-benzylaminopurine (BA), 6 furfurylaminopurine (KIN), N6- (2-isopentenyl) adenine (2iP), indole-3-butyric acid (IBA), indole-3-acetic acid (IAA) and a-naphthaleneacetic acid (NAA) on axillary shoot multiplication rates for wild cherry (Prunus aviurn...
USDA-ARS?s Scientific Manuscript database
Monitoring the growth of in vitro natural rubberwas accomplished by high resolution size exclusion chromatography, SEC.Washed rubber particles isolated from H. brasiliensis latex, containing the rubber transferase enzyme, were used to catalyze the polymerization of synthetic isopentenyl pyrophosphat...
Soft-tissue sarcoma: imaged with technetium-99m pyrophosphate
DOE Office of Scientific and Technical Information (OSTI.GOV)
Blatt, C.J.; Hayt, D.B.; Desai, M.
1977-11-01
A liposarcoma showed intense concentration of technetium-99m pyrophosphate. An angiogram demonstrated a highly vascular lesion, and it is suggested that blood flow played a major role in allowing the tumor to be demonstrated on scintiphotography. There was some histologic evidence of calcification which probably also contributed to bone-tracer disposition. Quantitative analysis of the specimen demonstrated that this calcification was located primarily in the areas of hemorrhage and necrosis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Forman, M.B.; Sandler, M.P.; Sacks, G.A.
1983-03-01
A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, /sup 201/Tl, /sup 67/Ga, and /sup 99m/Tc pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.
Hinshaw, W Banks; DeLong, Allyn F
2016-01-01
The documented history of the development of the bisphosphonate drugs is reviewed in sufficient detail to permit independent evaluation of the consistency of the conclusions reached from the available data. The evidence developed during the early interval of these studies 1960-1975 was sufficient to establish that pyrophosphate shares the subsequently established dual bisphosphonate characteristics of bone resorption inhibition and prevention of tissue mineralization.
The Thiamin Pyrophosphate-Motif
NASA Technical Reports Server (NTRS)
Dominiak, P.; Ciszak, E.
2003-01-01
Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits and two catalytic centers. Each catalytic center (PP:PYR) is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and amhopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core (PP:PYR)(sub 2) within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GXPhiX(sub 4)(G)PhiXXGQ and GDGX(sub 25-30)NN in the PP-domain, and the EX(sub 4)(G)PhiXXGPhi in the PYR-domain, where Phi corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.
Escherichia coli DnaE Polymerase Couples Pyrophosphatase Activity to DNA Replication
Lapenta, Fabio; Montón Silva, Alejandro; Brandimarti, Renato; Lanzi, Massimiliano; Gratani, Fabio Lino; Vellosillo Gonzalez, Perceval; Perticarari, Sofia; Hochkoeppler, Alejandro
2016-01-01
DNA Polymerases generate pyrophosphate every time they catalyze a step of DNA elongation. This elongation reaction is generally believed as thermodynamically favoured by the hydrolysis of pyrophosphate, catalyzed by inorganic pyrophosphatases. However, the specific action of inorganic pyrophosphatases coupled to DNA replication in vivo was never demonstrated. Here we show that the Polymerase-Histidinol-Phosphatase (PHP) domain of Escherichia coli DNA Polymerase III α subunit features pyrophosphatase activity. We also show that this activity is inhibited by fluoride, as commonly observed for inorganic pyrophosphatases, and we identified 3 amino acids of the PHP active site. Remarkably, E. coli cells expressing variants of these catalytic residues of α subunit feature aberrant phenotypes, poor viability, and are subject to high mutation frequencies. Our findings indicate that DNA Polymerases can couple DNA elongation and pyrophosphate hydrolysis, providing a mechanism for the control of DNA extension rate, and suggest a promising target for novel antibiotics. PMID:27050298
A Pyrophosphate Based Energy Generating Module
2008-12-01
OMB control number. 1. REPORT DATE DEC 2008 2 . REPORT TYPE N/A 3 . DATES COVERED - 4. TITLE AND SUBTITLE A Pyrophosphate Based Energy...for each substrate (PPi, PEP, and AMP) using double reciprocal Lineweaver-Burk plots of saturation data. 10| 2 10| 3 10|4 10|5 10|6 10|7 10-11 10- 10...Partitioning 1 2 3 4 Bilayer - + + + α-Hemolysin - - + + Upper Reservoir +PPi, +PEP +PPi, +PEP +PPi, +PEP +PPi, +PEP, +Luc Lower Reservoir +AMP
Simple tools for assembling and searching high-density picolitre pyrophosphate sequence data.
Parker, Nicolas J; Parker, Andrew G
2008-04-18
The advent of pyrophosphate sequencing makes large volumes of sequencing data available at a lower cost than previously possible. However, the short read lengths are difficult to assemble and the large dataset is difficult to handle. During the sequencing of a virus from the tsetse fly, Glossina pallidipes, we found the need for tools to search quickly a set of reads for near exact text matches. A set of tools is provided to search a large data set of pyrophosphate sequence reads under a "live" CD version of Linux on a standard PC that can be used by anyone without prior knowledge of Linux and without having to install a Linux setup on the computer. The tools permit short lengths of de novo assembly, checking of existing assembled sequences, selection and display of reads from the data set and gathering counts of sequences in the reads. Demonstrations are given of the use of the tools to help with checking an assembly against the fragment data set; investigating homopolymer lengths, repeat regions and polymorphisms; and resolving inserted bases caused by incomplete chain extension. The additional information contained in a pyrophosphate sequencing data set beyond a basic assembly is difficult to access due to a lack of tools. The set of simple tools presented here would allow anyone with basic computer skills and a standard PC to access this information.
Kim, Yong-Kyoung; Kim, Yeon Bok; Uddin, Md Romij; Lee, Sanghyun; Kim, Soo-Un; Park, Sang Un
2014-10-17
To elucidate the function of mevalonate-5-pyrophosphate decarboxylase (MVD) and farnesyl pyrophosphate synthase (FPS) in triterpene biosynthesis, the genes governing the expression of these enzymes were transformed into Panax ginseng hairy roots. All the transgenic lines showed higher expression levels of PgMVD and PgFPS than that by the wild-type control. Among the hairy root lines transformed with PgMVD, M18 showed the highest level of transcription compared to the control (14.5-fold higher). Transcriptions of F11 and F20 transformed with PgFPS showed 11.1-fold higher level compared with control. In triterpene analysis, M25 of PgMVD produced 4.4-fold higher stigmasterol content (138.95 μg/100 mg, dry weight [DW]) than that by the control; F17 of PgFPS showed the highest total ginsenoside (36.42 mg/g DW) content, which was 2.4-fold higher compared with control. Our results indicate that metabolic engineering in P. ginseng was successfully achieved through Agrobacterium rhizogenes-mediated transformation and that the accumulation of phytosterols and ginsenosides was enhanced by introducing the PgMVD and PgFPS genes into the hairy roots of the plant. Our results suggest that PgMVD and PgFPS play an important role in the triterpene biosynthesis of P. ginseng.
Chemical cross-linking of polypropylenes towards new shape memory polymers.
Raidt, Thomas; Hoeher, Robin; Katzenberg, Frank; Tiller, Joerg C
2015-04-01
In this work, syndiotactic polypropylene (sPP) as well as isotactic polypropylene (iPP) are cross-linked to gain a shape memory effect. Both prepared PP networks exhibit maximum strains of 700%, stored strains of up to 680%, and recoveries of nearly 100%. While x-iPP is stable for many cycles, x-sPP ruptures after the first shape-memory cycle. It is shown by wide-angle X-ray scattering (WAXS) experiments that cross-linked iPP exhibits homoepitaxy in the temporary, stretched shape but in contrast to previous reports it contains a higher amount of daughter than mother crystals. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Shakoor, Rana A; Kim, Heejin; Cho, Woosuk; Lim, Soo Yeon; Song, Hannah; Lee, Jung Woo; Kang, Jeung Ku; Kim, Yong-Tae; Jung, Yousung; Choi, Jang Wook
2012-07-18
As an attempt to develop lithium ion batteries with excellent performance, which is desirable for a variety of applications including mobile electronics, electrical vehicles, and utility grids, the battery community has continuously pursued cathode materials that function at higher potentials with efficient kinetics for lithium insertion and extraction. By employing both experimental and theoretical tools, herein we report multicomponent pyrophosphate (Li(2)MP(2)O(7), M = Fe(1/3)Mn(1/3)Co(1/3)) cathode materials with novel and advantageous properties as compared to the single-component analogues and other multicomponent polyanions. Li(2)Fe(1/3)Mn(1/3)Co(1/3)P(2)O(7) is formed on the basis of a solid solution among the three individual transition-metal-based pyrophosphates. The unique crystal structure of pyrophosphate and the first principles calculations show that different transition metals have a tendency to preferentially occupy either octahedral or pyramidal sites, and this site-specific transition metal occupation leads to significant improvements in various battery properties: a single-phase mode for Li insertion/extraction, improved cell potentials for Fe(2+)/Fe(3+) (raised by 0.18 eV) and Co(2+)/Co(3+) (lowered by 0.26 eV), and increased activity for Mn(2+)/Mn(3+) with significantly reduced overpotential. We reveal that the favorable energy of transition metal mixing and the sequential redox reaction for each TM element with a sufficient redox gap is the underlying physical reason for the preferential single-phase mode of Li intercalation/deintercalation reaction in pyrophosphate, a general concept that can be applied to other multicomponent systems. Furthermore, an extremely small volume change of ~0.7% between the fully charged and discharged states and the significantly enhanced thermal stability are observed for the present material, the effects unseen in previous multicomponent battery materials.
Larson, Eric T.; Kim, Jessica E.; Zucker, Frank H.; Kelley, Angela; Mueller, Natascha; Napuli, Alberto J.; Verlinde, Christophe L.M.J.; Fan, Erkang; Buckner, Frederick S.; Van Voorhis, Wesley C.; Merritt, Ethan A.; Hol, Wim G.J.
2011-01-01
Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 Å resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg2+ ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of E. coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS-tRNAMet complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme. PMID:21144880
Design Time Optimization for Hardware Watermarking Protection of HDL Designs
Castillo, E.; Morales, D. P.; García, A.; Parrilla, L.; Todorovich, E.; Meyer-Baese, U.
2015-01-01
HDL-level design offers important advantages for the application of watermarking to IP cores, but its complexity also requires tools automating these watermarking algorithms. A new tool for signature distribution through combinational logic is proposed in this work. IPP@HDL, a previously proposed high-level watermarking technique, has been employed for evaluating the tool. IPP@HDL relies on spreading the bits of a digital signature at the HDL design level using combinational logic included within the original system. The development of this new tool for the signature distribution has not only extended and eased the applicability of this IPP technique, but it has also improved the signature hosting process itself. Three algorithms were studied in order to develop this automated tool. The selection of a cost function determines the best hosting solutions in terms of area and performance penalties on the IP core to protect. An 1D-DWT core and MD5 and SHA1 digital signatures were used in order to illustrate the benefits of the new tool and its optimization related to the extraction logic resources. Among the proposed algorithms, the alternative based on simulated annealing reduces the additional resources while maintaining an acceptable computation time and also saving designer effort and time. PMID:25861681
Yoon, Hun-Young; Mann, F. A.; Lee, Suhwon
2013-01-01
Four thoracic evacuation techniques for pneumothorax elimination after diaphragmatic defect closure were compared in 40 canine cadavers. After creating a defect in the left side of the diaphragm, thoracic drainage was performed by thoracostomy tube insertion through the defect and a small (DD-SP) or large (DD-LP) puncture created in the caudal mediastinum, or through both the diaphragmatic defect and intact contralateral diaphragm with a small (DI-SP) or large (DI-LP) puncture in made in the caudal mediastinum. Differences in intrapleural pressure (IPP) between the right and left hemithoraxes after air evacuation along with differences in IPP before making a defect and after air evacuation in each hemithorax were calculated. A difference (p ≤ 0.0011) in IPP between the left and right hemithoraxes after air evacuation as well as before making a defect and after air evacuation in the right hemithorax was detected for the DD-SP group. No significant differences (p ≥ 0.0835) were observed for the DI-LP, DD-LP, or DI-SP groups. Creation of a large mediastinal puncture or thoracic evacuation through both a diaphragmatic defect and intact contralateral diaphragm can facilitate proper pneumothorax elimination bilaterally after diaphragmatic defect closure in dogs with a small puncture in the caudal mediastinum. PMID:23814472
Gum, Lyn Frances; Lloyd, Andrea; Lawn, Sharon; Richards, Janet Noreen; Lindemann, Iris; Sweet, Linda; Ward, Helena; King, Alison; Bramwell, Donald
2013-11-01
This article is based on a partnership between a primary health service and a university whose shared goal was to prepare students and graduates for interprofessional practice (IPP). This collaborative process led to the development of consensus on an interprofessional capability framework. An action research methodology was adopted to study the development and progress of the partnership between university and health service providers. The initial aim was to understand their perceptions of IPP. Following this, the findings and draft capabilities were presented back to the groups. Finalisation of the capabilities took place with shared discussion and debate on how to implement them in the primary care setting. Several ideas and strategies were generated as to how to prepare effective interprofessional learning experiences for students in both environments (university and primary health care setting). Extensive stakeholder consultation from healthcare providers and educators has produced a framework, which incorporates the shared views and understandings, and can therefore be widely used in both settings. Development of a framework of capabilities for IPP, through a collaborative process, is a useful strategy for achieving agreement. Such a framework can guide curriculum for use in university and health service settings to assist incorporation of interprofessional capabilities into students' learning and practice.
Design of a phase contrast imaging diagnostic for the Wendelstein 7-X stellarator
NASA Astrophysics Data System (ADS)
Edlund, E. M.; Porkolab, M.; Grulke, O.; Böttger, L.-G.; Sehren, C.
2016-10-01
The Wendelstein 7-X stellarator at IPP Greifswald commenced operation in 2015, and while its design has been aimed at minimizing neoclassical transport, turbulent transport is expected to be strongly affected by the magnetic geometry. With this in mind, MIT and IPP-Greifswald scientists have undertaken a project to design and implement a phase contrast imaging (PCI) diagnostic to measure turbulence in W7-X in the OP1.2 operating phase starting in 2017. The principle and design aspects of the PCI method have been described in numerous past publications. In W7-X the PCI system will have two imaging systems differing only in the angle of the spatial mask that selects for magnetic pitch angle, and will produce measurements of poloidal and radial correlations. A series of remotely controllable optics will allow the beam size and image magnification to be adjustable. We expect sensitivity to fluctuations in the range of 2 kHz to approximately 2 MHz and wavenumbers in the range of 1 cm-1 to 30 cm-1 which should allow us to detect ITG, TEM and possibly ETG turbulence. The MIT portion of this project is supported by the US DOE under Grant DE-SC0014229, and the IPP part is funded under Euratom Grant agreement No 633053.
Clark, Phillip G
2014-01-01
Health and social care professionals increasingly use narrative approaches to focus on the patient and to communicate with each other. Both effective interprofessional education (IPE) and practice (IPP) require recognizing the various values and voices of different professions, how they relate to the patient's life story, and how they interact with each other at the level of the healthcare team. This article analyzes and integrates the literature on narrative to explore: self-narrative as an expression of one's professional identity; the co-creation of the patient's narrative by the professional and the patient; and the interprofessional multi-vocal narrative discourse as co-constructed by members of the healthcare team. Using a narrative approach to thinking about professional identity, provider-patient communication, and interprofessional teamwork expands our thinking about both IPE and IPP by providing new insights into the nature of professional practice based on relationships to oneself, the patient, and others on the team. How professionals define themselves, gather and present information from the patient, and communicate as members of a clinical team all have important dimensions that can be revealed by a narrative approach. Implications and conclusions for the further development of the narrative approach in IPE and IPP are offered.
USDA-ARS?s Scientific Manuscript database
A fractional factorial design was used to assess the combined effects of four internal temperatures (55.0, 57.5, 60.0 and 62.5C) and five concentrations of sodium chloride (NaCl) (0.0, 1.5, 3.0, 4.5 and 6.0 wt/wt%) and sodium pyrophosphate (SPP) (0.0, 0.1, 0.15, 0.2 and 0.3 wt/wt%) on the heat resis...
The hydrophilic-coated inflatable penile prosthesis: 1-year experience.
Wolter, Christopher E; Hellstrom, Wayne J G
2004-09-01
Penile prosthesis infections are a devastating complication for both patient and surgeon. Efforts to reduce the risk of infection from these elective procedures are a major focus of research and development by the major prosthesis companies. The Titan inflatable penile prosthesis (Mentor Corporation, Santa Barbara, CA) is coated with polyvinylpyrrolidone (PVP), a hydrophilic substance that reduces bacterial adherence and absorbs and elutes the antibiotics the device is immersed in intraoperatively. The Titan device was introduced to the American market in September 2002. This study reports the 1-year experience in the U.S. with the Titan and compares infection rates with the noncoated Alpha-1 IPP made by Mentor. Two thousand three hundred and fifty-seven Titan prostheses were implanted in the U.S. from September 2002 to August 2003, compared with the 482 noncoated Alpha-1 IPPs implanted over the same time period. Infection rates were compared, along with bacterial culture data. All data were collected from Mentor's internal database, as generated from the FDA's mandatory reporting of explanted medical devices, and available on the internet. The infection rate for the coated Titan IPP was 1.06% (25/2,357). During the same time period, the infection rate for the Alpha-1 noncoated prosthesis was 2.07% (10/482). Staphylococcus species predominated in both groups (9/25 Titan, 6/10 Alpha-1). At 1 year of follow-up, the data demonstrate that the hydrophilic coating on the Titan IPP confers a significant advantage in reducing the rate of infection over the noncoated device. Long-term follow-up on this first year database is needed before this innovation is accepted as the standard of care for prosthetic surgery. Nevertheless, the theoretical reduction in bacterial adhesion conferred by the hydrophilic PVP surface and the ability to choose which antibiotic the device is immersed in intraoperatively gives the implanting surgeon distinct advantages with this new product.
Managing the difficult penile prosthesis patient.
Trost, Landon W; Baum, Neil; Hellstrom, Wayne J G
2013-04-01
Inflatable penile prostheses (IPPs) are associated with excellent long-term outcomes and patient/partner satisfaction. A small percentage of patients remain dissatisfied, despite acceptable surgical results. This study aims to evaluate factors associated with patient satisfaction and dissatisfaction, define patient characteristics, which may identify elevated risk of postoperative dissatisfaction, and describe management strategies to optimize functional and psychological patient outcomes. A review of urologic and non-urologic cosmetic surgery literature was performed to identify factors associated with patient satisfaction/dissatisfaction. Emphasis was placed on articles defining "high risk" or psychologically challenging patients. Preoperative factors associated with patient satisfaction/dissatisfaction and character traits, which may identify elevated risk of postoperative dissatisfaction or otherwise indicate a psychologically challenging patient. Contemporary patient and partner satisfaction rates following IPP are 92-100% and 91-95%, respectively. Factors associated with satisfaction include decreased preoperative expectations, favorable female partner sexual function, body mass index ≤30, and absence of Peyronie's disease or prior prostatectomy. Determinants of dissatisfaction include perceived/actual loss of penile length, decreased glanular engorgement, altered erectile/ejaculatory sensation, pain, diminished cosmetic outcome, difficulty with device function, partner dissatisfaction and perception of unnatural sensation, complications, and extent of alternative treatments offered. Personality characteristics which may indicate psychologically challenging IPP patients include obsessive/compulsive tendencies, unrealistic expectations, patients undergoing revision surgery, those seeking multiple surgical opinions, feeling of entitlement, patients in denial of their prior erectile/sexual function and current disease status, or those with other psychiatric disorders. The mnemonic CURSED Patient is presented: "Compulsive/obsessive, Unrealistic, Revision, Surgeon Shopping, Entitled, Denial, and Psychiatric." Although the majority of IPP patients experience excellent, durable satisfaction and outcomes, a challenging subset of patients may be at increased risk of postoperative dissatisfaction. Appropriate recognition/prevention and management of this cohort may help to establish and strengthen relationships, reduce physical, emotional, and legal risk, and ultimately enhance patient satisfaction. © 2013 International Society for Sexual Medicine.
Singh, Raksha; Lee, Jae-Eun; Dangol, Sarmina; Choi, Jihyun; Yoo, Ran Hee; Moon, Jae Sun; Shim, Jae-Kyung; Rakwal, Randeep; Agrawal, Ganesh Kumar; Jwa, Nam-Soo
2014-01-01
The mitogen-activated protein kinase (MAPK) cascade is composed at least of MAP3K (for MAPK kinase kinase), MAP2K, and MAPK family modules. These components together play a central role in mediating extracellular signals to the cell and vice versa by interacting with their partner proteins. However, the MAP3K-interacting proteins remain poorly investigated in plants. Here, we utilized a yeast two-hybrid system and bimolecular fluorescence complementation in the model crop rice (Oryza sativa) to map MAP3K-interacting proteins. We identified 12 novel nonredundant interacting protein pairs (IPPs) representing 11 nonredundant interactors using 12 rice MAP3Ks (available as full-length cDNA in the rice KOME (http://cdna01.dna.affrc.go.jp/cDNA/) at the time of experimental design and execution) as bait and a rice seedling cDNA library as prey. Of the 12 MAP3Ks, only six had interacting protein partners. The established MAP3K interactome consisted of two kinases, three proteases, two forkhead-associated domain-containing proteins, two expressed proteins, one E3 ligase, one regulatory protein, and one retrotransposon protein. Notably, no MAP3K showed physical interaction with either MAP2K or MAPK. Seven IPPs (58.3%) were confirmed in vivo by bimolecular fluorescence complementation. Subcellular localization of 14 interactors, together involved in nine IPPs (75%) further provide prerequisite for biological significance of the IPPs. Furthermore, GO of identified interactors predicted their involvement in diverse physiological responses, which were supported by a literature survey. These findings increase our knowledge of the MAP3K-interacting proteins, help in proposing a model of MAPK modules, provide a valuable resource for developing a complete map of the rice MAPK interactome, and allow discussion for translating the interactome knowledge to rice crop improvement against environmental factors. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
NASA Astrophysics Data System (ADS)
Tripathy, S. C.; Ishizaka, J.; Siswanto, E.; Shibata, T.; Mino, Y.
2012-01-01
The vertically generalized production model (VGPM), which was designed for open ocean waters ( Behrenfeld and Falkowski, 1997a; henceforth BF), was evaluated using in situ measurements of primary productivity (PP) in the characteristically turbid coastal waters of Ariake Bay, southwestern Japan, to develop a regionally modified version of the model. The euphotic depth ( Z eu)-integrated PP (IPP) calculated from the VGPM using in situ chlorophyll a (Chl a) and sea surface temperature (SST) was significantly overestimated (by factors of 2-3), but 52% of the observed variability was explained. The weak correlation could have partially resulted from overestimations by the sub-models embedded in the original VGPM model for estimation of Z eu ( Morel and Berthon, 1989; henceforth MB) and the optimal Chl a-normalized PP ( poptB). The sub-model estimates of poptB and Z eu with in situpoptB and Z eu showed significant improvement, accounting for 84% of the variability and causing less overestimation. Z eu was the most important parameter influencing the modeled IPP variation in Ariake Bay. Previous research suggested that the Z eu model, which was based on surface Chl a, overestimated in situ Z eu by a factor of 2-3, resulting in weak correlation between the modeled and in situ IPP. The Z eu sub-model was not accurate in the present study area because it was basically developed for clear (case 1) waters. A better estimation of Z eu could be obtained from the in situ remote sensing reflectance ( R rs) using a quasi-analytical algorithm (QAA) in this turbid water ecosystem. Among the parameters of PP models, poptB is conventionally considered the most important. However, in this study poptB was of secondary importance because the contribution of poptB to the variation in modeled IPP was less than the contribution of Z eu. The modeled and in situpoptB were weakly correlated with 50% of the data points that overestimated the in situ values. The estimation of Chl a was improved by optimizing the Chl a algorithm with in situ R rs data. Incorporating the QAA-based Z eu and the optimized Chl a and constant (median) poptB value led to improved performance of the VGPM for the study area. Thus, even though the VGPM is a global open ocean model, when coupled with turbid water algorithms for Z eu and Chl a and constant (median) poptB, it provided realistic estimates of IPP in the turbid water ecosystem of Ariake Bay.
Conical-Domain Model for Estimating GPS Ionospheric Delays
NASA Technical Reports Server (NTRS)
Sparks, Lawrence; Komjathy, Attila; Mannucci, Anthony
2009-01-01
The conical-domain model is a computational model, now undergoing development, for estimating ionospheric delays of Global Positioning System (GPS) signals. Relative to the standard ionospheric delay model described below, the conical-domain model offers improved accuracy. In the absence of selective availability, the ionosphere is the largest source of error for single-frequency users of GPS. Because ionospheric signal delays contribute to errors in GPS position and time measurements, satellite-based augmentation systems (SBASs) have been designed to estimate these delays and broadcast corrections. Several national and international SBASs are currently in various stages of development to enhance the integrity and accuracy of GPS measurements for airline navigation. In the Wide Area Augmentation System (WAAS) of the United States, slant ionospheric delay errors and confidence bounds are derived from estimates of vertical ionospheric delay modeled on a grid at regularly spaced intervals of latitude and longitude. The estimate of vertical delay at each ionospheric grid point (IGP) is calculated from a planar fit of neighboring slant delay measurements, projected to vertical using a standard, thin-shell model of the ionosphere. Interpolation on the WAAS grid enables estimation of the vertical delay at the ionospheric pierce point (IPP) corresponding to any arbitrary measurement of a user. (The IPP of a given user s measurement is the point where the GPS signal ray path intersects a reference ionospheric height.) The product of the interpolated value and the user s thin-shell obliquity factor provides an estimate of the user s ionospheric slant delay. Two types of error that restrict the accuracy of the thin-shell model are absent in the conical domain model: (1) error due to the implicit assumption that the electron density is independent of the azimuthal angle at the IPP and (2) error arising from the slant-to-vertical conversion. At low latitudes or at mid-latitudes under disturbed conditions, the accuracy of SBAS systems based upon the thin-shell model suffers due to the presence of complex ionospheric structure, high delay values, and large electron density gradients. Interpolation on the vertical delay grid serves as an additional source of delay error. The conical-domain model permits direct computation of the user s slant delay estimate without the intervening use of a vertical delay grid. The key is to restrict each fit of GPS measurements to a spatial domain encompassing signals from only one satellite. The conical domain model is so named because each fit involves a group of GPS receivers that all receive signals from the same GPS satellite (see figure); the receiver and satellite positions define a cone, the satellite position being the vertex. A user within a given cone evaluates the delay to the satellite directly, using (1) the IPP coordinates of the line of sight to the satellite and (2) broadcast fit parameters associated with the cone. The conical-domain model partly resembles the thin-shell model in that both models reduce an inherently four-dimensional problem to two dimensions. However, unlike the thin-shell model, the conical domain model does not involve any potentially erroneous simplifying assumptions about the structure of the ionosphere. In the conical domain model, the initially four-dimensional problem becomes truly two-dimensional in the sense that once a satellite location has been specified, any signal path emanating from a satellite can be identified by only two coordinates; for example, the IPP coordinates. As a consequence, a user s slant-delay estimate converges to the correct value in the limit that the receivers converge to the user s location (or, equivalently, in the limit that the measurement IPPs converge to the user s IPP).
NASA Technical Reports Server (NTRS)
Prabahar, K. J.; Ferris, J. P.
1997-01-01
The oligomerization of adenosine 5'-phosphoro-4-(dimethylamino)pyridinium (4-(CH3)2-NpypA) and diadenosine 5',5'-pyrophosphate (A5'ppA) (9:1) on Na(+)-montmorillonite was studied. The oligomers were isolated and analyzed by selective enzymatic hydrolyses and the oligomeric composition and the percent of 3',5'-phosphodiester linkages present in each fraction was determined. The longest oligomers formed (11-mers) are slightly shorter than those produced in the absence of A5'ppA (12-mers). Smaller amounts of A5'ppA are incorporated into the oligomers than in the ImpA/A5'ppA reaction. The regioselectivity of 3',5'-phosphodiester bond formation is comparable to that of the oligomerization of 4-(CH3)2NpypA alone. An explanation of these data is proposed and the possible effect of dinucleoside pyrophosphate on prebiotic RNA formation is discussed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wizenberg, T.A.; Muz, J.; Sohn, Y.H.
1982-04-01
Ten consecutive patients with tissue-proven amyloidosis, seven of whom presented with congestive heart failure, were found to exhibit intense diffuse uptake of technetium-99m-pyrophosphate (Tc-99m-PYP) on cardiac radionuclide imaging. The patients exhibited echocardiographic and systolic time interval abnormalities suggesting combined restrictive and congestive cardiomyopathic changes. On M-mode echocardiograms, there was symmetrically increased thickness of the interventricular septum and left ventricular (LV) posterior wall in diastole (10 of 10), decreased fractional shortening of the LV minor axis diameter in systole (eight of nine), and decreased percent thickening of the LV minor axis diameter in systole (eight of nine) and LV posterior wallmore » (10 of 10) in systole. Three patients demonstrated enlarged LV end-diastolic diameter. All 10 patients had abnormal PEP/LVET and eight had shortened LVETI. When combined with noninvasive tests of LV performance, positive myocardial pyrophosphate (PYP) scanning provides a new and useful adjunct in the diagnosis of amyloid heart disease.« less
PREPARATION OF ALKYL PYROPHOSPHATE EXTRACTANTS
Levine, C.A.; Skiens, W.E.; Moore, G.R.
1960-08-01
A process for providing superior solvent extractants for metal recovery processes is given wherein the extractant comprises an alkyl pyrophosphoric acid ester dissolved in an organic solvent diluent. Finely divided solid P/sub 2/O/ sub 5/ is slurried in an organic solvent-diluent selected from organic solvents such as kerosene, benzene, chlorobenzene, toluene, etc. An alcohol selected from the higher alcohols having 4 to 17 carbon atoms. e.g.. hexanol-1. heptanol-3, octanol-1. 2.6-dimethyl-heptanol-4, and decanol-1, is rapidly added to the P/sub 2/O/sub 5/ slurry in the amount of about 2 moles of alcohol to 1 mole of P/sub 2/ O/sub 5/. The temperature is maintained below about 110 deg C during the course of the P/sub 2/O/sub 5/-alcohol reaction. An alkyl pyrophosphate extractant compound is formed as a consequence of the reaction process. The alkyl pyrophosphate solvent-diluent extractant phase is useful in solvent extraction metal recovery processes.
The Thiamin Pyrophosphate-Motif
NASA Technical Reports Server (NTRS)
Dominiak, Paulina M.; Ciszak, Ewa M.
2003-01-01
Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits, two catalytic centers, common amino acid sequence, and specific contacts to provide a flip-flop, or alternate site, mechanism of action. Each catalytic center [PP:PYR] is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and aminopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core [PP:PYR]* within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GX@&(G)@XXGQ, and GDGX25-30 within the PP- domain, and the E&(G)@XXG@ within the PYR-domain, where Q, corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-02
...This notice contains the final wage indices, hospital reclassifications, payment rates, impacts, and other related tables effective for the fiscal year (FY) 2010 hospital inpatient prospective payment systems (IPPS) and rate year 2010 long-term care hospital (LTCH) prospective payment system (PPS). The rates, tables, and impacts included in this notice reflect changes required by or resulting from the implementation of several provisions of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010. These provisions require the extension of the expiration date for certain geographic reclassifications and special exception wage indices through September 30, 2010; and certain market basket updates for the IPPS and LTCH PPS.
Rivas, Manuel; Casanovas, Jordi; del Valle, Luis J; Bertran, Oscar; Revilla-López, Guillermo; Turon, Pau; Puiggalí, Jordi; Alemán, Carlos
2015-06-07
The adsorption of orthophosphate, pyrophosphate, triphosphate and a trisphosphonate onto hydroxyapatite has been examined using experiments and quantum mechanical calculations. Adsorption studies with FTIR and X-ray photoelectron spectroscopies have been performed considering both crystalline hydroxyapatite (HAp) and amorphous calcium phosphate particles, which were specifically prepared and characterized for this purpose. Density functional theory (DFT) calculations have been carried out considering the (100) and (001) surfaces of HAp, which were represented using 1 × 2 × 2 and 3 × 3 × 1 slab models, respectively. The adsorption of phosphate onto the two crystallographic surfaces is very much favored from an energetic point of view, which is fully consistent with current interpretations of the HAp growing process. The structures calculated for the adsorption of pyrophosphate and triphosphate evidence that this process is easier for the latter than for the former. Thus, the adsorption of pyrophosphate is severely limited by the surface geometry while the flexibility of triphosphate allows transforming repulsive electrostatic interactions into molecular strain. On the other hand, calculations predict that the trisphosphonate only adsorbs onto the (001) surface of HAp. Theoretical predictions are fully consistent with experimental data. Thus, comparison of DFT results and spectroscopic data suggests that the experimental conditions used to prepare HAp particles promote the predominance of the (100) surface. Accordingly, experimental identification of the adsorption of trisphosphonate onto such crystalline particles is unclear while the adsorption of pyrophosphate and triphosphate is clearly observed.
CRYSTALLINE INORGANIC PYROPHOSPHATASE ISOLATED FROM BAKER'S YEAST
Kunitz, M.
1952-01-01
Crystalline inorganic pyrophosphatase has been isolated from baker's yeast. The crystalline enzyme is a protein of the albumin type with an isoelectric point near pH 4.8. Its molecular weight is of the order of 100,000. It contains about 5 per cent tyrosine and 3.5 per cent tryptophane. It is most stable at pH 6.8. The new crystalline protein acts as a specific catalyst for the hydrolysis of inorganic pyrophosphate into orthophosphate ions. It does not catalyze the hydrolysis of the pyrophosphate radical of such organic esters as adenosine di- and triphosphate, or thiamine pyrophosphate. Crystalline pyrophosphatase requires the presence of Mg, Co, or Mn ions as activators. These ions are antagonized by calcium ions. Mg is also antagonized by Co or Mn ions. The rate of the enzymatic hydrolysis of inorganic pyrophosphate is proportional to the concentration of enzyme and is a function of pH, temperature, concentration of substrate, and concentration of activating ion. The approximate conditions for optimum rate are: 40°C. and pH 7.0 at a concentration of 3 to 4 x 10–3 M Na4P2O7 and an equivalent concentration of magnesium salt. The enzymatic hydrolysis of Na4P2O7 or K4P2O7 proceeds to completion and is irreversible under the conditions at which hydrolysis is occurring. Details are given of the method of isolation of the crystalline enzyme. PMID:14898026
NASA Astrophysics Data System (ADS)
Ausaf, Muhammad Farhan; Gao, Liang; Li, Xinyu
2015-12-01
For increasing the overall performance of modern manufacturing systems, effective integration of process planning and scheduling functions has been an important area of consideration among researchers. Owing to the complexity of handling process planning and scheduling simultaneously, most of the research work has been limited to solving the integrated process planning and scheduling (IPPS) problem for a single objective function. As there are many conflicting objectives when dealing with process planning and scheduling, real world problems cannot be fully captured considering only a single objective for optimization. Therefore considering multi-objective IPPS (MOIPPS) problem is inevitable. Unfortunately, only a handful of research papers are available on solving MOIPPS problem. In this paper, an optimization algorithm for solving MOIPPS problem is presented. The proposed algorithm uses a set of dispatching rules coupled with priority assignment to optimize the IPPS problem for various objectives like makespan, total machine load, total tardiness, etc. A fixed sized external archive coupled with a crowding distance mechanism is used to store and maintain the non-dominated solutions. To compare the results with other algorithms, a C-matric based method has been used. Instances from four recent papers have been solved to demonstrate the effectiveness of the proposed algorithm. The experimental results show that the proposed method is an efficient approach for solving the MOIPPS problem.
NASA Astrophysics Data System (ADS)
Husin, Asnawi; Abdullah, M.; Momani, M. A.
2011-04-01
Using vertical total electron content (VTEC) data that were derived from the Malaysia Real Time Kinematic GPS network (MyRTKnet), we analyzed the time variation of the VTEC with the occurrence of medium-scale traveling ionospheric disturbances (MSTIDs) based on ionospheric pierce point (IPP) trajectories. MSTIDs are known as ionospheric disturbance phenomena that generally induce perturbations in important ionospheric parameters such as the ionospheric total electron content (TEC). A method was developed to detect the existence of MSTIDs by identifying rapid fluctuations in the TEC by subjecting the TEC data time series to high-pass filtering. Data were evaluated using the GPS MyRTKnet network over Peninsular Malaysia in the month of September 2007 (a time period with relatively low geomagnetic activity). Two-dimensional maps over Peninsular Malaysia were constructed based on the IPP trajectories. Analysis of the cross correlation of detrended VTEC data from six MyRTKnet stations (PASP, KRAI, GMUS, CAME, TLKI and SBKB) yielded MSTID velocities of around 100 ± 50 m s-1 in the daytime and 60 ± 30 m s-1 in the nighttime, with occurrences of 17.6% and 13.7%, respectively. The results show that although the MSTID wave structure propagates southwestward, some waves also move northward. These waves were connected to the effect of the meridional neutral wind in the upper regions of the ionosphere (400 km).
Mixing of Isotactic and Syndiotactic Polypropylenes in the Melt
DOE Office of Scientific and Technical Information (OSTI.GOV)
CLANCY,THOMAS C.; PUTZ,MATHIAS; WEINHOLD,JEFFREY D.
2000-07-14
The miscibility of polypropylene (PP) melts in which the chains differ only in stereochemical composition has been investigated by two different procedures. One approach used detailed local information from a Monte Carlo simulation of a single chain, and the other approach takes this information from a rotational isomeric state model devised decades ago, for another purpose. The first approach uses PRISM theory to deduce the intermolecular packing in the polymer blend, while the second approach uses a Monte Carlo simulation of a coarse-grained representation of independent chains, expressed on a high-coordination lattice. Both approaches find a positive energy change uponmore » mixing isotactic PP (iPP) and syndiotactic polypropylene (sPP) chains in the melt. This conclusion is qualitatively consistent with observations published recently by Muelhaupt and coworkers. The size of the energy chain on mixing is smaller in the MC/PRISM approach than in the RIS/MC simulation, with the smaller energy change being in better agreement with the experiment. The RIS/MC simulation finds no demixing for iPP and atactic polypropylene (aPP) in the melt, consistent with several experimental observations in the literature. The demixing of the iPP/sPP blend may arise from attractive interactions in the sPP melt that are disrupted when the sPP chains are diluted with aPP or iPP chains.« less
Woo, Tae-Gyun; Yoon, Min-Ho; Hong, Shin-Deok; Choi, Jiyun; Ha, Nam-Chul; Sun, Hokeun; Park, Bum-Joon
2017-04-04
Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human cancer and speculated as a target of novel anti-tumor drug. In previous, we also showed that PAK1 is highly activated in the Smad4-deficient condition and suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding and phosphorylation. On the basis of this result, we have tried to find novel PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA), which selectively blocks the PAK1-PUMA binding and also suppresses cell proliferation via PUMA-dependent manner. Indeed, in PUMA-deficient cells, this chemical did not show anti-proliferating effect. This chemical possessed very strong PAK1 inhibition activity that it suppressed BAD (Bcl-2-asoociated death promoter) phosphorylation and meta-phase arrest via Aurora kinase inactivation in lower concentration than that of previous PAK1 kinase, FRAX486 and AG879. Moreover, our chemical obviously induced p21/WAF1/CIP1 (Cyclin-dependent kinase inhibitor 1A) expression by releasing from Bcl-2 (B-cell lymphoma-2) and by inhibition of AKT-mediated p21 suppression. Considering our result, IPP-14 and its derivatives would be possible candidates for PAK1 and p21 induction targeted anti-cancer drug.
The 140 GHZ, 1 MW Gyrotron - Status and Recent Results
NASA Astrophysics Data System (ADS)
Gantenbein, G.; Dammertz, G.; Illy, S.; Kern, S.; Leonhardt, W.; Piosczyk, B.; Schmid, M.; Thumm, M.; Braune, H.; Erckmann, V.; Laqua, H. P.; Michel, G.; Kasparek, W.; Lechte, C.; Legrand, F.; Lievin, C.; Prinz, O.
2009-04-01
A 10 MW ECRH system is currently under construction for the stellarator W7-X which will be built up and operated by IPP in Greifswald, Germany. The present status of the complete system is reported in [1]. The RF power will be provided by 10 gyrotrons. A European collaboration has been established to develop and build the 10 gyrotrons each with an output power of 1 MW for continuous wave (CW) operation [2]. Nine gyrotrons are being manufactured by Thales Electron Devices (TED), Vélizy, France, one gyrotron was produced by CPI, Palo Alto, CA and passed the acceptance tests at IPP. The acceptance tests of the TED gyrotrons are performed at the test stand at FZK and on site at IPP. The first series tube yielded a total output power of 0.98 MW, with an efficiency of 31 % (without a single stage depressed collector) in short pulse operation and of 0.92 MW in pulses of 1800 s (efficiency of almost 45 % at a depression voltage of 29 kV) [3], The Gaussian mode output power was 0.91 MW. The RF power, measured in a calorimetric load at the end of a 25 m long quasi-optical transmission line with seven mirrors, was 0.87 MW. In this contribution typical results of the next series gyrotrons will be reported.
Bristow, S M; Gamble, G D; Pasch, A; O'Neill, W C; Stewart, A; Horne, A M; Reid, I R
2016-03-01
Calcium supplements have been associated with increased cardiovascular risk, but the mechanism is unknown. We investigated the effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50). Changes in serum calcium were related to changes in T50. Calcium supplements have been associated with increased cardiovascular risk; however, it is unknown whether this is related to an increase in vascular calcification. We investigated the acute and 3-month effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50), and on three possible regulators of calcification: fetuin-A, pyrophosphate and fibroblast growth factor-23 (FGF23). We randomized 41 postmenopausal women to 1 g/day of calcium as carbonate, or to a placebo containing no calcium. Measurements were performed at baseline and then 4 and 8 h after their first dose, and after 3 months of supplementation. Fetuin-A, pyrophosphate and FGF23 were measured in the first 10 participants allocated to calcium carbonate and placebo who completed the study. T50 declined in both groups, the changes tending to be greater in the calcium group. Pyrophosphate declined from baseline in the placebo group at 4 h and was different from the calcium group at this time point (p = 0.04). There were no other significant between-groups differences. The changes in serum total calcium from baseline were significantly related to changes in T50 at 4 h (r = -0.32, p = 0.05) and 8 h (r = -0.39, p = 0.01), to fetuin-A at 3 months (r = 0.57, p = 0.01) and to pyrophosphate at 4 h (r = 0.61, p = 0.02). These correlative findings suggest that serum calcium concentrations modulate the propensity of serum to calcify (T50), and possibly produce counter-regulatory changes in pyrophosphate and fetuin-A. This provides a possible mechanism by which calcium supplements might influence vascular calcification.
Taste and acceptance of pyrophosphates by rats and mice.
McCaughey, Stuart A; Giza, Barbara K; Tordoff, Michael G
2007-06-01
The palatability and taste quality of pyrophosphates were evaluated in a series of behavioral and electrophysiological experiments. In two-bottle choice tests with water, rats strongly preferred some concentrations of Na3HP2O7 and Na4P2O7, moderately preferred some concentrations of K4P2O7 and Fe4(P2O7)3, and were indifferent to or avoided all concentrations of Ca2P2O7 and Na2H2P2O7. The contribution of sodium to the preference for sodium pyrophosphates was ascertained: 1) Rats with a choice between Na4P2O7 and NaCl preferred 1 mM Na4P2O7 to 4 mM NaCl but preferred 40 or 150 mM NaCl to 10 mM Na4P2O7, 2) blocking salt taste transduction by mixing Na4P2O7 with amiloride reduced preferences but did not eliminate them, and 3) three mouse strains (FVB/J, C57BL/6J, and CBA/J) known to differ in sodium preference had the same rank order of preferences for Na3HP2O7 and NaCl, but peak preferences were higher for Na3HP2O7 than for NaCl. The taste qualities of pyrophosphates were determined by measuring taste-evoked responses of neurons in the nucleus of the solitary tract of rats. Across-neuron patterns of activity for sodium pyrophosphates were similar to that of NaCl but the pattern of Na3HP2O7 plus amiloride was unique from those of sweet, salty, sour, bitter, and umami stimuli. Taken together, the results indicate that the high palatability of some concentrations of Na3HP2O7 and Na4P2O7 is due partially to their salty taste, but there must also be another cause, which may include a novel orosensory component distinct from the five major taste qualities.
Ceramic High Efficiency Particulate Air (HEPA) Filter Final Report CRADA No. TC02102.0
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mitchell, M.; Morse, T.
This was a collaborative effort between Lawrence Livermore National Security, LLC (formerly The Regents of the University of California)/Lawrence Livermor e National Laboratory (LLNL) and Flanders-Precisionaire (Flanders), to develop ceramic HEP A filters under a Thrust II Initiative for Proliferation Prevention (IPP) project. The research was conducted via the IPP Program at Commonwe alth of Independent States (CIS) Institutes, which are handled under a separate agreement. The institutes (collectively referred to as "CIS Institutes") involved with this project were: Bochvar: Federal State Unitarian Enterprise All-Russia Scientific and Research Institute of Inorganic Materials (FSUE VNIINM); Radium Khlopin: Federal State Unitarian Enterprisemore » NPO Radium Institute named (FSUE NPO Radium Institute); and Bakor: Science and Technology Center Bakor (STC Bakor).« less
Kraus, W; Briefi, S; Fantz, U; Gutmann, P; Doerfler, J
2014-02-01
Large RF driven negative hydrogen ion sources are being developed at IPP Garching for the future neutral beam injection system of ITER. The overall power efficiency of these sources is low, because for the RF power supply self-excited generators are utilized and the plasma is generated in small cylindrical sources ("drivers") and expands into the source main volume. At IPP experiments to reduce the primary power and the RF power required for the plasma production are performed in two ways: The oscillator generator of the prototype source has been replaced by a transistorized RF transmitter and two alternative driver concepts, a spiral coil, in which the field is concentrated by ferrites, which omits the losses by plasma expansion and a helicon source are being tested.
Déprescrire les inhibiteurs de la pompe à protons
Farrell, Barbara; Pottie, Kevin; Thompson, Wade; Boghossian, Taline; Pizzola, Lisa; Rashid, Farah Joy; Rojas-Fernandez, Carlos; Walsh, Kate; Welch, Vivian; Moayyedi, Paul
2017-01-01
Résumé Objectif Formuler des lignes directrices fondées sur les données probantes pour aider les cliniciens à décider du moment et de la façon sécuritaire de réduire la dose des inhibiteurs de la pompe à protons (IPP) ou d’en arrêter le traitement; se concentrer sur le niveau le plus élevé des données disponibles et obtenir les commentaires des professionnels de première ligne durant le processus de rédaction, de révision et d’adoption des lignes directrices. Méthodologie L’équipe était formée de 5 professionnels de la santé (1 médecin de famille, 3 pharmaciens et 1 gastro-entérologue) et de 5 membres sans droit de vote; les membres ont divulgué tout conflit d’intérêts. Le processus d’élaboration des lignes directrices a eu recours à l’approche GRADE (Grading of Recommendations Assessment, Development and Evaluation), de même qu’à un examen minutieux des données probantes dans le cadre de rencontres en personne, au téléphone et en ligne. Particulièrement, le processus d’élaboration des lignes directrices a inclus une revue systématique d’essais portant sur la déprescription des IPP et un examen de comptes rendus sur les torts liés à l’emploi continu des IPP. Les synthèses narratives sur les préférences des patients ainsi que les publications traitant des répercussions sur les ressources ont éclairé les recommandations. L’équipe a peaufiné le texte sur le contenu et les recommandations des lignes directrices par consensus, et a synthétisé les considérations cliniques afin de répondre aux questions courantes des cliniciens de première ligne. Une version préliminaire des lignes directrices a été distribuée aux cliniciens, puis aux associations de professionnels de la santé aux fins d’examen, et des révisions ont été apportées au texte à chaque étape. Un algorithme d’appui décisionnel a été conçu de concert avec les lignes directrices. Recommandations Les présentes lignes directrices recommandent de déprescrire les IPP (réduire la dose, mettre fin au traitement ou passer à l’administration « sur demande ») chez les adultes qui ont terminé un traitement d’au moins 4 semaines avec un IPP contre le pyrosis, l’œsophagite ou le reflux gastro-œsophagien léger à modéré, et dont les symptômes sont disparus. Les recommandations ne s’appliquent pas aux patients atteints ou qui ont déjà été atteints de l’œsophage de Barrett, d’une œsophagite grave de stade C ou D, ou d’antécédents connus d’ulcères gastro-intestinaux hémorragiques. Conclusion Les présentes lignes directrices émettent des recommandations pratiques pour décider du moment et de la façon de réduire la dose des inhibiteurs de la pompe à protons (IPP) ou d’en arrêter le traitement. Elles visent à contribuer au processus de décision conjointement avec le patient et non à dicter la décision.
Chen, Chong-Maw; Kristopeit, Susan M.
1981-01-01
Two forms (F-I and F-II) of 5′-nucleotidases (5′-ribonucleotide phosphohydrolase, EC 3.1.3.5) which catalyze the dephosphorylation of N6-(Δ2-isopentenyl)adenosine 5′-monophosphate and AMP to form the corresponding nucleosides were partially purified from the cytosol of wheat (Triticum aestivum) germ. Both the F-I (molecular weight, 57,000) and F-II (molecular weight, 110,000) 5′-nucleotidases dephosphorylate the ribonucleotides at an optimum pH of 7. The Km values for the cytokinin nucleotide are 3.5 micromolar (F-I enzyme) and 12.8 micromolar (F-II enzyme) in 100 millimolar Tris-maleate buffer (pH 7) at 37 C. The F-I enzyme is less rapidly inactivated by heating than is the F-II enzyme. Both nucleotidases hydrolyze purine ribonucleoside 5′-phosphates, AMP being the preferred substrate. N6-(Δ2-isopentenyl)Adenosine 5′-monophosphate is hydrolyzed at a rate 72 and 86% that of AMP by the F-I and F-II nucleotides, respectively. Phenylphosphate and 3′-AMP are not substrates for the enzymes. It is proposed that dephosphorylation of cytokinin nucleotide by cytosol 5′-nucleotidases may play an important role in regulating levels of “active cytokinin” in plant cells. PMID:16661701
Hatch, Nan E; Li, Yan; Franceschi, Renny T
2009-01-01
Pyrophosphate is an established inhibitor of hydroxyapatite deposition and crystal growth, yet when hydrolyzed into phosphate, it becomes a substrate for hydroxyapatite deposition. Pyrophosphate-generating enzyme (PC-1), Ank, and tissue nonspecific alkaline phosphatase (Tnap) are three factors that regulate extracellular pyrophosphate levels through its generation, transport, and hydrolysis. We previously showed that fibroblast growth factor 2 (FGF2) induces PC-1 and Ank while inhibiting Tnap expression and mineralization in MC3T3E1(C4) calvarial pre-osteoblast cells. In this study, we showed similar FGF2 regulation of these genes in primary pre-osteoblast cultures. In contrast to Ank and Tnap that are regulated by FGF2 in multiple cell types, we found regulation of PC-1 to be selective to pre-osteoblastic cells and to require the osteoblast-related transcription factor, Runx2. Specifically, FGF2 was unable to induce PC-1 expression in Runx2-negative nonbone cells or in calvarial cells from Runx2-deficient mice. Transfection of these cells with a Runx2 expression vector restored FGF2 responsiveness. FGF2 was also shown to stimulate recruitment of Runx2 to the endogenous PC-1 promoter in MC3T3E1(C4) cells, as measured by chromatin immunoprecipitation. Taken together, our results establish that FGF2 is a specific inducer of PC-1 in pre-osteoblast cells and that FGF2 induces PC-1 expression through a mechanism involving Runx2. PMID:19049325
Effects of regular and whitening dentifrices on remineralization of bovine enamel in vitro.
Kielbassa, Andrej M; Tschoppe, Peter; Hellwig, Elmar; Wrbas, Karl-Thomas
2009-02-01
To compare in vitro the remineralizing effects of different regular dentifrices and whitening dentifrices (containing pyrophosphates) on predemineralized enamel. Specimens from 84 bovine incisors were embedded in epoxy resin, partly covered with nail varnish, and demineralized in a lactic acid solution (37 degrees C, pH 5.0, 8 days). Parts of the demineralized areas were covered with nail varnish, and specimens were randomly assigned to 6 groups. Subsequently, specimens were exposed to a remineralizing solution (37 degrees C, pH 7.0, 60 days) and brushed 3 times a day (1:3 slurry with remineralizing solution) with 1 of 3 regular dentifrices designed for anticaries (group 1, amine; group 2, sodium fluoride) or periodontal (group 3, amine/stannous fluoride) purposes or whitening dentifrice containing pyrophosphates (group 4, sodium fluoride). An experimental dentifrice (group 5, without pyrophosphates/fluorides) and a whitening dentifrice (group 6, monofluorophosphate) served as controls. Mineral loss and lesion depths were evaluated from contact microradiographs, and intergroup comparisons were performed using the closed-test procedure (alpha =.05). Compared to baseline, specimens brushed with the dentifrices containing stannous/amine fluorides revealed significant mineral gains and lesion depth reductions (P < .05). Concerning the reacquired mineral, the whitening dentifrice performed worse than the regular dentifrices (P > .05), while mineral gain, as well as lesion depth, reduction was negligible with the control groups. Dentifrices containing pyrophosphates perform worse than regular dentifrices but do not necessarily affect remineralization. Unless remineralizing efficacy is proven, whitening dentifrices should be recommended only after deliberate consideration in caries-prone patients.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gertz, M.A.; Brown, M.L.; Hauser, M.F.
Thirty-four patients with amyloidosis proved by biopsy specimen were studied using technetium Tc 99m pyrophosphate scintigraphy to assess its utility in the diagnosis of amyloid heart involvement. Of 14 patients studied retrospectively, only three had intense uptake judged to be diagnostic of cardiac amyloidosis. In a prospective analysis of 20 patients with amyloidosis, all of whom had evidence of cardiac involvement by two-dimensional echocardiography, 17 had abnormal scans. Fourteen of the 17 scans had only 1+ or 2+ uptake, a finding that also was present in 15 of the 20 control patients (without amyloid heart disease). Only three of themore » 20 patients with cardiac amyloidosis had intense uptake that was considered unequivocal and diagnostic of amyloidosis. Of the five patients with biopsy specimen proof of endomyocardial amyloidosis, only one had intense uptake and one had no uptake. When intense uptake of technetium Tc 99m pyrophosphate is found in the heart of a patient, amyloidosis is highly likely. The technique, however, is not sufficiently sensitive to warrant routine screening of patients with amyloidosis or cardiomyopathies. Cross-sectional echocardiography is superior to pyrophosphate scintigraphy for recognition of cardiac amyloidosis.« less
Label-Free Pyrophosphate Recognition with Functionalized Asymmetric Nanopores.
Ali, Mubarak; Ahmed, Ishtiaq; Ramirez, Patricio; Nasir, Saima; Niemeyer, Christof M; Mafe, Salvador; Ensinger, Wolfgang
2016-04-01
The label-free detection of pyrophosphate (PPi) anions with a nanofluidic sensing device based on asymmetric nanopores is demonstrated. The pore surface is functionalized with zinc complexes based on two di(2-picolyl)amine [bis(DPA)] moieties using carbodiimide coupling chemistry. The complexation of zinc (Zn(2+) ) ion is achieved by exposing the modified pore to a solution of zinc chloride to form bis(Zn(2+) -DPA) complexes. The chemical functionalization is demonstrated by recording the changes in the observed current-voltage (I-V) curves before and after pore modification. The bis(Zn(2+) -DPA) complexes on the pore walls serve as recognition sites for pyrophosphate anion. The experimental results show that the proposed nanofluidic sensor has the ability to sense picomolar concentrations of PPi anion in the surrounding environment. On the contrary, it does not respond to other phosphate anions, including monohydrogen phosphate, dihydrogen phosphate, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate. The experimental results are described theoretically by using a model based on the Poisson-Nernst-Planck equations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Structural genes for thiamine biosynthetic enzymes (thiCEFGH) in Escherichia coli K-12.
Vander Horn, P B; Backstrom, A D; Stewart, V; Begley, T P
1993-01-01
Escherichia coli K-12 synthesizes thiamine pyrophosphate (vitamin B1) de novo. Two precursors [4-methyl-5-(beta-hydroxyethyl)thiazole monophosphate and 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophosphate] are coupled to form thiamine monophosphate, which is then phosphorylated to make thiamine pyrophosphate. Previous studies have identified two classes of thi mutations, clustered at 90 min on the genetic map, which result in requirements for the thiazole or the hydroxymethylpryimidine. We report here our initial molecular genetic analysis of the thi cluster. We cloned the thi cluster genes and examined their organization, structure, and function by a combination of phenotypic testing, complementation analysis, polypeptide expression, and DNA sequencing. We found five tightly linked genes, designated thiCEFGH. The thiC gene product is required for the synthesis of the hydroxymethylpyrimidine. The thiE, thiF, thiG, and thiH gene products are required for synthesis of the thiazole. These mutants did not respond to 1-deoxy-D-threo-2-pentulose, indicating that they are blocked in the conversion of this precursor compound to the thiazole itself. Images PMID:8432721
Mawai, Kiran; Nathani, Sandip; Roy, Partha; Singh, U P; Ghosh, Kaushik
2018-05-08
A compartmental chemosensor probe HL has been designed and synthesized for the selective recognition of zinc ions over other transition metal ions via fluorescence "ON" strategy. The chemosensing behaviour of HL was demonstrated through fluorescence, absorption and NMR spectroscopic techniques. The molecular structure of the zinc complex derived from HL was determined by X-ray crystallography. A probable mechanism of this selective sensing behavior was described on the basis of spectroscopic results and theoretical studies by density functional theory (DFT). The biological applicability of the chemosensor HL was examined via cell imaging on HeLa cells. The HL-zinc complex served as a secondary fluorescent probe responding to the pyrophosphate anion specifically over other anions. The fluorescence enhancement of HL in association with Zn2+ ions was quenched in the presence of pyrophosphate (PPi). Thus, a dual response was established based on "OFF-ON-OFF" strategy for detection of both cation and anion. This phenomenon was utilized in the construction of a "INHIBIT" logic gate.
Mobarak, E H
2011-01-01
To evaluate the influence of 2% and 5% chlorhexidine (CHX) pretreatment on bond durability of a self-etching adhesive to normal (ND) and caries-affected (AD) dentin after 2-years of aging in artificial saliva and under simulated intrapulpal pressure (IPP). One hundred twenty freshly extracted carious teeth were ground to expose ND and AD. Specimens were distributed into three equal groups (n=40) according to whether the dentin substrates were pretreated with 2% or 5% CHX or with water (control). Clearfil SE Bond (Kuraray) was applied to both substrates and composite cylinders (0.9 mm diameter and 0.7 mm height) were formed. Pretreatment and bonding were done while the specimens were subjected to 15 mm Hg IPP. After curing, specimens were aged in artificial saliva at 37°C and under IPP at 20 mm Hg until being tested after 24 hours or 2 years (n=20/group). Microshear bond strength was evaluated. Failure modes were determined using a scanning electron microscope (SEM) at 400× magnification. Data were statistically analyzed using three-way analysis of variance (ANOVA); one-way ANOVA tests, and t-test (p<0.05). Additional specimens (n=5/group) were prepared to evaluate interfacial silver precipitation. For the 24-hour groups, there were no significant differences among the ND groups and AD groups. For ND aged specimens, the 5% CHX group had the highest value followed by the 2% CHX and control groups, although the difference was statistically insignificant. For AD aged specimens, the 5% CHX group revealed statistically higher bond values compared to the 2% CHX and control groups. Fracture modes were predominately adhesive and mixed. Different interfacial silver depositions were recorded. Two percent or 5% CHX pretreatment has no adverse effect on the 24-hour bonding to ND and AD. Five percent CHX was able to diminish the loss in bonding to AD after 2years of aging in artificial saliva and under simulated IPP.
Lu, Shasha; Zhou, Min; Guan, Xingliang; Tao, Lizao
2015-03-01
A large number of mathematical models have been developed for supporting optimization of land-use allocation; however, few of them simultaneously consider land suitability (e.g., physical features and spatial information) and various uncertainties existing in many factors (e.g., land availabilities, land demands, land-use patterns, and ecological requirements). This paper incorporates geographic information system (GIS) technology into interval-probabilistic programming (IPP) for land-use planning management (IPP-LUPM). GIS is utilized to assemble data for the aggregated land-use alternatives, and IPP is developed for tackling uncertainties presented as discrete intervals and probability distribution. Based on GIS, the suitability maps of different land users are provided by the outcomes of land suitability assessment and spatial analysis. The maximum area of every type of land use obtained from the suitability maps, as well as various objectives/constraints (i.e., land supply, land demand of socioeconomic development, future development strategies, and environmental capacity), is used as input data for the optimization of land-use areas with IPP-LUPM model. The proposed model not only considers the outcomes of land suitability evaluation (i.e., topography, ground conditions, hydrology, and spatial location) but also involves economic factors, food security, and eco-environmental constraints, which can effectively reflect various interrelations among different aspects in a land-use planning management system. The case study results at Suzhou, China, demonstrate that the model can help to examine the reliability of satisfying (or risk of violating) system constraints under uncertainty. Moreover, it may identify the quantitative relationship between land suitability and system benefits. Willingness to arrange the land areas based on the condition of highly suitable land will not only reduce the potential conflicts on the environmental system but also lead to a lower economic benefit. However, a strong desire to develop lower suitable land areas will bring not only a higher economic benefit but also higher risks of violating environmental and ecological constraints. The land manager should make decisions through trade-offs between economic objectives and environmental/ecological objectives.
NASA Astrophysics Data System (ADS)
Yoon, Joonsung
The primary objective of this research is to investigate the morphological and mechanical properties of composite materials and porous materials prepared by thermally induced phase separation. High melting crystallizable diluents were mixed with polymers so that the phase separation would be induced by the solidification of the diluents upon cooling. Theoretical phase diagrams were calculated using Flory-Huggins solution thermodynamics which show good agreement with the experimental results. Porous materials were prepared by the extraction of the crystallized diluents after cooling the mixtures (hexamethylbenzene/polyethylene and pyrene/polyethylene). Anisotropic structures show strong dependence on the identity of the diluents and the composition of the mixtures. Anisotropic crystal growth of the diluents was studied in terms of thermodynamics and kinetics using DSC, optical microscopy and SEM. Microstructures of the porous materials were explained in terms of supercooling and dendritic solidification. Dual functionality of the crystallizable diluents for composite materials was evaluated using isotactic polypropylene (iPP) and compatible diluents that crystallize upon cooling. The selected diluents form homogeneous mixtures with iPP at high temperature and lower the viscosity (improved processability), which undergo phase separation upon cooling to form solid particles that function as a toughening agent at room temperature. Tensile properties and morphology of the composites showed that organic crystalline particles have the similar effect as rigid particles to increase toughness; de-wetting between the particle and iPP matrix occurs at the early stage of deformation, followed by unhindered plastic flow that consumes significant amount of fracture energy. The effect of the diluents, however, strongly depends on the identity of the diluents that interact with the iPP during solidification step, which was demonstrated by comparing tetrabromobisphenol-A and phthalic anhydride. A simple method to prepare composite surfaces that can change the wettability in response to the temperature change was proposed and evaluated. Composite surfaces prepared by nanoporous alumina templates filled with polymers showed surface morphology and wettability that depend on temperature. This effect is attributed to the significant difference in thermal conductivity and the thermal expansion coefficient between the alumina and the polymers. The reversibility in thermal response depends on the properties of the polymers.
Technetium-99m Pyrophosphate: Comparison of ED50 for Tetany and Acidosis with Acute LD500
electrocardiogram and chemical analysis revealed that the hypocalcemic effect occurs at a much lower dosage than for the LD50. Polyphosphate was found to be more...toxic by the LD50 analysis than pyrophosphate. It is emphasized that the hypocalcemic toxic effects should be the determining factor in deciding what...to 1 with regard to the first signs of hypocalcemia by electrocardiographic measurements (i.e., 2 mg/kg). On this basis an injection of no more than 1 mg/kg is recommended to maintain a safety factor of around 10 to 1.
Zhang, Qingfeng; Zhang, Cuiyun; Yang, Meiding; Yu, Donghong; Yu, Cong
2017-11-01
A sensitive and convenient flow-injection chemiluminescence (FI-CL) turn-on assay for alkaline phosphatase (ALP) activity without any label and synthesis is developed. Cu 2+ can catalyze the luminol-H 2 O 2 CL reaction. Pyrophosphate (PPi) can chelate Cu 2+ and therefore the Cu 2+ -mediated luminol-H 2 O 2 CL reaction is inhibited. The addition of ALP can catalyze the hydrolysis of PPi into phosphate ions, Cu 2+ is released and the chemiluminescence recovers. A detection limit of 1 mU/mL ALP is obtained. Copyright © 2017 John Wiley & Sons, Ltd.
D-lysergic acid-activating enzyme from the ergot fungus Claviceps purpurea.
Keller, U; Zocher, R; Krengel, U; Kleinkauf, H
1984-01-01
A D-lysergic acid-activating enzyme from the ergot fungus Claviceps purpurea was purified about 145-fold. The enzyme was able to catalyse both the D-lysergic acid-dependent ATP-pyrophosphate exchange and the formation of ATP from D-lysergic acid adenylate and pyrophosphate. Both reactions were also catalysed to a decreased but significant extent with respect to dihydrolysergic acid. The molecular mass of the enzyme was estimated to lie between 135 and 140 kDa. The involvement of the enzyme in the biosynthesis of ergot peptide alkaloids is discussed. Images Fig. 4. PMID:6326747
Selective detection of pyrophosphate anion by a simple Cd(II) based terpyridine complex
NASA Astrophysics Data System (ADS)
Purohit, Aditya Kumar; Ghosh, Biswa Nath; Kar, Pravin Kumar
2018-01-01
A simple ratiometric terpyridine-Cd(ll) complex was synthesized by the treatment of CdCl2 with terpyridine ligand 4‧-(4-N,N‧-dimethylaminophenyl)-2,2‧:6‧,2″-terpyridine. The synthesized complex was found to act as a selective fluorescent chemosensor for pyrophosphate P2O74 - (PPi) over other anions like F-, Cl-, Br-, CO32 -, SO32 -, AcO-, NO2-, and H2PO4-. Furthermore, the receptor probe was also successfully employed in HeLa cell for PPi detection, which indicates this can be used as a chemosensor for cells.
Cyclic peptide unguisin A is an anion receptor with high affinity for phosphate and pyrophosphate.
Daryl Ariawan, A; Webb, James E A; Howe, Ethan N W; Gale, Philip A; Thordarson, Pall; Hunter, Luke
2017-04-05
Unguisin A (1) is a marine-derived, GABA-containing cyclic heptapeptide. The biological function of this flexible macrocycle is obscure. Here we show that compound 1 lacks any detectable activity in antimicrobial growth inhibition assays, a result that runs contrary to a previous report. However, we find that 1 functions as a promiscuous host molecule in a variety of anion-binding interactions, with high affinity particularly for phosphate and pyrophosphate. We also show that a series of rigidified, backbone-fluorinated analogues of 1 displays altered affinity for chloride ions.
2013-01-01
Background Molecules involved in pheromone biosynthesis may represent alternative targets for insect population control. This may be particularly useful in managing the reproduction of Lutzomyia longipalpis, the main vector of the protozoan parasite Leishmania infantum in Latin America. Besides the chemical identity of the major components of the L. longipalpis sex pheromone, there is no information regarding the molecular biology behind its production. To understand this process, obtaining information on which genes are expressed in the pheromone gland is essential. Methods In this study we used a transcriptomic approach to explore the pheromone gland and adjacent abdominal tergites in order to obtain substantial general sequence information. We used a laboratory-reared L. longipalpis (one spot, 9-Methyl GermacreneB) population, captured in Lapinha Cave, state of Minas Gerais, Brazil for this analysis. Results From a total of 3,547 cDNA clones, 2,502 high quality sequences from the pheromone gland and adjacent tissues were obtained and assembled into 1,387 contigs. Through blast searches of public databases, a group of transcripts encoding proteins potentially involved in the production of terpenoid precursors were identified in the 4th abdominal tergite, the segment containing the pheromone gland. Among them, protein-coding transcripts for four enzymes of the mevalonate pathway such as 3-hydroxyl-3-methyl glutaryl CoA reductase, phosphomevalonate kinase, diphosphomevalonate descarboxylase, and isopentenyl pyrophosphate isomerase were identified. Moreover, transcripts coding for farnesyl diphosphate synthase and NADP+ dependent farnesol dehydrogenase were also found in the same tergite. Additionally, genes potentially involved in pheromone transportation were identified from the three abdominal tergites analyzed. Conclusion This study constitutes the first transcriptomic analysis exploring the repertoire of genes expressed in the tissue containing the L. longipalpis pheromone gland as well as the flanking tissues. Using a comparative approach, a set of molecules potentially present in the mevalonate pathway emerge as interesting subjects for further study regarding their association to pheromone biosynthesis. The sequences presented here may be used as a reference set for future research on pheromone production or other characteristics of pheromone communication in this insect. Moreover, some matches for transcripts of unknown function may provide fertile ground of an in-depth study of pheromone-gland specific molecules. PMID:23497448
NASA Astrophysics Data System (ADS)
Gai, E. V.; Ignatyuk, A. V.; Lunev, V. P.; Shubin, Yu. N.
2001-11-01
General problems arising in development of intense neutron sources as a part of accelerator-driven systems and first experience accumulated in IPPE during last several years are briefly discussed. The calculation and analysis of nuclear-physical properties of the targets, such as the accumulation of spallation reaction products, activity and heat release for various versions of heavy liquid metal targets were performed in IPPE. The sensitivity of the results of calculations to the various sets of nuclear data was considered. The main radiology characteristics of the lead-bismuth target, which is now under construction in the frame of ISTC Project # 559, are briefly described. The production of short-lived nuclides was estimated, the total activity and volatile nuclide accumulation, residual heat release, the energies of various decay modes were analysed.
An introductory pharmacy practice experience based on a medication therapy management service model.
Agness, Chanel F; Huynh, Donna; Brandt, Nicole
2011-06-10
To implement and evaluate an introductory pharmacy practice experience (IPPE) based on the medication therapy management (MTM) service model. Patient Care 2 is an IPPE that introduces third-year pharmacy students to the MTM service model. Students interacted with older adults to identify medication-related problems and develop recommendations using core MTM elements. Course outcome evaluations were based on number of documented medication-related problems, recommendations, and student reviews. Fifty-seven older adults participated in the course. Students identified 52 medication-related problems and 66 medical problems, and documented 233 recommendations relating to health maintenance and wellness, pharmacotherapy, referrals, and education. Students reported having adequate experience performing core MTM elements. Patient Care 2 may serve as an experiential learning model for pharmacy schools to teach the core elements of MTM and provide patient care services to the community.
Shear-induced conformational ordering, relaxation, and crystallization of isotactic polypropylene.
An, Haining; Li, Xiangyang; Geng, Yong; Wang, Yunlong; Wang, Xiao; Li, Liangbin; Li, Zhongming; Yang, Chuanlu
2008-10-02
The shear-induced coil-helix transition of isotactic polypropylene (iPP) has been studied with time-resolved Fourier transform infrared spectroscopy at various temperatures. The effects of temperature, shear rate, and strain on the coil-helix transition were studied systematically. The induced conformational order increases with the shear rate and strain. A threshold of shear strain is required to induce conformational ordering. High temperature reduces the effect of shear on the conformational order, though a simple correlation was not found. Following the shear-induced conformational ordering, relaxation of helices occurs, which follows the first-order exponential decay at temperatures well above the normal melting point of iPP. The relaxation time versus temperature is fitted with an Arrhenius law, which generates an activation energy of 135 kJ/mol for the helix-coil transition of iPP. At temperatures around the normal melting point, two exponential decays are needed to fit well on the relaxation kinetic of helices. This suggests that two different states of helices are induced by shear: (i) isolated single helices far away from each other without interactions, which have a fast relaxation kinetic; (ii) aggregations of helices or helical bundles with strong interactions among each other, which have a much slower relaxation process. The helical bundles are assumed to be the precursors of nuclei for crystallization. The different helix concentrations and distributions are the origin of the three different processes of crystallization after shear. The correlation between the shear-induced conformational order and crystallization is discussed.
Content and cultural validity in the development of the Indigenous Play Partner Scale.
Dender, Alma M; Stagnitti, Karen E
2017-08-01
Culturally relevant assessments of Australian Indigenous children's social pretend play do not exist. This study investigated the content validity and cultural validity of the Indigenous Play Partner Scale (I-PPS). Six pairs of children (i.e. 12 children) aged four-six years from a remote Australian town were videoed playing in pairs, and 14 community elders and mothers participated across three focus groups. The social interactions between the children were transcribed from the videos. Nineteen verbs, grouped into five categories of social interaction, described the social interactions between the pairs of children. The descriptions of the social interaction verbs were presented to the community elders and mothers in a focus group. The themes from the focus groups were 'background of Indigenous understanding of play' and 'proposed social interaction verbs'. The first theme reflected community collaboration, children playing in multi-aged groups and the role of older children within the play. Guided by the focus group discussion, the videos were re-analysed and 20 social interaction verbs were described that reflected the cultural context of play. The content and cultural validity of the I-PPS was established through community consultation. Twenty social interaction verbs, which form the basis of the items of the I-PPS, reflected Indigenous cultural values of being non-judgemental of Indigenous children's social interactions during pretend play. Culturally relevant assessments for Australian Indigenous children do not disadvantage this population group and are essential for practice in occupational therapy. © 2017 Occupational Therapy Australia.
DeLay, Kenneth; Diao, Linley; Nguyen, Hoang Minh Tue; Zurawin, Jonathan; Libby, Russell; Yafi, Faysal; Hellstrom, Wayne J G
2017-12-01
To determine the success and feasibility of surgically correcting residual curvature after intralesional collagenase clostridium histolyticum (CCH) for the treatment of Peyronie disease (PD). We performed a retrospective analysis of patients who had intralesional CCH treatment for PD and who subsequently underwent penile plication (PP), plaque incision and grafting (PIG), or inflatable penile prosthesis (IPP) placement. Ten men who underwent PP, PIG, or IPP for the treatment of residual curvature after intralesional CCH were identified. Six patients underwent PP; 1 patient underwent PIG; and 3 patients underwent IPP with ancillary straightening maneuvers. The mean time from the last CCH injection to surgical correction was 150.9 days, or 5 months. The mean pre-CCH curvature was 67 degrees and the mean post-CCH curvature was 51 degrees. Eight of 10 patients had no residual curvature after surgical treatment. The mean postprocedure curvature was 4.5 degrees. The mean operative time was 72.1 minutes. The mean estimated blood loss was 20 mL. Increased fibrosis with increased surgical difficulty was noted in 3 (all <6 months post CCH treatment) of 10 patients. No postoperative complications were noted. The surgical treatment of PD after intralesional CCH is safe and effective. If surgery is considered, this should be performed at least 6 months after the last CCH injection, given the potential for an increased inflammatory reaction in this area. Copyright © 2017 Elsevier Inc. All rights reserved.
Modeling for waste management associated with environmental-impact abatement under uncertainty.
Li, P; Li, Y P; Huang, G H; Zhang, J L
2015-04-01
Municipal solid waste (MSW) treatment can generate significant amounts of pollutants, and thus pose a risk on human health. Besides, in MSW management, various uncertainties exist in the related costs, impact factors, and objectives, which can affect the optimization processes and the decision schemes generated. In this study, a life cycle assessment-based interval-parameter programming (LCA-IPP) method is developed for MSW management associated with environmental-impact abatement under uncertainty. The LCA-IPP can effectively examine the environmental consequences based on a number of environmental impact categories (i.e., greenhouse gas equivalent, acid gas emissions, and respiratory inorganics), through analyzing each life cycle stage and/or major contributing process related to various MSW management activities. It can also tackle uncertainties existed in the related costs, impact factors, and objectives and expressed as interval numbers. Then, the LCA-IPP method is applied to MSW management for the City of Beijing, the capital of China, where energy consumptions and six environmental parameters [i.e., CO2, CO, CH4, NOX, SO2, inhalable particle (PM10)] are used as systematic tool to quantify environmental releases in entire life cycle stage of waste collection, transportation, treatment, and disposal of. Results associated with system cost, environmental impact, and the related policy implication are generated and analyzed. Results can help identify desired alternatives for managing MSW flows, which has advantages in providing compromised schemes under an integrated consideration of economic efficiency and environmental impact under uncertainty.
Woo, Tae-Gyun; Yoon, Min-Ho; Hong, Shin-Deok; Choi, Jiyun; Ha, Nam-Chul; Sun, Hokeun; Park, Bum-Joon
2017-01-01
Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human cancer and speculated as a target of novel anti-tumor drug. In previous, we also showed that PAK1 is highly activated in the Smad4-deficient condition and suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding and phosphorylation. On the basis of this result, we have tried to find novel PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA), which selectively blocks the PAK1-PUMA binding and also suppresses cell proliferation via PUMA-dependent manner. Indeed, in PUMA-deficient cells, this chemical did not show anti-proliferating effect. This chemical possessed very strong PAK1 inhibition activity that it suppressed BAD (Bcl-2-asoociated death promoter) phosphorylation and meta-phase arrest via Aurora kinase inactivation in lower concentration than that of previous PAK1 kinase, FRAX486 and AG879. Moreover, our chemical obviously induced p21/WAF1/CIP1 (Cyclin-dependent kinase inhibitor 1A) expression by releasing from Bcl-2 (B-cell lymphoma-2) and by inhibition of AKT-mediated p21 suppression. Considering our result, IPP-14 and its derivatives would be possible candidates for PAK1 and p21 induction targeted anti-cancer drug. PMID:28423593
Cercamondi, Colin I; Duchateau, Guus S M J E; Harika, Rajwinder K; van den Berg, Robin; Murray, Peter; Koppenol, Wieneke P; Zeder, Christophe; Zimmermann, Michael B; Moretti, Diego
2016-08-01
Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.
Sankar, Kalimuthu Vijaya; Seo, Youngho; Lee, Su Chan; Chan Jun, Seong
2018-03-07
For several decades, one of the great challenges for constructing a high-energy supercapacitor has been designing electrode materials with high performance. Herein, we report for the first time to our knowledge a novel hybrid supercapacitor composed of battery-type nickel pyrophosphate one-dimensional (1D) nanorods and capacitive-type N-doped reduced graphene oxide as the cathode and anode, respectively, in an aqueous redox-added electrolyte. More importantly, ex situ microscopic images of the nickel pyrophosphate 1D nanorods revealed that the presence of the battery-type redox additive enhanced the charge storage capacity and cycling life as a result of the microstructure stability. The nickel pyrophosphate 1D nanorods exhibited their maximum specific capacitance (8120 mF cm -2 at 5 mV s -1 ) and energy density (0.22 mWh cm -2 at a power density of 1.375 mW cm -2 ) in 1 M KOH + 75 mg K 3 [Fe(CN) 6 ] electrolyte. On the other side, the N-doped reduced graphene oxide delivered an excellent electrochemical performance, demonstrating that it was an appropriate anode. A hybrid supercapacitor showed a high specific capacitance (224 F g -1 at a current density of 1 A g -1 ) and high energy density (70 Wh kg -1 at a power density of 750 W kg -1 ), as well as a long cycle life (a Coulombic efficiency of 96% over 5000 cycles), which was a higher performance than most of those in recent reports. Our results suggested that the materials and redox additive in this novel design hold great promise for potential applications in a next-generation hybrid supercapacitor.
Villasuso, Ana L.; Wilke, Natalia; Maggio, Bruno; Machado, Estela
2014-01-01
Diacylglycerol pyrophosphate (DGPP) is a minor lipid that attenuates the phosphatidic acid (PA) signal, and also DGPP itself would be a signaling lipid. Diacylglycerol pyrophosphate is an anionic phospholipid with a pyrophosphate group attached to diacylglycerol that was shown to respond to changes of pH, thus affecting the surface organization of DGPP and their interaction with PA. In this work, we have investigated how the presence of Zn2+ modulates the surface organization of DGPP and its interaction with PA at acidic and basic pHs. Both lipids formed expanded monolayers at pHs 5 and 8. At pH 5, monolayers formed by DGPP became stiffer when Zn2+was added to the subphase, while the surface potential decreased. At this pH, Zn2+ induced a phase transition from an expanded to a condensed-phase state in monolayers formed by PA. Conversely, at pH 8 the effects induced by the presence of Zn2+ on the surface behaviors of the pure lipids were smaller. Thus, the interaction of the bivalent cation with both lipids was modulated by pH and by the ionization state of the polar head groups. Mixed monolayers of PA and DGPP showed a non-ideal behavior and were not affected by the presence of Zn2+ at pH 8. This could be explained considering that when mixed, the lipids formed a closely packed monolayer that could not be further modified by the cation. Our results indicate that DGPP and PA exhibit expanded- and condensed-phase states depending on pH, on the proportion of each lipid in the film and on the presence of Zn2+. This may have implications for a possible role of DGPP as a signaling lipid molecule. PMID:25120554
Gras, Pierre; Baker, Annabelle; Combes, Christèle; Rey, Christian; Sarda, Stéphanie; Wright, Adrian J; Smith, Mark E; Hanna, John V; Gervais, Christel; Laurencin, Danielle; Bonhomme, Christian
2016-02-01
Hydrated calcium pyrophosphates (CPP, Ca2P2O7·nH2O) are a fundamental family of materials among osteoarticular pathologic calcifications. In this contribution, a comprehensive multinuclear NMR (Nuclear Magnetic Resonance) study of four crystalline and two amorphous phases of this family is presented. (1)H, (31)P and (43)Ca MAS (Magic Angle Spinning) NMR spectra were recorded, leading to informative fingerprints characterizing each compound. In particular, different (1)H and (43)Ca solid state NMR signatures were observed for the amorphous phases, depending on the synthetic procedure used. The NMR parameters of the crystalline phases were determined using the GIPAW (Gauge Including Projected Augmented Wave) DFT approach, based on first-principles calculations. In some cases, relaxed structures were found to improve the agreement between experimental and calculated values, demonstrating the importance of proton positions and pyrophosphate local geometry in this particular NMR crystallography approach. Such calculations serve as a basis for the future ab initio modeling of the amorphous CPP phases. The general concept of NMR crystallography is applied to the detailed study of calcium pyrophosphates (CPP), whether hydrated or not, and whether crystalline or amorphous. CPP are a fundamental family of materials among osteoarticular pathologic calcifications. Their prevalence increases with age, impacting on 17.5% of the population after the age of 80. They are frequently involved or associated with acute articular arthritis such as pseudogout. Current treatments are mainly directed at relieving the symptoms of joint inflammation but not at inhibiting CPP formation nor at dissolving these crystals. The combination of advanced NMR techniques, modeling and DFT based calculation of NMR parameters allows new original insights in the detailed structural description of this important class of biomaterials. Copyright © 2016. Published by Elsevier Ltd.
Holloway, Daniel E; Chavali, Gayatri B; Leonidas, Demetres D; Baker, Matthew D; Acharya, K Ravi
2009-01-01
Ribonuclease A is the archetype of a functionally diverse superfamily of vertebrate-specific ribonucleases. Inhibitors of its action have potential use in the elucidation of the in vivo roles of these enzymes and in the treatment of pathologies associated therewith. Derivatives of adenosine 5′-pyrophosphate are the most potent nucleotide-based inhibitors known. Here, we use X-ray crystallography to visualize the binding of four naturally-occurring derivatives that contain 5′-pyrophosphate-linked extensions. 5′-ATP binds with the adenine occupying the B2 subsite in the manner of an RNA substrate but with the γ-phosphate at the P1 subsite. Diadenosine triphosphate (Ap3A) binds with the adenine in syn conformation, the β-phosphate as the principal P1 subsite ligand and without order beyond the γ-phosphate. NADPH and NADP+ bind with the adenine stacked against an alternative rotamer of His119, the 2′-phosphate at the P1 subsite, and without order beyond the 5′-α-phosphate. We also present the structure of the complex formed with pyrophosphate ion. The structural data enable existing kinetic data on the binding of these compounds to a variety of ribonucleases to be rationalized and suggest that as the complexity of the 5′-linked extension increases, the need to avoid unfavorable contacts places limitations on the number of possible binding modes. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 995–1008, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com PMID:19191310
Distinguishing erosive osteoarthritis and calcium pyrophosphate deposition disease.
Rothschild, Bruce M
2013-04-18
Erosive osteoarthritis is a term utilized to describe a specific inflammatory condition of the interphalangeal and first carpal metacarpal joints of the hands. The term has become a part of medical philosophical semantics and paradigms, but the issue is actually more complicated. Even the term osteoarthritis (non-erosive) has been controversial, with some suggesting osteoarthrosis to be more appropriate in view of the perspective that it is a non-inflammatory process undeserving of the "itis" suffix. The term "erosion" has also been a source of confusion in osteoarthritis, as it has been used to describe cartilage, not bone lesions. Inflammation in individuals with osteoarthritis actually appears to be related to complicating phenomena, such as calcium pyrophosphate and hydroxyapatite crystal deposition producing arthritis. Erosive osteoarthritis is the contentious term. It is used to describe a specific form of joint damage to specific joints. The damage has been termed erosions and the distribution of the damage is to the interphalangeal joints of the hand and first carpal metacarpal joint. Inflammation is recognized by joint redness and warmth, while X-rays reveal alteration of the articular surfaces, producing a smudged appearance. This ill-defined, joint damage has a crumbling appearance and is quite distinct from the sharply defined erosions of rheumatoid arthritis and spondyloarthropathy. The appearance is identical to those found with calcium pyrophosphate deposition disease, both in character and their unique responsiveness to hydroxychloroquine treatment. Low doses of the latter often resolve symptoms within weeks, in contrast to higher doses and the months required for response in other forms of inflammatory arthritis. Reconsidering erosive osteoarthritis as a form of calcium pyrophosphate deposition disease guides physicians to more effective therapeutic intervention.
Distinguishing erosive osteoarthritis and calcium pyrophosphate deposition disease
Rothschild, Bruce M
2013-01-01
Erosive osteoarthritis is a term utilized to describe a specific inflammatory condition of the interphalangeal and first carpal metacarpal joints of the hands. The term has become a part of medical philosophical semantics and paradigms, but the issue is actually more complicated. Even the term osteoarthritis (non-erosive) has been controversial, with some suggesting osteoarthrosis to be more appropriate in view of the perspective that it is a non-inflammatory process undeserving of the “itis” suffix. The term “erosion” has also been a source of confusion in osteoarthritis, as it has been used to describe cartilage, not bone lesions. Inflammation in individuals with osteoarthritis actually appears to be related to complicating phenomena, such as calcium pyrophosphate and hydroxyapatite crystal deposition producing arthritis. Erosive osteoarthritis is the contentious term. It is used to describe a specific form of joint damage to specific joints. The damage has been termed erosions and the distribution of the damage is to the interphalangeal joints of the hand and first carpal metacarpal joint. Inflammation is recognized by joint redness and warmth, while X-rays reveal alteration of the articular surfaces, producing a smudged appearance. This ill-defined, joint damage has a crumbling appearance and is quite distinct from the sharply defined erosions of rheumatoid arthritis and spondyloarthropathy. The appearance is identical to those found with calcium pyrophosphate deposition disease, both in character and their unique responsiveness to hydroxychloroquine treatment. Low doses of the latter often resolve symptoms within weeks, in contrast to higher doses and the months required for response in other forms of inflammatory arthritis. Reconsidering erosive osteoarthritis as a form of calcium pyrophosphate deposition disease guides physicians to more effective therapeutic intervention. PMID:23610748
Fluorenone based fluorescent probe for selective "turn-on" detection of pyrophosphate and alanine
NASA Astrophysics Data System (ADS)
Daniel Thangadurai, T.; Nithya, I.; Manjubaashini, N.; Bhuvanesh, N.; Bharathi, G.; Nandhakumar, R.; Nataraj, D.
2018-06-01
To sense biologically important entities with different size and dimensions, a fluorenone based fluorescent receptor was designed and synthesized. Probe 1 displayed a distinct fluorescence enhancement emission at 565 nm for pyrophosphate and 530 nm for alanine in polar solvent. The fluorescence titration experiments confirm 1:1 stoichiometric ratio with high-binding constant and very low limit of detection (LoD) values. Receptor 1 showed a highly selective and sensitive recognition to HP2O73 - and to alanine over other competitive anions and amino acids. In addition, the fluorescence lifetime measurement and reversible binding study results support the practical importance of 1.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Panikkar, S.K.; Char, T.L.R.
1958-02-01
Results of studies on the electrodeposition of nickel-zinc and nickel-- molybdenum alloys in a pyrophosphate bath using platinium electrodes are presented. The fects of varying current density and metal contents of the electrolyte on alloy deposit composition, cathode efficiency, and cathode potential are presented in tabular form. (J.R.D.) l2432 A study was made of the effect of homogenization on the mechanical properties of solution-treated and aged aluminum and the quantitative effects of several variables on hardness. The effect of alloying elements on the increase in hardness of aluminum is shown. (J.E.D.)
Saavedra-Lira, E; Ramirez-Silva, L; Perez-Montfort, R
1998-01-15
The parasite Entamoeba histolytica is an organism whose main energetic source comes from glycolysis. It has the singularity that several of its glycolytic enzymes use pyrophosphate as an alternative phosphate donor. Thus, pyruvate phosphate dikinase (PPDK), an inorganic pyrophosphate (PPi)-dependent enzyme, substitutes pyruvate kinase present in humans. We previously cloned and sequenced the gene that codifies for PPDK in E. histolytica. We now report its expression in a bacterial system and its purification to 98% homogeneity. We determined its K(m) for phosphoenolpyruvate, AMP and PPi (21, < 5 and 100 microM, respectively). Unlike PPDK from maize and bacteria and pyruvate kinase from other cells, EhPPDk is dependent on divalent cations but does not require monovalent cations for activity. The enzyme has an optimum pH of 6.0, it is labile to low temperatures and has a tetrameric structure. Since EhPPDK is a PPi-dependent enzyme, we also tested the effect of some pyrophosphate analogs as inhibitors of activity. Studies on the function and structure of this enzyme may be important for therapeutic research in several parasitic diseases, since it has no counterpart in humans.
NASA Technical Reports Server (NTRS)
Ciszak, Ewa; Korotchkina, Lioubov G.; Dominiak, Paulina M.; Sidhu, Sukdeep; Patel, Mulchand S.
2003-01-01
The biologically active derivative of vitamin B1; thiamin pyrophosphate; is used as cofactor by many enzymes that perform a wide range of catalytic functions in the pathways of energy production. In alpha2beta2-heterotetrameric human pyruvate dehydrogenase, the first catalytic component enzyme of human pyruvate dehydrogenase complex, this cofactor is used to cleave the C(sup alpha)-C(=0) bond of pyruvate followed by reductive acetyl transfer to lipoyl-dihydrolipoamide acetyltransferase, the second catalytic component of the complex. The dynamic nonequivalence of two, otherwise chemically equivalent, catalytic sites have puzzled researchers from earlier functional studies of this enzyme. In order to gain insight into the mechanism of action of this enzyme, we determined the crystal structure of the holoform of human pyruvate dehydrogenase at 1.958, resolution. We propose a kinetic model for the flip-flop action of this enzyme through the concerted approx. 2A, shuttle-like motion of the heterodimers. The similarity of thiamin pyrophosphate binding in human pyruvate dehydrogenase and other functionally related enzymes suggests this newly defined mechanism of shuttle-like motion of domains to be common for the family of thiamin pyrophosphate-dependent enzymes.
Flores-Espinosa, Rosa María; Ordoñez-Regil, Eduardo; Fernández-Valverde, Suilma Marisela
2017-01-01
This work addresses the synthesis of titanium pyrophosphate, as well as the characterization and evaluation of the sorption process of europium, for removal of trivalent heavy metals and actinides simulate. The evaluation of the surface properties of titanium pyrophosphate was carried out determining the surface roughness and surface acidity constants. The values obtained from the determination of the surface roughness of the synthesized solid indicate that the surface of the material presents itself as slightly smooth. The FITEQL program was used to fit the experimental titration curves to obtain the surface acidity constants: logK+ = 3.59 ± 0.06 and logK− = −3.90 ± 0.05. The results of sorption kinetics evidenced that the pseudo-order model explains the retention process of europium, in which the initial sorption velocity was 8.3 × 10−4 mg g−1 min−1 and kinetic constant was 1.8 × 10−3 g mg min−1. The maximum sorption capacity was 0.6 mg g−1. The results obtained from sorption edge showed the existence of two bidentate complexes on the surface. PMID:28785720
Chemistry and biotechnology of carotenoids.
Namitha, K K; Negi, P S
2010-09-01
Carotenoids are one of the most widespread groups of pigments in nature and more than 600 of these have been identified. Beside provitamin A activity, carotenoids are important as antioxidants and protective agents against various diseases. They are isoprenoids with a long polyene chain containing 3 to 15 conjugated double bonds, which determines their absorption spectrum. Cyclization at one or both ends occurs in hydrocarbon carotene, while xanthophylls are formed by the introduction of oxygen. In addition, modifications involving chain elongation, isomerization, or degradation are also found. The composition of carotenoids in food may vary depending upon production practices, post-harvest handling, processing, and storage. In higher plants they are synthesized in the plastid. Both mevalonate dependent and independent pathway for the formation of isopentenyl diphosphate are known. Isopentenyl diphosphate undergoes a series of addition and condensation reactions to form phytoene, which gets converted to lycopene. Cyclization of lycopene either leads to the formation of β-carotene and its derivative xanthophylls, β-cryptoxanthin, zeaxanthin, antheraxanthin, and violaxanthin or α-carotene and lutein. Even though most of the carotenoid biosynthetic genes have been cloned and identified, some aspects of carotenoid formation and manipulation in higher plants especially remain poorly understood. In order to enhance the carotenoid content of crop plants to a level that will be required for the prevention of diseases, there is a need for research in both the basic and the applied aspects.
Post, Janina; van Deenen, Nicole; Fricke, Julia; Kowalski, Natalie; Wurbs, David; Schaller, Hubert; Eisenreich, Wolfgang; Huber, Claudia; Twyman, Richard M; Prüfer, Dirk; Gronover, Christian Schulze
2012-03-01
Certain Taraxacum species, such as Taraxacum koksaghyz and Taraxacum brevicorniculatum, produce large amounts of high-quality natural rubber in their latex, the milky cytoplasm of specialized cells known as laticifers. This high-molecular mass biopolymer consists mainly of poly(cis-1,4-isoprene) and is deposited in rubber particles by particle-bound enzymes that carry out the stereospecific condensation of isopentenyl diphosphate units. The polymer configuration suggests that the chain-elongating enzyme (rubber transferase; EC 2.5.1.20) is a cis-prenyltransferase (CPT). Here, we present a comprehensive analysis of transgenic T. brevicorniculatum plants in which the expression of three recently isolated CPTs known to be associated with rubber particles (TbCPT1 to -3) was heavily depleted by laticifer-specific RNA interference (RNAi). Analysis of the CPT-RNAi plants by nuclear magnetic resonance, size-exclusion chromatography, and gas chromatography-mass spectrometry indicated a significant reduction in rubber biosynthesis and a corresponding 50% increase in the levels of triterpenes and the main storage carbohydrate, inulin. Transmission electron microscopy revealed that the laticifers in CPT-RNAi plants contained fewer and smaller rubber particles than wild-type laticifers. We also observed lower activity of hydroxymethylglutaryl-coenzyme A reductase, the key enzyme in the mevalonate pathway, reflecting homeostatic control of the isopentenyl diphosphate pool. To our knowledge, this is the first in planta demonstration of latex-specific CPT activity in rubber biosynthesis.
Erectile Dysfunction: MedlinePlus Health Topic
... Men's Health (Hormone Health Network) Also in Spanish Sex and the Man With Cancer (American Cancer Society) Also in Spanish Specifics Bent Penis (Mayo Foundation for Medical Education and Research) Videos and Tutorials Simultaneous Inflatable Penile Prosthesis (IPP) and ...
[Implementing Inter-Professional Education (IPE): Challenges and Strategies].
Lee, Chia-Lun; Hung, Chich-Hsiu
2017-12-01
Inter-professional practice (IPP), necessary in today's healthcare environment, should be guided and practiced through inter-professional education (IPE). Within the context of an effective IPE program, collaborative medical professionals must be cognizant of the demands of patients' integrated care, organize a collaborative inter-professional team, and achieve the objectives of patient-centered care. However, the many challenges of IPE include insufficient understanding of inter-professional care, occupational culture-related boundary issues, lack of a college education, and insufficient support from academic and medical institutions. This article suggests adopting effective strategies to promote inter-professional recognition, create a harmonious medical culture, eliminate barriers to education, and enhance support for academic and medical institutions. Inter-professional collaboration between academic and clinical institutions must provide resources and substantive professional training. Effectively implementing IPE and IPP is expected to elicit trust, respect, and efficient communication from team members.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dobrzyńska-Mizera, Monika, E-mail: monika.dobrzynska-mizera@doctorate.put.poznan.pl; Sterzyński, Tomasz; Dutkiewicz, Michał
Composites based on polypropylene (iPP) modified with a sorbitol derivative (NX8000) and siloxane-silsesquioxane resin (SiOPh) containing maleated polypropylene (MAPP) as compatibilizer were prepared by melt extrusion. Calorimetric investigations were carried out using differential scanning calorimetry (DSC), whereas the morphological and mechanical properties were investigated by scanning electron microscopy (SEM) and static tensile tests. DSC measurements revealed no influence of SiOPh and a slight effect of MAPP addition on the crystallization kinetics of polypropylene. Additionally, the introduction of MAPP into the iPP+NX8000+SiOPh composites increased plastic properties of the samples. All the above was attributed to the compatibilizing effect of MAPP whichmore » improved interfacial adhesion between iPP, NX8000 and SiOPh. This phenomenon was also confirmed by the SEM images illustrating more homogenous distribution of the filler in the compatibilized samples.« less
Profit-based conventional resource scheduling with renewable energy penetration
NASA Astrophysics Data System (ADS)
Reddy, K. Srikanth; Panwar, Lokesh Kumar; Kumar, Rajesh; Panigrahi, B. K.
2017-08-01
Technological breakthroughs in renewable energy technologies (RETs) enabled them to attain grid parity thereby making them potential contenders for existing conventional resources. To examine the market participation of RETs, this paper formulates a scheduling problem accommodating energy market participation of wind- and solar-independent power producers (IPPs) treating both conventional and RETs as identical entities. Furthermore, constraints pertaining to penetration and curtailments of RETs are restructured. Additionally, an appropriate objective function for profit incurred by conventional resource IPPs through reserve market participation as a function of renewable energy curtailment is also proposed. The proposed concept is simulated with a test system comprising 10 conventional generation units in conjunction with solar photovoltaic (SPV) and wind energy generators (WEG). The simulation results indicate that renewable energy integration and its curtailment limits influence the market participation or scheduling strategies of conventional resources in both energy and reserve markets. Furthermore, load and reliability parameters are also affected.
Metzger, Nicole L; Chesson, Melissa M; Momary, Kathryn M
2015-09-25
Objective. To create, implement, and assess a simulated medication reconciliation and an order verification activity using hospital training software. Design. A simulated patient with medication orders and home medications was built into existing hospital training software. Students in an institutional introductory pharmacy practice experience (IPPE) reconciled the patient's medications and determined whether or not to verify the inpatient orders based on his medical history and laboratory data. After reconciliation, students identified medication discrepancies and documented their rationale for rejecting inpatient orders. Assessment. For a 3-year period, the majority of students agreed the simulation enhanced their learning, taught valuable clinical decision-making skills, integrated material from previous courses, and stimulated their interest in institutional pharmacy. Overall feedback from student evaluations about the IPPE also was favorable. Conclusion. Use of existing hospital training software can affordably simulate the pharmacist's role in order verification and medication reconciliation, as well as improve clinical decision-making.
NASA Astrophysics Data System (ADS)
Dobrzyńska-Mizera, Monika; Dutkiewicz, Michał; Sterzyński, Tomasz; Di Lorenzo, Maria Laura
2015-12-01
Composites based on polypropylene (iPP) modified with a sorbitol derivative (NX8000) and siloxane-silsesquioxane resin (SiOPh) containing maleated polypropylene (MAPP) as compatibilizer were prepared by melt extrusion. Calorimetric investigations were carried out using differential scanning calorimetry (DSC), whereas the morphological and mechanical properties were investigated by scanning electron microscopy (SEM) and static tensile tests. DSC measurements revealed no influence of SiOPh and a slight effect of MAPP addition on the crystallization kinetics of polypropylene. Additionally, the introduction of MAPP into the iPP+NX8000+SiOPh composites increased plastic properties of the samples. All the above was attributed to the compatibilizing effect of MAPP which improved interfacial adhesion between iPP, NX8000 and SiOPh. This phenomenon was also confirmed by the SEM images illustrating more homogenous distribution of the filler in the compatibilized samples.
Impact of hybrid delivery of education on student academic performance and the student experience.
Congdon, Heather Brennan; Nutter, Douglas A; Charneski, Lisa; Butko, Peter
2009-11-12
To compare student academic performance and the student experience in the first-year doctor of pharmacy (PharmD) program between the main and newly opened satellite campuses of the University of Maryland. Student performance indicators including graded assessments, course averages, cumulative first-year grade point average (GPA), and introductory pharmacy practice experience (IPPE) evaluations were analyzed retrospectively. Student experience indicators were obtained via an online survey instrument and included involvement in student organizations; time-budgeting practices; and stress levels and their perceived effect on performance. Graded assessments, course averages, GPA, and IPPE evaluations were indistinguishable between campuses. Students' time allocation was not different between campuses, except for time spent attending class and watching lecture videos. There was no difference between students' stress levels at each campus. The implementation of a satellite campus to expand pharmacy education yielded academic performance and student engagement comparable to those from traditional delivery methods.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lehman, A.T.; Khanna, R.
1996-11-01
Diverse environmental reviews and approvals are required by both Government and non-government organizations (NGOs) for licensing or permitting of major thermal power plants in Asia; specifically, India and Philippines. The number and type of approvals required for a specific project vary depending on site characteristics, fuel source, project-specific design and operating parameters as well as type of project financing. A model 400 MW coal-fired project located in Asia is presented to illustrate the various lender and host country environmental guidelines. A case study of the environmental reviews and approvals for Ogden Quezon Power, Inc. Project (Quezon Province, Republic of themore » Philippines) is also included. A list of acronyms is provided at the paper`s end. As independent power project (IPP) developers seek financing for these capital-intensive infrastructure projects, a number of international finance/lending institutions are likely to become involved. Each lender considers different environmental aspects of a project. This paper compares relevant environmental requirements of various lenders which finance IPPs and their interest in a project`s environmental review. Finally, the authors of this paper believe that the environmental review process can bring together many parties involved with IPP development, including local and central governments, non government organizations, various lenders (such as multilateral and export credit agencies) as well as project proponents. Environmental review provides input opportunity for interested and affected parties. Airing environmental issues in open forums such as public hearings or meetings helps ensure projects are not evaluated without public input.« less
Augusto Negro, Carlo Luigi; Paradiso, Matteo; Rocca, Alessandro; Bardari, Franco
2016-01-01
Implantation of an inflatable penile prosthesis (IPP) is a well-established definitive solution for erectile dysfunction when conservative treatments fail. Penile implants may shorten the penis. The AMS 700 LGX IPP is in common use but reports on its mechanical reliability, medium-term postsurgical patient satisfaction, and mean penile length preservation are lacking. We investigate the mean penile length, mechanical reliability, and patient satisfaction at 6 and 12 months after implantation of the AMS 700 LGX. This prospective study consecutively enrolled men undergoing first-time IPP implant surgery from February 2009 to April 2012. Stretched flaccid penile length, penile length at 50% and 100% of stiffness (P50 and P100) and International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores, were measured at 6 and 12 months postsurgery. Of 45 patients who underwent AMS 700 LGX implantation (median age 61 years) and completed 6 months’ follow-up, 36 (80%) completed the study. A significant difference in stretched flaccid penile length was seen between 6 and 12 months (P = 0.033). P100 was also significantly increased at 6 and 12 months, with a mean 10% increase (1.3 ± 0.4 cm) from baseline to 12 months. Differences in mean IIEF scores at 6 and 12 months were significant for the desired domain (P = 0.0001) and for overall satisfaction (P = 0.002); however, mean EDITS scores at 6 and 12 months were not significantly improved. AMS 700 LGX is a powerful tool for preserving penile length in men undergoing penile prosthesis implantation. PMID:26112480
El-Deeb, H A; Al Sherbiney, H H; Mobarak, E H
2013-01-01
To evaluate the dentin bond strength durability of adhesives containing modified-monomer with/without-fluoride after storage in artificial saliva and under intrapulpal pressure simulation (IPPS). The occlusal enamel of 48 freshly extracted teeth was trimmed to expose midcoronal dentin. Roots were sectioned to expose the pulp chamber and to connect the specimens to the pulpal-pressure assembly. Specimens were assigned into four groups (n=12) according to adhesive system utilized: a two-step etch-and-rinse adhesive system (SB, Adper Single Bond 2, 3M ESPE), a two-step self-etch adhesive system (CSE, Clearfil SE Bond, Kuraray Medical Inc), and two single-step self-etch adhesives with the same modified monomer (bis-acrylamide)-one with fluoride (AOF, AdheSE One F, Ivoclar-Vivadent) and the other without (AO, AdheSE One, Ivoclar-Vivadent). Bonding was carried out while the specimens were subjected to 15-mm Hg IPPS. Resin composite (Valux Plus, 3M ESPE) buildups were made. After curing, specimens were aged in artificial saliva and under 20-mm Hg IPPS at 37°C in a specially constructed incubator either for 24 hours or six months prior to testing. Bonded specimens (n=6/group) were sectioned into sticks (n=24/group) with a cross section of 0.9 ± 0.01 mm(2) and subjected to microtensile bond strength (μTBS) testing using a universal testing machine. Data were statistically analyzed using two-way analysis of variance (ANOVA) with repeated measures, one-way ANOVA tests, and a t-test (p<0.05). Failure modes were determined using a scanning electron microscope. The μTBS values of SB and CSE fell significantly after six-month storage in artificial saliva and under IPPS, yet these values remained significantly higher than those for the other two adhesives with modified monomers. There was no significant difference in the bond strength values between fluoride-containing and fluoride-free self-etch adhesive systems (AOF and AO) after 24 hours or six months. Modes of failure were mainly adhesive and mixed. Based on the results of this study, 1) Fluoride addition did not affect dentin bond durability; and 2) despite the fact that the single-step adhesive system with modified monomer showed stability, bond strengths associated with these systems remained lower than those of multistep adhesive systems.
Modeling of ultrasonic degradation of non-volatile organic compounds by Langmuir-type kinetics.
Chiha, Mahdi; Merouani, Slimane; Hamdaoui, Oualid; Baup, Stéphane; Gondrexon, Nicolas; Pétrier, Christian
2010-06-01
Sonochemical degradation of phenol (Ph), 4-isopropylphenol (4-IPP) and Rhodamine B (RhB) in aqueous solutions was investigated for a large range of initial concentrations in order to analyze the reaction kinetics. The initial rates of substrate degradation and H(2)O(2) formation as a function of initial concentrations were determined. The obtained results show that the degradation rate increases with increasing initial substrate concentration up to a plateau and that the sonolytic destruction occurs mainly through reactions with hydroxyl radicals in the interfacial region of cavitation bubbles. The rate of H(2)O(2) formation decreases with increasing substrate concentration and reaches a minimum, followed by almost constant production rate for higher substrate concentrations. Sonolytic degradation data were analyzed by the models of Okitsu et al. [K. Okitsu, K. Iwasaki, Y. Yobiko, H. Bandow, R. Nishimura, Y. Maeda, Sonochemical degradation of azo dyes in aqueous solution: a new heterogeneous kinetics model taking into account the local concentration OH radicals and azo dyes, Ultrason. Sonochem. 12 (2005) 255-262.] and Seprone et al. [N. Serpone, R. Terzian, H. Hidaka, E. Pelizzetti, Ultrasonic induced dehalogenation and oxidation of 2-, 3-, and 4-chlorophenol in air-equilibrated aqueous media. Similarities with irradiated semiconductor particulates, J. Phys. Chem. 98 (1994) 2634-2640.] developed on the basis of a Langmuir-type mechanism. The five linearized forms of the Okitsu et al.'s equation as well as the non-linear curve fitting analysis method were discussed. Results show that it is not appropriate to use the coefficient of determination of the linear regression method for comparing the best-fitting. Among the five linear expressions of the Okitsu et al.'s kinetic model, form-2 expression very well represent the degradation data for Ph and 4-IPP. Non-linear curve fitting analysis method was found to be the more appropriate method to determine the model parameters. An excellent representation of the experimental results of sonolytic destruction of RhB was obtained using the Serpone et al.'s model. The Serpone et al.'s model gives a worse fit for the sonolytic degradation data of Ph and 4-IPP. These results indicate that Ph and 4-IPP undergo degradation predominantly at the bubble/solution interface, whereas RhB undergoes degradation at both bubble/solution interface and in the bulk solution. (c) 2010 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Davison, R.; Spies, S.M.; Przybylek, J.
1979-08-01
Thirty consecutive patients underwent technetium-99m stannous pyrophosphate myocardial scintigraphy 48 to 72 h after successful cardiopulmonary resuscitation and direct current cardioversion. Five patients with transmural myocardial infarctions by ECG and enzyme determinations were correctly identified by scintigraphy. Myocardial scans were positive in five of nine patients with nontransmural infarction. Of 16 patients without evidence of myocardial infarction, only two (13%) had false-positive myocardial scans. The overall accuracy of imaging in this series was 80%. We conclude that false-positive scans after cardiopulmonary resuscitation with electrical cardioversion are infrequent, and do not significantly detract from the value of myocardial scintigraphy in themore » diagnosis of myocardial infarction.« less
Jiao, Shu-Yan; Li, Kun; Zhang, Wei; Liu, Yan-Hong; Huang, Zeng; Yu, Xiao-Qi
2015-01-21
The terpyridine anthracene ligand was synthesized and characterized. is a ratiometric fluorescent probe for Cd(2+) with a recognition mechanism based on intramolecular charge transfer (ICT). An complex was isolated, and its structure was established using single-crystal XRD. The complex was able to serve as a novel reversible chemosensing ensemble to allow ratiometric response to pyrophosphate (PPi) in aqueous media. Moreover, the fluorescence imaging in living cells from these two emission channels suggested that was a ratiometric probe for Cd(2+), and the in situ generated complex was also a ratiometric ensemble for PPi detection in living cells.
Onoda, Hiroaki; Yamaguchi, Taisuke
2013-04-01
In this study, titanium phosphates were prepared from titanium chloride and phosphoric acid, sodium pyrophosphate and sodium triphosphate solutions with water retention compounds in hydrothermal process as a novel white pigment for cosmetics. Their chemical composition, powder properties, photo catalytic activity, water retention and smoothness were studied. The addition of glycerin in the preparation from sodium pyrophosphate has the useful method to obtain homogenized spherical particles of titanium phosphate pigments for the cosmetics. These titanium phosphates had less photo catalytic activity to protect the sebum on the skin. © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.
Jacques, Thibaut; Michelin, Paul; Badr, Sammy; Nasuto, Michelangelo; Lefebvre, Guillaume; Larkman, Neal; Cotten, Anne
2017-09-01
This article reviews the main radiographic features of crystal deposition diseases. Gout is linked to monosodium urate crystals. Classic radiographic features include subcutaneous tophi, large and well-circumscribed paraarticular bone erosions, and exuberant bone hyperostosis. Calcium pyrophosphate deposition (CPPD) can involve numerous structures, such as hyaline cartilages, fibrocartilages, or tendons. CPPD arthropathy involves joints usually spared by osteoarthritis. Basic calcium phosphate deposits are periarticular or intraarticular. Periarticular calcifications are amorphous, dense, and round or oval with well-limited borders, and most are asymptomatic. When resorbing, they become cloudy and less dense with an ill-defined shape and can migrate into adjacent structures. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, V.W.; Caldarone, A.G.; Falk, R.H.
1983-07-01
A prospective, comparative study was made of the efficacy of technetium-99m pyrophosphate (Tc PYP) and technetium-99m methylene diphosphonate (Tc MDP) in detecting soft-tissue amyloidois. Tc PYP and Tc MDP scans were obtained within ten-day intervals in seven patients with histologically proven amyloidosis. Tc PYP was a better scanning agent for soft-tissue amyloidosis in all patients. Cardiac and hepatic involvement were proved by autopsy in one patient. Involvement of the heart was confirmed by echocardiography in five patients. The potential use of tc PYP scannning as a screening test for soft-tissue amyloidosis is discussed.
Overexpression of Plastid Transketolase in Tobacco Results in a Thiamine Auxotrophic Phenotype[OPEN
Khozaei, Mahdi; Fisk, Stuart; Lawson, Tracy; Gibon, Yves; Sulpice, Ronan; Stitt, Mark; Lefebvre, Stephane C.; Raines, Christine A.
2015-01-01
To investigate the effect of increased plastid transketolase on photosynthetic capacity and growth, tobacco (Nicotiana tabacum) plants with increased levels of transketolase protein were produced. This was achieved using a cassette composed of a full-length Arabidopsis thaliana transketolase cDNA under the control of the cauliflower mosaic virus 35S promoter. The results revealed a major and unexpected effect of plastid transketolase overexpression as the transgenic tobacco plants exhibited a slow-growth phenotype and chlorotic phenotype. These phenotypes were complemented by germinating the seeds of transketolase-overexpressing lines in media containing either thiamine pyrophosphate or thiamine. Thiamine levels in the seeds and cotyledons were lower in transketolase-overexpressing lines than in wild-type plants. When transketolase-overexpressing plants were supplemented with thiamine or thiamine pyrophosphate throughout the life cycle, they grew normally and the seed produced from these plants generated plants that did not have a growth or chlorotic phenotype. Our results reveal the crucial importance of the level of transketolase activity to provide the precursor for synthesis of intermediates and to enable plants to produce thiamine and thiamine pyrophosphate for growth and development. The mechanism determining transketolase protein levels remains to be elucidated, but the data presented provide evidence that this may contribute to the complex regulatory mechanisms maintaining thiamine homeostasis in plants. PMID:25670766
Stockbridge, Randy B.; Wolfenden, Richard
2011-01-01
To estimate the proficiency of inorganic pyrophosphatase as a catalyst, 31P NMR was used to determine rate constants and thermodynamics of activation for the spontaneous hydrolysis of inorganic pyrophosphate (PPi) in the presence and absence of Mg2+ at elevated temperatures. These values were compared with rate constants and activation parameters determined for the reaction catalyzed by Escherichia coli inorganic pyrophosphatase using isothermal titration calorimetry. At 25 °C and pH 8.5, the hydrolysis of MgPPi2− proceeds with a rate constant of 2.8 × 10−10 s−1, whereas E. coli pyrophosphatase was found to have a turnover number of 570 s−1 under the same conditions. The resulting rate enhancement (2 × 1012-fold) is achieved entirely by reducing the enthalpy of activation (ΔΔH‡ = −16.6 kcal/mol). The presence of Mg2+ ions or the transfer of the substrate from bulk water to dimethyl sulfoxide was found to increase the rate of pyrophosphate hydrolysis by as much as ∼106-fold. Transfer to dimethyl sulfoxide accelerated PPi hydrolysis by reducing the enthalpy of activation. Mg2+ increased the rate of PPi hydrolysis by both increasing the entropy of activation and reducing the enthalpy of activation. PMID:21460215
Ferriols, Victor Marco Emmanuel N; Yaginuma, Ryoko; Adachi, Masao; Takada, Kentaro; Matsunaga, Shigeki; Okada, Shigeru
2015-05-21
The diatom Rhizosolenia setigera Brightwell produces highly branched isoprenoid (HBI) hydrocarbons that are ubiquitously present in marine environments. The hydrocarbon composition of R. setigera varies between C25 and C30 HBIs depending on the life cycle stage with regard to auxosporulation. To better understand how these hydrocarbons are biosynthesized, we characterized the farnesyl pyrophosphate (FPP) synthase (FPPS) enzyme of R. setigera. An isolated 1465-bp cDNA clone contained an open reading frame spanning 1299-bp encoding a protein with 432 amino acid residues. Expression of the RsFPPS cDNA coding region in Escherichia coli produced a protein that exhibited FPPS activity in vitro. A reduction in HBI content from diatoms treated with an FPPS inhibitor, risedronate, suggested that RsFPPS supplies precursors for HBI biosynthesis. Product analysis by gas chromatography-mass spectrometry also revealed that RsFPPS produced small amounts of the cis-isomers of geranyl pyrophosphate and FPP, candidate precursors for the cis-isomers of HBIs previously characterized. Furthermore, RsFPPS gene expression at various life stages of R. setigera in relation to auxosporulation were also analyzed. Herein, we present data on the possible role of RsFPPS in HBI biosynthesis, and it is to our knowledge the first instance that an FPPS was cloned and characterized from a diatom.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Strempel, Verena E.; Naumann d'Alnoncourt, Raoul, E-mail: r.naumann@bascat.tu-berlin.de; Löffler, Daniel
2016-01-15
Atomic layer deposition is mainly used to deposit thin films on flat substrates. Here, the authors deposit a submonolayer of phosphorus on V{sub 2}O{sub 5} in the form of catalyst powder. The goal is to prepare a model catalyst related to the vanadyl pyrophosphate catalyst (VO){sub 2}P{sub 2}O{sub 7} industrially used for the oxidation of n-butane to maleic anhydride. The oxidation state of vanadium in vanadyl pyrophosphate is 4+. In literature, it was shown that the surface of vanadyl pyrophosphate contains V{sup 5+} and is enriched in phosphorus under reaction conditions. On account of this, V{sub 2}O{sub 5} with themore » oxidation state of 5+ for vanadium partially covered with phosphorus can be regarded as a suitable model catalyst. The catalytic performance of the model catalyst prepared via atomic layer deposition was measured and compared to the performance of catalysts prepared via incipient wetness impregnation and the original V{sub 2}O{sub 5} substrate. It could be clearly shown that the dedicated deposition of phosphorus by atomic layer deposition enhances the catalytic performance of V{sub 2}O{sub 5} by suppression of total oxidation reactions, thereby increasing the selectivity to maleic anhydride.« less
Lan, Jian-bin; Yu, Rang-cai; Yu, Yun-yi; Fan, Yan-ping
2013-04-15
Farnesyl pyrophosphate synthase (FPPS EC 2.5.1.10) catalyzes the production of farnesyl pyrophosphate (FPP), which is a key precursor for many sesquiterpenoids such as floral scent and defense volatiles against herbivore attack. Here we report a new full-length cDNA encoding farnesyl diphosphate synthase from Hedychium coronarium. The open reading frame for full-length HcFPPS encodes a protein of 356 amino acids, which is 1068 nucleotides long with calculated molecular mass of 40.7 kDa. Phylogenetic tree analysis indicates that HcFPPS belongs to the plant FPPS super-family and has strong relationship with FPPS from Musa acuminata. Expression of the HcFPPS gene in Escherichia coli yielded FPPS activity. Tissue-specific and developmental analyses of the HcFPPS mRNA and corresponding volatile sesquiterpenoid levels in H. coronarium flowers revealed that the HcFPPS might play a regulatory role in floral volatile sesquiterpenoid biosynthesis. The emission of the FPP-derived volatile terpenoid correlates with strong expression of HcFPPS induced by mechanical wounding and Udaspes folus-damage in leaves, which suggests that HcFPPS may have an important ecological function in H. coronarium vegetative organ. Copyright © 2013 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Tao, Zhengxu; Zhang, Wanqi; Huang, Yanlin; Wei, Donglei; Seo, Hyo Jin
2014-08-01
A novel pyrophosphate BaCr2(P2O7)2 was synthesized by the conventional solid-state reaction. The X-ray diffraction (XRD), FTIR spectrum, scanning electron microscopy (SEM) and ultraviolet-visible (UV-Vis) near infrared (NIR) reflectance spectra were applied to characterize the powders. The refractive indexes and nature of the VB and CB were determined. The structure, color properties and application were investigated. The results reveal that the anomalist bodies with smooth surfaces were obtained at 1200 °C with a mean size of 3 μm. A high reflectance peak at 535 nm was observed in the visible region, which is associated with the brilliant and deep green color of this pigment. With all the acids, alkali and deionized water treatment, the polycrystalline pigment BaCr2(P2O7)2 was found to be durable in chemical stability. The significantly high NIR solar reflectance of BaCr2(P2O7)2 is 90.0%, a higher cooling ability, so it has been selected to be tested as cool green pigment in ceramics. Moreover, this novel pyrophosphate pigment has great potential as cool pigment for surface coating applications.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hongo, M.; Hirayama, J.; Fujii, T.
1987-03-01
To determine whether technetium-99m-pyrophosphate (Tc-99m-PYP) scanning or two-dimensional echocardiography can detect amyloid heart disease in an earlier stage of familial amyloid polyneuropathy, 15 patients were examined. Although 10 of the 15 patients had no clinical evidence of congestive heart failure, as well as normal ventricular wall thickness and normal values for left ventricular systolic function, five (50%) of them showed mild or moderate myocardial uptake. On the other hand, none had characteristic highly refractile myocardial echoes on the two-dimensional echocardiographic images (p less than 0.01), and values for diastolic function were reduced in four of the five and normal inmore » the remaining one. In 85 control subjects, diffuse positive pyrophosphate scans of the heart were found in four (5%) of them (three with dilated cardiomyopathy and one with sarcoidosis), and highly refractile granular sparkling echoes were observed in nine (11%) (five with hypertrophic cardiomyopathy, three with aortic stenosis, and one with hypereosinophilic syndrome). We conclude that Tc-99m-PYP scanning is a more sensitive and specific method and may have the potential ability to detect amyloid heart disease in the earlier stage of familial amyloid polyneuropathy than two-dimensional echocardiography.« less
Farrell, S; Barker, M L; Gerlach, R W; Putt, M S; Milleman, J L
2009-01-01
This randomized controlled clinical trial was conducted to evaluate whether daily use of a hydrogen peroxide/ pyrophosphate-containing antitartar whitening strip might safely yield clinical reductions in post-prophylaxis calculus accumulation. A three-month, randomized controlled trial was conducted to compare calculus accumulation with a daily 6% hydrogen peroxide/pyrophosphate strip versus regular brushing. After an eight-week run-in phase to identify calculus formers, a prophylaxis was administered, and 77 subjects were randomly assigned to daily strip or brushing only groups. All subjects received an anticavity dentifrice (Crest Cavity Protection) and manual brush for use throughout the three-month study; for subjects assigned to the experimental group, strip application was once daily for five minutes on the facial and lingual surfaces of the mandibular teeth. Efficacy was measured as mm calculus (VMI) before prophylaxis and after six and 12 weeks of treatment, while safety was assessed from examination and interview. Subjects ranged in age from 21-87 years, with groups balanced (p > 0.26) on pertinent demographic and behavioral parameters, and pre-prophylaxis calculus baseline mean scores (16.0 mm). At Week 6, calculus accumulation was lower in the strip group, with adjusted mean (SE) lingual VMI of 12.0 (0.87) for the strip group and 17.0 (0.88) for the brushing control. At Week 12, calculus accumulation was lower in the strip group, with adjusted mean (SE) lingual VMI of 14.3 (0.85) for the strip group and 17.2 (0.86) for the brushing control. Treatments differed significantly (p < 0.02) on calculus accumulation at both time points. A total of three subjects (8%) in the strip group and two subjects (5%) in the brushing control had mild oral irritation or tooth sensitivity during treatment; no one discontinued early due to an adverse event. Daily use of hydrogen peroxide whitening strips with pyrophosphate reduced calculus formation by up to 29% versus regular brushing, without meaningful adverse events.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-15
...-through devices, brachytherapy sources, intraoperative radiation therapy (IORT), brachytherapy composite... Modulated Radiation Therapy I/OCE Integrated Outpatient Code Editor IOL Intraocular lens IOM Institute of Medicine IORT Intraoperative radiation treatment IPF Inpatient Psychiatric Facility IPPS [Hospital...
Mornet, René; Theiler, Jane B.; Leonard, Nelson J.; Schmitz, Ruth Y.; Moore, F. Hardy; Skoog, Folke
1979-01-01
Four series of azidopurines have been synthesized and tested for cytokinin activity in the tobacco callus bioassay: 2- and 8-azido-N6-benzyladenines, -N6-(Δ2-isopentenyl)adenines, and -zeatins, and N6-(2- and 4-azidobenzyl)adenines. The compounds having 2-azido substitution on the adenine ring are as active as the corresponding parent compounds, while those with 8-azido substitution are about 10 or more times as active. The 8-azidozeatin, which is the most active cytokinin observed, exhibited higher than minimal detectable activity at 1.2 × 10−5 micromolar, the lowest concentration tested. The shape of the growth curve indicates that even a concentration as low as 5 × 10−6 micromolar would probably be effective. By comparison, the lowest active concentration ever reported for zeatin has been 5 × 10−5 micromolar, representing a sensitivity rarely attained. All of the azido compounds have been submitted to photolysis in aqueous ethanol, and the photoproducts have been detected and identified by low and high resolution mass spectrometry. They are rationalized as products of abstraction and insertion reactions of the intermediate nitrenes. The potential of the major released products as cytokinins was also assessed by bioassay. 2-Azido-N6-(Δ2-isopentenyl)adenine competed with [14C]kinetin for the cytokinin-binding protein isolated from wheat germ. When the azido compound was photolysed in the presence of this protein, its attachment effectively blocked the binding of [14C]kinetin. PMID:16661017
Post, Janina; van Deenen, Nicole; Fricke, Julia; Kowalski, Natalie; Wurbs, David; Schaller, Hubert; Eisenreich, Wolfgang; Huber, Claudia; Twyman, Richard M.; Prüfer, Dirk; Gronover, Christian Schulze
2012-01-01
Certain Taraxacum species, such as Taraxacum koksaghyz and Taraxacum brevicorniculatum, produce large amounts of high-quality natural rubber in their latex, the milky cytoplasm of specialized cells known as laticifers. This high-molecular mass biopolymer consists mainly of poly(cis-1,4-isoprene) and is deposited in rubber particles by particle-bound enzymes that carry out the stereospecific condensation of isopentenyl diphosphate units. The polymer configuration suggests that the chain-elongating enzyme (rubber transferase; EC 2.5.1.20) is a cis-prenyltransferase (CPT). Here, we present a comprehensive analysis of transgenic T. brevicorniculatum plants in which the expression of three recently isolated CPTs known to be associated with rubber particles (TbCPT1 to -3) was heavily depleted by laticifer-specific RNA interference (RNAi). Analysis of the CPT-RNAi plants by nuclear magnetic resonance, size-exclusion chromatography, and gas chromatography-mass spectrometry indicated a significant reduction in rubber biosynthesis and a corresponding 50% increase in the levels of triterpenes and the main storage carbohydrate, inulin. Transmission electron microscopy revealed that the laticifers in CPT-RNAi plants contained fewer and smaller rubber particles than wild-type laticifers. We also observed lower activity of hydroxymethylglutaryl-coenzyme A reductase, the key enzyme in the mevalonate pathway, reflecting homeostatic control of the isopentenyl diphosphate pool. To our knowledge, this is the first in planta demonstration of latex-specific CPT activity in rubber biosynthesis. PMID:22238421
Wagatsuma, Tadao; Maejima, Eriko; Watanabe, Toshihiro; Toyomasu, Tomonobu; Kuroda, Masaharu; Muranaka, Toshiya; Ohyama, Kiyoshi; Ishikawa, Akifumi; Usui, Masami; Hossain Khan, Shahadat; Maruyama, Hayato; Tawaraya, Keitaro; Kobayashi, Yuriko; Koyama, Hiroyuki
2018-01-23
Aluminum-sensitive rice (Oryza sativa L.) cultivars showed increased Al tolerance under dark conditions, because less Al accumulated in the root tips (1 cm) under dark than under light conditions. Under dark conditions, the root tip concentration of total sterols, which generally reduce plasma membrane permeabilization, was higher in the most Al-sensitive japonica cultivar, Koshihikari (Ko), than in the most Al-tolerant cultivar, Rikuu-132 (R132), but the phospholipid content did not differ between the two. The Al treatment increased the proportion of stigmasterol (which has no ability to reduce membrane permeabilization) out of total sterols similarly in both cultivars under light conditions, but it decreased more in Ko under dark conditions. The carotenoid content in the root tip of Al-treated Ko was significantly lower under dark than under light conditions, indicating that isopentenyl diphosphate transport from the cytosol to plastids was decreased under dark conditions. HMG2 and HMG3 (encoding the key sterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl CoA reductase) transcript levels in the root tips were enhanced under dark conditions. We suggest that the following mechanisms contribute to the increase in Al tolerance under dark conditions: inhibition of stigmasterol formation to retain membrane integrity; greater partitioning of isopentenyl diphosphate for sterol biosynthesis; and enhanced expression of HMGs to increase sterol biosynthesis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Cui, Tao; Terlecki, Ryan; Mirzazadeh, Majid
2015-12-01
Complications related to inflatable penile prosthesis (IPP) and artificial urinary sphincter (AUS) reservoirs are rare, potentially life threatening, and poorly described in the literature. As more devices are implanted, the incidence of reservoir-related complications may increase, and it will be important to recognize the relevant signs and symptoms. We present a case series of reservoir-related complications presenting to our institution for treatment. We also reviewed all accounts of reservoir-related complications within the urologic literature. Three cases of reservoir-related complications are presented. Case 1 involves erosion of an intact AUS reservoir into the cecum of a patient with a history of myelomeningocele and bladder augmentation. Case 2 involves an IPP reservoir causing vascular compression, resulting in open exploration and repositioning of the reservoir. Case 3 involves intraperitoneal migration of a retained IPP reservoir to a subhepatic area, which was then removed laparoscopically. Literature review yielded descriptions of eight cases of intestinal complications, five cases of vascular complications, but zero reports of migration to a subhepatic area. Other notable complications include 20 reported cases of reservoir erosion into the bladder and inguinal herniation of the reservoir. Complications involving urologic prosthesis reservoirs, although rare, can have serious implications for patients. A high index of suspicion and familiarity with treatment options is required in order to allow timely diagnosis and appropriate treatment. Patients with prior major abdominal surgeries seem to be more prone to intestinal complications of reservoirs and warrant special concern. Cui T, Terlecki R, and Mirzazadeh M. Infrequent reservoir-related complications of urologic prosthetics: A case series and literature review. Sex Med 2015;3:334-338.
Terlecki, Ryan; Mirzazadeh, Majid
2015-01-01
Abstract Introduction and Aim Complications related to inflatable penile prosthesis (IPP) and artificial urinary sphincter (AUS) reservoirs are rare, potentially life threatening, and poorly described in the literature. As more devices are implanted, the incidence of reservoir‐related complications may increase, and it will be important to recognize the relevant signs and symptoms. Methods and Main Outcome Measures We present a case series of reservoir‐related complications presenting to our institution for treatment. We also reviewed all accounts of reservoir‐related complications within the urologic literature Results Three cases of reservoir‐related complications are presented. Case 1 involves erosion of an intact AUS reservoir into the cecum of a patient with a history of myelomeningocele and bladder augmentation. Case 2 involves an IPP reservoir causing vascular compression, resulting in open exploration and repositioning of the reservoir. Case 3 involves intraperitoneal migration of a retained IPP reservoir to a subhepatic area, which was then removed laparoscopically. Literature review yielded descriptions of eight cases of intestinal complications, five cases of vascular complications, but zero reports of migration to a subhepatic area. Other notable complications include 20 reported cases of reservoir erosion into the bladder and inguinal herniation of the reservoir. Conclusion Complications involving urologic prosthesis reservoirs, although rare, can have serious implications for patients. A high index of suspicion and familiarity with treatment options is required in order to allow timely diagnosis and appropriate treatment. Patients with prior major abdominal surgeries seem to be more prone to intestinal complications of reservoirs and warrant special concern. Cui T, Terlecki R, and Mirzazadeh M. Infrequent reservoir‐related complications of urologic prosthetics: A case series and literature review. Sex Med 2015;3:334–338. PMID:26797069
Ávila-Orta, Carlos A.; Quiñones-Jurado, Zoe V.; Waldo-Mendoza, Miguel A.; Rivera-Paz, Erika A.; Cruz-Delgado, Víctor J.; Mata-Padilla, José M.; González-Morones, Pablo; Ziolo, Ronald F.
2015-01-01
Isotactic polypropylenes (iPP) with different melt flow indexes (MFI) were used to fabricate nanocomposites (NCs) with 10 wt % loadings of multi-wall carbon nanotubes (MWCNTs) using ultrasound-assisted extrusion methods to determine their effect on the morphology, melt flow, and electrical properties of the NCs. Three different types of iPPs were used with MFIs of 2.5, 34 and 1200 g/10 min. Four different NC fabrication methods based on melt extrusion were used. In the first method melt extrusion fabrication without ultrasound assistance was used. In the second and third methods, an ultrasound probe attached to a hot chamber located at the exit of the die was used to subject the sample to fixed frequency and variable frequency, respectively. The fourth method is similar to the first method, with the difference being that the carbon nanotubes were treated in a fluidized air-bed with an ultrasound probe before being used in the fabrication of the NCs with no ultrasound assistance during extrusion. The samples were characterized by MFI, Optical microscopy (OM), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), electrical surface resistivity, and electric charge. MFI decreases in all cases with addition of MWCNTs with the largest decrease observed for samples with the highest MFI. The surface resistivity, which ranged from 1013 to 105 Ω/sq, and electric charge, were observed to depend on the ultrasound-assisted fabrication method as well as on the melt flow index of the iPP. A relationship between agglomerate size and area ratio with electric charge was found. Several trends in the overall data were identified and are discussed in terms of MFI and the different fabrication methods. PMID:28793686
DOE Office of Scientific and Technical Information (OSTI.GOV)
Regoushevsky, V I; Tambovtsev, S D; Dvukhsherstnov, V G
2009-05-18
For over ten years SSC RF-IPPE, together with the US DOE National Laboratories, has been working on implementing automated control and accountability methods for nuclear materials and other items. Initial efforts to use adhesive bar codes or ones printed (painted) onto metal revealed that these methods were inconvenient and lacked durability under operational conditions. For NM disk applications in critical stands, there is the additional requirement that labels not affect the neutron characteristics of the critical assembly. This is particularly true for the many stainless-steel clad disks containing highly enriched uranium (HEU) and plutonium that are used at SSC RF-IPPEmore » for modeling nuclear power reactors. In search of an alternate method for labeling these disks, we tested several technological options, including laser marking and two-dimensional codes. As a result, the method of laser coloring was chosen in combination with Data Matrix ECC200 symbology. To implement laser marking procedures for the HEU disks and meet all the nuclear material (NM) handling standards and rules, IPPE staff, with U.S. technical and financial support, implemented an automated laser marking system; there are also specially developed procedures for NM movements during laser marking. For the laser marking station, a Zenith 10F system by Telesis Technologies (10 watt Ytterbium Fiber Laser and Merlin software) is used. The presentation includes a flowchart for the automated system and a list of specially developed procedures with comments. Among other things, approaches are discussed for human-factor considerations. To date, markings have been applied to numerous steel-clad HEU disks, and the work continues. In the future this method is expected to be applied to other MC&A items.« less
MacLachlan, Malcolm; Mannan, Hasheem; Huss, Tessy; Munthali, Alister; Amin, Mutamad
2015-11-16
The application of EquiFrame in the analysis of sexual and reproductive health policies by Ivanova et al to a new thematic area, their selection of only some of the Core Concepts of human rights in health service provision and the addition of new vulnerable groups relevant to the purpose of their analysis, are all very welcome developments. We also applaud their application of EquiFrame to policies in countries where it has not previously been used, along with their use of interviews with policy-makers to produce a deeper understanding of policy processes. We argue that clear justification for the inclusion of additional, or replacement of some exiting vulnerable groups within EquiFrame should be accompanied by clear definitions of such groups, along with the evidence-base that justifies their classification as a vulnerable or marginalised group. To illustrate the versatility of EquiFrame, we summarise a range of ways in which it has been used across a number of regions; including a brief Case Study of its use to develop the National Health Policy of Malawi. While EquiFrame focuses on policy content, we preview a new policy analysis tool - Equity and Inclusion in Policy Processes (EquIPP) - which assesses the extent of equity and inclusion in broader policy processes. Together, EquiFrame and EquIPP can be used to help governments and civil society ensure that policies are addressing the much stronger emphasis on social inclusion, now apparent in the Sustainable Development Goals (SDGs). © 2016 by Kerman University of Medical Sciences.
Butler, John E; Wertz, Nancy
2006-10-15
Fetal piglets offer an in vivo model for determining whether Ag-independent IgG subclass transcription proceeds in a manner that differs from subclass transcription in pigs exposed to environmental Ags and TLR ligands. Our data from approximately 12,000 Cgamma clones from > 60 piglets provide the first report on the relative usage of all known porcine Cgamma genes in fetal and young pigs. Studies revealed that among the six Cgamma genes, allelic variants of IgG1 comprised 50-80% of the repertoire, and IgG2 alleles comprised < 10% in nearly all tissues. However, relative transcription of allelic variants of IgG1 randomly deviate from the 1:1 ratio expected in heterozygotes. Most surprising was the finding that IgG3 accounted for half of all Cgamma transcripts in the ileal Peyer's patches (IPPs) and mesenteric lymph nodes but on average only approximately 5% of the clones from the thymus, tonsil, spleen, peripheral blood, and bone marrow of newborns. Lymphoid tissues from late term fetuses revealed a similar expression pattern. Except for IgG3 in the IPPs and mesenteric lymph nodes, no stochastic pattern of Cgamma expression during development was seen in animals from mid-gestation through 5 mo. The age and tissue dependence of IgG3 transcription paralleled the developmental persistence of the IPP, and its near disappearance corresponds to the diversification of the preimmune VDJ repertoire in young piglets. We hypothesize that long-hinged porcine IgG3 may be important in preadaptive responses to T cell-independent Ags similar to those described for its murine namesake.
El-Dawlatly, Abdelazeem Ali; Al-Dohayan, Abdullah; Abdel-Meguid, Mohamed Essam; Turkistani, Ahmed; Alotaiby, Wadha Mubarak; Abdelaziz, Emad Mansoor
2003-12-01
Endoscopic thoracic sympathectomy (ETS) is the preferred surgery for treatment of intractable palmar hyperhidrosis (PH). General anesthesia with onelung collapsed ventilation (OLCV) using single-lumen tracheal tube (SLT), is our preferred anesthetic technique for ETS. Intrapleural CO(2) insufflation (capnothorax) was used to ensure lung collapse. The current study examined the effects of capnothorax on dynamic lung compliance (DLC) of the ventilated lung during ETS. After obtaining written informed consent, 10 adult male patients ASA I&II undergoing ETS were studied. Their average age and weight were 25 +/- 7 yr and 67 +/- 8 kg. General anesthesia with SLT and OLCV technique was used. Capnothorax with intrapleural pressure (IPP) of 10 mmHg was initially used, then it was reduced and maintained at 5 mmHg throughout the operation. Anesthesia delivery unit (Datex Ohmeda type A_Elec, Promma, Sweden) was used where airway pressures and DLC were displayed during OLCV. A computer program (SPSS 9.0 for Windows; SPSS Inc., Chicago, IL) was used for statistical analysis of the data obtained. One way analysis of variance (ANOVA) was used for analysis of data before, during and after OLCV. P<0.05 was considered significant. The mean values of the DLC were 52 +/- 6, 30 +/- 3, 39 +/- 5 and 53 +/- 9 ml/cmH(2)O before, during (at 10 and 5 mmHg IPP) and after OLCV respectively with significant differences before and at 10 and 5mmHg IPP. In conclusions, during OLCV and capnothorax for ETS, DLC tends to decrease with increasing of intrapleural CO(2) insufflation pressure. However, in short procedures it has no deleterious postoperative effect. To the best of our knowledge this is the first study performed to investigate DLC changes during OLCV with capnothorax.
Lamontagne, Marie-Eve; Perreault, Kadija; Gagnon, Marie-Pierre
2014-04-10
Despite growing interest in the importance of, and challenges associated with the involvement of patient and population (IPP) in the process of developing and adapting clinical practice guidelines (CPGs), there is a lack of knowledge about the best method to use. This is especially problematic in the field of rehabilitation, where individuals with disabilities might face many barriers to their involvement in the guideline development and adaptation process. The goal of this pilot trial is to document the acceptability, feasibility and effectiveness of two methods of involving patients with a disability (traumatic brain injury) in CPG development. A single-blind, randomized, crossover pragmatic trial will be performed with 20 patients with traumatic brain injury (TBI). They will be randomized into two groups, and each will try two alternative methods of producing recommendations; a discussion group (control intervention) and a Wiki, a webpage that can be modified by those who have access to it (experimental intervention). The participants will rate the acceptability of the two methods, and feasibility will be assessed using indicators such as the number of participants who accessed and completed the two methods, and the number of support interventions required. Twenty experts, blinded to the method of producing the recommendations, will independently rate the recommendations produced by the participants for clarity, accuracy, appropriateness and usefulness. Our trial will allow for the use of optimal IPP methods in a larger project of adapting guidelines for the rehabilitation of individuals with TBI. Ultimately the results will inform the science of CPG development and contribute to the growing knowledge about IPP in rehabilitation settings. Clinical trial KT Canada 87776.
Hybrid Imaging for Extended Depth of Field Microscopy
NASA Astrophysics Data System (ADS)
Zahreddine, Ramzi Nicholas
An inverse relationship exists in optical systems between the depth of field (DOF) and the minimum resolvable feature size. This trade-off is especially detrimental in high numerical aperture microscopy systems where resolution is pushed to the diffraction limit resulting in a DOF on the order of 500 nm. Many biological structures and processes of interest span over micron scales resulting in significant blurring during imaging. This thesis explores a two-step computational imaging technique known as hybrid imaging to create extended DOF (EDF) microscopy systems with minimal sacrifice in resolution. In the first step a mask is inserted at the pupil plane of the microscope to create a focus invariant system over 10 times the traditional DOF, albeit with reduced contrast. In the second step the contrast is restored via deconvolution. Several EDF pupil masks from the literature are quantitatively compared in the context of biological microscopy. From this analysis a new mask is proposed, the incoherently partitioned pupil with binary phase modulation (IPP-BPM), that combines the most advantageous properties from the literature. Total variation regularized deconvolution models are derived for the various noise conditions and detectors commonly used in biological microscopy. State of the art algorithms for efficiently solving the deconvolution problem are analyzed for speed, accuracy, and ease of use. The IPP-BPM mask is compared with the literature and shown to have the highest signal-to-noise ratio and lowest mean square error post-processing. A prototype of the IPP-BPM mask is fabricated using a combination of 3D femtosecond glass etching and standard lithography techniques. The mask is compared against theory and demonstrated in biological imaging applications.
The steps to forming a joint venture IPP in Poland
DOE Office of Scientific and Technical Information (OSTI.GOV)
Allen, Z.; Colligan, M.J.
Poland represents the largest market in Central Europe with 38 million people and an installed electrical generating capacity of about 32 gigawatts. Since 1989, when the process of governmental restructuring along free market principals began, the allure to IPP developers has been evident, but is of yet unrealized. The natural model for IPP development in Poland would seem to be joint ventures with Polish generating companies. These enterprises already have sites, franchises, and a going business to contribute to a joint company. There are a number of reasons why so few deals have been concluded in Poland to date, andmore » a number of barriers still exist that tend to hamper the realization of project finance funded power joint ventures. But, these barriers are not insurmountable. Overcoming them in the context of a joint venture relationship with a domestic partner requires patience, work, and an ability to bridge the gaps between the realities of working in a post-Communist environment and the practicalities of structuring projects that can be financed in the international capital markets. The new Energy Law in Poland establishes a framework for a viable private sector power generation business. But the enabling regulations are yet to be published or approved. There is still effective political risk on account of the uncertainty this creates. Pressure is mounting on the Polish Government, especially due to its expressed interest in joining the EU, to get the power sector to operate on private sector terms, if not in private hands. The trends are pointing in the direction of increased market driven policies and practices. The conclusion is that, despite the delays of the past, independent power projects will start to happen in Poland on a joint venture basis, with increasing frequency in the next years.« less
Chao, Duobin; Ni, Shitan
2016-05-20
Great efforts have been made to develop fluorescent probes for pyrophosphate (PPi) detection. Nucleus staining with fluorescence microscopy has been also widely investigated. But fluorescent probes for PPi detection with high sensitivity in water medium and nucleus staining with low-cost non-precious metal complexes in living cells are still challenging. Herein, we report simple terpyridine-Zn(II) complexes for selective nanomolar PPi detection over ATP and ADP in water based on aggregation induced emission (AIE) and intramolecular charge transfer (ICT). In addition, these terpyridine-Zn(II) complexes were successfully employed for nucleus staining in living cells. These results demonstrated simply obtained terpyridine-Zn(II) complexes are powerful tool for PPi detection and the development of PPi-related studies.
Resnick, D; Niwayama, G; Coutts, R D
1977-05-01
A comprehensive study of femoral heads of patients and cadavers with osteoarthritis, rheumatoid arthritis, osteonecrosis, and calcium pyrophosphate dihydrate deposition disease allows insight into the radiographic and pathologic appearance of subchondral radiolucencies in these disorders. The term geode, rather than cyst or pseudocyst, may be a more appropriate decription of these lesions. In osteoarthritis, goedes occur on the pressure segment of the femoral head in association with loss of articular space; in rheumatoid arthritis, they are initially noted at the chondro-osseous junction and subsequently involve the entire femoral head. In osteonecrosis, geodes appear in the necrotic segment of the femoral head. In calcium pyrophosphate deposition disease, geodes resemble those in osteoarthritis but are larger, more numerous, and more widespread.
Electronic structure of lead pyrophosphate
NASA Astrophysics Data System (ADS)
Suewattana, Malliga; Singh, David
2007-03-01
Lead Pyrophosphate Pb2P2O7 is of interest for potential radiation detection applications and use in long term waste storage. It forms in triclinic P1 crystals and can also be grown as glasses. We performed electronic structure calculations using the crystal structure which determined by Mullica et. al (J. Solid State Chem (1986)) using x-ray diffraction and found large forces on atoms suggesting that the refined atomic positions were not fully correct. Here we report first principles structure relaxation and a revised crystal structure for this compound. We analyze the resulting structure using pair distribution functions and discuss the implications for the electronic properties. This work was supported by DOE NA22 and the Office of Naval Research.
Non-standard amino acid recognition by Escherichia coli leucyl-tRNA synthetase
NASA Technical Reports Server (NTRS)
Martinis, S. A.; Fox, G. E.
1997-01-01
Recombinant E. coli leucyl-tRNA synthetase was screened for amino acid-dependent pyrophosphate exchange activity using noncognate aliphatic amino acids including norvaline, homocysteine, norleucine, methionine, and homoserine. [32P]-labeled reaction products were separated by thin layer chromatography using a novel solvent system and then quantified by phosphorimaging. Norvaline which differs from leucine by only one methyl group stimulated pyrophosphate exchange activity as did both homocysteine and norleucine to a lesser extent. The KM parameters for leucine and norvaline were measured to be 10 micromoles and 1.5 mM, respectively. Experiments are in progress to determine if norvaline is transferred to tRNA(Leu) and/or edited by a pre- or post-transfer mechanism.
A Model for Speedup of Parallel Programs
1997-01-01
Sanjeev. K Setia . The interaction between mem- ory allocation and adaptive partitioning in message- passing multicomputers. In IPPS Workshop on Job...Scheduling Strategies for Parallel Processing, pages 89{99, 1995. [15] Sanjeev K. Setia and Satish K. Tripathi. A compar- ative analysis of static
40 CFR 52.2570 - Identification of plan.
Code of Federal Regulations, 2012 CFR
2012-07-01
...) On March 3, 1972, the control strategy (IPP) for the Southeast Wisconsin Interstate was submitted by... representing reasonably available control technology which are necessary for the attainment of the ozone... submitted revisions to regulations NR 154.01 and NR 154.13 representing reasonably available control...
40 CFR 52.2570 - Identification of plan.
Code of Federal Regulations, 2013 CFR
2013-07-01
...) On March 3, 1972, the control strategy (IPP) for the Southeast Wisconsin Interstate was submitted by... representing reasonably available control technology which are necessary for the attainment of the ozone... submitted revisions to regulations NR 154.01 and NR 154.13 representing reasonably available control...
40 CFR 52.2570 - Identification of plan.
Code of Federal Regulations, 2014 CFR
2014-07-01
...) On March 3, 1972, the control strategy (IPP) for the Southeast Wisconsin Interstate was submitted by... representing reasonably available control technology which are necessary for the attainment of the ozone... submitted revisions to regulations NR 154.01 and NR 154.13 representing reasonably available control...
Industrial Preparedness Planning: A Review of the Literature
1988-03-01
the President created the Office of Defense Mobilization and made its head a member of his cabinet. As the Korean War receded from memory , frequent...expan- sion, and sustention planning appeared in government IPP directives. The words collectively addressed whether firms were producing required items
Federal Register 2010, 2011, 2012, 2013, 2014
2013-12-10
..., for issues related to OPPS pass-through devices, brachytherapy sources, intraoperative radiation... cardioverter defibrillator ICU Intensive care unit IHS Indian Health Service IMRT Intensity Modulated Radiation... Intraoperative radiation treatment IPPS [Hospital] Inpatient Prospective Payment System IQR [Hospital] Inpatient...
A three-year reflective writing program as part of introductory pharmacy practice experiences.
Nuffer, Wesley; Vaughn, Jessica; Kerr, Kevin; Zielenski, Christopher; Toppel, Brianna; Johnson, Lauren; McCauley, Patrina; Turner, Christopher J
2013-06-12
To implement and evaluate a 3-year reflective writing program incorporated into introductory pharmacy practice experiences (IPPEs) in the first- through third-year of a doctor of pharmacy (PharmD) program. Reflective writing was integrated into 6 IPPE courses to develop students' lifelong learning skills. In their writing, students were required to self-assess their performance in patient care activities, identify and describe how they would incorporate learning opportunities, and then evaluate their progress. Practitioners, faculty members, and fourth-year PharmD students served as writing preceptors. The success of the writing program was assessed by reviewing class performance and surveying writing preceptor's opinions regarding the student's achievement of program objectives. Class pass rates averaged greater than 99% over the 8 years of the program and the large majority of the writing preceptors reported that student learning objectives were met. A support pool of 99 writing preceptors was created. A 3-year reflective writing program improved pharmacy students' reflection and reflective writing skills.
Office evaluation of male patients with lower urinary tract symptoms.
Tabatabaei, Shahin; Talab, Saman Shafaat; Zangi, Mahdi; Woo, Henry H
2012-12-01
Lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) are one of the most common urologic disorders in men. Accurate history-taking and focused physical examination allows us to diagnose the majority of cases. A better understanding of risk factors helps us tailor our treatment and predict outcomes more accurately. Population studies are crucial in our understanding of LUTS/BPH natural history. Temporary prostatic urethral stents that are used for the management of urinary retention may also be used for evaluation of patients with detrusor hypo-contractility. The use of ultrasound to measure intravesical prostatic protrusion (IPP) and the Doppler study for prostate capsular artery resistive index are promising. Near-infrared spectroscopy (NIRS) examines the tissue oxygenation that may be affected by bladder outlet obstruction. The mathematical algorithm needs some fine-tuning, and its reproducibility is debatable. Serum and urinary biomarkers may help us to diagnose the disorder, and more effectively monitor patients' response to therapy. Among all, IPP is clinically more applicable at this time.
Disseminating Comparative Effectiveness Research Through Community-based Experiential Learning.
Hansen, Richard A; Williamson, Margaret; Stevenson, Lynn; Davis, Brandy R; Evans, R Lee
2017-02-25
Objectives. To launch and evaluate a comparative effectiveness research education and dissemination program as part of an introductory pharmacy practice experience (IPPE). Methods. First- through third-year PharmD students received training on comparative effectiveness research and disseminated printed educational materials to patients in the community who they were monitoring longitudinally (n=314). Students completed an assessment and initial visit documentation form at the first visit, and a follow-up assessment and documentation form at a subsequent visit. Results. Twenty-three diabetes patients, 29 acid-reflux patients, 30 osteoarthritis patients, and 50 hypertension patients received materials. Aside from the patient asking questions, which was the most common outcome (n=44), the program resulted in 38 additional actions, which included stopping, starting, or changing treatments or health behaviors, or having additional follow-up or diagnostic testing. Small but positive improvements in patient understanding, confidence, and self-efficacy were observed. Conclusions. Dissemination of comparative effectiveness research materials in an IPPE program demonstrated a positive trend in markers of informed decision-making.
NASA Astrophysics Data System (ADS)
Zhu, Peng-wei; Phillips, Andrew; Tung, Jason; Edward, Graham
2005-05-01
The orientation distribution of sheared isotactic polypropylene (iPP) containing different amount of sodium benzoate (SB) has been investigated through the gradient of shear flow field using microbeam of synchrotron wide-angle x-ray techniques. The degree of the overall orientation of α-phase crystal is found to increase with increasing concentration of SB. Compared with the sheared iPP in the absence of SB, the orientation of α-phase crystal is found to distribute over a broader range of shear flow field in the presence of SB. The overall orientation of α-phase crystal is explained in terms of a parent-daughter model or lamella-branched shish-kebab structure. As the concentration of SB increases, the contribution from the c-axis orientation of parent lamellae decreases in the flow direction. The contribution from the a*-axis orientation of daughter lamellae is developed to be dominant in the flow direction when the concentration of SB exceeds a critical value.
Impact of Hybrid Delivery of Education on Student Academic Performance and the Student Experience
Nutter, Douglas A.; Charneski, Lisa; Butko, Peter
2009-01-01
Objectives To compare student academic performance and the student experience in the first-year doctor of pharmacy (PharmD) program between the main and newly opened satellite campuses of the University of Maryland. Methods Student performance indicators including graded assessments, course averages, cumulative first-year grade point average (GPA), and introductory pharmacy practice experience (IPPE) evaluations were analyzed retrospectively. Student experience indicators were obtained via an online survey instrument and included involvement in student organizations; time-budgeting practices; and stress levels and their perceived effect on performance. Results Graded assessments, course averages, GPA, and IPPE evaluations were indistinguishable between campuses. Students' time allocation was not different between campuses, except for time spent attending class and watching lecture videos. There was no difference between students' stress levels at each campus. Conclusions The implementation of a satellite campus to expand pharmacy education yielded academic performance and student engagement comparable to those from traditional delivery methods. PMID:19960080
Stone, Devin A; Dickensheets, Bridget A; Poisal, John A
2018-02-01
To compare Medicaid fee-for-service (FFS) inpatient hospital payments to expected Medicare payments. Medicaid and Medicare claims data, Medicare's MS-DRG grouper and inpatient prospective payment system pricer (IPPS pricer). Medicaid FFS inpatient hospital claims were run through Medicare's MS-DRG grouper and IPPS pricer to compare Medicaid's actual payment against what Medicare would have paid for the same claim. Average inpatient hospital claim payments for Medicaid were 68.8 percent of what Medicare would have paid in fiscal year 2010, and 69.8 percent in fiscal year 2011. Including Medicaid disproportionate share hospital (DSH), graduate medical education (GME), and supplemental payments reduces a substantial proportion of the gap between Medicaid and Medicare payments. Medicaid payments relative to expected Medicare payments tend to be lower and vary by state Medicaid program, length of stay, and whether payments made outside of the Medicaid claims process are included. © Health Research and Educational Trust.
NASA Astrophysics Data System (ADS)
Sharma, A. K.; Gurav, O. B.; Gaikwad, H. P.; Chavan, G. A.; Nade, D. P.; Nikte, S. S.; Ghodpage, R. N.; Patil, P. T.
2018-04-01
The nightglow observations of OI 630.0 nm emission carried out from low latitude station Kolhapur using All Sky Imager (ASI) with 140° field of view (FOV) for the month of April 2011 are used. The images were processed to study the field aligned irregularities often called as equatorial plasma bubbles (EPBs). The present study focuses on the occurrence of scintillation during the traversal of EPBs over ionospheric pierce point (IPP). Here we dealt with the depletion level (depth) of the EPB structures and its effect on VHF signals. We compared VHF scintillation data with airglow intensities at Ionospheric pierce point (IPP) from the same location and found that the largely depleted EPBs make stronger scintillation. From previous literature, it is believed that the small scale structures are present near the steeper walls of EPBs which often degrades the communication, the analysis presented in this paper confirms this belief.
Effect of condensed tannin profile on wheat flour dough rheology
USDA-ARS?s Scientific Manuscript database
Proanthocyanidins (PA) crosslink proteins and could expand wheat gluten functionality. Effect PA MW profile (sorghum versus grape seed PA) on rheology of flours with different gluten composition (high versus low insoluble polymeric protein, IPP) was evaluated using mixograph, large (TA.XT2i) and sm...
77 FR 6553 - Combined Notice of Filings #2
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-08
.... Applicants: American Electric Power Service Corporation, AEP Energy Partners, Inc., CSW Energy Services, Inc., Central and South West Services, Inc. Description: Notice of change in status of American Electric Power.... Applicants: Black Hills/Colorado Electric Utility Co, LP, Black Hills Colorado IPP, LLC, Black Hills Power...
76 FR 59389 - Privacy Act of 1974; System of Records
Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-26
... balances and leave history. Deductions from Pay: Tax information (Federal, state and local) based on... data bases via the Enterprise Information Web (EIW). AF-IPPS will also allow Air Force Manpower and... duties related to approved research projects, and for processing and adjudicating claims, determining...
2002-01-01
the Public Utility Regulatory Policy Act ( PURPA ), one of five statutes aimed at reducing U.S. dependence on foreign oil.77 This law required utilities...restructuring was in the area of pricing. Under the framework established by PURPA and the FERC orders, a wholesale power market between utilities and IPPs
NASA Astrophysics Data System (ADS)
Rachkov, V. I.; Kalyakin, S. G.; Kukharchuk, O. F.; Orlov, Yu. I.; Sorokin, A. P.
2014-05-01
Successful commissioning in the 1954 of the World's First nuclear power plant constructed at the Institute for Physics and Power Engineering (IPPE) in Obninsk signaled a turn from military programs to peaceful utilization of atomic energy. Up to the decommissioning of this plant, the AM reactor served as one of the main reactor bases on which neutron-physical investigations and investigations in solid state physics were carried out, fuel rods and electricity generating channels were tested, and isotope products were bred. The plant served as a center for training Soviet and foreign specialists on nuclear power plants, the personnel of the Lenin nuclear-powered icebreaker, and others. The IPPE development history is linked with the names of I.V. Kurchatov, A.I. Leipunskii, D.I. Blokhintsev, A.P. Aleksandrov, and E.P. Slavskii. More than 120 projects of various nuclear power installations were developed under the scientific leadership of the IPPE for submarine, terrestrial, and space applications, including two water-cooled power units at the Beloyarsk NPP in Ural, the Bilibino nuclear cogeneration station in Chukotka, crawler-mounted transportable TES-3 power station, the BN-350 reactor in Kazakhstan, and the BN-600 power unit at the Beloyarsk NPP. Owing to efforts taken on implementing the program for developing fast-neutron reactors, Russia occupied leading positions around the world in this field. All this time, IPPE specialists worked on elaborating the principles of energy supertechnologies of the 21st century. New large experimental installations have been put in operation, including the nuclear-laser setup B, the EGP-15 accelerator, the large physical setup BFS, the high-pressure setup SVD-2; scientific, engineering, and technological schools have been established in the field of high- and intermediate-energy nuclear physics, electrostatic accelerators of multicharge ions, plasma processes in thermionic converters and nuclear-pumped lasers, physics of compact nuclear reactors and radiation protection, thermal physics, physical chemistry and technology of liquid metal coolants, and physics of radiation-induced defects, and radiation materials science. The activity of the institute is aimed at solving matters concerned with technological development of large-scale nuclear power engineering on the basis of a closed nuclear fuel cycle with the use of fast-neutron reactors (referred to henceforth as fast reactors), development of innovative nuclear and conventional technologies, and extension of their application fields.
Gadgil, Anirudh A; Eisenstein, Stephan M; Darby, Alan; Cassar Pullicino, Victor
2002-10-01
A case of bilateral symptomatic facet joint synovial cysts arising in association with calcium pyrophosphate deposition disease is reported. To present a previously unreported cause for symptomatic synovial cysts of the lumbar spine. Synovial cysts of the facet joints occur most commonly in association with degenerative disease of the spine in older individuals. The association of these cysts with trauma, rheumatoid arthritis, spondylolysis, and kissing spinous processes also has been reported. These cysts can cause symptoms and signs from direct compression of the dura. Chondrocalcinosis has not been previously reported to cause symptomatic synovial cysts. A 67-year-old woman presented with right lower limb sciatica caused by a right L4-L5 facet joint cyst, which resolved after surgical decompression. A year later, she presented with left lower limb sciatica caused by development of a new L4-L5 facet joint cyst, which also resolved after surgical decompression. Histopathologic examination of each cyst showed a cyst wall of fibrous tissue with synovial lining, inflammation, and granulation tissue. Examination of the tissue under polarized light showed positively birefringent, short blunt crystals of calcium pyrophosphate dihydrate. In patients with a history of gout or pseudogout, a rare possibility of a synovial cyst should be considered in the differential diagnosis during investigation for the cause of neural compression resulting in sciatic syndrome.
Peller, L
1977-02-08
The free-energy change of phosphodiester bond formation from nucleoside triphosphates is more favorable than with nucleoside diphosphates as substrates. Base-stacking interactions can make significant contributions to both delta G degrees ' values. Pyrophosphate hydrolysis when it accompanies the former reaction dominates all thermodynamic considerations. Three experimental situations are discussed in which high-molecular-weight polynucleotides are synthesized without a strong driving force for covalent bond formation. For one of these, a kinetic scheme is presented which encompasses an early narrow Poisson distribution of chain lengths with ultimate passage to a disperse equilibrium population of chain sizes. Hydrolytic removal of pyrophosphate expands the time scale for this undesirable process by a factor of 10(9), while it enormously elevates the thermodynamic ceiling for the average degrees of polymerization in the other two examples. The electron micrographically revealed broad size population from an early study of partial replication of a T7 DNA template is found to adhere (fortuitously) to a disperse most probable representation. Some possible origins are examined for the branched structures in this product, as well as in a later investigation of replication of this nucleic acid. The achievement of both very high molecular weights and sharply peaked size distributions in polynucleotides synthesized in vitro will require coupling to inorganic pyrophosphatase action as in vivo.
Ferriols, Victor Marco Emmanuel N.; Yaginuma, Ryoko; Adachi, Masao; Takada, Kentaro; Matsunaga, Shigeki; Okada, Shigeru
2015-01-01
The diatom Rhizosolenia setigera Brightwell produces highly branched isoprenoid (HBI) hydrocarbons that are ubiquitously present in marine environments. The hydrocarbon composition of R. setigera varies between C25 and C30 HBIs depending on the life cycle stage with regard to auxosporulation. To better understand how these hydrocarbons are biosynthesized, we characterized the farnesyl pyrophosphate (FPP) synthase (FPPS) enzyme of R. setigera. An isolated 1465-bp cDNA clone contained an open reading frame spanning 1299-bp encoding a protein with 432 amino acid residues. Expression of the RsFPPS cDNA coding region in Escherichia coli produced a protein that exhibited FPPS activity in vitro. A reduction in HBI content from diatoms treated with an FPPS inhibitor, risedronate, suggested that RsFPPS supplies precursors for HBI biosynthesis. Product analysis by gas chromatography-mass spectrometry also revealed that RsFPPS produced small amounts of the cis-isomers of geranyl pyrophosphate and FPP, candidate precursors for the cis-isomers of HBIs previously characterized. Furthermore, RsFPPS gene expression at various life stages of R. setigera in relation to auxosporulation were also analyzed. Herein, we present data on the possible role of RsFPPS in HBI biosynthesis, and it is to our knowledge the first instance that an FPPS was cloned and characterized from a diatom. PMID:25996801
NASA Astrophysics Data System (ADS)
Kellman, L. M.; Gabriel, C. E.
2015-12-01
Soil organic matter (SOM) in northern forest soils is associated with a suite of minerals that can confer SOM stability, resulting in the potential for long-term storage of carbon. Increasingly, evidence is suggesting that SOM in certain mineral phases is dynamic and vulnerable to soil disturbance. The objective of this research was to investigate changes in a suite of mineral-associated pools of SOM through depth in a temperate forest soil to determine which mineral-associated carbon pools are most sensitive to forest harvesting disturbance. Sequential selective dissolutions representing increasingly stable SOM pools (soluble minerals (deionized water); humus-mineral complexes (Na-pyrophosphate); poorly crystalline minerals (HCl hydroxylamine); and crystalline secondary minerals (Na-dithionite + HCl)) of mineral soils through depth to 50 cm were carried out in podzolic soils sampled from temperate red spruce forests of contrasting stand age in Nova Scotia, Canada. Results of this analysis point to a loss of carbon from SOM within the B-horizon of the most recently harvested site from the pyrophosphate-extracted humus mineral complexed SOM, suggesting that it is this exchangeable pool that appears to be destabilized following clearcut harvesting at these study sites. This suggests that recovery from this landuse disturbance is dependent upon increasing storage of this SOM pool, and that mineral-associated pools, particularly pyrophosphate-extractable SOM, may be a useful indicator of changes to soil carbon storage following land use change.
Presence of a plant-like proton-pumping pyrophosphatase in acidocalcisomes of Trypanosoma cruzi.
Scott, D A; de Souza, W; Benchimol, M; Zhong, L; Lu, H G; Moreno, S N; Docampo, R
1998-08-21
The vacuolar-type proton-translocating pyrophosphatase (V-H+-PPase) is an enzyme previously described in detail only in plants. This paper demonstrates its presence in the trypanosomatid Trypanosoma cruzi. Pyrophosphate promoted organellar acidification in permeabilized amastigotes, epimastigotes, and trypomastigotes of T. cruzi. This activity was stimulated by K+ ions and was inhibited by Na+ ions and pyrophosphate analogs, as is the plant activity. Separation of epimastigote extracts on Percoll gradients yielded a dense fraction that contained H+-PPase activity measured both by proton uptake and phosphate release but lacked markers for mitochondria, lysosomes, glycosomes, cytosol, and plasma membrane. Antiserum raised against specific sequences of the plant V-H+-PPase cross-reacted with a T. cruzi protein, which was also detectable in the dense Percoll fraction. The organelles in this fraction appeared by electron microscopy to consist mainly of acidocalcisomes (acidic calcium storage organelles). This identification was confirmed by x-ray microanalysis. Immunofluorescence and immunoelectron microscopy indicated that the V-H+-PPase was located in the plasma membrane and acidocalcisomes of the three different forms of the parasite. Pyrophosphate was able to drive calcium uptake in permeabilized T. cruzi. This uptake depended upon a proton gradient and was reversed by a specific V-H+-PPase inhibitor. Our results imply that the phylogenetic distribution of V-H+-PPases is much wider than previously perceived but that the enzyme has a unique subcellular location in trypanosomes.
Della Lucia, Ceres M; Vaz Tostes, Maria das Graças; Silveira, Carlos Mário M; Bordalo, Lívia A; Rodrigues, Fabiana C; Pinheiro-Sant'Ana, Helena Maria; Martino, Hércia S D; Costa, Neuza Maria B
2013-03-01
This study aimed to evaluate iron (Fe) bioavailability in Wistar rats fed with rice fortified with micronized ferric pyrophosphate (FP) by Ultra Rice (UR) technology with or without addition of yacon flour as a source of 7.5% of fructooligosaccharides (FOS). Diets were supplied with 12 mg iron/kg from the following sources: ferrous sulfate (FS - control diet), fortified rice with micronized ferric pyrophosphate (Ultra Rice) (UR diet), ferrous sulfate + yacon flour (FS + Y diet) or Ultra Rice + yacon flour (UR + Y diet). Blood samples were collected at the end of depletion and repletion stages for determination of hemoglobin concentration and calculation of the relative biological value (RBV). Also, the content of short chain fatty acids (SCFA) (acetic, propionic and butyric acids) from animals' stools and caecum weight were determined. The UR diet showed high iron bioavailability (RBV = 84.7%). However, the addition of yacon flour in the diet containing fortified rice (UR + Y diet) decreased RBV (63.1%) significantly below the other three groups (p < 0.05). Groups that received yacon flour showed higher acetic acid values compared to those who did not. In conclusion, fortified UR with micronized ferric pyrophosphate showed high iron bioavailability but the addition of yacon flour at 7.5% FOS reduced iron bioavailability despite increased caecum weight and SCFA concentration.
Diner, Bruce A; Fan, Janine; Scotcher, Miles C; Wells, Derek H; Whited, Gregory M
2018-01-01
There is a growing interest in the use of microbial fermentation for the generation of high-demand, high-purity chemicals using cheap feedstocks in an environmentally friendly manner. One example explored here is the production of isoprene (C 5 H 8 ), a hemiterpene, which is primarily polymerized to polyisoprene in synthetic rubber in tires but which can also be converted to C 10 and C 15 biofuels. The strictly anaerobic, acetogenic bacterium Clostridium ljungdahlii , used in all of the work described here, is capable of glycolysis using the Embden-Meyerhof-Parnas pathway and of carbon fixation using the Wood-Ljungdahl pathway. Clostridium - Escherichia coli shuttle plasmids, each bearing either 2 or 3 different heterologous genes of the eukaryotic mevalonic acid (MVA) pathway or eukaryotic isopentenyl pyrophosphate isomerase (Idi) and isoprene synthase (IspS), were constructed and electroporated into C. ljungdahlii These plasmids, one or two of which were introduced into the host cells, enabled the synthesis of mevalonate and of isoprene from fructose and from syngas (H 2 , CO 2 , and CO) and the conversion of mevalonate to isoprene. All of the heterologous enzymes of the MVA pathway, as well as Idi and IspS, were shown to be synthesized at high levels in C. ljungdahlii , as demonstrated by Western blotting, and were enzymatically active, as demonstrated by in vivo product synthesis. The quantities of mevalonate and isoprene produced here are far below what would be required of a commercial production strain. However, proposals are made that could enable a substantial increase in the mass yield of product formation. IMPORTANCE This study demonstrates the ability to synthesize a heterologous metabolic pathway in C. ljungdahlii , an organism capable of metabolizing either simple sugars or syngas or both together (mixotrophy). Syngas, an inexpensive source of carbon and reducing equivalents, is produced as a major component of some industrial waste gas, and it can be generated by gasification of cellulosic biowaste and of municipal solid waste. Its conversion to useful products therefore offers potential cost and environmental benefits. The ability of C. ljungdahlii to grow mixotrophically also enables the recapture, should there be sufficient reducing equivalents available, of the CO 2 released upon glycolysis, potentially increasing the mass yield of product formation. Isoprene is the simplest of the terpenoids, and so the demonstration of its production is a first step toward the synthesis of higher-value products of the terpenoid pathway. Copyright © 2017 Diner et al.
Fan, Janine; Scotcher, Miles C.; Wells, Derek H.; Whited, Gregory M.
2017-01-01
ABSTRACT There is a growing interest in the use of microbial fermentation for the generation of high-demand, high-purity chemicals using cheap feedstocks in an environmentally friendly manner. One example explored here is the production of isoprene (C5H8), a hemiterpene, which is primarily polymerized to polyisoprene in synthetic rubber in tires but which can also be converted to C10 and C15 biofuels. The strictly anaerobic, acetogenic bacterium Clostridium ljungdahlii, used in all of the work described here, is capable of glycolysis using the Embden-Meyerhof-Parnas pathway and of carbon fixation using the Wood-Ljungdahl pathway. Clostridium-Escherichia coli shuttle plasmids, each bearing either 2 or 3 different heterologous genes of the eukaryotic mevalonic acid (MVA) pathway or eukaryotic isopentenyl pyrophosphate isomerase (Idi) and isoprene synthase (IspS), were constructed and electroporated into C. ljungdahlii. These plasmids, one or two of which were introduced into the host cells, enabled the synthesis of mevalonate and of isoprene from fructose and from syngas (H2, CO2, and CO) and the conversion of mevalonate to isoprene. All of the heterologous enzymes of the MVA pathway, as well as Idi and IspS, were shown to be synthesized at high levels in C. ljungdahlii, as demonstrated by Western blotting, and were enzymatically active, as demonstrated by in vivo product synthesis. The quantities of mevalonate and isoprene produced here are far below what would be required of a commercial production strain. However, proposals are made that could enable a substantial increase in the mass yield of product formation. IMPORTANCE This study demonstrates the ability to synthesize a heterologous metabolic pathway in C. ljungdahlii, an organism capable of metabolizing either simple sugars or syngas or both together (mixotrophy). Syngas, an inexpensive source of carbon and reducing equivalents, is produced as a major component of some industrial waste gas, and it can be generated by gasification of cellulosic biowaste and of municipal solid waste. Its conversion to useful products therefore offers potential cost and environmental benefits. The ability of C. ljungdahlii to grow mixotrophically also enables the recapture, should there be sufficient reducing equivalents available, of the CO2 released upon glycolysis, potentially increasing the mass yield of product formation. Isoprene is the simplest of the terpenoids, and so the demonstration of its production is a first step toward the synthesis of higher-value products of the terpenoid pathway. PMID:29054870
Effects of phosphates on shellfish and on calcium carbonate crystallization in vitro. Final report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wilbur, K.M.
1986-07-17
It has been known that inorganic phosphate inhibits the precipitation of calcium carbonate in artificial sea water. This work addresses the question of whether phosphate also affects the deposition of CaCO/sub 3/ in the exoskeletons of invertebrates. Tetrasodiumpyrophosphate and pentasodiumtripolyphosphate in concentrations of 15 ppM caused abnormality, mortality, and inhibition of shell deposition in trochophore larvae of the oyster Crassostrea. Inhibition of shell growth resulting from pollution at 15 ppM could be expected in Rangia with orthophosphate, tetrasodium pyrophosphate, and sodiumtripolyphosphate, in Helisoma with tetrasodium pyrophosphate, and pentasodium tripolyphosphate, and in larvae of Crassostea the relative inhibitory action of shellmore » growth was tetrasodiumpyrophosphate > sodiumtripolyphosphate > sodium orthophosphate greater than or equal to sodium hexametaphosphate. 4 refs.« less
NASA Technical Reports Server (NTRS)
Visscher, J.; Bakker, C. G.; Schwartz, Alan W.
1990-01-01
The effect of a 3-prime-5-prime pyrophosphate-linked oligomer of pTp on oligomerizations of pdAp and of its 3-prime-5-prime, 3-prime-3-prime, and 5-prime-5-prime dimers was investigated, using HPLC to separate the reaction mixtures; peak detection was by absorbance monitoring at 254 nm. It was expected that the dimers would form stable complexes with the template, with the degree of stability depending upon the internal linkage of each dimer. It was found that, although the isomers differ substantially in their oligomerization behavior in the absence of template, the analog-template catalyzes the oligomerization to about the same extent in all three cases.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-13
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NASA Astrophysics Data System (ADS)
Garber, Klaus; Ausserer, Oskar; Giacomuzzi, Salvatore
"New learning" is basically an individualized learning style. "New learning" starts by the individual itself. The individual is the basis for conditions, learning contents, rhythm, duration and intensity of the teaching. The appropriate slogan is: fetch the individual at his personal conditions.
NASA Technical Reports Server (NTRS)
Cox, Robert S.
2006-01-01
A viewgraph presentation describing JPL's non-NASA Programs is shown. The contents include: 1) JPL/Caltech: National Security Heritage; 2) Organization and Portfolio; 3) Synergistic Areas of Interest; 4) Business Environment; 5) National Space Community; 6) New Business Environment; 7) Technology Transfer Techniques; 8) Innovative Partnership Program (IPP); and 9) JPL's Track Record.
76 FR 35195 - Privacy Act of 1974; System of Records
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Interprofessional Education and Practice in Athletic Training
ERIC Educational Resources Information Center
Breitbach, Anthony P.; Richardson, Russ
2015-01-01
Professional preparation in athletic training has grown from modest roots based in physical education in the 1960s to its emergence as a recognized health profession today. The profession has long embraced interprofessional practice (IPP), but many times has not been included in discussions held at the institutional, governmental, and…
Calcium pyrophosphate arthritis
... disease that can cause attacks of arthritis. Like gout, crystals form in the joints. But in this ... CPPD arthritis can be confused with: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis Exams and Tests Most arthritic ...
Light influences cytokinin biosynthesis and sensing in Nostoc (cyanobacteria).
Frébortová, Jitka; Plíhal, Ondřej; Florová, Vendula; Kokáš, Filip; Kubiasová, Karolina; Greplová, Marta; Šimura, Jan; Novák, Ondřej; Frébort, Ivo
2017-06-01
Cytokinins are an important group of plant hormones that are also found in other organisms, including cyanobacteria. While various aspects of cytokinin function and metabolism are well understood in plants, the information is limited for cyanobacteria. In this study, we first experimentally confirmed a prenylation of tRNA by recombinant isopentenyl transferase NoIPT2 from Nostoc sp. PCC 7120, whose encoding gene we previously identified in Nostoc genome along with the gene for adenylate isopentenyl transferase NoIPT1. In contrast to NoIPT2, the transcription of NoIPT1 was strongly activated during the dark period and was followed by an increase in the cytokinin content several hours later in the light period. Dominant cytokinin metabolites detected at all time points were free bases and monophosphates of isopentenyladenine and cis-zeatin, while N-glucosides were not detected at all. Whole transcriptome differential expression analysis of cultures of the above Nostoc strain treated by cytokinin compared to untreated controls indicated that cytokinin together with light trigger expression of several genes related to signal transduction, including two-component sensor histidine kinases and two-component hybrid sensors and regulators. One of the affected histidine kinases with a cyclase/histidine kinase-associated sensory extracellular domain similar to the cytokinin-binding domain in plant cytokinin receptors was able to modestly bind isopentenyladenine. The data show that the genetic disposition allows Nostoc not only to produce free cytokinins and prenylate tRNA but also modulate the cytokinin biosynthesis in response to light, triggering complex changes in sensing and regulation. © 2017 Phycological Society of America.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barta, Michael L.; Skaff, D. Andrew; McWhorter, William J.
The polyisoprenoid compound undecaprenyl phosphate is required for biosynthesis of cell wall peptidoglycans in Gram-positive bacteria, including pathogenic Enterococcus, Streptococcus, and Staphylococcus spp. In these organisms, the mevalonate pathway is used to produce the precursor isoprenoid, isopentenyl 5-diphosphate. Mevalonate diphosphate decarboxylase (MDD) catalyzes formation of isopentenyl 5-diphosphate in an ATP-dependent irreversible reaction and is therefore an attractive target for inhibitor development that could lead to new antimicrobial agents. To facilitate exploration of this possibility, we report the crystal structure of Staphylococcus epidermidis MDD (1.85 {angstrom} resolution) and, to the best of our knowledge, the first structures of liganded MDD. Thesemore » structures include MDD bound to the mevalonate 5-diphosphate analogs diphosphoglycolyl proline (2.05 {angstrom} resolution) and 6-fluoromevalonate diphosphate (FMVAPP; 2.2 {angstrom} resolution). Comparison of these structures provides a physical basis for the significant differences in K{sub i} values observed for these inhibitors. Inspection of enzyme/inhibitor structures identified the side chain of invariant Ser{sup 192} as making potential contributions to catalysis. Significantly, Ser {yields} Ala substitution of this side chain decreases k{sub cat} by {approx}10{sup 3}-fold, even though binding interactions between FMVAPP and this mutant are similar to those observed with wild type MDD, as judged by the 2.1 {angstrom} cocrystal structure of S192A with FMVAPP. Comparison of microbial MDD structures with those of mammalian counterparts reveals potential targets at the active site periphery that may be exploited to selectively target the microbial enzymes. These studies provide a structural basis for previous observations regarding the MDD mechanism and inform future work toward rational inhibitor design.« less
Calcium Pyrophosphate Deposition (CPPD)
... Keep me signed in Passwords are Case Sensitive. Ex. Enter smith as follows: Smith Forgot Username/Password? ... Erythematosus (Juvenile) Takayasu's Arteritis Tendinitis & Bursitis Tumor Necrosis Factor Receptor Associated Periodic Syndrome (Juvenile) Vasculitis Enfermedades y ...
Code of Federal Regulations, 2014 CFR
2014-04-01
... section. For the purpose of inhibiting the development of struvite crystals, sodium acid pyrophosphate may... section. Beginning with the top sieve, lift and drop each sieve by its open edge three times. Each time...
Code of Federal Regulations, 2013 CFR
2013-04-01
... section. For the purpose of inhibiting the development of struvite crystals, sodium acid pyrophosphate may... section. Beginning with the top sieve, lift and drop each sieve by its open edge three times. Each time...
Effect of Na4O7P2 on Cu powder preparation from Cu2O-water slurry system.
Ahn, J G; Hoang, T H; Kim, D J; Kim, M S; Kim, C O; Chung, H S
2008-03-01
A unique approach is presented for preparing highly dispersed ultrafine copper particles from cuprous oxide slurry using a wet chemical reaction with hydrazine (N2H4) as a reductant along with an appropriate addition of sodium pyrophosphate (Na4O7P2) as a surfactant. It was found that very thin oxidized surfaces on the copper particles are formed during the reaction in the solution and subsequently sodium pyrophosphate plays an important role in the zeta potential of the particles, affecting their dispersion and growth significantly. The copper particles at low zeta potential easily aggregate and grow to bigger ones, whereas they at high zeta potential keep away each other and grew individually to ultrafine size. Additionally, a model for the copper particles growth in accordance with dispersion is proposed.
Trofimova, E S; Zykova, M V; Ligacheva, A A; Sherstoboev, E Y; Zhdanov, V V; Belousov, M V; Yusubov, M S; Krivoshchekov, S V; Danilets, M G; Dygai, A M
2017-04-01
We studied activation of macrophages with humic acids extracted from peat of large deposits in the Tomsk region by two extraction methods: by hydroxide or sodium pyrophosphate. Humic acid of lowland peat types containing large amounts of aromatic carbon, phenolic and alcohol groups, carbohydrate residues and ethers, irrespectively of the extraction methods contained LPS admixture that probably determines their activating properties. Humic acid of upland peat types characterized by high content of carbonyl, carboxyl, and ester groups enhance NO production and reduce arginase expression, but these effects were minimized when sodium hydroxide was used as an extraction solvent. Pyrophosphate samples of the upland peat types were characterized by aromaticity and diversity of functional groups and have a significant advantage because of they induce specific endotoxin-independent stimulating action on antigen presenting cells.